HepCCATT: a multilevel intervention for hepatitis C among vulnerable populations in Chicago.

BACKGROUND: Hepatitis C infection could be eliminated. Underdiagnosis and lack of treatment are the barriers to cure, especially for vulnerable populations (i.e. unable to pay for health care). METHODS: A multilevel intervention from September 2014 to September 2019 focused on the providers and organizations in 'the safety net' (providing health care to populations unable to pay), including: (i) public education, (ii) training for primary care providers (PCPs) and case managers, (iii) case management for high-risk populations, (iv) policy advice and (v) a registry (Registry) for 13 health centers contributing data. The project tracked the number of PCPs trained and, among Registry sites, the number of people screened, engaged in care (i.e. clinical follow-up after diagnosis), treated and/or cured. RESULTS: In Chicago, 215 prescribing PCPs and 56 other health professionals, 86% of whom work in the safety net, were trained to manage hepatitis C. Among Registry sites, there was a 137% increase in antibody screening and a 32% increase in current hepatitis C diagnoses. Engagement in care rose by 18%. CONCLUSIONS: Hepatitis C Community Alliance to Test and Treat (HepCCATT) successfully targeted safety net providers and organizations with a comprehensive care approach. While there were challenges, HepCCATT observed increased hepatitis C screening, diagnosis and engagement in care in the Chicago community.

Impact of age on viral kinetics of peginterferon alfa-2a/ribavirin in chronic hepatitis C: final analysis from the PROPHESYS cohort.

The population of patients with chronic hepatitis C viral infection is ageing; however, elderly, hepatitis C-infected patients are understudied and less frequently treated. This subanalysis of data from the multinational PROPHESYS study examined associations between age (≤65 vs >65 years), on-treatment virological response and sustained virological response (SVR) in patients treated with peginterferon alfa-2a (40KD)/ribavirin in accordance with local licences. PROPHESYS comprised three cohorts studied in 19 countries according to country-specific legal and regulatory requirements. This subanalysis includes treatment-naive HCV mono-infected patients assigned to receive peginterferon alfa-2a (40KD)/ribavirin, with 6276 individuals aged ≤65 years and 349 aged >65 years. Rapid virological response (RVR) rates by Week 4 were consistently lower in older genotype (G) 1 (21.6% vs 27.2% in younger patients), G2 (80.7% vs 85.1%) and G3 (60.0% vs 74.2%) patients. SVR rates were significantly lower (29.8% vs 43.0%) and relapse rates significantly higher (43.1% vs 26.7%) in older G1 patients (P = 0.0002 vs ≤65 years). In contrast, SVR and relapse rates were similar in G2 and G3 patients regardless of age. The positive predictive value of RVR for SVR was comparable in older and younger G1 patients (66.7% vs 68.6%, respectively) and higher in older G2 (80.7% vs 75.6%) and G3 (77.8% vs 66.8%) patients. Virological response rates are generally lower in elderly CHC patients, and RVR is a reliable positive predictor of SVR in patients >65 years.

How different conceptions of risk are used in the organ market debate.

The success of kidney and liver transplantation is hindered by a shortage of organs available for transplantation. Although currently illegal in nearly all parts of the world, a living 'donor' or 'vendor' kidney market has been proposed as a means to reduce or even end this shortage. Physician members of the American Society of Transplantation, the American Society of Transplant Surgeons and the American Association for the Study of Liver Disease were surveyed regarding organ markets for both living kidney and living liver transplantation. The survey queried respondents about their attitudes toward directed living donation, nondirected living donation, the potential legalization of living donor organ markets and the reasons for their support or opposition to organ markets. Partial or completed surveys were returned by 346 of 697 eligible respondents (50%). While virtually all supported or strongly supported directed living donation (98% and 95% for kidney and liver lobes, respectively), the vast majority disagreed or strongly disagreed with the legalization of living donor organ markets (80% for kidneys and 90% for liver lobes). Both those who support and those who oppose a legalized living donor organ market rate risk to the donor among the most important factors to justify their position.

Heterogeneous nuclear ribonucleoprotein K is a transcription factor.

The CT element is a positively acting homopyrimidine tract upstream of the c-myc gene to which the well-characterized transcription factor Spl and heterogeneous nuclear ribonucleoprotein (hnRNP) K, a less well-characterized protein associated with hnRNP complexes, have previously been shown to bind. The present work demonstrates that both of these molecules contribute to CT element-activated transcription in vitro. The pyrimidine-rich strand of the CT element both bound to hnRNP K and competitively inhibited transcription in vitro, suggesting a role for hnRNP K in activating transcription through this single-stranded sequence. Direct addition of recombinant hnRNP K to reaction mixtures programmed with templates bearing single-stranded CT elements increased specific RNA synthesis. If hnRNP K is a transcription factor, then interactions with the RNA polymerase II transcription apparatus are predicted. Affinity columns charged with recombinant hnRNP K specifically bind a component(s) necessary for transcription activation. The depleted factors were biochemically complemented by a crude TFIID phosphocellulose fraction, indicating that hnRNP K might interact with the TATA-binding protein (TBP)-TBP-associated factor complex. Coimmunoprecipitation of a complex formed in vivo between hnRNP K and epitope-tagged TBP as well as binding in vitro between recombinant proteins demonstrated a protein-protein interaction between TBP and hnRNP K. Furthermore, when the two proteins were overexpressed in vivo, transcription from a CT element-dependent reporter was synergistically activated. These data indicate that hnRNP K binds to a specific cis element, interacts with the RNA polymerase II transcription machinery, and stimulates transcription and thus has all of the properties of a transcription factor.

Nuclear localization signal peptides enhance cationic liposome-mediated gene therapy.

The use of genes as therapeutic drugs will likely involve non-viral delivery systems. While traditionally less effective for gene expression, the advantages of a non-viral delivery system include ease of production, lower toxicity, and no risk of infection. However, most non-viral systems do not incorporate a mechanism for gene transport into the nucleus. Nuclear localization signal peptides can combine the increased expression of viral delivery systems with the safety and ease of preparation of non-viral delivery systems. A novel non-viral delivery vehicle consisting of a conglomerate of a synthetic nuclear localization signal peptide derived from the SV40 virus, a luciferase encoding PGL3 plasmid, and a cationic lipid DOTAP:DOPE (1:1 w/w) liposome was transfected into SKnSH mammalian neuroblastoma cells. A three-fold increase in luciferase expression was seen with the delivery system containing a NLS peptide over cationic liposome controls. Examination of the factors that limit the rate of transgene expression can potentially lead to the discovery of new ways to improve the efficiency and efficacy of nonviral methods of gene therapy.

¿Qué espera el clínico del informe radiológico? / What does the clinician expect from the radiological report?

Introduction: The written radiology report is the most relevant component of any radiological examination. Few studies about referring clinicians opinion concerning structure and contents of radiology reports have been conducted. Objective: To investigate which radiology report issues are significant to the clinician. Methodology: One hundred and sixty-four physicians, among surgeons, internists, residents, and general practitioners were surveyed. Results: According to surveyed clinicians the most important element in any radiologic examination is the reporting radiologist (67.7 percent); 93.9 percent of them expect the radiology report to address the referral diagnosis; 95.7 percent expects the report to present a conclusion, whilst 73 percent of referring clinicians consider ultrasonography as the imaging procedure that commonly exhibits more errors. Surgeons, generally understimate radiologists recommendations for complementary studies. Conclusion: An experienced reporting radiologist is considered the most significant element of any imaging procedure. The radiology report should be problem-oriented (answering clinical question), and contain a conclusion, which should begin by answering the clinician s concerns. General practitioners, internists and residents value further studies reccommended by radiologists.

Introducción. El informe es lo más relevante de un examen radiológico. Escasas publicaciones han estudiado la opinión del clínico. Objetivo. Establecer qué aspectos del informe son relevantes para el clínico. Metodología. Se aplicó una encuesta a cirujanos, internistas, residentes y médicos generales. Resultados. Se encuestó a 164 médicos. Al pedir un examen radiológico, lo más relevante (67,7 por ciento) fue el radiólogo informante; 93,9 por ciento considera importante que se haga referencia al diagnóstico de derivación; 95,7 por ciento estima que debe haber conclusión. El 73 por ciento cree que el examen en el que se cometen más errores es la ecotomografía. Los cirujanos son los que menos valoran las recomendaciones de estudios posteriores. Conclusión. El radiólogo que informa es considerado lo más importante en un examen. El informe debe hacer referencia al diagnóstico, tener conclusión, la que debe comenzar respondiendo la inquietud del clínico. Los médicos generales, internistas y residentes valoran que se sugieran estudios complementarios.

The impact of space travel on dosage form design and use.

NASA: The author speculates on potential factors that may influence the utilization of dosage forms in space. A key assumption is that most of the arguments will be based on current understanding of how dosage forms work on earth. Factors discussed include dosage form stability; and administration of drugs, particularly inhalation and aerosols. A sample experiment used a tissue culture model of drug transfer for passively absorbed drugs to address how alterations in hydrostatic pressure would change paracellular transport.^ieng

Evaluation of adjuvants that enhance the effectiveness of antisense oligodeoxynucleotides.

PURPOSE: A factor limiting the effectiveness of antisense (AS) deoxyoligonucleotides (ODNs) is inefficient transport to their sites of action in the cytoplasm and in the nucleus. The extent of ODN transfer from endosomes to cytosol seems to be an important determinant of ODN effects. Consequently, the development of compounds (adjuvants) that enhance endosome to cytosol transfer may be vital in AS ODN therapeutics. METHODS: In this report, we evaluated compounds for their potential to enhance the effects of phosphorothioate ODNs. The test system used a CHO cell line expressing the enzyme chloramphenicol acetyl-transferase (CAT) under the control of an inducible promoter. Several potential endosomal disrupting adjuvants were screened, including: (a) fusogenic peptides; (b) a pH sensitive polymer; (c) polymeric dendrimers, (d) cationic liposomes and (e) a pH sensitive surfactant N-dodecyl 2-imidazole-propionate (DIP). ODN effects were evaluated at the protein level by quantitating levels of CAT. RESULTS: The use of AS ODN in co-incubation with the GALA peptide, cationic liposomes or 5th generation dendrimers resulted in a 35-40% reduction in CAT expression. The mis-matched ODN had no effect on CAT expression. Only modest effects were observed with the other adjuvants. DIP did not increase ODN activity by itself; however, when the liposomal form was used a significant reduction (48%) in CAT activity was seen. CONCLUSIONS: We found the fusogenic peptide GALA, dendrimers, as well as the liposomal form of DIP, could significantly enhance the effects of ODNs.