Caffeine supplementation improves the cognitive abilities and shooting performance of elite e-sports players: a crossover trial.

We explored the effect of 3 mg/kg of caffeine supplementation on the cognitive ability and shooting performance of elite e-sports players. Nine e-sports players who had received professional training in e-sports and had won at least eighth place in national-level e-sports shooting competitions. After performing three to five familiarization tests, we employed a single blind, randomized crossover design to divide participants into caffeine trial (CAF) and placebo trial (PL). The CAF trial took capsules with 3 mg/kg of caffeine, whereas the PL trial took a placebo capsule. After a one-hour rest, the Stroop task, the visual search ability test, and the shooting ability test were conducted. The CAF trial's performance in the Stroop task in terms of congruent condition (P = 0.023) and visual search reaction time with 20 items (P = 0.004) was significantly superior to those of the PL trial. In the shooting test, the CAF trial's kill ratio (P = 0.020) and hit accuracy (P = 0.008) were significantly higher, and the average time to target (P = 0.001) was significantly shorter than those of the PL trial. Caffeine supplementation significantly improves e-sports players' reaction times and shooting performance.

Factors influencing the effects of the mindfulness-based interventions of patients with substance abuse: A qualitative systematic review and meta-synthesis.

Objective: This article aims to provide the experiences of mindfulness treatments from the perspectives of patients with a history of substance abuse. Data source: Peer-reviewed articles on 5 databases, namely, PubMed, PsychINFO, Medline, CINAHL and the Cochrane Library, between the year of 2000 and 2023. Study Inclusion and Exclusion Criteria: Studies were included if they were published in the English language and reported on qualitative studies that directly engaged patients with experiences of substance abuse and mindfulness treatments. Data extraction: After our initial search, 5355 studies were reviewed by title and abstract, consequently, 10 studies were included. Data synthesis: Meta-ethnography were used in this study. Data were obtained from the quotations from participants and text under the heading "results" or "findings" from the included 10 studies. Results: Effective mindfulness-based interventions (MBI) influence recovery from substance abuse. Four themes were identified as factors influencing the MBI treatment effect. They were (1) engaging in mindfulness: entry and retention, (2) perceived benefits of MBIs, (3) implementation of treatment group and (4) maintenance of treatment effect. Conclusion: This article examines the scientific literature to date and presents the evidence on the factors that influentially impact the effect of MBIs in patients with substance abuse. The findings of this study should be helpful in guiding clinical practice, policy, and future research focused on the treatment effect of MBIs for person with substance use.

The mismatch negativity to abstract relationship of tone pairs is independent of attention.

The mismatch negativity (MMN) implicating a comparison process between the deviant and the memory trace of the standard can be elicited by not only changes in physical features but also violations of abstract patterns. It is considered pre-attentive, yet the use of the passive design makes it difficult to exclude the possibility of attention leak. In contrast to how this issue has been well addressed with the MMN to physical changes, much less research directly investigated the attentional effect on the MMN to abstract relationships. Here we conducted an electroencephalography (EEG) experiment to study whether and how the MMN to abstract relationships is modulated by attention. We adapted the oddball paradigm of Kujala et al. by presenting occasional descending tone pairs among frequent ascending tone pairs, while additionally implementing a novel control of attention. Participants' attention was either directed away from the sounds (with an engaging task of visual target detection, so that the sounds were task-irrelevant) or toward the sounds (with a conventional task of auditory deviant detection, so that the sounds were task-relevant). The MMN to abstract relationships appeared regardless of attention, confirming the pre-attentive assumption. The attention-independence of the frontocentral and supratemporal components of the MMN supported the notion that attention is not required to generate the MMN. At the individual level, a relatively equal number of participants showed attention enhancement and attention suppression. It is unlike the attentional modulation on the P3b, which was robustly elicited in the attended condition only. The concurrent collection of these two neurophysiological markers in both unattended and attended conditions might be potentially suitable for testing clinical populations showing heterogeneous deficits in auditory function independent/dependent of attention.

The association between mortality and use of Chinese herbal medicine among incident stage IV esophageal cancer patients: A retrospective cohort study with core herbs exploration.

Esophageal cancer (EC) remains a leading cause of death worldwide and in Taiwan. The prognosis of advanced-stage EC is notably poor, and the treatment options are limited. Chinese herbal medicine (CHM) has been widely used as a complementary treatment for cancer, yet the long-term effect of CHM in stage IV EC remains unclear. The multi-institutional cohort obtained from the Chang Gung research database (CGRD) was used to study the long-term outcome of CHM use among incident stage IV EC patients from 1 January 2002, to 31 December 2018. All patients were followed up to 5 years or the occurrence of death. The overall survival (OS) and disease-specific survival rates were conducted using Kaplan-Meier estimation. Overlap weighing and landmark analysis were used to eliminate confounding and immortal time biases. Furthermore, we demonstrated the core CHMs for stage IV EC by using the Chinese herbal medicine network (CMN) analysis on prescriptions. Nine hundred eighty-five stage IV EC patients were analyzed, including 74 CHM users and 911 non-CHM users. We found the use of CHM was associated with a higher 5-year overall survival rate than CHM nonusers (the cumulative probability: 19.52% versus 6.04%, log-rank test: p < 0.001, and the p < 0.001 with overlap weighting). In addition, the overall median survival time was about 7 months longer among CHM users. Moreover, the lower 1-, 3-, 5-year disease-specific survival rates were higher among CHM users. Additionally, the risk of all-cause mortality was lower among CHM users when considering accessible demographic covariates (adjusted hazard ratio: 0.59, 95%CI: 0.39, 0.89, p = 0.011). Furthermore, the CMN analysis revealed that CHMs improved health while relieving tumor burden. For example, Hedyotis diffusa Willd . was the core CHM with an anti-cancer effect, while Fritillaria thunbergii Miq and Sevilla maindronide Rochebrune were used together to relieve cancer-related gastrointestinal discomfort. The use of CHM seems safe and possibly beneficial among stage IV EC patients with a higher 5-year OS. Further clinical trials on CHM were guaranteed to explore the role of CHM in managing stage IV EC patients.

The Characteristics and Mortality of Chinese Herbal Medicine Users among Newly Diagnosed Inoperable Huge Hepatocellular Carcinoma (≥10 cm) Patients: A Retrospective Cohort Study with Exploration of Core Herbs.

For patients with inoperable huge hepatocellular carcinoma (H-HCC, tumor size ≥10 cm), treatment options are limited. This study aimed to evaluate the characteristics and outcomes of patients with H-HCC who use Chinese herbal medicine (CHM). Multi-institutional cohort data were obtained from the Chang Gung Research Database (CGRD) between 1 January 2002 and 31 December 2018. All patients were followed up for 3 years or until the occurrence of death. Characteristics of CHM users and risk of all-cause mortality were assessed, and core CHMs with potential pharmacologic pathways were explored. Among 1618 patients, clinical features of CHM users (88) and nonusers (1530) were similar except for lower serum α-fetoprotein (AFP) and higher serum albumin levels in CHM users. CHM users had significantly higher 3 year overall survival rates (15.0% vs. 9.7%) and 3 year liver-specific survival rates (13.4% vs. 10.7%), about 3 months longer median survival time, and lower risk of all-cause mortality. Core CHMs were discovered from the prescriptions, including Hedyotis diffusa Willd combined with Scutellaria barbata D.Don, Salvia miltiorrhiza Bunge., Curcuma longa L., Rheum palmatum L., and Astragalus mongholicus Bunge. CHM use appears safe and is possibly beneficial for inoperable H-HCC patients; however, further clinical trials are still required.

The Potential Complementary Role of Using Chinese Herbal Medicine with Western Medicine in Treating COVID-19 Patients: Pharmacology Network Analysis.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic in 2019-coronavirus disease (COVID-19). More and more Western medicine (WM) and Chinese herbal medicine (CHM) treatments have been used to treat COVID-19 patients, especially among Asian populations. However, the interactions between WM and CHM have not been studied. This study aims at using the network pharmacology approach to explore the potential complementary effects among commonly used CHM and WM in a clinical setting from a biomolecular perspective. Three well-published and widely used CHM formulas (National Research Institute of Chinese Medicine 101 (NRICM101), Qing-Fei-Pai-Du-Tang (QFPDT), Hua-Shi-Bai-Du-Formula (HSBDF)) and six categories of WM (Dexamethasone, Janus kinase inhibitors (JAKi), Anti-Interleukin-6 (Anti-IL6), anticoagulants, non-vitamin K antagonist oral anticoagulants (NOAC), and Aspirin) were included in the network pharmacology analysis. The target proteins on which these CHM and WM had direct effects were acquired from the STITCH database, and the potential molecular pathways were found in the REACTOME database. The COVID-19-related target proteins were obtained from the TTD database. For the three CHM formulas, QFPDT covered the most proteins (714), and 27 of them were COVID-19-related, while HSBDF and NRICM101 covered 624 (24 COVID-19-related) and 568 (25 COVID-19-related) proteins, respectively. On the other hand, WM covered COVID-19-related proteins more precisely and seemed different from CHM. The network pharmacology showed CHM formulas affected several inflammation-related proteins for COVID-19, including IL-10, TNF-α, IL-6, TLR3, and IL-8, in which Dexamethasone and Aspirin covered only IL-10 and TNF-α. JAK and IL-6 receptors were only inhibited by WM. The molecular pathways covered by CHM and WM also seemed mutually exclusive. WM had advantages in cytokine signaling, while CHM had an add-on effect on innate and adaptive immunity, including neutrophil regulation. WM and CHM could be used together to strengthen the anti-inflammation effects for COVID-19 from different pathways, and the combination of WM and CHM may achieve more promising results. These findings warrant further clinical studies about CHM and WM use for COVID-19 and other diseases.

Deciphering the Efficacy and Mechanisms of Chinese Herbal Medicine for Diabetic Kidney Disease by Integrating Web-Based Biochemical Databases and Real-World Clinical Data: Retrospective Cohort Study.

BACKGROUND: Diabetic kidney disease (DKD) is one of the most crucial causes of chronic kidney disease (CKD). However, the efficacy and biomedical mechanisms of Chinese herbal medicine (CHM) for DKD in clinical settings remain unclear. OBJECTIVE: This study aimed to analyze the outcomes of DKD patients with CHM-only management and the possible molecular pathways of CHM by integrating web-based biomedical databases and real-world clinical data. METHODS: A total of 152,357 patients with incident DKD from 2004 to 2012 were identified from the National Health Insurance Research Database (NHIRD) in Taiwan. The risk of mortality was estimated with the Kaplan-Meier method and Cox regression considering demographic covariates. The inverse probability of treatment weighting was used for confounding bias between CHM users and nonusers. Furthermore, to decipher the CHM used for DKD, we analyzed all CHM prescriptions using the Chinese Herbal Medicine Network (CMN), which combined association rule mining and social network analysis for all CHM prescriptions. Further, web-based biomedical databases, including STITCH, STRING, BindingDB, TCMSP, TCM@Taiwan, and DisGeNET, were integrated with the CMN and commonly used Western medicine (WM) to explore the differences in possible target proteins and molecular pathways between CHM and WM. An application programming interface was used to assess these online databases to obtain the latest biomedical information. RESULTS: About 13.7% (20,947/131,410) of patients were classified as CHM users among eligible DKD patients. The median follow-up duration of all patients was 2.49 years. The cumulative mortality rate in the CHM cohort was significantly lower than that in the WM cohort (28% vs 48%, P<.001). The risk of mortality was 0.41 in the CHM cohort with covariate adjustment (99% CI 0.38-0.43; P<.001). A total of 173,525 CHM prescriptions were used to construct the CMN with 11 CHM clusters. CHM covered more DKD-related proteins and pathways than WM; nevertheless, WM aimed at managing DKD more specifically. From the overrepresentation tests carried out by the online website Reactome, the molecular pathways covered by the CHM clusters in the CMN and WM seemed distinctive but complementary. Complementary effects were also found among DKD patients with concurrent WM and CHM use. The risk of mortality for CHM users under renin-angiotensin-aldosterone system (RAAS) inhibition therapy was lower than that for CHM nonusers among DKD patients with hypertension (adjusted hazard ratio [aHR] 0.47, 99% CI 0.45-0.51; P<.001), chronic heart failure (aHR 0.43, 99% CI 0.37-0.51; P<.001), and ischemic heart disease (aHR 0.46, 99% CI 0.41-0.51; P<.001). CONCLUSIONS: CHM users among DKD patients seemed to have a lower risk of mortality, which may benefit from potentially synergistic renoprotection effects. The framework of integrating real-world clinical databases and web-based biomedical databases could help in exploring the roles of treatments for diseases.

Associations Between Using Chinese Herbal Medicine and Long-Term Outcome Among Pre-dialysis Diabetic Nephropathy Patients: A Retrospective Population-Based Cohort Study.

Background: Chronic kidney disease (CKD) has become a worldwide burden due to the high co-morbidity and mortality. Diabetic nephropathy (DN) is one of the leading causes of CKD, and pre-dialysis is one of the most critical stages before the end-stage renal disease (ESRD). Although Chinese herbal medicine (CHM) use is not uncommon, the feasibility of using CHM among pre-dialysis DN patients remains unclear. Materials and methods: We analyzed a population-based cohort, retrieved from Taiwan's National Health Insurance Research Database, to study the long-term outcome of using CHM among incident pre-dialysis DN patients from January 1, 2004, to December 31, 2007. All patients were followed up to 5 years or the occurrence of mortality. The risks of all-cause mortality and ESRD were carried out using Kaplan-Meier and competing risk estimation, respectively. Further, we demonstrated the CHM prescriptions and core CHMs using the Chinese herbal medicine network (CMN) analysis. Results: A total of 6,648 incident pre-dialysis DN patients were analyzed, including 877 CHM users and 5,771 CHM nonusers. With overlap weighing for balancing all accessible covariates between CHM users and nonusers, we found the use of CHM was associated with lower all-cause mortality (0.22 versus 0.56; log-rank test: p-value <0.001), and the risk of mortality was 0.42 (95% CI: 0.36-0.49; p-value <0.001) by adjusting all accessible covariates. Further, the use of CHM was associated with a lower risk of ESRD (cause-specific hazard ratio: 0.59, 95%CI: 0.55-0.63; p-value <0.001). Also, from the 5,901 CHM prescriptions, we found Ji-Sheng-Shen-Qi-Wan, Astragalus mongholicus Bunge or (Astragalus membranaceus (Fisch.) Bge.), Plantago asiatica L. (or Plantago depressa Willd.), Salvia miltiorrhiza Bunge, and Rheum palmatum L. (or Rheum tanguticum (Maxim. ex Regel) Balf., Rheum officinale Baill.) were used as core CHMs for different CHM indications. Use of core CHMs was associated with a lower risk of mortality than CHM users without using core CHMs. Conclusions: The use of CHM seemed feasible among pre-dialysis DN patients; however, the beneficial effects still need to be validated by well-designed clinical trials.

Identifying the Chinese Herbal Medicine Network and Core Formula for Allergic Rhinitis on a Real-World Database.

MATERIALS AND METHODS: Patients with a primary diagnosis of AR (ICD-9-CM code: 477.9) in 2010 were included, and the National Health Insurance Research Database in Taiwan was used as the data source. Association rule mining and social network analysis were used to establish and explore the CHM network. Possible molecular pathways of the CHM network were summarized and compared with commonly used western medicine (WM) by conducting overrepresentation analysis in the Reactome pathway database. The potential proteins acted by CHMs were obtained from the CHM ingredient-protein databases, including STITCH, TCMSP, TCMID, and TCM@Taiwan. RESULTS: There were 89,148 AR subjects found in 2010, and a total of 33,507 patients ever used CHM. On an average, 5.6 types of CHMs were utilized per prescription. Xin-Yi-Qing-Fei-Tang was used most frequently (25.5% of 222,279 prescriptions), while Xiao-Qing-Long-Tang with Xin-Yi-San was the most commonly prescribed CHM-CHM combination. Up to six distinctive clusters could be found among the CHM network, and core CHMs could be found for AR, such as Xiao-Qing-Long-Tang and Xin-Yi-Qing-Fei-Tang. A total of 140 molecular pathways were covered by the CHM network (2,432 ingredients from 31 kinds of CHMs), while 39 WMs covered 55 pathways. Among pathways responding to the immune system, WM mainly acted on cytokine signaling-related pathways, while CHM mostly acted on neutrophil/macrophage-related innate pathways and dendritic cell-related adaptive immunity pathways. CONCLUSION: Our study demonstrated and analyzed the CHM network for AR. Core CHM for AR and possible molecular pathways were presented as well, and this information is crucial for researchers to select candidates for CHM-related studies.

Team-based care improves quality of diabetes care -Family Practice Integrated Care Project in Taiwan.

BACKGROUND: The Family Practice Integrated Care Project (FPICP) is a team-based program in Taiwan initiated in 2003. This study investigates the influence of FPICP on the quality of diabetes care. METHODS: This population-based cohort study used Taiwan's National Health Insurance Administration data on FPICP (fiscal year 2015-2016, with follow-up duration of one year). Participants included diabetic patients aged ≥30 in primary care clinics. We used conditional logistic regression modeling of patient characteristics and annual diabetes examinations and compared FPICP participants with non-participating candidates. Main outcome measures included completion of annual diabetes examinations, including glycated hemoglobin (A1c), low-density lipoprotein (LDL), urine microalbumin (MAU), routine urinalysis (UR), and fundus examination (FE). RESULTS: The sample included 298,208 FPICP participants and 478,778 non-participating candidates. After 1:1 propensity score matching, the examination completion rates for FPICP participants and non-participants, respectively, were 94.4% versus 93.6% in A1c, 84.2% versus 83.8% in LDL, 61.9% versus 60.1% in MAU, 59.2% versus 58.0% in UR, and 30.1% versus 32.4% in FE. CONCLUSION: Our findings indicate that a program like FPICP helps improve the quality of diabetes care through regular examinations of Alc, LDL, MAU, and UR.

Natural History of Acromegaly: Incidences, Re-operations, Cancers, and Mortality Rates in a National Cohort.

BACKGROUND: Acromegaly is so rare that its natural history, including incidence, risk of cancers, and mortality rates, remains elusive. This natural study utilized a nationwide database to provide a better understanding of acromegaly's disease course. METHODS: A cohort of 1,195 acromegaly patients were identified and followed-up from 1997 to 2013. Incidence, operation, and re-operation rates were calculated. Excessive mortality and cancer risk related to acromegaly were estimated by standardized mortality ratio (SMR) and standardized incidence ratio (SIR). RESULTS: The incidence was 2.78 per million-person-years, with little gender predominance (female vs. male, 49.5 vs. 50.5%, respectively). There was female predominance only among 50 and 60 year-olds (incidence rate ratio: 1.37 and 1.43, p < 0.001 and p = 0.002). Among them, 673 (56.3%) had hypophysectomy surgery, and the young-onset (<40 years) patients had more re-operations (15.5%, p = 0.01). The overall mortality rate was 22.3 per 1,000 person-years, with a median survival of 4.67 years (with no gender differences, p = 0.38). The overall SMR of acromegaly patients was 1.41, and the onset-age-specific SMRs of the early- and middle-onset patients were higher than for those with late-onset. There were 87 newly diagnosed cancers in the cohort, with an incidence rate of 10.6 per 1,000 person-years (median 5.4 years). The overall SIR of cancers was 1.91, and there were no differences among gender, onset-age, and disease duration (all SIR >1, approximately 2). CONCLUSION: Acromegaly is associated with an excessive risk of mortality and two-fold higher risk of cancers. Patients with acromegaly should be managed appropriately after the diagnosis.

Traditional Chinese medicine use is associated with lower end-stage renal disease and mortality rates among patients with diabetic nephropathy: a population-based cohort study.

BACKGROUND: Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) that imposes an enormous burden on the healthcare system. Although some studies show that traditional Chinese medicine (TCM) treatments confer a protective effect on DN, the long-term impact remains unclear. This study aims to examine end-stage renal disease (ESRD) and mortality rates among TCM users with DN. METHODS: A total of 125,490 patients with incident DN patients from 2004 to 2006 were identified from the National Health Insurance Research Database in Taiwan and followed until 2012. The landmark method was applied to avoid immortal time bias, and propensity score matching was used to select 1:1 baseline characteristics-matched cohort. The Kaplan-Meier method and competing-risk analysis were used to assess mortality and ESRD rates separately. RESULTS: Among all eligible subjects, about 60% of patients were classified as TCM users (65,812 TCM users and 41,482 nonusers). After 1:1 matching, the outcomes of 68,882 patients were analyzed. For the ESRD rate, the 8-year cumulative incidence was 14.5% for TCM users [95% confidence interval (CI): 13.9-15.0] and 16.6% for nonusers (95% CI: 16.0-17.2). For the mortality rate, the 8-year cumulative incidence was 33.8% for TCM users (95% CI: 33.1-34.6) and 49.2% for nonusers (95% CI: 48.5-49.9). After adjusting for confounding covariates, the cause-specific hazard ratio of ESRD was 0.81 (95% CI: 0.78-0.84), and the hazard ratio of mortality for TCM users was 0.48 (95% CI: 0.47-0.50). The cumulative incidence of mortality increased rapidly among TCM users with ESRD (56.8, 95% CI: 54.6-59.1) when compared with TCM users without ESRD (30.1, 95% CI: 29.4-30.9). In addition, TCM users who used TCM longer or initiated TCM treatments after being diagnosed with DN were associated with a lower risk of mortality. These results were consistent across sensitivity tests with different definitions of TCM users and inverse probability weighting of subjects. CONCLUSIONS: The lower ESRD and mortality rates among patients with incident DN correlates with the use of TCM treatments. Further studies about specific TCM modalities or medications for DN are still needed.

Atypical Anxiety-Related Amygdala Reactivity and Functional Connectivity in Sant Mat Meditation.

While meditation has drawn much attention in cognitive neuroscience, the neural mechanisms underlying its emotional processing remains elusive. Sant Mat meditators were recruited, who adopt a loving-kindness mode of meditation along with a vegetarian diet and an alcohol-restricted lifestyle and novices. We assessed their State-Trait Anxiety Inventory (STAI) and scanned their amygdala reactivity in response to an explicit and implicit (backward masked) perception of fearful and happy faces. In contrast with novices, meditators reported lower STAI scores. Meditators showed stronger amygdala reactivity to explicit happiness than to fear, whereas novices exhibited the opposite pattern. The amygdala reactivity was reduced in meditators regardless of implicit fear or happiness. Those who had more lifetime practice in meditation reported lower STAI and showed a weaker amygdala response to fear. Furthermore, the amygdala in meditators, relative to novices, had a stronger positive functional connectivity with the ventrolateral prefrontal cortex (PFC) to explicit happiness, but a more negative connectivity with the insula and medial orbitofrontal cortex (OFC) to explicit fear. Mediation analysis indicated the amygdala reactivity as the mediator for the linkage between meditation experience and trait anxiety. The findings demonstrate the neural correlates that underpin the beneficial effects of meditation in Sant Mat. Long-term meditation could be functionally coupled with the amygdala reactivity to explicit and implicit emotional processing, which would help reduce anxiety and potentially enhance well-being.

Identifying Chinese Herbal Medicine Network for Endometriosis: Implications from a Population-Based Database in Taiwan.

BACKGROUND: Endometriosis is a common but bothersome gynecological disease, and Chinese herbal medicine (CHM) is used for treating endometriosis. The aim of this study is to explore CHM network and core treatments for endometriosis by analyzing nationwide CHM prescription database. METHODS: From 1998 to 2013, the CHM prescriptions made primarily for endometriosis among women diagnosed with endometriosis (ICD-9-CM code: 671) by gynecologists during their reproductive age were collected. CHM network analysis was then carried out by using association rule mining and social network analysis. RESULTS: A total of 12,986 CHM prescriptions made for endometriosis were analyzed. There were 556 kinds of CHM ever used, and, in average, each prescription was composed of 6.2 CHMs. Gui-Zhi-Fu-Ling-Wan (GZFLW) was used most frequently, followed by Cyperus rotundus (28.1% and 18.8% of all prescriptions, resp.). Additionally, the combination of Cyperus rotundus with GZFLW (8.0%) was the most frequently used combination of two CHMs. CHM network showed that GZFLW was the core CHM for endometriosis and graphically demonstrated the extensive coverage of TCM syndromes and pathogenesis of endometriosis. CONCLUSIONS: CHM network provides graphical demonstration and summary of commonly used CHMs for endometriosis, and further studies are warranted based on these findings.

Risk of spinal cord injury in patients with cervical spondylotic myelopathy and ossification of posterior longitudinal ligament: a national cohort study.

OBJECTIVE This study aimed to estimate the risk of spinal cord injury (SCI) in patients with cervical spondylotic myelopathy (CSM) with and without ossification of posterior longitudinal ligament (OPLL). Also, the study compared the incidence rates of SCI in patients who were managed surgically and conservatively. METHODS This retrospective cohort study covering 15 years analyzed the incidence of SCI in patients with CSM. All patients, identified from the National Health Insurance Research Database, were hospitalized with the diagnosis of CSM and followed up during the study period. These patients with CSM were categorized into 4 groups according to whether they had OPLL or not and whether they received surgery or not: 1) surgically managed CSM without OPLL; 2) conservatively managed CSM without OPLL; 3) surgically managed CSM with OPLL; and 4) conservatively managed CSM with OPLL. The incidence rates of subsequent SCI in each group during follow-up were then compared. Kaplan-Meier and Cox regression analyses were performed to compare the risk of SCI between the groups. RESULTS Between January 1, 1999, and December 31, 2013, there were 17,258 patients with CSM who were followed up for 89,003.78 person-years. The overall incidence of SCI in these patients with CSM was 2.022 per 1000 person-years. Patients who had CSM with OPLL and were conservatively managed had the highest incidence of SCI, at 4.11 per 1000 person-years. Patients who had CSM with OPLL and were surgically managed had a lower incidence of SCI, at 3.69 per 1000 person-years. Patients who had CSM without OPLL and were conservatively managed had an even lower incidence of SCI, at 2.41 per 1000 person-years. Patients who had CSM without OPLL and were surgically managed had the lowest incidence of SCI, at 1.31 per 1000 person-years. The Cox regression model demonstrated that SCIs are significantly more likely to happen in male patients and in those with OPLL (HR 2.00 and 2.24, p < 0.001 and p = 0.007, respectively). Surgery could significantly lower the risk for approximately 50% of patients (HR 0.52, p < 0.001). CONCLUSIONS Patients with CSM had an overall incidence rate of SCI at approximately 0.2% per year. Male sex, the coexistence of OPLL, and conservative management are twice as likely to be associated with subsequent SCI. Surgery is therefore suggested for male patients with CSM who also have OPLL.

Characteristics of traditional Chinese medicine users and prescription analysis for pediatric atopic dermatitis: a population-based study.

BACKGROUND: Atopic dermatitis among children is an important issue due to relapses and skin manifestations. Traditional Chinese medicine (TCM) is commonly used to treat children with atopic dermatitis. The aim of this study was to investigate the characteristics and TCM prescriptions of patients with atopic dermatitis using a nationwide database. METHODS: Children younger than 12 years of age diagnosed with atopic dermatitis, defined as ICD-9-CM codes 691.8 and 692.x, were identified from the database. Data on age, diagnosis codes, area of residence and use of corticosteroids of the TCM users were recorded. Association rule mining was used to analyze the prescriptions used for atopic dermatitis. RESULTS: We identified 13,646 children with atopic dermatitis using TCM in 2007. Female gender (OR: 0.83 for male gender), adolescence (OR: 10.0, 95 % CI: 8.88-11.15) and allergic rhinitis (OR: 2.44, 95 % CI: 2.10-2.85) were associated with the use of TCM. Fewer of the TCM users were prescribed with corticosteroids (35.8 % of all TCM users), but the TCM users had a higher rate of long-term topical corticosteroid therapy (10.6 % for TCM users versus 2.0 % for those who did not use TCM). Chinese herbal medicine (CHM) was used by 93.7 % of all TCM users in 36,398 prescriptions. On average, 5.6 kinds of CHM were used in combination. The relationship between the CHMs constituted a network, in which Xiao-Feng-San was the core treatment for atopic dermatitis. CONCLUSIONS: In this study, we described the characteristics of children with atopic dermatitis who use TCM in Taiwan. and identified the core CHM treatment. Further research on the safety and efficacy of this treatment are still needed.

Developmental changes in brain response to speech perception in late-talking children: A longitudinal MMR study.

This study used a longitudinal design to examine the development of mismatch responses (MMRs) to Mandarin lexical tones, an index of neural speech discriminative responses, in late talkers and typical controls at 3, 5, and 6 years of age. Lexical tones are phonetic suprasegments that distinguish the lexical meanings of syllables in tonal languages. The 2 year-old late talkers were later divided into persistent language delay and late bloomer groups according to their performance on standardized language tests at 4 years. Results showed that children with persistent language delay demonstrated more positive mismatch responses than the typical controls at 3 years of age. At the age of 5, no group difference were found in the amplitude of MMRs, but the maturation of MMRs could be observed in the change of topography, with more prominent negative response in the frontal sites only in the typical group. Correlations were found between the index of MMRs at 3 years and children's language performance outcome at 6 years. Our results indicate that the development of fine-grained tone representations is delayed in late-talking children between 3 and 5 years and may be one of the underlying mechanisms which associated with later language performance.

Identifying Chinese herbal medicine network for treating acne: Implications from a nationwide database.

ETHNO-PHARMACOLOGICAL RELEVANCE: Acne is a highly prevalent inflammatory skin disease which causes patients great psychological stress, especially teenagers. Chinese herbal medicine (CHM) is commonly used to treat acne with personalized but complicated prescriptions. The aim of this study is to determine a CHM network and core CHM treatments for acne by analyzing a nationwide database. MATERIALS AND METHODS: From January 1st to December 31st, 2011, all CHM prescriptions made for acne (ICD-9-CM code: 706.0 or 706.1) were included in this study. Visits with acupuncture, manual therapy or other treatment modalities were excluded, and CHM visits with other diagnoses were also excluded in final analysis. Association rule mining (ARM) and social network analysis (SNA) were used to explore and demonstrate a CHM network. RESULTS: A total of 91,129 patients used traditional Chinese medicine, and 99% of them chose CHM for acne treatment. Most CHM users were teenagers, and there were twice as many female patients as male patients. A total of 279,823 CHM prescriptions were made for acne in 2011. Qing-Shang-Fang-Feng-Tang was the most commonly used CHM (31.2% of all prescriptions), and Zhen-Ren-Huo-Ming-Yin combined with Forsythia suspensa (Thunb.) Vahl. (Lian Qiao) was the most commonly used CHM-CHM combination. Thirty-one important CHM-CHM combinations were identified, and the CHM network could be built. Extensive coverage of the known pathogenesis of acne could be found in the CHM network when incorporating CHM pharmacological mechanisms into the network. Anti-inflammatory and anti-bacterial effects were commonly found in the CHM network, and CHMs with anti-androgen, anti-depressive and skin whitening effects were frequently used in combination. CONCLUSIONS: The CHM combination patterns and core treatments for acne were disclosed in this study by applying network analysis to a CHM prescription database. These results may be beneficial for further bench or clinical studies when choosing target CHM.

Chinese herbal medicine network and core treatments for allergic skin diseases: Implications from a nationwide database.

ETHNO-PHARMACOLOGICAL RELEVANCE: Chinese herbal medicine (CHM) is commonly used to treat skin diseases, but CHM prescription patterns are difficult to understand due to their complexity and inter-connections. This study aimed to demonstrate CHM core treatments and network for treatment of allergic skin diseases by analyzing a nationwide prescription database. MATERIALS AND METHODS: All CHM prescriptions made for atopic dermatitis (with age limitation ≤ 12 years) and urticaria for the entire year of 2011 were included. Association rule mining (ARM) combined with social network analysis (SNA) were used to analyze CHM prescriptions and explore the CHM prescription pattern and network. RESULTS: A total of 27,350 and 97,188 prescriptions for atopic dermatitis and urticaria, respectively, were analyzed. Xiao-Feng-San (XFS) was the most commonly used CHM (32% of prescriptions for atopic dermatitis and 47.4% for urticaria) and was the core treatment for both diseases. Moreover, 42 and 82 important CHM-CHM combinations were identified to establish the CHM network, and XFS with Dictamnus dasycarpus Turcz was the most prevalent (6.4% for atopic dermatitis and 9.1% for urticaria). Traditional Chinese Medicine heat syndrome was most prevalent cause. Extensive anti-inflammation, anti-allergy, anti-oxidation, and anti-bacterial effects were also found among the CHMs. CONCLUSIONS: Network analysis on CHM prescriptions provides graphic and comprehensive illustrations regarding CHM treatment for atopic dermatitis and urticaria. The CHM network analysis of prescriptions is essential to realize the CHM treatments and to select suitable candidates for clinical use or further studies.

Identifying chinese herbal medicine network for eczema: implications from a nationwide prescription database.

Eczema is a highly prevalent dermatological disease that can severely affect the patient's quality of life. Chinese herbal medicine (CHM) is commonly used in combination for eczema due to the complicated pathogenesis. This study aimed to identify a CHM network for the treatment of eczema by using a nationwide database. During 2011, 381,282 CHM prescriptions made for eczema (ICD-9-CM 692.x) were obtained from the National Health Insurance Research Database (NHIRD) in Taiwan and analyzed by using association rule mining and social network analysis. Among 661 available CHMs, 44 important combinations were identified. Among the CHM networks, seven clusters with the predominant traditional Chinese medicine (TCM) pattern were recognized. The largest CHM cluster was used to treat the wind-dampness-heat pattern, and Xiao-Feng-San (24.1% of all prescriptions) was the core of this cluster with anti-inflammation, antioxidation, and antiallergic effects. Lonicera japonica (11.0% of all prescriptions) with Forsythia suspense (17.0% of all prescriptions) was the most commonly used CHM combination and was also the core treatment for treating the heat pattern, in which an antimicrobial effect is found. CHM network analysis is helpful for TCM doctors or researchers to choose candidates for clinical practice or further studies.