Science communication in the media and human mobility during the COVID-19 pandemic: a time series and content analysis.

OBJECTIVES: The relationship between human mobility and nature of science (NOS) salience in the UK news media was examined. STUDY DESIGN: This is a mixed-method study. METHODS: A time series NOS salience data set was established from the content analysis of 1520 news articles related to non-pharmaceutical interventions of COVID-19. Data were taken from articles published between November 2021 and February 2022, which correlates with period of the change from pandemic to endemic status. Vector autoregressive model fitting with human mobility took place. RESULTS: The findings suggest that it was not the number of COVID-19 news articles nor the actual number of cases/deaths, but the specific NOS content that was associated with mobility change during the pandemic. Data indicate a Granger causal negative direction (P < 0.1) for the effect of the NOS salience represented in the news media on mobility in parks, as well as the effect of scientific practice, scientific knowledge and professional activities communicated in news media on recreational activities and grocery shopping. NOS salience was not associated with the mobility for transit, work or residential locations (P > 0.1). CONCLUSIONS: The findings of the study suggest that the ways in which the news media discuss epidemics can influence changes in human mobility. It is therefore essential that public health communicators emphasise the basis of scientific evidence to eliminate potential media bias in health and science communication for the promotion of public health policy. The present study approach, which combines time series and content analysis and uses an interdisciplinary lens from science communication, could also be adopted to other interdisciplinary health-related topics.

Significant positive association of endotoxemia with histological severity in 237 patients with non-alcoholic fatty liver disease.

BACKGROUND: Patients with nonalcoholic steatohepatitis (NASH) have gut dysbiosis and intestinal bacterial overgrowth. AIM: To test the hypothesis that endotoxemia is associated with the histological severity of nonalcoholic fatty liver disease (NAFLD) and determine factors associated with endotoxemia. METHODS: The endotoxemia markers lipopolysaccharide-binding protein (LBP) and endotoxin levels were measured in 237 NAFLD patients 1 day before liver biopsy. Biomarkers of liver injury and transient elastography were performed as additional markers of disease severity. RESULTS: A total of 114/237 (48%) patients had NASH and 80/237 (34%) had F2-4 fibrosis. LBP was correlated with lobular inflammation (P=.001), while both LBP (P=.0004) and endotoxin levels (P=0.008) were correlated with fibrosis. LBP was also correlated with cytokeratin-18 fragments (P=.002) and aspartate aminotransferase-to-alanine aminotransferase ratio (P=.006), and both LBP (P=.019) and endotoxin (P=.006) were correlated with liver stiffness measurement by transient elastography. LBP was increased in patients with NASH (15.3±4.6 vs 13.8±3.3 µg/mL; P=.005) and F2-4 fibrosis (15.4±4.4 vs 14.0±3.7 µg/mL; P=.008). Interestingly, patients harbouring the TM6SF2 rs58542926 T allele that predispose to NAFLD/NASH had higher LBP level. By multivariate analysis, gender, higher body mass index and glycated haemoglobin, and TM6SF2 variants were independent factors associated with increased LBP level. CONCLUSIONS: Endotoxemia is positively associated with NASH and significant fibrosis. The association between TM6SF2 and endotoxemia warrants further investigations. The findings may shed light on the pathogenesis of NASH and inform a novel treatment target.

Transformation of excess mortality in people with schizophrenia and bipolar disorder in Taiwan.

BACKGROUND: Given the concerns regarding the adverse health outcomes associated with weight gain and metabolic syndrome in relation to use of second-generation antipsychotics (SGAs), we aimed in this study to explore whether the increase in the use of SGAs would have any impacts on the trend of excess mortality in people with schizophrenia and bipolar disorder (BPD). METHOD: Two nationwide samples of individuals with schizophrenia and BPD were identified in Taiwan's National Health Insurance Research Database in 2003 and in 2008, respectively. Age- and gender-standardized mortality ratios (SMRs) were calculated for each of the 3-year observation periods. The SMRs were compared between the calendar year cohorts, by disease group, and by causes of death. RESULTS: The mortality gap for people with schizophrenia decreased slightly, revealing an SMR of 3.40 (95% CI 3.30-3.50) for the 2003 cohort and 3.14 (3.06-3.23) for the 2008 cohort. The mortality gap for BPD individuals remained relatively stable with only those aged 15-44 years having an SMR rising significantly from 7.04 (6.38-7.76) to 9.10 (8.44-9.79). Additionally, in this group of BPD patients aged 15-44 years, the natural-cause-SMR increased from 5.65 (4.93-6.44) to 7.16 (6.46-7.91). CONCLUSIONS: Compared with the general population, the gap in the excess mortality for people with schizophrenia reduced slightly. However, the over 200% difference between the cohorts in the excess mortality for BPD individuals aged 15-44 years could be a warning sign. Future research to further examine the related factors underlying those changes is warranted.

Liver fibrosis and fatty liver in Asian HIV-infected patients.

BACKGROUND: Little is known about the importance of liver fibrosis and fatty liver in HIV-monoinfected individuals without hepatitis virus co-infection, particularly among the Asian population. AIM: To evaluate prevalence and risk factors for liver fibrosis and fatty liver in Asian HIV-monoinfected individuals. METHODS: Eighty asymptomatic HIV-monoinfected individuals (tested negative for HBV/HCV) were compared with 160 matched HIV-uninfected healthy controls. Transient elastography and proton-magnetic resonance spectroscopy ((1) H-MRS) were performed to measure liver stiffness and hepatic steatosis respectively. Blood samples were analysed for metabolic profiles and markers of steatohepatitis (e.g. cytokeratin-18). RESULTS: All HIV-infected individuals (mean ± s.d. age 54 ± 11 years, male 93%, Chinese 94%; diagnosis median duration 8 (IQR 4-13 years) were stable on anti-retrovirals (PI-based 58.7%, NNRTI-based 25.0% integrase-inhibitors 16.3%); diabetes, dyslipidaemia, and metabolic syndrome were common. Fatty liver disease was detected in 28.7%. There was significantly higher degree of liver stiffness [4.9 (IQR 4.1-6.2) kPa vs. 4.2 (IQR 3.6-5.0) kPa, P < 0.001], and greater proportions developed significant fibrosis (7.0 kPa, 14.3% vs. 3.1%, P = 0.001) and cirrhosis (10.3 kPa, 5.2% vs. 0.6%, P = 0.040) compared with controls. HIV infection was an independent risk factor for significant fibrosis (adjusted OR 4.00, 95% CI 1.29-12.41, P = 0.016). HIV-infected individuals with fatty liver had excessive liver stiffness and fibrosis. Two cases of asymptomatic hepatocellular carcinoma were detected. CONCLUSIONS: HIV-monoinfected patients are at risk for liver fibrosis and cirrhosis. HIV-related mechanisms and fatty liver disease may play important roles. Screening and intervention to prevent severe outcomes should be considered.

Serum interferon-inducible protein 10 levels predict hepatitis B s antigen seroclearance in patients with chronic hepatitis B.

BACKGROUND: Hepatitis B s antigen (HBsAg) seroclearance is regarded as the optimal virological end-point. AIM: To investigate the dynamic changes in serum cytokine levels around the time of HBsAg seroclearance. METHODS: This was a case-control study. Consecutive patients with chronic hepatitis B (CHB) who lost HBsAg were matched with those remained positive for HBsAg with same age, gender, HBeAg status and presence of cirrhosis in 1:2 ratio. Relevant serum cytokines [interleukin (IL)-2, IL-3, IL-4, IL-7, IL-9, IL-10, IL-12, IL-15, IL-21 interferon-γ, tumour necrosis factor-α (TNF-α), granulocyte macrophage colony-stimulating factor (GM-CSF) and interferon-inducible protein 10 (IP-10)] were assayed at the time (Year 0) and 3 years before (Year -3) HBsAg seroclearance. RESULTS: Seventy-one and 142 CHB patients who did and did not achieve HBsAg seroclearance were included. Mean age was 48 ± 11 years; 76% were male, 20% had positive HBeAg, 99 (46%) patients received anti-viral therapy, and mean baseline HBV DNA was 3.78 ± 2.28 log IU/mL vs. 4.36 ± 2.13 log IU/mL respectively (P = 0.05). In those who achieved HBsAg seroclearance, serum IL-15 and GM-CSF levels decreased significantly from Year -3 to Year 0 (P = 0.017 and 0.05 respectively). When compared to controls, only serum IP-10 level was significantly lower at Year 0 than at Year -3 in patients with HBsAg seroclearance. Lower serum IP-10 level at Year 0 was the only factor associated with HBsAg seroclearance. There was no correlation between serum IP-10 and HBsAg levels around the time of HBsAg seroclearance. CONCLUSION: Lower serum IP-10 level at Year 0 was the only factor associated with HBsAg seroclearance.

Fiber-laser-pumped, high-energy, mid-IR, picosecond optical parametric oscillator with a high-harmonic cavity.

We demonstrate the generation of high-energy, mid-IR, picosecond pulses in a high-harmonic-cavity optical parametric oscillator (OPO) that has a relatively compact cavity with a length that is a small fraction of that required to match the pump repetition rate. The OPO, based on an MgO-doped periodically poled LiNbO3 crystal, is pumped by a fiber master-oscillator-power-amplifier system employing direct amplification and delivering 11-µJ, 150-ps pulses at 1035 nm. For a 1.554-m-long OPO cavity, resonating near-infrared signal pulses with a repetition rate that is the 193rd harmonic of the 1-MHz pump are demonstrated. The mid-infrared idler output pulses, tunable from 2300 nm to 3500 nm, are generated at a 1-MHz repetition rate and have energies as high as 1.5 µJ.

Bacterial endotoxin and non-alcoholic fatty liver disease in the general population: a prospective cohort study.

BACKGROUND: Patients with non-alcoholic steatohepatitis (NASH) have increased intestinal permeability and small intestine bacterial overgrowth. AIMS: To test the hypothesis that endotoxemia is associated with non-alcoholic fatty liver disease (NAFLD) in the general population, and to study dietary factors associated with endotoxemia. METHODS: Nine hundred and twenty adults were randomly selected from the government's census database and underwent proton-magnetic resonance spectroscopy to assess hepatic steatosis. Endotoxemia was assessed using the limulus amebocyte lysate, lipopolysaccharide-binding protein (LBP) and EndoCab immunoglobulin G (IgG) assays. RESULTS: Two hundred and sixty-three (29%) subjects had NAFLD. Subjects with NAFLD had slightly higher LBP (P < 0.001) and EndoCab IgG (P = 0.013) levels. EndoCab IgG remained an independent factor associated with intrahepatic triglycerides after adjusting for other metabolic factors. Among 565 subjects without NAFLD at baseline who had repeated assessment at a median interval of 47 months, 78 (13.8%) developed incident NAFLD and they also had higher LBP (P = 0.016). Moreover, LBP was associated with insulin resistance and dyslipidaemia, and modestly increased with the cytokeratin-18 fragment level but not liver stiffness measurement by transient elastography. Although total energy consumption and individual macronutrients were not associated with endotoxemia, current drinkers (mostly <140 g/week) had lower endotoxin, EndoCab IgG and fetuin-A levels than nondrinkers. CONCLUSIONS: Endotoxin markers are associated with NAFLD in the general population, but do not have a major effect on NASH and fibrosis. People with modest alcohol consumption have lower serum endotoxin. This may partly explain the lower risk of NAFLD and NASH in modest drinkers in previous observational studies.

Efficacy of tenofovir switch therapy for nucleos(t)ide-experienced patients with chronic hepatitis B.

BACKGROUND: Tenofovir disoproxil fumarate has been used in chronic hepatitis B patients with suboptimal virologic response to nucleos(t)ide analogues. The efficacy of tenofovir switch therapy has not been well studied in Asian patients. AIM: To evaluate the efficacy of tenofovir switch therapy in nucleos(t)ide-experienced patients, and identify the factors associated with treatment response of tenofovir switch therapy. METHODS: Nucleos(t)ide-experienced hepatitis B e antigen-positive and -negative patients prescribed with tenofovir were retrospectively identified and recruited for prospective analysis. Hepatitis B virus (HBV) DNA and other biochemical parameters were monitored in regular 3-6 monthly follow-up visits. Primary efficacy endpoint was maintained-virologic response with tenofovir switch therapy, defined as undetectable HBV DNA (<20 IU/mL) until the last follow-up visit. RESULTS: An overall of 214/252 (84.9%) patients achieved maintained-virologic response after 22 (7-55) months of tenofovir switch therapy. On multivariate analysis, a lower HBV DNA level at the time of switching to tenofovir was an independent factor associated with treatment efficacy. Maintained-virologic response after switching to tenofovir was achieved in 177/190 (93.2%) patients with HBV DNA <20 000 IU/mL vs. 37/62 (59.7%) patients with HBV DNA ≥20 000 IU/mL (P < 0.001). Absence of genotypic resistance to lamivudine or adefovir dipivoxil was not associated with improved treatment outcome. CONCLUSIONS: Tenofovir switch therapy is an effective treatment strategy in nucleos(t)ide-experienced chronic hepatitis B patients. However, in patients with HBV DNA ≥20 000 IU/mL at the time of switching to tenofovir, the chance of achieving maintained undetectable HBV DNA is significantly reduced.

The effectiveness of a computer reminder system for laboratory monitoring of metabolic syndrome in schizophrenic outpatients using second-generation antipsychotics.

INTRODUCTION: A computer reminder system (CRS) may help psychiatrists follow guidelines and monitor patients at risk of metabolic syndrome. This study explores the effectiveness of a CRS for outpatients with schizophrenia. METHODS: The study data were collected from July 2004 to July 2008. A CRS was implemented in July 2006. The intervention group was patients taking either clozapine, olanzapine, risperidone, or quetiapine with a CRS. The control group was patients taking either sulpiride or zotepine without a CRS. We defined a qualified patient visit (QPV) as a visit in which metabolic monitoring adhered to established guidelines when the patient visit was within 6 months of performing the recommended laboratory examinations. We compared the percentage difference in QPVs between the 2 study groups. RESULTS: The percentage of QPVs in the intervention group was significantly higher than the control group (OR=3.51, 95% CI=1.83~6.73, P=0.0002) after adjusting potential confounding factors. The intervention group was divided into a high metabolic risk (clozapine and olanzapine) subgroup and an intermediate metabolic risk (risperidone and quetiapine) subgroup and compared with the control group. The percentage of QPVs in the high risk subgroup was significantly higher than the intermediate risk subgroup (OR=4.27, 95% CI=2.71~6.75, p<0.0001) and control group (OR=6.99, 95% CI=3.48~14.07, p<0.0001). DISCUSSION: The percentage of QPVs in the intervention group was higher than the control group and the different metabolic risk of SGAs also influenced the performance of laboratory examinations. Further studies are needed to confirm the results of our studies.

Lean techniques for the improvement of patients' flow in emergency department.

BACKGROUND: Emergency departments (EDs) face problems with overcrowding, access block, cost containment, and increasing demand from patients. In order to resolve these problems, there is rising interest to an approach called "lean" management. This study aims to (1) evaluate the current patient flow in ED, (2) to identify and eliminate the non-valued added process, and (3) to modify the existing process. METHODS: It was a quantitative, pre- and post-lean design study with a series of lean management work implemented to improve the admission and blood result waiting time. These included structured re-design process, priority admission triage (PAT) program, enhanced communication with medical department, and use of new high sensitivity troponin-T (hsTnT) blood test. Triage waiting time, consultation waiting time, blood result time, admission waiting time, total processing time and ED length of stay were compared. RESULTS: Among all the processes carried out in ED, the most time consuming processes were to wait for an admission bed (38.24 minutes; SD 66.35) and blood testing result (mean 52.73 minutes, SD 24.03). The triage waiting time and end waiting time for consultation were significantly decreased. The admission waiting time of emergency medical ward (EMW) was significantly decreased from 54.76 minutes to 24.45 minutes after implementation of PAT program (P<0.05). CONCLUSION: The application of lean management can improve the patient flow in ED. Acquiescence to the principle of lean is crucial to enhance high quality emergency care and patient satisfaction.

Coincidental metabolic syndrome increases the risk of liver fibrosis progression in patients with chronic hepatitis B--a prospective cohort study with paired transient elastography examinations.

BACKGROUND: Metabolic syndrome is a known risk factor of cirrhosis in chronic hepatitis B (CHB). AIM: To investigate the effects of coincidental metabolic syndrome on liver fibrosis progression in treatment-naïve CHB patients. METHODS: A total of 1466 CHB patients underwent liver stiffness measurement (LSM) by transient elastography in 2006-2008; 663 patients remained treatment-naïve and had second LSM in 2010-2012. Liver fibrosis progression was defined as an increase in LSM ≥30% at the second assessment. The impact of coincidental metabolic syndrome and its factors on liver fibrosis progression were evaluated after adjustment for viral load and hepatitis activity. RESULTS: At baseline, the mean age was 43 ± 12 years, 55% were males, serum alanine aminotransferase (ALT) was 44 ± 40 IU/L, HBV DNA was 4.0 ± 2.0 log IU/mL and LSM was 6.3 ± 3.6 kPa. Metabolic syndrome was diagnosed in 80 (12%) and 142 (21%) patients at baseline and follow-up visit, respectively; 84 (13%) and 22 (3%) patients had coincidental and resolved metabolic syndrome respectively. After an interval of 44 ± 7 months, 107 (16%) patients developed liver fibrosis progression. Coincidental metabolic syndrome [adjusted odds ratio (aOR) 2.0, 95% confidence interval (CI) 1.1-3.5, P = 0.015], central obesity (aOR 2.0, 95% CI 1.0-4.1, P = 0.05) and low level of high-density lipoprotein cholesterol (aOR 1.9, 95% CI 1.0-3.7, P = 0.04) were associated with liver fibrosis progression independent of change in viral load and ALT level. The effects of coincidental metabolic syndrome were most apparent in the immune-tolerant phase. CONCLUSION: Coincidental metabolic syndrome increases the risk of liver fibrosis progression in patients with chronic hepatitis B infection, independent of viral load and hepatitis activity.

PNPLA3 gene polymorphism accounts for fatty liver in community subjects without metabolic syndrome.

BACKGROUND: The rs738409 GG variant in patatin-like phospholipase 3 (PNPLA3) is associated with non-alcoholic fatty liver disease (NAFLD) and disease severity. However, it remains unclear if it contributes to the development of NAFLD through affecting dietary pattern. AIM: To examine the association among PNPLA3 gene polymorphism, dietary pattern, metabolic factors and NAFLD. METHODS: Liver fat and fibrosis were assessed by proton-magnetic resonance spectroscopy and transient elastography in 920 subjects from a population screening project (251 had NAFLD). Dietary nutrient intake was recorded using a locally validated food-frequency questionnaire. RESULTS: The prevalence of GG genotype in NAFLD subjects was 20.7%, compared to 10.6% in controls (P < 0.001). Macronutrient intake was similar among subjects with different PNPLA3 genotypes. The presence of G allele was a predictor of NAFLD independent of nutrient intake and other metabolic factors (adjusted odds ratio to CC: CG, 2.00; GG, 2.68). In subjects without metabolic syndrome, G allele was even more closely correlated with NAFLD diagnosis (adjusted odds ratio to CC: CG, 2.22; GG, 3.39). The prevalence of NAFLD was only 12% in subjects with CC genotype and no metabolic syndrome, and increased to 34% in those with GG genotype and no metabolic syndrome. While NAFLD subjects had significantly lower fibre intake, there was no significant interaction between PNPLA3 and dietary pattern. CONCLUSIONS: The G allele in PNPLA3 rs738409 increases the risk of NAFLD in the general population, especially in subjects without metabolic syndrome, independent of dietary pattern and metabolic factors.

Non-invasive algorithm of enhanced liver fibrosis and liver stiffness measurement with transient elastography for advanced liver fibrosis in chronic hepatitis B.

BACKGROUND: The accuracy of Enhanced Liver Fibrosis (ELF; ADVIA Centaur, Siemens Healthcare Diagnostics, Tarrytown, NY, USA) in assessing liver fibrosis in chronic hepatitis B (CHB) is to be determined. AIM: To derive and validate a combined ELF-liver stiffness measurement (LSM) algorithm to predict advanced fibrosis in CHB patients. METHODS: Using the data of a previously reported cohort of 238 CHB patients, an ALT-based LSM algorithm for liver fibrosis was used as a training cohort to evaluate the performance of ELF against liver histology. The best combined ELF-LSM algorithm was then validated in new cohort of 85 CHB patients not previously reported. RESULTS: In the training cohort, LSM has better performance of diagnosing advanced (≥F3) fibrosis (area under the receiver operating characteristics curve [AUROC] 0.83, 95% confidence interval [CI 0.76-0.91] than ELF (AUROC 0.69, 95% CI 0.63-0.75). The optimal cut-off values of ELF were 8.4 to exclude advanced fibrosis, and 10.8 to confirm advanced fibrosis. In the training cohort, an ELF ≤ 8.4 had a sensitivity of 95% to exclude advanced fibrosis; an ELF > 10.8 had a specificity of 92% to confirm advanced fibrosis. In the combined algorithm, low ELF or low LSM could be used to exclude advanced fibrosis as both of them had high sensitivity (≥90%). To confirm advanced fibrosis, agreement between high ELF and high LSM could improve the negative predictive value specificity (from 65% and 74% to 80%). CONCLUSIONS: An Enhanced Liver Fibrosis - liver stiffness measurement algorithm could improve the accuracy of prediction of either ELF or LSM alone. Liver biopsy could be correctly avoided in approximately 60% of patients.

Assessment of non-alcoholic fatty liver disease using serum total cell death and apoptosis markers.

BACKGROUND: The diagnosis of non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH) and fibrosis relies on liver biopsy. Non-invasive assessments are urgently needed. AIM: To evaluate cell apoptotic marker cytokeratin-18 M30 and total cell death markers cytokeratin-18 M65/M65ED for the assessment and monitoring of NAFLD. METHODS: A cohort of 147 patients with biopsy-proven NAFLD and 73 controls were enrolled, including 51 patients who received paired liver biopsies 36 months apart. Biomarkers were determined by enzyme-linked immunosorbent assay. RESULTS: M30, M65 and M65ED increased in a stepwise fashion in control subjects, patients with non-NASH, NAFLD and NASH (all P < 0.001). All biomarkers had similarly high accuracy over 0.9 in predicting NAFLD and moderate accuracy around 0.7 in predicting NASH. Among patients with paired liver biopsies, changes in M30, M65 and M65ED positively correlated with disease progression (rho = 0.42, 0.32 and 0.39; P = 0.002, 0.023 and 0.005 respectively), and only changes in M65 and M65ED correlated with fibrosis progression (rho = 0.29, 0.34; P = 0.038, 0.015 respectively). Both M30 and M65 had area under receiver-operating characteristics curve above 0.8 in predicting disease progression. At cut-off of 236 U/L, changes of M65ED had 88% NPV and 59% PPV to exclude and predict fibrosis progression. CONCLUSIONS: Cytokeratin-18 M30 and M65/M65ED have moderate accuracy in detecting non-alcoholic steatohepatitis. Changes in the biomarkers also correlate with histological progression. However, development of new biomarkers is still required to improve the diagnostic accuracy.

Undetectable HBV DNA at month 12 of entecavir treatment predicts maintained viral suppression and HBeAg-seroconversion in chronic hepatitis B patients at 3 years.

BACKGROUND: On-treatment monitoring of serum hepatitis B virus (HBV) DNA to guide treatment strategy for patients on entecavir has received little attention. AIM: To investigate the predictive value of on-treatment HBV DNA levels for responses to entecavir. METHODS: This was a retrospective cohort study among nucleos(t)ide analogue-naïve HBV-infected patients on entecavir with a minimum follow-up of 2 years. Maintained virological suppression was defined as undetectable HBV DNA (<20 IU/mL) until the last visit. Genotypic drug resistance was screened by using the INNO-LiPA DR assay. RESULTS: A total of 440 chronic hepatitis B patients (160 HBeAg-positive) followed for 34 ± 9 months were included. The cumulative probability of maintained virological suppression at year 1, 2 and 3 were 76.5%, 83.0% and 88.3% respectively. On multivariate analysis, lower baseline HBV DNA, undetectable HBV DNA at month 12 and negative HBeAg were the independent predictors of maintained virological suppression. M12 responders (who had undetectable HBV DNA at month 12) had higher probability of maintained virological suppression at 3 years (99.1%) as compared to non responders (57.5%; P < 0.001). The cumulative probability of HBeAg-seroconversion at year 1, 2 and 3 were 19.0%, 27.2% and 33.5% respectively. M12 responders had higher probability of HBeAg-seroconversion at 3 years (43.2%) than the non responders (19.0%; P = 0.003). M12 responders had lower probability of drug resistance at 3 years (0%) than the non responders (2.6%; P = 0.004). CONCLUSION: Month 12 HBV DNA responses could predict the probability of maintained virological suppression, HBeAg-seroconversion and risk of drug resistance among patients on entecavir treatment at 3 years.

Risperidone and olanzapine versus another first generation antipsychotic in patients with schizophrenia inadequately responsive to first generation antipsychotics.

OBJECTIVE: This study compares the efficacy of risperidone and olanzapine to that of first-generation antipsychotics (FGAs) in patients with schizophrenia, who failed to show a response to initial trials of FGAs. METHOD: This study was an 8-week treatment, randomized, rater-blind, active-control study with 3 treatment arms. 48 patients, who showed inadequate response to 1 FGA, were enrolled and randomized into risperidone, olanzapine, or FGA (haloperidol or trifluoperazine) groups. They were blindly assessed with the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression Scale-Severity, and the Extrapyramidal Symptom Rating Scale (ESRS) at baseline and biweekly. RESULTS: All 3 groups demonstrated a significant decrease in the PANSS total, positive, and general scores from baseline to endpoint (p-values range from 0.003 to 0.021). There were no significant differences among the 3 groups in score changes. The olanzapine group had significant score reductions than the risperidone and FGAs groups in terms of the ESRS subjective total score and did not experience a significant increase in the dose of anticholinergics. The FGA group demonstrated that extrapyramidal syndrome (EPS) worsened under an increased dosage of anti-EPS drugs. Olanzapine was associated with significant body weight gain (2.69 ± 4.0 kg, p=0.026), but there were no significant group differences on weight gain. CONCLUSIONS: Haloperidol or trifluoperazine demonstrated similar efficacy as risperidone or olanzapine for patients with schizophrenia who had failed their first trial with a FGA. Related double-blind, fixed dose studies with a larger sample size are needed to confirm the results of our study.

Management options for lamivudine-resistant chronic hepatitis B patients with suboptimal virological suppression by adefovir.

BACKGROUND: In chronic hepatitis B (CHB) patients, adefovir is commonly used as a rescue therapy for lamivudine resistance, but often results in incomplete virological suppression. AIM: To study the factors predicting response to adefovir rescue, and the treatment response of tenofovir and entecavir in suboptimal responders to adefovir in CHB patients. METHODS: Chronic hepatitis B patients who took adefovir for at least 6 months for lamivudine resistance were studied. Early virological response was defined as undetectable HBV DNA at month 6. Maintained virological response was defined as undetectable HBV DNA till the last follow-up. RESULTS: Among 136 patients on adefovir for 39 (5-117) months, 30 (22%) had early virological response. The 3-year cumulative probability of maintained virological response was similar between patients on adefovir monotherapy (n = 53, 57.9%) and those on combination of lamivudine and adefovir treatment (n = 83, 56.5%). The month 6 HBV DNA was the only independent factor associated with maintained virological response (adjusted hazard ratio 0.49, 95% confidence interval 0.37-0.65, P < 0.001). Twenty-six of 30 (87%) early responders and 36 of 106 (34%) non-early responders had maintained virological response on adefovir (P < 0.001). Among 106 non-early responders, 18 and 11 were switched to tenofovir and entecavir, respectively. The 1-year cumulative probability of maintained virological response was higher in patients switched to tenofovir (87.5%) than those switched to entecavir (37.5%; P = 0.048) or continued with adefovir (8.7%; P < 0.001). CONCLUSIONS: In adefovir rescue for lamivudine resistance, month 6 HBV DNA predicts maintained virological response in CHB patients. Switching to tenofovir achieved best viral suppression among suboptimal responders to adefovir.

Serum HBsAg quantification to predict response to peginterferon therapy of e antigen positive chronic hepatitis B.

BACKGROUND: On-treatment predictors of response to peginterferon can guide individualization of therapy in chronic hepatitis B virus infection. AIM: To investigate the use of serum hepatitis B surface antigen quantification to predict sustained response. METHODS: Hepatitis B e antigen-positive chronic hepatitis B patients who received peginterferon for 32-48 weeks with or without lamivudine combination were studied. Sustained response was defined as hepatitis B e antigen seroconversion and chronic hepatitis B virus DNA <10 000 copies/mL until 12 months post-treatment. RESULTS: Twenty-one of 92 (23%) patients achieved sustained response. At month 6, the area under receiver operating characteristics curve for hepatitis B surface antigen to predict sustained response was 0.77 (95% confidence interval 0.65-0.89, P < 0.001). An hepatitis B surface antigen cutoff at 300 IU/mL at month 6 could give the maximum combination of sensitivity (62%) and specificity (89%) to predict sustained response. Nine of 21 (43%) sustained responders vs. 9 of 71 (13%) nonsustained responders had >1 log hepatitis B surface antigen reduction at month 6 (P < 0.001). Combined hepatitis B surface antigen ≤ 300 IU/mL and >1 log reduction at month 6 had sensitivity, specificity, positive and negative predictive values of 43%, 96%, 75% and 85% to predict sustained response, respectively. CONCLUSION: On-treatment serum hepatitis B surface antigen can predict response to peginterferon therapy in chronic hepatitis B.

Metabolic syndrome increases the risk of liver cirrhosis in chronic hepatitis B.

BACKGROUND: Metabolic syndrome is associated with non-alcoholic steatohepatitis and cryptogenic cirrhosis. Whether metabolic syndrome affects the severity of chronic hepatitis B (CHB) is unclear. AIM: We aimed to study the relationship between metabolic syndrome and the risk of liver cirrhosis in patients with CHB. METHODS: We prospectively recruited patients with CHB from primary care and hospital clinics for liver stiffness measurement (LSM) with transient elastography to diagnose early cirrhosis. Probable cirrhosis was defined as LSM >or=13.4 kPa. We analysed a subgroup of patients with paired LSM and liver biopsies to validate the accuracy of LSM. RESULTS: 1466 patients had reliable LSM and 134 (9%) patients had adequate liver biopsy. 188 (13%) patients had metabolic syndrome. Histological liver cirrhosis was present in 32/134 (24%) patients. Histological liver cirrhosis was more common among patients who had metabolic syndrome (38%) versus those who did not (11%, p<0.001). The specificity of probable cirrhosis on LSM for histological cirrhosis was 94%. Probable cirrhosis was present in 187 (13%) patients. Metabolic syndrome was more prevalent in patients with probable cirrhosis (24%) than those without cirrhosis (11%, p<0.001). After adjustment for anthropometric, biochemical and virological factors, metabolic syndrome remained an independent factor associated with probable cirrhosis (odds ratio 1.7, 95% confidence interval (CI) 1.1 to 2.6). The odds ratios of probable cirrhosis were 1.4 (95% CI, 0.9 to 2.3), 2.6 (95% CI, 1.7 to 4.3), 4.1 (95% CI, 2.4 to 7.1), 4.0 (95% CI, 1.9 to 8.4) and 5.5 (95% CI, 1.8 to 16.7) in patients with one, two, three, four and five components of metabolic syndrome, respectively. CONCLUSION: Metabolic syndrome is an independent risk factor of liver cirrhosis in CHB.

Dexras1 interacts with FE65 to regulate FE65-amyloid precursor protein-dependent transcription.

FE65 is an adaptor protein that binds to and forms a transcriptionally active complex with the gamma-secretase-derived amyloid precursor protein (APP) intracellular domain. The regulatory mechanisms of FE65-APP-mediated transcription are still not clear. In this report, we demonstrate that Dexras1, a Ras family small G protein, binds to FE65 PTB2 domain and potently suppresses the FE65-APP-mediated transcription. The suppression is not via competition for binding of FE65 between Dexras1 and APP because the two proteins can simultaneously bind to the FE65 PTB2 domain. Phosphorylation of FE65 tyrosine 547 within the PTB2 domain has been shown to enhance FE65-APP-mediated transcription but not to influence binding to APP. Here we find that this phosphorylation event reduces the binding between Dexras1 and FE65. We also demonstrate that Dexras1 inhibits the FE65-APP-mediated transcription of glycogen synthase kinase 3beta (GSK3 beta). Moreover, small interfering RNA knockdown of Dexras1 enhances GSK3 beta expression and increases phosphorylation of Tau, a GSK3 beta substrate. Thus, Dexras1 functions as a suppressor of FE65-APP-mediated transcription, and FE65 tyrosine 547 phosphorylation enhances FE65-APP-mediated transcription, at least in part, by modulating the interaction between FE65 and Dexras1. These findings reveal a novel regulatory mechanism for FE65-APP-mediated signaling.