Adherence to medication interventions: Following attending physicians or online support?

Medication interventions are clinical interventions that delay or prevent the recurrence. In this research, we built upon the social network theory (SNT) to examine how trust in attending physicians and different sources of online social support would affect patients\u27 adherence to medication interventions. We conducted a mixed-method approach for different types of target populations. An online survey involving 311 patients with recent hospitalization experience was conducted, and the results confirmed that accessing support from online professionals made patients deviate from the medication interventions. Besides, patients’ trust in ability of their attending physicians would promote the adherence behaviors. Considering more senior patients, we conducted ten in-depth interviews to obtain further insight into patients\u27 dilemmas and challenges in integrating eHealth platforms into their treatment. This research contributes to the existing literature by revealing the potential problems in eHealth platform development and operation, in integrating the eHealth platform with physical healthcare systems

The Influence of Cross-Language Similarity on within- and between-Language Stroop Effects in Trilinguals

This study investigated effects of cross-language similarity on within- and between-language Stroop interference and facilitation in three groups of trilinguals. Trilinguals were either proficient in three languages that use the same-script (alphabetic in German–English–Dutch trilinguals), two similar scripts and one different script (Chinese and alphabetic scripts in Chinese–English–Malay trilinguals), or three completely different scripts (Arabic, Chinese, and alphabetic in Uyghur–Chinese–English trilinguals). The results revealed a similar magnitude of within-language Stroop interference for the three groups, whereas between-language interference was modulated by cross-language similarity. For the same-script trilinguals, the within- and between-language interference was similar, whereas the between-language Stroop interference was reduced for trilinguals with languages written in different scripts. The magnitude of within-language Stroop facilitation was similar across the three groups of trilinguals, but smaller than within-language Stroop interference. Between-language Stroop facilitation was also modulated by cross-language similarity such that these effects became negative for trilinguals with languages written in different scripts. The overall pattern of Stroop interference and facilitation effects can be explained in terms of diverging and converging color and word information across languages

Genetic linkage analysis of longitudinal hypertension phenotypes using three summary measures

BACKGROUND: Longitudinal data often have multiple (repeated) measures recorded along a time trajectory. For example, the two cohorts from the Framingham Heart Study (GAW13 Problem 1) contain 21 and 5 repeated measures for hypertension phenotypes as well as epidemiological risk factors, respectively. Direct modelling of a large number of serially and biologically correlated traits in the context of linkage analysis can be prohibitively complex. Alternatively, we may consider using univariate transformation for linkage analysis of longitudinal repeated measures. RESULTS: We evaluated the utility of three conventional summary measures (mean, slope, and principal components) for genetic linkage analysis of longitudinal phenotypes by analyzing the chromosome 10 data of the Framingham Heart Study. Except for the temporal slope, all of the summary methods and the multivariate analysis identified the previously reported region, marker GATA64A09, for systolic blood pressure or high blood pressure. Further analysis revealed that this region may harbor gene(s) affecting human blood pressure at multiple stages of life. CONCLUSION: We conclude that mean and principal components are feasible alternatives for genetic linkage analysis of longitudinal phenotypes, but the slope might have a separate genetic basis from that of the original longitudinal phenotypes

Multivariate sib-pair linkage analysis of longitudinal phenotypes by three step-wise analysis approaches

BACKGROUND: Current statistical methods for sib-pair linkage analysis of complex diseases include linear models, generalized linear models, and novel data mining techniques. The purpose of this study was to further investigate the utility and properties of a novel pattern recognition technique (step-wise discriminant analysis) using the chromosome 10 linkage data from the Framingham Heart Study and by comparing it with step-wise logistic regression and linear regression. RESULTS: The three step-wise approaches were compared in terms of statistical significance and gene localization. Step-wise discriminant linkage analysis approach performed best; next was step-wise logistic regression; and step-wise linear regression was the least efficient because it ignored the categorical nature of disease phenotypes. Nevertheless, all three methods successfully identified the previously reported chromosomal region linked to human hypertension, marker GATA64A09. We also explored the possibility of using the discriminant analysis to detect gene × gene and gene × environment interactions. There was evidence to suggest the existence of gene × environment interactions between markers GATA64A09 or GATA115E01 and hypertension treatment and gene × gene interactions between markers GATA64A09 and GATA115E01. Finally, we answered the theoretical question "Is a trichotomous phenotype more efficient than a binary?" Unlike logistic regression, discriminant sib-pair linkage analysis might have more power to detect linkage to a binary phenotype than a trichotomous one. CONCLUSION: We confirmed our previous speculation that step-wise discriminant analysis is useful for genetic mapping of complex diseases. This analysis also supported the possibility of the pattern recognition technique for investigating gene × gene or gene × environment interactions

Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatophepatitis

OBJECTIVE: Insulin resistance and lipotoxicity are pathognomonic in non-alcoholic steatohepatitis (NASH). Glucagon-like peptide-1 (GLP-1) analogues are licensed for type 2 diabetes, but no prospective experimental data exists in NASH. This study determined the effect of a long-acting GLP-1 analogue, liraglutide, on organ-specific insulin sensitivity, hepatic lipid handling and adipose dysfunction in biopsy-proven NASH.DESIGN: 14 patients were randomised to 1.8mg liraglutide or placebo for 12-weeks of the mechanistic component of a double-blind, randomized, placebo-controlled trial (ClinicalTrials.gov-NCT01237119). Patients underwent paired hyperinsulinaemic euglycaemic clamps, stable isotope tracers, adipose microdialysis and serum adipocytokine/metabolic profiling. In vitro isotope experiments on lipid flux were performed on primary human hepatocytes.RESULTS: Liraglutide reduced BMI (-1.9 vs. +0.04 kg/m2;p&lt;0.001), HbA1c (-0.3 vs. +0.3%;p&lt;0.01), cholesterol-LDL (-0.7 vs. +0.05 mmol/L;p&lt;0.01), ALT (-54 vs -4.0 IU/L;p&lt;0.01) and serum leptin, adiponectin, and CCL-2 (all p&lt;0.05). Liraglutide increased hepatic insulin sensitivity (-9.36 vs. -2.54% suppression of hepatic endogenous glucose production with low-dose insulin;p&lt;0.05). Liraglutide increased adipose tissue insulin sensitivity enhancing the ability of insulin to suppress lipolysis both globally (-24.9 vs. +54.8 pmol/L insulin required to ½ maximally suppress serum NEFA; p&lt;0.05), and specifically within subcutaneous adipose tissue (p&lt;0.05). In addition, liraglutide decreased hepatic DNL in-vivo (-1.26 vs. +1.30%; p&lt;0.05); a finding endorsed by the effect of GLP-1 receptor agonist on primary human hepatocytes (24.6% decrease in lipogenesis vs. untreated controls; p&lt;0.01).CONCLUSIONS: Liraglutide reduces metabolic dysfunction, insulin resistance and lipotoxicity in the key metabolic organs in the pathogenesis of NASH. Liraglutide may offer the potential for a disease-modifying intervention in NASH.</p

Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatophepatitis

Background & AimsInsulin resistance and lipotoxicity are pathognomonic in non-alcoholic steatohepatitis (NASH). Glucagon-like peptide-1 (GLP-1) analogues are licensed for type 2 diabetes, but no prospective experimental data exists in NASH. This study determined the effect of a long-acting GLP-1 analogue, liraglutide, on organ-specific insulin sensitivity, hepatic lipid handling and adipose dysfunction in biopsy-proven NASH.MethodsFourteen patients were randomised to 1.8mg liraglutide or placebo for 12-weeks of the mechanistic component of a double-blind, randomised, placebo-controlled trial (ClinicalTrials.gov-NCT01237119). Patients underwent paired hyperinsulinaemic euglycaemic clamps, stable isotope tracers, adipose microdialysis and serum adipocytokine/metabolic profiling. In vitro isotope experiments on lipid flux were performed on primary human hepatocytes.ResultsLiraglutide reduced BMI (−1.9 vs. +0.04kg/m2; p<0.001), HbA1c (−0.3 vs. +0.3%; p<0.01), cholesterol-LDL (−0.7 vs. +0.05mmol/L; p<0.01), ALT (−54 vs. −4.0IU/L; p<0.01) and serum leptin, adiponectin, and CCL-2 (all p<0.05). Liraglutide increased hepatic insulin sensitivity (−9.36 vs. −2.54% suppression of hepatic endogenous glucose production with low-dose insulin; p<0.05). Liraglutide increased adipose tissue insulin sensitivity enhancing the ability of insulin to suppress lipolysis both globally (−24.9 vs. +54.8pmol/L insulin required to ½ maximally suppress serum non-esterified fatty acids; p<0.05), and specifically within subcutaneous adipose tissue (p<0.05). In addition, liraglutide decreased hepatic de novo lipogenesis in vivo (−1.26 vs. +1.30%; p<0.05); a finding endorsed by the effect of GLP-1 receptor agonist on primary human hepatocytes (24.6% decrease in lipogenesis vs. untreated controls; p<0.01).ConclusionsLiraglutide reduces metabolic dysfunction, insulin resistance and lipotoxicity in the key metabolic organs in the pathogenesis of NASH. Liraglutide may offer the potential for a disease-modifying intervention in NASH

Development and validation of a casemix classification to predict costs of specialist palliative care provision across inpatient hospice, hospital and community settings in the UK: a study protocol

Introduction Provision of palliative care is inequitable with wide variations across conditions and settings in the UK. Lack of a standard way to classify by case complexity is one of the principle obstacles to addressing this. We aim to develop and validate a casemix classification to support the prediction of costs of specialist palliative care provision.Methods and analysis Phase I: A cohort study to determine the variables and potential classes to be included in a casemix classification. Data are collected from clinicians in palliative care services across inpatient hospice, hospital and community settings on: patient demographics, potential complexity/casemix criteria and patient-level resource use. Cost predictors are derived using multivariate regression and then incorporated into a classification using classification and regression trees. Internal validation will be conducted by bootstrapping to quantify any optimism in the predictive performance (calibration and discrimination) of the developed classification. Phase II: A mixed-methods cohort study across settings for external validation of the classification developed in phase I. Patient and family caregiver data will be collected longitudinally on demographics, potential complexity/casemix criteria and patient-level resource use. This will be triangulated with data collected from clinicians on potential complexity/casemix criteria and patient-level resource use, and with qualitative interviews with patients and caregivers about care provision across difference settings. The classification will be refined on the basis of its performance in the validation data set.Ethics and dissemination The study has been approved by the National Health Service Health Research Authority Research Ethics Committee. The results are expected to be disseminated in 2018 through papers for publication in major palliative care journals; policy briefs for clinicians, commissioning leads and policy makers; and lay summaries for patients and public

Advances in Cellular Characterization of the Sirtuin Isoform, SIRT7

SIRT7 is one of seven mammalian sirtuins that functions as an NAD+-dependent histone/protein deacetylase. SIRT7 is the least well-known member of the sirtuin family, but recent efforts have identified its involvement in various cellular processes, such as ribosome biogenesis, gene expression, cellular metabolism and cancer. Here we provide an update on the functions and mechanisms of SIRT7 in cellular regulation and disease

Effect of scavenger receptor BI antagonist ITX5061 in patients with hepatitis C virus infection undergoing liver transplantation

Hepatitis C virus (HCV) entry inhibitors have been hypothesized to prevent infection of the liver after transplantation. ITX5061 is a Scavenger Receptor B-I (SR-BI) antagonist that blocks HCV entry and infection in vitro. We assessed the safety and efficacy of ITX5061 to limit HCV infection of the graft. The study included 23 HCV infected patients undergoing liver transplantation. The first 13 "control" patients did not receive drug. The subsequent 10 patients received ITX5061 150 mg immediately pre- and post-transplant, and daily for 1 week thereafter. ITX5061 pharmacokinetics and plasma HCV RNA were quantified. Viral genetic diversity was measured by ultradeep pyrosequencing. ITX5061 was well tolerated with measurable plasma concentrations during therapy. Whilst the median HCV RNA reduction was greater in ITX treated patients at all time points in the first week after transplantation there was no difference in the overall change in the area over the HCV RNA curve in the 7-day treatment period. However, in genotype 1 infected patients treatment was associated with a sustained reduction in HCV RNA levels compared to the control group (area over the HCV RNA curve analysis, p=0.004). Ultradeep pyrosequencing revealed a complex and evolving pattern of HCV variants infecting the graft during the first week. ITX5061 significantly limited viral evolution where the median divergence between day 0 and day 7 was 3.5% in the control group compared to 0.1% in the treated group.CONCLUSIONS: ITX5061 reduces plasma HCV RNA post transplant notably in genotype 1 infected patients and slows viral evolution. Following liver transplantation the likely contribution of extrahepatic reservoirs of HCV necessitates combining entry inhibitors such as ITX5061 with inhibitors of replication in future studies. Clinicaltrials.gov NCT01292824. This article is protected by copyright. All rights reserved.</p

Local-regional recurrence in women with small node-negative, HER2-positive breast cancer: results from a prospective multi-institutional study (the APT trial).

PurposeWomen with HER2-positive breast cancer treated prior to effective anti-HER2 therapy have higher rates of local-regional recurrence (LRR) than those with HER2-negative disease. Effective systemic therapy, however, has been shown to decrease LRR. This study examines LRR in women with HER2-positive breast cancer treated on a single-arm prospective multicenter trial of adjuvant trastuzumab (H) and paclitaxel (T).MethodsPatients with HER2-positive tumors ≤ 3.0 cm with negative axillary nodes or micrometastatic disease were eligible. Systemic therapy included weekly T and H for 12 weeks followed by continuation of H to complete 1 year. Radiation therapy (RT) was required following breast-conserving surgery (BCS), but dose and fields were not specified. Disease-free survival (DFS) and LRR-free survival were calculated using the Kaplan-Meier method.ResultsOf the 410 patients enrolled from September 2007 to September 2010, 406 initiated protocol therapy and formed the basis of this analysis. A total of 272 (67%) had hormone receptor-positive tumors. Of 162 patients undergoing mastectomy, local therapy records were unavailable for two. None of the 160 for whom records were available received RT. Among 244 BCS patients, detailed RT records were available for 217 (89%). With a median follow-up of 6.5 years, 7-year DFS was 93.3% (95% CI 90.4-96.2), and LRR-free survival was 98.6% (95% CI 97.4-99.8).ConclusionLRR in this select group of early-stage patients with HER2-positive disease receiving effective anti-HER2 therapy is extremely low. If confirmed in additional studies, future investigational efforts should focus on de-escalating local therapy