Regorafenib for Taiwanese patients with unresectable hepatocellular carcinoma after sorafenib failure: Impact of alpha-fetoprotein levels.

BACKGROUND AND AIMS: Regorafenib has demonstrated its survival benefit for unresectable hepatocellular carcinoma (uHCC) patients in a phase III clinical trial. We aimed to assess the efficacy and tolerability of regorafenib and the predictors of treatment outcomes in Taiwanese patients. METHODS: We analyzed the survival, best overall response, predictors of treatment outcomes, and safety for uHCC patients who had tumor progression on sorafenib therapy and received regorafenib as salvage therapy between March 2018 and November 2020. RESULTS: Eighty-six patients with uHCC were enrolled (median age, 66.5 years; 76.7% male). The median regorafenib treatment duration was 4.0 months (95% confidence interval [CI], 3.6-4.6). The most frequently reported adverse events were hand-foot skin reaction (44.2%), diarrhea (36.0%), and fatigue (29.1%). No unpredictable toxicity was observed during treatment. The median overall survival (OS) with regorafenib was 12.4 months (95% CI, 7.8-17.0) and the median progression-free survival (PFS) was 4.2 months (95% CI, 3.7-4.7). Of 82 patients with regorafenib responses assessable, 4 patients (4.9%) achieved a partial response, and 33 (40.2%) had stable disease, leading to a disease control rate (DCR) of 45.1% (n = 37). Patients possessing baseline AFP < 400 ng/ml exhibited a markedly longer median OS, median PFS, and higher DCR compared with their counterparts (15.7 vs. 8.1 months, 4.6 vs. 3.7 months, 60.9% vs. 27.5%, respectively). Despite possessing high baseline AFP levels, patients with early AFP response (>10% reduction at 4 weeks or >20% reduction at 8 weeks after regorafenib administration) exhibited comparable treatment outcomes to those with baseline AFP < 400 ng/ml. CONCLUSIONS: The results of this real-world study verified the tolerability and efficacy of regorafenib treatment for uHCC patients who failed prior sorafenib therapy, especially for those with lower baseline AFP levels or with early AFP response.

Acupuncture Treatment is Associated with a Decreased Risk of Dementia in Patients with Depression: A Propensity Score-Matched Cohort Study.

BACKGROUND: Depression is one of the most disabling disorders, which causes long-term complications such as neurodegenerative disorder and cerebrovascular disease. Some patients with depression seek acupuncture treatment. We aimed to investigate the association between acupuncture treatment and the risk of dementia in patients with depression from the perspective of real-world evidence. METHODS: Patients over 18 years old and newly diagnosed with depression between 1997 and 2010 were selected from the Taiwanese National Health Insurance Research Database and followed up until the end of 2013. Propensity score was used to match equal numbers of patients 1:1 (N = 16,609 per group) into acupuncture and non-acupuncture cohorts based on characteristics including sex, age, baseline comorbidity and drug use. The outcome measurement was the comparison of dementia incidence in the two cohorts. RESULTS: Compared with the non-acupuncture cohort, patients who received acupuncture treatment had a decreased risk of dementia (adjusted hazard ratio (aHR) = 0.54; 95% confidence interval (CI) = 0.50-0.58, P < 0.001) after adjustment for age, sex, comorbidities and drug use. Compared with depression patients who did not receive acupuncture, the aHR of vascular dementia and Alzheimer's disease incidences for patients who had acupuncture therapy was 0.59 (95% CI 0.48-0.71) and 0.51 (95% CI 0.39-0.67), respectively. The cumulative incidence of dementia was significantly lower in the acupuncture cohort than in the non-acupuncture cohort (Log rank test, p < 0.001). CONCLUSION: The present study from real-world data revealed that acupuncture reduced the risk of dementia in depression patients, which supports healthcare decisions in clinical practice.

Anti-inflammatory effects of powdered product of Bu Yang Huan Wu decoction: Possible role in protecting against Transient Focal Cerebral Ischemia.

Bu Yang Huan Wu decoction (BYHW) is a traditional Chinese medicine (TCM) that consists of several herbs and has been used in patients with ischemic stroke for centuries. Although powdered formula of BYHW has widely been prescribed in clinic nowadays, evidence-based effectiveness and mechanism of action of BYHW powdered product in stroke remain to be characterized. Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 90 min followed by reperfusion for 24 h (ischemia/reperfusion; I/R) or sham surgery. After I/R, the rats were then given low dose (0.5 g/kg) and high dose (2.5 g/kg) of BYHW or vehicle by oral gavage twice a day for seven consecutive days. The results showed that I/R induced obvious cerebral infarction and neurobehavioral defects, in parallel with histological aberrations and extensive signaling of proinflammatory cytokines, including tumor necrosis factor (TNF-α) and interleukin-6 (IL-6), in the stroke model. Post-I/R treatment with BYHW powdered product significantly reduced the infarct area and ameliorated neurofunctional defects in a dose-dependent manner. The dose dependence was associated with TNF-α downregulation and interleukin-10 (IL-10) induction. In summary, the present findings demonstrated that BYHW powdered product exhibited therapeutic efficacy for experimental stroke and a higher dose treatment may strengthen the effectiveness via inflammatory modulation.

Hydrolyzed Chicken Extract (ProBeptigen®) on Cognitive Function in Healthy Middle-Aged People: A Randomized Double-Blind Trial.

Cognitive decline is an important issue of global public health. Cognitive aging might begin at middle adulthood, the period particularly vulnerable to stress in lifespan. Essence of chicken (EOC) has consistently demonstrated its beneficial effects on various cognitive domains as nutritional supplementation. This study primarily aimed to examine the cognitive enhancement effects of ProBeptigen® (previously named CMI-168), hydrolyzed peptides extracted from EOC, in healthy middle-aged people under mild stress. Ninety healthy subjects were randomly assigned into the ProBeptigen® or placebo group for eight weeks. Neurocognitive assessment, event-related potentials (ERPs), and blood tests were conducted before, during, and after the treatment. The ProBeptigen® group outperformed placebo group on Logical Memory subtests of Wechsler Memory Scale-third edition (WMS-III) and Spatial Working Memory task in the Cambridge Neuropsychological Test Automated Battery (CANTAB). The anti-inflammatory effects of ProBeptigen® in humans were also confirmed, with progressively declining high-sensitivity C-reactive protein (hs-CRP) levels. Regular dietary supplementation of ProBeptigen® is suggested to improve verbal short- and long-term memory as well as spatial working memory, and reduce inflammation in middle-aged healthy individuals with stress. The effects of ProBeptigen® on cognition warrant further investigation. (NCT03612752).

Utilization of Chinese herbal medicine and its association with the risk of fracture in patients with Parkinson's disease in Taiwan.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has been used for over two thousand years to treat motor impairments corresponding to the clinical manifestations of Parkinson's disease (PD). AIM OF THE STUDY: This study aimed to investigate the prescription of Chinese herbal medicine (CHM) for the management of PD and further determine whether CHM can improve motor function and decrease the risk of incident fracture. MATERIALS AND METHODS: Patients older than 40 years newly diagnosed with PD between January 1997 and December 2010 were selected from the National Health Insurance Research Database (NHIRD) and followed up until the end of 2013. We used 1:1 frequency matching by age, sex, index year, and initial diagnostic year to compare the TCM users and non-TCM users. We used a Cox regression model and the Kaplan-Meier method to estimate the risk of developing fracture among the TCM and non-TCM users. RESULTS: In total, 7197 patients older than 40 years were newly diagnosed with PD between 1997 and 2010 in Taiwan. Among these patients, 3456 were TCM users, and 3730 were non-TCM users. We compared 2007 PD patients with comparable demographic characteristics and comorbidity profiles between the two cohorts. During the follow-up period, compared with the non-TCM cohort, fewer patients in the TCM cohort had incident fractures (adjusted hazard ratio: 0.5, 95% CI: 0.44-0.56). The cumulative incidence of fracture was lower in the TCM cohort (log-rank test, p < 0.0001). Shi-Chang-Pu (Acorus gramineus Aiton), Yuan-Zhi (Polygala tenuifolia Willd), Bei-Mu (Fritillaria cirrhosa D. Don), Hai-Piao-Xiao (Sepiella maindronide Rochebrune; Sepia esculenta Hoyle), and Tian-Ma (Gastrodia elata Blume) constituted the core Chinese herbal medicine prescriptions used to treat PD patients. CONCLUSIONS: The present study identified the core prescription pattern for the management of PD in Taiwan. Complementary CHM therapy was associated with a reduced risk of fracture in PD patients.

Identification of groups with poor cost-effectiveness of peginterferon plus ribavirin for naïve hepatitis C patients with a real-world cohort and database.

BACKGROUND: For decades, peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (CHC) infection. However, the actual cost-effectiveness of this therapy remains unclear. We purposed to explore the real-world cost effectiveness for subgroups of treatment-naïve CHC patients with PegIFN/RBV therapy in a large real-world cohort using a whole population database. METHODS: A total of 1809 treatment-naïve chronic hepatitis C virus (HCV) patients (829 HCV genotype 1 [G1] and 980 HCV G2) treated with PegIFN/RBV therapies were linked to the National Health Insurance Research Database, covering the entire population of Taiwan from 1998 to 2013 to collect the total medical-care expenses of outpatient (antiviral agents, nonantiviral agents, laboratory, and consultation costs) and inpatient (medication, logistic, laboratory, and intervention costs) visits. The costs per treatment and the cost per sustained virological response (SVR) achieved were calculated. RESULTS: The average medical-care cost was USD $4823 (±$2984) per treatment and $6105 (±$3778) per SVR achieved. With SVR rates of 68.6% and 87.8%, the cost/SVR was significantly higher in G1 than those in G2 patients, respectively ($8285 vs $4663, P < .001). Treatment-naïve G1 patients of old ages, those with advanced fibrosis, high viral loads, or interleukin-28B unfavorable genotypes, or those without a rapid virological response (RVR: undetectable HCV RNA at week 4), or those with complete early virological response (cEVR: undetectable HCV RNA at week 12). Treatment-naïve G2 patients with high viral loads or without RVR or cEVR incurred significantly higher costs per SVR than their counterparts. The cost/SVR was extremely high among patients without RVR and in patients without cEVR. CONCLUSION: We investigated the real-world cost effectiveness data for different subgroups of treatment-naïve HCV patients with PegIFN/RBV therapies, which could provide useful, informative evidence for making decisions regarding future therapeutic strategies comprising costly direct-acting antivirals.

Effectiveness of Essence of Chicken in Improving Cognitive Function in Young People Under Work-Related Stress: A Randomized Double-Blind Trial.

Work-related stress (WS) can result in considerable and extensive changes in physiological and psychological performance. WS beyond the optimal levels induces anxiety, confusion, exhaustion, and burnout. Chronic WS affects neurocognitive performance, particularly attention and visuospatial memory. Essence of chicken (EC) has been reported to improve neurocognitive function after mental stress.To investigate the beneficial effects of EC in improving neurocognitive performance under WS, we conducted a randomized, double blind trial. Total 102 young workers in New Taipei City with high WS, evaluated using the Individual Subjective Perception Job Stress Scale scores (>36 for job leaders and 33 for nonleaders) were recruited. Fifty-one participants received 70 mL of EC and 51 received a placebo daily for 2 weeks. Blood tests and neurocognitive assessment were performed before treatment, at the end of treatment, and 2 weeks after treatment.EC improved the performance of participants with high depression scores in the form-color associative memory test, used for assessing short-term memory. Although creatinine and glutamic-pyruvic transaminase (GPT) levels increased in week 2, but the levels returned to the baseline in week 4. Blood urea nitrogen (BUN) levels decreased in week 4.EC significantly improved short-term memory in participants with high WS and concomitant depressive mood, although it slightly increased GPT and creatinine levels and reduced BUN levels. The long-term treatment effects of EC warrant further investigation.

Cancer incidence in people with affective disorder: nationwide cohort study in Taiwan, 1997-2010.

BACKGROUND: Cancer is a serious public health problem worldwide, and its relationship with affective disorders is not clear. Aims To investigate alcohol- and tobacco-related cancer risk among patients with affective disorders in a large Taiwanese cohort. METHOD: Records of newly admitted patients with affective disorders from January 1997 through December 2002 were retrieved from the Psychiatric Inpatient Medical Claims database in Taiwan. Cancers were stratified by site and grouped into tobacco- or alcohol-related cancers. Standardised incidence ratios (SIRs) were calculated to compare the risk of cancer between those with affective disorders and the general population. RESULTS: Some 10 207 patients with bipolar disorder and 9826 with major depression were included. The risk of cancer was higher in patients with major depression (SIR = 2.01, 95% CI 1.85-2.19) than in those with bipolar disorder (SIR 1.39, 95% CI 1.26-1.53). The elevated cancer risk among individuals ever admitted to hospital for affective disorders was more pronounced in tobacco- and/or alcohol-related cancers. CONCLUSIONS: Elevated cancer risk was found in patients who had received in-patient care for affective disorders. They require holistic approaches to lifestyle behaviours and associated cancer risks.

In silico identification of potent pancreatic triacylglycerol lipase inhibitors from traditional Chinese medicine.

Pancreatic triacylglycerol lipase (PNLIP) are primary lipases that are critical for triacylglyceride digestion in human. Since reduced metabolism of triacylglyceride might be a plausible concept for weight loss, we screened for potential PNLIP inhibitors from traditional Chinese medicine (TCM) with the aim to identify weight loss candidate compounds. TCM candidates Aurantiamide, Cnidiadin, and 2-hexadecenoic acid exhibited higher Dock Scores than the commercial drug Orlistat, and were also predicted to have inhibitory characteristics against PNLIP using constructed MLR (R(2) = 0.8664) and SVM (R(2) = 0.9030) models. Molecular dynamics indicated that the TCM-PNLIP complexes formed were stable. We identified that the PNLIP binding site has several residues that can serve as anchors, and a hydrophobic corridor that provides additional stability to the complex. Aurantiamide, Cnidiadin, and 2-hexadecenoic acid all have features that correspond to these binding site features, indicating their potential as candidates for PNLIP inhibitors. The information presented in this study may provide helpful insights to designing novel weight-control drugs.

Management of severe community-acquired septic meningitis in adults: from emergency department to intensive care unit.

BACKGROUND/PURPOSE: To study the clinical features, diagnostic processes, timing of antibiotic administration and outcomes of patients with severe community-acquired septic meningitis at an emergency department (ED), who required intensive care unit (ICU) admission. METHODS: From January 1993 to December 2005, the medical records of patients admitted to the ICU with a diagnosis of community-acquired septic meningitis were reviewed. The clinical characteristics, including causative pathogens, treatment course, and outcomes were collected and analyzed. RESULTS: A total of 40 patients were included, with an overall in-hospital mortality rate of 77.5%. The most common pathogen was Klebsiella pneumoniae (n=20, 50%), followed by Streptococcus pneumoniae (n=6, 15%), and Cryptococcus neoformans (n=5, 12.5%). There was a mean duration of 8.9 hours between ED arrival and initiation of antibiotic therapy. Effective antibiotics were administered for a mean period of 23.8 hours after arrival. Time delay from ED arrival to ICU admission was correlated with time delay of effective antibiotics administration, head computed tomography, and cerebrospinal fluid study (r=0.32, 0.47, and 0.53, respectively; p=0.05, 0.006, and 0.001, respectively). Earlier ICU admission was demonstrated in survivors as compared with those who died (11.1 vs. 38.0 hours, p=0.01). CONCLUSION: Severe septic meningitis remains a disease with high mortality and morbidity. Expeditious diagnostic processes with early appropriate antibiotic treatment and ICU admission at the ED are important in improving the quality of care and patient outcome.