Sex-specific incidence of hepatitis B virus flares among Bcr-Abl tyrosine kinase inhibitor users in Taiwan.

BACKGROUND: The use of Bcr-Abl TKI was found to be associated with hepatitis B (HBV) flares, with a more profound risk observed in females. This study was conducted to characterize the clinical features of patients with HBV flare among Bcr-Abl TKI users, to estimate sex-specific incidence rates of HBV flare, and to evaluate potential cumulative effect of Bcr-Abl TKI. METHODS: Bcr-Abl TKI users with chronic HBV infection were identified from Taiwan's National Health Insurance database. The HBV flare cases were identified within the cohort. Incidence rates of HBV flare between men and women were assessed. Nested case-control analysis was used to evaluate the cumulative effect of Bcr-Abl TKI use on HBV flare. RESULTS: Among 415 patients with chronic HBV infection treated with Bcr-Abl TKI from 2005 through 2018, 45 flare cases (28 males and 17 females) were identified. Days between Bcr-Abl TKI initiation and HBV flare was 319 days in women compared to 610 days in men. 66.7% of the flares occurred during TKI therapy. Twelve of the 45 patients died, half of them died around 6 months after hepatitis B flare. Incidence rates of HBV flare were 2.34 and 3.33 per 100 person-years in males and females, respectively. Higher incidence was observed among patients with chronic myeloid leukemia. Cumulative effect of Bcr-Abl TKI on HBV flare was not observed. CONCLUSION: Approximately 10% of HBV carriers who used Bcr-Abl TKI experienced HBV flare in Taiwan. The risk was higher in women and among patients with chronic myeloid leukemia.

Glucose metabolic heterogeneity correlates with pathological features and improves survival stratification of resectable lung adenocarcinoma.

OBJECTIVE: We investigated whether glycolytic heterogeneity correlated with histopathology, and further stratified the survival outcomes pertaining to resectable lung adenocarcinoma. METHODS: We retrospectively analyzed the 18F-fluorodeoxyglucose positron emission tomography-derived entropy and histopathology from 128 patients who had undergone curative surgery for lung adenocarcinoma. Disease-free survival (DFS) and overall survival (OS) were analyzed using univariate and multivariate Cox regression models. Independent predictors were used to construct survival prediction models. RESULTS: Entropy significantly correlated with histopathology, including tumor grades, lympho-vascular invasion, and visceral pleural invasion. Furthermore, entropy was an independent predictor of unfavorable DFS (p = 0.031) and OS (p = 0.004), while pathological nodal metastasis independently predicted DFS (p = 0.009). Our entropy-based models outperformed the traditional staging system (c-index = 0.694 versus 0.636, p = 0.010 for DFS; c-index = 0.704 versus 0.630, p = 0.233 for OS). The models provided further survival stratification in subgroups comprising different tumor grades (DFS: HR = 2.065, 1.315, and 1.408 for grade 1-3, p = 0.004, 0.001, and 0.039, respectively; OS: HR = 25.557, 6.484, and 2.570, for grade 1-3, p = 0.006, < 0.001, and = 0.224, respectively). CONCLUSION: The glycolytic heterogeneity portrayed by entropy is associated with aggressive histopathological characteristics. The proposed entropy-based models may provide more sophisticated survival stratification in addition to histopathology and may enable personalized treatment strategies for resectable lung cancer.

A Dietitian-Led Vegan Program May Improve GlycA, and Other Novel and Traditional Cardiometabolic Risk Factors in Patients With Dyslipidemia: A Pilot Study.

Background: Systematic inflammation and lipid profiles are two major therapeutic targets for cardiovascular diseases. The effect of a nutritionally balanced vegan diet on systematic inflammation and lipoprotein subclass awaits further examination. Objective: To investigate the change in novel and traditional cardiometabolic risk factors before and after a dietitian-led vegan program, and to test the bioavailability of vitamin B12 in Taiwanese purple laver as part of a vegan diet. Design: A one-arm pilot intervention study. Participants/Setting: Nine patients with dyslipidemia participated in this 12-week vegan program. Main Outcome Measures: Nuclear Magnetic Resonance (NMR) detected GlycA signals (systematic inflammation) and lipoprotein subclass (atherogenicity); trimethylamine N-oxide (TMAO); and other cardiometabolic risk factors. Statistical Analyses Performed: Wilcoxon signed-rank test. Results: In this 12-week vegan intervention emphasizing whole foods, systematic inflammation improved as indicated by a reduction in GlycA (median: -23 µmol/L, p = 0.01). LDL-c (low-density lipoprotein cholesterol) (median -24 mg/dl, p = 0.04) and LDL-p (low-density lipoprotein particles) (median -75 nmol/L, p = 0.02) both decreased significantly. VLDL (very-low-density lipoprotein) and chylomicron particles showed a decreasing trend (-23.6 nmol/L, p = 0.05). Without caloric restriction, body mass index (BMI) (-0.7 kg/m2, p = 0.03), waist circumferences (-2.0 cm, p < 0.001), HbA1c (-0.2%, p = 0.02), and (HOMA-IR) homeostatic model assessment for insulin resistance (-0.7, p = 0.04) have all improved. The change in the TMAO and vitamin B12 status as measured by holo-transcobalamin appeared to depend on baseline diets, TMAO, and vitamin B12 status. Conclusions: A dietitian-led vegan program may improve systematic inflammation and other novel and traditional cardiometabolic risk factors in high-risk individuals.

Tumor glycolytic heterogeneity improves detection of regional nodal metastasis in patients with lung adenocarcinoma.

OBJECTIVE: The diagnostic performance of 18F-FDG PET for detecting regional lymph node metastasis in resectable lung cancer is variable, and its sensitivity for adenocarcinoma is even lower. We aimed to evaluate the value of 18F-FDG PET-derived features in predicting pathological lymph node metastasis in patients with lung adenocarcinoma. METHODS: We retrospectively analyzed pretreatment 18F-FDG PET-derived features of 126 lung adenocarcinoma patients who underwent curative surgery. A logistic regression model was used to analyze the association between study variables and pathological regional lymph node status obtained from the curative surgery. Furthermore, Cox regression analysis was used to test the effect of the study variables on survival outcomes, including disease-free survival (DFS) and overall survival (OS). RESULTS: The primary tumor entropy (OR = 1.7, p = 0.014) and visual interpretation of regional nodes via 18F-FDG PET (OR = 2.5, p = 0.026) independently predicted pathological regional lymph node metastasis. The areas under the receiver-operating-characteristic curves were 0.631, 0.671, and 0.711 for visual interpretation, primary tumor entropy, and their combination, respectively. Based on visual interpretation, a primary tumor entropy ≥ 3.0 improved the positive predictive value of positive visual interpretation from 51.2% to 63.0%, whereas an entropy < 3.0 improved the negative predictive value of negative visual interpretation from 75.3% to 82.6%. In cases with positive visual interpretation and low entropy, or negative visual interpretation and high entropy, the nodal metastasis rates were approximately 30%. In the survival analyses, the primary tumor entropy was also independently associated with DFS (HR = 2.7, p = 0.001) and OS (HR = 4.8, p = 0.001). CONCLUSIONS: Our preliminary results show that the primary tumor entropy may improve 18F-FDG PET visual interpretation in predicting pathological nodal metastasis in lung adenocarcinoma, and may also show a survival prognostic value. This versatile biomarker may facilitate tailored therapeutic strategies for patients with resectable lung adenocarcinoma.

Prognostic Value of Combing Primary Tumor and Nodal Glycolytic-Volumetric Parameters of 18F-FDG PET in Patients with Non-Small Cell Lung Cancer and Regional Lymph Node Metastasis.

We investigated whether the combination of primary tumor and nodal 18F-FDG PET parameters predict survival outcomes in patients with nodal metastatic non-small cell lung cancer (NSCLC) without distant metastasis. We retrospectively extracted pre-treatment 18F-FDG PET parameters from 89 nodal-positive NSCLC patients (stage IIB-IIIC). The Cox proportional hazard model was used to identify independent prognosticators of overall survival (OS) and progression-free survival (PFS). We devised survival stratification models based on the independent prognosticators and compared the model to the American Joint Committee on Cancer (AJCC) staging system using Harrell's concordance index (c-index). Our results demonstrated that total TLG (the combination of primary tumor and nodal total lesion glycolysis) and age were independent risk factors for unfavorable OS (p < 0.001 and p = 0.001) and PFS (both p < 0.001), while the Eastern Cooperative Oncology Group scale independently predicted poor OS (p = 0.022). Our models based on the independent prognosticators outperformed the AJCC staging system (c-index = 0.732 versus 0.544 for OS and c-index = 0.672 versus 0.521 for PFS, both p < 0.001). Our results indicate that incorporating total TLG with clinical factors may refine risk stratification in nodal metastatic NSCLC patients and may facilitate tailored therapeutic strategies in this patient group.

Association of Bcr-Abl Tyrosine Kinase Inhibitors With Hepatitis B Virus Reactivation Requiring Antiviral Treatment in Taiwan.

Importance: The US Food and Drug Administration (FDA) highlighted the potential risk of hepatitis B reactivation that was associated with Bcr-Abl tyrosine kinase inhibitor (TKI) treatment and has required updated product labels. Objective: To examine the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non-Bcr-Abl TKIs. Design, Setting, and Participants: This nested case-control study included patients who entered a hepatitis B carrier cohort in Taiwan after January 1, 2005. Patients who received their first antiviral agents for hepatitis B flare for more than 28 days after the cohort entry date were included as case patients. For each case, a corresponding risk set was formed that included all eligible patients in the study cohort who had the same age (within 1 year), same sex, and were at risk of developing hepatitis B flare at the case date. As many as 10 control patients were randomly selected from the risk set for each case patient. TKIs were evaluated before the hepatitis B flare for case patients and before the corresponding index date for control patients. Data were collected from the Taiwan National Health Insurance research database from January 2000 to 2015. Data analysis was conducted from January to June 2019. Exposure: Use of Bcr-AbL TKIs. Main Outcomes and Measures: Conditional logistic regression was used to estimate the rate ratio for the association between hepatitis B flare and exposure to Bcr-Abl TKIs compared with non-Bcr-Abl TKIs. Results: Among 698 342 patients who carried incident hepatitis B virus, 66 702 patients with hepatitis B flare that required antiviral treatment (47 492 [71.2%] men; mean [SD] age at index date, 50.2 [13.8] years) were included as case patients, and 666 989 age and sex-matched patients (474 903 [71.2%] men; mean [SD] age, 50.2 [13.8] years) were included as control patients. Analysis revealed that Bcr-Abl TKI use during the previous 90 days was independently associated with a 56% higher risk of hepatitis B flare (adjusted rate ratio [aRR], 1.56; 95% CI, 1.11-2.20), and the aRR increased to 1.66 (95% CI, 1.20-2.28) for Bcr-Abl TKI use during the previous 365 days. Use of Bcr-AbL TKIs during the previous 60 days was associated with a significantly increased risk of flare among women (aRR, 3.20; 95% CI, 1.70-6.03) but not among men (aRR, 1.14; 95% CI, 0.72-1.81). Conclusions and Relevance: These findings suggest that sex-specific strategies may be needed to monitor for hepatitis B reactivation among patients receiving Bcr-Abl TKIs.

Incorporating radiomic feature of pretreatment 18F-FDG PET improves survival stratification in patients with EGFR-mutated lung adenocarcinoma.

BACKGROUND: To investigate the survival prognostic value of the radiomic features of 18F-FDG PET in patients who had EGFR (epidermal growth factor receptor) mutated lung adenocarcinoma and received targeted TKI (tyrosine kinase inhibitor) treatment. METHODS: Fifty-one patients with stage III-IV lung adenocarcinoma and actionable EGFR mutation who received first-line TKI were retrospectively analyzed. All patients underwent pretreatment 18F-FDG PET/CT, and we calculated the PET-derived radiomic features. Cox proportional hazard model was used to examine the association between the radiomic features and the survival outcomes, including progression-free survival (PFS) and overall survival (OS). A score model was established according to the independent prognostic predictors and we compared this model to the TNM staging system using Harrell's concordance index (c-index). RESULTS: Forty-eight patients (94.1%) experienced disease progression and 41 patients (80.4%) died. Primary tumor SUV entropy > 5.36, and presence of pleural effusion were independently associated with worse OS (both p < 0.001) and PFS (p = 0.001, and 0.003, respectively). We used these two survival predictors to devise a scoring system (score 0-2). Patients with a score of 1 or 2 had a worse survival than those with a score of 0 (HR for OS: 3.6, p = 0.006 for score 1, and HR: 21.8, p < 0.001 for score 2; HR for PFS: 2.2, p = 0.027 for score 1 and HR: 8.8, p < 0.001 for score 2). Our scoring system surpassed the TNM staging system (c-index = 0.691 versus 0.574, p = 0.013 for OS, and c-index = 0.649 versus 0.517, p = 0.004 for PFS). CONCLUSIONS: In this preliminary study, combining PET radiomics with clinical risk factors may improve survival stratification in stage III-IV lung adenocarcinoma with actionable EFGR mutation. Our proposed scoring system may assist with optimization of individualized treatment strategies in these patients.

Preoperative F-18 fluorocholine PET/CT for the detection of hyperfunctioning parathyroid glands in patients with secondary or tertiary hyperparathyroidism: comparison with Tc-99m sestamibi scan and neck ultrasound.

OBJECTIVES: Currently, neck ultrasound is the preferred preoperative imaging in patients with secondary/tertiary hyperparathyroidism, and the use of Tc-99m sestamibi scan is limited in these patients. We conducted this study to compare the diagnostic utilities of F-18 fluorocholine PET/CT, Tc-99m sestamibi scintigraphy, and neck ultrasound for localizing hyperfunctioning parathyroid glands in secondary/tertiary hyperparathyroidism. METHODS: We prospectively enrolled 30 dialysis patients with a diagnosis of secondary/tertiary hyperparathyroidism; of these, 27 participants underwent all three imaging modalities, including dual-phase F-18 fluorocholine PET/CT (PET acquired 5 and 60 min after tracer injection), dual-phase Tc-99 m sestamibi SPECT/CT, and neck ultrasound. All patients underwent parathyroidectomy after imaging. We compared the lesion-based sensitivity, specificity, and accuracy of the three image tools using histopathology as the reference. RESULTS: A total of 27 patients (107 lesions) underwent all three imaging modalities and entered the final analysis. The lesion-based sensitivities of F-18 fluorocholine PET/CT, Tc-99m sestamibi, and ultrasound were 86%, 55%, and 62%, respectively (both p < 0.001, when comparing F-18 fluorocholine PET/CT to Tc-99 m sestamibi scan and to ultrasound). F-18 fluorocholine PET/CT, Tc-99m sestamibi, and ultrasound had similar specificities of 93%, 80%, and 87%, respectively. The accuracy of F-18 fluorocholine PET/CT (87%) was significantly higher than that of Tc-99m sestamibi (59%) and ultrasound (65%) (both p < 0.001). F-18 fluorocholine PET/CT identified more hyperplastic glands than ultrasound in 52% (14/27) patients. The sensitivity of F-18 fluorocholine PET/CT reached 95% for hyperplastic parathyroid masses as low as 200 mg. CONCLUSIONS: F-18 fluorocholine PET/CT shows superior accuracy over the conventional imaging modalities in patients with secondary or tertiary hyperparathyroidism. The combination of F-18 fluorocholine PET/CT and neck ultrasound may enable better surgical planning in these patients. REGISTRATION IDENTIFICATION NUMBER: NCT04316845.

Continuous positive pressure therapy usage and incident stroke in patients with obstructive sleep apnea: A nationwide population-based cohort study.

INTRODUCTION: Continuous positive airway pressure (CPAP) is the main treatment for obstructive sleep apnea (OSA). To date, the link between CPAP usage and incident stroke has been inconsistent. OBJECTIVE: This nationwide population study is designed to examine the effect of CPAP on stroke incidence in OSA patients. METHODS: Using Taiwan's National Health Insurance Research Database (NHIRD), this study collected data from 4275 OSA patients diagnosed between 2000 and 2011 and divided them into two groups according to whether they received CPAP treatment. After matching baseline demographics and comorbidities, both cohorts contained 959 OSA patients and were followed to a newly diagnosed stroke or until the end of 2013. Cox regression analysis was performed to examine the incidence of stroke between patients with OSA receiving CPAP or no CPAP treatment. RESULTS: CPAP treatment for OSA patients predicted a lower incidence rate (3.41 vs 5.43 per 1000 person-years) and tended to protect against the development of stroke (hazard ratio (HR): 0.68, 95% confidence interval (95% CI): 0.38-1.23) compared to those without CPAP treatment, but the estimate was not statistically significant. Similar results were also observed by dividing stroke into ischemic (2.65 vs 4.30 per 1000 person-years; HR: 0.67, 95% CI: 0.35-1.31) or hemorrhagic origin (0.76 vs 1.12 per 1000 person-years; HR: 0.67, 95% CI: 0.19-2.40). CONCLUSIONS: It is possible that treatment with CPAP might be beneficial for protection against stroke, but this conclusion should be interpreted with caution. Future studies with satisfactory CPAP quality and duration are needed to validate this observation.

Vegetarian diet and incidence of total, ischemic, and hemorrhagic stroke in 2 cohorts in Taiwan.

OBJECTIVE: To determine how a vegetarian diet affects stroke incidence in 2 prospective cohorts and to explore whether the association is modified by dietary vitamin B12 intake. METHODS: Participants without stroke in the Tzu Chi Health Study (cohort 1, n = 5,050, recruited in 2007-2009) and the Tzu Chi Vegetarian Study (cohort 2, n = 8,302, recruited in 2005) were followed until the end of 2014. Diet was assessed through food frequency questionnaires in both cohorts at baseline. Stroke events and baseline comorbidities were identified through the National Health Insurance Research Database. A subgroup of 1,528 participants in cohort 1 were assessed for serum homocysteine, vitamin B12, and folate. Associations between vegetarian diet and stroke incidences were estimated by Cox regression with age as time scale, adjusted for sex, education, smoking, alcohol, physical activities, body mass index (only in cohort 1), hypertension, diabetes, dyslipidemia, and ischemic heart diseases. RESULTS: Vegetarians had lower serum vitamin B12 and higher folate and homocysteine than nonvegetarians. In cohort 1, 54 events occurred in 30,797 person-years follow-up. Vegetarians (vs nonvegetarians) experienced lower risk of ischemic stroke (hazard ratio [HR], 0.26; 95% confidence interval [CI], 0.08-0.88). In cohort 2, 121 events occurred in 76,797 person-years follow-up. Vegetarians (vs nonvegetarians) experienced lower risk of overall stroke (HR, 0.52; 95% CI, 0.33-0.82), ischemic stroke (HR, 0.41; 95% CI, 0.19-0.88), and hemorrhagic stroke (HR, 034; 95% CI, 0.12-1.00). Our explorative analysis showed that vitamin B12 intake may modify the association between vegetarian diet and overall stroke (p interaction = 0.046). CONCLUSION: Taiwanese vegetarian diet is associated with a lower risk of ischemic and hemorrhagic strokes.

Combining the radiomic features and traditional parameters of 18F-FDG PET with clinical profiles to improve prognostic stratification in patients with esophageal squamous cell carcinoma treated with neoadjuvant chemoradiotherapy and surgery.

OBJECTIVES: To investigate the role of the traditional and radiomic parameters of 18F-FDG PET for predicting the outcomes of patients with esophageal squamous cell carcinoma (SqCC). METHODS: Forty-four patients with primary esophageal SqCC who underwent neoadjuvant chemoradiotherapy (CCRT) followed by esophagectomy (tri-modality treatment) were retrospectively analyzed. All patients underwent 18F-FDG PET/CT before and after neoadjuvant CCRT. The radiomic features were calculated using the pre-treatment PET scan. Pre-treatment radiomic features and changes in the PET-derived traditional parameters after neoadjuvant CCRT were analyzed according to the pathological response to esophagectomy, disease-free survival (DFS), and overall survival (OS). We further developed a scoring system based on the independent survival prognosticators and compared our model to the traditional TNM staging system and surgical pathology. RESULTS: A pre-treatment primary tumor histogram entropy ≥ 3.69 predicts an unfavorable response to neoadjuvant CCRT (OR = 19.25, p = 0.009). An SUVmax reduction ratio ≤ 0.76, a pre-treatment primary tumor code similarity ≤ 0.0235, and incomplete pathological remission were independently associated with poor OS (p = 0.019, 0.033, and 0.038, respectively) and DFS (p = 0.049, 0.021, and 0.009, respectively). The three survival prognosticators were used to construct a scoring system (score 0-1, 2, and 3). Patients with a score of 2 or 3 had a significantly worse survival outcome than those with a score of 0-1 (HRs for OS: 3.58 for score 2, and 15.19 for score 3, p < 0.001; HRs for DFS: 1.39 for score 2 and 6.04 for score 3, p = 0.001).This survival prediction model was superior to the traditional TNM staging system (p < 0.001 versus p = 0.061 for OS, and p = 0.001 versus p = 0.027 for DFS) and the model based on surgical pathology (p < 0.001 versus p = 0.049 for OS, and p = 0.001 versus p = 0.022 for DFS). CONCLUSIONS: The 18F-FDG PET-derived radiomic parameter is useful for predicting the surgical pathological response in patients with esophageal SqCC treated with the tri-modality method. Using a combination of traditional and radiomic PET parameters with clinical profiles enables better stratification of patients into subgroups with various survival rates.

Borderline personality disorder is associated with an increased risk of sexually transmitted infections: A nationwide population-based cohort study in Taiwan.

BACKGROUND: Several features of borderline personality disorder (BPD) are likely to be associated with sexual health problems, such as unstable attachment, unstable sexual identity and sexual impulsivity. Since the issue of sex is not openly discussed in Taiwanese society, sexual health needs, including screening and prevention of sexually transmitted infections (STI), are often neglected in this population. OBJECTIVE: The study aims to determine whether BPD is associated with an increased risk of subsequent STI in Taiwan. METHODS: Overall 669 patients with BPD and 2676 controls matched by gender and age were enrolled between 2000 and 2012 and followed until the end of 2013 using Taiwan's National Health Insurance Research Database. During the follow-up period, participants who developed STI (human immunodeficiency virus, syphilis, genital warts, gonorrhoea, chlamydia and trichomoniasis) were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (CI) of the STI incidence rate between patients with BPD and unaffected controls. RESULTS: Patients with BPD were predisposed to developing STI (HR: 4.17, 95% CI 1.62 to 10.8) after adjusting for demographic data and psychiatric comorbidities. The stratification analysis revealed a similar risk trend with BPD and subsequent STI in each gender and age group and was significant in the subgroups of male (HR: 11.3, 95% CI 2.97 to 42.7) and those aged 18-34 years (HR: 4.85, 95% CI 1.71 to 13.7). Also, the comorbidity stratification analysis revealed that, when the effect of comorbidities was excluded, patients with pure BPD significantly exhibited the risk association for subsequent STI after adjusting for all variables (HR: 4.24, 95% CI 1.25 to 14.4). CONCLUSION: Given the greater potential of BPD to be associated with an increased risk of STI, there should be direct implications for the development of targeted prevention interventions in Taiwan's mental health clinics.

Assessing whether the association between rheumatoid arthritis and schizophrenia is bidirectional: A nationwide population-based cohort study.

Since many studies have shown a reduction in the incidence of rheumatoid arthritis (RA) in patients with schizophrenia (SCZ), little effort has been devoted to studying this link in the Asian population. Moreover, the relationship between these two disorders could be bidirectional, but the influence of RA on the SCZ incidence is unclear. The study aims to determine whether there is a bidirectional association between RA and SCZ in an Asian population. We analyzed a 10-year population- based longitudinal cohort using the National Health Insurance Research Database of Taiwan. In the first analysis, we included a total of 58,847 SCZ patients and 235,382 non-SCZ controls, and in the second analysis, a total of 30,487 RA patients and 121,833 non-RA controls, both matched by gender, age, and index date. Cox regression analyses were performed to examine the risk of RA incidence in the first analysis and the risk of SCZ incidence in the second analysis. The main finding of this study was the discovery of a lower incidence of RA in patients with SCZ (hazard ratio (HR): 0.48, 95% confidence interval (95% CI): 0.31-0.77) after adjustment for baseline demographics and comorbidities. Additionally, the presence of RA predicted a reduced incidence rate for SCZ, but the estimate was not statistically significant (HR: 0.77, 95% CI: 0.44-1.37). The study found a unidirectional association between RA and SCZ. However, RA has an age of onset later than RA, and the protective effect of RA on SCZ incidence would be biased due to the limited number of cases.

Tourette's syndrome is associated with an increased risk of traumatic brain injury: A nationwide population-based cohort study.

INTRODUCTION: Violent motor tics or severe self-harm behaviors have been reported in patients with Tourette's syndrome (TS) and leading to traumatic brain injury (TBI). The study aimed to determine the risk of TBI in TS patients, the effects associated with concurrent psychiatric disorders (attention-deficit/hyperactivity disorder (ADHD), obsessive-compulsive disorder (OCD), or depressive disorder), and the effects of medication treatment (antipsychotics, antidepressants, or clonidine) on the risk of TBI. METHODS: Using the National Health Insurance Research Database of Taiwan, 2261 TS patients and 20349 non-TS controls matched by gender and age were enrolled between 2000 and 2012, and followed until the end of 2013. Participants who developed TBI during the follow-up period were identified. Cox regression analysis was performed to examine the risk of TBI between TS patients and non-TS controls. RESULTS: TS patients were associated with an increased risk of TBI compared to non-TS controls (hazard ratio (HR): 1.59, 95% confidence interval (95% CI): 1.37-1.85). Also, this study revealed TS patients with ADHD, OCD, or depressive disorder predicted a higher TBI incidence rate than those who did not, but the estimate was not statistically significant. Moreover, this study found that TS patients with frequent use of antipsychotics were associated with a lower risk of TBI than infrequent users (HR: 0.76, 95% CI: 0.57-0.99). CONCLUSIONS: This study highlights the need to pay more attention to the risk of TBI in TS patients, and the importance of adequate antipsychotic medication may reduce the risk of TBI.

The impact of obesity in cognitive and memory dysfunction in obstructive sleep apnea syndrome.

OBJECTIVE: Obstructive sleep apnea (OSA), a sleep disorder, results in decreased daytime alertness and neurocognitive dysfunction. Obesity is considered a major risk factor for the development and progression of OSA and the resulting cognitive dysfunction. However, the effect of obesity on neurocognitive dysfunction in OSA has been rarely investigated. METHODS: Eighty-three patients with moderate to severe OSA syndrome were recruited in our study. After matching for education, age, and body mass index (BMI), 40 patients were enrolled into our study with matched obese (BMI ≧ 30) and non-obese (BMI < 30) groups. All enrolled patients completed a polysomnographic study, sleepiness questionnaires, and attention, cognitive, and memory function tests. RESULTS: Compared to obese OSA patients, non-obese OSA patients had shorter reaction times in the psychomotor vigilance task but not the Flanker or Stroop cognitive tasks. Additionally, obese OSA patients had a reduced capacity for working memory relative to non-obese OSA patients. CONCLUSIONS: Obesity had a significant effect on OSA patients in our study, including delayed reaction times in the psychomotor vigilance task and a decrease in working memory.

Value of early evaluation of treatment response using 18F-FDG PET/CT parameters and the Epstein-Barr virus DNA load for prediction of outcome in patients with primary nasopharyngeal carcinoma.

PURPOSE: To determine the value of early evaluation of response to concurrent chemoradiotherapy (CCRT) using 18F-FDG PET-derived parameters and the Epstein-Barr virus (EBV) DNA titre in outcome prediction in patients with primary nasopharyngeal carcinoma (NPC). METHODS: Sixty patients with primary NPC were prospectively enrolled. All patients underwent 18F-FDG PET/CT before and during CCRT. The plasma EBV DNA titre was measured along with the PET/CT-derived parameters. Changes in EBV DNA titre and PET/CT-derived parameters during CCRT were analysed in relation to response to treatment, recurrence-free survival (RFS) and overall survival (OS). RESULTS: A total lesion glycolysis (TLG) reduction ratio of ≤0.6 and a detectable EBV DNA titre during CCRT were predictors of an unfavourable response to treatment, RFS and OS. In multivariate analysis, a TLG reduction ratio of ≤0.6 predicted incomplete remission (p = 0.002) and decreased RFS (p = 0.003). The proportion of patients with a TLG reduction ratio of >0.6 who achieved a complete response was more than twice that of patients with a TLG reduction ratio of ≤0.6. A detectable EBV DNA titre, a TLG reduction ratio of ≤0.6 and older age were independently associated with a poorer OS (p = 0.037, 0.009 and 0.016, respectively). A scoring system was developed based on these independent predictors of OS. Patients with a score of 1 and 2/3 had poorer survival outcomes than those with a score of 0 (hazard ratio 4.756, p = 0.074, and hazard ratio 18.973, p = 0.001, respectively). This scoring system appeared to be superior to the traditional TNM staging system (p < 0.001 versus p = 0.175). CONCLUSION: Early evaluation of response to CCRT using 18F-FDG PET-derived parameters and the EBV DNA titre can predict outcome in patients with primary NPC. A combination of interim PET parameters and the EBV DNA titre enables better stratification of patients into subgroups with different survival rates.

Systemic autoimmune diseases are associated with an increased risk of obsessive-compulsive disorder: a nationwide population-based cohort study.

PURPOSE: Studies suggested autoimmunity plays a role in the etiology of obsessive-compulsive disorder (OCD). The purpose of this study was to determine if a history of systemic autoimmune diseases (SADs) is associated with an increased risk of subsequent onset of OCD. METHODS: Patients with or without SADs were identified in the Taiwan National Health Insurance Program. The SADs cohort consisted of 63,165, while the comparison cohort consisted of 315,825 patients. The incidence rates of OCD with a maximum follow-up period of 10 years between patients with and without SADs were compared using a Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). RESULTS: The major finding was the discovery of a higher incidence of subsequent OCD among patients with SADs (HR: 1.85; 95% CI 1.41-2.43) after adjusted for other demographic characteristics. Specifically, the risk of OCD was observed to be significant increase in systemic lupus erythematosus (1.65, 1.07-2.54) dermatomyositis (3.25, 1.04-10.17), and Sjögren's syndrome (2.38, 1.53-3.72). Also, this study revealed some potential risk factors for developing OCD, including younger age (less than or equal to 50-year-old) and some comorbidities (alcohol use disorder, liver cirrhosis, and malignancies). Conversely, this study found that steroid use was a potential protective factor for the development of OCD. CONCLUSIONS: This study confirms that SADs are associated with higher incidence of OCD, suggesting that abnormal autoimmune process is associated with increased expression of psychiatric disturbances.

Risk of obstructive sleep apnea in patients with bipolar disorder: A nationwide population-based cohort study in Taiwan.

AIM: Previous studies have found a high prevalence of risk factors for obstructive sleep apnea (OSA) in patients with bipolar disorder (BD). This study aimed to determine whether BD patients are associated with an increased risk of incident OSA. METHODS: Using the National Health Insurance Research Database of Taiwan, 3650 BD patients and 18 250 non-BD controls matched by sex and age were enrolled between 2000 and 2010 and followed until the end of 2013. Patients who developed OSA confirmed by a polysomnographic examination during the follow-up period were identified. Cox regression analysis was performed to examine the risk of OSA between BD patients and comparative controls. RESULTS: BD patients were prone to developing OSA in the crude analysis (hazard ratio [HR]: 1.63, 95% confidence interval [CI]: 1.07-2.49). After adjusting for demographics and comorbidities, the HR declined and was only marginally significant (HR: 1.54, 95%CI: 0.99-2.37). The stratification analysis by sex revealed that the risk trend with BD and subsequent OSA was mainly contributed by male BD patients (HR: 1.72, 95%CI: 1.02-2.91) and female BD patients weakened the overall association. Additionally, this study found that older age, higher income, living in urbanized areas, and some metabolic comorbidities were potential risk factors for developing OSA. CONCLUSION: This study shows that male BD patients are associated with an increased risk of OSA, which has direct implications for the development of targeted prevention interventions or the implementation of a screening algorithm for OSA to reduce its negative health impact.

Hypercapnia impaired cognitive and memory functions in obese patients with obstructive sleep apnoea.

Obstructive sleep apnoea (OSA) is a sleep disorder involving repeated nocturnal desaturation and sleep fragmentation. OSA can result in decreased daytime alertness and neurocognitive dysfunction. Hypercapnia status is also related to neurocognitive dysfunction in patients with pulmonary diseases. We evaluated the effects of hypercapnia on cognitive performance and memory function in a prospective case-controlled study. We enrolled thirty-nine obese patients with OSA and collected their arterial blood samples. All the participants provided arterial blood samples, and completed two questionnaires (the Pittsburgh Sleep Quality Index and the Epworth Sleepiness Scale) and six cognitive tasks (the psychomotor vigilance task [PVT], the Stroop task, the Eriksen flanker task, processing speed [DSST], and verbal and visual memory [LM&FM]), which were used to evaluate daytime sleepiness, cognitive function, and memory function within one week of a polysomnographic study. When compared to the OSA without diurnal hypoventilation, the patients with stable hypercapnia (OHS) had increased reaction times in the PVT, Stroop task, and flanker task. Hypercapnic obese patients with OSA also had comparatively significantly lower scores in the processing speed and logical memory tests. OHS had increased reaction times in the attention and cognitive function assessments, and deficits in the logical memory, when compared to those with OSA without diurnal hypoventilation.

Autoimmune diseases are associated with an increased risk of schizophrenia: A nationwide population-based cohort study.

OBJECTIVES: Studies have suggested a possible autoimmune contribution in a subset of patients with schizophrenia. The purpose of this study was to determine if a history of autoimmune diseases (AD) is associated with an increased risk of later onset of schizophrenia. METHODS: Taiwan's National Health Insurance Research Database was used to identify a total of 64,817 AD patients and an equal number of age-matched control patients. The incidence rates of schizophrenia with a maximum follow-up period of 10 years between patients with and without AD were compared using a Cox proportional hazard model to estimate the hazard ratio (HR) and 95% confidence interval (95% CI). RESULTS: The main finding was the discovery of a higher incidence of subsequent schizophrenia in patients with AD (HR: 1.72, 95% CI: 1.23-2.4) after adjustment for other demographic characteristics. Specifically, the risk of schizophrenia was observed to be a significant increase in systemic lupus erythematosus (3.73, 2.07-6.72), rheumatoid arthritis (2.89, 1.97-4.23), dermatomyositis (5.85, 1.32-25.94) and autoimmune vasculitis (2.44, 1.17-5.06). Also, this study revealed some potential risk factors for developing schizophrenia, including younger age (less than or equal to 50 years) and some comorbidities (hypertension, chronic obstructive pulmonary disease, and alcohol use disorder). Conversely, this study found that steroid use was a potential protective factor for the development of schizophrenia. CONCLUSIONS: This study found that AD were associated with an increased risk of developing schizophrenia, suggesting that the abnormal autoimmune process was associated with an increase in the expression of psychiatric disturbances.