Efficacy and safety of simeprevir and sofosbuvir with and without ribavirin in subjects with recurrent genotype 1 hepatitis C postorthotopic liver transplant: the randomized GALAXY study

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/136282/1/tri12896.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/136282/2/tri12896_am.pd

Temporal changes in HCV genotype distribution in three different high risk populations in San Francisco, California

Abstract Background Hepatitis C virus (HCV) genotype (GT) has become an important measure in the diagnosis and monitoring of HCV infection treatment. In the United States (U.S.) HCV GT 1 is reported as the most common infecting GT among chronically infected patients. In Europe, however, recent studies have suggested that the epidemiology of HCV GTs is changing. Methods We assessed HCV GT distribution in 460 patients from three HCV-infected high risk populations in San Francisco, and examined patterns by birth cohort to assess temporal trends. Multiple logistic regression was used to assess factors independently associated with GT 1 infection compared to other GTs (2, 3, and 4). Results Overall, GT 1 was predominant (72.4%), however younger injection drug users (IDU) had a lower proportion of GT 1 infections (54.7%) compared to older IDU and HIV-infected patients (80.5% and 76.6%, respectively). Analysis by birth cohort showed increasing proportions of non-GT 1 infections associated with year of birth: birth before 1970 was independently associated with higher adjusted odds of GT 1: AOR 2.03 (95% CI: 1.23, 3.34). African-Americans as compared to whites also had higher adjusted odds of GT 1 infection (AOR: 3.37; 95% CI: 1.89, 5.99). Conclusions Although, HCV GT 1 remains the most prevalent GT, especially among older groups, changes in GT distribution could have significant implications for how HCV might be controlled on a population level and treated on an individual level

A description of a knowledge broker role implemented as part of a randomized controlled trial evaluating three knowledge translation strategies

<p>Abstract</p> <p>Background</p> <p>A knowledge broker (KB) is a popular knowledge translation and exchange (KTE) strategy emerging in Canada to promote interaction between researchers and end users, as well as to develop capacity for evidence-informed decision making. A KB provides a link between research producers and end users by developing a mutual understanding of goals and cultures, collaborates with end users to identify issues and problems for which solutions are required, and facilitates the identification, access, assessment, interpretation, and translation of research evidence into local policy and practice. Knowledge-brokering can be carried out by individuals, groups and/or organizations, as well as entire countries. In each case, the KB is linked with a group of end users and focuses on promoting the integration of the best available evidence into policy and practice-related decisions.</p> <p>Methods</p> <p>A KB intervention comprised one of three KTE interventions evaluated in a randomized controlled trial.</p> <p>Results</p> <p>KB activities were classified into the following categories: initial and ongoing needs assessments; scanning the horizon; knowledge management; KTE; network development, maintenance, and facilitation; facilitation of individual capacity development in evidence informed decision making; and g) facilitation of and support for organizational change.</p> <p>Conclusion</p> <p>As the KB role developed during this study, central themes that emerged as particularly important included relationship development, ongoing support, customized approaches, and opportunities for individual and organizational capacity development. The novelty of the KB role in public health provides a unique opportunity to assess the need for and reaction to the role and its associated activities. Future research should include studies to evaluate the effectiveness of KBs in different settings and among different health care professionals, and to explore the optimal preparation and training of KBs, as well as the identification of the personality characteristics most closely associated with KB effectiveness. Studies should also seek to better understand which combination of KB activities are associated with optimal evidence-informed decision making outcomes, and whether the combination changes in different settings and among different health care decision makers.</p

Height, selected genetic markers and prostate cancer risk:Results from the PRACTICAL consortium

Background: Evidence on height and prostate cancer risk is mixed, however, recent studies with large data sets support a possible role for its association with the risk of aggressive prostate cancer. Methods: We analysed data from the PRACTICAL consortium consisting of 6207 prostate cancer cases and 6016 controls and a subset of high grade cases (2480 cases). We explored height, polymorphisms in genes related to growth processes as main effects and their possible interactions. Results: The results suggest that height is associated with high-grade prostate cancer risk. Men with height 4180cm are at a 22% increased risk as compared to men with height o173cm (OR 1.22, 95% CI 1.01–1.48). Genetic variants in the growth pathway gene showed an association with prostate cancer risk. The aggregate scores of the selected variants identified a significantly increased risk of overall prostate cancer and high-grade prostate cancer by 13% and 15%, respectively, in the highest score group as compared to lowest score group. Conclusions: There was no evidence of gene-environment interaction between height and the selected candidate SNPs. Our findings suggest a role of height in high-grade prostate cancer. The effect of genetic variants in the genes related to growth is seen in all cases and high-grade prostate cancer. There is no interaction between these two exposures.</p

Ledipasvir and Sofosbuvir Plus Ribavirin for Treatment of HCV Infection in Patients With Advanced Liver Disease

BACKGROUND & AIMS: There are no effective and safe treatments for chronic hepatitis C virus (HCV) infection of patients who have advanced liver disease. METHODS: In this phase 2, open-label study, we assessed treatment with the NS5A inhibitor ledipasvir, the nucleotide polymerase inhibitor sofosbuvir, and ribavirin in patients infected with HCV genotypes 1 or 4. Cohort A enrolled patients with cirrhosis and moderate or severe hepatic impairment who had not undergone liver transplantation. Cohort B enrolled patients who had undergone liver transplantation: those without cirrhosis; those with cirrhosis and mild, moderate, or severe hepatic impairment; and those with fibrosing cholestatic hepatitis. Patients were assigned randomly (1:1) to receive 12 or 24 weeks of a fixed-dose combination tablet containing ledipasvir and sofosbuvir, once daily, plus ribavirin. The primary end point was sustained virologic response at 12 weeks after the end of treatment (SVR12). RESULTS: We enrolled 337 patients, 332 (99%) with HCV genotype 1 infection and 5 (1%) with HCV genotype 4 infection. In cohort A (nontransplant), SVR12 was achieved by 86%-89% of patients. In cohort B (transplant recipients), SVR12 was achieved by 96%-98% of patients without cirrhosis or with compensated cirrhosis, by 85%-88% of patients with moderate hepatic impairment, by 60%-75% of patients with severe hepatic impairment, and by all 6 patients with fibrosing cholestatic hepatitis. Response rates in the 12- and 24-week groups were similar. Thirteen patients (4%) discontinued the ledipasvir and sofosbuvir combination prematurely because of adverse events; 10 patients died, mainly from complications related to hepatic decompensation. CONCLUSION: The combination of ledipasvir, sofosbuvir, and ribavirin for 12 weeks produced high rates of SVR12 in patients with advanced liver disease, including those with decompensated cirrhosis before and after liver transplantation. ClinTrials.gov: NCT01938430

Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

TRY plant trait database – enhanced coverage and open access

Plant traits - the morphological, anatomical, physiological, biochemical and phenological characteristics of plants - determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits - almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Relationship Between Literacy, Knowledge, Self-Care Behaviors, and Heart Failure-Related Quality of Life Among Patients With Heart Failure

ABSTRACTBACKGROUNDWe sought to examine the relationship between literacy and heart failure-related quality of life (HFQOL), and to explore whether literacy-related differences in knowledge, self-efficacy and/or self-care behavior explained the relationship.METHODSWe recruited patients with symptomatic heart failure (HF) from four academic medical centers. Patients completed the short version of the Test of Functional Health Literacy in Adults (TOFHLA) and questions on HF-related knowledge, HF-related self-efficacy, and self-care behaviors. We assessed HFQOL with the Heart Failure Symptom Scale (HFSS) (range 0–100), with higher scores denoting better quality of life. We used bivariate (t-tests and chi-square) and multivariate linear regression analyses to estimate the associations between literacy and HF knowledge, self-efficacy, self-care behaviors, and HFQOL, controlling for demographic characteristics. Structural equation modeling was conducted to assess whether general HF knowledge, salt knowledge, self-care behaviors, and self-efficacy mediated the relationship between literacy and HFQOL.RESULTSWe enrolled 605 patients with mean age of 60.7years; 52% were male; 38% were African-American and 16% Latino; 26% had less than a high school education; and 67% had annual incomes under $25,000. Overall, 37% had low literacy (marginal or inadequate on TOFHLA). Patients with adequate literacy had higher general HF knowledge than those with low literacy (mean 6.6 vs. 5.5, adjusted difference 0.63, p < 0.01), higher self-efficacy (5.0 vs. 4.1 ,adjusted difference 0.99, p < 0.01), and higher prevalence of key self-care behaviors (p < 0.001). Those with adequate literacy had better HFQOL scores compared to those with low literacy (63.9 vs. 55.4, adjusted difference 7.20, p < 0.01), but differences in knowledge, self-efficacy, and self-care did not mediate this difference in HFQOL.CONCLUSIONLow literacy was associated with worse HFQOL and lower HF-related knowledge, self-efficacy, and self-care behaviors, but differences in knowledge, self-efficacy and self-care did not explain the relationship between low literacy and worse HFQOL

The Movember Foundation's GAP3 cohort: a profile of the largest global prostate cancer active surveillance database to date

OBJECTIVES: The Movember Foundation launched the Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative to create a global consensus on the selection and monitoring of men with low‐risk prostate cancer (PCa) on active surveillance (AS). The aim of this study is to present data on inclusion and follow‐up for AS in this unique global AS database. PATIENTS AND METHODS: Between 2014 and 2016, the database was created by combining patient data from 25 established AS cohorts worldwide (USA, Canada, Australasia, UK and Europe). Data on a total of 15 101 patients were included. Descriptive statistics were used to report patients' clinical and demographic characteristics at the time of PCa diagnosis, clinical follow‐up, discontinuation of AS and subsequent treatment. Cumulative incidence curves were used to report discontinuation rates over time. RESULTS: At diagnosis, the median (interquartile range [IQR]) patient age was 65 (60–70) years and the median prostate‐specific antigen level was 5.4 (4.0–7.3) ng/mL. Most patients had clinical stage T1 disease (71.8%), a biopsy Gleason score of 6 (88.8%) and one tumour‐positive biopsy core (60.3%). Patients on AS had a median follow‐up time of 2.2 (1.0–5.0) years. After 5, 10 and 15 years of follow‐up, respectively, 58%, 39% and 23% of patients were still on AS. The current version of GAP3 has limited data on magnetic resonance imaging (MRI), quality of life and genomic testing. CONCLUSIONS: GAP3 is the largest worldwide collaboration integrating patient data from men with PCa on AS. The results will allow individual patients and clinicians to have greater confidence in the personalized decision to either delay or proceed with active treatment. Longer follow‐up and the evaluation of MRI, new genomic markers and patient‐related outcomes will result in even more valuable data and eventually in better patient outcomes

The Movember Foundation&apos;s GAP3 cohort : a profile of the largest global prostate cancer active surveillance database to date

Objectives: The Movember Foundation launched the Global Action Plan Prostate Cancer Active Surveillance (GAP3) initiative to create a global consensus on the selection and monitoring of men with low-risk prostate cancer (PCa) on active surveillance (AS). The aim of this study is to present data on inclusion and follow-up for AS in this unique global AS database. Patients and Methods: Between 2014 and 2016, the database was created by combining patient data from 25 established AS cohorts worldwide (USA, Canada, Australasia, UK and Europe). Data on a total of 15 101 patients were included. Descriptive statistics were used to report patients' clinical and demographic characteristics at the time of PCa diagnosis, clinical follow-up, discontinuation of AS and subsequent treatment. Cumulative incidence curves were used to report discontinuation rates over time. Results: At diagnosis, the median (interquartile range [IQR]) patient age was 65 (60\u201370) years and the median prostate-specific antigen level was 5.4 (4.0\u20137.3) ng/mL. Most patients had clinical stage T1 disease (71.8%), a biopsy Gleason score of 6 (88.8%) and one tumour-positive biopsy core (60.3%). Patients on AS had a median follow-up time of 2.2 (1.0\u20135.0) years. After 5, 10 and 15 years of follow-up, respectively, 58%, 39% and 23% of patients were still on AS. The current version of GAP3 has limited data on magnetic resonance imaging (MRI), quality of life and genomic testing. Conclusions: GAP3 is the largest worldwide collaboration integrating patient data from men with PCa on AS. The results will allow individual patients and clinicians to have greater confidence in the personalized decision to either delay or proceed with active treatment. Longer follow-up and the evaluation of MRI, new genomic markers and patient-related outcomes will result in even more valuable data and eventually in better patient outcomes