Desirable Characteristics of Hepatitis C Treatment Regimens: A Review of What We Have and What We Need.

There have been dramatic advancements in the treatment of chronic hepatitis C (HCV) infection. This is largely due to the approval of several direct-acting antiviral agents (DAAs) from a variety of medication classes with novel mechanisms of action. These therapies are a welcomed advancement given their improved efficacy and tolerability compared to pegylated interferon and ribavirin (RBV)-based regimens. These convenient, all-oral regimens treat a variety of genotypes and often offer high cure rates in a variety of HCV-infected populations. While there are several benefits associated with these therapies, there are also notable shortcomings. Shortcomings include diminished response or need for adjunctive RBV in difficult-to-treat populations (decompensated cirrhosis, active substance abuse patients, advanced kidney disease, etc.), activity against select genotypes, substantial drug-drug interaction potential, and high cost. Therefore, while current DAA-based therapies have several favorable attributes, each also has its limitations. The purpose of this review is to (1) identify the characteristics of an ideal HCV treatment regimen, (2) describe desirable features of existing regimens, (3) summarize limitations of existing regimens, and (4) introduce promising emerging therapies. This manuscript will serve as a guide for evaluating the caliber of future HCV treatment regimens

Teaching the Use of Systems Dynamics for Strategic Decision Making in Healthcare

Having worked in the healthcare system and taught healthcare MBAs for over a decade, we have observed that healthcare systems and departments operate in independent silos. This paper shows how to use systems dynamics as a method to help students examine the big picture of how components fit together to form a system. We demonstrate the application of this approach and provide an example from one of our healthcare professional graduate student teams

Outdoor music festivals: Cacophonous consumption or melodious moderation?

Large outdoor music festivals have emerged as part of a general expansion of licensed recreational activities, but in research terms they have been largely impenetrable due to commercial sensitivities. These sensitivities notwithstanding, the number and scale of such events necessitate a greater understanding of alcohol and drug use and the potential to promote normative protective behaviours in this context. This study examines self-reported alcohol and drug behaviours of 1589 attendees at a music festival in Scotland during the summer of 2008. Similarities between the outdoor rock music festivals and the dance club scene are considered alongside the challenges associated with risk reduction in these settings. Results show that alcohol was consumed by the majority of samples; however, negative consequences were reported by a minority of respondents, suggesting evidence of controlled hedonism within a situation traditionally associated with unrestrained excess. Similarly, the majority of samples did not use drugs. The majority also report a number of self-regulating protective behaviours suggesting that alcohol and drug use is contained within a developing social culture of ‘controlled intoxication’. Results further suggest that although music festivals are transitory events, there is a degree of consistency amongst attendees. Music festivals may therefore be atypical but potentially effective environments to increase protective behaviours using normative messaging and modern communications media. This study was resourced exclusively by local alcohol and drug partnerships

Strategic Directions in Supermarket Deli/Prepared Foods

A.E. Res. 90-1

Psychosis Prevention: A Modified Clinical High Risk Perspective From the Recognition and Prevention (RAP) Program

OBJECTIVE: Early intervention and prevention of psychosis remain a major challenge. Prediction would be greatly advanced with improved ability to identify individuals at true risk, which, at present, is moderate at best. The authors tested a modified strategy to improve prediction by selecting a more homogeneous high-risk sample (attenuated positive symptom criteria only, age range of mid-teens to early 20s) than is currently standard, combined with a systematic selection of neurodevelopmental deficits. METHOD: A sample of 101 treatment-seeking adolescents (mean age, 15.9 years) at clinical high risk for psychosis were followed clinically for up to 5 years (mean follow-up time, 3.0 years, SD=1.6). Adolescents were included only if they exhibited one or more attenuated positive symptoms at moderate to severe, but not psychotic, severity levels. Cox regression was used to derive a risk index. RESULTS: The overall conversion rate to psychosis was 28.3%. The final predictor model, with a positive predictive validity of 81.8%, consisted of four variables: disorganized communication, suspiciousness, verbal memory deficits, and decline in social functioning during follow-up. Significant effects also suggest narrowing the risk age range to 15-22 years. CONCLUSIONS: Clinical high risk criteria that emphasize disorganized communication and suspiciousness while also including compromised verbal memory and declining social functioning have the potential to improve predictive accuracy compared with attenuated positive symptoms used alone. On the resulting risk index (a weighted combination of the predictors), low scores were interpreted as signifying minimal risk, with little treatment necessary, high scores as suggesting aggressive intervention, and intermediate scores, although less informative, as supporting psychosocial treatment

Knockdown of the schizophrenia susceptibility gene TCF4 alters gene expression and proliferation of progenitor cells from the developing human neocortex

BACKGROUND: Common variants in the TCF4 gene are among the most robustly supported genetic risk factors for schizophrenia. Rare TCF4 deletions and loss-of-function point mutations cause Pitt-Hopkins syndrome, a developmental disorder associated with severe intellectual disability. METHODS: To explore molecular and cellular mechanisms by which TCF4 perturbation could interfere with human cortical development, we experimentally reduced the endogenous expression of TCF4 in a neural progenitor cell line derived from the developing human cerebral cortex using RNA interference. Effects on genome-wide gene expression were assessed by microarray, followed by Gene Ontology and pathway analysis of differentially expressed genes. We tested for genetic association between the set of differentially expressed genes and schizophrenia using genome-wide association study data from the Psychiatric Genomics Consortium and competitive gene set analysis (MAGMA). Effects on cell proliferation were assessed using high content imaging. RESULTS: Genes that were differentially expressed following TCF4 knockdown were highly enriched for involvement in the cell cycle. There was a nonsignificant trend for genetic association between the differentially expressed gene set and schizophrenia. Consistent with the gene expression data, TCF4 knockdown was associated with reduced proliferation of cortical progenitor cells in vitro. LIMITATIONS: A detailed mechanistic explanation of how TCF4 knockdown alters human neural progenitor cell proliferation is not provided by this study. CONCLUSION: Our data indicate effects of TCF4 perturbation on human cortical progenitor cell proliferation, a process that could contribute to cognitive deficits in individuals with Pitt-Hopkins Syndrome and risk for schizophrenia

Dynamics of the Globular Cluster System Associated with M49 (NGC4472): Cluster Orbital Properties and the Distribution of Dark Matter

We have measured radial velocities for 196 globular clusters (GCs) around M49, the brightest member of the Virgo Cluster. Combined with published data, they bring the total number of GCs with measured radial velocities in this galaxy to 263. Using this sample, we extract the projected kinematics of the full sample of GCs, and of the separate metal-poor and metal-rich subsamples. In agreement with previous results for the global GC kinematics based on smaller datasets, we find that the GC system as a whole exhibits a slow overall rotation that is due almost entirely to a net rotation of the metal-poor GC subsystem alone. In a spatial average, the metal-rich GCs shows essentially no rotation. We note, however, the presence of a well defined grouping of 10 metal-rich GCs that are located at opposite poles along the galaxy's major axis and which appear to be rotating at nearly 300 km/s about the minor axis. This grouping may be the relic of a past merger or accretion event. Using a Jeans-equation analysis, we show that the GC radial velocities alone point unequivocally (and independently of X-ray observations) to the need for a massive dark halo associated with M49 and the Virgo B subcluster around it. We also show that the GC system as a whole is consistent with an almost perfectly isotropic velocity ellipsoid. M49 is now the second elliptical galaxy (after M87) for which we have been able to demonstrate velocity isotropy in the globular cluster system overall, when no division based on GC color or metallicity is attempted. Thus, the data for these two galaxies lend support the general assumption of isotropy when using GC kinematics to study the dark-matter distribution in early-type galaxies. (ABRIDGED)Comment: 63 pages, 21 postscript figures. Accepted for publication in the Astrophysical Journa

Primary care physicians’ perspectives on computer-based health risk assessment tools for chronic diseases: a mixed methods study

Background Health risk assessment tools compute an individual’s risk of developing a disease. Routine use of such tools by primary care physicians (PCPs) is potentially useful in chronic disease prevention. We sought physicians’ awareness and perceptions of the usefulness, usability and feasibility of performing assessments with computer-based risk assessment tools in primary care settings.Methods Focus groups and usability testing with a computer-based risk assessment tool were conducted with PCPs from both university-affiliated and community-based practices. Analysis was derived from grounded theory methodology.Results PCPs (n = 30) were aware of several risk assessment tools although only select tools were used routinely. The decision to use a tool depended on how use impacted practice workflow and whether the tool had credibility. Participants felt that embedding tools in the electronic medical records (EMRs) system might allow for health information from the medical record to auto-populate into the tool. User comprehension of risk could also be improved with computer-based interfaces that present risk in different formats.Conclusions In this study, PCPs chose to use certain tools more regularly because of usability and credibility. Despite there being differences in the particular tools a clinical practice used, there was general appreciation for the usefulness of tools for different clinical situations. Participants characterised particular features of an ideal tool, feeling strongly that embedding risk assessment tools in the EMR would maximise accessibility and use of the tool for chronic disease management. However, appropriate practice workflow integration and features that facilitate patient understanding at point-of-care are also essential.

F.A.R.O.G. FORUM, Vol. 3 No. 5

https://digitalcommons.library.umaine.edu/francoamericain_forum/1012/thumbnail.jp