Decisive gene strategy on osteoarthritis: a comprehensive whole-literature based approach for conclusive gene targets.

BACKGROUND: Previous meta-analyses only examined the association between single or several gene polymorphisms and osteoarthritis (OA), whereas no studies have concluded that there are existing all gene loci that associate with OA. OBJECTIVE: To assess whether a definite conclusion of the association between the gene loci and OA can be drawn. METHODS: Decisive gene strategy (DGS), a literature-based approach, was used to search PubMed, Embase, and Cochrane databases for all meta-analyses that associated gene polymorphisms and OA. Trial Sequential Analysis (TSA) examined the sufficiency of the cumulative sample size. Finally, we assessed the importance of gene loci in OA based on whether there were enough sample sizes and the heterogeneity of the literatures with I2 value. RESULTS: After excluding 179 irrelevant publications, 80 meta-analysis papers were recruited. Among Caucasians, SMAD3 rs12901499 (OR = 1.20, 95% CI: 1.12-1.29) was a risk factor with validation of sufficient sample sizes through TSA model. Among Asians, there were 3 gene loci risk factors with validation of sufficient sample sizes through TSA model: ESR1 rs2228480, SMAD3 rs12901499, and MMP-1 rs1799750 (OR = 1.35, 95% CI: 1.08-1.69; OR = 1.34, 95% CI: 1.07-1.69; OR = 1.43, 95% CI: 1.18-1.74, respectively). Besides, 3 gene loci, DVWA rs7639618, GDF5 rs143383, and VDR rs7975232 (OR = 0.78, 95% CI: 0.67-0.90; OR = 0.74, 95% CI: 0.67-0.81; OR = 0.56, 95% CI: 0.35-0.90, respectively) were identified as protective factors through TSA model. CONCLUSIONS: We used DGS to identify conclusive gene loci associated with OA. These findings provide implications of precision medicine in OA and may potentially advance genetic therapy.

Secular Increasing Trends in Female Thyroid Cancer Incidence in Taiwan.

BACKGROUND: Thyroid cancer incidence has increased globally in recent decades, especially in females, although its trends in Taiwan have not been studied extensively. This study aimed to investigate changes in female incidence and possible causes of thyroid cancer in Taiwan. METHODS: Using the Taiwan Cancer Registry (TCR) Database, age-standardized incidence rates, age-specific incidence rates and birth cohorts were calculated. Correlation between female thyroid cancer incidence and cohort fertility rates were examined. RESULTS: Thyroid cancer incidence increased in Taiwanese female, with age-adjusted rates per 100,000 people increasing from 7.37 during 1995-1999 to 20.53 during 2015-2019; the annual percentage change (APC) was 5.9% (95% CI, 5.3-6.5). Age-specific incidence rates increased with age, with peak rates occurring at younger ages. The APCs in the 50-54 age group were the highest (6.8%, 95% CI, 6.1-7.5). Incidence rates also increased with later birth cohorts. We observed a significant negative correlation between thyroid cancer incidence and fertility rates in the same birth cohort. CONCLUSIONS: We hypothesize that overdiagnosis may be a main reason for the rapidly increasing thyroid cancer incidence in Taiwanese females. Notably, we observed a strong negative correlation between fertility and thyroid cancer incidence. However, our study is limited by the absence of individual-level cancer data in the TCR database. These associations with fertility will be an important subject for future thyroid cancer research.

Enhancing anatomy education through cooperative learning: harnessing virtual reality for effective gross anatomy learning.

The advent of virtual reality (VR) in education offers unique possibilities for facilitating cooperative learning strategies, particularly in fields demanding intricate spatial understanding, such as gross anatomy. This study investigates the impact of integrating cooperative learning strategies within a VR-based gross anatomy curriculum, focusing on enhancing students' anatomy knowledge and skills. We analyzed the performance of two cohorts of first-year nursing students across five semesters (2016-2020), where traditional learning methods were used in the first three semesters (2016-2018), and a VR-based cooperative learning approach was adopted in the last two semesters (2019-2020). Our findings suggest that the VR-based cooperative learning group achieved significantly higher scores in their gross anatomy laboratory courses compared to their counterparts learning through traditional methods. This research provides valuable insights into how the integration of VR technology and cooperative learning strategies can not only enhance learning outcomes but also improve the VR learning experience by reducing motion sickness. It accentuates the potential of VR-based cooperative learning as an impactful educational tool in anatomy education. Future research should further explore the optimal integration of VR and cooperative learning strategies in diverse course types and their potential to enhance educational outcomes and the learning experience.

High-Fat Diet Exacerbates Autistic-Like Restricted Repetitive Behaviors and Social Abnormalities in CC2D1A Conditional Knockout Mice.

Autism spectrum disorder (ASD) represents a heterogeneous group of neurodevelopmental disorders characterized by deficits in social communication, social interaction, and the presence of restricted repetitive behaviors. The cause of ASD involves complex interactions between genetic and environmental factors. Haploinsufficiency of the Coiled-coil and C2 domain containing 1A (Cc2d1a) gene is causally linked to ASD, and obesity has been associated with worse outcomes for ASD. High-fat diet (HFD) feeding leads to the development of obesity and metabolic dysfunction; however, the effect of HFD on pre-existing autistic-like phenotypes remains to be clarified. Here, we report that male Cc2d1a conditional knockout (cKO) mice fed with HFD, from weaning onwards and throughout the experimental period, show a marked aggravation in autistic-like phenotypes, manifested in increased restricted repetitive behaviors and impaired performance in the preference for social novelty, but not in sociability and cognitive impairments assessed using the object location memory, novel object recognition, and Morris water maze tests. HFD feeding also results in increased numbers of reactive microglia and astrocytes, and exacerbates reductions in dendritic complexity and spine density of hippocampal CA1 pyramidal neurons. Furthermore, we demonstrate that chronic treatment with minocycline, a semisynthetic tetracycline-derived antibiotic, rescues the observed behavioral and morphological deficits in Cc2d1a cKO mice fed with HFD. Collectively, these findings highlight an aggravating role of HFD in pre-existing autistic-like phenotypes and suggest that minocycline treatment can alleviate abnormal neuronal morphology and behavioral symptoms associated with ASD resulted from the interplay between genetic and environmental risk factors.

Metformin, Statin Use, and Female Colorectal Cancer: A Population-Based Cohort Study in Taiwan.

In the last few years, the incidence of colorectal cancer (CRC) in women has gradually increased. However, epidemiological studies on the relationship between type II diabetes mellitus (T2DM) and female CRC and the effect of metformin or statins on female CRC are insufficient. To determine their association, we conducted a population-based cohort study on women in Taiwan. We collected data on a total of 396,521 women aged 40 to 64 years old from 1 January 2007 to 31 December 2009 from the National Health Insurance Research Database. We followed up on all participants in the cohort until the occurrence of CRC, the date for all death, or 31 December 2015. Full development of CRC was identified using the International Classification of Disease (ICD), 9th Revision, code 153. We estimated hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using the Cox proportional hazards model. Both metformin (adjusted hazard ratio, aHR = 1.12; 95% CI: 0.934-1.335, p = 0.227) and statin (aHR = 1.03; 95% CI: 0.906-1.172, p = 0.645) use showed no association with female CRC in a multivariate analysis. The findings indicate that metformin and statin use showed no protective effect against female colorectal cancer (CRC). An additional randomized trial is necessary to investigate the effect of metformin and statin use in CRC prevention.

Risk Factors for Female Breast Cancer: A Population Cohort Study.

BACKGROUND: The incidence of female BC among the Eastern and Southeastern Asian populations has gradually increased in recent years. However, epidemiological studies on the relationship between a sedentary lifestyle and female BC are insufficient. In order to determine the association between this lifestyle and the incidence of female BC, we conducted a population-based cohort study on women in Taiwan. METHODS: We followed a prospective cohort of 5879 women aged 30 years and over enrolled in the 2001 National Health Interview Survey (NHIS), who developed female BC over a period of 72,453 person years, and we estimated the hazard ratios (HRs) and corresponding 95% confidence intervals (CIs) using the Cox proportional hazards model. RESULTS: RFs associated with female BC incidence included parity (adjusted HR = 0.63; 95% CI: 0.44-0.91), body mass index (adjusted HR = 1.34; 95% CI: 1.04-1.71), and ≥3 h/day spent sitting (adjusted HR = 1.89; 95% CI: 1.08-3.32). The incidence of female BC in participants who sat for ≥3 h/day and consumed sugary drinks was 2.5 times greater than that in those who sat for <3 h/day and did not consume sugary drinks (adjusted HR = 2.51; 95% CI: 1.01-6.23). CONCLUSIONS: The findings of this study indicate that sedentary behavior and sugary drink intake may increase the risk of developing female BC. These are modifiable RFs; therefore, a healthy lifestyle and diet can reduce the incidence of female BC.

Sedative and Immunosuppressive Effects of Dexmedetomidine in Transplantation.

Dexmedetomidine, an α2-adrenergic receptor agonist, is used as an anti-anxiety medication. It exerts a cholinergic effect, thereby reducing the release of tumor necrosis factor alpha (TNF-α). We hypothesized that the use of dexmedetomidine as a sedative agent in transplantation would also protect allografts. We examined our patients who underwent living donor liver transplantation. Subsequently, we generated a series of mouse models to investigate the effect of dexmedetomidine on sedation-based tolerance post transplantation. A total of 49 liver recipients were enrolled in this study, of which 23 (47%) were administered dexmedetomidine through 24 h infusion on postoperative day 1. A trend toward the improvement of hepatocyte injury along with better liver function was observed in the dexmedetomidine-treated group during the first postoperative week. In animal models, dexmedetomidine inhibited the proliferation of CD4+ and CD8+ T cells and TNF-α production in a dose-dependent manner. We used dexmedetomidine to treat skin-transplanted mice and observed a significantly prolonged graft survival in mice that were administered a higher dose of dexmedetomidine. Our results revealed that dexmedetomidine exerts a dual effect of sedation and immunosuppression. This light-sedation approach will not only make patients calmer in the intensive care unit but also protect allografts from injury.

The Decisive Case-Control Study Elaborates the Null Association between ESR1 XbaI and Osteoarthritis in Asians: A Case-Control Study and Meta-Analysis.

(1) Background: The prevalence of knee osteoarthritis (OA) in women is significantly higher than in men. The estrogen receptor α (ERα) has been considered to play a key role due to a large gender difference in its expression. ERα is encoded by the gene estrogen receptor 1 (ESR1), which is widely studied to explore the gender difference in knee OA. Several polymorphisms in ESR1 [PvuII (rs2234693) and BtgI (rs2228480)] were confirmed as the risk factors of OA. However, the evidence of the last widely investigated polymorphism, ESR1 Xbal (rs9340799), is still insufficient for concluding its effect on knee OA. (2) Objective: This study proposed a case-control study to investigate the association between ESR1 Xbal and knee OA. Moreover, a meta-analysis and trial sequential analysis (TSA) were conducted to enlarge the sample size for obtaining a conclusive evidence. (3) Methods: In total, 497 knee OA cases and 473 healthy controls were recruited between March 2015 and July 2018. The Kellgren-Lawrence grading system was used to identify the knee OA cases. To improve the evidence level of our study, we conducted a meta-analysis including the related studies published up until December 2018 from PubMed, Embase, and previous meta-analysis. The results are expressed as odds ratios (ORs) with corresponding 95% confidence intervals (CI) for evaluating the effect of this polymorphism on knee OA risk. TSA was used to estimate the sample sizes required in this issue. (4) Results: We found non-significant association between the G allele and knee OA [Crude-OR: 0.97 (95% CI: 0.78-1.20) and adjusted-OR: 0.90 (95% CI: 0.71-1.15) in allele model] in the present case-control study, and the analysis of other genetic models showed a similar trend. After including six published studies and our case-control studies, the current evidence with 3174 Asians showed the conclusively null association between ESR1 XbaI and knee OA [OR: 0.78 (95% CI: 0.59-1.04)] with a high heterogeneity (I2: 78%). The result of Caucasians also concluded the null association [OR: 1.05 (95% CI: 0.56-1.95), I2: 87%]. (5) Conclusions: The association between ESR1 XbaI and knee OA was not similar with other polymorphisms in ESR1, which is not a causal relationship. This study integrated all current evidence to elaborate this conclusion for suggesting no necessity of future studies.

Possible increased risk of colonic diverticular disease from alcohol intoxication or abuse.

Alcohol consumption has been suggested as a potential risk factor for diverticular diseases. This study investigated the association between alcohol intoxication or abuse and colonic diverticular disease (CDD).Using the National Health Insurance Research Database of Taiwan from January 1, 2000, to December 31, 2008, 51, 866 subjects newly diagnosed with alcohol intoxication were enrolled in this study as the alcohol intoxication cohort. The control (nonalcohol intoxication) cohort was frequency-matched 1:4 by age, sex and index year. Data were analyzed using a Cox proportional hazards model.The overall incidence of CDD (per 10,000 person-years) for the alcohol intoxication and control cohorts was 16.4 and 3.46, respectively. Compared with patients in the control cohort (95% confidence interval [CI] = 2.76-3.74), those with alcohol intoxication exhibited a 3.21-fold risk of CDD; the risk was particularly higher in male patients (adjusted hazard ratio [aHR] = 3.19, 95% CI = 2.72-3.74) and in those aged <45 years (aHR = 4.95, 95% CI = 3.91-6.27). The alcohol intoxication still had higher risk of CDD than nonalcohol intoxication, regardless of subjects without comorbidity (aHR = 3.38, 95% CI = 2.77-4.11) or with (aHR = 2.85, 95% CI = 2.25-3.61).There was a significant relationship between alcohol intoxication or abuse and CDD.

Increased risk of developing psychiatric disorders in children with attention deficit and hyperactivity disorder (ADHD) receiving sensory integration therapy: a population-based cohort study.

Parents of children with attention deficit hyperactivity disorder (ADHD) have been found to prefer sensory integration (SI) training rather than guideline-recommended ADHD treatment. This study investigated whether SI intervention for children with ADHD was associated with a reduced risk of subsequent mental disorders. From children < 8-years-old newly diagnosed with ADHD in a nationwide population-based dataset, we established a SI cohort and a non-SI cohort (N =  1945) matched by propensity score. Incidence and hazard ratios of subsequent psychiatric disorders were compared after a maximum follow-up of 9 years. The incidence of psychiatric disorders was 1.4-fold greater in the SI cohort, with an adjusted hazard ratio of 1.41 (95% confidence interval 1.20-1.67), comparing to the non-SI cohort. Risks were elevated for emotional disturbances, conduct disorders, and adjustment disorders independent of age, gender, or comorbidity. Among children with only psychosocial intervention, the incidence of psychiatric disorders was 3.5-fold greater in the SI cohort than in the non-SI cohort. To our knowledge, this is the first study to report an increased risk of developing psychiatric disorders for children with ADHD who received SI compared to those who did not. Potential adverse effects of SI for ADHD children should be carefully examined and discussed before practice.

Increased Risk for Hip Fractures among Patients with Cholangitis: A Nationwide Population-Based Study.

BACKGROUND: Cholangitis is the infectious disease involving the biliary tract, which may induce systemic inflammation. Bone loss is a well-known sequelae after systemic inflammatory disease, and one grave complication after osteoporosis is hip fracture. We want to know whether cholangitis can contribute to increased risk of hip fracture. METHODS: All the patients diagnosed with cholangitis since January 1, 2001, to December 31, 2009, were assessed. All the subjects with cancer history, traumatic accident, and previous fracture were excluded. We selected the controls without cholangitis and matched the controls to cholangitis patients by age, sex, osteoporosis, and the use of steroid for more than 30 days by approximately 1:4 ratio. RESULTS: There were 2735 subjects in the cholangitis cohort and 10915 in the noncholangitis cohort. There were 101 hip fractures in the cholangitis cohort with the incidence density of 7.58 per 1000 person-years. As for the noncholangitis cohort, 366 individuals suffered from hip fracture with the incidence density of 5.86 per 1000 person-years. The risk of hip fracture was higher in the cholangitis cohort with a 1.29-fold increased risk than the noncholangitis cohort (hazard ratio = 1.29, 95% confidence interval = 1.03-1.61). The association between cholangitis and the hip fracture was more prominent among subjects less than 65 years (hazard ratio = 2.65, 95% confidence interval =1.30-5.39) and the subjects without comorbidities (hazard ratio = 3.01, 95% confidence interval = 1.42-6.41). CONCLUSIONS: Cholangitis is associated with higher risk for hip fracture, especially among young subjects free from medical comorbidities.

Alcohol use disorder increases the risk of necrotizing fasciitis: A nationwide retrospective cohort study.

This nationwide retrospective cohort study determined the association between alcohol use disorder (AUD) and the risk of necrotizing fasciitis (NF).This study used health insurance claims data of 52,212 in-patients with AUD and 208,848 controls randomly frequency-matched by age and sex at a 1:4 ratio. The AUD cohort included patients newly diagnosed with AUD between January 1, 2000 and December 31, 2008. The NF event occurrence was observed until December 31, 2011. We used the Kaplan-Meier method to present the cumulative incidence curve and Cox proportional hazard models to depict the risk of NF in patients with AUD.The incidence of NF was 19.4 per 10,000 person-years in the AUD cohort, which was nearly 7.73-fold higher than that in the comparison cohort (2.54 per 10,000 person-years). After adjustment for age, sex, and comorbidities, the patients with AUD exhibited a 3.55-fold higher risk of NF than did the controls (hazard ratio [HR] = 3.55, 95% confidence interval [CI] = 3.00-4.20). Nevertheless, in the AUD groups without any comorbidity, patients with AUD exhibited a significant 15.2-fold higher risk of NF than did the comparison cohort (HR = 15.2, 95% CI = 10.9-21.3). Moreover, the adjusted HRs of NF risk with respect to the severity of AUD were 2.15 (95% CI = 1.76-2.62), 4.54 (95% CI = 3.67-5.62), and 10.7 (95% CI = 8.66-13.2) for mild, moderate, and severe AUD, respectively.This study indicated that AUD should be considered an independent and significant risk factor for NF.

High risk of developing subsequent epilepsy in patients with sleep-disordered breathing.

PURPOSE: Sleep-disordered breathing (SDB) is often associated with other medical disorders. Whether SDB interacts with other factors for developing subsequent epilepsy remains unclear. METHODS: This population-based cohort study was conducted using the National Health Insurance Research Database of Taiwan. Patients aged >20 years and diagnosed with SDB between 2000 and 2010 comprised the SDB cohort (n = 138,507), and their data were compared with those of the comparison cohort (n = 138,507). The adjusted hazard ratio (aHR) for epilepsy was calculated using a multivariate Cox proportional hazards model. RESULTS: The SDB cohort had an increased risk of epilepsy (aHR = 1.50, 95% confidence interval [CI] = 1.36-1.66). The sex-stratified analysis revealed a significant adjusted hazard ratio (aHR) for epilepsy with a 1.51-fold higher risk for female patients, and also a significantly 1.49-fold higher risk for male patients in the SDB cohort. Although epilepsy incidence increased with age in both cohorts, different age groups in the SDB cohort all had a significantly higher risk of developing epilepsy than comparison cohort. CONCLUSION: This population-based cohort study indicates that patients with SDB are at a high risk of developing subsequent epilepsy, in both sexes and all age groups.

Selective Serotonin Reuptake Inhibitors and Poststroke Epilepsy: A Population-Based Nationwide Study.

OBJECTIVE: To investigate the effects of selective serotonin reuptake inhibitors (SSRIs) on poststroke epilepsy in a population-based nationwide study. PATIENTS AND METHODS: The SSRI group included patients who received a stroke diagnosis from January 1, 2000, through December 31, 2009, and were prescribed SSRIs after stroke. The non-SSRI group enrolled patients with stroke who were not prescribed SSRIs from the Taiwan National Health Insurance Research Database and used propensity score matching based on the index year, duration time, sex, age, type of stroke, and duration of hospitalization. Cox proportional hazards models were used to estimate the risk of epilepsy between the SSRI and comparison groups. RESULTS: A total of 4688 patients with stroke (2344 in each of the SSRI and non-SSRI cohorts) were enrolled. The cumulative incidence of epilepsy in the SSRI group was significantly higher than that in the comparison group (log-rank P<.001). In the SSRI group, the risk of poststroke epilepsy increased 2.45-fold (95% CI, 1.69- to 3.57-fold) compared with that in the comparison group. Furthermore, the risk of poststroke epilepsy increased with the defined daily dose of SSRIs. For patients with ischemic stroke, SSRIs users had a 2.74-fold higher risk of epilepsy than non users (95% CI, 1.79- to 4.22-fold). CONCLUSION: In this study, SSRI users had a higher risk of poststroke epilepsy than nonusers. Further study is warranted to investigate the causal relationship between SSRI exposure and poststroke epilepsy.

Female schizophrenia patients and risk of breast cancer: A population-based cohort study.

OBJECTIVE: Breast cancer is the most common type of cancer in women. This population-based cohort study aimed to examine the association between breast cancer in female schizophrenia patients and its association with the use of antipsychotics drugs. METHODS: All study subjects were selected from the Taiwan Insurance Claims Data (1998-2008). We compared the risk for breast cancer between female schizophrenia patients receiving antipsychotics (n=29,641) with female patients without any serious mental illnesses nor receiving antipsychotic drugs (n=59,282). We also compared between patients on 1) first-generation antipsychotics (FGAs) alone; 2) combination of first and second generation antipsychotics (SGAs); and 3) SGAs alone. We then stratified those on SGAs into two subgroups according to their prolactin-elevating properties: risperidone (RIS), paliperidone (PAL) or amisulpride (AMI) and all other SGAs. RESULTS: After adjusting for confounding factors, the risk of breast cancer in female schizophrenia patients was 1.94 higher than the non-schizophrenia cohort (aHR: 1.94, 95% CI: 1.43-2.63). Schizophrenia patients receiving a combination of FGAs and SGAs had a slightly higher risk of breast cancer than non-schizophrenic patients (aHR: 2.17, 95% CI: 1.56-3.01). Patients on RIS, PAL, and AMI had a 1.96-fold risk of breast cancer compared to the non-schizophrenic cohort (95% CI: 1.36-2.82). CONCLUSIONS: This study raises awareness among both clinicians and patients about the importance of breast cancer screening and the promotion of healthy lifestyle choices. Due to the nature of our database, confounding factors - such as parity, obesity, hormone therapy, and smoking - could not be controlled for.

Association between use of short-acting benzodiazepines and migraine occurrence: a nationwide population-based case-control study.

AIM: To evaluate the association between using benzodiazepines (BZDs) with short- or long-acting durations and migraine occurrence. METHODS: The migraine group comprised 9616 subjects older than 20 years and newly diagnosed with migraine between 2005 and 2011, and the comparison group comprised 38,464 subjects without migraine. The BZDs used in the subjects were dichotomously defined as short-acting (half-life ≤24 h) and long-acting substances. A logistic regression model was used to calculate the odds ratio (OR) of migraine associated with BZD exposure and other diseases. RESULTS: The adjusted OR of migraine associated with BZD exposure was 1.73 (95% confidence interval [CI] = 1.63-1.84). Either exposure to a short-acting BZD alone or using it combining with a long-acting BZD had significant higher risks of migraine (adjusted OR = 1.69, 95% CI = 1.59-1.80; adjusted OR = 2.06, 95% CI = 1.91-2.24, respectively), whereas only long-acting BZD use was not associated with an increase of migraine. Meanwhile, sleep disorders, anxiety, and stroke were strongly associated with migraine (adjusted OR = 2.00, 1.91, and 1.57, respectively). CONCLUSIONS: We observed a significant increase of migraine occurrence in subjects using short-acting BZDs, either alone or in combination with long-acting ones.

Male, old age and low income to predispose epilepsy in migraineurs.

BACKGROUND: This study investigated whether sex, age, income and any comorbidity affect subsequent epilepsy development in migraineurs. MATERIALS AND METHODS: A total of 4915 men diagnosed with migraine who were aged older than 20 years were identified as the study cohort. A total of 4882 female migraineurs were included in the comparison cohort. We calculated the adjusted hazard ratio (aHR) for the risk of epilepsy in the two cohorts after adjustment for age and comorbidity. Kaplan-Meier analysis was used to analyse the cumulative epilepsy incidence, and the log-rank test was used to estimate the differences between the two cumulative incidence curves. RESULTS: The risk of epilepsy was 2·31-fold higher in male migraineurs than in female migraineurs. The income-specific analysis showed that the risk of epilepsy was high in migraineurs with a low monthly income [aHR: 2·73 for 15 000-25 000 new Taiwan dollar (NTD; approximately 500-833 USD) and aHR: 2·71 for < 15 000 NTD]. Among patients with one or more comorbidity, a 2·48-fold (95% confidence interval: 1·65-3·74) high risk of epilepsy was noted in male migraineurs, regardless of the presence of head injury. Additional analyses revealed that male migraineurs aged 65 years or older had the highest risk of epilepsy. CONCLUSION: Migraineurs have an increased risk of subsequent epilepsy. Male sex, old age and low income may interact with migraine and result in a high risk of epilepsy in migraineurs.

Association of Respiratory Tuberculosis with Incident Bone Fracture: Bridging the Tuberculosis Airway Infection and the Osteoporotic Bone.

OBJECTIVE: The relationship between respiratory tuberculosis (RT) and incident fragility fracture and osteoporosis/fragility fracture in the general population is not well determined; therefore, we conducted a nationwide cohort study to investigate this relationship. METHODS: We used the National Health Insurance Research Database of Taiwan to identify 6612 newly diagnosed patients with RT (RT cohort) and 13220 patients without RT (non-RT cohort) from 1999 to 2005. The mean durations of follow-up were (6.73 ± 4.00 years, 8.11 ± 3.24 years) in the (RT cohort, non- RT cohort); respectively. The occurrence of incident fragility fracture and osteoporosis/fragility fracture were followed up until the end of 2011. The adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) and 98% CIs of incident fragility fracture and osteoporosis/fragility fracture were estimated using the multivariable Cox proportional hazard model after adjusting for age, sex, occupation, drug use, and comorbidities. RESULTS: A Cox proportional hazards regression analysis was performed and showed the aHRs of [incident fragility fracture; osteoporosis/fragility fracture] were [1.69 (95% CI = 1.26-2.28, 98% CI = 1.18-2.44); 1.42 (95% CI = 1.25-1.61, 98% CI = 1.21-1.65)] between the RT and non-RT cohorts. Regarding the sex, the aHRs of the [incident fragility fracture; osteoporosis / fragility fracture] were [1.57 (98% CI = 1.10-2.23, 98% CI = 1.02-2.41); 1.15 (95% CI = 0.97-1.36, 98% CI = 0.94-1.41)] in the men. The aHRs of the RT cohort without oral steroid use in the [incident fragility fracture; osteoporosis / fragility fracture] were [1.87 (95% CI = 1.20-2.90, 98% CI = 1.09-3.19); 1.41 (95% CI = 1.19-1.67, 98% CI = 1.14-1.74)]. CONCLUSION: The RT associated with the incident fragility fracture, either in men or absence of oral steroid use.

Increased risk of a suicide event in patients with primary fibromyalgia and in fibromyalgia patients with concomitant comorbidities: A nationwide population-based cohort study.

An increased risk of suicide ideation and death has been reported in patients with fibromyalgia. This study aimed to evaluate the risk of a suicide event in patients with primary fibromyalgia and in fibromyalgia patients with comorbidities. We used the Longitudinal Health Insurance Database, a subset of the national insurance claim dataset, which enrolled 1 million Taiwanese people from 2000 to 2005, to identify 95,150 patients with incident fibromyalgia (ICD-9-CM 729.0-729.1) and 190,299 reference subjects matched by sex, age, and index date of diagnosis, with a mean of 8.46 ±â€Š2.37 years of follow-up until 2011. The risk of a suicide event (ICD-9-CM, External-Cause Codes 950-959) was analyzed with a Cox proportional hazards model. Stratification analysis was performed by separating fibromyalgia patients and reference subjects with respect to each comorbidity to determine the risk of suicide in fibromyalgia patients with or without comorbidity relative to subjects who had neither fibromyalgia nor comorbidity. In this Taiwanese dataset, there were 347 suicide events in patients with fibromyalgia (4.16 per 10 person-years) and 424 in matched reference subjects (2.63 per 10 person-years) with a significant crude hazard ratio (HR) of 1.58 (95% confidence interval [CI] 1.38-1.83) and an adjusted HR of 1.38 (95% CI 1.17-1.71) for fibromyalgia patients relative to the matched reference subjects. According to the 2 × 2 stratification analysis, we found that fibromyalgia patients without comorbidity had an independent but mild risk of a suicide event with adjusted HRs ranging from 1.33 to 1.69 relative to subjects with neither fibromyalgia nor comorbidity. Meanwhile, fibromyalgia patients with comorbidity led to a markedly enhanced risk of a suicide event relative to the matched reference subjects, with adjusted HRs ranging from 1.51 to 8.23. Our analysis confirmed a mild-to-moderate risk of a suicide event in patients with primary fibromyalgia. Attention should be paid to the prevention of suicide in fibromyalgia patients with concomitant comorbidities.

Effect of Alcoholic Intoxication on the Risk of Inflammatory Bowel Disease: A Nationwide Retrospective Cohort Study.

PURPOSE: This study investigated whether alcoholic intoxication (AI) increases the risk of inflammatory bowel disease (IBD) by using a population-based database in Taiwan. METHODS: This retrospective matched-cohort study included 57 611 inpatients with new-onset AI (AI cohort) and 230 444 randomly selected controls (non-AI cohort). Each patient was monitored for 10 years to individually identify those who were subsequently diagnosed with Crohn disease (CD) and ulcerative colitis (UC) during the follow-up period. Cox proportional hazard regression analysis was conducted to determine the risk of IBD in patients with AI compared with controls without AI. RESULTS: The incidence rate of IBD during the 10-year follow-up period was 2.69 per 1 000 person-years and 0.49 per 1 000 person-years in the AI and non-AI cohorts, respectively. After adjustment for age, sex, and comorbidity, the AI cohort exhibited a 3.17-fold increased risk of IBD compared with the non-AI cohort (hazard ratio [HR] = 3.17, 95% confidence interval [CI] = 2.19-4.58). Compared with the non-AI cohort, the HRs of CD and UC were 4.40 and 2.33 for the AI cohort, respectively. After stratification for the severity of AI according to the duration of hospital stay, the adjusted HRs exhibited a significant correlation with the severity; the HRs of IBD were 1.76, 6.83, and 19.9 for patients with mild, moderate, and severe AI, respectively (p for the trend < .0001). CONCLUSION: The risk of IBD was higher in patients with AI and increased with the length of hospital stay.