Epidemiology, Treatment Patterns, and Healthcare Resource Utilization Study of Patients With Alopecia Areata in Taiwan's National Health Insurance Research Database.

OBJECTIVES: This study investigated the epidemiology, treatment patterns, and resource utilization in patients with alopecia areata (AA) in Taiwan using the National Health Insurance Research Database. AA severity was determined by treatment use and diagnostic codes in the year after enrollment (including corticosteroids, systemic immunosuppressants, topical immunotherapy, and phototherapy). METHODS: The cross-sectional analysis was conducted to estimate the incidence and prevalence of AA from 2016 to 2020. For the longitudinal analysis, 2 cohorts were identified: mild/moderate and severe. The cohorts were matched based on age, gender, and comorbidities. Patients were enrolled upon their first claim with an AA diagnosis during the index period of 2017-2018. RESULTS: The number of patients with AA increased from 3221 in 2016 to 3855 in 2020. The longitudinal analysis identified 1808 mild/moderate patients and 452 severe patients. Mild/moderate patients used higher levels of topical corticosteroids (82.41%) than severe patients (73.45%). Conversely, severe patients used more topical nonsteroids (41.81%) and systemic therapies (51.77%) than mild/moderate patients (0.44% and 16.15%, respectively). Oral glucocorticoids use was higher in severe patients (47.57%) relative to mild/moderate patients (14.88%), whereas the use of injectable forms was similar. The most used systemic immunosuppressants were methotrexate, cyclosporin, and azathioprine. Topical immunotherapy utilization decreased with subsequent treatment lines for severe patients. Treatment persistence at 6 months was low for all treatments. Severe patients had higher annual AA-related outpatient visits than the mild/moderate cohort. CONCLUSIONS: These findings highlight the need for additional innovations and therapies to address the clinical and economic burden of AA.

Treatment pattern and health care resource utilization for Taiwanese patients with migraine: a population-based study.

Objectives: Given the substantial disease burden, appropriate and effective management of migraine is a public health priority. To gain insights into real-world migraine management practices in Taiwan, current treatment patterns, costs, and health care resource use were assessed. Methods: This was a retrospective, longitudinal study using the Taiwan National Health Insurance Research Database. Included patients had an initial diagnosis of migraine (defined using International Classification of Diseases codes) between 1 January 2013 and 31 December 2017. Data analyzed included demographics; the use, number, and type of acute and preventive medications; and drug and medical services costs. Data were stratified according to migraine type (chronic [CM] or episodic [EM] migraine). Results: A total of 312,718 patients were included in the analyses: 53,992 (17.3%) had CM and 258,726 (82.7%) had EM. Most patients (81.7%) had used acute and/or preventive medications; acute medications used more frequently than preventive medications (78.0% vs. 20.2%). Acute medications were used by 81.6 and 77.3% of patients with CM and EM, respectively. Commonly used acute medications were acetaminophen (68.8%), ergots (49.4%), and non-steroidal anti-inflammatory drugs (38.4%); the use of triptans (6.0%), tramadol (3.1%), and other opioids (0.2%) was less common. A total of 28.6 and 18.5% of patients with CM and EM, respectively, used preventive medications. Flunarizine (68.9%), propranolol (40.7%), and topiramate (16.0%) were the most commonly used preventive medications. Most patients had used 1-2 acute or preventive medications, with the use of ≥3 acute or preventive medications more common in patients with CM than EM. Average total medical cost per annum was 4,169 New Taiwan Dollars (NTDs) per CM patient and 2,928 NTDs per EM patient, with CM patients having higher costs associated with medical service utilization and acute medication use. Conclusion: These real-world data suggest unmet needs for Taiwanese patients with migraine, including under-utilization of preventive medications and greater costs and health care resource use for patients with CM versus EM. These findings provide important information on treatment patterns, cost, and health care resource use for patients with migraine in Taiwan.

Patient Characteristics, Treatment Patterns, Healthcare Resource Utilization, and Costs of Targeted Therapy-Eligible Atopic Dermatitis Patients in Taiwan-A Real-World Study.

INTRODUCTION: The objective of this study was to conduct a retrospective analysis to understand the patient profile, treatment patterns, healthcare resource utilization, and cost of atopic dermatitis (AD) of patients eligible for targeted therapy in Taiwan. METHODS: A retrospective, claims-based analysis was undertaken using Taiwan's National Health Insurance Research Database from 01 January 2014 to 31 December 2017. Patients aged ≥ 2 years and with at least one diagnosis code for AD during 2015 were identified. Patients with comorbid autoimmune diseases were excluded. Enrolled AD patients were categorized using claims-based treatment algorithms by disease severity and their eligibility for targeted therapy treatment. A cohort of targeted therapy-eligible patients was formed, and a matched cohort using patients not eligible for targeted therapy was derived using propensity score matching based on age, gender, and the Charlson Comorbidity Index (CCI). Treatment patterns, resource utilization, and costs were measured during a 1-year follow-up period. RESULTS: A total of 377,423 patients with AD were identified for this study. Most patients had mild AD (84.5%; n = 318,830) with 11.9% (n = 45,035) having moderate AD, and 3.6% (n = 13,558) having severe AD. Within the 58,593 moderate-to-severe AD patients, 1.5% (n = 897) were included in the targeted therapy-eligible cohort. The matched cohort consisted of 3558 patients. During the 1-year follow-up period, targeted therapy-eligible patients utilized antihistamines (85.5%), topical treatments (80.8%), and systemic anti-inflammatories (91.6%) including systemic corticosteroids (51.4%) and azathioprine (59.1%). During the first year of follow-up, targeted therapy-eligible patients (70.5%; 7.01 [SD = 8.84] visits) had higher resource utilization rates and frequency of AD-related outpatient visits compared with the matched cohort (40.80%; 1.85 [SD = 4.71] visits). Average all-cause direct costs during 1-year follow-up were $2850 (SD = 3629) and $1841 (SD = 6434) for the eligible targeted therapy and matched cohorts, respectively. AD-related costs were 17.7% ($506) of total costs for the targeted therapy eligible cohort and 2.2% ($41) for the matched cohort. CONCLUSIONS: AD patients eligible for targeted therapy in Taiwan experienced high resource and economic burden compared with their non-targeted-therapy-eligible counterparts.

Management of Refractory Status Epilepticus: An International Cohort Study (MORSE CODe) Analysis of Patients Managed in the ICU.

BACKGROUND AND OBJECTIVES: Status epilepticus that continues after the initial benzodiazepine and a second anticonvulsant medication is known as refractory status epilepticus (RSE). Management is highly variable because adequately powered clinical trials are missing. We aimed to determine whether propofol and midazolam were equally effective in controlling RSE in the intensive care unit, focusing on management in resource-limited settings. METHODS: Patients with RSE treated with midazolam or propofol between January 2015 and December 2018 were retrospectively identified among 9 centers across 4 continents from upper-middle-income economies in Latin America and high-income economies in North America, Europe, and Asia. Demographics, Status Epilepticus Severity Score, etiology, treatment details, and discharge modified Rankin Scale (mRS) were collected. The primary outcome measure was good functional outcome defined as a mRS score of 0-2 at hospital discharge. RESULTS: Three hundred eighty-seven episodes of RSE (386 patients) were included, with 162 (42%) from upper-middle-income and 225 (58%) from high-income economies. Three hundred six (79%) had acute and 79 (21%) remote etiologies. Initial RSE management included midazolam in 266 (69%) and propofol in 121 episodes (31%). Seventy episodes (26%) that were initially treated with midazolam and 42 (35%) with propofol required the addition of a second anesthetic to treat RSE. Baseline characteristics and outcomes of patients treated with midazolam or propofol were similar. Breakthrough (odds ratio [OR] 1.6, 95% CI 1.3-2.0) and withdrawal seizures (OR 2.0, 95% CI 1.7-2.5) were associated with an increased number of days requiring continuous intravenous anticonvulsant medications (cIV-ACMs). Prolonged EEG monitoring was associated with fewer days of cIV-ACMs (1-24 hours OR 0.5, 95% CI 0.2-0.9, and >24 hours OR 0.7, 95% CI 0.5-1.0; reference EEG <1 hour). This association was seen in both, high-income and upper-middle-income economies, but was particularly prominent in high-income countries. One hundred ten patients (28%) were dead, and 80 (21%) had good functional outcomes at hospital discharge. DISCUSSION: Outcomes of patients with RSE managed in the intensive care unit with propofol or midazolam infusions are comparable. Prolonged EEG monitoring may allow physicians to decrease the duration of anesthetic infusions safely, but this will depend on the implementation of RSE management protocols. Goal-directed management approaches including EEG targets may hold promise for patients with RSE. CLASSIFICATION OF EVIDENCE: This study provides Class III data that propofol and midazolam are equivalently efficacious for RSE.

Identifying prognostic factors and developing accurate outcome predictions for in-hospital cardiac arrest by using artificial neural networks.

BACKGROUND: Accurate estimation of neurological outcomes after in-hospital cardiac arrest (IHCA) provides crucial information for clinical management. This study used artificial neural networks (ANNs) to determine the prognostic factors and develop prediction models for IHCA based on immediate preresuscitation parameters. METHODS: The derived cohort comprised 796 patients with IHCA between 2006 and 2014. We applied ANNs to develop prediction models and evaluated the significance of each parameter associated with favorable neurological outcomes. An independent dataset of 108 IHCA patients receiving targeted temperature management was used to validate the identified parameters. The generalizability of the models was assessed through fivefold cross-validation. The performance of the models was assessed using the area under the curve (AUC). RESULTS: ANN model 1, based on 19 baseline parameters, and model 2, based on 11 prearrest parameters, achieved validation AUCs of 0.978 and 0.947, respectively. ANN model 3 based on 30 baseline and prearrest parameters achieved an AUC of 0.997. The key factors associated with favorable outcomes were the duration of cardiopulmonary resuscitation; initial cardiac arrest rhythm; arrest location; and whether the patient had a malignant disease, pneumonia, and respiratory insufficiency. On the basis of these parameters, the validation performance of the ANN models achieved an AUC of 0.906 for IHCA patients who received targeted temperature management. CONCLUSION: The ANN models achieved highly accurate and reliable performance for predicting the neurological outcomes of successfully resuscitated patients with IHCA. These models can be of significant clinical value in assisting with decision-making, especially regarding optimal postresuscitation strategies.

The effect of monoamine oxidase-B inhibitors on the alleviation of depressive symptoms in Parkinson's disease: meta-analysis of randomized controlled trials.

BACKGROUND: Depression is a major nonmotor symptom of Parkinson's disease (PD). However, few treatments exist for PD depression. Monoamine oxidase-B inhibitors (MAOB-Is) provide symptomatic relief for the motor symptoms of PD and exert antidepressive effects. The present meta-analysis of randomized controlled trials (RCTs) investigated the effects of MAOB-Is on depressive symptoms in patients with PD. METHODS: Articles on PD-management-related RCTs using one of three MAOB-Is approved by the US Food and Drug Administration, that is, selegiline, rasagiline, and safinamide, were identified. The primary outcomes were the benefits of MAOB-Is for depressive symptoms. Subgroup analysis included the effects of MAOB-Is on patients in the early versus middle-to-late stages of PD and the effect of short-term versus long-term treatment. RESULTS: Overall, six studies were included, four of which were conducted on patients with early stage PD. Overall, MAOB-Is significantly reduced the severity of depressive symptoms [standardized mean difference (SMD): -0.14, 95% confidence interval (CI): -0.21 to -0.06, p < 0.001]. Subgroup analysis indicated that the positive effect of MAOB-Is was significant in patients with early stage PD (SMD: -0.20, 95% CI: -0.31 to -0.09, p < 0.001), but not in those with middle-to-late-stage PD (SMD: -0.07, 95% CI: -0.17 to 0.03, p = 0.18). The antidepressive effect was significant for short-term treatment, that is, 90-120 days (SMD: -0.23, 95% CI: -0.35 to -0.10, p < 0.001), but not long-term treatment, that is, 24 weeks to 18 months (SMD: -0.08, 95% CI: -0.18 to 0.01, p = 0.09). CONCLUSION: In addition to the treatment of PD motor symptoms, MAOB-Is may help reduce the severity of depressive symptoms in PD, especially in patients with early stage PD. Considering the tolerability and simultaneous benefits of MAOB-Is, further RCTs are warranted to confirm their therapeutic effects in moderate-to-severe PD depression.

Efficacy of levetiracetam for migraine prophylaxis: A systematic review and meta-analysis.

BACKGROUND: Migraine is characterized by moderate to severe recurrent headache lasting for 4-72 h. Cortical hyperexcitability may play a crucial role in migraine onset. Therefore, antiepileptic drugs, such as levetiracetam, may be beneficial. METHODS: We performed a systematic review and meta-analysis of randomized controlled trials (RCTs) and prospective studies that evaluated the efficacy of levetiracetam in migraine prophylaxis. Electronic databases, including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, were searched for articles on migraine prophylaxis and levetiracetam published before May 2020. The main outcomes were number of patients with >50% headache frequency reduction, frequency of headache, and headache severity. RESULTS: We identified 4 RCTs involving 192 patients and 4 prospective studies involving 85 patients. The overall data on number of patients with >50% headache frequency reduction, headache frequency, and headache severity were subjected to meta-analysis, which revealed significant differences between the levetiracetam and the placebo groups (risk ratio [RR] of number of patients with >50% headache frequency reduction = 0.46, 95% confidence interval [CI] = 0.35 to 0.61; weighted mean difference [WMD] of headache frequency per month = -3.78, 95% CI = -5.52 to -2.03; standard mean difference [SMD] of headache severity = -2.42, 95% CI = -4.47 to -0.37). CONCLUSION: Our study indicated that levetiracetam can significantly reduce headache frequency and severity in adults and children. Thus, oral levetiracetam can be a therapeutic option for migraine prophylaxis, especially concerning with the adverse effects or teratogenicity of other preventive treatments.

Predicting major neurologic improvement and long-term outcome after thrombolysis using artificial neural networks.

OBJECTIVE: To develop artificial neural network (ANN)-based functional outcome prediction models for patients with acute ischemic stroke (AIS) receiving intravenous thrombolysis based on immediate pretreatment parameters. METHODS: The derived cohort consisted of 196 patients with AIS treated with intravenous thrombolysis between 2009 and 2017 at Shuang Ho Hospital in Taiwan. We evaluated the predictive value of parameters associated with major neurologic improvement (MNI) at 24 h after thrombolysis as well as the 3-month outcome. ANN models were applied for outcome prediction. The generalizability of the model was assessed through 5-fold cross-validation. The performance of the models was assessed according to the accuracy, sensitivity, specificity, and area under the receiver operating characteristic curve (AUC), RESULTS: The parameters associated with MNI were blood pressure (BP), heart rate, glucose level, consciousness level, National Institutes of Health Stroke Scale (NIHSS) score, and history of diabetes mellitus (DM). The parameters associated with the 3-month outcome were age, consciousness level, BP, glucose level, hemoglobin A1c, history of DM, stroke subtype, and NIHSS score. After adequate training, ANN Model 1 to predict MNI achieved an AUC of 0.944. Accuracy, sensitivity, and specificity were 94.6%, 89.8%, and 95.9%, respectively. ANN Model 2 to predict the 3-month outcome achieved an AUC of 0.933, with accuracy, sensitivity, and specificity of 88.8%, 94.7%, and 86.5%, respectively. CONCLUSIONS: The ANN-based models achieved reliable performance to predict MNI and 3-month outcomes after thrombolysis for AIS. The models proposed have clinical value to assist in decision-making, especially when invasive adjuvant strategies are considered.

Low-Level Laser Therapy for Fibromyalgia: A Systematic Review and Meta-Analysis.

BACKGROUND: Fibromyalgia is a chronic disorder characterized by widespread pain and tenderness. Low-level laser therapy (LLLT), an emerging nonpharmacological treatment, has been used for relieving musculoskeletal or neuropathic pain. OBJECTIVE: The objective of this review and meta-analysis was to determine the efficacy of LLLT on patients with fibromyalgia. STUDY DESIGN: This study involved systematic review and quantitative meta-analysis of published randomized controlled trials (RCTs). SETTING: This study examined all RCTs evaluating the effect of LLLT on fibromyalgia. METHODS: We performed a systematic review and meta-analysis of RCTs evaluating the effect of LLLT on patients with fibromyalgia. PubMed, EMBASE, and the Cochrane Library were searched for articles published before August 2018. RCTs meeting our selection criteria were included. The methodological quality of the RCTs was evaluated according to the Cochrane risk-for-bias method. Review Manager version 5.3 was used to perform the meta-analysis. The primary outcomes were the total scores on the Fibromyalgia Impact Questionnaire (FIQ), pain severity, and number of tender points. The secondary outcomes were changes in fatigue, stiffness, anxiety, and depression. Standardized mean difference (SMD), 95% confidence intervals (CI), and P values were calculated for outcome analysis. RESULTS: We identified 9 RCTs that included 325 fibromyalgia patients undergoing LLLT or placebo laser treatment with or without an exercise program. The meta-analysis showed that patients receiving LLLT demonstrated significantly greater improvement in their FIQ scores (SMD: 1.16; 95% CI, 0.64-1.69), pain severity (SMD: 1.18; 95% CI, 0.82-1.54), number of tender points (SMD: 1.01; 95% CI, 0.49-1.52), fatigue (SMD: 1.4; 95% CI, 0.96-1.84), stiffness (SMD: 0.92; 95% CI, 0.36-1.48), depression (SMD: 1.46; 95% CI, 0.93-2.00), and anxiety (SMD: 1.46; 95% CI, 0.45-2.47) than those receiving placebo laser. Furthermore, when compared with the standardized exercise program alone, LLLT plus the standardized exercise program provided no extra advantage in the relief of symptoms. On the other hand, the results of the only RCT using combined LLLT/LED phototherapy showed significant improvement in most outcomes except for depression when compared to placebo. When compared with pure exercise therapy, combined LLLT/LED phototherapy plus exercise therapy had additional benefits in reducing the severity of pain, number of tender points, and fatigue. LIMITATIONS: There were some limitations in this review, mostly because of the low-to-middle methodological quality of the selected studies; for example, there was no clear allocation process and only patients were blinded in most studies. In addition, one study used per-protocol analysis with a 20% loss to follow-up. On the other hand, the differences in laser types, energy sources, exposure times, and associated medication status in these studies may have resulted in some heterogeneity. CONCLUSIONS: Our results provided the most up-to-date and relevant evidence regarding the effects of LLLT in fibromyalgia. LLLT is an effective, safe, and well-tolerated treatment for fibromyalgia. KEY WORDS: Low-level laser therapy, fibromyalgia, meta-analysis, FIQ, pain, tender points,exercise.

Association Between Acid-Sensing Ion Channel 3 Gene Variants and Balance Impairment in People With Mild Traumatic Brain Injury.

Introduction: Dizziness and balance impairment are common symptoms of mild traumatic brain injury (mTBI). Acid-sensing ion channel 3 (ASIC3) is expressed in the vestibular and proprioceptive systems and associated with balance functions. However, whether the genetic variants of ASIC3 are associated with people who suffer dizziness and balance impairment after mTBI remained unknown. Materials and methods: A total of 200 people with mTBI and 109 non-mTBI controls were recruited. Dizziness, balance functions, and the ability to perform daily activities were assessed by Dizziness Handicap Inventory (DHI), and objective balance functions were investigated by the postural stability test. Three diseases-related genetic variants of ASIC3 were determined through polymerase chain reaction and followed by restriction fragment length polymorphism. The Student's t-test and Mann-Whitney U-test were used for normal and abnormal distributed data, respectively. The regression was applied to adjust gender and age. The normality of continuous data was evaluated by Shapiro-Wilk test. Results: In the mTBI people, the rs2288645-A allele carriers exhibited a significantly worse physical domain DHI score (A-allele carriers: 11.39 ± 8.42, non-A carriers: 8.76 ± 7.87, p = 0.03). The rs4148855-GTC deletion carriers an exhibited significantly worse overall postural stability (GTC deletion carriers: 0.53 ± 0.33, non-carriers: 0.46 ± 0.20, p = 0.03). In the controls, rs2288646-A allele carriers were significant worse in the medial-to-lateral postural stability (A-allele carriers: 0.31 ± 0.17, non-A carriers: 0.21 ± 0.10, p = 0.01). Conclusion: The present study demonstrated that ASIC3 genetic variants were associated with certain aspects of balance functions and dizziness questionnaires in people of mTBI and non-mTBI. It provides a possible evidence that ASIC3 could be a new target for the management of the balancing disorders. However, further investigations are warranted to elucidate the underlying mechanisms and clinical significance.

Widespread interictal epileptic discharge more likely than focal discharges to unveil the seizure onset zone in EEG-fMRI.

OBJECTIVE: We hypothesized that the number of interictal epileptic discharges (IEDs) during scan and their spatial extent are contributing factors in obtaining appropriate activations that reveal the seizure onset zone (SOZ) in EEG-fMRI. METHODS: 157 IED types, each corresponding to one EEG scalp distribution, in 64 consecutive EEG-fMRI studies from 64 patients with refractory localization-related epilepsy were reviewed. To determine reliable activation, we used the threshold corresponding to corrected whole-brain topological false discovery rate (FDR). The location with maximum activation was compared to the presumed SOZ as defined by a comprehensive evaluation for each patient. RESULTS: The number of IEDs was significantly higher in the types with t-value above FDR than with t-value below FDR. The presumed SOZ could be delineated in 30 of the 64 patients. Among these patients, the types of IED concordant with the SOZ had significantly larger extent on scalp EEG than the IED types discordant with the SOZ. CONCLUSIONS: The number of IEDs is important factor in obtaining reliable activations in EEG-fMRI. IEDs with larger spatial extent are more likely to reveal, on maximum BOLD, accurate location of the SOZ. SIGNIFICANCE: Widespread discharges are more likely to yield a reliable activation for SOZ in EEG-fMRI.

Development and validation of risk score to estimate 1-year late poststroke epilepsy risk in ischemic stroke patients.

OBJECTIVE: This study aimed to develop and validate a prognostic model for the 1-year risk of late poststroke epilepsy (PSE). MATERIALS AND METHODS: We included patients initially diagnosed with ischemic stroke between 2003 and 2014 in a National Health Insurance claims-based cohort in Taiwan. Patients were further divided into development and validation cohorts based on their year of stroke diagnosis. Multivariable Cox regression with backward elimination was used to analyze the association between 1-year PSE and risk factors before and on stroke admission. RESULTS: In total, 1,684 (1.93%) and 725 (1.87%) ischemic stroke patients comprising the development and validation cohorts, respectively, experienced late PSE within 1 year after stroke. Seven clinical variables were examined to be independently associated with 1-year risk of PSE. We developed a risk score called "PSEiCARe" ranging from 0 to 16 points, comprising the following factors: prolonged hospital stay (>2 weeks, 1 point), seizure on admission (6 points), elderly patients (age ≥80 years, 1 point), intensive care unit stay on admission (3 points), cognitive impairment (dementia, 2 points), atrial fibrillation (2 points), and respiratory tract infection (pneumonia) on admission (1 point). Patients were further classified into low-, medium-, high-, and very-high-risk groups. The incidence (per 100 person-years) was 0.64 (95% CI: 0.56-0.71) for the low-risk, 2.62 (95% CI: 2.43-2.82) for the medium-risk, 10.3 (95% CI: 9.48-11.3) for the high-risk, and 28.2 (95% CI: 24.0-33.0) for the very-high-risk groups. Discrimination and calibration were satisfactory, with a Harrell's C of 0.762 in the development model and 0.792 in the validation model. CONCLUSION: PSEiCARe is an easy-to-use prognostic score that integrates patient characteristics and clinical factors on stroke admission to predict 1-year PSE risk; it has the potential to assist individualized patient management and improve clinical practice, thereby preventing the occurrence of late PSE.

The Association of Apolipoprotein E Allele 4 Polymorphism with the Recovery of Sleep Disturbance after Mild Traumatic Brain Injury.

PURPOSE: Mild traumatic brain injury (mTBI) is a major public health concern. The apolipoprotein E (APOE) gene contains three polymorphisms, and the APOE4 polymorphism may affect several physiological states, such as the recovery from mTBI as well as sleep. This study aims to investigate the association between APOE4 with the recovery of sleep disturbance after mTBI. METHODS: From May 2012 to Aug 2015, 189 mTBI patients completed baseline (1st week post-mTBI) and follow-up (6th week post-mTBI) sleep assessments that involved using the Pittsburgh Sleep Quality Index (PSQI). APOE genotypes were determined by sequencing the products of polymerase chain reaction from genomic DNA. Statistical analyses were performed using the Wilcox signed-rank or chi-square test. RESULTS: Thirty-five (18.5%) participants were APOE4 carriers. At baseline, the demographic data and the severity of sleep disturbance were similar in both groups. APOE4 carriers demonstrated significant improvement in the overall PSQI score (8.34±3.9 at baseline and 7.43±3.99 at follow-up, p = 0.05) and scores of several PSQI subscales, including sleep disturbance, sleep latency, daytime dysfunction caused by sleepiness, and overall sleep quality, which was similar to APOE4 noncarriers. CONCLUSION: APOE4 is not associated with the recovery of sleep disturbance after mTBI.

Effect of acupuncture on aromatase inhibitor-induced arthralgia in patients with breast cancer: A meta-analysis of randomized controlled trials.

PURPOSE: Aromatase inhibitor (AI)-induced arthralgia (AIA) is a common side effect that may lead to premature discontinuation of effective hormonal therapy in patients with breast cancer. Acupuncture may relieve joint pain in patients with AIA. We conducted a meta-analysis of randomized controlled trials (RCTs) to evaluate the effectiveness of acupuncture in pain relief in AIA. METHODS: The PubMed, Embase, Cochrane Library, and Scopus databases and the ClinicalTrials.gov registry were searched for studies published before February 2017. Individual effect sizes were standardized, and a meta-analysis was conducted to calculate the pooled effect size by using a random effect model. Pain was assessed using the Brief Pain Inventory (BPI) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 3-4, 6-8, and 12 weeks. Secondary outcomes included disability level, upper extremity function, physical performance, and quality of life. RESULTS: Five trials involving 181 patients were reviewed. Significant pain reduction was observed after 6-8 weeks of acupuncture treatment. Patients receiving acupuncture showed a significant decrease in the BPI worst pain score (weighted mean difference [WMD]: -3.81, 95% confidence interval [CI]: -5.15 to -2.47) and the WOMAC pain score (WMD: -130.77, 95% CI: -230.31 to -31.22) after 6-8 weeks of treatment. One of the 4 trials reported 18 minor adverse events in 8 patients during 398 intervention episodes. CONCLUSION: Acupuncture is a safe and viable nonpharmacologic treatment that may relieve joint pain in patients with AIA. Additional studies involving a higher number of RCTs are warranted.

Chronic obstructive pulmonary disease is associated with increased recurrent peptic ulcer bleeding risk.

BACKGROUND: The association between chronic obstructive pulmonary disease (COPD) and the risk of recurrent peptic ulcer bleeding (PUB) remains unclear. In this study, we compared the risk of recurrent PUB between patients with and those without COPD. METHODS: Using the Taiwan National Health Insurance Research Database, we first selected patients newly diagnosed with PUB in 2002-2009. Two groups comprising 13,732 COPD cases and 13,732 non-COPD matched controls were created using propensity score matching, thereby making the differences in basic demographics, medication use, and disease conditions between the two groups negligible. Cox proportional hazard regression was used to evaluate the risk of recurrent PUB during the follow-up period. RESULTS: The cumulative recurrence rate of PUB was significantly higher in the patients with COPD than in the non-COPD matched controls (2years: 10.8% vs 9.3%; 6years: 18.3% vs 15.7%, P all <0.05), with an adjusted hazard ratio (HR) of 1.17 (95% confidence interval [CI], 1.08-1.26, P<0.001) and 1.19 (95% CI, 1.12-1.26, P<0.001) within 2-year and 6-year follow-ups, respectively. Patients with COPD using steroids were at a marginally higher risk of recurrent PUB than those who did not use steroids. Multivariate stratified analysis revealed similar results in many subgroups. CONCLUSIONS: The risk of recurrent PUB is higher in patients with COPD than in patients without COPD.

Newly Diagnosed Anemia Increases Risk of Parkinson's disease: A Population-Based Cohort Study.

Anemia and low hemoglobin have been identified to increase Parkinson's disease (PD) risk. This population-based cohort study investigated PD risk in newly diagnosed anemic patients by using data from the Taiwan National Health Insurance Research Database. All newly diagnosed anemic patients (n = 86,334) without a history of stroke, neurodegenerative diseases, traumatic brain injury, major operations, or blood loss diseases were enrolled. A cohort of nonanemic controls, 1:1 matched with anemic patients on the basis of the demographics and pre-existing medical conditions, was also included. Competing risk analysis was used to evaluate PD risk in anemic patients compared with that in their matched controls. The adjusted hazard ratio (aHR) of PD risk in the anemic patients was 1.36 (95% confidence interval [CI]: 1.22-1.52, p < 0.001). Iron deficiency anemia (IDA) patients tended to exhibit a higher PD risk (aHR: 1.49; 95% CI: 1.24-1.79, p < 0.001). Furthermore, Iron supplement did not significantly affect the PD risk: the aHRs for PD risk were 1.32 (95% CI: 1.07-1.63, p < 0.01) and 1.86 (95% CI: 1.46-2.35, p < 0.001) in IDA patients with and without iron supplementation, respectively. The population-based cohort study indicated newly diagnosed anemia increases PD risk.

Intranasal corticosteroid therapy in the treatment of obstructive sleep apnea: A meta-analysis of randomized controlled trials.

AIM: To assess the efficacy of intranasal corticosteroid therapy in the treatment of obstructive sleep apnea (OSA) based on current evidence. METHODS: A number of medical literature data bases: PubMed, Cochrane Library, Scopus, and CINAHL, were searched comprehensively to identify randomized controlled trials (RCT) that reported on the efficacy of intranasal corticosteroid therapy for OSA. The selected studies were subjected to a meta-analysis and a risk-of-bias assessment. RESULTS: Seven RCTs met our eligibility criteria, five of these were included in our meta-analysis. The results indicated that intranasal corticosteroid therapy has a better effect in decreasing the apnea-hypopnea index compared with those participants who received placebo (standard mean difference 0.95 [95% confidence interval, -1.42 to -0.47]) (n = 221, I(2) = 62%). CONCLUSION: Our study results showed that patients who received intranasal corticosteroid therapy had a significant improvement in OSA. However, this evidence was limited by the potential risk of bias and heterogeneity of the selected RCTs.

Effects of Modafinil and Armodafinil in Patients With Obstructive Sleep Apnea: A Meta-analysis of Randomized Controlled Trials.

PURPOSE: Obstructive sleep apnea (OSA) is associated with nocturnal hypoxemia, excessive daytime sleepiness (EDS), and sympathetic hyperactivation. Continuous positive airway pressure is the first-line treatment for OSA. However, some patients may have residual EDS. Modafinil and its R-enantiomer, armodafinil, are wakefulness-promoting agents known to be effective in alleviating sleepiness. METHODS: We performed a systematic review and meta-analysis of data from published randomized controlled trials (RCTs) that evaluated the efficacy of modafinil and armodafinil in treating EDS in patients with OSA. Electronic databases, including PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, were searched for articles on OSA published before October 2015. FINDINGS: We identified 11 RCTs of modafinil involving 723 patients and 5 RCTs of armodafinil involving 1009 patients. A pooled estimate of the mean differences in sleepiness parameters versus placebo were calculated using the random-effects model. Epworth Sleepiness Scale scores improved significantly in the modafinil group (weighted mean difference [WMD], -2.96 [95% confidence interval (CI), -3.73 to -2.19]) and in the armodafinil group (WMD, -2.63; 95% CI, -3.4 to -1.85) compared with those in the placebo group. Sleep latency, as measured on the Maintenance of Wakefulness Test, was significantly prolonged in the modafinil group (WMD, 2.51 [95% CI, 1.5-3.52]) and in the armodafinil group (WMD, 2.71 [95% CI, 0.04-5.37]). Patients tolerated the adverse events with both medications well. IMPLICATIONS: The findings from our study suggest that both modafinil and armodafinil significantly improved subjective and objective daytime sleepiness. Thus, modafinil and armodafinil may be recommended to patients with OSA, particularly those with EDS.

Serum Bilirubin Is Inversely Associated with Increased Arterial Stiffness in Men with Pre-Hypertension but Not Normotension.

OBJECTIVE: Serum bilirubin level has shown to be inversely associated with coronary atherosclerosis, and may serve as a protective biomarker of coronary artery disease. Serum bilirubin has also been shown to be negatively associated with brachial-ankle pulse wave velocity (baPWV) in men without a history of hypertension, and in men with hypertension. It is unknown whether such associations can be observed in the pre-hypertensive or normotensive population. This study thus aimed to investigate the relationship between serum bilirubin level and increased arterial stiffness in subjects with pre-hypertension and normotension for both genders. METHODS: A cross-sectional sample of 3,399 apparently healthy subjects undergoing a medical check-up at National Cheng Kung University Hospital was enrolled between October 2006 and August 2009, after excluding subjects with serum total bilirubin level greater than 20.52 µmol/L. Increased arterial stiffness was defined as baPWV of 1,400 cm/s or higher as the dichotomous variable and bilirubin as the continuous variable. RESULTS: Based on multiple linear regression analysis, serum bilirubin level was inversely associated with baPWV in non-hypertensive men (ß = -0.066, p < 0.001) but not in non-hypertensive women. In addition, the inverse relationship between bilirubin level and baPWV was found statistically significant only in pre-hypertensive men (ß = -0.110, p < 0.001). Multiple logistic regression analysis showed that serum bilirubin was inversely associated with increased arterial stiffness in men with pre-hypertension (odds ratio = 0.955, 95% confidence interval = 0.916-0.996, p < 0.05) but not normotension after adjustment for other confounding factors. However, the relationship between total bilirubin level and increased arterial stiffness did not reach statistical significance for female subjects with pre-hypertension and normotension. CONCLUSION: Serum bilirubin is inversely associated with increased arterial stiffness in men with pre-hypertension but not normotension. The association between bilirubin level and arterial stiffness was not found significant in women.