Substance use before or during pregnancy and the risk of child mortality, perinatal morbidities and congenital anomalies.

AIMS: We aimed to investigate child mortality, perinatal morbidities and congenital anomalies born by women with substance misuse during or before pregnancy (DP or BP). METHODS: Taiwan Birth Registration from 2004 to 2014 linking Integrated Illicit Drug Databases used to include substance misuse participates. Children born by mothers convicted of substance misuse DP or BP were the substance-exposed cohort. Two substance-unexposed comparison cohorts were established: one comparison cohort selected newborns from the rest of the population on a ratio of 1:1 and exact matched by the child's gender, child's birth year, mother's birth year and child's first use of the health insurance card; another comparison cohort matched newborns from exposed and unexposed mothers by their propensity scores calculated from logistic regression. RESULTS: The exposure group included 1776 DP, 1776 BP and 3552 unexposed individuals in exact-matched cohorts. A fourfold increased risk of deaths in children born by mothers exposed to substance during pregnancy was found compared to unexposed group (hazard ratio [HR] = 4.54, 95% confidence interval (CI): 2.07-9.97]. Further multivariate Cox regression models with adjustments and propensity matching substantially attenuated HRs on mortality in the substance-exposed cohort (aHR = 1.62, 95% CI: 1.10-2.39). Raised risks of perinatal morbidities and congenital anomalies were also found. CONCLUSIONS: Increased risks of child mortality, perinatal morbidities or congenital anomalies were found in women with substance use during pregnancy. From estimates before and after adjustments, our results showed that having outpatient visits or medical utilizations during pregnancy were associated with substantially attenuated HRs on mortality in the substance-exposed cohort. Therefore, the excess mortality risk might be partially explained by the lack of relevant antenatal clinical care. Our finding may suggest that the importance of early identification, specific abstinence program and access to appropriate antenatal care might be helpful in reducing newborn mortality. Adequate prevention policies may be formulated.

A global spatial analysis of factors associated with case and mortality rates for coronavirus disease 2019 during the first year of the pandemic.

BACKGROUND: A increasing number of studies have revealed associations between country-level determinants and coronavirus disease 2019 (COVID-19) outcomes. This ecological study was conducted to analyze country-level parameters related to COVID-19 infections and deaths during the first year of the pandemic. METHODS: The examined predictors comprised demographics, economic factors, disease prevalence and healthcare system status, and the relevant data were obtained from public databases. The index dates were set to 15 July 2020 (Time 1) and 15 December 2020 (Time 2). The adjusted spatial autoregression models used a first-order queen contiguity spatial weight for the main analysis and a second-order queen contiguity spatial weight for a sensitivity analysis to examine the predictors associated with COVID-19 case and mortality rates. RESULTS: Obesity was significantly and positively associated with COVID-19 case and mortality rates in both the main and sensitivity analyses. The sensitivity analysis revealed that a country's gross domestic product, population density, life expectancy and proportion of the population older than 65 y are positively associated with COVID-19 case and mortality rates. CONCLUSIONS: With the increasing global prevalence of obesity, the relationship between obesity and COVID-19 disease at the country level must be clarified and continually monitored.

Influence of Personal, Environmental, and Community Factors on Cigarette Smoking in Adolescents: A Population-Based Study from Taiwan.

Understanding the factors that influence cigarette smoking among adolescents is critical. We identified personal, community, and environmental factors associated with current cigarette smoking among adolescents. This population-based cross-sectional analysis study was conducted using the 2012 Taiwan Global Youth Tobacco Survey and the sociodemographic statistics of the city or county from Taiwan's Ministry of the Interior. A total of 27,524 participants (age: 12-18-years) was included. The associated factors were identified through logistic regression. A path analysis was performed to examine the pathway from the associated factors to current cigarette smoking. According to this analysis, the following factors were prominently and positively associated with adolescent cigarette smoking: one personal factor (pocket money), five environmental factors (home secondhand smoke (SHS) exposure, smoker friends, outside SHS exposure, school SHS exposure, and smoker parents), and two community factors (free cigarettes from tobacco companies and indigenous population). By contrast, five personal factors (feeling less comfortable smoking at social occasions, feeling indifferent about smoking or not smoking at social occasions, female sex, feeling that quitting is difficult, and feeling that quitting after having smoked is harmful to health) and one environmental factor (school antismoking education) had negative effects. Thus, comprehensive interventions promoting the perception of harm caused by smoking and interrupting access to cigarettes through social networks can reduce cigarette smoking in adolescents.

Methylphenidate and TBI in ADHD and co-occurring epilepsy and mental disorders: a self-controlled case series study.

It is suggested that medication for attention-deficit hyperactivity disorder (ADHD) links to lower risk of traumatic brain injury (TBI). Little is known about whether the beneficial effect of methylphenidate is persistent in individuals with other comorbid mental disorders and epilepsy. We identified 90,634 participants who were less than 18 years old and diagnosed with ADHD from Taiwan's National Health Insurance Research Database (NHIRD) from January 1, 2000 to December 31, 2013. Cox proportional hazards models with hazard ratio (HR) and 95% confidence interval were conducted to compare the risks of TBI event between groups of ADHD-only and ADHD with co-occurring other mental disorders. Within-individual comparisons using a self-controlled case series study design were conducted using conditional Poisson regression models with relative incidence (RR) and 95% CI to examine the effect of methylphenidate on TBI with adjustment for medication of psychotropics and anticonvulsants. For children and adolescents with ADHD, we found comorbid mental disorders and epilepsy increase the risk of TBI, with HRs ranged from 1.21 to 1.75. For the effect of MPH, we found reduced risks for TBI in ADHD (RR = 0.83, 95% CI = 0.70-0.98). Similar results were found among individuals with co-occurring oppositional defiant disorders or conduct disorder, MDD, tic disorders and epilepsy. Methylphenidate treatment was linked to lower risk for TBI in patients with ADHD and the inverse association was persistent among those with other comorbid mental disorders and epilepsy.

Strategies for supplying face masks to the population of Taiwan during the COVID-19 pandemic.

BACKGROUND: The use of face masks has become ubiquitous in Taiwan during the early COVID-19 pandemic. A name-based rationing system was established to enable the population of Taiwan to purchase face masks. This study is to assess the extent and fairness of face mask supply to the public in Taiwan. METHODS: The weekly face marks supplies were collected from name-based rationing system administrative statistics included national health insurance card and e-Mask selling record. National registered population statistics by age, gender, and district were collected from department of statistics ministry of the interior. The number of COVID-19 non-imported cases of Taiwan was collected from Taiwan centers of disease control. RESULTS: A total of 146,831,844 person times purchase records from February 6, 2020, to July 19, 2020, the weekly average face mask supply is 0.5 mask (per person) at the start of name-based rationing system, and gradually expanded to the maximum 5.1 masks (per person). Comparing the highest weekly total face mask supply (from Apr 9, 2020, to Apr 15, 2020) in aged 0-9 -, 10-19 -, 20-29 -, 30-39 -, 40-49 -, 50-59 -, 60-69 -,70-79 -, 80-89 -, 90-99, and > 100 years to the register population showed similar distribution between mask supplied people and total population (all standardized difference < 0.1). CONCLUSION: The masks supply strategies has gradually escalated the number of face masks for the public, it not only has dominant decreased the barrier of acquiring face mask, but a fair supply for total population use of Taiwan.

Exploring prior diseases associated with pancreatic cancer.

Background Pancreatic cancer (PC) is among the most deadly forms of cancer; however, the risk factors of PC have yet to be sufficiently identified. In the present study, we sought to screen all prior diseases associated with PC incidence concurrently and construct pathways for the diseases. Materials and methods This total population-based case-control study used data collected from Taiwan's National Health Insurance Research Database for the period covering 1997-2013. The case group included 3726 patients newly diagnosed with PC, who were precisely matched to 3726 controls based on gender, age, residence, and insurance premiums. Stepwise multivariate logistic regression was used to screen previous diseases in windows of 1, 2 …, 9 years prior to the first diagnosis of PC. Path analysis was used to construct the pathways between relevant prior diseases and PC. Results Within 1 year prior to PC diagnosis, a total of 11 diseases were significantly correlated with PC, included 9 positive and 2 negative associations. Path analysis identified diabetes, pancreatitis as diseases with direct positive pathways to PC incidence, and dementia with direct negative pathways. Conclusions It appears that diabetes, peptic ulcer, and digestive conditions were the prior diseases associated with PC incidence.

Prison sentencing increases the risk of unemployment among illegal heroin users in Taiwan.

BACKGROUND: Previous studies have rarely explored the effect of type of sentencing on employment status among illegal heroin users, therefore, we aims to examine the association of the sentencing types and employment outcomes among illegal heroin users in Taiwan. METHODS: Participants with illegal heroin use were identified through the national prison register system and deferred prosecution system: 2406 with deferred prosecutions, 4741 with observation and rehabilitation, 15 compulsory rehabilitation and 1958 sentenced to prison in calendar 2011. Logistic regression models were built to estimate the effect of sentencing type on unemployment status at 2 years after release. Stratification analysis was conducted to determine the effect of sentencing type based on the offender's employment status before sentencing. RESULTS: Illegal heroin users receiving a prison sentence were more than twice as likely to be unemployed 2 years later than those receiving deferred prosecution. The unemployment rate was also higher for those with observation and rehabilitation and compulsory rehabilitation than deferred prosecution in the 2 years following sentencing. Males, older users, without a job before sentencing, divorced or widowed and higher prior drug use criminal records were also higher risk of unemployment. Subgroup analysis by prior employment status revealed that being sentenced to prison, observation and rehabilitation and compulsory rehabilitation affected the subsequent employment status only for those heroin users with a job before sentencing. The strength of associations showed dose-dependent relationship between different sentencing types (sentenced to prison> compulsory rehabilitation> observation and rehabilitation) and employment outcomes. CONCLUSIONS: Illegal heroin users who receive a prison sentence have a much higher risk of unemployment than those who receive deferred prosecution after controlling potential confounders, especially those who had a job before sentencing. The implication is the stronger freedom of punishment, the higher risk of unemployment outcomes. Our study support that illegal heroin user is legally regarded as a patient before being regarded as a criminal, so giving priority to quit addition rather than imprisonment.

Methylphenidate and mortality in children with attention-deficit hyperactivity disorder: population-based cohort study.

BACKGROUND: Little is known about methylphenidate (MPH) use and mortality outcomes. AIMS: To investigate the association between MPH use and mortality among children with an attention-deficit hyperactivity disorder (ADHD) diagnosis. METHOD: This population-based cohort study analysed data from Taiwan's National Health Insurance Research Database (NHIRD). A total of 68 096 children and adolescents aged 4-17 years with an ADHD diagnosis and prescribed MPH between 2000 and 2010 were compared with 68 096 without an MPH prescription, matched on age, gender and year of first ADHD diagnosis. All participants were followed to death, migration, withdrawal from the National Health Insurance programme or 31 December 2013. MPH prescriptions were measured on a yearly basis during the study period, and the association between MPH use and mortality was analysed using a repeated-measures time-dependent Cox regression model. The outcome measures included all-cause, unnatural-cause (including suicide, accident and homicide) and natural-cause mortality, obtained from linkage to the National Mortality Register in Taiwan. RESULTS: The MPH group had lower unadjusted all-cause, natural-, unnatural- and accident-cause mortality than the comparison group. After controlling for potential confounders, MPH use was associated with a significantly lower all-cause mortality (adjusted hazard ratio AHR = 0.81, 95% CI 0.67-0.98, P = 0.027), delayed use of MPH was associated with higher mortality (AHR = 1.05, 95% CI 1.01-1.09) and longer MPH use was associated with lower mortality (AHR = 0.83, 95% CI 0.70-0.98). CONCLUSIONS: MPH use is associated with a reduced overall mortality in children with ADHD in this cohort study, but unmeasured confounding cannot be excluded absolutely.

Methylphenidate and the risk of burn injury among children with attention-deficit/hyperactivity disorder.

AIMS: Attention-deficit/hyperactivity disorder (ADHD) is associated with a higher risk of burn injury than in the normal population. Nevertheless, the influence of methylphenidate (MPH) on the risk of burn injury remains unclear. This retrospective cohort study analysed the effect of MPH on the risk of burn injury in children with ADHD. METHOD: Data were from Taiwan's National Health Insurance Research Database (NHIRD). The sample comprised individuals younger than 18 years with a diagnosis of ADHD (n = 90 634) in Taiwan's NHIRD between January 1996 and December 2013. We examined the cumulative effect of MPH on burn injury risk using Cox proportional hazards models. We conducted a sensitivity analysis for immortal time bias using a time-dependent Cox model and within-patient comparisons using the self-controlled case series model. RESULTS: Children with ADHD taking MPH had a reduced risk of burn injury, with a cumulative duration of treatment dose-related effect, compared with those not taking MPH. Compared with children with ADHD not taking MPH, the adjusted hazard ratio for burn injury was 0.70 in children taking MPH for <90 days (95% confidence interval (CI) 0.64-0.77) and 0.43 in children taking MPH for ≥90 days (95% CI 0.40-0.47), with a 50.8% preventable fraction. The negative association of MPH was replicated in age-stratified analysis using time-dependent Cox regression and self-controlled case series models. CONCLUSION: This study showed that MPH treatment was associated with a lower risk of burn injury in a cumulative duration of treatment dose-related effect manner.

Association Between Attention Deficit Hyperactivity Disorder and Risk of Burn Injury: A Propensity-Matched Cohort Study.

PURPOSE: Literature suggests that attention deficit hyperactivity disorder (ADHD) is associated with a high risk of unintentional injury. However, few studies have focused on whether risk of burn injury is relatively high among patients with ADHD. The aim of this study was to investigate whether ADHD affects the risk of burn injury. MATERIALS AND METHODS: Individuals aged <18 years with a current diagnosis of ADHD (N = 52,705) and age-, sex-, and other comorbidity-matched controls were selected from Taiwan's National Health Insurance Research Database for the period of January 1996 to December 2013. Burn injury was identified in both groups, and risk was evaluated using Cox proportional hazards models. We also explored the effects of age and sex on the association. RESULTS: We determined that patients with ADHD had an increased probability of burn injury compared with the control group (ADHD vs controls, 4.6% vs 2.6%; adjusted hazard ratio [aHR] = 1.78; 95% confidence interval [CI] = 1.66-1.90). The effect of ADHD on burn injury was more prominent among those aged <6 years (aHR = 1.96; 95% CI = 1.75-2.20) relative to those aged ≥6 years (aHR = 1.69; 95% CI = 1.56-1.83). Both sexes had similar risk profiles. CONCLUSION: The study findings contribute to the increasing body of evidence that ADHD is associated with proneness to burn injury, particularly in children aged <6 years.

Relevant Work Factors Associated with Voice Disorders in Early Childhood Teachers: A Comparison between Kindergarten and Elementary School Teachers in Yancheng, China.

Background: Early childhood teachers consist of kindergarten and elementary school teachers in the lower grades. Young children at school may increase the vocal load of these teachers. Therefore, the objectives of this study were to determine the prevalence of voice disorders and the associated factors in early childhood teachers, and to determine if differences exist between kindergarten and elementary school teachers. Method: A cross-sectional survey was performed in July 2019 as a network questionnaire. Through cluster sampling, teachers (n = 414) from all five public kindergartens (n = 211) in the urban area of Yancheng, China, and four public elementary schools (n = 203) in the same school district participated in this study. Multivariate logistic regression models were used to analyze the associations among the prevalence of voice disorders in the teachers, school type, and relevant factors. Results: Our results indicated, based on the Voice Handicap Index scale (VHI-10, China), that the prevalence of voice disorders in early childhood teachers was 59.7%, while that in elementary school teachers (65.5%) was significantly higher than that in kindergarten teachers (54.0%) during the previous semester. Contributing factors included daily class hours, classroom air humidity, and speaking loudly during teaching. Additionally, certain types of voice usage in teaching such as falsetto speak, speaking more than other teachers, not using vocal techniques, and habitual voice clearing, were significantly associated with voice disorders. Conclusion: Most early childhood teachers have voice disorders. Compared with the kindergarten teachers, the elementary school teachers experienced a significantly higher prevalence of voice disorders. Several factors among work organization, work environment, and types of voice usage in teaching were associated with the voice disorders in early childhood teachers. The finding suggests that voice training should be provided for early childhood teachers, classroom teaching time should be decreased, and the number of teachers in basic subjects should be increased in the lower grades of elementary schools.

Exploring prior diseases associated with incident late-onset Alzheimer's disease dementia.

Studies have identified prior conditions associated with late-onset Alzheimer's disease dementia (LOAD), but all prior diseases have rarely been screened simultaneously in the literature. Our objective in the present study was to identify prior conditions associated with LOAD and construct pathways for them. We conducted a population-based matched case-control study based on data collected in the National Health Insurance Research database of Taiwan and the Catastrophic Illness Certificate database for the years 1997-2013. Prior diseases definitions were based on the first three digits of the codes listed in the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Inclusion criteria required that each ICD-code existed for at least 1 year and incurred at least 2 outpatient visits or inpatient diagnosis. The case group comprised 4,600 patients newly diagnosed with LOAD in 2007-2013. The LOAD patients were matched by sex and age to obtain 4,600 controls. Using stepwise multivariate logistic regression analysis, diseases were screened for 1, 2 …, 9 years prior to the first diagnosis of LOAD. Path analysis was used to construct pathways between prior diseases and LOAD. Our results revealed that the following conditions were positively associated with the incidence of LOAD: anxiety (ICD-code 300), functional digestive disorder (ICD code 564), psychopathology-specific symptoms (ICD-code 307), disorders of the vestibular system (ICD-code 386), concussion (ICD-code 850), disorders of the urethra and urinary tract (ICD-code 599), disorders of refraction and accommodation (ICD-code 367), and hearing loss (ICD-code 389). A number of the prior diseases have previously been described in the literature in a manner identical to that in the present study. Our study supports the assertion that mental, hearing, vestibular system, and functional digestive disorders may play an important role in the pathogenesis of LOAD.

Association of Hearing Loss With Dementia.

Importance: Hearing loss (HL) may be a modifiable risk factor for dementia, and longitudinal studies are needed to examine the association of HL and dementia. Objective: To investigate the association of HL with incident dementia in Taiwanese adults in the general population. Design, Setting, and Participants: This population-based cohort study collected data from the National Health Insurance Research Database of Taiwan. Patients newly diagnosed with HL from January 1, 2000, through December 31, 2011 (n = 8135), constituted the exposed (HL) group. The HL group patients were matched by sex, age, residence, and insurance premium to individuals without HL (non-HL group) (n = 8135). Data were analyzed from January 1, 2000, to December 31, 2013. Exposure: Hearing loss defined according to International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. Main Outcomes and Measures: Dementia classified according to ICD-9-CM codes. Results: Of a total of 16 270 participants (9286 [57.1%] men; mean [SD] age, 65.2 [11.1] years), 1868 developed dementia. The dementia incidence rate in the HL group was higher than that in the non-HL group (19.38 [95% CI, 18.25-20.57] per 1000 person-years vs 13.98 [95% CI, 13.01-15.00] per 1000 person-years) during the follow-up period. In the fully adjusted multivariate Cox proportional hazards regression model applied for risk analysis, patients with HL had a significant risk of dementia (hazard ratio [HR], 1.17; 95% CI, 1.07-1.29; false discovery rate [FDR] P = .003). Subgroup analysis revealed that, among 3 age groups (45-64, 65-74, and ≥75 years), the group aged 45 to 64 years was associated with a risk of dementia (HR, 2.21 [95% CI, 1.57-3.12]; FDR P < .001). In sensitivity analysis, the presence of HL among those aged 45 to 64 years (HR, 1.40; 95% CI, 1.12-1.75; FDR P = .01) was associated with a risk of dementia. Conclusions and Relevance: In this study, hearing loss was positively associated with a risk of dementia, especially in patients aged 45 to 64 years. Hearing protection, screening, and treatment may be used as strategies for mitigating this potential risk factor.

Attention-Deficit/Hyperactivity Disorder and Mortality Risk in Taiwan.

Importance: Few studies have investigated levels of mortality in patients with attention-deficit/hyperactivity disorder (ADHD), and findings have been inconsistent and lacking information on specific causes of deaths. Objective: To investigate the association between ADHD and causes of death in Taiwan. Design, Setting, and Participants: A nationwide population-based cohort study was conducted using a cross-national Taiwanese registry. The ADHD group comprised 275 980 individuals aged 4 to 44 years with a new diagnosis between January 1, 2000, and December 31, 2012. All individuals with ADHD were compared with 1 931 860 sex- and age-matched controls without ADHD. Exposures: The association between ADHD and mortality was analyzed using a Cox regression model that controlled for sex, age, residence, insurance premium, outpatient visits, congenital anomaly, intellectual disability, depression disorder, autism, substance use disorder, conduct disorder, and oppositional defiant disorder. The analysis of suicide, unintentional injury, homicide, and natural-cause mortality was performed by a competing risk adjusted Cox regression controlling for other causes of mortality and potential confounding factors. Main Outcomes and Measures: Data on mortality from all causes, suicide, unintentional injury, homicide, and natural causes collected from a national mortality database. Results: There were 275 980 individuals with ADHD and 1 931 860 comparison individuals without ADHD in this study. Sex and age at index date were matched. The mean (SD) age was 9.61 (5.74) years for both groups. Most of the participants were male (209 406 in the ADHD group; 1 465 842 in the non-ADHD group; 75.88% for both groups). A total of 4321 participants from both cohorts died during the follow-up period (15.1 million person-years), including 727 (0.26%) from the ADHD group and 3594 (0.19%) from the non-ADHD group. Of those who died, 546 (75.1%) in the ADHD group and 2852 (79.4%) in the non-ADHD group were male. After adjusting for potential confounders, compared with the non-ADHD group, patients with ADHD showed higher overall mortality (adjusted hazard ratio, 1.07; 95% CI, 1.00-1.17) and higher injury-cause mortality from suicide (adjusted hazard ratio, 2.09; 95% CI, 1.62-2.71), unintentional injury (adjusted hazard ratio, 1.30; 95% CI, 1.10-1.52), and homicide (adjusted hazard ratio, 2.00; 95% CI, 1.09-3.68). No increased risk of natural-cause mortality was observed after adjustment. Conclusions and Relevance: In this study, ADHD was associated with higher injury-cause mortality, particularly that due to suicide, unintentional injury, and homicide. Although the risk of injury mortality was significantly higher in patients with ADHD than in the non-ADHD group, the absolute risk of mortality was low.

Type II diabetes mellitus and the incidence of amyotrophic lateral sclerosis.

OBJECTIVE: The aim of this study was to investigate the relationship between type II diabetes mellitus (T2DM) and ALS incidence using the National Health Insurance Research Database and Serious Disabling Disease database of Taiwan. METHODS: This was a population-based cohort study. The index date was the date of the first T2DM diagnosis + 365 days. We included T2DM patients diagnosis between 2000 and 2013 (n = 2,135,427). These patients were matched by sex, age, urbanization, and insurance premium at a ratio of 1:1 to include patients without diabetes mellitus. Competing risk-adjusted Cox regression analysis was performed to investigate the association between T2DM and the incidence of ALS. RESULTS: In the patients not stratified by age, T2DM was not associated with the incidence of ALS after controlling for confounding factors. The interaction test of age subgroup (< 55 and ≥ 55 years) and T2DM on ALS risk was significance (p < 0.001). Subgroup analysis showed that T2DM was negatively associated with ALS in patients whose age at the first T2DM diagnosis was ≥ 55 years. Among T2DM patients, T2DM combined with hypertension was negatively associated with ALS among patients whose age at the first T2DM diagnosis was ≥ 55 years. Among T2DM patients, T2DM combined with hyperlipidemia was positively associated with ALS among patients whose age at the first T2DM diagnosis was < 55 years. CONCLUSIONS: The late-onset of T2DM may exert negative association with ALS, especially when combined with hypertension. The early-onset of T2DM may exert positive association with ALS, especially when combined with hyperlipidemia.

Finding diseases associated with amyotrophic lateral sclerosis: a total population-based case-control study.

OBJECTIVE: To investigate diseases associated with amyotrophic lateral sclerosis (ALS) by using a total population-based medical database. METHODS: This study included 705 ALS patients aged older than 15 years diagnosed from January 1, 2007, to December 31, 2013, along with 14,100 controls matching in sex, age, residence, and insurance premium. Data from the National Health Insurance Research Database (NHIRD) and Serious Disabling Diseases (SDD) database in Taiwan were used to conduct a total population-based case-control study. Prior diseases were categorized as being diagnosed 1, 3, 5, 7, or 9 years before first ALS diagnosis. Chi-square or t test was used to examine differences in demographic characteristics between the new patients with ALS and controls. Previous diseases were screened using a conditional logistic regression model. Multivariate analysis was performed using stepwise selection to evaluate the association between these diseases and the risk of ALS. The path analysis was conducted to analyze the pathway between prior diseases and ALS. RESULTS: In total, 28 diseases were associated with ALS, including 17 positive associations and 11 negative associations. The path analysis revealed that the 11 negatively associated diseases could be attributed to diabetes mellitus and its comorbidities. The 17 positively associated diseases could be categorized as metabolic syndrome, neuroinflammation, head trauma, sports injuries, infections, and their comorbidities. CONCLUSIONS: Our results support the hypothesis that diseases developing prior to ALS diagnoses are hypermetabolic disorders. Hypometabolic disorders may have a beneficial effect on ALS incidence. Defective energy metabolism may play a role in ALS pathogenesis.

New use for old drugs: The protective effect of atypical antipsychotics on hepatocellular carcinoma.

It has been encouraged to use large existing data like insurance claims data to investigate the new indications of old drugs. New strategies of research are warranted to identify feasible drugs. We conducted a dual research model with a population-based case-control study using Taiwan's National Health Insurance Research Database and an in vitro study to investigate the association between atypical antipsychotic and Hepatocellular carcinoma (HCC) risk. The study herein consists of two components. The first is a population-based case-control study using existing data from the Taiwan National Health Insurance Research Database. The second component was an in vitro study in which HCC cell lines (Huh7 and Hep G2) were treated with risperidone, quetiapine and clozapine. after treatment of the foregoing antipsychotics, the HCC cell lines were assessed for cell proliferation, invasion and apoptosis. Multivariate conditional logistic regression analysis revealed that antipsychotic use was independently and inversely associated with HCC risk (adjusted odds-ratio [aOR]:0.85, 95% CI: 0.81-0.89). The protective effect was dose-dependent: compared to the low cumulative defined daily dose (cDDD) group (0-29 cDDD), the 30-89 cDDD and ≥90 cDDD groups were associated with significantly reduced risk for HCC (aOR: 0.56, 95% CI: 0.41-0.76; aOR: 0.37, 95% CI: 0.27-0.50, respectively). In vitro study results indicated that risperidone, quetiapine and clozapine significantly inhibited cell proliferation, invasion and induced apoptosis in human HCC cell lines. Our results herein suggested that antipsychotic use might reduce the risk of HCC and may provide evidence for new uses of old drugs.

Effects of physician's specialty on regular chronic kidney disease care in predialysis: A population-based cross-sectional study.

Late referral in chronic kidney disease (CKD) is associated with irregular care and poor prognosis. How the specialty of healthcare provider affect late referral and irregular CKD care remain unclear.We conducted a population-based cross-sectional study to include incident dialysis patients from 2002 to 2007 in Taiwan and observed for 1, 2, and 3 years before dialysis. The medical visits-related information was evaluated every 3 months, retrospectively. Irregular follow-up was defined as missing a follow-up during more than one interval every year.A total of 46,626 patients were included. At 1, 2, and 3 years prior to maintenance dialysis, 87%, 66%, and 50% of patients had regular medical visits; however, only 49%, 23%, and 12% had estimated glomerular filtration rate (eGFR) regularly monitored, respectively. Independent factors of less regular eGFR follow-up included age (adjusted odds ratio (OR) 0.995, 95% confidence interval 0.993-0.998), cardiac disorder (0.90, 0.82-0.99), and stroke (0.76, 0.69-0.84), as well as regular visits at some other specialties (adjusted OR range: from 0.77 to 0.88); whereas, independent factors of less regular visits at nephrology included diabetes mellitus (0.48, 0.46-0.51), cardiac disorder (0.61, 0.56-0.66), stroke (0.53, 0.48-0.58), and regular visits at any other specialty (adjusted OR range: from 0.22 to 0.78).Regular medical visits were quite common in late CKD patients, but they received regular eGFR measurement and visit at nephrology much less frequently. Physicians play a major role in the late referrals in CKD and its irregular care.

SSRIs associated with decreased risk of hepatocellular carcinoma: A population-based case-control study.

BACKGROUND: Hepatocellular carcinoma (HCC) is the second leading cancer-related cause of mortality worldwide. Antidepressants, especially selective serotonin reuptake inhibitors (SSRIs), are commonly used worldwide. Available evidence investigating the association between SSRIs use and HCC risk is limited. OBJECTIVE: The present study aimed to investigate if the effect of all kinds of SSRIs on HCC was the same or not using population-based study. METHODS: The nationwide population-based study herein using Taiwan's National Health Insurance Research Database included a total of 59 859 cases with HCC and 285 124 matched controls. Conditional logistic regression analyses were adjusted for confounding variables. RESULTS: All common kinds of SSRIs including fluoxetine, sertraline, paroxetine, citalopram, escitalopram, and fluvoxamine were associated with lower HCC risk, and the findings were dose-dependent (eg, fluoxetine: 1-28 DDD [defined daily dose]: adjusted odds ratio [aOR]: 0.81, 95% confidence interval [CI], 0.73-0.89; 29-365 DDD: aOR: 0.71, 95% CI, 0.64-0.79; and ≥366 DDD: aOR: 0.55, 95% CI, 0.45-0.67) (P for trend < .001). CONCLUSIONS: All kinds of SSRIs were associated with decreased risk of HCC.

Risk of ADHD After Multiple Exposures to General Anesthesia: A Nationwide Retrospective Cohort Study.

OBJECTIVE: To study the association between general anesthesia exposure before age 3 years and having a later ADHD diagnosis. METHOD: In a birth cohort, data were collected from a nationwide population database for children born between 1997 and 1999 who were exposed to general anesthesia before their third birthday. Age- and gender-matched enrollees without general anesthesia exposure were taken as the comparison. Groups were compared to identify the incidence of ADHD after age 4 and anesthesia-related predictive factors. RESULTS: Among the 1,146 exposed children, 74 ADHD cases were identified, and 158 ADHD cases were identified in 3,438 matched controls. After adjusting for comorbid conditions and possible confounding factors, if exposure on more than one occasion or ≥3 hr, an increased likelihood of having a later ADHD diagnosis was found (HR, 1.71 and 2.43, respectively). CONCLUSION: Children with multiple or ≥3 hr general anesthesia exposures before age 3 years have an increased likelihood of a later ADHD diagnosis.