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Sample records for clinical status virologic

  1. Clinical virology in real time.

    PubMed

    Niesters, Hubert G M

    2002-12-01

    The ability to detect nucleic acids has had and still has a major impact on diagnostics in clinical virology. Both quantitative and qualitative techniques, whether signal or target amplification based systems, are currently used routinely in most if not all virology laboratories. Technological improvements, from automated sample isolation to real time amplification technology, have given the ability to develop and introduce systems for most viruses of clinical interest, and to obtain clinical relevant information needed for optimal antiviral treatment options. Both polymerase chain reaction (PCR) and nucleic acid sequence-based amplification (NASBA) can currently be used together with real time detection to generate results in a short turn-around time and to determine whether variants relevant for antiviral resistance are present. These new technologies enable the introduction of an individual patient disease management concept. Within our clinical setting, we have introduced this e.g. for quantitative detection of Epstein-Barr Virus (EBV) in T-dell depleted allogeneic stem cell transplant patients. This enabled us to develop models for pre-emptive anti B-cell immunotherapy for EBV reactivation, thereby effectively reducing not the incidence of EBV-lymphoproliferative disease but the virus related mortality. Furthermore, additional clinically relevant viruses can now easily be detected simultaneously. It also becomes more feasible to introduce molecular testing for those viruses that can easily be detected using classical virological methods, like culture techniques or antigen detection. Prospective studies are needed to evaluate the clinical importance of the additional positive samples detected. It should however be made clear that a complete exchange of technologies is unlikely to occur, and that some complementary technologies should stay operational enabling the discovery of new viruses. The implementation of these molecular diagnostic technologies furthermore

  2. Clinical progression of severely immunosuppressed HIV-infected patients depends on virological and immunological improvement irrespective of baseline status.

    PubMed

    Ferrer, Elena; Curto, Jordi; Esteve, Anna; Miro, Jose M; Tural, Cristina; Murillas, Javier; Segura, Ferran; Barrufet, Pilar; Casabona, Jordi; Podzamczer, Daniel

    2015-12-01

    The aim of this study was to analyse factors associated with progression to AIDS/death in severely immunosuppressed HIV-infected patients receiving ART. This study included naive patients from the PISCIS Cohort with CD4 <200 cells/mm(3) at enrolment and who initiated ART consisting of two nucleoside analogues plus either a PI or an NNRTI between 1998 and 2011. The PISCIS Cohort is a multicentre, observational study of HIV-infected individuals aged >18 years followed at 14 participating hospitals in Catalonia and the Balearic Islands (Spain). Clinical and laboratory parameters were assessed every 3-4 months during follow-up. Cox regression models were used to assess the effect of CD4 and viral load on the risk of progression to AIDS/death, adjusting for baseline variables and confounders. 2295 patients were included and, after 5 years, 69.9% reached CD4 ≥200 cells/mm(3), 64.4% had an undetectable viral load and 482 (21%) progressed to AIDS/death. The lowest rate of disease progression was found in patients who reached both immunological and viral responses during follow-up, regardless of their baseline situation (1.9% in baseline CD4 >100 cells/mm(3) and viral load <5 log copies/mL; 2.3% in baseline CD4 ≤100 cells/mm(3) and/or viral load >5 log copies/mL). Achieving a CD4 count ≥200 cells/mm(3) was the main predictor of decreased progression to AIDS/death. In those not reaching this CD4 threshold, virological response reduced disease progression by half. Even in the worse baseline scenario of CD4 ≤100 cells/mm(3) and high baseline viral loads, positive virological and immunological responses were associated with dramatic decreases in progression. © The Author 2015. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  3. European Society for Clinical Virology - winter meeting.

    PubMed

    Westh, Henrik

    2004-02-01

    The European Society for Clinical Virology annual winter meeting mainly appeals to clinical virologists interested in human disease. Basic and clinical data were presented, highlighting a number of interesting findings. This report briefly describes options in HIV antiviral treatment, and focuses on fusion inhibitors, a new anti-HIV class of drugs. Recent improvements in experimental DNA vaccines are also presented.

  4. Hepatitis delta: virological and clinical aspects.

    PubMed

    Botelho-Souza, Luan Felipo; Vasconcelos, Mariana Pinheiro Alves; Dos Santos, Alcione de Oliveira; Salcedo, Juan Miguel Villalobos; Vieira, Deusilene Souza

    2017-09-13

    There are an estimated 400 million chronic carriers of HBV worldwide; between 15 and 20 million have serological evidence of exposure to HDV. Traditionally, regions with high rates of endemicity are central and northern Africa, the Amazon Basin, eastern Europe and the Mediterranean, the Middle East and parts of Asia. There are two types of HDV/HBV infection which are differentiated by the previous status infection by HBV for the individual. Individuals with acute HBV infection contaminated by HDV is an HDV/HBV co-infection, while individuals with chronic HBV infection contaminated by HDV represent an HDV/HBV super-infection. The appropriate treatment for chronic hepatitis delta is still widely discussed since it does not have an effective drug. Alpha interferon is currently the only licensed therapy for the treatment of chronic hepatitis D. The most widely used drug is pegylated interferon but only approximately 25% of patients maintain a sustained viral response after 1 year of treatment. The best marker of therapeutic success would be the clearance of HBsAg, but this data is rare in clinical practice. Therefore, the best way to predict a sustained virologic response is the maintenance of undetectable HDV RNA levels.

  5. Applying proteomic technology to clinical virology.

    PubMed

    Mancone, C; Ciccosanti, F; Montaldo, C; Perdomo, A B; Piacentini, M; Alonzi, T; Fimia, G M; Tripodi, M

    2013-01-01

    Developing antiviral drugs, vaccines and diagnostic markers is still the most ambitious challenge in clinical virology. In the past few decades, data from high-throughput technologies have allowed for the rapid development of new antiviral therapeutic strategies, thus making a profound impact on translational research. Most of the current preclinical studies in virology are aimed at evaluating the dynamic composition and localization of the protein platforms involved in various host-virus interactions. Among the different possible approaches, mass spectrometry-based proteomics is increasingly being used to define the protein composition in subcellular compartments, quantify differential protein expression among samples, characterize protein complexes, and analyse protein post-translational modifications. Here, we review the current knowledge of the most useful proteomic approaches in the study of viral persistence and pathogenicity, with a particular focus on recent advances in hepatitis C research.

  6. Total quality management in clinical virology laboratories.

    PubMed

    Tibbets, M W; Gomez, R; Kannangai, R; Sridharan, G

    2006-10-01

    The diagnostic laboratories in India are progressively promoting higher standards and are moving towards accreditation and international acceptance. Hence, the concept of "Quality" will need to be understood and implemented. Total quality management (TQM) in a laboratory is an integrated program involving all laboratory staff and management. TQM is a framework to operate and it is aiming for integration, consistency, increase in efficiency and a continuous drive for improvement. A well structured clinical virology service will include serology setup, cell culture facility and capacity for molecular diagnosis. The quality of results from the laboratory is significantly influenced by many pre-analytical and post-analytical factors which needed attention. The end goal of the TQM should be to provide the best care possible for the patient.

  7. [Herpetic keratitis: clinical-virological correlation].

    PubMed

    Martínez, M J; Vogel, M; Stoppel, J; Charlin, R; Squella, O; Srur, M; Traipe, L; Verdaguer, J; Suárez, M

    1997-06-01

    Herpetic keratitis is the main infectious cause of corneal opacity. The existence of effective antiviral agents underscores the need of an early diagnosis. To correlate clinical features of herpetic keratitis with virological studies. Forty one patients with a clinical diagnosis of herpetic keratitis were studied. Viral isolation, polymerase chain reaction (PCR) and typification were done in a sample taken by swabbing the ocular lesion. Twenty six patients (31% female) had epithelial keratitis, that was mild or moderate in 88% of cases and acute in 77% of them. In 20 patients (77%), viral isolation and PCR were positive (HSV-2 in one case). Fifteen patients (67% female) had stromal keratitis, 93% of cases were moderate or severe and 53% were acute. Viral isolation was negative in all cases and in 20% PCR was positive. Viral isolation and PCR were equally sensitive in epithelial keratitis, but in stromal keratitis only PCR could detect the virus. Moderate acute dendrite was the predominant clinical manifestation. The higher proportion of women with stromal keratitis supports its possibly autoimmune etiology. HSV-2 is seldomly isolated and possibly associated to vertical transmission.

  8. Myocarditis in puppies: clinical, pathological and virological findings.

    PubMed

    Gagnon, A N; Crowe, S P; Allen, D G; Downey, R S

    1980-07-01

    The clinical, pathological and virological findings in puppies affected with myocarditis are reported. A parvo-like virus was isolated from pooled heart specimens, which is similar to the virus isolated from gastroenteritis cases.

  9. Verification and validation of diagnostic laboratory tests in clinical virology.

    PubMed

    Rabenau, Holger F; Kessler, Harald H; Kortenbusch, Marhild; Steinhorst, Andreas; Raggam, Reinhard B; Berger, Annemarie

    2007-10-01

    This review summarizes major issues of verification and validation procedures and describes minimum requirements for verification and validation of diagnostic assays in clinical virology including instructions for CE/IVD-labeled as well as for self-developed ("home-brewed") tests or test systems. It covers techniques useful for detection of virus specific antibodies, for detection of viral antigens, for detection of viral nucleic acids, and for isolation of viruses on cell cultures in the routine virology laboratory.

  10. Deep sequencing: becoming a critical tool in clinical virology.

    PubMed

    Quiñones-Mateu, Miguel E; Avila, Santiago; Reyes-Teran, Gustavo; Martinez, Miguel A

    2014-09-01

    Population (Sanger) sequencing has been the standard method in basic and clinical DNA sequencing for almost 40 years; however, next-generation (deep) sequencing methodologies are now revolutionizing the field of genomics, and clinical virology is no exception. Deep sequencing is highly efficient, producing an enormous amount of information at low cost in a relatively short period of time. High-throughput sequencing techniques have enabled significant contributions to multiples areas in virology, including virus discovery and metagenomics (viromes), molecular epidemiology, pathogenesis, and studies of how viruses to escape the host immune system and antiviral pressures. In addition, new and more affordable deep sequencing-based assays are now being implemented in clinical laboratories. Here, we review the use of the current deep sequencing platforms in virology, focusing on three of the most studied viruses: human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus.

  11. Deep Sequencing: Becoming a Critical Tool in Clinical Virology

    PubMed Central

    QUIÑONES-MATEU, Miguel E.; AVILA, Santiago; REYES-TERAN, Gustavo; MARTINEZ, Miguel A.

    2014-01-01

    Population (Sanger) sequencing has been the standard method in basic and clinical DNA sequencing for almost 40 years; however, next-generation (deep) sequencing methodologies are now revolutionizing the field of genomics, and clinical virology is no exception. Deep sequencing is highly efficient, producing an enormous amount of information at low cost in a relatively short period of time. High-throughput sequencing techniques have enabled significant contributions to multiples areas in virology, including virus discovery and metagenomics (viromes), molecular epidemiology, pathogenesis, and studies of how viruses to escape the host immune system and antiviral pressures. In addition, new and more affordable deep sequencing-based assays are now being implemented in clinical laboratories. Here we review the use of the current deep sequencing platforms in virology, focusing on three of the most studied viruses: human immunodeficiency virus (HIV), hepatitis C virus (HCV), and influenza virus. PMID:24998424

  12. The potential advantages of digital PCR for clinical virology diagnostics.

    PubMed

    Hall Sedlak, Ruth; Jerome, Keith R

    2014-05-01

    Digital PCR (dPCR), a new nucleic acid amplification technology, offers several potential advantages over real-time or quantitative PCR (qPCR), the current workhorse of clinical molecular virology diagnostics. Several studies have demonstrated dPCR assays for human cytomegalovirus or HIV, which give more precise and reproducible results than qPCR assays without sacrificing sensitivity. Here we review the literature comparing dPCR and qPCR performance in viral molecular diagnostic assays and offer perspective on the future of dPCR in clinical virology diagnostics.

  13. Molecular virology in the clinical laboratory.

    PubMed

    Josko, Deborah

    2010-01-01

    As one can see by the tests listed at www.amp.org, molecular diagnostic techniques have enabled the laboratory professionals to play an integral role in the identification and quantitation of viral infectious agents. Viral loads can be determined for HIV, HBV, and HCV using a variety of molecular methods such as real-time PCR, TMA, NASBA, and bDNA. Determining the amount of viral particles in a sample can not only monitor the status and progression of the disease, but can also guide recommendations for antiviral therapy. Other assays listed include cytomegalovirus, enterovirus, and human metapneumovirus detection, HPV testing, influenza and respiratory virus panels, and West Nile virus detection in blood donations using a variety of molecular methodologies. The use of molecular methodologies in the detection of viral pathogens has grown at an astounding rate, especially in the past two decades. It is now widely accepted that PCR is the "gold standard" for nucleic acid detection in the clinical laboratory as well as in research facilities. This article only touched on some of the common, widely used assays and platforms used in the identification process. With more and more assays being developed, the cost behind molecular testing has decreased since there are more competitors on the market. At one point, laboratorians may have thought of routine molecular testing as the wave of the future. It is obvious the future is upon us. Molecular diagnostics has become part of the daily, routine workload in most clinical laboratories. The advent of fully automated systems with faster turn around times has given laboratory professionals the tools necessary to report out accurate and sensitive results to clinicians who can ultimately improve patient care and outcomes by rendering a correct and rapid diagnosis.

  14. Basic overview of method validation in the clinical virology laboratory.

    PubMed

    Newman, Howard; Maritz, Jean

    2017-08-30

    Diagnostic virology laboratories are an essential part of the health system and are often relied upon to provide information to clinicians that will inform clinical decision making. It is therefore imperative that diagnostic results produced in the laboratory are reliable. One way of ensuring quality results is by ensuring that all tests are either validated (for tests developed in-house) or verified (for commercial assays that are FDA-approved or CE-labeled). In the diagnostic virology laboratory, these processes can be complex as both qualitative and quantitative measurements for serological and molecular tests are routinely offered. While there are numerous guidelines governing quality assurance in the virology laboratory, all accrediting agencies would insist on tests being validated or verified prior to implementation without providing explicit guidance to the process. As there is no universal guideline on the optimal way to perform validation/verification experiments, this review will provide a basic overview of method validation/verification, specific for clinical virology laboratories, and includes explanation of statistical analysis and acceptance/rejection criteria. Copyright © 2017 John Wiley & Sons, Ltd.

  15. Trends in virological and clinical outcomes in individuals with HIV-1 infection and virological failure of drugs from three antiretroviral drug classes: a cohort study.

    PubMed

    Costagliola, Dominique; Lodwick, Rebecca; Ledergerber, Bruno; Torti, Carlo; van Sighem, Ard; Podzamczer, Daniel; Mocroft, Amanda; Dorrucci, Maria; Masquelier, Bernard; de Luca, Andrea; Jansen, Klaus; De Wit, Stephane; Obel, Niels; Fätkenheuer, Gerd; Touoloumi, Giota; Mussini, Cristina; Castagna, Antonella; Stephan, Cristoph; García, Federico; Zangerle, Robert; Duval, Xavier; Pérez-Hoyos, Santiago; Meyer, Laurence; Ghosn, Jade; Fabre-Colin, Céline; Kjaer, Jesper; Chene, Genevieve; Grarup, Jesper; Phillips, Andrew

    2012-02-01

    Limited treatment options have been available for people with HIV who have had virological failure of the three original classes of HIV antiretroviral drugs-so-called triple-class virological failure (TCVF). However, introduction of new drugs and drug classes might have improved outcomes. We aimed to assess trends in virological and clinical outcomes for individuals with TCVF in 2000-09. In our cohort study, we analysed data for adults starting antiretroviral therapy from 1998 in cohorts participating in the PLATO II project, which is part of COHERE, a collaboration of European cohorts. TCVF was defined as virological failure to at least two nucleoside reverse transcriptase inhibitors, one non-nucleoside reverse-transcriptase inhibitor, and one ritonavir-boosted protease inhibitor, with virological failure of a drug defined as one viral-load measurement of greater than 500 copies per mL after at least 4 months of continuous use. We used multivariable generalised estimating equation logistic models and Poisson regression models to study trends in virological suppression and incidence of AIDS or death after TCVF. We adjusted for sex, transmission group, age, AIDS status, CD4 cell count, plasma viral loads at TCVF, achievement of virological response (<50 copies per mL), and number of drug failures before TCVF. 28 of 33 cohorts in COHERE contributed data to the PLATO II project, of which four had no participants eligible for inclusion in this study. 2476 (3%) of 91 764 participants from the remaining 24 cohorts had TCVF and at least one viral load measurement in 2000-09. The proportion of patients with virological response after TCVF increased from 19·5% in 2000 to 57·9% in 2009 (adjusted p<0·0001). Incidence of AIDS decreased from 7·7 per 100 person-years in 2000-02 to 2·3 in 2008 and 1·2 in 2009 (adjusted p<0·0001). Mortality decreased from 4·0 per 100 person-years between 2000 and 2002 to 1·9 in 2007 and 1·4 in 2008 (unadjusted p=0·023), but the trend

  16. A role for arrays in clinical virology: fact or fiction?

    PubMed

    Clewley, Jonathan P

    2004-01-01

    Microarrays of DNA probes have at least three roles in clinical virology. These are: firstly, in diagnosis, to recognise the causative agent of an illness; secondly, for molecular typing for (i) patient management, (ii) epidemiological reasons (e.g. investigating routes of transmission), (iii) purposes related to vaccine use; and thirdly, in research, to investigate the interactions between the virus and the host cell. Microarrays intended for syndromic diagnostic purposes require genome specific probes to capture the unknown target viral sequences and thereby reveal the presence of that virus in a test sample. Microarrays intended for typing and patient management, e.g. monitoring antiviral drug resistant mutations require a set of probes representing the important sequence variants of one or more viral genes. Microarrays intended for research into virus-host interactions require probes representative of each individual gene or mRNA of either the virus or the host genome. Diagnostic microarrays are dependent for their utility and versatility on generic, multiplex or random polymerase chain reactions that will amplify any of several (unknown) viral target sequences from a patient sample. In this review, the existing and potential applications of microarrays in virology, and the problems that need to be overcome for future success, are discussed.

  17. Quantification of HBsAg: basic virology for clinical practice.

    PubMed

    Lee, Jung Min; Ahn, Sang Hoon

    2011-01-21

    Hepatitis B surface antigen (HBsAg) is produced and secreted through a complex mechanism that is still not fully understood. In clinical fields, HBsAg has long served as a qualitative diagnostic marker for hepatitis B virus infection. Notably, advances have been made in the development of quantitative HBsAg assays, which have allowed viral replication monitoring, and there is an opportunity to make maximal use of quantitative HBsAg to elucidate its role in clinical fields. Yet, it needs to be underscored that a further understanding of HBsAg, not only from clinical point of view but also from a virologic point of view, would enable us to deepen our insights, so that we could more widely expand and apply its utility. It is also important to be familiar with HBsAg variants and their clinical consequences in terms of immune escape mutants, issues resulting from overlap with corresponding mutation in the P gene, and detection problems for the HBsAg variants. In this article, we review current concepts and issues on the quantification of HBsAg titers with respect to their biologic nature, method principles, and clinically relevant topics.

  18. Development of working reference materials for clinical virology.

    PubMed

    Fryer, Jacqueline F; Baylis, Sally A; Gottlieb, Anna L; Ferguson, Morag; Vincini, Giuseppe A; Bevan, Valerie M; Carman, William F; Minor, Philip D

    2008-12-01

    Nucleic acid amplification technique (NAT)-based assays are replacing traditional diagnostic methods in clinical laboratories. However, many of these assays are developed in-house and the lack of standardised reference materials has hindered assay implementation and control. Consequently, in the UK, the Clinical Virology Network (CVN), the National Institute for Biological Standards and Control (NIBSC), and the Health Protection Agency (HPA), are working in collaboration to develop working standards or 'run controls' for diagnostic NAT-based assays, particularly real-time PCR. These run controls are intended for use in microbiology laboratories and are designed to be extracted and amplified in the same way as clinical samples and included in each assay run. The aim is to enable clinical laboratories to continuously monitor the performance of their diagnostic NAT assays on a run-by-run basis allowing inter-laboratory comparisons, and ultimately improving the consistency of results. At present, eight candidate run controls representing clinically relevant viral targets have been prepared for evaluation by CVN laboratories. Data have been returned on the performance of each run control in routine diagnostic assays. Preliminary results presented here indicate a high level of variability in intra- and inter-assay detection of these targets, highlighting the need for standardisation of assays within molecular diagnostics.

  19. Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy

    PubMed Central

    Veldt, B J; Saracco, G; Boyer, N; Cammà, C; Bellobuono, A; Hopf, U; Castillo, I; Weiland, O; Nevens, F; Hansen, B E; Schalm, S W

    2004-01-01

    Background: The key end point for treatment efficacy in chronic hepatitis C is absence of detectable virus at six months after treatment. However, the incidence of clinical events during long term follow up of patients with sustained virological response is still poorly documented and may differ between the Eastern and Western world. Aims: To assess clinical end points during long term follow up of European patients with a sustained virological response to interferon monotherapy. Methods: Meta-analysis of individual patient data from eight European protocolled follow up studies of interferon treatment for chronic hepatitis C. Results: A total of 286 sustained virological responders and 50 biochemical responders (detectable virus but normal alanine aminotransferase levels) were followed up for 59 months. Fifteen sustained virological responders (5.2%) had cirrhosis before treatment and 112 (39%) had genotype 1. The late virological relapse rate after five years of follow up was 4.7% (95% confidence interval (CI) 2.0–7.4) among sustained virological responders; all late relapses occurred within four years after treatment. Among sustained virological responders, the rate of decompensation after five years of follow up was 1.0% (95% CI 0.0–2.3) and none developed hepatocellular carcinoma (HCC). Survival was comparable with the general population, matched for age and sex, the standard mortality ratio being 1.4 (95% CI 0.3–2.5). Clinical outcome of patients with cirrhosis was similar to other sustained virological responders. For biochemical responders, the rates of development of decompensation and HCC during long term follow up were 9.1% (95% CI 0.5–17.7) and 7.1% (95% CI 0–15.0), respectively. Conclusions: Five year survival of European sustained virological responders was similar to the overall population, matched for age and sex. No HCCs were detected during long term follow up. PMID:15361504

  20. Virological efficacy of PI monotherapy for HIV-1 in clinical practice

    PubMed Central

    El Bouzidi, Kate; Collier, Dami; Nastouli, Eleni; Copas, Andrew J.; Miller, Robert F.; Gupta, Ravindra K.

    2016-01-01

    Background Clinical trials of PI monotherapy indicate that most participants maintain viral suppression and emergent protease resistance is rare. However, outcomes among patients receiving PI monotherapy for clinical reasons, such as toxicity or adherence issues, are less well studied. Methods An observational study of patients attending an HIV treatment centre in London, UK, who had received PI monotherapy between 2004 and 2013, was conducted using prospectively collected clinical data and genotypic resistance reports. Survival analysis techniques were used to examine the times to virological failure and treatment discontinuation. Results Ninety-five patients had PI monotherapy treatment for a median duration of 126 weeks. Virological failure occurred during 64% of episodes and 8% of patients developed emergent protease mutations. We estimate failure occurs in half of episodes within 2 years following initiation. Where PI monotherapy was continued following virological failure, 68% of patients achieved viral re-suppression. Despite a high incidence of virological failure, many patients continued PI monotherapy and 79% of episodes were ongoing at the end of the study. The type of PI used, the presence of baseline protease mutations and the plasma HIV RNA at initiation did not have a significant impact on treatment outcomes. Conclusions There was a higher incidence of virological failure and emerging resistance in our UK clinical setting than described in PI monotherapy clinical trials and other European observational studies. Despite this, many patients continued PI monotherapy and regained viral suppression, indicating this strategy remains a viable option in certain individuals following careful clinical evaluation. PMID:27402006

  1. Comparing HIV viral load assays and frequency of low level virological rebound in clinical practice.

    PubMed

    Briggs, R; Templeton, K; Fernando, I

    2014-12-01

    Research suggests that some low-level virological rebound results occurring for no obvious clinical cause, in patients stable on antiretroviral therapy (ART), may be a consequence of the viral load assay used. We compared the relative frequency of clinically unexplained low-level virological rebound results when using the Roche HIV Taqman version-1 (CTM v1), the Roche HIV Taqman version-2 (CTM v2) and the Abbott RealTime (Abbott RT) assays in clinical practice. In all, 247 patients from our centre who had their viral loads measured by the three different assays over a period of 3 consecutive years (each assay used for a period of 1 year each) were included in the study. Low-level virological rebound was defined as <1000 copies/ml. Over similar time periods, there was significant discrepancy between the three assays when considering the proportion of clinically unexplained low-level virological rebound results in patients stable on ART: the CTM v2 assay produced the highest percentage (93%), CTM v1 much lower (65%) and Abbott RT even less (35%). There is further research required regarding what, if any, implications this has for patients who experience clinically unexplained low-level virological rebound on the more sensitive assays. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  2. Application of MALDI-TOF Mass Spectrometry in Clinical Virology: A Review

    PubMed Central

    Cobo, Fernando

    2013-01-01

    MALDI-TOF mass spectrometry is a diagnostic tool of microbial identification and characterization based on the detection of the mass of molecules. In the majority of clinical laboratories, this technology is currently being used mainly for bacterial diagnosis, but several approaches in the field of virology have been investigated. The introduction of this technology in clinical virology will improve the diagnosis of infections produced by viruses but also the discovery of mutations and variants of these microorganisms as well as the detection of antiviral resistance. This review is focused on the main current applications of MALDI-TOF MS techniques in clinical virology showing the state of the art with respect to this exciting new technology. PMID:24222805

  3. Application of maldi-tof mass spectrometry in clinical virology: a review.

    PubMed

    Cobo, Fernando

    2013-01-01

    MALDI-TOF mass spectrometry is a diagnostic tool of microbial identification and characterization based on the detection of the mass of molecules. In the majority of clinical laboratories, this technology is currently being used mainly for bacterial diagnosis, but several approaches in the field of virology have been investigated. The introduction of this technology in clinical virology will improve the diagnosis of infections produced by viruses but also the discovery of mutations and variants of these microorganisms as well as the detection of antiviral resistance. This review is focused on the main current applications of MALDI-TOF MS techniques in clinical virology showing the state of the art with respect to this exciting new technology.

  4. Hepatitis B virus in Buenos Aires, Argentina: genotypes, virological characteristics and clinical outcomes.

    PubMed

    Pezzano, S C; Torres, C; Fainboim, H A; Bouzas, M B; Schroder, T; Giuliano, S F; Paz, S; Alvarez, E; Campos, R H; Mbayed, V A

    2011-02-01

    Hepatitis B virus (HBV) is classified into eight major genotypes, A-H, which are geographically distributed worldwide. The aim of this work was to describe the clinical characteristics associated with the HBV genotypes circulating in Buenos Aires city. The study included 139 patients infected with HBV, whose clinical courses were classified as acute symptomatic self-limiting hepatitis, inactive carrier state and chronic active hepatitis (HBV e-antigen (HBeAg)-positive and HBeAg-negative). The HBV genotypes were determined in 128 patients by PCR-restriction fragment length polymorphism and phylogenetic analysis. Biochemical, virological, clinical and histological features were analysed. A differential distribution of genotypes between acute symptomatic and chronic infections was found. Among the acute cases, genotype F was predominant (65.2%, 30/46) and genotype D was rare (4.3%, 2/46), whereas among the chronic infections, a homogeneous distribution of genotypes A (26.8%, 22/82), D (31.7%, 26/82) and F (36.6%, 30/82), with an unusual presence of genotypes B (1.2%, 1/82) and C (3.7%, 3/82), was observed. Regarding the liver histology of chronically infected patients, genotype F tended to display higher histological activity indexes. Mutations related to HBV surface antigen immunoreactivity, antiviral resistance and HBeAg-negative status were studied. This work constitutes, to our knowledge, the first description of the clinical characteristics related to HBV genotypes in Argentina, where the distribution of genotypes in patients with acute infection has not been reported previously. Finally, it was established that genotype F is the prevalent genotype among the acute symptomatic infections in Buenos Aires city, and that it shows a tendency to cause an adverse disease outcome among the chronic cases.

  5. HIV-1 Amino Acid Changes Among Participants With Virologic Failure: Associations With First-line Efavirenz or Atazanavir Plus Ritonavir and Disease Status

    PubMed Central

    Mollan, Katie; Daar, Eric S.; Sax, Paul E.; Balamane, Maya; Collier, Ann C.; Fischl, Margaret A.; Lalama, Christina M.; Bosch, Ronald J.; Tierney, Camlin; Katzenstein, David

    2012-01-01

    Background. Although specific human immunodeficiency virus type 1 (HIV-1) drug resistance mutations are well studied, little is known about cumulative amino acid changes, or how regimen and participant characteristics influence these changes. Methods. In the AIDS Clinical Trials Group randomized study A5202 of treatment-naive HIV-infected participants, cumulative HIV-1 amino acid changes from pretreatment to virologic failure were evaluated in protease and reverse transcriptase (RT) gene sequences. Results. Among 265 participants with virologic failure, those assigned atazanavir plus ritonavir (ATV/r) did not have significantly more protease changes compared with those assigned efavirenz (EFV) (P ≥ .13). In contrast, participants with virologic failure assigned EFV had more RT changes, including and excluding known resistance codons (P < .001). At pretreatment, lower CD4 cell count, major resistance, more amino acid mixtures (all P < .001), hepatitis C antibody negativity (P = .05), and black race/ethnicity (P = .02) were associated with more HIV-1 amino acid changes. Conclusions. Virologic failure following EFV-containing treatment was associated with more HIV-1 amino acid changes compared to failure of ATV/r-containing treatment. Furthermore, we show that non–drug resistance mutations occurred more frequently among those failing EFV, the clinical relevance of which warrants further investigation. Pretreatment immunologic status may play a role in viral evolution during treatment, as evidenced by increased amino acid changes among those with lower pretreatment CD4 count. Clinical Trials Registration. NCT00118898. PMID:23148287

  6. The laboratory of clinical virology in monitoring patients undergoing monoclonal antibody therapy.

    PubMed

    Cavallo, R

    2011-12-01

    The relevant efficacy of monoclonal antibodies (mAbs) has resulted in the successful treatment of several diseases, although susceptibility to infections remains a major problem. This review summarizes aspects of the literature regarding viral infections and mAbs, specifically addressing the risk of infection/reactivation, the measures that can reduce this risk, and the role played by the laboratory of clinical virology in monitoring patients undergoing mAb therapy.

  7. Clinical and Virological Features of Dengue in Vietnamese Infants

    PubMed Central

    Bich Chau, Tran Nguyen; Anders, Katherine L.; Lien, Le Bich; Hung, Nguyen Thanh; Minh Hieu, Lu Thi; Tuan, Nguyen Minh; Thuy, Tran Thi; Phuong, Le Thi; Hong Tham, Nguyen Thi; Lanh, Mai Ngoc; Farrar, Jeremy J.; Whitehead, Stephen S.; Simmons, Cameron P.

    2010-01-01

    Background Infants account for a small proportion of the overall dengue case burden in endemic countries but can be clinically more difficult to manage. The clinical and laboratory features in infants with dengue have not been extensively characterised. Methodology/Principal Findings This prospective, cross-sectional descriptive study of infants hospitalized with dengue was conducted in Vietnam from November 2004 to December 2007. More than two-thirds of 303 infants enrolled on clinical suspicion of dengue had a serologically confirmed dengue virus (DENV) infection. Almost all were primary dengue infections and 80% of the infants developed DHF/DSS. At the time of presentation and during hospitalization, the clinical signs and symptoms in infants with dengue were difficult to distinguish from those with other febrile illnesses, suggesting that in infants early laboratory confirmation could assist appropriate management. Detection of plasma NS1 antigen was found to be a sensitive marker of acute dengue in infants with primary infection, especially in the first few days of illness. Conclusions/Significance Collectively, these results provide a systematic description of the clinical features of dengue in infants and highlight the value of NS1 detection for diagnosis. PMID:20405057

  8. Vitamin D Status and Virologic Response to HCV Therapy in the HALT-C and VIRAHEP-C Trials

    PubMed Central

    Loftfield, Erikka; O’Brien, Thomas R.; Pfeiffer, Ruth M.; Howell, Charles D.; Horst, Ron; Prokunina-Olsson, Ludmila; Weinstein, Stephanie J.; Albanes, Demetrius; Morgan, Timothy R.; Freedman, Neal D.

    2016-01-01

    More than 150 million people worldwide are chronically infected with hepatitis C virus (HCV) and face higher risk of cirrhosis and hepatocellular carcinoma. Highly effective HCV treatments have recently been developed; however, they are costly and therefore poorly suited for application in resource-limited settings where HCV burden is high. Pegylated-interferon alpha (PEG-IFNα) and ribavirin (RBV) therapy is far less costly, but also less effective. Vitamin D supplementation has been proposed as an inexpensive adjuvant to treatment, however, prior epidemiological evidence on its effectiveness is inconsistent, with little data available among African Americans who naturally have lower vitamin D concentrations. We thus evaluated associations between baseline vitamin D status, measured by circulating 25-hydroxyvitamin D (25(OH)D), which is considered to be the best marker of vitamin D status in humans, and subsequent response to PEG-IFNα/RBV therapy in two large clinical trials that together included 1292 patients infected with HCV genotype 1. We used race-stratified logistic regression models to evaluate multivariable-adjusted associations of 25(OH)D with early virologic response (EVR; 2-log10 HCV RNA decline at week 12) and sustained virologic response (SVR). Among African Americans, we saw no associations. Among European Americans, we saw no association with low vitamin D (≤20 ng/mL) versus sufficient concentrations (20-<30 ng/mL). However, patients with 25(OH)D ≥30 ng/mL were actually less likely to attain EVR (OR = 0.64, 95% CI = 0.43–0.94) than those with sufficient concentrations, with a similar but non-significant association observed for SVR (OR = 0.49, 95% CI = 0.20–1.17). Conclusion Higher vitamin D status was not beneficially associated with responses to therapy; if anything, patients with higher vitamin D concentrations were less likely to attain SVR. Our data do not support a role for vitamin D supplementation as an adjuvant therapy for HCV

  9. Virology, Immunology, and Clinical Course of HIV Infection.

    ERIC Educational Resources Information Center

    McCutchan, J. Allen

    1990-01-01

    Presents overview of medical aspects of human immunodeficiency virus Type 1 (HIV-1) disease. Addresses structure and replication of virus, current methods for detecting HIV-1 in infected persons, effects of the virus on immune system, and clinical course of HIV-1 disease. Emphasizes variable causes of progression through HIV-1 infection stages;…

  10. Oncolytic parvoviruses: from basic virology to clinical applications.

    PubMed

    Marchini, Antonio; Bonifati, Serena; Scott, Eleanor M; Angelova, Assia L; Rommelaere, Jean

    2015-01-29

    Accumulated evidence gathered over recent decades demonstrated that some members of the Parvoviridae family, in particular the rodent protoparvoviruses H-1PV, the minute virus of mice and LuIII have natural anticancer activity while being nonpathogenic to humans. These studies have laid the foundations for the launch of a first phase I/IIa clinical trial, in which the rat H-1 parvovirus is presently undergoing evaluation for its safety and first signs of efficacy in patients with glioblastoma multiforme. After a brief overview of the biology of parvoviruses, this review focuses on the studies which unraveled the antineoplastic properties of these agents and supported their clinical use as anticancer therapeutics. Furthermore, the development of novel parvovirus-based anticancer strategies with enhanced specificity and efficacy is discussed, in particular the development of second and third generation vectors and the combination of parvoviruses with other anticancer agents. Lastly, we address the key challenges that remain towards a more rational and efficient use of oncolytic parvoviruses in clinical settings, and discuss how a better understanding of the virus life-cycle and of the cellular factors involved in virus infection, replication and cytotoxicity may promote the further development of parvovirus-based anticancer therapies, open new prospects for treatment and hopefully improve clinical outcome.

  11. Virology, Immunology, and Clinical Course of HIV Infection.

    ERIC Educational Resources Information Center

    McCutchan, J. Allen

    1990-01-01

    Presents overview of medical aspects of human immunodeficiency virus Type 1 (HIV-1) disease. Addresses structure and replication of virus, current methods for detecting HIV-1 in infected persons, effects of the virus on immune system, and clinical course of HIV-1 disease. Emphasizes variable causes of progression through HIV-1 infection stages;…

  12. Next-generation sequencing technology in clinical virology.

    PubMed

    Capobianchi, M R; Giombini, E; Rozera, G

    2013-01-01

    Recent advances in nucleic acid sequencing technologies, referred to as 'next-generation' sequencing (NGS), have produced a true revolution and opened new perspectives for research and diagnostic applications, owing to the high speed and throughput of data generation. So far, NGS has been applied to metagenomics-based strategies for the discovery of novel viruses and the characterization of viral communities. Additional applications include whole viral genome sequencing, detection of viral genome variability, and the study of viral dynamics. These applications are particularly suitable for viruses such as human immunodeficiency virus, hepatitis B virus, and hepatitis C virus, whose error-prone replication machinery, combined with the high replication rate, results, in each infected individual, in the formation of many genetically related viral variants referred to as quasi-species. The viral quasi-species, in turn, represents the substrate for the selective pressure exerted by the immune system or by antiviral drugs. With traditional approaches, it is difficult to detect and quantify minority genomes present in viral quasi-species that, in fact, may have biological and clinical relevance. NGS provides, for each patient, a dataset of clonal sequences that is some order of magnitude higher than those obtained with conventional approaches. Hence, NGS is an extremely powerful tool with which to investigate previously inaccessible aspects of viral dynamics, such as the contribution of different viral reservoirs to replicating virus in the course of the natural history of the infection, co-receptor usage in minority viral populations harboured by different cell lineages, the dynamics of development of drug resistance, and the re-emergence of hidden genomes after treatment interruptions. The diagnostic application of NGS is just around the corner.

  13. Pandemic and Avian Influenza A Viruses in Humans: Epidemiology, Virology, Clinical Characteristics, and Treatment Strategy.

    PubMed

    Li, Hui; Cao, Bin

    2017-03-01

    The intermittent outbreak of pandemic influenza and emergence of novel avian influenza A virus is worldwide threat. Although most patients present with mild symptoms, some deteriorate to severe pneumonia and even death. Great progress in the understanding of the mechanism of disease pathogenesis and a series of vaccines has been promoted worldwide; however, incidence, morbidity, and mortality remains high. To step up vigilance and improve pandemic preparedness, this article elucidates the virology, epidemiology, pathogenesis, clinical characteristics, and treatment of human infections by influenza A viruses, with an emphasis on the influenza A(H1N1)pdm09, H5N1, and H7N9 subtypes.

  14. Influence of delta virus infection on the virologic status in Egyptian patients with chronic hepatitis B virus genotype D.

    PubMed

    Fouad, Rabab; Abdo, Mahmoud; Eldeen, Hadeel Gamal; Sabry, Dina; Atef, Mira; Ahmed, Rasha; Zayed, Naglaa

    2016-05-01

    Hepatitis delta virus (HDV) usually have an unfavorable clinical outcome in chronic hepatitis B virus (HBV) patients. In Egypt, data about epidemiology, the spectrum of disease, and impact of HDV on HBV infection are rare. To assess the prevalence, clinical and virological characteristics of HDV infection among Egyptian patients with chronic HBV. Adult patients with Hepatitis B surface antigen (HBsAg)-positive were evaluated for the presence of HDV using anti HDV-IgG and HDV RNA by RT-PCR. Routine laboratory investigations, genotypes and subtypes for both HBV and HDV, abdominal sonography, and transient elastography (TE) were done. Liver biopsy was performed only in whenever indicated. One hundred and twenty-one treatment-naïve chronic HBV patients were included. Wild HBV genotype-D2 was found in 98.2% and 81.9% were HBeAg negative. Prevalence of HDV was 8.3% by anti-HDV IgG and 9.9% by RT-PCR. Wild HDV genotype-IIb was reported in 83.3%. HDV infection was more common in males, 90.9% of delta patients were HBeAg negative. Compared to the mono-infected HBV, concomitant HBV/HDV infection was not associated with more derangment in ALT nor advanced stage of fibrosis. 66.7% of HDV patients had significantly lower HBV-DNA level compared to the non-delta patients (P < 0.001). HDV is not uncommon in Egypt. HBV genotype-D was associated with HDV genotype-IIb. Delta infection was associated with negative HBeAg status, reduction of HBV replication, but neither influenced the clinical course nor increased significant liver damage risk.

  15. Efavirenz versus boosted atazanavir-containing regimens and immunologic, virologic, and clinical outcomes

    PubMed Central

    Cain, Lauren E.; Caniglia, Ellen C.; Phillips, Andrew; Olson, Ashley; Muga, Roberto; Pérez-Hoyos, Santiago; Abgrall, Sophie; Costagliola, Dominique; Rubio, Rafael; Jarrín, Inma; Bucher, Heiner; Fehr, Jan; van Sighem, Ard; Reiss, Peter; Dabis, François; Vandenhende, Marie-Anne; Logan, Roger; Robins, James; Sterne, Jonathan A. C.; Justice, Amy; Tate, Janet; Touloumi, Giota; Paparizos, Vasilis; Esteve, Anna; Casabona, Jordi; Seng, Rémonie; Meyer, Laurence; Jose, Sophie; Sabin, Caroline; Hernán, Miguel A.

    2016-01-01

    Abstract Objective: To compare regimens consisting of either ritonavir-boosted atazanavir or efavirenz and a nucleoside reverse transcriptase inhibitor (NRTI) backbone with respect to clinical, immunologic, and virologic outcomes. Design: Prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States included in the HIV-CAUSAL Collaboration. Methods: HIV-positive, antiretroviral therapy-naive, and acquired immune deficiency syndrome (AIDS)-free individuals were followed from the time they started an atazanavir or efavirenz regimen. We estimated an analog of the “intention-to-treat” effect for efavirenz versus atazanavir regimens on clinical, immunologic, and virologic outcomes with adjustment via inverse probability weighting for time-varying covariates. Results: A total of 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths) and 18,786 individuals started an efavirenz regimen (389 deaths, 825 AIDS-defining illnesses or deaths). During a median follow-up of 31 months, the hazard ratios (95% confidence intervals) were 0.98 (0.77, 1.24) for death and 1.09 (0.91, 1.30) for AIDS-defining illness or death comparing efavirenz with atazanavir regimens. The 5-year survival difference was 0.1% (95% confidence interval: −0.7%, 0.8%) and the AIDS-free survival difference was −0.3% (−1.2%, 0.6%). After 12 months, the mean change in CD4 cell count was 20.8 (95% confidence interval: 13.9, 27.8) cells/mm3 lower and the risk of virologic failure was 20% (14%, 26%) lower in the efavirenz regimens. Conclusion: Our estimates are consistent with a smaller 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with atazanavir regimens. No overall differences could be detected with respect to 5-year survival or AIDS-free survival. PMID:27741139

  16. Quantitative nucleic acid amplification methods and their implications in clinical virology.

    PubMed

    Singh, Mini P; Galhotra, Shipra; Saigal, Karnika; Kumar, Archit; Ratho, Radha Kanta

    2017-01-01

    Recently, a number of techniques have been approved for quantification of viral nucleic acids in clinical samples. Viral load (VL) tests have considerable importance in the management of patients and are widely used in routine diagnosis. In clinical virology, VL testing are important to monitor the antiviral treatment, to initiate preemptive therapy, to understand pathogenesis, and to evaluate the infectivity. These tests have now become a part of many diagnostic and treatment guidelines. Considering the various challenges for in-house viral testing related to the standardization, validation, and precision; they are gradually being replaced by the United States Food and Drug Administration (US FDA) cleared tests. This review summarizes the various viral quantification methods and also discusses the clinical applicability of these in human immunodeficiency virus, Hepatitis B virus, Hepatitis C virus, Cytomegalovirus, and Epstein Barr virus infected patients. Further the challenges and future perspectives of VL testing have also been discussed.

  17. Quantitative nucleic acid amplification methods and their implications in clinical virology

    PubMed Central

    Singh, Mini P; Galhotra, Shipra; Saigal, Karnika; Kumar, Archit; Ratho, Radha Kanta

    2017-01-01

    Recently, a number of techniques have been approved for quantification of viral nucleic acids in clinical samples. Viral load (VL) tests have considerable importance in the management of patients and are widely used in routine diagnosis. In clinical virology, VL testing are important to monitor the antiviral treatment, to initiate preemptive therapy, to understand pathogenesis, and to evaluate the infectivity. These tests have now become a part of many diagnostic and treatment guidelines. Considering the various challenges for in-house viral testing related to the standardization, validation, and precision; they are gradually being replaced by the United States Food and Drug Administration (US FDA) cleared tests. This review summarizes the various viral quantification methods and also discusses the clinical applicability of these in human immunodeficiency virus, Hepatitis B virus, Hepatitis C virus, Cytomegalovirus, and Epstein Barr virus infected patients. Further the challenges and future perspectives of VL testing have also been discussed. PMID:28251100

  18. Swine influenza: clinical, serological, pathological, and virological cross-sectional studies in nine farms in Argentina.

    PubMed

    Dibárbora, Marina; Cappuccio, Javier; Olivera, Valeria; Quiroga, Maria; Machuca, Mariana; Perfumo, Carlos; Pérez, Daniel; Pereda, Ariel

    2013-12-01

    Influenza A viruses (IAV) are important pathogens responsible for economic losses in the swine industry and represent a threat to public health. In Argentina, clinical, pathological, and virological findings suggest that IAV infection is widespread among pig farms. In addition, several subtypes of IAV, such as pH1N1, H3N2, δ1H1N1, and δ2H1N2, have been reported. To evaluate the infection patterns of influenza virus in nine pig farms in Argentina. Clinical, serological, pathological, and virological cross-sectional studies were conducted. Clinical and pathological results were characteristic of endemic influenza infection in eight of the nine farms studied. By rRT-PCR, six of the nine farms were positive to influenza. Five IAV were obtained. Genome analysis determined that four of the isolations were pH1N1 and that the remaining one was a reassortant human origin H3N2 virus containing pandemic internal genes. Serological results showed that all farms were positive to influenza A antibodies. Moreover, the hemagglutination inhibition test showed that infection with viruses containing HA's from different subtypes (pH1, δ1H1, δ2H1, and H3) is present among the farms studied and that coinfections with two or more subtypes were present in 80.5% of positive pigs. Because vaccines against IAV are not licensed in Argentina, these results reflect the situation of IAV infection in non-vaccinated herds. This study provides more information about the circulation and characteristics of IAV in a poorly surveyed region. This study provides more data that will be used to evaluate the tools necessary to control this disease. © 2013 Blackwell Publishing Ltd.

  19. Keeping kids in care: virological failure in a paediatric antiretroviral clinic and suggestions for improving treatment outcomes.

    PubMed

    Purchase, Susan; Cunningham, Jayne; Esser, Monika; Skinner, Donald

    2016-09-01

    The burden of paediatric HIV in South Africa is extremely high. Antiretrovirals (ARVs) are now widely accessible in the country and the clinical emphasis has shifted from initiation of treatment to retention in care. This study describes the cumulative virological failure rate amongst children on ARVs in a peri-urban clinic, and suggests ways in which clinics and partners could improve treatment outcomes. The study was conducted by the non-profit organisation HOPE Cape Town Association. A retrospective file audit determined the cumulative virological failure rate, that is, the sum of all children with a viral load >1000 copies/ml, children on monotherapy, children who had stopped treatment, children lost to follow-up (LTFU) and children who had died. Interviews were conducted with a purposive sample of 12 staff members and a random sample of 21 caregivers and 4 children attending care. Cumulative virological failure rate was 42%, with most of those children having been LTFU. Both staff and caregivers consistently identified pharmacy queues, ongoing stigma and unpalatable ARVs as barriers to adherence. Staff suggestions included use of adherence aids, and better education and support groups for caregivers. Caregivers also requested support groups, as well as "same day" appointments for caregivers and children, but rejected the idea of home visits. Simple, acceptable and cost-effective strategies exist whereby clinics and their partners could significantly reduce the cumulative virological failure rate in paediatric ARV clinics. These include actively tracing defaulters, improving education, providing support groups, and campaigning for palatable ARV formulations.

  20. [Caprine arthritis-encephalitis: trial of an adjuvant vaccine preparation. I. Clinical and virological study].

    PubMed

    Russo, P; Vitu, C; Fontaine, J J; Vignoni, M

    1993-04-01

    In purpose to protect goats against caprine arthritis encephalitis virus (CAEV), the first group of kids (I) was inoculated with purified, inactivated and adjuvant-treated virions, the second group (II) with adjuvant and the third one (III) with culture medium. 2-4 months later, the three groups were challenged with virulent CAEV by intraarticular route. On the clinical level, vaccinated and challenged kids show more early and severe arthritis than other groups. On the virological level, isolation of lentivirus from white blood cells and different organs is more important in group I than groups II and III. Therefore, vaccinations with inactivated and adjuvant-treated virions do not protect against a virulent challenge; there is an enhancement of lesions. We note that the adjuvant elicits a mild non-specific protection against virulent challenge.

  1. Clinical and virologic efficacy of herpes simplex virus type 2 suppression by acyclovir in a multi-continent clinical trial

    PubMed Central

    Fuchs, Jonathan; Celum, Connie; Wang, Jing; Hughes, James; Sanchez, Jorge; Cowan, Frances; Reid, Stewart; Delany-Moretlwe, Sinead; Corey, Lawrence; Wald, Anna

    2010-01-01

    Acyclovir suppressive therapy (400 mg twice daily) reduces herpes simplex virus type 2 (HSV-2) associated genital ulcer disease (GUD) and lesional HSV shedding. In an international trial of acyclovir for HSV-2 suppression to prevent HIV acquisition (HPTN 039), acyclovir had a smaller effect on the frequency of GUD as well as the frequency and quantity of lesional HSV DNA in African women and Peruvian men compared with men in the United States. The observed regional variation in the clinical and virologic efficacy of acyclovir for HSV suppression warrants further evaluation of determinants of responses to acyclovir. PMID:20214474

  2. Sex differences in the clinical, immunological and virological parameters of HIV-infected patients treated with HAART.

    PubMed

    Collazos, Julio; Asensi, Víctor; Cartón, José A

    2007-04-23

    To compare the clinical, virological and immunological parameters of men and women at baseline and during antiretroviral treatment. Analysis over time of data collected prospectively from of 2620 patients in a large cohort of HIV-infected patients followed for 12 months after initiating a nelfinavir-based antiretroviral regimen. Women had higher CD4 cell counts (P < 0.001), lower viral load (P < 0.001) and more favourable clinical profile (P < 0.001) than men at baseline. Following treatment, antiretroviral drug-naive women had higher CD4 cell count (P = 0.01) over time than drug-naive men but similar virological responses (P = 0.6); among drug-experienced individuals, women had also better immunological (P = 0.06) and similar virological (P = 0.3) responses compared with men. Consequently, the viroimmunological profile was significantly more favourable in women at each time point. The rates of clinical progression or death were also lower in women (P = 0.008), although drug toxicity was observed more commonly in women (P = 0.09). The highest viroimmunological responses were observed during the first 3 months of therapy in both sexes, although virological responses were achieved up to the 6th month in drug-naive patients. Sex was significantly associated with clinical (P = 0.01), virological (P = 0.01) and immunological (P = 0.006) responses to antiretroviral treatment in multivariate analyses after adjustment for other variables. The differences between genders were not explained by different adherence to therapy. Women have more favourable clinical and viroimmunological patterns than men both at baseline and during antiretroviral treatment. Sex has a small but significant influence on the clinical and laboratory outcomes of HIV infection.

  3. The vulnerability of men to virologic failure during antiretroviral therapy in a public routine clinic in Burkina Faso

    PubMed Central

    Penot, Pauline; Héma, Arsène; Bado, Guillaume; Kaboré, Firmin; Soré, Ibrahim; Sombié, Diamasso; Traoré, Jean-Richard; Guiard-Schmid, Jean-Baptiste; Fontanet, Arnaud; Slama, Laurence; Sawadogo, Adrien Bruno; Laurent, Christian

    2014-01-01

    Introduction Gender differences in antiretroviral therapy (ART) outcomes are critical in sub-Saharan Africa. We assessed the association between gender and virologic failure among adult patients treated in a public routine clinic (one of the largest in West Africa) in Burkina Faso. Methods We performed a case-control study between July and October 2012 among patients who had received ART at the Bobo Dioulasso Day Care Unit. Patients were eligible if they were 15 years or older, positive for HIV-1 or HIV-1+2, and on first-line ART for at least six months. Cases were all patients with two consecutive HIV loads >1000 copies/mL (Biocentric Generic or Abbott Real Time assays), or one HIV load >1000 copies/mL associated with immunologic or clinical failure criteria. Controls were all patients who only had HIV loads <300 copies/mL. The association between gender and virologic failure was assessed using a multivariate logistic regression, adjusted on age, level of education, baseline CD4+ T cell count, first and current antiretroviral regimens and time on ART. Results Of 2303 patients (74.2% women; median age: 40 years; median time on ART: 34 months), 172 had virologic failure and 2131 had virologic success. Among the former, 130 (75.6%) had confirmed virologic failure, 38 (22.1%) had viro-immunologic failure, and four (2.3%) had viro-clinical failure. The proportion of men was significantly higher among the cases than among the controls (37.2% vs. 24.9%; p<0.001). Compared to controls, cases were also younger, more immunodeficient at ART initiation, less likely to receive a protease inhibitor-based antiretroviral regimen and had spent a longer period of time on ART. After adjustment, male gender remained strongly associated with virologic failure (odds ratio 2.52, 95% CI: 1.77–3.60; p<0.001). Conclusions Men on ART appeared more vulnerable to virologic failure than women. Additional studies are needed to confirm the poorer prognosis of men in this setting and to

  4. Virological and clinical characteristics of hepatitis delta virus in South Asia

    PubMed Central

    2011-01-01

    Background & Aims There is a paucity of data on the impact of hepatitis D virus (HDV) in patients with hepatitis B virus (HBV) infection from South Asia. We studied the impact of HDV co-infection on virological and clinical characteristics. Methods We collected data of 480 patients with HBsAg positive and a detectable HBV DNA PCR, who presented to the Aga Khan University, Karachi and Isra University in Hyderabad, Pakistan in the last 5 years. HDV co-infection was diagnosed on the basis of anti-HDV. ALT, HBeAg, HBeAb and HBV DNA PCR quantitative levels were checked in all patients. We divided all patients into two groups based on anti-HDV, and compared their biochemical, serological & virological labs and clinical spectrum. Clinical spectrum of disease included asymptomatic carrier (AC), chronic active hepatitis (CAH), immuno-tolerant phase (IP), and compensated cirrhosis (CC). Results HDV co-infection was found in 169 (35.2%). There were 164 (34.6%) HBeAg positive and 316 (65.4%) HBeAg negative patients. Mean ALT level was 66 ± 73 IU. 233 (48.5%) had raised ALT. HBV DNA level was ≥ 10e5 in 103(21.5%) patients. Overall, among HBV/HDV co-infection, 146/169 (86.4%) had suppressed HBV DNA PCR as compared to 231/311 (74.3%) patients with HBV mono-infection; p-value = 0.002. Among HBeAg negative patients 71/128(55.5%) had raised ALT levels among HBV/HDV co-infection as compared to 71/188 (37.8%) with HBV mono-infection (p-value = 0.002); levels of HBV DNA were equal in two groups; there were 27/128 (21%) patients with CC among HBV/HDV co-infection as compared to 23 (12%) in HBV mono-infection (p-value = 0.009); there were less AC (p-value = 0.009) and more CAH (p-value = 0.009) among HBV/HDV co-infection patients. Among HBeAg positive patients, serum ALT, HBV DNA levels and the spectrum of HBV were similar in the two groups. Conclusions HBV/HDV co-infection results in the suppression of HBV DNA. A fair proportion of HBV/HDV co-infected patients with HBeAg negative

  5. Virologic Monitoring of Hepatitis B Virus Therapy in Clinical Trials and Practice: Recommendations for a Standardized Approach

    PubMed Central

    PAWLOTSKY, JEAN–MICHEL; DUSHEIKO, GEOFFREY; HATZAKIS, ANGELOS; LAU, DARYL; LAU, GEORGE; LIANG, T. JAKE; LOCARNINI, STEPHEN; MARTIN, PAUL; RICHMAN, DOUGLAS D.; ZOULIM, FABIEN

    2009-01-01

    Treatment of chronic hepatitis B virus (HBV) infection is aimed at suppressing viral replication to the lowest possible level, and thereby to halt the progression of liver disease and prevent the onset of complications. Two categories of drugs are used in HBV therapy: the interferons, including standard interferon alfa or pegylated interferon alfa, and specific nucleoside or nucleotide HBV inhibitors that target the reverse-transcriptase function of HBV-DNA polymerase. The reported results of clinical trials have used varying definitions of efficacy, failure, and resistance based on different measures of virologic responses. This article discusses HBV virologic markers and tests, and their optimal use both for planning and reporting clinical trials and in clinical practice. PMID:18242209

  6. Clinical and virologic efficacy of herpes simplex virus type 2 suppression by acyclovir in a multicontinent clinical trial.

    PubMed

    Fuchs, Jonathan; Celum, Connie; Wang, Jing; Hughes, James; Sanchez, Jorge; Cowan, Frances; Reid, Stewart; Delany-Moretlwe, Sinead; Corey, Lawrence; Wald, Anna

    2010-04-15

    Acyclovir suppressive therapy (400 mg twice daily) reduces herpes simplex virus (HSV) type 2-associated genital ulcer disease and lesional HSV shedding. In an international trial of acyclovir for suppression of HSV type 2 to prevent human immunodeficiency virus (HIV) acquisition (HIV Prevention Trials Network 039), acyclovir had a smaller effect on the frequency of genital ulcer disease as well as a smaller effect on the frequency and quantity of lesional HSV DNA in African women and Peruvian men, compared with its effects in men in the United States. The observed regional variation in the clinical and virologic efficacy of acyclovir for HSV suppression warrants further evaluation of determinants of responses to acyclovir. (ClinicalTrials.gov identifier: NCT00076232.).

  7. Comparison of Adherence Monitoring Tools and Correlation to Virologic Failure in a Pediatric HIV Clinical Trial

    PubMed Central

    Intasan, Jintana; Vonthanak, Saphonn; Kosalaraksa, Pope; Hansudewechakul, Rawiwan; Kanjanavanit, Suparat; Ngampiyaskul, Chaiwat; Wongsawat, Jurai; Luesomboon, Wicharn; Apornpong, Tanakorn; Kerr, Stephen; Ananworanich, Jintanat; Puthanakit, Thanyawee

    2014-01-01

    Abstract There is no consensus on a gold standard for monitoring adherence to antiretroviral therapy (ART). We compared different adherence monitoring tools in predicting virologic failure as part of a clinical trial. HIV-infected Thai and Cambodian children aged 1–12 years (N=207) were randomized to immediate-ART or deferred-ART until CD4% <15%. Virologic failure (VF) was defined as HIV-RNA >1000 copies/mL after ≥6 months of ART. Adherence monitoring tools were: (1) announced pill count, (2) PACTG adherence questionnaire (form completed by caregivers), and (3) child self-report (self-reporting from children or caregivers to direct questioning by investigators during the clinic visit) of any missed doses in the last 3 days and in the period since the last visit. The Kappa statistic was used to describe agreement between each tool. The median age at ART initiation was 7 years with median CD4% 17% and HIV-RNA 5.0 log10copies/mL and 92% received zidovudine/lamivudine/nevirapine. Over 144 weeks, 13% had VF. Mean adherence by announced pill count before VF in VF children was 92% compared to 98% in children without VF (p=0.03). Kappa statistics indicated slight to fair agreement between tools. In multivariate analysis adjusting for gender, treatment arm ethnicity and caregiver education, significant predictors of VF were poor adherence by announced pill count (OR 4.56; 95%CI 1.78–11.69), reporting any barrier to adherence in the PACTG adherence questionnaire (OR 7.08; 95%CI 2.42–20.73), and reporting a missed dose in the 24 weeks since the last HIV-RNA assessment (OR 8.64; 95%CI 1.96–38.04). In conclusion, we recommend the child self-report of any missed doses since last visit for use in HIV research and in routine care settings, because it is easy and quick to administer and a strong association with development of VF. PMID:24901463

  8. Epidemiologic, clinical, and virologic characteristics of human rhinovirus infection among otherwise healthy children and adults

    PubMed Central

    Chen, Wei-Ju; Arnold, John C.; Fairchok, Mary P.; Danaher, Patrick J.; McDonough, Erin A.; Blair, Patrick J.; Garcia, Josefina; Halsey, Eric S.; Schofield, Christina; Ottolini, Martin; Mor, Deepika; Ridoré, Michelande; Burgess, Timothy H.; Millar, Eugene V.

    2015-01-01

    Background Human rhinovirus (HRV) is a major cause of influenza-like illness (ILI) in adults and children. Differences in disease severity by HRV species have been described among hospitalized patients with underlying illness. Less is known about the clinical and virologic characteristics of HRV infection among otherwise healthy populations, particularly adults. Objectives To characterize molecular epidemiology of HRV and association between HRV species and clinical presentation and viral shedding. Study design Observational, prospective, facility-based study of ILI was conducted from February 2010 to April 2012. Collection of nasopharyngeal specimens, patient symptoms, and clinical information occurred on days 0, 3, 7, and 28. Patients recorded symptom severity daily for the first 7 days of illness in a symptom diary. HRV was identified by RT-PCR and genotyped for species determination. Cases who were co-infected with other viral respiratory pathogens were excluded from the analysis. We evaluated the associations between HRV species, clinical severity, and patterns of viral shedding. Results Eighty-four HRV cases were identified and their isolates genotyped. Of these, 62 (74%) were >18y. Fifty-four were HRV-A, 11 HRV-B, and 19 HRV-C. HRV-C infection was more common among children than adults (59% vs. 10%, P<0.001). Among adults, HRV-A was associated with higher severity of upper respiratory symptoms compared to HRV-B (P=0.02), but no such association was found in children. In addition, adults shed HRV-A significantly longer than HRV-C (Ptrend=0.01). Conclusions Among otherwise healthy adults with HRV infection, we observed species-specific differences in respiratory symptom severity and duration of viral shedding. PMID:25728083

  9. Hepatitis C virus genotype 6: virology, epidemiology, genetic variation and clinical implication.

    PubMed

    Thong, Vo Duy; Akkarathamrongsin, Srunthron; Poovorawan, Kittiyod; Tangkijvanich, Pisit; Poovorawan, Yong

    2014-03-21

    Hepatitis C virus (HCV) is a serious public health problem affecting 170 million carriers worldwide. It is a leading cause of chronic hepatitis, cirrhosis, and liver cancer and is the primary cause for liver transplantation worldwide. HCV genotype 6 (HCV-6) is restricted to South China, South-East Asia, and it is also occasionally found in migrant patients from endemic countries. HCV-6 has considerable genetic diversity with 23 subtypes (a to w). Although direct sequencing followed by phylogenetic analysis is the gold standard for HCV-6 genotyping and subtyping, there are also now rapid genotyping tests available such as the reverse hybridization line probe assay (INNO-LiPA II; Innogenetics, Zwijnaarde, Belgium). HCV-6 patients present with similar clinical manifestations as patients infected with other genotypes. Based on current evidence, the optimal treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk, although a shortened treatment duration of 24 wk could be sufficient in patients with low pretreatment viral load who achieve rapid virological response. In addition, the development of direct-acting antiviral agents is ongoing, and they give high response rate when combined with standard therapy. Herein, we review the epidemiology, classification, diagnosis and treatment as it pertain to HCV-6.

  10. Hepatitis C virus genotype 6: Virology, epidemiology, genetic variation and clinical implication

    PubMed Central

    Thong, Vo Duy; Akkarathamrongsin, Srunthron; Poovorawan, Kittiyod; Tangkijvanich, Pisit; Poovorawan, Yong

    2014-01-01

    Hepatitis C virus (HCV) is a serious public health problem affecting 170 million carriers worldwide. It is a leading cause of chronic hepatitis, cirrhosis, and liver cancer and is the primary cause for liver transplantation worldwide. HCV genotype 6 (HCV-6) is restricted to South China, South-East Asia, and it is also occasionally found in migrant patients from endemic countries. HCV-6 has considerable genetic diversity with 23 subtypes (a to w). Although direct sequencing followed by phylogenetic analysis is the gold standard for HCV-6 genotyping and subtyping, there are also now rapid genotyping tests available such as the reverse hybridization line probe assay (INNO-LiPA II; Innogenetics, Zwijnaarde, Belgium). HCV-6 patients present with similar clinical manifestations as patients infected with other genotypes. Based on current evidence, the optimal treatment duration of HCV-6 with pegylated interferon/ribavirin should be 48 wk, although a shortened treatment duration of 24 wk could be sufficient in patients with low pretreatment viral load who achieve rapid virological response. In addition, the development of direct-acting antiviral agents is ongoing, and they give high response rate when combined with standard therapy. Herein, we review the epidemiology, classification, diagnosis and treatment as it pertain to HCV-6. PMID:24659883

  11. Systematic review of severe fever with thrombocytopenia syndrome: virology, epidemiology, and clinical characteristics.

    PubMed

    Liu, Shelan; Chai, Chengliang; Wang, Chengmin; Amer, Said; Lv, Huakun; He, Hongxuan; Sun, Jimin; Lin, Junfen

    2014-03-01

    Severe fever with thrombocytopenia syndrome (SFTS) was firstly discovered in China in 2010, followed by several reports from many other countries worldwide. SFTS virus (SFTSV) has been identified as the causative agent of the disease and has been recognized as a public health threat. This novel Bunyavirus belongs to the Phlebovirus genus in the family Bunyaviridae. This review also describes the different aspects of virology, pathogenesis, epidemiology, and clinical symptoms on the basis of the published article surveillance data and phylogenetic analyses of viral sequences of large, medium, and small segments retrieved from database using mega 5.05, simplot 3.5.1, network 4.611, and epi information system 3.5.3 software. SFTS presents with fever, thrombocytopenia, leukocytopenia, and considerable changes in several serum biomarkers. The disease has 10~15% mortality rate, commonly because of multiorgan dysfunction. SFTSV is mainly reported in the rural areas of Central and North-Eastern China, with seasonal occurrence from May to September, mainly targeting those of ≥50 years of age. A wide range of domesticated animals, including sheep, goats, cattle, pigs, dogs, and chickens have been proven seropositive for SFTSV. Ticks, especially Haemaphysalis longicornis, are suspected to be the potential vector, which have a broad animal host range in the world. More studies are needed to elucidate the vector-animal-human ecological cycle, the pathogenic mechanisms in high level animal models and vaccine development.

  12. Vitamin D status does not predict sustained virologic response or fibrosis stage in chronic hepatitis C genotype 1 infection.

    PubMed

    Kitson, Matthew T; Dore, Gregory J; George, Jacob; Button, Peter; McCaughan, Geoffrey W; Crawford, Darrell H G; Sievert, William; Weltman, Martin D; Cheng, Wendy S; Roberts, Stuart K

    2013-03-01

    The relationship between vitamin D status and response to antiviral therapy and liver histology in hepatitis C virus genotype 1 (HCV-1) infection remains unclear, with studies to date yielding inconsistent results and failing to use reference assay methodology. We therefore analyzed pre-treatment 25-hydroxyvitamin D [25(OH)D] level, using reference liquid chromatography-tandem mass spectrometry methodology, in a cohort of treatment-naïve patients with HCV-1 to evaluate the association between vitamin D status, virologic response, and liver histology. 274 patients, with pre-treatment liver biopsy and up to 48 weeks of pegylated interferon alfa-2a plus ribavirin therapy, were tested for serum 25(OH)D level. Predictors of sustained virologic response (SVR), and variables associated with fibrosis stage, activity grade and 25(OH)D status were identified using multivariate analysis. Mean 25(OH)D level was 79.6 nmol/L, with a prevalence of 25(OH)D <75 nmol/L and <50 nmol/L of 48% and 16%, respectively. Season, race and geographic latitude were independent predictors of 25(OH)D status, while vitamin D deficiency was more prevalent in those with high activity grade (21% vs. 11%; p=0.03). Mean 25(OH)D level was lower (76.6 vs. 84.7 nmol/L; p=0.03) and 25(OH)D <75 nmol/L more prevalent (53% vs. 40%; p=0.03) in patients with an SVR, but no association between 25(OH)D status and SVR was found in multivariate analysis. Mean 25(OH)D level did not vary between fibrosis stage or activity grade. Baseline 25(OH)D level is not independently associated with SVR or fibrosis stage in HCV-1, but vitamin D deficiency is associated with high activity grade. Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  13. Updates and achievements in virology.

    PubMed

    Buonaguro, Franco M; Campadelli-Fiume, Gabriella; De Giuli Morghen, Carlo; Palù, Giorgio

    2010-07-01

    The 4th European Congress of Virology, hosted by the Italian Society for Virology, attracted approximately 1300 scientists from 46 countries worldwide. It also represented the first conference of the European Society for Virology, which was established in Campidoglio, Rome, Italy in 2009. The main goal of the meeting was to share research activities and results achieved in European virology units/institutes and to strengthen collaboration with colleagues from both western and developing countries. The worldwide representation of participants is a testament to the strength and attraction of European virology. The 5-day conference brought together the best of current virology; topics covered all three living domains (bacteria, archaea and eucarya), with special sessions on plant and veterinary virology as well as human virology, including two oral presentations on mimiviruses. The conference included five plenary sessions, 31 workshops, one hepatitis C virus roundtable, ten special workshops and three poster sessions, as well as 45 keynote lectures, 191 oral presentations and 845 abstracts. Furthermore, the Gesellschaft fur Virologie Loeffler-Frosch medal award was given to Peter Vogt for his long-standing career and achievements; the Gardner Lecture of the European Society for Clinical Virology was presented by Yoshihiro Kawaoka, and the Pioneer in Virology Lecture of the Italian Society for Virology was presented by Ulrich Koszinowski.

  14. Clinical and virological descriptive study in the 2011 outbreak of dengue in the Amazonas, Brazil.

    PubMed

    Martins, Valquiria do Carmo Alves; Bastos, Michele de Souza; Ramasawmy, Rajendranath; de Figueiredo, Regina Pinto; Gimaque, João Bosco Lima; Braga, Wornei Silva Miranda; Nogueira, Mauricio Lacerda; Nozawa, Sergio; Naveca, Felipe Gomes; Figueiredo, Luiz Tadeu Moraes; Mourão, Maria Paula Gomes

    2014-01-01

    Dengue is a vector-borne disease in the tropical and subtropical region of the world and is transmitted by the mosquito Aedes aegypti. In the state of Amazonas, Brazil during the 2011 outbreak of dengue all the four Dengue virus (DENV) serotypes circulating simultaneously were observed. The aim of the study was to describe the clinical epidemiology of dengue in Manaus, the capital city of the state of the Amazonas, where all the four DENV serotypes were co-circulating simultaneously. Patients with acute febrile illness during the 2011 outbreak of dengue, enrolled at the Fundação de Medicina Tropical Dr. Heitor Viera Dourado (FMT-HVD), a referral centre for tropical and infectious diseases in Manaus, were invited to participate in a clinical and virological descriptive study. Sera from 677 patients were analyzed by RT-nested-PCRs for flaviviruses (DENV 1-4, Saint Louis encephalitis virus-SLEV, Bussuquara virus-BSQV and Ilheus virus-ILHV), alphavirus (Mayaro virus-MAYV) and orthobunyavirus (Oropouche virus-OROV). Only dengue viruses were detected in 260 patients (38.4%). Thirteen patients were co-infected with more than one DENV serotype and six (46.1%) of them had a more severe clinical presentation of the disease. Nucleotide sequencing showed that DENV-1 belonged to genotype V, DENV-2 to the Asian/American genotype, DENV-3 to genotype III and DENV-4 to genotype II. Co-infection with more than one DENV serotype was observed. This finding should be warning signs to health authorities in situations of the large dispersal of serotypes that are occurring in the world.

  15. Clinical, virological, and biological parameters associated with outcomes of Ebola virus infection in Macenta, Guinea

    PubMed Central

    Vernet, Marie-Astrid; Reynard, Stéphanie; Fizet, Alexandra; Schaeffer, Justine; Pannetier, Delphine; Rives, Max; Georges, Nadia; Garcia-Bonnet, Nathalie; Sylla, Aboubacar I.; Grovogui, Péma; Kerherve, Jean-Yves; Savio, Christophe; Savio-Coste, Sylvie; de Séverac, Marie-Laure; Linares, Sandrine; Harouna, Souley; Abdoul, Bing M’Lebing; Petitjean, Frederic; Samake, Nenefing; Kinda, Moumouni; Koundouno, Fara Roger; Mateo, Mathieu; Lecine, Patrick; Page, Audrey; Tchamdja, Tang Maleki; Schoenhals, Matthieu; Barbe, Solenne; Simon, Bernard; Tran-Minh, Tuan; L’Hériteau, François

    2017-01-01

    BACKGROUND. The pathogenesis of Ebola virus (EBOV) disease (EVD) is poorly characterized. The establishment of well-equipped diagnostic laboratories close to Ebola treatment centers (ETCs) has made it possible to obtain relevant virological and biological data during the course of EVD and to assess their association with the clinical course and different outcomes of the disease. METHODS. We were responsible for diagnosing EBOV infection in patients admitted to two ETCs in forested areas of Guinea. The pattern of clinical signs was recorded, and an etiological diagnosis was established by RT-PCR for EBOV infection or a rapid test for malaria and typhoid fever. Biochemical analyses were also performed. RESULTS. We handled samples from 168 patients between November 29, 2014, and January 31, 2015; 97 patients were found to be infected with EBOV, with Plasmodium falciparum coinfection in 18%. Overall mortality for EVD cases was 58%, rising to 86% if P. falciparum was also present. Viral load was higher in fatal cases of EVD than in survivors, and fatal cases were associated with higher aspartate aminotransferase (AST) and alanine aminotransferase (ALT), C-reactive protein (CRP), and IL-6 levels. Furthermore, regardless of outcome, EVD was characterized by higher creatine kinase (CPK), amylase, and creatinine levels than in febrile patients without EVD, with higher blood urea nitrogen (BUN) levels in fatal cases of EVD only. CONCLUSION. These findings suggest that a high viral load at admission is a marker of poor EVD prognosis. In addition, high AST, ALT, CRP, and IL-6 levels are associated with a fatal outcome of EVD. Damage to the liver and other tissues, with massive rhabdomyolysis and, probably, acute pancreatitis, is associated with EVD and correlated with disease severity. Finally, biochemical analyses provide substantial added value at ETCs, making it possible to improve supportive rehydration and symptomatic care for patients. FUNDING. The French Ministry of

  16. The effect of efavirenz versus nevirapine-containing regimens on immunologic, virologic and clinical outcomes in a prospective observational study.

    PubMed

    Cain, Lauren E; Phillips, Andrew; Lodi, Sara; Sabin, Caroline; Bansi, Loveleen; Justice, Amy; Tate, Janet; Logan, Roger; Robins, James M; Sterne, Jonathan A C; van Sighem, Ard; de Wolf, Frank; Bucher, Heiner C; Elzi, Luigia; Touloumi, Giota; Vourli, Georgia; Esteve, Anna; Casabona, Jordi; del Amo, Julia; Moreno, Santiago; Seng, Rémonie; Meyer, Laurence; Pérez-Hoyos, Santiago; Muga, Roberto; Abgrall, Sophie; Costagliola, Dominique; Hernán, Miguel A

    2012-08-24

    To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes. Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration. Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the 'intention-to-treat' effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting. A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/μl and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens. Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins

  17. The effect of efavirenz versus nevirapine-containing regimens on immunologic, virologic and clinical outcomes in a prospective observational study

    PubMed Central

    2013-01-01

    Objective To compare regimens consisting of either efavirenz or nevirapine and two or more nucleoside reverse transcriptase inhibitors (NRTIs) among HIV-infected, antiretroviral-naive, and AIDS-free individuals with respect to clinical, immunologic, and virologic outcomes. Design Prospective studies of HIV-infected individuals in Europe and the US included in the HIV-CAUSAL Collaboration. Methods Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started an NRTI, efavirenz or nevirapine, classified as following one or both types of regimens at baseline, and censored when they started an ineligible drug or at 6 months if their regimen was not yet complete. We estimated the ‘intention-to-treat’ effect for nevirapine versus efavirenz regimens on clinical, immunologic, and virologic outcomes. Our models included baseline covariates and adjusted for potential bias introduced by censoring via inverse probability weighting. Results A total of 15 336 individuals initiated an efavirenz regimen (274 deaths, 774 AIDS-defining illnesses) and 8129 individuals initiated a nevirapine regimen (203 deaths, 441 AIDS-defining illnesses). The intention-to-treat hazard ratios [95% confidence interval (CI)] for nevirapine versus efavirenz regimens were 1.59 (1.27, 1.98) for death and 1.28 (1.09, 1.50) for AIDS-defining illness. Individuals on nevirapine regimens experienced a smaller 12-month increase in CD4 cell count by 11.49 cells/μl and were 52% more likely to have virologic failure at 12 months as those on efavirenz regimens. Conclusions Our intention-to-treat estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a larger 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with nevirapine. PMID:22546987

  18. Clinical, virological, immunological and pathological evaluation of four porcine circovirus type 2 vaccines.

    PubMed

    Seo, Hwi Won; Han, Kiwon; Park, Changhoon; Chae, Chanhee

    2014-04-01

    The objective of this study was to rigorously compare the efficacy of four porcine circovirus type 2 (PCV2) vaccines of varying antigen type and dose under experimental conditions based on well-defined clinical (average daily weight gain [ADWG]), virological (evidence of viraemia), immunological (presence of PCV2-specific neutralising antibodies [NA], interferon-γ-secreting cells [IFN-γ-SCs], and CD3(+) and CD4(+) T cell subsets), and pathological (lymphoid lesion and PCV2 antigen score) criteria. A total of 60, 3-week old piglets were assigned to six groups of 10/group and were vaccinated either with 1/4 commercially available one-dose vaccines or were not vaccinated. At 7 weeks of age, vaccinated and control animals were inoculated intranasally with 2 mL of PCV2b. All pigs were euthanased and subjected to post-mortem examination at 25 weeks of age. From 9 to 16 weeks of age, the ADWG of vaccinated animals was significantly higher than that of non-vaccinates. Significant (P<0.05) differences were observed between vaccinated and positive control groups in the quantity of log-transformed PCV2b DNA in the blood and nasal swabs, log-transformed NA titres, and PCV2-specific IFN-γ-SCs at 0, 7, 14, 21, and 42 days post challenge (dpc). The proportion of CD4(+) cells at 7 and 14 dpc was also significantly different between vaccinated and control pigs (P<0.05). The histopathological lesions and PCV2-antigen scores in the lymph nodes were significantly lower (P<0.05) in vaccinated animals. All four vaccines were found to be highly efficacious in controlling experimental PCV2 challenge based on this range of criteria.

  19. Performance and Logistical Challenges of Alternative HIV-1 Virological Monitoring Options in a Clinical Setting of Harare, Zimbabwe

    PubMed Central

    Bronze, Michelle; Wellington, Maureen; Boender, Tamara Sonia; Manting, Corry; Steegen, Kim; Luethy, Rudi; Rinke de Wit, Tobias

    2014-01-01

    We evaluated a low-cost virological failure assay (VFA) on plasma and dried blood spot (DBS) specimens from HIV-1 infected patients attending an HIV clinic in Harare. The results were compared to the performance of the ultrasensitive heat-denatured p24 assay (p24). The COBAS AmpliPrep/COBAS TaqMan HIV-1 test, version 2.0, served as the gold standard. Using a cutoff of 5,000 copies/mL, the plasma VFA had a sensitivity of 94.5% and specificity of 92.7% and was largely superior to the VFA on DBS (sensitivity = 61.9%; specificity = 99.0%) or to the p24 (sensitivity = 54.3%; specificity = 82.3%) when tested on 302 HIV treated and untreated patients. However, among the 202 long-term ART-exposed patients, the sensitivity of the VFA decreased to 72.7% and to 35.7% using a threshold of 5,000 and 1,000 RNA copies/mL, respectively. We show that the VFA (either on plasma or on DBS) and the p24 are not reliable to monitor long-term treated, HIV-1 infected patients. Moreover, achieving acceptable assay sensitivity using DBS proved technically difficult in a less-experienced laboratory. Importantly, the high level of virological suppression (93%) indicated that quality care focused on treatment adherence limits virological failure even when PCR-based viral load monitoring is not available. PMID:25025031

  20. Clinical laboratory, virologic, and pathologic changes in hamsters experimentally infected with Pirital virus (Arenaviridae): a rodent model of Lassa fever.

    PubMed

    Sbrana, Elena; Mateo, Rosa I; Xiao, Shu-Yuan; Popov, Vsevolod L; Newman, Patrick C; Tesh, Robert B

    2006-06-01

    The clinical laboratory, virologic, and pathologic changes occurring in hamsters after infection with Pirital virus (Arenaviridae) are described. Pirital virus infection in the hamsters was characterized by high titered viremia, leukocytosis, coagulopathy, pulmonary hemorrhage and edema, hepatocellular and splenic necrosis, and marked elevation of serum transaminase levels. All of the animals died within 9 days. The clinical and histopathological findings in the Pirital virus-infected hamsters were very similar to those reported in severe human cases of Lassa fever, suggesting that this new animal model could serve as a low-cost and relatively safe alternative for studying the pathogenesis and therapy of Lassa fever.

  1. Does short-term virologic failure translate to clinical events in antiretroviral-naïve patients initiating antiretroviral therapy in clinical practice?

    PubMed Central

    The Antiretroviral Cohort Collaboration (ART-CC); Mugavero, Michael J.; May, Margaret; Harris, Ross; Saag, Michael S.; Costagliola, Dominique; Egger, Matthias; Phillips, Andrew; Günthard, Huldrych F.; Dabis, Francois; Hogg, Robert; De Wolf, Frank; Fatkenheuer, Gerd; John Gill, M.; Justice, Amy; D'Arminio Monforte, Antonella; Lampe, Fiona; Miró, Jose M.; Staszewski, Schlomo; Sterne, Jonathan A. C.

    2008-01-01

    Objective To determine if differences in short-term virologic failure among commonly used ART regimens translate to differences in clinical events in antiretroviral-naïve patients initiating ART. Design Observational cohort study of patients initiating ART between January 2000 and December 2005. Setting The Antiretroviral Therapy Cohort Collaboration (ART-CC) is a collaboration of 15 HIV cohort studies from Canada, Europe, and the United States. Subjects, participants A total of 13,546 antiretroviral-naïve HIV-positive patients initiating ART with efavirenz (EFV), nevirapine (NVP), lopinavir/ritonavir (LPV/r), nelfinavir (NFV), or abacavir (ABC) as third drugs in combination with a zidovudine and lamivudine NRTI backbone. Main outcome measures Short-term (24-week) virologic failure (>500 copies/mL) and clinical events within 2 years of ART initiation (incident AIDS-defining event, death, and a composite measure of these two outcomes). Results Compared with EFV as initial third drug, short-term virologic failure was more common with all other third drugs evaluated; NVP (adjusted odds ratio=1.87, 95%CI=1.58,2.22), LPV/r (1.32, 95%CI=1.12–1.57), NFV (3.20, 95%CI=2.74,3.74), and ABC (2.13, 95%CI=1.82,2.50). However, the rate of clinical events within 2 years of ART initiation appeared higher only with NVP (adjusted hazard ratio for composite outcome measure 1.27, 95%CI=1.04,1.56) and ABC (1.22, 95%CI=1.00,1.48). Conclusions Among antiretroviral-naïve patients initiating therapy, between-ART regimen differences in short-term virologic failure do not necessarily translate to differences in clinical outcomes. Our results should be interpreted with caution because of the possibility of residual confounding by indication. PMID:19005271

  2. The trichodysplasia spinulosa-associated polyomavirus: virological background and clinical implications.

    PubMed

    Kazem, Siamaque; van der Meijden, Els; Feltkamp, Mariet C W

    2013-08-01

    Trichodysplasia spinulosa-associated polyomavirus (TSPyV) is a new species of the family Polyomaviridae that was discovered in 2010. TSPyV infects humans and is associated with the development of a rare disease called trichodysplasia spinulosa. Trichodysplasia spinulosa is a skin disease of severely immunocompromised hosts characterized by follicular distention and keratotic spine formation especially on the face. Electron microscopy, immunohistochemistry, and viral load measurements indicate an etiological role of active TSPyV infection in the development of this disease. This review will address virological and pathogenic properties of TSPyV, as well as epidemiologic, diagnostic, and therapeutic aspects of TSPyV infection.

  3. Virological and Immunological Status of the People Living with HIV/AIDS Undergoing ART Treatment in Nepal

    PubMed Central

    Dumre, Shyam Prakash

    2016-01-01

    Antiretroviral therapy (ART) has increased the life span of the people living with HIV (PLHIV), but their virological and immunological outcomes are not well documented in Nepal. The study was conducted at a tertiary care center including 826 HIV-1 seropositive individuals undergoing ART for at least six months. Plasma viral load (HIV-1 RNA) was detected by Real Time PCR and CD4+ T-lymphocyte (CD4+) counts were estimated by flow cytometry. The mean CD4+ count of patients was 501 (95% CI = 325–579) cells/cumm, but about 35% of patients had CD4+ T cell counts below 350 cells/cumm. With increasing age, average CD4+ count was found to be decreasing (p = 0.005). Of the total cases, 82 (9.92%) were found to have virological failure (viral load: >1000 copies/ml). Tenofovir/Lamivudine/Efavirenz (TDF/3TC/EFV), the frequently used ART regimen in Nepal, showed virological failure in 11.34% and immunological failure in 37.17% of patients. Virological failure rate was higher among children < 15 years (14.5%) (p = 0.03); however, no association was observed between ART outcomes and gender or route of transmission. The study suggests there are still some chances of virological and immunological failures despite the success of highly active ART (HAART). PMID:27547761

  4. Durability and Effectiveness of Maraviroc-Containing Regimens in HIV-1-Infected Individuals with Virological Failure in Routine Clinical Practice

    PubMed Central

    Potard, Valérie; Reynes, Jacques; Ferry, Tristan; Aubin, Céline; Finkielsztejn, Laurent; Yazdanpanah, Yazdan; Costagliola, Dominique

    2015-01-01

    Introduction Limited data are available on the durability and effectiveness of maraviroc in routine clinical practice. We assessed the durability of maraviroc-containing regimens during a 30-month period, as well as their immunovirological and clinical efficacy, according to viral tropism in treatment-experienced individuals with viral load (VL) >50 copies/ml in the French Hospital Database on HIV. Methods Virological success was defined as VL<50 copies/ml, immunological success as a confirmed increase of at least 100 CD4 cells/mm3 measured twice at least one month apart, and clinical failure as hospitalization for a non-AIDS event, an AIDS event, or death. Multivariable Cox regression models adjusted for potential confounders were used to assess the influence of viral tropism on durability, the immunovirological responses, and clinical outcome. Results 356 individuals started maraviroc with VL>50 copies/ml of whom 223 harbored R5 viruses, 44 non-R5 viruses and 89 viruses of unknown tropism. Individuals with non-R5 viruses were more likely than individuals with R5 viruses to discontinue maraviroc (75% vs 34%, p<0.0001). At 30 months, the estimated rates of virological and immunological success were respectively 89% and 51% in individuals with R5 viruses and 48% and 23% in individuals with non-R5 viruses. In multivariable analysis, non-R5 viruses were associated with a lower likelihood of both virological success (hazard ratio (HR): 0.42; 95% confidence interval (CI), 0.25–0.70) and immunological success (HR: 0.37; 95% CI, 0.18–0.77). No difference in clinical outcome was found between individuals with R5 and non-R5 viruses. The effectiveness of maraviroc-containing regimens in individuals with unknown viral tropism was not significantly different from that in individuals with R5 viruses. A limitation of the study is the absence of genotypic susceptibility score. Conclusion In this observational study, maraviroc-containing regimens yielded high rates of viral

  5. Durability and Effectiveness of Maraviroc-Containing Regimens in HIV-1-Infected Individuals with Virological Failure in Routine Clinical Practice.

    PubMed

    Potard, Valérie; Reynes, Jacques; Ferry, Tristan; Aubin, Céline; Finkielsztejn, Laurent; Yazdanpanah, Yazdan; Costagliola, Dominique

    2015-01-01

    Limited data are available on the durability and effectiveness of maraviroc in routine clinical practice. We assessed the durability of maraviroc-containing regimens during a 30-month period, as well as their immunovirological and clinical efficacy, according to viral tropism in treatment-experienced individuals with viral load (VL) >50 copies/ml in the French Hospital Database on HIV. Virological success was defined as VL<50 copies/ml, immunological success as a confirmed increase of at least 100 CD4 cells/mm3 measured twice at least one month apart, and clinical failure as hospitalization for a non-AIDS event, an AIDS event, or death. Multivariable Cox regression models adjusted for potential confounders were used to assess the influence of viral tropism on durability, the immunovirological responses, and clinical outcome. 356 individuals started maraviroc with VL>50 copies/ml of whom 223 harbored R5 viruses, 44 non-R5 viruses and 89 viruses of unknown tropism. Individuals with non-R5 viruses were more likely than individuals with R5 viruses to discontinue maraviroc (75% vs 34%, p<0.0001). At 30 months, the estimated rates of virological and immunological success were respectively 89% and 51% in individuals with R5 viruses and 48% and 23% in individuals with non-R5 viruses. In multivariable analysis, non-R5 viruses were associated with a lower likelihood of both virological success (hazard ratio (HR): 0.42; 95% confidence interval (CI), 0.25-0.70) and immunological success (HR: 0.37; 95% CI, 0.18-0.77). No difference in clinical outcome was found between individuals with R5 and non-R5 viruses. The effectiveness of maraviroc-containing regimens in individuals with unknown viral tropism was not significantly different from that in individuals with R5 viruses. A limitation of the study is the absence of genotypic susceptibility score. In this observational study, maraviroc-containing regimens yielded high rates of viral suppression and immunological responses in

  6. Clinical and virological heterogeneity of hepatitis delta in different regions world-wide: The Hepatitis Delta International Network (HDIN).

    PubMed

    Wranke, Anika; Pinheiro Borzacov, Lourdes M; Parana, Raymundo; Lobato, Cirley; Hamid, Saeed; Ceausu, Emanoil; Dalekos, George N; Rizzetto, Mario; Turcanu, Adela; Niro, Grazia A; Lubna, Farheen; Abbas, Minaam; Ingiliz, Patrick; Buti, Maria; Ferenci, Peter; Vanwolleghem, Thomas; Hayden, Tonya; Dashdorj, Naranjargal; Motoc, Adriana; Cornberg, Markus; Abbas, Zaigham; Yurdaydin, Cihan; Manns, Michael P; Wedemeyer, Heiner; Hardtke, Svenja

    2017-09-29

    Chronic hepatitis D (delta) is a major global health burden. Clinical and virological characteristics of patients with hepatitis D virus (HDV) infection and treatment approaches in different regions world-wide are poorly defined. The Hepatitis Delta International Network (HDIN) registry was established in 2011 with centres in Europe, Asia, North- and South America. Here, we report on clinical/ virological characteristics of the first 1576 patients with ongoing or past HDV infection included in the database until October 2016 and performed a retrospective outcome analysis. The primary aim was to investigate if the region of origin was associated with HDV replication and clinical outcome. The majority of patients was male (n=979, 62%) and the mean age was 36.7 years (range 1-79, with 9% of patients younger than 20 years). Most patients were HBeAg-negative (77%) and HDV-RNA positive (85%). Liver cirrhosis was reported in 48.7% of cases which included 13% of patients with previous or ongoing liver decompensation. Hepatocellular carcinoma (HCC) developed in 30 patients (2.5%) and 44 (3.6%) underwent liver transplantation. Regions of origin were independently associated with clinical endpoints and detectability of HDV RNA. Antiviral therapy was administered to 356 patients with different treatment uptakes in different regions. Of these, 264 patients were treated with interferon-a and 92 were treated with HBV-Nucs only. The HDIN registry confirms the severity of hepatitis delta but also highlights the heterogeneity of patient characteristics and clinical outcomes in different regions. There is an urgent need for novel treatment options for HDV infection. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  7. Virologic response and safety of the abacavir/lamivudine fixed-dose formulation as part of highly active antiretroviral therapy: analyses of six clinical studies.

    PubMed

    Ha, Belinda; Liao, Qiming M; Dix, Lynn P; Pappa, Keith A

    2009-01-01

    We analyzed virologic response and safety data from six recent clinical studies conducted in antiretroviral-naïve subjects treated with ABC/3TC or its components to assess the impact of baseline viral load on efficacy and safety endpoints used in the ACTG5202 protocol. Primary endpoints were time to virologic failure (confirmed HIV-1 RNA > or = 1,000 copies/mL at 16-24 weeks or > or = 200 copies/mL at > or = 24 weeks) and time to first grade 3 or 4 adverse event or laboratory abnormality that was at least one grade higher than at baseline. The survival distributions of both endpoints were estimated using the Kaplan-Meier method overall and by baseline viral load (<100,000 vs. 100,000 copies/mL). A weighted mean of the virologic response and 95% confidence intervals (CI) were calculated by inverse-variance weighting for baseline viral load 100,000 copies/mL across studies. For subjects with baseline HIV-1 RNA 100,000 copies/mL, the rate of virologic survival ranged from 87% to 95% by 48 weeks. Few subjects treated with ABC/3TC developed grade 3 or 4 adverse events, laboratory toxicities, or changes in lipid levels. The weighted mean (CI) for the pooled virologic response was 91% (87%-96%). Based on the A5202 endpoints, ABC/3TC-containing regimens in this analysis had a high rate of virologic survival and were generally well tolerated in antiretroviral-naïve subjects regardless of baseline viral load. The pooled virologic response for ABC/3TC in our analysis is higher than the A5202 estimate.

  8. Pediatric Virology

    PubMed Central

    Portnoy, Bernard

    1965-01-01

    Pediatric virology is not an isolàted discipline. Rather, the syndromes associated with viral infection are modified by the unique characteristics of infancy and childhood. Fortunately for the pediatrician, and certainly for children, viral infections in childhood are rarely fatal, and are almost never serious. Future efforts of the pediatrician and virologist should be directed toward increased fetal salvage as with rubella and the prevention of severe, viral lower respiratory tract disease. PMID:14298871

  9. Clinical Utility of Pharmacy-Based Adherence Measurement in Predicting Virologic Outcomes in an Adult HIV-Infected Cohort in Jos, North Central Nigeria.

    PubMed

    Abah, Isaac Okoh; Ojeh, Victor Bazim; Musa, Jonah; Ugoagwu, Placid; Agaba, Patricia Aladi; Agbaji, Oche; Okonkwo, Prosper

    2016-01-01

    We examined the association between adherence to drug-refill visits and virologic outcomes in a cohort of HIV-infected adults on combination antiretroviral therapy (cART) in North Central Nigeria. Retrospectively, 588 HIV-infected, cART-naive adults (aged ≥15 years), initiated on first-line ART between 2009 and 2010 at the Jos University Teaching Hospital, were evaluated. Association between adherence to drug-refill visits, virologic (viral load>1000 copies/mL), and immunologic failure was assessed using multivariable logistic regression. After a median of 12 months on cART, 16% (n=94) and 10% (n=59) of patients had virologic and immunologic failures, respectively. In the final multivariable model, suboptimal adherence to drug-refill visits was a significant predictor of both virologic (adjusted odds ratio [AOR] 1.6; 95% confidence interval [CI]:1.2-2.3) and immunologic (AOR 1.92; 95% CI:1.06-3.49) failures. Adherence to drug refill is a useful predictor of successful virologic control and could be utilized for routine monitoring of adherence to cART in our clinical setting. © The Author(s) 2014.

  10. Regimen Simplification to Atazanavir-Ritonavir Alone as Maintenance Antiretroviral Therapy: Final 48-Week Clinical and Virologic Outcomes

    PubMed Central

    Wilkin, Timothy J.; McKinnon, John E.; DiRienzo, A. Gregory; Mollan, Katie; Fletcher, Courtney V.; Margolis, David M.; Bastow, Barbara; Thal, Gary; Woodward, William; Godfrey, Catherine; Wiegand, Ann; Maldarelli, Frank; Palmer, Sarah; Coffin, John M.; Mellors, John W.; Swindells, Susan

    2009-01-01

    Background Simplified maintenance therapy with ritonavir-boosted atazanavir (ATV/RTV) alone is attractive because of nucleoside reverse-transcriptase inhibitor (NRTI)–sparing benefits, low pill burden, once-daily dosage, and safety. Methods Subjects with virologic suppression after ≥48 weeks of initial antiretroviral therapy with 2 NRTIs and a protease inhibitor (PI) were enrolled. Subjects switched to ATV/RTV at entry and discontinued NRTIs after 6 weeks. The primary end point was time to virologic failure (confirmed HIV-1 RNA level ≥200 copies/mL). Drug resistance at virologic failure was evaluated by standard genotyping and single-genome sequencing (SGS). Residual viremia (1.1– 49 copies/mL) was measured by single-copy assay. Results Thirty-four subjects simplified to ATV/RTV alone, of whom 30 (88%) did not experience virologic failure by 48 weeks after simplification. Residual viremia did not change significantly after NRTI discontinuation among those without virologic failure but did increase 4 –12 weeks before confirmed virologic failure. No major PI-resistance mutations were identified at virologic failure by standard genotyping or SGS. Conclusions In this pilot study, simplified maintenance therapy with ATV/RTV alone maintained viral suppression in most subjects through 48 weeks. PI resistance was not detected among subjects experiencing virologic failure. Larger, randomized trials are warranted to further define the efficacy and safety of this strategy. PMID:19191590

  11. Human enterovirus 71 disease in Sarawak, Malaysia: a prospective clinical, virological, and molecular epidemiological study.

    PubMed

    Ooi, Mong How; Wong, See Chang; Podin, Yuwana; Akin, Winnie; del Sel, Syvia; Mohan, Anand; Chieng, Chae Hee; Perera, David; Clear, Daniela; Wong, Darin; Blake, Emma; Cardosa, Jane; Solomon, Tom

    2007-03-01

    Human enterovirus (HEV)-71 causes large outbreaks of hand-foot-and-mouth disease with central nervous system (CNS) complications, but the role of HEV-71 genogroups or dual infection with other viruses in causing severe disease is unclear. We prospectively studied children with suspected HEV-71 (i.e., hand-foot-and-mouth disease, CNS disease, or both) over 3.5 years, using detailed virological investigation and genogroup analysis of all isolates. Seven hundred seventy-three children were recruited, 277 of whom were infected with HEV-71, including 28 who were coinfected with other viruses. Risk factors for CNS disease in HEV-71 included young age, fever, vomiting, mouth ulcers, breathlessness, cold limbs, and poor urine output. Genogroup analysis for the HEV-71-infected patients revealed that 168 were infected with genogroup B4, 68 with C1, and 41 with a newly emerged genogroup, B5. Children with HEV-71 genogroup B4 were less likely to have CNS complications than those with other genogroups (26 [15%] of 168 vs. 30 [28%] of 109; odds ratio [OR], 0.48; 95% confidence interval [CI], 0.26-0.91; P=.0223) and less likely to be part of a family cluster (12 [7%] of 168 vs. 29 [27%] of 109; OR, 0.21; 95% CI, 0.10-0.46; P<.0001); children with HEV-71 genogroup B5 were more likely to be part of a family cluster (OR, 6.26; 95% CI, 2.77-14.18; P<.0001). Children with HEV-71 and coinfected with another enterovirus or adenovirus were no more likely to have CNS disease. Genogroups of HEV-71 may differ with regard to the risk of causing CNS disease and the association with family clusters. Dual infections are common, and all possible causes should be excluded before accepting that the first virus identified is the causal agent.

  12. Early Warning Indicators for First-Line Virologic Failure Independent of Adherence Measures in a South African Urban Clinic

    PubMed Central

    Wu, Baohua; Hampton, Jane; Ordóñez, Claudia E.; Johnson, Brent A.; Singh, Dinesh; John, Sally; Gordon, Michelle; Hare, Anna; Murphy, Richard; Nachega, Jean; Kuritzkes, Daniel R.; del Rio, Carlos; Sunpath, Henry

    2013-01-01

    Abstract We sought to develop individual-level Early Warning Indicators (EWI) of virologic failure (VF) for clinicians to use during routine care complementing WHO population-level EWI. A case-control study was conducted at a Durban clinic. Patients after≥5 months of first-line antiretroviral therapy (ART) were defined as cases if they had VF [HIV-1 viral load (VL)>1000 copies/mL] and controls (2:1) if they had VL≤1000 copies/mL. Pharmacy refills and pill counts were used as adherence measures. Participants responded to a questionnaire including validated psychosocial and symptom scales. Data were also collected from the medical record. Multivariable logistic regression models of VF included factors associated with VF (p<0.05) in univariable analyses. We enrolled 158 cases and 300 controls. In the final multivariable model, male gender, not having an active religious faith, practicing unsafe sex, having a family member with HIV, not being pleased with the clinic experience, symptoms of depression, fatigue, or rash, low CD4 counts, family recommending HIV care, and using a TV/radio as ART reminders (compared to mobile phones) were associated with VF independent of adherence measures. In this setting, we identified several key individual-level EWI associated with VF including novel psychosocial factors independent of adherence measures. PMID:24320011

  13. Hepatitis B virus infection in undocumented immigrants and refugees in Southern Italy: demographic, virological, and clinical features.

    PubMed

    Coppola, Nicola; Alessio, Loredana; Gualdieri, Luciano; Pisaturo, Mariantonietta; Sagnelli, Caterina; Minichini, Carmine; Di Caprio, Giovanni; Starace, Mario; Onorato, Lorenzo; Signoriello, Giuseppe; Macera, Margherita; Angelillo, Italo Francesco; Pasquale, Giuseppe; Sagnelli, Evangelista

    2017-02-09

    The data on hepatitis b virus (HBV) infection in immigrants population are scanty. The porpoise of this study was to define the demographic, virological, and clinical characteristics of subjects infected with HBV chronic infection in a cohort of immigrants living in Naples, Italy. A screening for HBV infection was offered to 1,331 immigrants, of whom 1,212 (91%) (831 undocumented immigrants and 381 refugees) accepted and were screened for hepatitis B surface antigen (HBsAg) and anti-hepatitis B core antibody (HBc). Those found to be HBsAg positive were further investigated at third-level infectious disease units. Of the 1,212 immigrants screened, 116 (9.6%) were HBsAg positive, 490 (40.4%) were HBsAg negative/anti-HBc positive, and 606 (50%) were seronegative for both. Moreover, 21 (1.7%) were anti-human immunodeficiency virus positive and 45 (3.7%) were anti-hepatitis C virus positive. The logistic regression analysis showed that male sex (OR: 1.79; 95%CI: 1.28-2.51), Sub-Saharan African origin (OR: 6.18; 95%CI: 3.37-11.36), low level of schooling (OR: 0.96; 95%CI: 0.94-0.99), and minor parenteral risks for acquiring HBV infection (acupuncture, tattoo, piercing, or tribal practices, OR: 1.54; 95%CI: 1.1-2.16) were independently associated with ongoing or past HBV infection. Of the 116 HBsAg-positive immigrants, 90 (77.6%) completed their diagnostic itinerary at a third-level infectious disease unit: 29 (32.2%) were asymptomatic non-viremic HBsAg carriers, 43 (47.8%) were asymptomatic viremic carriers, 14 (15.6%) had chronic hepatitis, and four (4.4%) had liver cirrhosis, with superimposed hepatocellular carcinoma in two. The data illustrate the demographic, clinical and virological characteristics of HBV infection in immigrants in Italy and indicate the need for Italian healthcare authorities to enhance their support for providing screening, HBV vaccination, treatment, and educational programs for this populations.

  14. Physical virology

    NASA Astrophysics Data System (ADS)

    Roos, W. H.; Bruinsma, R.; Wuite, G. J. L.

    2010-10-01

    Viruses are nanosized, genome-filled protein containers with remarkable thermodynamic and mechanical properties. They form by spontaneous self-assembly inside the crowded, heterogeneous cytoplasm of infected cells. Self-assembly of viruses seems to obey the principles of thermodynamically reversible self-assembly but assembled shells (`capsids') strongly resist disassembly. Following assembly, some viral shells pass through a sequence of coordinated maturation steps that progressively strengthen the capsid. Nanoindentation measurements by atomic force microscopy enable tests of the strength of individual viral capsids. They show that concepts borrowed from macroscopic materials science are surprisingly relevant to viral shells. For example, viral shells exhibit `materials fatigue' and the theory of thin-shell elasticity can account - in part - for atomic-force-microscopy-measured force-deformation curves. Viral shells have effective Young's moduli ranging from that of polyethylene to that of plexiglas. Some of them can withstand internal osmotic pressures that are tens of atmospheres. Comparisons with thin-shell theory also shed light on nonlinear irreversible processes such as plastic deformation and failure. Finally, atomic force microscopy experiments can quantify the mechanical effects of genome encapsidation and capsid protein mutations on viral shells, providing virological insight and suggesting new biotechnological applications.

  15. Dipeptidyl Peptidase IV Inhibition Does Not Adversely Affect Immune or Virological Status in HIV Infected Men And Women: A Pilot Safety Study

    PubMed Central

    Goodwin, Scott R.; Reeds, Dominic N.; Royal, Michael; Struthers, Heidi; Laciny, Erin

    2013-01-01

    Context: People infected with HIV have a higher risk for developing insulin resistance, diabetes, and cardiovascular disease than the general population. Dipeptidyl peptidase IV (DPP4) inhibitors are glucose-lowering medications with pleiotropic actions that may particularly benefit people with HIV, but the immune and virological safety of DPP4 inhibition in HIV is unknown. Objective: DPP4 inhibition will not reduce CD4+ T lymphocyte number or increase HIV viremia in HIV-positive adults. Design: This was a randomized, placebo-controlled, double-blind safety trial of sitagliptin in HIV-positive adults. Setting: The study was conducted at an academic medical center. Participants: Twenty nondiabetic HIV-positive men and women (9.8 ± 5.5 years of known HIV) taking antiretroviral therapy and with stable immune (625 ± 134 CD4+ T cells per microliter) and virological (<48 copies HIV RNA per milliliter) status. Intervention: The intervention included sitagliptin (100 mg/d) vs matching placebo for up to 24 weeks. Main Outcome Measures: CD4+ T cell number and plasma HIV RNA were measured every 4 weeks; fasting serum regulated upon activation normal T-cell expressed and secreted (RANTES), stromal derived factor (SDF)-1α, Soluble TNF receptor II, and oral glucose tolerance were measured at baseline, week 8, and the end of study. ANOVA was used for between-group comparisons; P < .05 was considered significant. Results: Compared with placebo, sitagliptin did not reduce CD4+ T cell count, plasma HIV RNA remained less than 48 copies/mL, RANTES and soluble TNF receptor II concentrations did not increase. SDF1α concentrations declined (P < .0002) in the sitagliptin group. The oral glucose tolerance levels improved in the sitagliptin group at week 8. Conclusions: Despite lowering SDF1α levels, sitagliptin did not adversely affect immune or virological status, or increase immune activation, but did improve glycemia in healthy, nondiabetic HIV-positive adults. These safety data

  16. Clinical, laboratory and virological data from suspected ZIKV patients in an endemic arbovirus area.

    PubMed

    Colombo, Tatiana Elias; Estofolete, Cássia Fernanda; Reis, Andréia Francesli Negri; da Silva, Natal Santos; Aguiar, Morgana Lima; Cabrera, Eliana Márcia Sotello; Dos Santos, Izalco Nuremberg Penha; Costa, Fabiana Rodrigues; Cruz, Lilian Elisa Arão Antônio; Rombola, Patrícia Lopes; Terzian, Ana Carolina Bernardes; Nogueira, Maurício Lacerda

    2017-09-09

    The emergence of Zika virus (ZIKV) presents new challenges to both clinicians and public health authorities. Overlapping clinical features between the diseases caused by ZIKV, dengue (DENV) and chikungunya (CHIKV) and the lack of validated serological assays for ZIKV make accurate diagnosis difficult. Brazilian authorities largely rely on clinical and epidemiological data for the epidemiological and clinical classifications of most ZIKV cases. To report the laboratory and clinical profiles of patients diagnosed with Zika fever based only on clinical and epidemiological data. We analyzed 433 suspected cases of ZIKV identified by the attending physician based on proposed clinical criteria. The samples were also screened for ZIKV, DENV and CHIKV using PCR. Of the 433 patients analyzed, 168 (38.8%) were laboratory-confirmed for arboviruses: 96 were positive for ZIKV, 67 were positive for DENV (56 for DENV-2, 9 for DENV-1, and 2 for DENV-4), four were positive for co-infection with ZIKV/DENV-2, and one was positive for CHIKV. The most common signs or symptoms in the patients with laboratory-confirmed ZIKV were rash (100%), arthralgia (77.1%), fever (74.0%), myalgia (74.0%) and non-purulent conjunctivitis (69.8%). In patients with laboratory-confirmed DENV infections, the most frequently observed symptoms were rash (100%), fever (79.1%), myalgia (74.6%), headache (73.1%) and arthralgia (70.1%). The measure of association between clinical manifestations and laboratory manifestations among patients with ZIKV and DENV detected a statistically significant difference only in abdominal pain (p=0.04), leukopenia (p=0.003), and thrombocytopenia (p=0.01). Our data suggests that clinical and epidemiological criteria alone are not a good tool for ZIKV and DENV differentiation, and that laboratory diagnosis should be mandatory. Copyright © 2017 Elsevier B.V. All rights reserved.

  17. Dengue Infections in the Philippines: Clinical and Virological Findings in 517 Hospitalized Patients

    DTIC Science & Technology

    1988-01-01

    DENGUE INFECTIONS IN THE PHILIPPINES: CLINICAL AND 1 VIRCI.OGICAL FINDINGS IN 517 HOSPITALIZED PATIENTS Curtis G. Hayes, Corazon R. Manaloto, Alicia...PATIENTS CURTIS G. HAYES,* CORAZON R. MANALOTO,* ALICIA GONZALES,t AND CATHERINE P. RANOAt *U.S. Naval Medical Research Unit No. 2, APO San Francisco 96528

  18. Zika Virus Outbreak in Rio de Janeiro, Brazil: Clinical Characterization, Epidemiological and Virological Aspects

    PubMed Central

    Calvet, Guilherme Amaral; Siqueira, André Machado; Wakimoto, Mayumi; de Sequeira, Patrícia Carvalho; Nobre, Aline; Quintana, Marcel de Souza Borges; de Mendonça, Marco Cesar Lima; Lupi, Otilia; de Souza, Rogerio Valls; Romero, Carolina; Zogbi, Heruza; Bressan, Clarisse da Silveira; Alves, Simone Sampaio; Lourenço-de-Oliveira, Ricardo; Nogueira, Rita Maria Ribeiro; Carvalho, Marilia Sá

    2016-01-01

    Background In 2015, Brazil was faced with the cocirculation of three arboviruses of major public health importance. The emergence of Zika virus (ZIKV) presents new challenges to both clinicians and public health authorities. Overlapping clinical features between diseases caused by ZIKV, Dengue (DENV) and Chikungunya (CHIKV) and the lack of validated serological assays for ZIKV make accurate diagnosis difficult. Methodology / Principal Findings The outpatient service for acute febrile illnesses in Fiocruz initiated a syndromic clinical observational study in 2007 to capture unusual presentations of DENV infections. In January 2015, an increase of cases with exanthematic disease was observed. Trained physicians evaluated the patients using a detailed case report form that included clinical assessment and laboratory investigations. The laboratory diagnostic algorithm included assays for detection of ZIKV, CHIKV and DENV. 364 suspected cases of Zika virus disease were identified based on clinical criteria between January and July 2015. Of these, 262 (71.9%) were tested and 119 (45.4%) were confirmed by the detection of ZIKV RNA. All of the samples with sequence information available clustered within the Asian genotype. Conclusions / Significance This is the first report of a ZIKV outbreak in the state of Rio de Janeiro, based on a large number of suspected (n = 364) and laboratory confirmed cases (n = 119). We were able to demonstrate that ZIKV was circulating in Rio de Janeiro as early as January 2015. The peak of the outbreak was documented in May/June 2015. More than half of the patients reported headache, arthralgia, myalgia, non-purulent conjunctivitis, and lower back pain, consistent with the case definition of suspected ZIKV disease issued by the Pan American Health Organization (PAHO). However, fever, when present, was low-intensity and short-termed. In our opinion, pruritus, the second most common clinical sign presented by the confirmed cases, should be added

  19. Zika Virus Outbreak in Rio de Janeiro, Brazil: Clinical Characterization, Epidemiological and Virological Aspects.

    PubMed

    Brasil, Patrícia; Calvet, Guilherme Amaral; Siqueira, André Machado; Wakimoto, Mayumi; de Sequeira, Patrícia Carvalho; Nobre, Aline; Quintana, Marcel de Souza Borges; Mendonça, Marco Cesar Lima de; Lupi, Otilia; de Souza, Rogerio Valls; Romero, Carolina; Zogbi, Heruza; Bressan, Clarisse da Silveira; Alves, Simone Sampaio; Lourenço-de-Oliveira, Ricardo; Nogueira, Rita Maria Ribeiro; Carvalho, Marilia Sá; de Filippis, Ana Maria Bispo; Jaenisch, Thomas

    2016-04-01

    In 2015, Brazil was faced with the cocirculation of three arboviruses of major public health importance. The emergence of Zika virus (ZIKV) presents new challenges to both clinicians and public health authorities. Overlapping clinical features between diseases caused by ZIKV, Dengue (DENV) and Chikungunya (CHIKV) and the lack of validated serological assays for ZIKV make accurate diagnosis difficult. The outpatient service for acute febrile illnesses in Fiocruz initiated a syndromic clinical observational study in 2007 to capture unusual presentations of DENV infections. In January 2015, an increase of cases with exanthematic disease was observed. Trained physicians evaluated the patients using a detailed case report form that included clinical assessment and laboratory investigations. The laboratory diagnostic algorithm included assays for detection of ZIKV, CHIKV and DENV. 364 suspected cases of Zika virus disease were identified based on clinical criteria between January and July 2015. Of these, 262 (71.9%) were tested and 119 (45.4%) were confirmed by the detection of ZIKV RNA. All of the samples with sequence information available clustered within the Asian genotype. This is the first report of a ZIKV outbreak in the state of Rio de Janeiro, based on a large number of suspected (n = 364) and laboratory confirmed cases (n = 119). We were able to demonstrate that ZIKV was circulating in Rio de Janeiro as early as January 2015. The peak of the outbreak was documented in May/June 2015. More than half of the patients reported headache, arthralgia, myalgia, non-purulent conjunctivitis, and lower back pain, consistent with the case definition of suspected ZIKV disease issued by the Pan American Health Organization (PAHO). However, fever, when present, was low-intensity and short-termed. In our opinion, pruritus, the second most common clinical sign presented by the confirmed cases, should be added to the PAHO case definition, while fever could be given less emphasis

  20. Efavirenz versus boosted atazanavir-containing regimens and immunologic, virologic, and clinical outcomes: A prospective study of HIV-positive individuals.

    PubMed

    Cain, Lauren E; Caniglia, Ellen C; Phillips, Andrew; Olson, Ashley; Muga, Roberto; Pérez-Hoyos, Santiago; Abgrall, Sophie; Costagliola, Dominique; Rubio, Rafael; Jarrín, Inma; Bucher, Heiner; Fehr, Jan; van Sighem, Ard; Reiss, Peter; Dabis, François; Vandenhende, Marie-Anne; Logan, Roger; Robins, James; Sterne, Jonathan A C; Justice, Amy; Tate, Janet; Touloumi, Giota; Paparizos, Vasilis; Esteve, Anna; Casabona, Jordi; Seng, Rémonie; Meyer, Laurence; Jose, Sophie; Sabin, Caroline; Hernán, Miguel A

    2016-10-01

    To compare regimens consisting of either ritonavir-boosted atazanavir or efavirenz and a nucleoside reverse transcriptase inhibitor (NRTI) backbone with respect to clinical, immunologic, and virologic outcomes. Prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States included in the HIV-CAUSAL Collaboration. HIV-positive, antiretroviral therapy-naive, and acquired immune deficiency syndrome (AIDS)-free individuals were followed from the time they started an atazanavir or efavirenz regimen. We estimated an analog of the "intention-to-treat" effect for efavirenz versus atazanavir regimens on clinical, immunologic, and virologic outcomes with adjustment via inverse probability weighting for time-varying covariates. A total of 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths) and 18,786 individuals started an efavirenz regimen (389 deaths, 825 AIDS-defining illnesses or deaths). During a median follow-up of 31 months, the hazard ratios (95% confidence intervals) were 0.98 (0.77, 1.24) for death and 1.09 (0.91, 1.30) for AIDS-defining illness or death comparing efavirenz with atazanavir regimens. The 5-year survival difference was 0.1% (95% confidence interval: -0.7%, 0.8%) and the AIDS-free survival difference was -0.3% (-1.2%, 0.6%). After 12 months, the mean change in CD4 cell count was 20.8 (95% confidence interval: 13.9, 27.8) cells/mm lower and the risk of virologic failure was 20% (14%, 26%) lower in the efavirenz regimens. Our estimates are consistent with a smaller 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for efavirenz compared with atazanavir regimens. No overall differences could be detected with respect to 5-year survival or AIDS-free survival.

  1. Virologic and clinical outcomes of hepatitis B virus infection in HIV-HBV coinfected transplant recipients.

    PubMed

    Coffin, C S; Stock, P G; Dove, L M; Berg, C L; Nissen, N N; Curry, M P; Ragni, M; Regenstein, F G; Sherman, K E; Roland, M E; Terrault, N A

    2010-05-01

    Liver transplantation (LT) is the treatment of choice for end-stage liver disease, but is controversial in patients with human immunodeficiency virus (HIV) infection. Using a prospective cohort of HIV-hepatitis B virus (HBV) coinfected patients transplanted between 2001-2007; outcomes including survival and HBV clinical recurrence were determined. Twenty-two coinfected patients underwent LT; 45% had detectable HBV DNA pre-LT and 72% were receiving anti-HBV drugs with efficacy against lamivudine-resistant HBV. Post-LT, all patients received hepatitis B immune globulin (HBIG) plus nucleos(t)ide analogues and remained HBsAg negative without clinical evidence of HBV recurrence, with a median follow-up 3.5 years. Low-level HBV viremia (median 108 IU/mL, range 9-789) was intermittently detected in 7/13 but not associated with HBsAg detection or ALT elevation. Compared with 20 HBV monoinfected patients on similar HBV prophylaxis and median follow-up of 4.0 years, patient and graft survival were similar: 100% versus 85% in HBV mono- versus coinfected patients (p = 0.08, log rank test). LT is effective for HIV-HBV coinfected patients with complications of cirrhosis, including those who are HBV DNA positive at the time of LT. Combination HBIG and antivirals is effective as prophylaxis with no clinical evidence of HBV recurrence but low-level HBV DNA is detectable in approximately 50% of recipients.

  2. Virologic and Clinical Outcomes of Hepatitis B Virus Infection in HIV-HBV Coinfected Transplant Recipients

    PubMed Central

    Coffin, C.S.; Stock, P.G.; Dove, L.M.; Berg, C.L.; Nissen, N.N.; Curry, M.P.; Ragni, M.; Regenstein, F.G.; Sherman, K.E.; Roland, M.E.; Terrault, N.A.

    2010-01-01

    Liver transplantation (LT) is the treatment of choice for endstage liver disease, but is controversial in patients with human immunodeficiency virus (HIV) infection. Using a prospective cohort of HIV-HBV coinfected patients transplanted between 2001–2007; outcomes including survival and HBV clinical recurrence were determined. Twenty-two coinfected patients underwent LT; 45% had detectable HBV DNA pre-LT and 72% were receiving anti-HBV drugs with efficacy against lamivudine-resistant HBV. Post-LT, all patients received hepatitis B immune globulin (HBIG) plus nucleos(t)ide analogues and remained HBsAg negative without clinical evidence of HBV recurrence, with a median follow-up 3.5 years. Low-level HBV viremia (median 108 IU/ml, range 9–789) was intermittently detected in 7/13 but not associated with HBsAg detection or ALT elevation. Compared with 20 HBV monoinfected patients on similar HBV prophylaxis and median follow-up of 4.0 years, patient and graft survival were similar: 100% vs. 85% in HBV mono- vs coinfected patients (p=0.08, log rank test). LT is effective for HIV-HBV coinfected patients with complications of cirrhosis, including those who are HBV DNA positive at the time of LT. Combination HBIG and antivirals is effective as prophylaxis with no clinical evidence of HBV recurrence but low level HBV DNA is detectable in ~50% of recipients. PMID:20346065

  3. Human rhinovirus infections in hospitalized children: clinical, epidemiological and virological features.

    PubMed

    Tran, D N; Trinh, Q D; Pham, N T K; Pham, T M H; Ha, M T; Nguyen, T Q N; Okitsu, S; Shimizu, H; Hayakawa, S; Mizuguchi, M; Ushijima, H

    2016-01-01

    Molecular epidemiology and clinical impact of human rhinovirus (HRV) are not well documented in tropical regions. This study compared the clinical characteristics of HRV to other common viral infections and investigated the molecular epidemiology of HRV in hospitalized children with acute respiratory infections (ARIs) in Vietnam. From April 2010 to May 2011, 1082 nasopharyngeal swabs were screened for respiratory viruses by PCR. VP4/VP2 sequences of HRV were further characterized. HRV was the most commonly detected virus (30%), in which 70% were diagnosed as either pneumonia or bronchiolitis. Children with single HRV infections presented with significantly higher rate of hypoxia than those infected with respiratory syncytial virus or parainfluenza virus (PIV)-3 (12·4% vs. 3·8% and 0%, respectively, P < 0·05), higher rate of chest retraction than PIV-1 (57·3% vs. 34·5%, P = 0·028), higher rate of wheezing than influenza A (63·2% vs. 42·3%, P = 0·038). HRV-C did not differ to HRV-A clinically. The genetic diversity and changes of types over time were observed and may explain the year-round circulation of HRV. One novel HRV-A type was discovered which circulated locally for several years. In conclusion, HRV showed high genetic diversity and was associated with significant morbidity and severe ARIs in hospitalized children.

  4. Phylogenetic, virological, and clinical characteristics of genotype C hepatitis B virus with TCC at codon 15 of the precore region.

    PubMed

    Chan, Henry Lik-Yuen; Tse, Chi-Hang; Ng, Eddie Yuen-Tok; Leung, Kwong-Sak; Lee, Kin-Hong; Tsui, Stephen Kwok-Wing; Sung, Joseph Jao-Yiu

    2006-03-01

    Hepatitis B virus (HBV) with T-1856 of the precore region is always associated with C-1858 (i.e., TCC at nucleotides 1856 to 1858), and it is reported only in genotype C HBV isolates. We aimed to investigate the phylogenetic, virological, and clinical characteristics of HBV isolates bearing TCC at nucleotides 1856 to 1858. We have previously reported on the presence of two major subgroups in genotype C HBV, namely, HBV genotype Cs (Southeast Asia) and HBV genotype Ce (Far East). We have designed a novel 5' nuclease technology based on the nucleotide polymorphism (C or A) at nucleotide 2733 to differentiate the two genotype C HBV subgroups. The mutations at the basal core promoter and precore regions were analyzed by direct sequencing. Among 214 genotype C HBV-infected patients, 31% had TCC, 37% had CCC, 3% had CTC, and 29% had CCT at nucleotides 1856 to 1858. All except one HBV strain with TCC at nucleotides 1856 to 1858 belonged to subgroup Cs, which has been reported only in Hong Kong; Guangzhou, China; and Vietnam. HBV with TCC at nucleotides 1856 to 1858 was associated with the G1898A mutation (64%). Patients infected with HBV harboring TCC had more liver cirrhosis than those infected with HBV harboring CCC (18% versus 5%; P = 0.008), and more of the patients infected with HBV harboring TCC were positive for HBeAg (58% versus 36%; P = 0.01) and had higher median alanine aminotransferase levels (65 IU/liter versus 49 IU/liter; P = 0.006); but similar proportions of patients infected with HBV harboring TCC and those infected with HBV harboring CCT had liver cirrhosis (18% versus 13%; P = 0.43). In summary, we report that HBV with TCC at nucleotides 1856 to 1858 of the precore region might represent a specific HBV strain associated with more aggressive liver disease than other genotype C HBV strains.

  5. The human polyomaviruses KI and WU: virological background and clinical implications.

    PubMed

    Babakir-Mina, Muhammed; Ciccozzi, Massimo; Perno, Carlo Federico; Ciotti, Marco

    2013-08-01

    In 2007, two novel polyomaviruses KI and WU were uncovered in the respiratory secretions of children with acute respiratory symptoms. Seroepidemiological studies showed that infection by these viruses is widespread in the human population. Following these findings, different biological specimens and body compartments have been screened by real-time PCR in the attempt to establish a pathogenetic role for KI polyomavirus (KIPyV) and WU polyomavirus (WUPyV) in human diseases. Although both viruses have been found mainly in respiratory tract samples of immunocompromised patients, a clear causative link with the respiratory disease has not been established. Indeed, the lack of specific clinical or radiological findings, the frequent co-detection with other respiratory pathogens, the detection in subjects without signs or symptoms of respiratory disease, and the variability of the viral loads measured did not allow drawing a definitive conclusion. Prospective studies carried out on a large sample size including both immunocompromised and immunocompetent patients with and without respiratory symptoms are needed. Standardized quantitative real-time PCR methods, definition of a clear clinical cutoff value, timing in the collection of respiratory samples, are also crucial to understand the pathogenic role, if any, of KIPyV and WUPyV in human pathology.

  6. Next-generation sequencing in clinical virology: Discovery of new viruses.

    PubMed

    Datta, Sibnarayan; Budhauliya, Raghvendra; Das, Bidisha; Chatterjee, Soumya; Vanlalhmuaka; Veer, Vijay

    2015-08-12

    Viruses are a cause of significant health problem worldwide, especially in the developing nations. Due to different anthropological activities, human populations are exposed to different viral pathogens, many of which emerge as outbreaks. In such situations, discovery of novel viruses is utmost important for deciding prevention and treatment strategies. Since last century, a number of different virus discovery methods, based on cell culture inoculation, sequence-independent PCR have been used for identification of a variety of viruses. However, the recent emergence and commercial availability of next-generation sequencers (NGS) has entirely changed the field of virus discovery. These massively parallel sequencing platforms can sequence a mixture of genetic materials from a very heterogeneous mix, with high sensitivity. Moreover, these platforms work in a sequence-independent manner, making them ideal tools for virus discovery. However, for their application in clinics, sample preparation or enrichment is necessary to detect low abundance virus populations. A number of techniques have also been developed for enrichment or viral nucleic acids. In this manuscript, we review the evolution of sequencing; NGS technologies available today as well as widely used virus enrichment technologies. We also discuss the challenges associated with their applications in the clinical virus discovery.

  7. Virological Surveillance of Influenza A Subtypes Isolated in 2014 from Clinical Outbreaks in Canadian Swine

    PubMed Central

    Grgić, Helena; Gallant, Jackie; Poljak, Zvonimir

    2017-01-01

    Influenza A viruses (IAVs) are respiratory pathogens associated with an acute respiratory disease that occurs year-round in swine production. It is currently one of the most important pathogens in swine populations, with the potential to infect other host species including humans. Ongoing research indicates that the three major subtypes of IAV—H1N1, H1N2, and H3N2—continue to expand in their genetic and antigenic diversity. In this study, we conducted a comprehensive genomic analysis of 16 IAVs isolated from different clinical outbreaks in Alberta, Manitoba, Ontario, and Saskatchewan in 2014. We also examined the genetic basis for probable antigenic differences among sequenced viruses. On the basis of phylogenetic analysis, all 13 Canadian H3N2 viruses belonged to cluster IV, eight H3N2 viruses were part of the IV-C cluster, and one virus belonged to the IV-B and one to the IV-D cluster. Based on standards used in this study, three H3N2 viruses could not be clearly classified into any currently established group within cluster IV (A to F). Three H1N2 viruses were part of the H1α cluster. PMID:28335552

  8. Clinical, virological and epidemiological characterization of dengue outbreak in Myanmar, 2015.

    PubMed

    Kyaw, A K; Ngwe Tun, M M; Moi, M L; Nabeshima, T; Soe, K T; Thwe, S M; Myint, A A; Maung, K T T; Aung, W; Hayasaka, D; Buerano, C C; Thant, K Z; Morita, K

    2017-07-01

    Hospital-based surveillance was conducted at two widely separated regions in Myanmar during the 2015 dengue epidemic. Acute phase serum samples were collected from 332 clinically diagnosed dengue patients during the peak season of dengue cases. Viremia levels were measured by quantitative real-time PCR and plaque assays using FcγRIIA-expressing and non-FcγRIIA-expressing BHK cells to specifically determine the infectious virus particles. By serology and molecular techniques, 280/332 (84·3%) were confirmed as dengue patients. All four serotypes of dengue virus (DENV) were isolated from among 104 laboratory-confirmed patients including two cases infected with two DENV serotypes. High percentage of primary infection was noted among the severe dengue patients. Patients with primary infection or DENV IgM negative demonstrated significantly higher viral loads but there was no significant difference among the severity groups. Viremia levels among dengue patients were notably high for a long period which was assumed to support the spread of the virus by the mosquito vector during epidemic. Phylogenetic analyses of the envelope gene of the epidemic strains revealed close similarity with the strains previously isolated in Myanmar and neighboring countries. DENV-1 dominated the epidemic in 2015 and the serotype (except DENV-3) and genotype distributions were similar in both study sites.

  9. The virology, epidemiology, and clinical impact of West Nile virus: a decade of advancements in research since its introduction into the Western Hemisphere.

    PubMed

    Murray, K O; Walker, C; Gould, E

    2011-06-01

    West Nile virus (WNV) is now endemic in the USA. After the widespread surge of virus activity across the USA, research has flourished, and our knowledge base has significantly expanded over the past 10 years since WNV was first recognized in New York City. This article provides a review of the virology of WNV, history, epidemiology, clinical features, pathology of infection, the innate and adaptive immune response, host risk factors for developing severe disease, clinical sequelae following severe disease, chronic infection, and the future of prevention.

  10. Clinical implications of virological "failure": interview with Steven Deeks, M.D., San Francisco General Hospital. Interview by John S. James.

    PubMed

    Deeks, S

    1998-02-20

    Physicians have recently noticed that some patients on protease inhibitor combination therapy are doing well clinically, even if the drugs are not suppressing their viral loads to non-detectable levels. These patients are considered to be in virological failure. The first extensive study, which tracked 143 patients for a median of 18 months, was presented at the 5th Conference on Retroviruses and Opportunistic Infections. The author of the study, Steven Deeks, is interviewed on the research methodology, the findings, and the potential implications for clinical care.

  11. Tropical spastic paraparesis and HTLV-1 associated myelopathy: clinical, epidemiological, virological and therapeutic aspects.

    PubMed

    Gessain, A; Mahieux, R

    2012-03-01

    In 1980, Human T cell leukemia/lymphoma virus type 1 (HTLV-1) was the first oncogenic human retrovirus to be discovered. HTLV-1 belongs to the Retroviridae family, the Orthoretrovirinae subfamily and to the deltaretrovirus genus. HTLV-1 preferentially infects CD4(+) lymphoid cells in vivo. Three molecules have been identified for binding and/or entry of HTLV-1: heparan sulfate proteoglycans, neuropilin-1, and glucose transporter 1. An efficient transfer of the virus from an infected cell to a target cell can occur through the formation of a viral synapse and/or by virofilm structure. As for all retroviruses, HTLV-1 genome possesses three major ORFs (gag, pol and env) encoding the structural and enzymatic proteins. HTLV-1 encodes also some regulatory and auxillary proteins including the tax protein with transforming activities and the HBZ protein which plays a role in the proliferation and maintenance of the leukemic cells. HTLV-1 is present throughout the world with clusters of high endemicity including mainly Southern Japan, the Caribbean region, areas in South America and in intertropical Africa. The worldwide HTLV-1 infected population is estimated to be around 10-20 million. HTLV-1 has three modes of transmission: (1): mother to child, mainly linked to prolonged breast-feeding; (2): sexual, mainly occurring from male to female and (3): contaminated blood products. HTLV-1 possesses a remarkable genetic stability. HTLV-1 is the etiological agent of mainly two severe diseases: a malignant T CD4(+) cell lymphoproliferation, of very poor prognosis, named Adult T cell Leukemia/Lymphoma (ATLL), and a chronic neuro-myelopathy named Tropical spastic paraparesis/HTLV-1 Associated Myelopathy (TSP/HAM). The lifetime risk among HTLV-1 carriers is estimated to be around 0.25 to 3%. TSP/HAM mainly occurs in adults, with a mean age at onset of 40-50 years and it is more common in women than in men. Blood transfusion is a major risk factor for TSP/HAM development. Clinically

  12. Molecular Virologic and Clinical Characteristics of a Chikungunya Fever Outbreak in La Romana, Dominican Republic, 2014

    PubMed Central

    Kautz, Tiffany F.; Auguste, Albert J.; Erasmus, Jesse H.; Kiaty-Figueroa, Liddy; Gerhardt, Renessa; Lin, David; Hari, Kumar L.; Jain, Ravi; Ruiz, Nicolas; Muruato, Antonio E.; Silfa, Jael; Bido, Franklin

    2016-01-01

    Since emerging in Saint Martin in 2013, chikungunya virus (CHIKV), an alphavirus transmitted by the Aedes aegypti mosquito, has infected approximately two million individuals in the Americas, with over 500,000 reported cases in the Dominican Republic (DR). CHIKV-infected patients typically present with a febrile syndrome including polyarthritis/polyarthralgia, and a macropapular rash, similar to those infected with dengue and Zika viruses, and malaria. Nevertheless, many Dominican cases are unconfirmed due to the unavailability and high cost of laboratory testing and the absence of specific treatment for CHIKV infection. To obtain a more accurate representation of chikungunya fever (CHIKF) clinical signs and symptoms, and confirm the viral lineage responsible for the DR CHIKV outbreak, we tested 194 serum samples for CHIKV RNA and IgM antibodies from patients seen in a hospital in La Romana, DR using quantitative RT-PCR and IgM capture ELISA, and performed retrospective chart reviews. RNA and antibodies were detected in 49% and 24.7% of participants, respectively. Sequencing revealed that the CHIKV strain responsible for the La Romana outbreak belonged to the Asian/American lineage and grouped phylogenetically with recent Mexican and Trinidadian isolates. Our study shows that, while CHIKV-infected individuals were infrequently diagnosed with CHIKF, uninfected patients were never falsely diagnosed with CHIKF. Participants testing positive for CHIKV RNA were more likely to present with arthralgia, although it was reported in just 20.0% of CHIKF+ individuals. High percentages of respiratory (19.6%) signs and symptoms, especially among children, were noted, though it was not possible to determine whether individuals infected with CHIKV were co-infected with other pathogens. These results suggest that CHIKV may have been underdiagnosed during this outbreak, and that CHIKF should be included in differential diagnoses of diverse undifferentiated febrile syndromes in the

  13. Molecular Virologic and Clinical Characteristics of a Chikungunya Fever Outbreak in La Romana, Dominican Republic, 2014.

    PubMed

    Langsjoen, Rose M; Rubinstein, Rebecca J; Kautz, Tiffany F; Auguste, Albert J; Erasmus, Jesse H; Kiaty-Figueroa, Liddy; Gerhardt, Renessa; Lin, David; Hari, Kumar L; Jain, Ravi; Ruiz, Nicolas; Muruato, Antonio E; Silfa, Jael; Bido, Franklin; Dacso, Matthew; Weaver, Scott C

    2016-12-01

    Since emerging in Saint Martin in 2013, chikungunya virus (CHIKV), an alphavirus transmitted by the Aedes aegypti mosquito, has infected approximately two million individuals in the Americas, with over 500,000 reported cases in the Dominican Republic (DR). CHIKV-infected patients typically present with a febrile syndrome including polyarthritis/polyarthralgia, and a macropapular rash, similar to those infected with dengue and Zika viruses, and malaria. Nevertheless, many Dominican cases are unconfirmed due to the unavailability and high cost of laboratory testing and the absence of specific treatment for CHIKV infection. To obtain a more accurate representation of chikungunya fever (CHIKF) clinical signs and symptoms, and confirm the viral lineage responsible for the DR CHIKV outbreak, we tested 194 serum samples for CHIKV RNA and IgM antibodies from patients seen in a hospital in La Romana, DR using quantitative RT-PCR and IgM capture ELISA, and performed retrospective chart reviews. RNA and antibodies were detected in 49% and 24.7% of participants, respectively. Sequencing revealed that the CHIKV strain responsible for the La Romana outbreak belonged to the Asian/American lineage and grouped phylogenetically with recent Mexican and Trinidadian isolates. Our study shows that, while CHIKV-infected individuals were infrequently diagnosed with CHIKF, uninfected patients were never falsely diagnosed with CHIKF. Participants testing positive for CHIKV RNA were more likely to present with arthralgia, although it was reported in just 20.0% of CHIKF+ individuals. High percentages of respiratory (19.6%) signs and symptoms, especially among children, were noted, though it was not possible to determine whether individuals infected with CHIKV were co-infected with other pathogens. These results suggest that CHIKV may have been underdiagnosed during this outbreak, and that CHIKF should be included in differential diagnoses of diverse undifferentiated febrile syndromes in the

  14. Clinical features and preliminary studies of virological correlates of neurocognitive impairment among HIV-infected individuals in Nigeria.

    PubMed

    Royal, Walter; Cherner, Mariana; Carr, Jean; Habib, Abdulrazaq G; Akomolafe, Abimbola; Abimiku, Alashl'e; Charurat, Manhattan; Farley, John; Oluyemisi, Akinwande; Mamadu, Ibrahim; Johnson, Joyce; Ellis, Ronald; McCutchan, J Allen; McCutchen, J Allen; Grant, Igor; Blattner, William A

    2012-06-01

    In Nigeria, the incidence and prevalence of human immunodeficiency virus (HIV)-related neurocognitive impairment (NCI) are unknown and there currently exists little information related to the viral correlates rates of NCI. Therefore, studies were performed to examine the potential utility of applying an established neuropsychological (NP) screening battery and detailed NP testing to detect NCI and correlations with functional impairment and the presence of specific viral signatures among infected subjects. A total of 60 HIV-1 seropositive antiretroviral-naive individuals and 56 seronegative control subjects were administered the International HIV Dementia Scale (IHDS) and assessed for functional impairment using the Karnofsky performance status scale. Fifteen HIV-infected patients and 11 controls were also administered a detailed NP battery. Blood samples from eight infected subjects, three with evidence of NCI, were obtained for molecular analysis of HIV-1 strain. Unadjusted scores on the IHDS showed that, using a recommended total score cutoff of 10, 28.8% of the HIV-1 seropositive and 16.0% of seropositive individuals scored abnormally. Results from testing using the full NP battery showed that, overall, the HIV seropositive group performed worse than the seronegative group, with effect sizes spanning from small (0.25 on the trail making test A) to large (0.82 on action fluency), and an average effect size across the battery of 0.45, which approaches that which has been recorded in other international settings. Sequencing of partial pol amplicons from viral isolates revealed that two of three patients with NCI were infected with subtype G virus and 1 with the circulating recombinant form (CRF)02_AG; all four individuals without NCI were infected with CRF_02AG. These studies demonstrate the utility of the IHDS in identifying cognitive impairment among HIV infected individuals in Nigeria. Future studies aimed at examining the burden of NCI among the population of

  15. Non-linear dynamics models characterizing long-term virological data from AIDS clinical trials.

    PubMed

    Verotta, Davide; Schaedeli, Franziska

    2002-04-01

    illustration we demonstrate an application of the models using real AIDS clinical trial data involving patients treated with a combination of anti-retroviral agents using a model which incorporates compliance data.

  16. Outbreak of Zika virus infection in Singapore: an epidemiological, entomological, virological, and clinical analysis.

    PubMed

    2017-08-01

    An outbreak of Zika virus infection was detected in Singapore in August, 2016. We report the first comprehensive analysis of a national response to an outbreak of Zika virus infection in Asia. In the first phase of the outbreak, patients with suspected Zika virus infection were isolated in two national referral hospitals until their serum tested negative for the virus. Enhanced vector control and community engagement measures were deployed in disease clusters, including stepped-up mosquito larvicide and adulticide use, community participation in source reduction (destruction of mosquito breeding sites), and work with the local media to promote awareness of the outbreak. Clinical and epidemiological data were collected from patients with confirmed Zika virus infection during the first phase. In the second phase, admission into hospitals for isolation was stopped but vector control efforts continued. Mosquitoes were captured from areas with Zika disease clusters to assess which species were present, their breeding numbers, and to test for Zika virus. Mosquito virus strains were compared with human strains through phylogenetic analysis after full genome sequencing. Reproductive numbers and inferred dates of strain diversification were estimated through Bayesian analyses. From Aug 27 to Nov 30, 2016, 455 cases of Zika virus infection were confirmed in Singapore. Of 163 patients with confirmed Zika virus infection who presented to national referral hospitals during the first phase of the outbreak, Zika virus was detected in the blood samples of 97 (60%) patients and the urine samples of 157 (96%) patients. There were 15 disease clusters, 12 of which had high Aedes aegypti breeding percentages. Captured mosquitoes were pooled into 517 pools for Zika virus screening; nine abdomen pools (2%) were positive for Zika virus, of which seven head and thorax pools were Zika-virus positive. In the phylogenetic analysis, all mosquito sequences clustered within the outbreak lineage

  17. Boosted lopinavir- versus boosted atazanavir-containing regimens and immunologic, virologic, and clinical outcomes: a prospective study of HIV-infected individuals in high-income countries.

    PubMed

    Cain, Lauren E; Phillips, Andrew; Olson, Ashley; Sabin, Caroline; Jose, Sophie; Justice, Amy; Tate, Janet; Logan, Roger; Robins, James M; Sterne, Jonathan A C; van Sighem, Ard; Reiss, Peter; Young, James; Fehr, Jan; Touloumi, Giota; Paparizos, Vasilis; Esteve, Anna; Casabona, Jordi; Monge, Susana; Moreno, Santiago; Seng, Rémonie; Meyer, Laurence; Pérez-Hoyos, Santiago; Muga, Roberto; Dabis, François; Vandenhende, Marie-Anne; Abgrall, Sophie; Costagliola, Dominique; Hernán, Miguel A

    2015-04-15

    Current clinical guidelines consider regimens consisting of either ritonavir-boosted atazanavir or ritonavir-boosted lopinavir and a nucleoside reverse transcriptase inhibitor (NRTI) backbone among their recommended and alternative first-line antiretroviral regimens. However, these guidelines are based on limited evidence from randomized clinical trials and clinical experience. We compared these regimens with respect to clinical, immunologic, and virologic outcomes using data from prospective studies of human immunodeficiency virus (HIV)-infected individuals in Europe and the United States in the HIV-CAUSAL Collaboration, 2004-2013. Antiretroviral therapy-naive and AIDS-free individuals were followed from the time they started a lopinavir or an atazanavir regimen. We estimated the 'intention-to-treat' effect for atazanavir vs lopinavir regimens on each of the outcomes. A total of 6668 individuals started a lopinavir regimen (213 deaths, 457 AIDS-defining illnesses or deaths), and 4301 individuals started an atazanavir regimen (83 deaths, 157 AIDS-defining illnesses or deaths). The adjusted intention-to-treat hazard ratios for atazanavir vs lopinavir regimens were 0.70 (95% confidence interval [CI], .53-.91) for death, 0.67 (95% CI, .55-.82) for AIDS-defining illness or death, and 0.91 (95% CI, .84-.99) for virologic failure at 12 months. The mean 12-month increase in CD4 count was 8.15 (95% CI, -.13 to 16.43) cells/µL higher in the atazanavir group. Estimates differed by NRTI backbone. Our estimates are consistent with a lower mortality, a lower incidence of AIDS-defining illness, a greater 12-month increase in CD4 cell count, and a smaller risk of virologic failure at 12 months for atazanavir compared with lopinavir regimens. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  18. Absence of Effect of Menopause Status at Initiation of First-Line Antiretroviral Therapy on Immunologic or Virologic Responses: A Cohort Study from Rio de Janeiro, Brazil

    PubMed Central

    Calvet, Guilherme Amaral; Velasque, Luciane; Luz, Paula Mendes; Cardoso, Sandra Wagner; Derrico, Monica; Moreira, Ronaldo Ismério; de Andrade, Angela Cristina Vasconcelos; Cytryn, Andrea; Pires, Elaine; Veloso, Valdiléa Gonçalves; Grinsztejn, Beatriz; Friedman, Ruth Khalili

    2014-01-01

    Objective To compare the effectiveness of first-line combination antiretroviral therapy (cART) between premenopausal and postmenopausal women. Methods ART-naïve women initiating cART between January 2000/June 2010 at the Instituto de Pesquisa Clínica Evandro Chagas Cohort were studied. Women were defined as postmenopausal after 12 consecutive months of amenorrhea. CD4 cell counts and HIV-1 RNA viral load (VL) measurements were compared between pre- and postmenopausal at 6, 12 and 24 months after cART initiation. Women who modified/discontinued a drug class or died due to an AIDS defining illness were classified as ART-failures. Variables were compared using Wilcoxon test, χ2 or Fisher’s exact test. The odds of cART effectiveness (VL<400 copies/mL and/or no need to change cART) were compared using logistic regression. Linear model was used to access relationship between CD4 change and menopause. Results Among 383 women, 328 (85%) were premenopausal and 55 (15%) postmenopausal. Median pre cART CD4 counts were 231 and 208 cells/mm3 (p = 0.14) in pre- and postmenopausal women, respectively. No difference in the median pre cART VL was found (both 4.8 copies/mL). Median CD4 changes were similar at 6 and 12 months. At 24 months after cART initiation, CD4 changes among postmenopausal women were significantly lower among premenopausal women (p = 0.01). When the analysis was restricted to women with VL<400 copies/mL, no statistical difference was observed. Overall, 63.7% achieved cART effectiveness at 24 months without differences between groups at 6, 12 and 24 months. Conclusion Menopause status at the time of first-line cART initiation does not impact CD4 cell changes at 24 months among women with a virologic response. No relationship between menopause status and virologic response was observed. PMID:24586673

  19. Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated With Virologic Failure: Results From the Multinational PEARLS (ACTG A5175) Clinical Trial

    PubMed Central

    Kantor, Rami; Smeaton, Laura; Vardhanabhuti, Saran; Hudelson, Sarah E.; Wallis, Carol L.; Tripathy, Srikanth; Morgado, Mariza G.; Saravanan, Shanmugham; Balakrishnan, Pachamuthu; Reitsma, Marissa; Hart, Stephen; Mellors, John W.; Halvas, Elias; Grinsztejn, Beatriz; Hosseinipour, Mina C.; Kumwenda, Johnstone; La Rosa, Alberto; Lalloo, Umesh G.; Lama, Javier R.; Rassool, Mohammed; Santos, Breno R.; Supparatpinyo, Khuanchai; Hakim, James; Flanigan, Timothy; Kumarasamy, Nagalingeswaran; Campbell, Thomas B.; Eshleman, Susan H.

    2015-01-01

    Background. Evaluation of pretreatment HIV genotyping is needed globally to guide treatment programs. We examined the association of pretreatment (baseline) drug resistance and subtype with virologic failure in a multinational, randomized clinical trial that evaluated 3 antiretroviral treatment (ART) regimens and included resource-limited setting sites. Methods. Pol genotyping was performed in a nested case-cohort study including 270 randomly sampled participants (subcohort), and 218 additional participants failing ART (case group). Failure was defined as confirmed viral load (VL) >1000 copies/mL. Cox proportional hazards models estimated resistance–failure association. Results. In the representative subcohort (261/270 participants with genotypes; 44% women; median age, 35 years; median CD4 cell count, 151 cells/µL; median VL, 5.0 log10 copies/mL; 58% non-B subtypes), baseline resistance occurred in 4.2%, evenly distributed among treatment arms and subtypes. In the subcohort and case groups combined (466/488 participants with genotypes), used to examine the association between resistance and treatment failure, baseline resistance occurred in 7.1% (9.4% with failure, 4.3% without). Baseline resistance was significantly associated with shorter time to virologic failure (hazard ratio [HR], 2.03; P = .035), and after adjusting for sex, treatment arm, sex–treatment arm interaction, pretreatment CD4 cell count, baseline VL, and subtype, was still independently associated (HR, 2.1; P = .05). Compared with subtype B, subtype C infection was associated with higher failure risk (HR, 1.57; 95% confidence interval [CI], 1.04–2.35), whereas non-B/C subtype infection was associated with longer time to failure (HR, 0.47; 95% CI, .22–.98). Conclusions. In this global clinical trial, pretreatment resistance and HIV-1 subtype were independently associated with virologic failure. Pretreatment genotyping should be considered whenever feasible. Clinical Trials

  20. Evaluation and management of early virological failure.

    PubMed

    Sax, Paul E

    2006-09-01

    To describe the causes, evaluation, and management of early virological failure in patients treated with their first antiretroviral regimen. Combination antiretroviral therapy predictably induces a rapid virological response, with the majority of patients achieving an undetectable HIV-RNA load by week 24. In clinical trials and cohorts, rates of virological suppression have improved over time. Poor adherence to therapy remains the most common cause of virological failure, and genotype resistance testing is a critical step in evaluating the optimal subsequent approach. Most studies suggest that transient HIV-RNA elevations do not warrant changing treatment, and may be a consequence of laboratory variation. For those who experience virological failure, resistance to individual components of the antiretroviral regimen is dependent on the initial choice of treatment. Once virological failure is confirmed and adherence issues addressed, a prompt change in treatment is warranted to limit the selection of further drug resistance. Resistance that occurs with early virological failure follows typical patterns, with limited resistance to most antiretroviral agents in the nucleoside reverse transcriptase and protease inhibitor classes. The likelihood of achieving virological suppression with subsequent regimens should be high so long as adherence can be assured.

  1. Occult HBV infection in HCC and cirrhotic tissue of HBsAg-negative patients: a virological and clinical study

    PubMed Central

    Coppola, Nicola; Onorato, Lorenzo; Iodice, Valentina; Starace, Mario; Minichini, Carmine; Farella, Nunzia; Liorre, Giulia; Filippini, Pietro; Sagnelli, Evangelista; de Stefano, Giorgio

    2016-01-01

    Aim To evaluate the virological and clinical characteristics of occult HBV infection (OBI) in 68 consecutive HBsAg-negative patients with biopsy-proven cirrhosis and HCC. Methods HBV DNA was sought and sequenced in plasma, HCC tissue and non-HCC liver tissue by PCRs using primers for HBV core, surface and x regions. OBI was identified by the presence of HBV DNA in at least two different PCRs. Results OBI was detected in HCC tissue of 13 (20%) patients and in non-HCC liver tissue of 3 of these 13. OBI was detected in HCC tissue of 54.5% of 11 anti-HBs- negative/anti-HBc-positive patients, in 29.4% of 17 anti-HBs/anti-HBc-positive and in 5% of 40 anti-HBs/anti-HBc-negative (p < 0.0005). The 13 patients with OBI in HCC tissue more frequently than the 55 without showed Child-B or -C cirrhosis (53.9% vs. 5.5%, p < 0.0001) and BCLC-B or -C stages (46.1% vs. 1.8%, p < 0.0001). The pre-S1, pre-S2 and S region sequences in HCC tissue showed amino acid (AA) substitutions (F19L, P24L, S59F, T131I, Q129H) and deletions (in positions 4,8, 17 and 86) in the S region, AA substitutions (T40S, P124K, L54P, G76A, N222T and I273L) in pre-S1 region and AA substitutions in pre-S2 region (P41H and P66L). In the 3 patients showing OBI also in non-HCC liver tissue the S, pre-S1 and pre-S2 sequencing displayed patterns of mutations different. Conclusions The study showed a significant correlation between OBI and the severity of liver damage, several patterns of mutations in the S, pre-S1 and pre-S2 regions in HCC tissue, some at their first description. PMID:27486882

  2. BCSH/BSBMT/UK clinical virology network guideline: diagnosis and management of common respiratory viral infections in patients undergoing treatment for haematological malignancies or stem cell transplantation.

    PubMed

    Dignan, Fiona L; Clark, Andrew; Aitken, Celia; Gilleece, Maria; Jayakar, Vishal; Krishnamurthy, Pramila; Pagliuca, Antonio; Potter, Michael N; Shaw, Bronwen; Skinner, Roderick; Turner, Andrew; Wynn, Robert F; Coyle, Peter

    2016-05-01

    A joint working group established by the Haemato-oncology subgroup of the British Committee for Standards in Haematology, the British Society for Bone Marrow Transplantation and the UK Clinical Virology Network has reviewed the available literature and made recommendations for the diagnosis and management of respiratory viral infections in patients with haematological malignancies or those undergoing haematopoietic stem cell transplantation. This guideline includes recommendations for the diagnosis, prevention and treatment of respiratory viral infections in adults and children. The suggestions and recommendations are primarily intended for physicians practising in the United Kingdom.

  3. Effect of double dose oseltamivir on clinical and virological outcomes in children and adults admitted to hospital with severe influenza: double blind randomised controlled trial

    PubMed Central

    2013-01-01

    . No important differences in tolerability were found. Conclusions There were no virological or clinical advantages with double dose oseltamivir compared with standard dose in patients with severe influenza admitted to hospital. Registration Clinical Trials NCT00298233 PMID:23723457

  4. Twenty-four mini-pool HCV RNA screening in a routine clinical virology laboratory setting: a six-year prospective study.

    PubMed

    Seme, Katja; Mocilnik, Tina; Poljak, Mario

    2011-01-01

    The usefulness of combined anti-HCV and 24 mini-pool HCV RNA screening strategy was re-evaluated after a six-year continuous routine use in a clinical virology laboratory, at which more than half of newly diagnosed hepatitis C patients are intravenous drug users. Pools of 24 samples were prepared from 20,448 anti-HCV negative serum samples and tested using an automated commercial PCR assay with a lower limit of detection of 50 IU/ml. After detection of anti-HCV negative/HCV RNA positive patients, responsible physicians provided follow-up samples. Thirty-eight (0.19%) anti-HCV negative/HCV RNA positive samples from 30 patients (28 intravenous drug users) were detected. Follow-up samples were available for 27/30 patients. Twenty, six and one patient seroconverted in the second, third and fourth available samples, respectively. The interval between the first HCV RNA positive and the first available anti-HCV positive sample was 17-517 days. The costs of detecting a single anti-HCV negative/HCV RNA positive patient were 1227 Euros. Combined anti-HCV and 24 mini-pool HCV RNA screening is a useful and cost effective strategy, not only in blood-transfusion settings but also in a routine clinical virology laboratory, at which a significant proportion of the tested population belongs to a high-risk population.

  5. Clinical and Virological Efficacy of Etravirine Plus Two Active Nucleos(t)ide Analogs in an Heterogeneous HIV-Infected Population

    PubMed Central

    López-Cortés, Luis F.; Viciana, Pompeyo; Girón-González, José A.; Romero-Palacios, Alberto; Márquez-Solero, Manuel; Martinez-Perez, Maria A.; López-Ruz, Miguel A.; de la Torre-Lima, Javier; Téllez-Pérez, Francisco; Delgado-Fernández, Marcial; Garcia-Lázaro, Milagros; Lozano, Fernando; Mohamed-Balghata, Mohamed O.

    2014-01-01

    Etravirine (ETV) is recommended in combination with a boosted protease inhibitor plus an optimized background regimen for salvage therapy, but there is limited experience with its use in combination with two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs). This multicenter study aimed to assess the efficacy of this combination in two scenarios: group A) subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors (NNRTIs) switched due to adverse events and group B) subjects switched after a virologic failure on an efavirenz- or nevirapine-based regimen. The primary endpoint was efficacy at 52 weeks analysed by intention-to-treat. Virologic failure was defined as the inability to suppress plasma HIV-RNA to <50 copies/mL after 24 weeks on treatment, or a confirmed viral load >200 copies/mL in patients who had previously achieved a viral suppression or had an undetectable viral load at inclusion. Two hundred eighty seven patients were included. Treatment efficacy rates in group A and B were 88.0% (CI95, 83.9–92.1%) and 77.4% (CI95, 65.0–89.7%), respectively; the rates reached 97.2% (CI95, 95.1–99.3%) and 90.5% (CI95, 81.7–99.3), by on-treatment analysis. The once-a-day ETV treatment was as effective as the twice daily dosing regimen. Grade 1–2 adverse events were observed motivating a treatment switch in 4.2% of the subjects. In conclusion, ETV (once- or twice daily) plus two analogs is a suitable, well-tolerated combination both as a switching strategy and after failure with first generation NNRTIs, ensuring full drug activity. Trial registration ClinicalTrials.gov NCT01437241 PMID:24836963

  6. Clinical and virological efficacy of etravirine plus two active Nucleos(t)ide analogs in an heterogeneous HIV-infected population.

    PubMed

    López-Cortés, Luis F; Viciana, Pompeyo; Girón-González, José A; Romero-Palacios, Alberto; Márquez-Solero, Manuel; Martinez-Perez, Maria A; López-Ruz, Miguel A; de la Torre-Lima, Javier; Téllez-Pérez, Francisco; Delgado-Fernández, Marcial; Garcia-Lázaro, Milagros; Lozano, Fernando; Mohamed-Balghata, Mohamed O

    2014-01-01

    Etravirine (ETV) is recommended in combination with a boosted protease inhibitor plus an optimized background regimen for salvage therapy, but there is limited experience with its use in combination with two nucleos(t)ide reverse-transcriptase inhibitors (NRTIs). This multicenter study aimed to assess the efficacy of this combination in two scenarios: group A) subjects without virologic failure on or no experience with non-nucleoside reverse-transcriptase inhibitors (NNRTIs) switched due to adverse events and group B) subjects switched after a virologic failure on an efavirenz- or nevirapine-based regimen. The primary endpoint was efficacy at 52 weeks analysed by intention-to-treat. Virologic failure was defined as the inability to suppress plasma HIV-RNA to <50 copies/mL after 24 weeks on treatment, or a confirmed viral load >200 copies/mL in patients who had previously achieved a viral suppression or had an undetectable viral load at inclusion. Two hundred eighty seven patients were included. Treatment efficacy rates in group A and B were 88.0% (CI95, 83.9-92.1%) and 77.4% (CI95, 65.0-89.7%), respectively; the rates reached 97.2% (CI95, 95.1-99.3%) and 90.5% (CI95, 81.7-99.3), by on-treatment analysis. The once-a-day ETV treatment was as effective as the twice daily dosing regimen. Grade 1-2 adverse events were observed motivating a treatment switch in 4.2% of the subjects. In conclusion, ETV (once- or twice daily) plus two analogs is a suitable, well-tolerated combination both as a switching strategy and after failure with first generation NNRTIs, ensuring full drug activity. ClinicalTrials.gov NCT01437241.

  7. Effectiveness of Ritonavir-Boosted Protease Inhibitor Monotherapy in Clinical Practice Even with Previous Virological Failures to Protease Inhibitor-Based Regimens

    PubMed Central

    López-Cortés, Luis F.; Castaño, Manuel A.; López-Ruz, Miguel A.; Rios-Villegas, María J.; Hernández-Quero, José; Merino, Dolores; Jiménez-Aguilar, Patricia; Marquez-Solero, Manuel; Terrón-Pernía, Alberto; Tellez-Pérez, Francisco; Viciana, Pompeyo; Orihuela-Cañadas, Francisco; Palacios-Baena, Zaira; Vinuesa-Garcia, David; Fajardo-Pico, Jose M.; Romero-Palacios, Alberto; Ojeda-Burgos, Guillermo; Pasquau-Liaño, Juan

    2016-01-01

    Background and Objective Significant controversy still exists about ritonavir-boosted protease inhibitor monotherapy (mtPI/rtv) as a simplification strategy that is used up to now to treat patients that have not experienced previous virological failure (VF) while on protease inhibitor (PI) -based regimens. We have evaluated the effectiveness of two mtPI/rtv regimens in an actual clinical practice setting, including patients that had experienced previous VF with PI-based regimens. Methods This retrospective study analyzed 1060 HIV-infected patients with undetectable viremia that were switched to lopinavir/ritonavir or darunavir/ritonavir monotherapy. In cases in which the patient had previously experienced VF while on a PI-based regimen, the lack of major HIV protease resistance mutations to lopinavir or darunavir, respectively, was mandatory. The primary endpoint of this study was the percentage of participants with virological suppression after 96 weeks according to intention-to-treat analysis (non-complete/missing = failure). Results A total of 1060 patients were analyzed, including 205 with previous VF while on PI-based regimens, 90 of whom were on complex therapies due to extensive resistance. The rates of treatment effectiveness (intention-to-treat analysis) and virological efficacy (on-treatment analysis) at week 96 were 79.3% (CI95, 76.8−81.8) and 91.5% (CI95, 89.6–93.4), respectively. No relationships were found between VF and earlier VF while on PI-based regimens, the presence of major or minor protease resistance mutations, the previous time on viral suppression, CD4+ T-cell nadir, and HCV-coinfection. Genotypic resistance tests were available in 49 out of the 74 patients with VFs and only four patients presented new major protease resistance mutations. Conclusion Switching to mtPI/rtv achieves sustained virological control in most patients, even in those with previous VF on PI-based regimens as long as no major resistance mutations are present for

  8. Clinical course of chronic hepatitis B patients receiving nucleos(t)ide analogues after virological breakthrough during monotherapy with lamivudine.

    PubMed

    De Francesco, Maria Antonia; Gargiulo, Franco; Spinetti, Angiola; Zaltron, Serena; Giagulli, Cinzia; Caccuri, Francesca; Castelli, Francesco; Caruso, Arnaldo

    2015-01-01

    Little is known about the optimal management of patients with chronic hepatitis B (CHB) who develop drug resistance. The aim of this study was to investigate the effectiveness of different drug regimens in chronically HBV-infected patients. HBV viral load was determined using a bDNA assay and the substitutions in HBV-DNA were studied by polymerase sequencing test. The study involved 38 patients who experienced a therapeutic failure to lamivudine (LAM). The sequential treatments used were: LAM + adefovir (ADV), LAM + tenofovir (TDF), entecavir (ETV) monotherapy, ADV monotherapy and TDF monotherapy. Similar activity against HBV replication was observed with all drug regimens. Of the patients treated with LAM, 44% developed resistance mutations. The rt M204I mutation was observed more frequently. Sequential ADV add-on LAM and TDF therapy induced the appearance of resistance in 3/18 (16.6%) and in 1/8 (5.5%) treated patients, respectively. Genotype D was the most prevalent (78.9%), followed by genotype A (13%), genotype E (5.2%) and genotype C (2.6%). Our study showed that baseline serum HBV DNA is an important predictor of virologic response and that virologic breakthrough is significantly associated with the insurgence of genotypic resistance.

  9. The influence of anti-HBc status on the sustained virological response rate in HCV-infected patients treated with pegylated interferon alfa 2 and ribavirin

    PubMed Central

    Simon, Krzysztof A; Serafińska, Sylwia; Janocha-Litwin, Justyna; Pazgan-Simon, Monika; Madej, Grzegorz

    2016-01-01

    Aim of the study To determine the influence of HBsAg and HBeAg negative but anti-HBc positive status on the sustained virological response (SVR) rate in HCV-infected patients treated with pegylated interferon alfa 2 (Peg-IFNα-2) and ribavirin (RBV). Material and methods The study was based on the retrospective analysis of medical records of HCV-infected patients who started Peg-IFNα and RBV treatment between 1 January 2011 and 31 December 2013 at the 1st and 2nd Department of Infectious Diseases of the Regional Hospital in Wrocław, Poland. Results Among 240 patients included in the analysis 99 were anti-HBc positive and 141 anti-HBc negative. In the genotype 1, anti-HBc positive group the SVR rate was 47% and in the anti-HBc negative group it was 42.7% (p = 0.591). In the genotype 3, anti-HBc positive group the SVR rate was 60% and in anti-HBc negative patients it was 63.2% (p = 0.79). Differences in SVR rates between anti-HBc positive and negative groups were not statistically significant. None of the anti-HBc positive patients developed reactivation of HBV infection during or in the 24 weeks following the end of treatment. Conclusions Anti-HBc determination does not seem to be useful in predicting treatment outcome of conventional Peg-IFNα/RBV therapy in patients infected with HCV genotypes 1 and 3. PMID:28856281

  10. Clinical and virologic follow-up in perinatally HIV-1-infected children and adolescents in Madrid with triple-class antiretroviral drug-resistant viruses.

    PubMed

    Rojas Sánchez, P; de Mulder, M; Fernandez-Cooke, E; Prieto, L; Rojo, P; Jiménez de Ory, S; José Mellado, M; Navarro, M; Tomas Ramos, J; Holguín, Á

    2015-06-01

    Drug resistance mutations compromise the success of antiretroviral treatment in human immunodeficiency virus type 1 (HIV-1)-infected children. We report the virologic and clinical follow-up of the Madrid cohort of perinatally HIV-infected children and adolescents after the selection of triple-class drug-resistant mutations (TC-DRM). We identified patients from the cohort carrying HIV-1 variants with TC-DRM to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors and protease inhibitors according to IAS-USA-2013. We recovered pol sequences or resistance profiles from 2000 to 2011 and clinical-immunologic-virologic data from the moment of TC-DRM detection until December 2013. Viruses harbouring TC-DRM were observed in 48 (9%) of the 534 children and adolescents from 2000 to 2011, rising to 24.4% among those 197 with resistance data. Among them, 95.8% were diagnosed before 2003, 91.7% were Spaniards, 89.6% carried HIV-1-subtype B and 75% received mono/dual therapy as first regimen. The most common TC-DRM present in ≥50% of them were D67NME, T215FVY, M41L and K103N (retrotranscriptase) and L90M (protease). The susceptibility to darunavir, tipranavir, etravirine and rilpivirine was 67.7%, 43.7%, 33.3% and 33.3%, respectively, and all reported high resistance to didanosine, abacavir and nelfinavir. Despite the presence of HIV-1 resistance mutations to the three main antiretroviral families in our paediatric cohort, some drugs maintained their susceptibility, mainly the new protease inhibitors (tipranavir and darunavir) and nonnucleoside reverse transcriptase inhibitors (etravirine and rilpivirine). These data will help to improve the clinical management of HIV-infected children with triple resistance in Spain.

  11. Clinical Outcome of HIV-Infected Patients with Sustained Virologic Response to Antiretroviral Therapy: Long-Term Follow-Up of a Multicenter Cohort

    PubMed Central

    Gutierrez, Félix; Padilla, Sergio; Masiá, Mar; Iribarren, José A.; Moreno, Santiago; Viciana, Pompeyo; Muñoz, Leopoldo; Sirvent, José L. Gómez; Vidal, Francesc; López-Aldeguer, José; Blanco, José R.; Leal, Manuel; Rodríguez-Arenas, María Angeles; Hoyos, Santiago Perez

    2006-01-01

    Background Limited information exists on long-term prognosis of patients with sustained virologic response to antiretroviral therapy. We aimed to assess predictors of unfavorable clinical outcome in patients who maintain viral suppression with HAART. Methods Using data collected from ten clinic-based cohorts in Spain, we selected all antiretroviral-naive adults who initiated HAART and maintained plasma HIV-1 RNA levels <500 copies/mL throughout follow-up. Factors associated with disease progression were determined by Cox proportional-hazards models. Results Of 2,613 patients who started HAART, 757 fulfilled the inclusion criteria. 61% of them initiated a protease inhibitor-based HAART regimen, 29.7% a nonnucleoside reverse-transcriptase inhibitor-based regimen, and 7.8% a triple-nucleoside regimen. During 2,556 person-years of follow-up, 22 (2.9%) patients died (mortality rate 0.86 per 100 person-years), and 40 (5.3%) died or developed a new AIDS-defining event. The most common causes of death were neoplasias and liver failure. Mortality was independently associated with a CD4-T cell response <50 cells/L after 12 months of HAART (adjusted hazard ratio [AHR], 4.26 [95% confidence interval {CI}, 1.68–10.83]; P = .002), and age at initiation of HAART (AHR, 1.06 per year; 95% CI, 1.02–1.09; P = .001). Initial antiretroviral regimen chosen was not associated with different risk of clinical progression. Conclusions Patients with sustained virologic response on HAART have a low mortality rate over time. Long-term outcome of these patients is driven by immunologic response at the end of the first year of therapy and age at the time of HAART initiation, but not by the initial antiretroviral regimen selected. PMID:17183720

  12. CD127 Expression, Exhaustion Status and Antigen Specific Proliferation Predict Sustained Virologic Response to IFN in HCV/HIV Co-Infected Individuals

    PubMed Central

    Kared, Hassen; Saeed, Sahar; Klein, Marina B.; Shoukry, Naglaa H.

    2014-01-01

    Hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in the HIV co-infected population. Interferon-alpha (IFN-α) remains a major component of anti-HCV therapy despite its deleterious effects on the immune system. Furthermore, IFN-α was recently shown to diminish the size of the latent HIV reservoir. The objectives of this study were to monitor the impact of IFN-α on T cell phenotype and proliferation of HIV and HCV-specific T cells during IFN therapy, and to identify immune markers that can predict the response to IFN in HICV/HIV co-infected patients. We performed longitudinal analyses of T cell numbers, phenotype and function in co-infected patients undergoing IFN-α therapy with different outcomes including IFN-α non-responders (NR) (n = 9) and patients who achieved sustained virologic response (SVR) (n = 19). We examined the expression of activation (CD38, HLA-DR), functional (CD127) and exhaustion markers (PD1, Tim-3, CD160 and CD244) on total CD4 and CD8 T cells before, during and after therapy. In addition, we examined the HIV- and HCV-specific proliferative responses against HIV-p24 and HCV-NS3 proteins. Frequencies of CD127+ CD4 T cells were higher in SVR than in NR patients at baseline. An increase in CD127 expression on CD8 T cells was observed after IFN-α therapy in all patients. In addition, CD8 T cells from NR patients expressed a higher exhaustion status at baseline. Finally, SVR patients exhibited higher proliferative response against both HIV and HCV antigens at baseline. Altogether, SVR correlated with higher expression of CD127, lower T cell exhaustion status and better HIV and HCV proliferative responses at baseline. Such factors might be used as non-invasive methods to predict the success of IFN–based therapies in co-infected individuals. PMID:25007250

  13. Clinical trial methodology and clinical cohorts: the importance of complete follow-up in trials evaluating the virological efficacy of anti-HIV medicines.

    PubMed

    Kirk, Ole; Lundgren, Jens D

    2004-02-01

    It has been common practice in randomized trials of HIV medicines to classify switches away from the original therapy as failures in analyses of virological effect, in line with an HIV-RNA measurement above a given level of quantification. This approach precludes the ability to identify the possible effects of a given therapy on those of a subsequent therapy. This review explores whether there have been changes in the reporting of randomized trials since the importance of continuous follow-up throughout the study period was initially raised 2 years ago. Follow-up is still likely to be discontinued at a premature switch from study medication in a large number of the randomized trials published in 2002-2003. However, some studies, all initiated by investigators, did follow patients throughout the study period. In three of the studies, the proportions of patients with virological failure assessed with and without data after the premature discontinuation of randomized therapy could be elicited. Substantial differences were seen in the comparisons of two highly active antiretroviral therapy regimens according to the choice of analytical approach. In all three studies significant differences were observed between the regimens according to one approach, but not to the other. The notation of treatment switch equals failure leads to an imprecise measurement of virological effect, and complete follow-up throughout the study period should be strongly encouraged, thus enabling several supplementary analyses of the virological effect of the treatment strategies being compared.

  14. The clinical impact of continuing to prescribe antiretroviral therapy in patients with advanced AIDS who manifest no virologic or immunologic benefit.

    PubMed

    Wohl, David A; Kendall, Michelle A; Feinberg, Judith; Alston-Smith, Beverly; Owens, Susan; Chafey, Suzette; Marco, Michael; Maxwell, Sharon; Benson, Constance; Keiser, Philip; van der Horst, Charles; Jacobson, Mark A

    2013-01-01

    Despite the efficacy and tolerability of modern antiretroviral therapy (ART), many patients with advanced AIDS prescribed these regimens do not achieve viral suppression or immune reconstitution as a result of poor adherence, drug resistance, or both. The clinical outcomes of continued ART prescription for such patients have not been well characterized. We examined the causes and predictors of all-cause mortality, AIDS-defining conditions, and serious non-AIDS-defining events among a cohort of participants in a clinical trial of pre-emptive therapy for CMV disease. We focused on participants who, despite ART had failed to achieve virologic suppression and substantive immune reconstitution. 233 ART-receiving participants entered with a median baseline CD4+ T cell count of 30/mm(3) and plasma HIV RNA of 5 log10 copies/mL. During a median 96 weeks of follow-up, 24.0% died (a mortality rate of 10.7/100 patient-years); 27.5% reported a new AIDS-defining condition, and 22.3% a new serious non-AIDS event. Of the deaths, 42.8% were due to an AIDS-defining condition, 44.6% were due to a non-AIDS-defining condition, and 12.5% were of unknown etiology. Decreased risk of mortality was associated with baseline CD4+ T cell count ≥25/mm(3) and lower baseline HIV RNA. Among patients with advanced AIDS prescribed modern ART who achieve neither virologic suppression nor immune reconstitution, crude mortality percentages appear to be lower than reported in cohorts of patients studied a decade earlier. Also, in contrast to the era before modern ART became available, nearly half of the deaths in our modern-era study were caused by serious non-AIDS-defining events. Even among the most advanced AIDS patients who were not obtaining apparent immunologic and virologic benefit from ART, continued prescription of these medications appears to alter the natural history of AIDS--improving survival and shifting the causes of death from AIDS- to non-AIDS-defining conditions.

  15. Pretreatment HIV Drug Resistance and HIV-1 Subtype C Are Independently Associated With Virologic Failure: Results From the Multinational PEARLS (ACTG A5175) Clinical Trial.

    PubMed

    Kantor, Rami; Smeaton, Laura; Vardhanabhuti, Saran; Hudelson, Sarah E; Wallis, Carol L; Tripathy, Srikanth; Morgado, Mariza G; Saravanan, Shanmugham; Balakrishnan, Pachamuthu; Reitsma, Marissa; Hart, Stephen; Mellors, John W; Halvas, Elias; Grinsztejn, Beatriz; Hosseinipour, Mina C; Kumwenda, Johnstone; La Rosa, Alberto; Lalloo, Umesh G; Lama, Javier R; Rassool, Mohammed; Santos, Breno R; Supparatpinyo, Khuanchai; Hakim, James; Flanigan, Timothy; Kumarasamy, Nagalingeswaran; Campbell, Thomas B; Eshleman, Susan H

    2015-05-15

    Evaluation of pretreatment HIV genotyping is needed globally to guide treatment programs. We examined the association of pretreatment (baseline) drug resistance and subtype with virologic failure in a multinational, randomized clinical trial that evaluated 3 antiretroviral treatment (ART) regimens and included resource-limited setting sites. Pol genotyping was performed in a nested case-cohort study including 270 randomly sampled participants (subcohort), and 218 additional participants failing ART (case group). Failure was defined as confirmed viral load (VL) >1000 copies/mL. Cox proportional hazards models estimated resistance-failure association. In the representative subcohort (261/270 participants with genotypes; 44% women; median age, 35 years; median CD4 cell count, 151 cells/µL; median VL, 5.0 log10 copies/mL; 58% non-B subtypes), baseline resistance occurred in 4.2%, evenly distributed among treatment arms and subtypes. In the subcohort and case groups combined (466/488 participants with genotypes), used to examine the association between resistance and treatment failure, baseline resistance occurred in 7.1% (9.4% with failure, 4.3% without). Baseline resistance was significantly associated with shorter time to virologic failure (hazard ratio [HR], 2.03; P = .035), and after adjusting for sex, treatment arm, sex-treatment arm interaction, pretreatment CD4 cell count, baseline VL, and subtype, was still independently associated (HR, 2.1; P = .05). Compared with subtype B, subtype C infection was associated with higher failure risk (HR, 1.57; 95% confidence interval [CI], 1.04-2.35), whereas non-B/C subtype infection was associated with longer time to failure (HR, 0.47; 95% CI, .22-.98). In this global clinical trial, pretreatment resistance and HIV-1 subtype were independently associated with virologic failure. Pretreatment genotyping should be considered whenever feasible. NCT00084136. © The Author 2015. Published by Oxford University Press on behalf of

  16. RNA and DNA bacteriophages as molecular diagnosis controls in clinical virology: a comprehensive study of more than 45,000 routine PCR tests.

    PubMed

    Ninove, Laetitia; Nougairede, Antoine; Gazin, Celine; Thirion, Laurence; Delogu, Ilenia; Zandotti, Christine; Charrel, Remi N; De Lamballerie, Xavier

    2011-02-09

    Real-time PCR techniques are now commonly used for the detection of viral genomes in various human specimens and require for validation both external and internal controls (ECs and ICs). In particular, ICs added to clinical samples are necessary to monitor the extraction, reverse transcription, and amplification steps in order to detect false-negative results resulting from PCR-inhibition or errors in the technical procedure. Here, we performed a large scale evaluation of the use of bacteriophages as ICs in routine molecular diagnosis. This allowed to propose simple standardized procedures (i) to design specific ECs for both DNA and RNA viruses and (ii) to use T4 (DNA) or MS2 (RNA) phages as ICs in routine diagnosis. Various technical formats for using phages as ICs were optimised and validated. Subsequently, T4 and MS2 ICs were evaluated in routine real-time PCR or RT-PCR virological diagnostic tests, using a series of 8,950 clinical samples (representing 36 distinct specimen types) sent to our laboratory for the detection of a variety of DNA and RNA viruses. The frequency of inefficient detection of ICs was analyzed according to the nature of the sample. Inhibitors of enzymatic reactions were detected at high frequency in specific sample types such as heparinized blood and bone marrow (>70%), broncho-alveolar liquid (41%) and stools (36%). The use of T4 and MS2 phages as ICs proved to be cost-effective, flexible and adaptable to various technical procedures of real-time PCR detection in virology. It represents a valuable strategy for enhancing the quality of routine molecular diagnosis in laboratories that use in-house designed diagnostic systems, which can conveniently be associated to the use of specific synthetic ECs. The high rate of inhibitors observed in a variety of specimen types should stimulate the elaboration of improved technical protocols for the extraction and amplification of nucleic acids.

  17. Clinical and Virologic Outcomes After Changes in First Antiretroviral Regimen at 7 Sites in the Caribbean, Central and South America Network.

    PubMed

    Wolff, Marcelo; Shepherd, Bryan E; Cortés, Claudia; Rebeiro, Peter; Cesar, Carina; Wagner Cardoso, Sandra; Pape, Jean W; Padgett, Denis; Sierra-Madero, Juan; Echevarria, Juan; McGowan, Catherine C

    2016-01-01

    HIV-infected persons in resource-limited settings may experience high rates of antiretroviral therapy (ART) change, particularly because of toxicity or other nonfailure reasons. Few reports address patient outcomes after these modifications. HIV-infected adults from the 7 Caribbean, Central and South America network clinical cohorts who modified >1 drug from the first ART regimen (ART-1) for any reason thereby starting a second regimen (ART-2) were included. We assessed cumulative incidence of, and factors associated with, death, virologic failure (VF), and regimen change after starting ART-2. Five thousand five hundred sixty-five ART-naive highly active ART initiators started ART-2 after a median of 9.8 months on ART-1; 39% changed to ART-2 because of toxicity and 11% because of failure. Median follow-up after starting ART-2 was 2.9 years; 45% subsequently modified ART-2. Cumulative incidences of death at 1, 3, and 5 years after starting ART-2 were 5.1%, 8.4%, and 10.5%, respectively. In adjusted analyses, death was associated with older age, clinical AIDS, lower CD4 at ART-2 start, earlier calendar year, and starting ART-2 because of toxicity (adjusted hazard ratio = 1.5 vs. failure, 95% confidence interval: 1.0 to 2.1). Cumulative incidences of VF after 1, 3, and 5 years were 9%, 19%, and 25%. In adjusted analyses, VF was associated with younger age, earlier calendar year, lower CD4 at the start of ART-2, and starting ART-2 because of failure (adjusted hazard ratio = 2.1 vs. toxicity, 95% confidence interval: 1.5 to 2.8). Among patients modifying the first ART regimen, risks of subsequent modifications, mortality, and virologic failure were high. Access to improved antiretrovirals in the region is needed to improve initial treatment success.

  18. High rates of virological failure and drug resistance in perinatally HIV-1-infected children and adolescents receiving lifelong antiretroviral therapy in routine clinics in Togo

    PubMed Central

    Salou, Mounerou; Dagnra, Anoumou Y; Butel, Christelle; Vidal, Nicole; Serrano, Laetitia; Takassi, Elom; Konou, Abla A; Houndenou, Spero; Dapam, Nina; Singo-Tokofaï, Assetina; Pitche, Palokinam; Atakouma, Yao; Prince-David, Mireille; Delaporte, Eric; Peeters, Martine

    2016-01-01

    their current ART regimen. Conclusions Our study provided important information on virological outcome on lifelong ART in perinatally HIV-1-infected children and adolescents who were still on ART and continued to attend antiretroviral (ARV) clinics for follow-up visits. Actual conditions for scaling up and monitoring lifelong ART in children in resource-limited countries can have dramatic long-term outcomes and illustrate that paediatric ART receives inadequate attention. PMID:27125320

  19. Clinical status of benzoporphyrin derivative

    NASA Astrophysics Data System (ADS)

    Levy, Julia G.; Chan, Agnes H.; Strong, H. Andrew

    1996-01-01

    Benzoporphyrin derivative monoacid ring A (BPD) is currently in Phase II clinical trials for the treatment of cutaneous malignancies (basal cell carcinoma and cutaneous metastases) and psoriasis. Results to date suggest that this photosensitizer has potential in both of these areas. Recently, a clinical trial with BPD was initiated for the treatment of age related macular degeneration, a neovascular condition in the eye which leads to blindness. BPD is a lipophilic photosensitizer which is rapidly taken up by activated cells and the vascular endothelium of neovasculature. The PDT effects seen with BPD appear to be a combination of vascular occlusion and direct killing of target cells. Since many diseases involve either activated cells and/or neovasculature, PDT with photosensitizer with characteristics like those of BPD, has applications far wider than oncology. A new area of interest involving photosensitizers is that of immune modulation. A number of photosensitizers have been shown to effect immune modulation in animal models of immune dysfunction including autoimmunity (rheumatoid arthritis, lupus), cutaneous hypersensitivity and allografts. BPD and PHOTOFRINR have both been shown to be effective in ameliorating arthritic symptoms in a number of animal models. The mechanisms by which immune modulation is affected in these studies still remains to be resolved.

  20. Effect of sustained virological response on long-term clinical outcome in 113 patients with compensated hepatitis C-related cirrhosis treated by interferon alpha and ribavirin

    PubMed Central

    Braks, Roland El; Ganne-Carrié, Nathalie; Fontaine, Hélène; Paries, Jacques; Grando-Lemaire, Véronique; Beaugrand, Michel; Pol, Stanislas; Trinchet, Jean-Claude

    2007-01-01

    AIM: To assess the long-term clinical benefit of sustained virological response (SVR) in patients with hepatitis C virus (HCV) cirrhosis treated by antiviral therapy using mostly ribavirin plus interferon either standard or pegylated. METHODS: One hundred and thirteen patients with uncomplicated HCV biopsy-proven cirrhosis, treated by at least one course of antiviral treatment ≥ 3 mo and followed ≥ 30 mo were included. The occurrence of clinical events [hepatocellular carcinoma (HCC), decompensation and death] was compared in SVR and non SVR patients. RESULTS: Seventy eight patients received bitherapy and 63 had repeat treatments. SVR was achieved in 37 patients (33%). During a mean follow-up of 7.7 years, clinical events occurred more frequently in non SVR than in SVR patients, with a significant difference for HCC (24/76 vs 1/37, P = 0.01). No SVR patient died while 20/76 non-SVR did (P = 0.002), mainly in relation to HCC (45%). CONCLUSION: In patients with HCV-related cirrhosis, SVR is associated with a significant decrease in the incidence of HCC and mortality during a follow-up period of 7.7 years. This result is a strong argument to perform and repeat antiviral treatments in patients with compensated cirrhosis. PMID:17948941

  1. Clinical and Virologic Manifestations of Primary Epstein-Barr Virus (EBV) Infection in Kenyan Infants Born to HIV-Infected Women

    PubMed Central

    Slyker, Jennifer A.; Casper, Corey; Tapia, Kenneth; Richardson, Barbra; Bunts, Lisa; Huang, Meei-Li; Maleche-Obimbo, Elizabeth; Nduati, Ruth; John-Stewart, Grace

    2013-01-01

    Background. Human immunodeficiency virus (HIV) infection is a risk factor for Epstein-Barr virus (EBV)–associated lymphomas. Characterizing primary infection may elucidate risk factors for malignancy. Methods. To describe clinical and virologic manifestations of primary EBV infection among infants born to HIV-infected women, specimens were utilized from a cohort study conducted in Nairobi, Kenya. HIV and EBV viral loads were measured serially in plasma. EBV serology was performed on EBV DNA–negative infants. Monthly clinical examinations were performed by pediatricians. Results. The probability of EBV infection by 1 year of age was .78 (95% CI, .67–.88) in HIV-infected and .49 (95% CI, .35–.65) in HIV-uninfected infants (P < .0001). At 2 years, probability of EBV infection was .96 (95% CI, .89–.99) in HIV-infected infants. Peak EBV loads were higher in HIV-infected versus HIV-uninfected infants (median 2.6 vs 2.1 log10 copies/mL; P < .0001). The majority of HIV-infected infants had detectable EBV DNA for >3 months (79%). Primary EBV infection was associated with cough, fever, otitis media, pneumonia, hepatomegaly, splenomegaly, and hospitalization in HIV-infected infants; conjunctivitis and rhinorrhea in HIV-uninfected infants. Conclusions. EBV infection occurs early in infants born to HIV-infected women. HIV infection was associated with more frequent and higher quantity EBV DNA detection. PMID:23493724

  2. Clinical and virologic manifestations of primary Epstein-Barr virus (EBV) infection in Kenyan infants born to HIV-infected women.

    PubMed

    Slyker, Jennifer A; Casper, Corey; Tapia, Kenneth; Richardson, Barbra; Bunts, Lisa; Huang, Meei-Li; Maleche-Obimbo, Elizabeth; Nduati, Ruth; John-Stewart, Grace

    2013-06-15

    Human immunodeficiency virus (HIV) infection is a risk factor for Epstein-Barr virus (EBV)-associated lymphomas. Characterizing primary infection may elucidate risk factors for malignancy. To describe clinical and virologic manifestations of primary EBV infection among infants born to HIV-infected women, specimens were utilized from a cohort study conducted in Nairobi, Kenya. HIV and EBV viral loads were measured serially in plasma. EBV serology was performed on EBV DNA-negative infants. Monthly clinical examinations were performed by pediatricians. The probability of EBV infection by 1 year of age was .78 (95% CI, .67-.88) in HIV-infected and .49 (95% CI, .35-.65) in HIV-uninfected infants (P < .0001). At 2 years, probability of EBV infection was .96 (95% CI, .89-.99) in HIV-infected infants. Peak EBV loads were higher in HIV-infected versus HIV-uninfected infants (median 2.6 vs 2.1 log10 copies/mL; P < .0001). The majority of HIV-infected infants had detectable EBV DNA for >3 months (79%). Primary EBV infection was associated with cough, fever, otitis media, pneumonia, hepatomegaly, splenomegaly, and hospitalization in HIV-infected infants; conjunctivitis and rhinorrhea in HIV-uninfected infants. EBV infection occurs early in infants born to HIV-infected women. HIV infection was associated with more frequent and higher quantity EBV DNA detection.

  3. Clinical Model for Predicting Hepatocellular Carcinomas in Patients with Post-Sustained Virologic Responses of Chronic Hepatitis C: A Case Control Study

    PubMed Central

    Zeng, Qing-Lei; Li, Bing; Zhang, Xue-Xiu; Chen, Yan; Fu, Yan-Ling; Lv, Jun; Liu, Yan-Min; Yu, Zu-Jiang

    2016-01-01

    Background/Aims No clinical model exists to predict the occurrence of hepatocellular carcinoma in sustained virologic response-achieving (HCC after SVR) patients with chronic hepatitis C (CHC). Methods We performed a case-control study using a clinical database to research the risk factors for HCC after SVR. A predictive model based on risk factors was established, and the area under the receiver operating characteristic curve (AUC) was calculated. Results In the multivariate model, an initial diagnosis of compensated cirrhosis and post-SVR albumin reductions of 1 g/L were associated with 21.7-fold (95% CI, 4.2 to 112.3; p<0.001) and 1.3-fold (95% CI, 1.1 to 1.7; p=0.004) increases in the risk of HCC after SVR, respectively. A predictive model based on an initial diagnosis of compensated cirrhosis (yes, +1; no, 0) and post-SVR albumin ≤36.0 g/L (yes, +1; not, 0) predicted the occurrence of HCC after SVR with a cutoff value of >0, an AUC of 0.880, a sensitivity of 0.833, a specificity of 0.896, and a negative predictive value of 0.956. Conclusions An initial diagnosis of compensated cirrhosis combined with a post-SVR albumin value of ≤36.0 g/L predicts the occurrence of HCC after SVR in patients with CHC. PMID:27257023

  4. Epidemiological, Clinical and Virological Characteristics of Influenza B Virus from Patients at the Hospital Tertiary Care Units in Bangkok during 2011-2014.

    PubMed

    Horthongkham, Navin; Athipanyasilp, Niracha; Pattama, Archiraya; Kaewnapan, Bualan; Sornprasert, Suthatta; Srisurapanont, Surangrat; Kantakamalakul, Wannee; Amaranond, Palanee; Sutthent, Ruengpung

    2016-01-01

    Influenza B virus, which causes acute respiratory infections, has increased in prevalence in recent years. Based on the nucleotide sequence of the hemagglutinin (HA) gene, influenza B virus can be divided into two lineages, Victoria and Yamagata, that co-circulate during the influenza season. However, analysis of the potential association between the clinical and virological characteristic and the lineage of influenza B viruses isolated in Thailand was lacking. To investigate influenza B virus genetically and determine its neuraminidase (NA) inhibitor susceptibility phenotype, a total of 6920 nasopharyngeal-wash samples were collected from patients with influenza-like illness between the years 2011 and 2014 and were screened for influenza B virus by real-time PCR. Of these samples, 3.1% (216/6920) were confirmed to contain influenza B viruses, and 110 of these influenza viruses were randomly selected for nucleotide sequence analysis of the HA and NA genes. Phylogenetic analysis of the HA sequences showed clustering into various clades: Yamagata clade 3 (11/110, 10%), Yamagata clade 2 (71/110, 64.5%), and Victoria clade 1 (28/110, 25.5%). The analysis of clinical characteristic demonstrated that the Victoria lineage was significantly associated with the duration of hospitalization, number of deceased cases, pneumonia, secondary bacterial infection and underlying disease. When combined with phylogenetic analysis of the NA sequences, four samples showed viruses with reassortant sequences between the Victoria and Yamagata lineages. Statistical analysis of the clinical outcomes and demographic data for the reassortant strains did not differ from those of the other strains in circulation. Oseltamivir-resistant influenza B viruses were not detected. Our findings indicated the co-circulation of the Victoria and Yamagata lineages over the past four cold seasons in Bangkok. We also demonstrated differences in the clinical symptoms between these lineages.

  5. Characterization of dengue virus infections in a sample of patients suggests unique clinical, immunological, and virological profiles that impact on the diagnosis of dengue and dengue hemorrhagic fever.

    PubMed

    Senaratne, Thamarasi; Wimalaratne, Harith; Alahakoon, D G S; Gunawardane, Nirmali; Carr, Jillian; Noordeen, Faseeha

    2016-10-01

    Dengue virus (DENV) infections are increasing with respect to incidence and severity in the Central Province of Sri Lanka. The objective of this study was to define the clinical, immunological, and virological profiles of patients admitted to the General Hospital, Kandy with clinically apparent dengue. Demographic, clinical, hematological parameters, liver enzymes (ALT and AST), and blood samples were collected from 292 patients with fever <5 days post onset and fulfilling the WHO criteria for the diagnosis of dengue fever/dengue hemorrhagic fever (DF/DHF). Samples were analyzed for, anti-DENV IgM, IgG, and DENV nucleic acid. Myalgia was the commonest complaint by 65% of the patients. Packed cell volume was >45% in 27% of the patients while 42.12% had reduced platelets and 62.67% had reduced white blood cell counts. In contrast to other studies, positive tourniquet test (PTT) and petechiae were not major indicators of DENV infection or severity of the disease. Clinical profiles were significantly different between DF and DHF/DSS and showed many similarities to that reported elsewhere. Altogether, 43 patients (14.73%) were viremic as detected by RT-PCR; 181 patients (62%) were positive for anti-DENV IgM, and 245 (84%) patients were positive for anti-DENV IgG. In combination, anti-DENV IgM and RT-PCR assays detected 224 (77.5%) of DENV infected cases, thus improving the DENV diagnosis rate. Hence, the diagnostic utility of PTT, anti-DENV IgM/IgG serology, or RT-PCR used alone in the early phase of illness is low in Sri Lanka but the diagnostic value can be improved by a combination of serology and RT-PCR. J. Med. Virol. 88:1703-1710, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  6. [Venezuelan Virology Network].

    PubMed

    Añez, Germán

    2005-03-01

    In November 2004, sponsored by the World Bank, the Venezuelan Foundation of Science, Technology and Innovation (Fonacit) and the Venezuelan Institute of Scientific Research (IVIC), delegates from the different virology research groups of the country, met in Caracas-Venezuela, with the aim to establish the "Venezuelan Virology Network". The symposium entitled "Molecular biology applied to virus of health importance in Venezuela", was divided into three areas, including human and animals viruses related to public health: 1) Dengue, others arboviruses and Hemorrhagic Fevers; 2) diarrhea-related and others veterinary viruses and 3) Hepatitis, HIV and others sexually transmitted viruses. This symposium allowed the delegates to evaluate the current strengths, weaknesses and needs of the different laboratories, becoming evident the necessity of developing collaborative work between the groups that share the same interests or lines of research; and also their need to exchange technical resources, human and bibliographical material and consequently, avoiding the duplication of efforts and the unnecessary cost of resources. One of the main strengths of Venezuelan virology is the presence, in most laboratories, of researchers with studies of fourth level and multidisciplinary teams of work. We aspire to achieve the raised objectives in the event, to the benefit of our virology and even more important, of our people.

  7. Impact of an adherence clinic on behavioral outcomes and virologic response in treatment of HIV infection: a prospective, randomized, controlled pilot study.

    PubMed

    Rathbun, R Chris; Farmer, Kevin C; Stephens, Johnny R; Lockhart, Staci M

    2005-02-01

    The aim of this randomized, controlled pilot study was to examine the impact of a pharmacist operated adherence clinic on adherence to highly active antiretroviral therapy (HAART) and viral suppression in patients with HIV over 28 weeks. Consecutive eligible patients initiating HAART at an indigent-care clinic were randomized to an adherence clinic or to standard care (information provided by physician or nurse practitioner) for education and monitoring. Group assignment was stratified before randomization according to regimen complexity and potential tolerability. Adherence (electronic monitoring and patient self-report) and viral load (reverse-transcription polymerase chain reaction) were assessed at weeks 4, 16, and 28. Thirty-three randomized patients (adherence clinic, n = 16; standard care, n = 17) comprised the intent-to-treat population. The groups were well-matched for demographics and antiretroviral regimen. The median age was 38.0 years in both groups. Most patients were male (85%), had previously used HAART (78%), and had an AIDS diagnosis (79%). Mean (SD) adherence at weeks 4, 16, and 28 was 86% (27%), 77% (28%), and 74% (31%) in the adherence clinic group versus 73% (32%), 56% (39%), and 51% (41%) in the standard care group (week-16 difference, 21% [90% CI, 1%-42%]; week-28 difference, 23% [90% CI, 1%-44%]). Sixty-nine percent of patients in the adherence clinic group took their medication on schedule versus 42% in the standard care group (P = 0.025); mean decline in adherence from weeks 4 to 28 was 12% in the adherence clinic group (P = 0.15) versus 22% in the standard care group (P = 0.002). HIV-1 RNA levels were <400 copies/mL at weeks 4, 16, and 28 in 63%, 100%, and 94% of the adherence clinic group and 29% (P = NS), 71% (P = 0.04), and 65% (P = NS) of the standard care group. In this preliminary trial, an adherence clinic model improved adherence to HAART and virologic response over 28 weeks in the patients studied.

  8. First external quality assurance program of the Italian HLA-B*57:01 Network assessing the performance of clinical virology laboratories in HLA-B*57:01 testing.

    PubMed

    Meini, Genny; Dello Russo, Cinzia; Allice, Tiziano; Barresi, Renata; D'Arrigo, Roberta; Falasca, Francesca; Lipsi, Maria Rosaria; Paolucci, Stefania; Zanussi, Stefania; Antonetti, Raffaele; Baldanti, Fausto; Basaglia, Giancarlo; Bruzzone, Bianca; Polilli, Ennio; Ghisetti, Valeria; Pucillo, Leopoldo Paolo; Turriziani, Ombretta; Pirazzoli, Antonella; Navarra, Pierluigi; Zazzi, Maurizio

    2016-05-01

    Since the HLA-B*57:01 allele is strongly associated with abacavir hypersensitivity reaction, testing for the presence of HLA-B*57:01 is mandatory before administration of abacavir. While HLA-B*57:01 testing is usually provided by pharmacogenetics, genetics or blood transfusion services, clinical virology laboratories can be an optimal opportunity for HLA-B*57:01 testing since they receive blood samples for routine HIV monitoring and have the expertise for convenient and less expensive PCR-based point mutation assays. The Italian HLA-B*57:01 Network gathers accredited clinical virology laboratories offering HLA-B*57:01 testing in Italy with the aim to share protocols, test new methods, develop and maintain external quality assurance (EQA) programs. A panel of 9HLA-B*57:01-positive and 16HLA-B*57:01-negative frozen blood samples were blindly distributed to 10 units including 9 clinical virology laboratories and one reference pharmacology laboratory. Each laboratory was free to use its own routine method for DNA extraction and HLA-B*57:01 testing. DNA was extracted by automated workstations in 6 units and by manual spin columns in 4. Eight units used the Duplicα Real Time HLA-B*57:01 kit by Euroclone and two units used two different PCR homemade protocols. All the 10 units correctly identified all the 25 samples. The first HLA-B*57:01 EQA program run in Italy showed that clinical virology units are equipped and proficient for providing HLA-B*57:01 testing by inexpensive assays easy to integrate into their routine. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Evaluation of a quality assurance program for quantitation of human immunodeficiency virus type 1 RNA in plasma by the AIDS Clinical Trials Group virology laboratories.

    PubMed

    Yen-Lieberman, B; Brambilla, D; Jackson, B; Bremer, J; Coombs, R; Cronin, M; Herman, S; Katzenstein, D; Leung, S; Lin, H J; Palumbo, P; Rasheed, S; Todd, J; Vahey, M; Reichelderfer, P

    1996-11-01

    A number of quantitative assays have been developed by using amplification techniques to measure human immunodeficiency virus type 1 RNA in the plasma of infected individuals. The Virology Committee of the AIDS Clinical Trials Group in the Division of AIDS, National Institute of Allergy and Infectious Diseases, has established a quality assurance program (QAP) for quantitative assays of HIV-1 RNA levels in plasma. The primary objective of the QAP was to ascertain that a laboratory could maintain the precision required to have a 90% power to detect a fivefold difference in RNA copy number between two samples in the same batch. To achieve this goal, the QAP required an intra-assay standard deviation of no greater than 0.15 log10 RNA copies per ml. Panels for proficiency testing consisted of coded replicate samples and a common set of standards. To date, 41 laboratories have participated in the program and have used both commercial and in-house assays. We demonstrated that 65% of the laboratories were capable of attaining the necessary level of intra-assay precision. The fitted regressions indicated that the differences among laboratories that used the same kit were generally greater than the differences among population-average regressions for the kits themselves. The use of an external QAP and a common set of standards reduced differences both among laboratories that used the same kit and among laboratories that used different kits. Thus, use of a common set of standards across clinical trial protocols would allow for cross-protocol comparisons.

  10. Clinical and virologic outcomes after changes in first antiretroviral regimen at 7 sites in the Caribbean, Central and South America Network (CCASAnet)

    PubMed Central

    Wolff, Marcelo; Shepherd, Bryan E.; Cortés, Claudia; Rebeiro, Peter; Cesar, Carina; Cardoso, Sandra Wagner; Pape, Jean W.; Padgett, Denis; Sierra-Madero, Juan; Echevarria, Juan; McGowan, Catherine C.

    2015-01-01

    Background HIV-infected persons in lower income countries may experience high rates of antiretroviral therapy (ART) change, particularly due to toxicity or other non-failure reasons. Few reports address patient outcomes after these modifications. Methods HIV-infected adults from 7 Caribbean, Central and South America network (CCASAnet) clinical cohorts who modified > or = 1 drug from first ART regimen (ART-1) for any reason thereby starting a second regimen (ART-2) were included. Results 5,565 ART-naïve HAART initiators started ART-2 after a median of 9.8 months on ART-1; 39% changed to ART-2 due to toxicity and 11% due to failure. Median follow-up after starting ART-2 was 2.9 years; 45% subsequently modified ART-2. Cumulative incidences of death at 1, 3, and 5 years after starting ART-2 were 5.1%, 8.4% and 10.5%, respectively. In adjusted analyses, death was associated with older age, clinical AIDS, lower CD4 at ART-2 start, earlier calendar year, and starting ART-2 because of toxicity (adjusted hazard ratio[aHR]=1.5 vs. failure, 95% confidence interval[CI]=1.0–2.1). Cumulative incidences of VF after 1, 3, and 5 years were 9%, 19%, and 25%. In adjusted analyses, VF was associated with younger age, earlier calendar year, lower CD4 at start of ART-2, and starting ART-2 because of failure (aHR=2.1 vs. toxicity, 95% CI=1.5–2.8). Conclusions Among patients modifying first ART regimen, risks of subsequent modifications, mortality, and virologic failure were high. Access to improved antiretrovirals in the region is needed to improve initial treatment success. PMID:26761273

  11. Standardization of sensitive human immunodeficiency virus coculture procedures and establishment of a multicenter quality assurance program for the AIDS Clinical Trials Group. The NIH/NIAID/DAIDS/ACTG Virology Laboratories.

    PubMed Central

    Hollinger, F B; Bremer, J W; Myers, L E; Gold, J W; McQuay, L

    1992-01-01

    An independent quality assurance program has been established by the Division of AIDS, National Institute of Allergy and Infectious Diseases, for monitoring virologic assays performed by nearly 40 laboratories participating in multicenter clinical trials in the United States. Since virologic endpoints are important in evaluating the timing and efficacy of therapeutic interventions, it is imperative that virologic measurements be accurate and uniform. When the quality assurance program was initially created, fewer than 40% of the laboratories could consistently recover human immunodeficiency virus (HIV) from peripheral blood mononuclear cells (PBMCs) of HIV-infected patients. By comparing coculture procedures in the more competent laboratories with those in laboratories who were struggling to isolate virus, optimal conditions were established and nonessential reagents and practices were eliminated. Changes were rapidly introduced into a laboratory when experience dictated that such modifications would result in a favorable outcome. Isolation of HIV was enhanced by optimizing the numbers and ratios of patient and donor cells used in cultures, by standardizing PBMC separation procedures, by using fresh rather than frozen donor PBMCs, by processing whole blood within 24 h, and by using natural delectinated interleukin 2 instead of recombinant interleukin 2 products in existence at that time. Delays of more than 8 h in the addition of phytohemagglutinin-stimulated donor cells to freshly separated patient PBMCs reduced recovery. Phytohemagglutinin in cocultures and the addition of Polybrene and anti-human alpha interferon to media were not important in HIV isolation. The introduction of a consensus protocol based on this information brought most laboratories quickly into compliance. In addition, monthly monitoring has successfully maintained proficiency among the laboratories, a process that is critical for the scientific integrity of collaborative multicenter trials

  12. Chikungunya fever: a clinical and virological investigation of outpatients on Reunion Island, South-West Indian Ocean.

    PubMed

    Thiberville, Simon-Djamel; Boisson, Veronique; Gaudart, Jean; Simon, Fabrice; Flahault, Antoine; de Lamballerie, Xavier

    2013-01-01

    Chikungunya virus (CHIKV) is responsible for acute febrile polyarthralgia and, in a proportion of cases, severe complications including chronic arthritis. CHIKV has spread recently in East Africa, South-West Indian Ocean, South-Asia and autochthonous cases have been reported in Europe. Although almost all patients are outpatients, medical investigations mainly focused on hospitalised patients. Here, we detail clinico-biological characteristics of Chikungunya (CHIK) outpatients in Reunion Island (2006). 76 outpatients with febrile arthralgia diagnosed within less than 48 hours were included by general practitioners during the CuraChik clinical trial. CHIK was confirmed in 54 patients and excluded in 22. A detailed clinical and biological follow-up was organised, that included analysis of viral intrahost diversity and telephone survey until day 300. The evolution of acute CHIK included 2 stages: the 'viral stage' (day 1-day 4) was associated with rapid decrease of viraemia and improvement of clinical presentation; the 'convalescent stage' (day 5-day 14) was associated with no detectable viraemia but a slower clinical improvement. Women and elderly had a significantly higher number of arthralgia at inclusion and at day 300. Based on the study clinico-biological dataset, scores for CHIK diagnosis in patients with recent febrile acute polyarthralgia were elaborated using arthralgia on hands and wrists, a minor or absent myalgia and the presence of lymphopenia (<1G/L) as major orientation criteria. Finally, we observed that CHIKV intra-host genetic diversity increased over time and that a higher viral amino-acid complexity at the acute stage was associated with increased number of arthralgia and intensity of sequelae at day 300. This study provided a detailed picture of clinico-biological CHIK evolution at the acute phase of the disease, allowed the elaboration of scores to assist CHIK diagnosis and investigated for the first time the impact of viral intra-host genetic

  13. The Epstein-Barr virus in the pathogenesis of posttransplant lymphoproliferative disorders. Clinical, pathologic, and virologic correlation.

    PubMed

    Hanto, D W; Sakamoto, K; Purtilo, D T; Simmons, R L; Najarian, J S

    1981-08-01

    Twelve renal transplant patients with lymphoproliferative disorders (LPDs) were studied. Two clinical patterns were identified: (1) Young patients present with an infectious mononucleosis-like illness with fever, sore throat, and lymphadenopathy soon after transplantation or antirejection therapy. Many organs are ultimately involved, and the clinical course is one of a rapidly fatal LPD. (2) Older patients present a longer time after transplantation with symptoms of solid tumors involving the central nervous system, oropharynx, liver, or small bowel. The clinical course is slower, but it is progressive and fatal. Morphologically these LPDs can all be classified as polymorphic diffuse B-cell hyperplasia (PDBH) or polymorphic diffuse B-cell lymphoma (PBL). Cell marker studies in four patients demonstrated a polyclonal B-cell proliferation. Transition from a polyclonal B-cell proliferation to a monoclonal tumor may occur. Epstein-Barr virus (EBV) specific antibody titers, anticomplement immunofluorescence staining of tumors for the presence of the Epstein-Barr nuclear antigen (EBNA), and EBV complementary ribonucleic acid (cRNA)/deoxyribonucleic acid (DNA) hybridization and vDNA/DNA reassociation analysis implicate EBV as the probable etiologic agent in these disorders. Successful management of these lethal LPDs may depend on discontinuation of immunosuppression and removal of the allograft. Antiviral therapy, however, may prove to be useful.

  14. The clinical and virological features of the first imported case causing MERS-CoV outbreak in South Korea, 2015.

    PubMed

    Lee, Ji Yeon; Kim, You-Jin; Chung, Eun Hee; Kim, Dae-Won; Jeong, Ina; Kim, Yeonjae; Yun, Mi-Ran; Kim, Sung Soon; Kim, Gayeon; Joh, Joon-Sung

    2017-07-14

    In 2015, the largest outbreak of Middle East respiratory syndrome coronavirus (MERS-CoV) infection outside the Middle East occurred in South Korea. We summarized the epidemiological, clinical, and laboratory findings of the first Korean case of MERS-CoV and analyzed whole-genome sequences of MERS-CoV derived from the patient. A 68-year-old man developed fever and myalgia 7 days after returning to Korea, following a 10-day trip to the Middle East. Before diagnosis, he visited 4 hospitals, potentially resulting in secondary transmission to 28 patients. On admission to the National Medical Center (day 9, post-onset of clinical illness), he presented with drowsiness, hypoxia, and multiple patchy infiltrations on the chest radiograph. He was intubated (day 12) because of progressive acute respiratory distress syndrome (ARDS) and INF-α2a and ribavirin treatment was commenced. The treatment course was prolonged by superimposed ventilator associated pneumonia. MERS-CoV PCR results converted to negative from day 47 and the patient was discharged (day 137), following rehabilitation therapy. The complete genome sequence obtained from a sputum sample (taken on day 11) showed the highest sequence similarity (99.59%) with the virus from an outbreak in Riyadh, Saudi Arabia, in February 2015. The first case of MERS-CoV infection had high transmissibility and was associated with a severe clinical course. The patient made a successful recovery after early treatment with antiviral agents and adequate supportive care. This first case in South Korea became a super-spreader because of improper infection control measures, rather than variations of the virus.

  15. Chikungunya Fever: A Clinical and Virological Investigation of Outpatients on Reunion Island, South-West Indian Ocean

    PubMed Central

    Thiberville, Simon-Djamel; Boisson, Veronique; Gaudart, Jean; Simon, Fabrice; Flahault, Antoine; de Lamballerie, Xavier

    2013-01-01

    Background Chikungunya virus (CHIKV) is responsible for acute febrile polyarthralgia and, in a proportion of cases, severe complications including chronic arthritis. CHIKV has spread recently in East Africa, South-West Indian Ocean, South-Asia and autochthonous cases have been reported in Europe. Although almost all patients are outpatients, medical investigations mainly focused on hospitalised patients. Methodology/Principal Findings Here, we detail clinico-biological characteristics of Chikungunya (CHIK) outpatients in Reunion Island (2006). 76 outpatients with febrile arthralgia diagnosed within less than 48 hours were included by general practitioners during the CuraChik clinical trial. CHIK was confirmed in 54 patients and excluded in 22. A detailed clinical and biological follow-up was organised, that included analysis of viral intrahost diversity and telephone survey until day 300. The evolution of acute CHIK included 2 stages: the ‘viral stage’ (day 1–day 4) was associated with rapid decrease of viraemia and improvement of clinical presentation; the ‘convalescent stage’ (day 5–day 14) was associated with no detectable viraemia but a slower clinical improvement. Women and elderly had a significantly higher number of arthralgia at inclusion and at day 300. Based on the study clinico-biological dataset, scores for CHIK diagnosis in patients with recent febrile acute polyarthralgia were elaborated using arthralgia on hands and wrists, a minor or absent myalgia and the presence of lymphopenia (<1G/L) as major orientation criteria. Finally, we observed that CHIKV intra-host genetic diversity increased over time and that a higher viral amino-acid complexity at the acute stage was associated with increased number of arthralgia and intensity of sequelae at day 300. Conclusions/Significance This study provided a detailed picture of clinico-biological CHIK evolution at the acute phase of the disease, allowed the elaboration of scores to assist CHIK

  16. Clinical, epidemiological and virological characteristics of the first detected human case of avian influenza A(H5N6) virus.

    PubMed

    Zhang, Rusheng; Chen, Tianmu; Ou, Xinhua; Liu, Ruchun; Yang, Yang; Ye, Wen; Chen, Jingfang; Yao, Dong; Sun, Biancheng; Zhang, Xixing; Zhou, Jianxiang; Sun, Yan; Chen, Faming; Wang, Shi-Ping

    2016-06-01

    A human infection with novel avian influenza A H5N6 virus emerged in Changsha city, China in February, 2014. This is the first detected human case among all human cases identified from 2014 to early 2016. We obtained and summarized clinical, epidemiological, and virological data from this patient. Complete genome of the virus was determined and compared to other avian influenza viruses via the construction of phylogenetic trees using the neighbor-joining approach. A girl aged five and half years developed fever and mild respiratory symptoms on Feb. 16, 2014 and visited hospital on Feb. 17. Throat swab specimens were obtained from the patient and a novel reassortant avian influenza A H5N6 virus was detected. All eight viral gene segments were of avian origin. The hemagglutinin (HA) and neuraminidase (NA) gene segments were closely related to A/duck/Sichuan/NCXN11/2014(H5N1) and A/chicken/Jiangxi/12782/2014(H10N6) viruses, respectively. The six internal genes were homologous to avian influenza A (H5N2) viruses isolated in duck from Jiangxi in China. This H5N6 virus has not gained genetic mutations necessary for human infection and was suggested to be sensitive to neuraminidase inhibitors, but resistant to adamantanes. Epidemiological investigation of the exposure history of the patient found that a live poultry market could be the source place of infection and the incubation period was 2-5days. This novel reassortant Avian influenza A(H5N6) virus could be low pathogenic in humans. The prevalence and genetic evolution of this virus should be closely monitored. Copyright © 2016 Elsevier B.V. All rights reserved.

  17. Clinical and virological improvement of hepatitis B virus-related or hepatitis C virus-related chronic hepatitis with concomitant hepatitis A virus infection.

    PubMed

    Sagnelli, Evangelista; Coppola, Nicola; Pisaturo, Mariantonietta; Pisapia, Raffaella; Onofrio, Mirella; Sagnelli, Caterina; Catuogno, Antonio; Scolastico, Carlo; Piccinino, Felice; Filippini, Pietro

    2006-06-01

    We evaluated the clinical and virological characteristics of hepatitis A virus infection in persons concomitantly infected with hepatitis B virus (HBV) or hepatitis C virus (HCV). We enrolled 21 patients with acute hepatitis A and chronic hepatitis with no sign of liver cirrhosis, 13 patients who were positive for hepatitis B surface antigen (case B group), 8 patients who were anti-HCV positive (case C group), and 21 patients with acute hepatitis A without a preexisting liver disease (control A group). Two control groups of patients with chronic hepatitis B (control B group) or C (control C group) were also chosen. All control groups were pair-matched by age and sex with the corresponding case group. Fulminant hepatitis A was never observed, and hepatitis A had a severe course in 1 patient in the case B group and in 1 patient in the control A group. Both patients recovered. On admission, HBV DNA was detected in 1 patient in the case B group (7.7%) and in 13 patients (50%) in the control B group; HCV RNA was found in no patient in the case C group and in 16 patients (81.2%) in the control C group. Of 9 patients in the case B group who were followed up for 6 months, 3 became negative for hepatitis B surface antigen and positive for hepatitis B surface antibody, 2 remained positive for hepatitis B surface antigen and negative for HBV DNA, and 4 became positive for HBV DNA with a low viral load [corrected] Of 6 patients in the case C group who were followed up for 6 months, 3 remained negative for HCV RNA, and 3 had persistently low viral loads. Concomitant hepatitis A was always self-limited, associated with a marked inhibition of HBV and HCV genomes, and possibly had a good prognosis for the underlying chronic hepatitis.

  18. Addition of pentoxifylline to pegylated interferon-alpha-2a and ribavirin improves sustained virological response to chronic hepatitis C virus: a randomized clinical trial.

    PubMed

    Jiménez-Luévano, Miguel Ángel; Lerma-Díaz, José Manuel; Hernández-Flores, Georgina; Jiménez-Partida, Miguel Ángel; Bravo-Cuellar, Alejandro

    2013-01-01

    The commonly accepted treatment for hepatitis C virus (HCV) infection, pegylated interferon alpha (PEG INF-alpha) and ribavirin, leads to 50-60% of sustained virological response (SVR). On the other hand, pentoxifylline (PTX) possesses antiviral and hepatoprotector properties. To investigate whether the addition of PTX to conventional hepatitis C treatment increases SVR. Seventy two patients of both genders were studied in a randomized fashion; the diagnosis of chronic HCV infection was made according to clinical and laboratory criteria and histopathologically classified according to METAVIR scoring system criteria. HCV viral load was tested by PCR, baseline, and after 6 months of treatment, as well as anti-HCV, anti-hepatitis B virus , and anti-human immunodeficiency virus antibodies by enzyme-linked immunosorbent assay. During 48 weeks, control group patients were treated with PEG INF-alpha- 2a plus ribavirin. PTX was administered to Experimental Group patients prior to the treatment. Demographic data were similar in both groups. Experimental- and control-group subjects were at F2 and F3 states according to the METAVIR classification. The most common HCV genotypes were 1a and 1b (39% in the control group in each case, and 42% in the experimental group in each case). At the end of the study, hepatic enzymes and viral load decreased in both groups to similar values. SVR in the experimental group increased significantly (p < 0.05) when compared with standard therapy alone. Addition of PTX to conventional chronic hepatitis C treatment may increase the percentage of patients with SVR.

  19. Clinical development and current status: Europe.

    PubMed

    Wirz, Dieter; Daniels, A U; Göpfert, Beat; Morscher, Erwin W

    2005-01-01

    This article reviews the development and current status of cemented fixation in total hip replacement in Europe. Key points include the wide country-to-country variation in use of cemented vs. non-cemented fixation and the largely overlooked importance of the choice of bone cement as a factor highly correlated with clinical outcome. Laboratory studies by the authors are also reviewed. Results suggest that the type of acrylic bone cement used affects wear phenomena at the implant/cement interface. Further studies by microcalorimetry suggest that certain aspects of acrylic starting materials (low molecular weight and use of radiation sterilization) affect long-term physico-chemical stability and may thus influence clinical outcomes.

  20. MITRE system for clinical assertion status classification

    PubMed Central

    Aberdeen, John; Coarr, Matt; Tresner-Kirsch, David; Wellner, Ben; Yeh, Alexander; Hirschman, Lynette

    2011-01-01

    Objective To describe a system for determining the assertion status of medical problems mentioned in clinical reports, which was entered in the 2010 i2b2/VA community evaluation ‘Challenges in natural language processing for clinical data’ for the task of classifying assertions associated with problem concepts extracted from patient records. Materials and methods A combination of machine learning (conditional random field and maximum entropy) and rule-based (pattern matching) techniques was used to detect negation, speculation, and hypothetical and conditional information, as well as information associated with persons other than the patient. Results The best submission obtained an overall micro-averaged F-score of 0.9343. Conclusions Using semantic attributes of concepts and information about document structure as features for statistical classification of assertions is a good way to leverage rule-based and statistical techniques. In this task, the choice of features may be more important than the choice of classifier algorithm. PMID:21515542

  1. Epidemiological, virological and clinical characteristics of HBV infection in 223 HIV co-infected patients: a French multi-centre collaborative study

    PubMed Central

    2013-01-01

    Background Chronic hepatitis B (CHB) is a clinical concern in human immunodeficiency virus (HIV)-infected individuals due to substantial prevalence, difficulties to treat, and severe liver disease outcome. A large nationwide cross-sectional multicentre analysis of HIV-HBV co-infected patients was designed to describe and identify parameters associated with virological and clinical outcome of CHB in HIV-infected individuals with detectable HBV viremia. Methods A multicenter collaborative cross-sectional study was launched in 19 French University hospitals distributed through the country. From January to December 2007, HBV load, genotype, clinical and epidemiological characteristics of 223 HBV-HIV co-infected patients with an HBV replication over 1000 IU/mL were investigated. Results Patients were mostly male (82%, mean age 42 years). Genotype distribution (A 52%; E 23.3%; D 16.1%) was linked to risk factors, geographic origin, and co-infection with other hepatitis viruses. This genotypic pattern highlights divergent contamination event timelines by HIV and HBV viruses. Most patients (74.7%) under antiretroviral treatment were receiving a drug with anti-HBV activity, including 47% receiving TDF. Genotypic lamivudine-resistance detected in 26% of the patients was linked to duration of lamivudine exposure, age, CD4 count and HIV load. Resistance to adefovir (rtA181T/V) was detected in 2.7% of patients. Advanced liver lesions were observed in 54% of cases and were associated with an older age and lower CD4 counts but not with viral load or genotype. Immune escape HBsAg variants were seldom detected. Conclusions Despite the detection of advanced liver lesions in most patients, few were not receiving anti-HBV drugs and for those treated with the most potent anti-HBV drugs, persistent replication suggested non-optimal adherence. Heterogeneity in HBV strains reflects epidemiological differences that may impact liver disease progression. These findings are strong arguments

  2. Clinical and Virological Study of Dengue Cases and the Members of Their Households: The Multinational DENFRAME Project

    PubMed Central

    Dussart, Philippe; Baril, Laurence; Petit, Laure; Beniguel, Lydie; Quang, Luong Chan; Ly, Sowath; Azevedo, Raimunda do Socorro Silva; Meynard, Jean-Baptiste; Vong, Sirenda; Chartier, Loïc; Diop, Aba; Sivuth, Ong; Duong, Veasna; Thang, Cao Minh; Jacobs, Michael; Sakuntabhai, Anavaj; Nunes, Marcio Roberto Teixeira; Huong, Vu Ti Que; Buchy, Philippe; Vasconcelos, Pedro Fernando da Costa

    2012-01-01

    Background Dengue has emerged as the most important vector-borne viral disease in tropical areas. Evaluations of the burden and severity of dengue disease have been hindered by the frequent lack of laboratory confirmation and strong selection bias toward more severe cases. Methodology A multinational, prospective clinical study was carried out in South-East Asia (SEA) and Latin America (LA), to ascertain the proportion of inapparent dengue infections in households of febrile dengue cases, and to compare clinical data and biological markers from subjects with various dengue disease patterns. Dengue infection was laboratory-confirmed during the acute phase, by virus isolation and detection of the genome. The four participating reference laboratories used standardized methods. Principal Findings Among 215 febrile dengue subjects—114 in SEA and 101 in LA—28 (13.0%) were diagnosed with severe dengue (from SEA only) using the WHO definition. Household investigations were carried out for 177 febrile subjects. Among household members at the time of the first home visit, 39 acute dengue infections were detected of which 29 were inapparent. A further 62 dengue cases were classified at early convalescent phase. Therefore, 101 dengue infections were found among the 408 household members. Adding these together with the 177 Dengue Index Cases, the overall proportion of dengue infections among the study participants was estimated at 47.5% (278/585; 95% CI 43.5–51.6). Lymphocyte counts and detection of the NS1 antigen differed significantly between inapparent and symptomatic dengue subjects; among inapparent cases lymphocyte counts were normal and only 20% were positive for NS1 antigen. Primary dengue infection and a specific dengue virus serotype were not associated with symptomatic dengue infection. Conclusion Household investigation demonstrated a high proportion of household members positive for dengue infection, including a number of inapparent cases, the frequency of

  3. The Epidemiology, Virology and Clinical Findings of Dengue Virus Infections in a Cohort of Indonesian Adults in Western Java.

    PubMed

    Kosasih, Herman; Alisjahbana, Bachti; Nurhayati; de Mast, Quirijn; Rudiman, Irani F; Widjaja, Susana; Antonjaya, Ungke; Novriani, Harli; Susanto, Nugroho H; Jusuf, Hadi; van der Ven, Andre; Beckett, Charmagne G; Blair, Patrick J; Burgess, Timothy H; Williams, Maya; Porter, Kevin R

    2016-02-01

    Dengue has emerged as one of the most important infectious diseases in the last five decades. Evidence indicates the expansion of dengue virus endemic areas and consequently the exponential increase of dengue virus infections across the subtropics. The clinical manifestations of dengue virus infection include sudden fever, rash, headache, myalgia and in more serious cases, spontaneous bleeding. These manifestations occur in children as well as in adults. Defining the epidemiology of dengue in a given area is critical to understanding the disease and devising effective public health strategies. Here, we report the results from a prospective cohort study of 4380 adults in West Java, Indonesia, from 2000-2004 and 2006-2009. A total of 2167 febrile episodes were documented and dengue virus infections were confirmed by RT-PCR or serology in 268 cases (12.4%). The proportion ranged from 7.6 to 41.8% each year. The overall incidence rate of symptomatic dengue virus infections was 17.3 cases/1,000 person years and between September 2006 and April 2008 asymptomatic infections were 2.6 times more frequent than symptomatic infections. According to the 1997 WHO classification guidelines, there were 210 dengue fever cases, 53 dengue hemorrhagic fever cases (including one dengue shock syndrome case) and five unclassified cases. Evidence for sequential dengue virus infections was seen in six subjects. All four dengue virus serotypes circulated most years. Inapparent dengue virus infections were predominantly associated with DENV-4 infections. Dengue virus was responsible for a significant percentage of febrile illnesses in an adult population in West Java, Indonesia, and this percentage varied from year to year. The observed incidence rate during the study period was 43 times higher than the reported national or provincial rates during the same time period. A wide range of clinical severity was observed with most infections resulting in asymptomatic disease. The circulation of

  4. The Epidemiology, Virology and Clinical Findings of Dengue Virus Infections in a Cohort of Indonesian Adults in Western Java

    PubMed Central

    Kosasih, Herman; Alisjahbana, Bachti; Nurhayati; de Mast, Quirijn; Rudiman, Irani F.; Widjaja, Susana; Antonjaya, Ungke; Novriani, Harli; Susanto, Nugroho H.; Jusuf, Hadi; van der Ven, Andre; Beckett, Charmagne G.; Blair, Patrick J.; Burgess, Timothy H.; Williams, Maya; Porter, Kevin R.

    2016-01-01

    Background Dengue has emerged as one of the most important infectious diseases in the last five decades. Evidence indicates the expansion of dengue virus endemic areas and consequently the exponential increase of dengue virus infections across the subtropics. The clinical manifestations of dengue virus infection include sudden fever, rash, headache, myalgia and in more serious cases, spontaneous bleeding. These manifestations occur in children as well as in adults. Defining the epidemiology of dengue in a given area is critical to understanding the disease and devising effective public health strategies. Methodology/Principal Findings Here, we report the results from a prospective cohort study of 4380 adults in West Java, Indonesia, from 2000–2004 and 2006–2009. A total of 2167 febrile episodes were documented and dengue virus infections were confirmed by RT-PCR or serology in 268 cases (12.4%). The proportion ranged from 7.6 to 41.8% each year. The overall incidence rate of symptomatic dengue virus infections was 17.3 cases/1,000 person years and between September 2006 and April 2008 asymptomatic infections were 2.6 times more frequent than symptomatic infections. According to the 1997 WHO classification guidelines, there were 210 dengue fever cases, 53 dengue hemorrhagic fever cases (including one dengue shock syndrome case) and five unclassified cases. Evidence for sequential dengue virus infections was seen in six subjects. All four dengue virus serotypes circulated most years. Inapparent dengue virus infections were predominantly associated with DENV-4 infections. Conclusions/Significance Dengue virus was responsible for a significant percentage of febrile illnesses in an adult population in West Java, Indonesia, and this percentage varied from year to year. The observed incidence rate during the study period was 43 times higher than the reported national or provincial rates during the same time period. A wide range of clinical severity was observed with

  5. Clinical and Virological Characteristics of Chronic Hepatitis B Patients with Coexistence of HBsAg and Anti-HBs.

    PubMed

    Liu, Yong; Zhang, Le; Zhou, Jin-Yong; Pan, Jinshun; Hu, Wei; Zhou, Yi-Hua

    2016-01-01

    Coexistence of hepatitis B surface antigen (HBsAg) and antibody against HBsAg (anti-HBs) comprises an atypical serological profile in patients with chronic hepatitis B virus (HBV) infection. In this study, in total 94 patients with coexisting HBsAg and anti-HBs and 94 age- and sex-matched patients with positive HBsAg were characterized by quantitatively measuring HBsAg and HBV DNA, sequencing large S genes, and observing clinical features. Compared with common hepatitis B patients, the patients with coexisting HBsAg and anti-HBs had lower HBsAg and HBV DNA levels. These two groups had similar rate of pre-S deletion mutations. However, in patients with coexisting HBsAg and anti-HBs, more amino acid substitutions in the a determinant of S gene were observed in HBV genotype C, but not in genotype B. Fourteen patients with coexisting HBsAg and anti-HBs were followed up for an average of 15.5 months. There were no significant changes in the levels of HBsAg, anti-HBs, HBV DNA and ALT over the follow-up period. Compared with the baseline sequences, amino acid substitutions in the MHR of HBsAg occurred in 14.3% (2/14) patients. In conclusion, coexistence of HBsAg and anti-HBs may be associated with higher frequency of mutations in the a determinant of HBV genotype C.

  6. Modifying Antiretroviral Therapy in Virologically Suppressed HIV-1-Infected Patients.

    PubMed

    Collins, Sean E; Grant, Philip M; Shafer, Robert W

    2016-01-01

    HIV-1-infected patients with suppressed plasma viral loads often require changes to their antiretroviral (ARV) therapy to manage drug toxicity and intolerance, to improve adherence, and to avoid drug interactions. In patients who have never experienced virologic failure while receiving ARV therapy and who have no evidence of drug resistance, switching to any of the acceptable US Department of Health and Human Services first-line therapies is expected to maintain virologic suppression. However, in virologically suppressed patients with a history of virologic failure or drug resistance, it can be more challenging to change therapy while still maintaining virologic suppression. In these patients, it may be difficult to know whether the discontinuation of one of the ARVs in a suppressive regimen constitutes the removal of a key regimen component that will not be adequately supplanted by one or more substituted ARVs. In this article, we review many of the clinical scenarios requiring ARV therapy modification in patients with stable virologic suppression and outline the strategies for modifying therapy while maintaining long-term virologic suppression.

  7. HIV-1 virologic failure and acquired drug resistance among first-line antiretroviral experienced adults at a rural HIV clinic in coastal Kenya: a cross-sectional study

    PubMed Central

    2014-01-01

    Background An increasing number of people on antiretroviral therapy (ART) in sub-Saharan Africa has led to declines in HIV related morbidity and mortality. However, virologic failure (VF) and acquired drug resistance (ADR) may negatively affect these gains. This study describes the prevalence and correlates of HIV-1 VF and ADR among first-line ART experienced adults at a rural HIV clinic in Coastal Kenya. Methods HIV-infected adults on first-line ART for ≥6 months were cross-sectionally recruited between November 2008 and March 2011. The primary outcome was VF, defined as a one-off plasma viral load of ≥400 copies/ml. The secondary outcome was ADR, defined as the presence of resistance associated mutations. Logistic regression and Fishers exact test were used to describe correlates of VF and ADR respectively. Results Of the 232 eligible participants on ART over a median duration of 13.9 months, 57 (24.6% [95% CI: 19.2 – 30.6]) had VF. Fifty-five viraemic samples were successfully amplified and sequenced. Of these, 29 (52.7% [95% CI: 38.8 – 66.3]) had at least one ADR, with 25 samples having dual-class resistance mutations. The most prevalent ADR mutations were the M184V (n = 24), K103N/S (n = 14) and Y181C/Y/I/V (n = 8). Twenty-six of the 55 successfully amplified viraemic samples (47.3%) did not have any detectable resistance mutation. Younger age (15–34 vs. ≥35 years: adjusted odd ratios [95% CI], p-value: 0.3 [0.1–0.6], p = 0.002) and unsatisfactory adherence (<95% vs. ≥95%: 3.0 [1.5–6.5], p = 0.003) were strong correlates of VF. Younger age, unsatisfactory adherence and high viral load were also strong correlates of ADR. Conclusions High levels of VF and ADR were observed in younger patients and those with unsatisfactory adherence. Youth-friendly ART initiatives and strengthened adherence support should be prioritized in this Coastal Kenyan setting. To prevent unnecessary/premature switches, targeted HIV drug resistance

  8. A text messaging intervention to improve retention in care and virologic suppression in a U.S. urban safety-net HIV clinic: study protocol for the Connect4Care (C4C) randomized controlled trial.

    PubMed

    Christopoulos, Katerina A; Riley, Elise D; Tulsky, Jacqueline; Carrico, Adam W; Moskowitz, Judith T; Wilson, Leslie; Coffin, Lara S; Falahati, Veesta; Akerley, Jordan; Hilton, Joan F

    2014-12-31

    Few data exist on the use of text messaging as a tool to promote retention in HIV care and virologic suppression at the clinic level in the United States. We describe the protocol for a study designed to investigate whether a text messaging intervention that supports healthy behaviors, encourages consistent engagement with care, and promotes antiretroviral persistence can improve retention in care and virologic suppression among patients in an urban safety-net HIV clinic in San Francisco. Connect4Care (C4C) is a single-site, randomized year-long study of text message appointment reminders vs. text message appointment reminders plus thrice-weekly supportive, informational, and motivational text messages. Eligible consenting patients are allocated 1:1 to the two arms within strata defined by HIV diagnosis within the past 12 months (i.e. "newly diagnosed") vs. earlier. Study participants must receive primary care at the San Francisco General Hospital HIV clinic, speak English, possess a cell phone and be willing to send/receive up to 25 text messages per month, a have viral load >200 copies/μL, and be either new to the clinic or have a history of poor retention. The primary efficacy outcome is virologic suppression at 12 months and the key secondary outcome, which will also be examined as a mediator of the primary outcome, is retention in HIV care, as operationalized by kept and missed primary care visits. Process outcomes include text message response rate and percent of time in study without cell phone service. Generalized estimating equation log-binomial models will be used for intent to treat, per protocol, and mediation analyses. An assessment of the cost and cost-effectiveness of the intervention is planned along with a qualitative evaluation of the intervention. Findings from this study will provide valuable information about the use of behavioral-theory based text messaging to promote retention in HIV care and virologic suppression, further elucidate the

  9. Virological and Immunological Response to Antiretroviral Regimens Containing Maraviroc in HIV Type 1-Infected Patients in Clinical Practice: Role of Different Tropism Testing Results and of Concomitant Treatments

    PubMed Central

    Bianco, Claudia; Bellazzi, Lara Ines; Bruzzone, Bianca; Colao, Grazia; Corsi, Paola; Monno, Laura; Pagano, Gabriella; Paolucci, Stefania; Punzi, Grazia; Setti, Maurizio; Zazzi, Maurizio; De Luca, Andrea

    2014-01-01

    Abstract We assessed the immunovirological response to antiretroviral regimens containing maraviroc in HIV-infected viremic patients with viral tropism predicted by different assays. We selected antiretroviral treatment-experienced HIV-1-infected patients initiating regimens containing maraviroc after different phenotypic or genotypic viral tropism assays, with at least one HIV-1 RNA determination during follow-up. Survival analysis was employed to assess the virological response as time to HIV-1 RNA <50 copies/ml and immunological response as time to a CD4 cell count increase of ≥100/μl from baseline. Predictors of these outcomes were analyzed by multivariate Cox regression models. In 191 treatments with maraviroc, virological response was achieved in 65.4% and the response was modestly influenced by the baseline viral load and concomitant drug activity but not influenced by the type of tropism assay employed. Immunological response was achieved in 58.1%; independent predictors were baseline HIV-1 RNA (per log10 higher: HR 1.29, 95% CI 1.05–1.60) and concomitant therapy with enfuvirtide (HR 2.05, 0.96–4.39) but not tropism assay results. Of 17 patients with baseline R5-tropic virus and available tropism results while viremic during follow-up on maraviroc, seven (41%) showed a tropism switch to non-R5 virus. A significant proportion of experienced patients treated with regimens containing maraviroc achieved virological response. The tropism test type used was not associated with immunovirological response and concomitant treatment with enfuvirtide increased the chance of immunological response. More than half of virological failures with maraviroc were not accompanied by tropism switch. PMID:23971941

  10. Association between efavirenz-based compared with nevirapine-based antiretroviral regimens and virological failure in HIV-infected children.

    PubMed

    Lowenthal, Elizabeth D; Ellenberg, Jonas H; Machine, Edwin; Sagdeo, Aditi; Boiditswe, Sefelani; Steenhoff, Andrew P; Rutstein, Richard; Anabwani, Gabriel; Gross, Robert

    2013-05-01

    Worldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with human immunodeficiency virus (HIV) infection. Data on the comparative effectiveness of these medications in children are limited. To investigate whether virological failure is more likely among children who initiated 1 or the other NNRTI-based HIV treatment. Retrospective cohort study of children (aged 3-16 years) who initiated efavirenz-based (n = 421) or nevirapine-based (n = 383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana. The primary outcome was time from initiation of therapy to virological failure. Virological failure was defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression. Cox proportional hazards regression analysis compared time to virological failure by regimen. Multivariable Cox regression controlled for age, sex, baseline immunologic category, baseline clinical category, baseline viral load, nutritional status, NRTIs used, receipt of single-dose nevirapine, and treatment for tuberculosis. With a median follow-up time of 69 months (range, 6-112 months; interquartile range, 23-87 months), 57 children (13.5%; 95% CI, 10.4%-17.2%) initiating treatment with efavirenz and 101 children (26.4%; 95% CI, 22.0%-31.1%) initiating treatment with nevirapine had virological failure. There were 11 children (2.6%; 95% CI, 1.3%-4.6%) receiving efavirenz and 20 children (5.2%; 95% CI, 3.2%-7.9%) receiving nevirapine who never achieved virological suppression. The Cox proportional hazard ratio for the combined virological failure end point was 2.0 (95% CI, 1.4-2.7; log rank P < .001, favoring efavirenz). None of the measured covariates affected the estimated hazard ratio in the multivariable analyses. Among children aged 3 to 16 years

  11. Association Between Efavirenz-Based Compared With Nevirapine-Based Antiretroviral Regimens and Virological Failure in HIV-Infected Children

    PubMed Central

    Lowenthal, Elizabeth D.; Ellenberg, Jonas H.; Machine, Edwin; Sagdeo, Aditi; Boiditswe, Sefelani; Steenhoff, Andrew P.; Rutstein, Richard; Anabwani, Gabriel; Gross, Robert

    2013-01-01

    Importance Worldwide, the nonnucleoside reverse transcriptase inhibitors (NNRTIs) efavirenz and nevirapine are commonly used in first-line antiretroviral regimens in both adults and children with human immunodeficiency virus (HIV) infection. Data on the comparative effectiveness of these medications in children are limited. Objective To investigate whether virological failure is more likely among children who initiated 1 or the other NNRTI-based HIV treatment. Design, Setting, and Participants Retrospective cohort study of children (aged 3–16 years) who initiated efavirenz-based (n=421) or nevirapine-based (n=383) treatment between April 2002 and January 2011 at a large pediatric HIV care setting in Botswana. Main Outcomes and Measures The primary outcome was time from initiation of therapy to virological failure. Virological failure was defined as lack of plasma HIV RNA suppression to less than 400 copies/mL by 6 months or confirmed HIV RNA of 400 copies/mL or greater after suppression. Cox proportional hazards regression analysis compared time to virological failure by regimen. Multivariable Cox regression controlled for age, sex, baseline immunologic category, baseline clinical category, baseline viral load, nutritional status, NRTIs used, receipt of single-dose nevirapine, and treatment for tuberculosis. Results With a median follow-up time of 69 months (range, 6–112 months; interquartile range, 23–87 months), 57 children (13.5%; 95% CI, 10.4%–17.2%) initiating treatment with efavirenz and 101 children (26.4%; 95% CI, 22.0%–31.1%) initiating treatment with nevirapine had virological failure. There were 11 children (2.6%; 95% CI, 1.3%–4.6%) receiving efavirenz and 20 children (5.2%; 95% CI, 3.2%–7.9%) receiving nevirapine who never achieved virological suppression. The Cox proportional hazard ratio for the combined virological failure end point was 2.0 (95% CI, 1.4–2.7; log rank P<.001, favoring efavirenz). None of the measured covariates

  12. Status of human monkeypox: clinical disease, epidemiology and research.

    PubMed

    Damon, Inger K

    2011-12-30

    Monkeypox, a vesiculo-pustular rash illness, was initially discovered to cause human infection in 1970 through the World Health Organization (WHO)-sponsored efforts of the Commission to Certify Smallpox Eradication in Western Africa and the Congo Basin. The virus had been discovered to cause a nonhuman primate rash illness in 1958, and was thus named monkeypox. The causative agents of monkeypox and smallpox diseases both are species of Orthopoxvirus. Orthopoxvirus monkeypox, when it infects humans as an epizootic, produces a similar clinical picture to that of ordinary human smallpox. Since 1970, extensive epidemiology, virology, ecology and public health research has enabled better characterization of monkeypox virus and the associated human disease. This work reviews the progress in this body of research, and reviews studies of this "newly" emerging zoonotic disease.

  13. Maintaining Life-saving Testing for Patients With Infectious Diseases: Infectious Diseases Society of America, American Society for Microbiology, and Pan American Society for Clinical Virology Recommendations on the Regulation of Laboratory-developed Tests.

    PubMed

    Caliendo, Angela M; Couturier, Marc R; Ginocchio, Christine C; Hanson, Kimberly E; Miller, Melissa B; Walker, Kimberly E; Frank, Gregory M

    2016-07-15

    In 2014, the US Food and Drug Administration (FDA) proposed to regulate laboratory-developed tests (LDTs)-diagnostics designed, manufactured, and used within a single laboratory. The Infectious Diseases Society of America, the American Society for Microbiology, and the Pan American Society for Clinical Virology recognize that the FDA is committed to protecting patients. However, our societies are concerned that the proposed regulations will limit access to testing and negatively impact infectious diseases (ID) LDTs. In this joint commentary, our societies discuss why LDTs are critical for ID patient care, hospital infection control, and public health responses. We also highlight how the FDA's proposed regulation of LDTs could impair patient access to life-saving tests and stifle innovation in ID diagnostics. Finally, our societies make specific recommendations for the FDA's consideration to reduce the burden of the proposed new rules on clinical laboratories and protect patients' access to state-of-the art, quality LDTs.

  14. Individualized treatment strategies and predictors of virological response for chronic hepatitis C: a multicenter prospective study from China.

    PubMed

    Nan, Yue-Min; Zhang, Yu-Guo; Zheng, Huan-Wei; An, Chun-Mian; Li, You-Sheng; Zhang, Ying; Sun, Dian-Xing; Li, Cang-You; Li, Qiang; Tong, Li-Xin; Kong, Ling-Bo; Zhao, Su-Xian; Wang, Rong-Qi; Meng, Ping; Su, Shan-Shan; He, Huan; Niu, Xue-Min

    2015-01-01

    Combination therapy comprising pegylated interferon-alpha (PegIFNα) and ribavirin (RBV) has been the standard of care for the chronic hepatitis C patients for more than a decade. Recently, direct antiviral agents show better efficacy, tolerance, and shorter treatment duration. However, the prohibitive costs of the regimens limit their use in developing countries where most of the HCV infection exists. Optimizing the treatment and understanding the host- and virus-factors associated with viral clearance were necessary for individualizing therapy to maximize sustained virologic response. To explore individualized antiviral strategies with PegIFNα-2a/IFNα-2b plus ribavirin for CHC patients, and to clarify predictive factors for virological response. A cohort of 314 patients were included in this open-label, prospective clinical trial, which received individualized doses of PegIFNα-2a or IFNα-2b combined with RBV according to body weight, disease status and complications, with the duration of 44 weeks after HCV RNA undetectable. All the IL-28B (rs8099917), IL-17A (rs8193036), IL-17B (rs2275913) and PD-1.1 SNPs were genotyped using the TaqMan system. The sustained virological response (SVR) in PegIFNα-2a group was significantly higher than that in IFNα-2b (85.8% vs 75.0%, P = 0.034), especially in HCV genotype 1 (84.0% vs 64.3%, P = 0.022). However, no significant differences were found in rapid virological response (RVR), complete early virological response (cEVR) and SVR between PegIFNα-2a and IFNα-2b according to different doses, respectively. The genotype frequency of IL-28B TT in patients with cEVR, SVR was higher than that in non-responsed patients (93.8% vs 78.1%, χ(2) = 7.827, P = 0.005; 95.9% vs 80.4%, χ(2) = 9.394, P = 0.002). No significant correlation between the genotype distribution of IL-17A, IL-17B and PD-1.1 with virological response. Individualized regimens of PegIFNα-2a/RBV and IFNα-2b/RBV could achieve satisfied virological response in

  15. Status of Clinical Supervision among School Counselors in Southeast Georgia

    ERIC Educational Resources Information Center

    Black, Anna Lila; Bailey, Carrie Lynn; Bergin, James J.

    2011-01-01

    Previous studies have investigated the role of clinical supervision in school counseling practice. This research explored the status and meaning of clinical supervision to school counselors employed in two southeastern Georgia counties. Results indicate that participants value clinical supervision even though their employers did not necessarily…

  16. Clinical and virological predictors of sustained response with an interferon-based simeprevir regimen for patients with chronic genotype 1 hepatitis C virus infection.

    PubMed

    D'Offizi, Gianpiero; Cammà, Calogero; Taibi, Chiara; Schlag, Michael; Weber, Karin; Palma, Maria; DeMasi, Ralph; Janssen, Katrien; Witek, James; Lionetti, Raffaella

    2017-01-01

    Simeprevir plus peg-interferon/ribavirin (PR) is approved to treat chronic hepatitis C (HCV) genotype 1 (GT1) and GT4 infection. This study aimed to assess baseline and on-treatment the factors predictive of sustained virologic response 12-weeks post-treatment (SVR12) in patients receiving 12 weeks of simeprevir plus PR followed by 12 or 36 weeks of PR. Data from participants in four studies (QUEST-1, QUEST-2, ATTAIN and PROMISE) were pooled to examine the efficacy and safety of simeprevir+PR in HCV GT1 patients. The predictive power of baseline variables for SVR12 was assessed using univariate and multivariate logistic regression models while the relationship between early (Week 4) on-treatment response and SVR12 was analyzed by GT1 subtype and treatment experience. Data for 1160 patients were analyzed (overall SVR12: 71%). Baseline factors predictive of SVR12 were: IL28B CC genotype, GT1a/Q80K-negative, treatment-naïve/prior relapser, no cirrhosis, HCV-RNA ≤2,000,000IU/mL, albumin >42g/L, platelets >200x109 /L. Patients with HCV GT1b (86%), IL28B CC genotype (87%), and treatment-naïve patients (83%) were predicted to achieve the highest SVR12 rates and rates of rapid virologic response. Week 4 early on-treatment response identified treatment-naïve and prior relapse patients likely to achieve SVR12. Patients likely to respond to simeprevir+PR can be identified using baseline factors. Early on-treatment response predicts treatment success.

  17. Virological Efficacy in Cerebrospinal Fluid and Neurocognitive Status in Patients with Long-Term Monotherapy Based on Lopinavir/Ritonavir: An Exploratory Study

    PubMed Central

    Santos, José R.; Muñoz-Moreno, José A.; Moltó, José; Prats, Anna; Curran, Adrià; Domingo, Pere; Llibre, Josep M.; McClernon, Daniel R.; Bravo, Isabel; Canet, Jaume; Watson, Victoria; Back, David; Clotet, Bonaventura

    2013-01-01

    Background Data on suppression of HIV replication in the CNS and on the subsequent risk of neurocognitive impairment using monotherapy with boosted protease inhibitors are limited. Methods Ours was an exploratory cross-sectional study in patients on lopinavir/ritonavir-based monotherapy (LPV/r-MT) or standard triple therapy (LPV/r-ART) for at least 96 weeks who maintained a plasma viral load <50 copies/mL. HIV-1 RNA in CSF was determined by HIV-1 SuperLow assay (lower limit of detection, 1 copy/mL). Neurocognitive functioning was assessed using a recommended battery of neuropsychological tests covering 7 areas. Neurocognitive impairment (NCI) was determined and also a global deficit score (GDS) for study comparisons. Results Seventeen patients on LPV/r-MT and 17 on LPV/r-ART were included. Fourteen (82.4%) patients on LPV/r-MT and 16 (94.1%) on LPV/r-ART had HIV-1 RNA <1 copy/mL in CSF (p = 0.601). NCI was observed in 7 patients on LPV/r-MT and in 10 on LPV/r-ART (41% vs 59%; p = 0.494). Mean (SD) GDS was 0.22 (0.20) in patients on LPV/r-MT and 0.47 (0.34) in those on LPV/r-ART (p = 0.012). Conclusions Suppression of HIV in CSF is similar in individuals with durable plasma HIV-1 RNA suppression who are receiving LPV/r-MT or LPV/r-ART for at least 96 weeks. Findings for HIV-1 replication in CSF and neurocognitive status indicate that this strategy seems to be safe for CNS functioning. PMID:23922957

  18. Virology Interest Group | Center for Cancer Research

    Cancer.gov

    The Virology Interest Group comprises researchers at NIH and in the local area who are interested in virology. The group organizes activities designed to promote interactions and exchange of information.

  19. 42 CFR 493.919 - Virology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Virology. 493.919 Section 493.919 Public Health... Proficiency Testing Programs by Specialty and Subspecialty § 493.919 Virology. (a) Types of services offered by laboratories. In virology, there are two types of laboratories for proficiency testing...

  20. 42 CFR 493.1205 - Condition: Virology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Condition: Virology. 493.1205 Section 493.1205 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1205 Condition: Virology. If the laboratory provides services in the subspecialty of Virology,...

  1. 42 CFR 493.919 - Virology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Virology. 493.919 Section 493.919 Public Health... Proficiency Testing Programs by Specialty and Subspecialty § 493.919 Virology. (a) Types of services offered by laboratories. In virology, there are two types of laboratories for proficiency testing...

  2. 42 CFR 493.919 - Virology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Virology. 493.919 Section 493.919 Public Health... Proficiency Testing Programs by Specialty and Subspecialty § 493.919 Virology. (a) Types of services offered by laboratories. In virology, there are two types of laboratories for proficiency testing...

  3. 42 CFR 493.1205 - Condition: Virology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Condition: Virology. 493.1205 Section 493.1205 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1205 Condition: Virology. If the laboratory provides services in the subspecialty of Virology,...

  4. 42 CFR 493.1205 - Condition: Virology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Condition: Virology. 493.1205 Section 493.1205 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1205 Condition: Virology. If the laboratory provides services in the subspecialty of Virology,...

  5. 42 CFR 493.1205 - Condition: Virology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Condition: Virology. 493.1205 Section 493.1205 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1205 Condition: Virology. If the laboratory provides services in the subspecialty of Virology,...

  6. 42 CFR 493.1205 - Condition: Virology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Condition: Virology. 493.1205 Section 493.1205 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES....1205 Condition: Virology. If the laboratory provides services in the subspecialty of Virology,...

  7. The Future of Digital Polymerase Chain Reaction in Virology.

    PubMed

    Vynck, Matthijs; Trypsteen, Wim; Thas, Olivier; Vandekerckhove, Linos; De Spiegelaere, Ward

    2016-10-01

    Driven by its potential benefits over currently available methods, and the recent development of commercial platforms, digital polymerase chain reaction (dPCR) has received increasing attention in virology research and diagnostics as a tool for the quantification of nucleic acids. The current technologies are more precise and accurate, but may not be much more sensitive, compared with quantitative PCR (qPCR) applications. The most promising applications with the current technology are the analysis of mutated sequences, such as emerging drug-resistant mutations. Guided by the recent literature, this review focuses on three aspects that demonstrate the potential of dPCR for virology researchers and clinicians: the applications of dPCR within both virology research and clinical virology, the benefits of the technique over the currently used real-time qPCR, and the importance and availability of specific data analysis approaches for dPCR. Comments are provided on current drawbacks and often overlooked pitfalls that need further attention to allow widespread implementation of dPCR as an accurate and precise tool within the field of virology.

  8. Clinical and virological factors associated with hepatitis B virus reactivation in HBsAg-negative and anti-HBc antibodies-positive patients undergoing chemotherapy and/or autologous stem cell transplantation for cancer.

    PubMed

    Borentain, P; Colson, P; Coso, D; Bories, E; Charbonnier, A; Stoppa, A M; Auran, T; Loundou, A; Motte, A; Ressiot, E; Norguet, E; Chabannon, C; Bouabdallah, R; Tamalet, C; Gérolami, R

    2010-11-01

    We studied clinical outcome and clinico-virological factors associated with hepatitis B virus reactivation (HBV-R) following cancer treatment in hepatitis B virus surface antigen (HBsAg)-negative/anti-hepatitis B core antibodies (anti-HBcAb)-positive patients. Between 11/2003 and 12/2005, HBV-R occurred in 7/84 HBsAg-negative/anti-HBcAb-positive patients treated for haematological or solid cancer. Virological factors including HBV genotype, core promoter, precore, and HBsAg genotypic and amino acid (aa) patterns were studied. Patients presenting with reactivation were men, had an hepatitis B virus surface antibody (HBsAb) titre <100 IU/L and underwent >1 line of chemotherapy (CT) significantly more frequently than controls. All were treated for haematological cancer, 3/7 received haematopoietic stem cell transplantation (HSCT), and 4/7 received rituximab. Using multivariate analysis, receiving >1 line of CT was an independent risk factor for HBV-R. Fatal outcome occurred in 3/7 patients (despite lamivudine therapy in two), whereas 2/4 survivors had an HBsAg seroconversion. HBV-R involved non-A HBV genotypes and core promoter and/or precore HBV mutants in all cases. Mutations known to impair HBsAg antigenicity were detected in HBV DNA from all seven patients. HBV DNA could be retrospectively detected in two patients prior cancer treatment and despite HBsAg negativity. HBV-R is a concern in HBsAg-negative/anti-HBcAb-positive patients undergoing cancer therapy, especially in males presenting with haematological cancer, a low anti-HBsAb titre and more than one chemotherapeutic agent. HBV DNA testing is mandatory to improve diagnosis and management of HBV-R in these patients. The role of specific therapies such as rituximab or HSCT as well as of HBV aa variability deserves further studies. © 2009 Blackwell Publishing Ltd.

  9. Present Status of Radiotherapy in Clinical Practice

    NASA Astrophysics Data System (ADS)

    Duehmke, Eckhart

    Aims of radiation oncology are cure from malignant diseases and - at the same time preservation of anatomy (e.g. female breast, uterus, prostate) and organ functions (e.g. brain, eye, voice, sphincter ani). At present, methods and results of clinical radiotherapy (RT) are based on experiences with natural history and radiobiology of malignant tumors in properly defined situations as well as on technical developments since World War II in geometrical and biological treatment planning in teletherapy and brachytherapy. Radiobiological research revealed tolerance limits of healthy tissues to be respected, effective total treatment doses of high cure probability depending on histology and tumor volume, and - more recently - altered fractionation schemes to be adapted to specific growth fractions and intrinsic radiosensitivities of clonogenic tumor cells. In addition, Biological Response Modifiers (BRM), such as cis-platinum, oxygen and hyperthermia may steepen cell survival curves of hypoxic tumor cells, others - such as tetrachiordekaoxid (TCDO) - may enhance repair of normal tissues. Computer assisted techniques in geometrical RT-planning based on individual healthy and pathologic anatomy (CT, MRT) provide high precision RT for well defined brain lesions by using dedicated linear accelerators (Stereotaxy). CT-based individual tissue compensators help with homogenization of distorted dose distributions in magna field irradiation for malignant lymphomas and with total body irradiation (TBI) before allogeneic bone marrow transplantation, e.g. for leukemia. RT with fast neutrons, Boron Neutron Capture Therapy (BNCT), RT with protons and heavy ions need to be tested in randomized trials before implementation into clinical routine.

  10. Clinical assessment of selenium status of livestock.

    PubMed

    Stowe, H D; Herdt, T H

    1992-12-01

    Assessment of the selenium status of livestock is an important aspect of production medicine, but variations in reported values between laboratories and between methods may be > 30%. Reliable interpretations require considerable experience with an assay and an extensive database from field and research case samples of a variety of species. The Michigan State University Animal Health Diagnostic Laboratory (MSU-ADHL) has offered Se analyses by acid-digestion and fluorometric detection since 1982. This laboratory expects serum Se values (nanograms per milliliter) of livestock to increase gradually with age from starting ranges for neonates of 50 to 80 for calves and sheep and 70 to 90 for foals and pigs. Expected or "normal" values for the adults are in the ranges of 70 to 100 for cattle, 120 to 150 for sheep, 130 to 160 for horses, and 180 to 220 for swine. Normal liver Se concentrations are considered to range between 1.2 and 2.0 micrograms/g on a dry weight basis, regardless of the species or age. Based on samples submitted to MSU-AHDL between September 1990 and August 1991, contemporary feeding practices in the Michigan area resulted in mean serum Se values (nanograms per milliliter) of 75 +/- 19 for adult Holsteins, 170 +/- 27 for adult swine (mixed breeds), and 137 +/- 30 for adult race horses. Within that period of time, two field cases of Se toxicity were diagnosed. One involved feeder pigs with a recorded high serum Se value of 1,525 ng/mL due to a commercial premix manufacturing error.(ABSTRACT TRUNCATED AT 250 WORDS)

  11. [Petit mal status epilepticus with unusual clinical manifestations].

    PubMed

    Savitskaia, O N; Karlov, V A; Gleĭzer, M A; Pmotskaia, E E

    1980-01-01

    A unique observation of an epileptic female examined in detail in a neurological clinic is presented. The patient was later hospitalized 3 times for disturbances of consciousness and extrapyramid disorders characterized by acute onset. An encephalographic examination carried out during such a state showed an epileptic status of atypic absence. The development of the Parkinsonian syndrome is regarded as a proof of the role of the caudate nucleus in the genesis of the petit mal epileptic status.

  12. Clinical decision making in seizures and status epilepticus.

    PubMed

    Teran, Felipe; Harper-Kirksey, Katrina; Jagoda, Andy

    2015-01-01

    Seizures and status epilepticus are frequent neurologic emergencies in the emergency department, accounting for 1% of all emergency department visits. The management of this time-sensitive and potentially life-threatening condition is challenging for both prehospital providers and emergency clinicians. The approach to seizing patients begins with differentiating seizure activity from mimics and follows with identifying potential secondary etiologies, such as alcohol-related seizures. The approach to the patient in status epilepticus and the patient with nonconvulsive status epilepticus constitutes a special clinical challenge. This review summarizes the best available evidence and recommendations regarding diagnosis and resuscitation of the seizing patient in the emergency setting.

  13. [Peliosis hepatis. A clinical status inventory].

    PubMed

    Spech, H J; Liehr, H

    1982-12-01

    Peliosis hepatis is a rare condition, recognizable by macroscopical view. It is characterized by multiple blood-filled cystic spaces in the liver parenchyma. According to 49 out of 152 more recent case reports (1951-1981/82) its spontaneous occurrence is frequently associated with malignant and toxic processes. However, in about 70% peliosis may be induced by the action of certain drugs, especially by 17 alpha-alkylated steroids. Usually peliosis is found by chance at autopsy or peritoneoscopy, as the clinical picture does not provide sufficient conclusive criteria to allow a definite diagnosis. The striking macroscopical appearance contrasts to the dispute on the as yet unestablished natural history. As most important complication spontaneous intraabdominal bleeding can occur in occasional cases. On the other hand, the patients predominantly die of their underlying diseases and not of a peliosis hepatis.

  14. Fosamprenavir clinical study meta-analysis in ART-naïve subjects: rare occurrence of virologic failure and selection of protease-associated mutations.

    PubMed

    Ross, Lisa; Vavro, Cindy; Wine, Brian; Liao, Qiming

    2006-01-01

    In recent ritonavir-boosted protease inhibitor (PI) studies, high efficacy rates have been observed, with few PI mutations detected. To better understand the types of mutations observed and their phenotypic impact and the likelihood of virologic failure (VF) on a regimen that includes either a ritonavir-boosted or unboosted PI, fosamprenavir, a meta-analysis of three studies (NEAT, SOLO, and KLEAN) of 922 ART-naïve participants receiving boosted (FPV/r) or unboosted fosamprenavir (FPV) plus abacavir/lamivudine was performed. 70% of participants by the missing and discontinuation equals failure analysis and 95% by the observed analysis had HIV-RNA <400 copies/mL through 48 weeks. Paired genotypes (baseline and follow-up) were obtained for 74/85 participants meeting VF analysis criteria. FPV-associated resistance mutations were detected in 5/74 patients with VF, with 4/5 receiving unboosted FPV; in four patients viruses developed I54L or M and one developed the V32I+I47V combination. No virus from patients with VF receiving FPV/r had reduced FPV susceptibility (RS), whereas virus from 3/4 of participants with VF who received unboosted FPV and who acquired FPV mutations had FPV RS. Little PI cross-resistance was detected in the VF virus; RS was observed for lopinavir, saquinavir, nelfinavir, atazanavir, and indinavir in 0, 0, 2, 0, and 1 of 5 subjects, respectively. These data suggest that inclusion of FPV as part of an initial HIV-treatment regimen is associated with low rates of VF. Selection of FPV resistance-associated mutations is unlikely, especially for FPV/r-containing regimens. If selection of FPV-associated mutations does occur, a second-line PI-containing regimen can be easily constructed.

  15. Kinetics of hepatitis C virus RNA decay, quasispecies evolution and risk of virological failure during telaprevir-based triple therapy in clinical practice.

    PubMed

    Cento, Valeria; Tontodonati, Monica; Di Maio, Velia Chiara; Bellocchi, Maria Concetta; Valenti, Fabrizio; Manunta, Alessandra; Fortuna, Serena; Armenia, Daniele; Carioti, Luca; Antonucci, Francesco Paolo; Bertoli, Ada; Trave, Francesca; Cacciatore, Pierluigi; Angelico, Mario; Navarra, Pierluigi; Neumann, Avidan U; Vecchiet, Jacopo; Parruti, Giustino; Babudieri, Sergio; Perno, Carlo Federico; Ceccherini-Silberstein, Francesca

    2015-03-01

    The used first generation protease inhibitors may be hampered by virological failure in partially interferon-sensitive patients. To investigate early hepatitis C virus (HCV)-RNA decay and quasispecies modifications, and disclose viral dynamics underlying failure. Viraemia decay at early time-points during telaprevir treatment was modelled according to Neumann et al. (1998). NS3-sequences were obtained by population-sequencing and ultradeep-454-pyrosequencing. 13 treatment-experienced (8 non-responders, 5 relapsers), and two cirrhotic naïve patients, received telaprevir+pegylated-interferon-α+ribavirin. Viraemia decay was biphasic. In all patients, first-phase was rapid and consistent, with a median [interquartile-range] viraemia decay of 2.8 [2.6-3.2]logIU/ml within 48h. Second-phase decay was slower, especially in failing patients: 3/3 showed <1logIU/ml decay between 48h and 2 weeks, and HCV-RNA >100IU/ml at week 2. Only one patient experiencing sustained viral response showed similar kinetics. By pyrosequencing, mutational freeze was observed in all 15 patients within the first 24h, but only in patients with sustained response afterwards. Indeed, 2/2 failing patients showed early resistance, as minor (V36A-T54A: prevalence <26% at 48h) or major (V36M/A-R155K: prevalence, 99.8% at week 2) variants. Following telaprevir administration, first-phase HCV-RNA decay is consistent with mutational freeze and limited/no viral replication, while second-phase is significantly slower in failing patients (with appearance of resistance), suggesting the usefulness of early HCV-RNA monitoring. Copyright © 2014 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  16. Summary of the 9th annual meeting of the Italian Society for Virology.

    PubMed

    Salata, Cristiano; Calistri, Arianna; Parolin, Cristina; Palù, Giorgio

    2011-01-01

    The 9th annual meeting of the Italian Society for Virology (SIV) comprised seven plenary sessions focused on: General virology and viral genetics; Virus-Host interaction and pathogenesis; Viral oncology; Emerging viruses and zoonotic, foodborne, and environmental pathways of transmission; Viral immunology and vaccines; Medical virology and antiviral therapy; Viral biotechnologies and gene therapy. Moreover, four hot topics were discussed in special lectures: the Pioneer in human virology lecture regarding the control of viral epidemics with particular emphasis on the human immunodeficiency virus (HIV), the Pioneer in plant virology lecture focused on cell responses to plant virus infection, a Keynote lecture on the epidemiology and genetic diversity of Crimea-Congo Hemorrhagic Fever virus, and the G.B. Rossi lecture on the molecular basis and clinical implications of human cytomegalovirus tropism for endothelial/epithelial cells. The meeting had an attendance of about 160 virologists. A summary of the plenary lectures and oral selected presentations is reported.

  17. Current Status of Operation and Management of Dental School Clinics.

    PubMed

    Reinhardt, John W

    2017-08-01

    This article summarizes the current status of the operation and management of dental school clinics as schools strive to provide excellent patient-centered care in an environment that is educationally sound, efficient, and financially strong. Clinical education is a large component of dental education and an area in which many dental schools have an opportunity to enhance revenue. Clinical efficiencies and alternative models of clinical education are evolving in U.S. dental schools, and this article describes some of those evolutionary changes. This article was written as part of the project "Advancing Dental Education in the 21(st) Century."

  18. General concepts of virology.

    PubMed

    Kennedy, Melissa; Greenacre, Cheryl B

    2005-01-01

    A basic understanding of viruses and how they replicate and produce disease can aid in the management of virus infections. Parameters, such as clinical signs, sample and test selection, prognosis, and control, are implicit in this understanding. Information increases almost daily about known and emerging viruses; this impacts our ability to manage and control infections.

  19. Status epilepticus in the elderly: epidemiology, clinical aspects and treatment

    PubMed Central

    de Assis, Telma M.R.; Costa, Gersonita; Bacellar, Aroldo; Orsini, Marco; Nascimento, Osvaldo J.M.

    2012-01-01

    The aim of the study was to review the epidemiology, clinical profile and discuss the etiology, prognosis and treatment options in patients aged 60 years or older presenting with status epilepticus. We performed a systematic review involving studies published from 1996 to 2010, in Medline/PubMed, Scientific Electronic Library on line (Scielo), Latin-American and Caribbean Center of Health Sciences Information (Lilacs) databases and textbooks. Related articles published before 1996, when relevant for discussing epilepsy in older people, were also included. Several population studies had shown an increased incidence of status epilepticus after the age of 60 years. Status epilepticus is a medical and neurological emergency that is associated with high morbidity and mortality, and is a major concern in the elderly compared to the general population. Prompt diagnosis and effective treatment of convulsive status epilepticus are crucial to avoid brain injury and reduce the fatality rate in this age group. PMID:23355930

  20. Clinical assessment of nutritional status and feeding programs in horses.

    PubMed

    Becvarova, Iveta; Pleasant, R Scott; Thatcher, Craig D

    2009-04-01

    Veterinarians are a primary source of nutritional information and advice for horse owners. This article reviews methods for clinical assessment of nutritional status and feeding programs that can be applied to an individual horse or group of horses. Physical examination, including measurement of body weight and evaluation of body condition score, estimation of nutrient requirements and the nutrient content of the horse's diet, and evaluation of the feeding method are important components of the assessment. Ongoing clinical assessment of health and body condition will gauge the need for reassessment of the feeding plan. Obvious indications for prompt reevaluation of diet and feeding include changes in health status (eg, body condition), life stage or physiologic state (eg, pregnancy), or performance status.

  1. Development and Current Status of Clinical Pharmacy Education in China

    PubMed Central

    Yee, Gary; Zhou, Naitong; Yang, Nan; Jiang, Xuehua; Klepser, Donald

    2014-01-01

    Objective. To describe the current status and developing trend of clinical pharmacy education in China. Methods. Descriptive analysis of data and information about the clinical pharmacy specialty, pharmacy colleges, and curriculum from literature, college websites, and statistics from the Ministry of Health (MOH) and Ministry of Education (MOE) websites was conducted. Results. Clinical pharmacy programs were established in China in 1989 but developed more fully after 2006. In 2012, there were 30 pharmacy colleges with clinical pharmacy undergraduate programs, which included a bachelor’s degree in clinical pharmacy and a clinical pharmacy concentration within the BS programs of pharmacy or medicine. More than 40 colleges within the university system offer 4 types of master’s degree programs in clinical pharmacy. Five universities offer a PhD program in clinical pharmacy. Three postgraduate programs exist, which train hospital pharmacists and clinical pharmacists: the 3+2 year Hospital Pharmacist Standardized Training Program at Peking hospitals; the 1-year Clinical Pharmacist Training Program sponsored by the MOH; and the 2-year Clinical Pharmacist Residency Program provided by West China Hospital at Sichuan University. Conclusion. A growing clinical pharmacy education system has been established and has become an important subfield in Chinese pharmacy education. Measures should be taken to further promote the development of clinical pharmacy education in China. PMID:25386022

  2. [The logic of diagnoses used in expert systems. II. Applications in virology].

    PubMed

    Cristea, A; Zaharia, C N

    1988-01-01

    Inference capacity of different clinical or paraclinical examinations are analyzed, whose results allow to establish the definitive diagnosis through gradual integrations. The knowledge of the inference capacity is very useful for the expert systems applied in virology.

  3. Classification of Use Status for Dietary Supplements in Clinical Notes.

    PubMed

    Fan, Yadan; He, Lu; Zhang, Rui

    2016-12-01

    Clinical notes contain rich information about dietary supplements, which are critical for detecting signals of dietary supplement side effects and interactions between drugs and supplements. One of the important factors of supplement documentation is usage status, such as started and discontinuation. Such information is usually stored in the unstructured clinical notes. We developed a rule-based classifier to identify supplement usage status in clinical notes. The categories referring to the patient's status of supplement use were classified into four classes: Continuing (C), Discontinued (D), Started (S), and Unclassified (U). Clinical notes containing 10 of the most commonly consumed supplements (i.e., alfalfa, echinacea, fish oil, garlic, ginger, ginkgo, ginseng, melatonin, St. John's Wort, and Vitamin E) were retrieved from the University of Minnesota Clinical Data Repository. The gold standard was defined by manually annotating 1000 randomly selected sentences or statements mentioning at least one of these 10 supplements. The rules in the classifier was initially developed on two-thirds of the set of 7 supplements (i.e., alfalfa, garlic, ginger, ginkgo, ginseng, St. John's Wort, and Vitamin E); the performance was evaluated on the remaining one-third of this set. To evaluate the generalizability of rules, we further validated the second testing set on other 3 supplements (i.e., echinacea, fish oil, and melatonin). The performance of the classifier achieved F-measures of 0.95, 0.97, 0.96, and 0.96 for status C, D, S, and U on 7 supplements, respectively. The classifier also showed good generalizability when it was applied to the other 3 supplements with F-measures of 0.96 for C, 0.96 for D, 0.95 for S, and 0.89 for U. This study demonstrated that the classifier can accurately classify supplement usage status, which can be further integrated as a module into the existing natural language processing pipeline for supporting dietary supplement knowledge discovery.

  4. [Virological research on appendicitis].

    PubMed

    Stănescu, D; Sternberg, D; Chirilă, R; Teleguţă, L; Tănase, M; Copelovici, Y

    1988-01-01

    Investigations were conducted on groups of subjects hospitalized in surgery services with a clinical diagnosis of acute or chronic appendicitis, to detect the presence of inframicrobial antibodies and antigens, as well as that of the C reactive protein in these patients as compared with a control group. The results of serological tests and of the examination of pieces of appendix are also presented. The obtained data are used as arguments for the theory of an inframicrobial infection part in some acute and chronic forms of appendicitis.

  5. Updates in immunoassays: virology.

    PubMed

    Josko, Deborah

    2012-01-01

    Virus identification is a challenge to the clinical microbiologist since growing viruses in traditional cell culture is labor intensive, time consuming, and subject to contamination. The advent of rapid and automated immunoassays has eliminated this problem by generating positive results in minutes to hours. For example, testing for infectious mononucleosis can yield a positive result in 3-8 minutes as seen with the Beckman Coulter, Inc. ICON Mono test or in 5-15 minutes with the MONO Mononucleosis Rapid Test Device marketed by ACON Laboratories, Inc. Fully automated immunoassay analyzers provide fast, accurate, sensitive results that aid in a prompt and accurate diagnosis for the patient. Turnaround times are shortened, allowing for timely medical intervention and treatment. The priority in any hospital or medical facility is to treat the patient as quickly and appropriately as possible. By using immunoassays, clinical laboratory professionals are able to report out correct results in a timely manner, ensuring overall positive patient outcomes and improved quality of healthcare.

  6. Treatment Extension of Pegylated Interferon Alpha and Ribavirin Does Not Improve SVR in Patients with Genotypes 2/3 without Rapid Virological Response (OPTEX Trial): A Prospective, Randomized, Two-Arm, Multicentre Phase IV Clinical Trial

    PubMed Central

    Heidrich, Benjamin; Cordes, Hans-Jörg; Klinker, Hartwig; Möller, Bernd; Naumann, Uwe; Rössle, Martin; Kraus, Michael R.; Böker, Klaus H.; Roggel, Christoph; Schuchmann, Marcus; Stoehr, Albrecht; Trein, Andreas; Hardtke, Svenja; Gonnermann, Andrea; Koch, Armin; Wedemeyer, Heiner; Manns, Michael P.; Cornberg, Markus

    2015-01-01

    Although sofosbuvir has been approved for patients with genotypes 2/3 (G2/3), many parts of the world still consider pegylated Interferon alpha (P) and ribavirin (R) as standard of care for G2/3. Patients with rapid virological response (RVR) show response rates >80%. However, SVR (sustained virological response) in non-RVR patients is not satisfactory. Longer treatment duration may be required but evidence from prospective trials are lacking. A total of 1006 chronic HCV genotype 2/3 patients treated with P/R were recruited into a German HepNet multicenter screening registry. Of those, only 226 patients were still HCV RNA positive at week 4 (non-RVR). Non-RVR patients with ongoing response after 24 weeks P-2b/R qualified for OPTEX, a randomized trial investigating treatment extension of additional 24 weeks (total 48 weeks, Group A) or additional 12 weeks (total 36 weeks, group B) of 1.5 μg/kg P-2b and 800-1400 mg R. Due to the low number of patients without RVR, the number of 150 anticipated study patients was not met and only 99 non-RVR patients (n=50 Group A, n=49 Group B) could be enrolled into the OPTEX trial. Baseline factors did not differ between groups. Sixteen patients had G2 and 83 patients G3. Based on the ITT (intention-to-treat) analysis, 68% [55%; 81%] in Group A and 57% [43%; 71%] in Group B achieved SVR (p= 0.31). The primary endpoint of better SVR rates in Group A compared to a historical control group (SVR 70%) was not met. In conclusion, approximately 23% of G2/3 patients did not achieve RVR in a real world setting. However, subsequent recruitment in a treatment-extension study was difficult. Prolonged therapy beyond 24 weeks did not result in higher SVR compared to a historical control group. Trial Registration ClinicalTrials.gov NCT00803309 PMID:26057627

  7. Clinical trials in acute repetitive seizures and status epilepticus.

    PubMed

    Shorvon, Simon

    2012-06-01

    This paper reviews the clinical trials in acute repetitive seizures and in tonic-clonic status epilepticus. There are good randomised controlled studies on the use of benzodiazepines in early status epilepticus, but an inadequate trial base in the later stages. Therapy has therefore to be based on open studies, although in the later stages there is also a dearth of open data. Tonic-clonic status epilepticus is a medical emergency and a condition with a significant mortality. The lack of information compromises optimal therapy. This paper reviews the reasons for the lack of data and the problems associated with collecting data. It is proposed that, in the first instance, the best way of improving the quality of evidence would be a multinational case registry of existing practice.

  8. Virological surveillance for dengue haemorrhagic fever in Indonesia using the mosquito inoculation technique*

    PubMed Central

    Gubler, D. J.; Suharyono, W.; Sumarmo; Wulur, H.; Jahja, E.; Saroso, J. Sulianti

    1979-01-01

    A dengue haemorrhagic fever surveillance system in Indonesia, based on virological and clinical observations, is described. The system uses the mosquito inoculation technique for virus isolation and is simple, economical, and well suited for endemic areas where support and facilities are limited. The data suggest that with good cooperation between the hospital and the virology laboratory, new serotypes and possibly even new strains of virus can be identified before the onset of epidemic activity. This type of virological surveillance may make it possible to prevent major epidemics in the future. PMID:43776

  9. The history of tumor virology.

    PubMed

    Javier, Ronald T; Butel, Janet S

    2008-10-01

    In the century since its inception, the field of tumor virology has provided groundbreaking insights into the causes of human cancer. Peyton Rous founded this scientific field in 1911 by discovering an avian virus that induced tumors in chickens; however, it took 40 years for the scientific community to comprehend the effect of this seminal finding. Later identification of mammalian tumor viruses in the 1930s by Richard Shope and John Bittner, and in the 1950s by Ludwik Gross, sparked the first intense interest in tumor virology by suggesting the possibility of a similar causal role for viruses in human cancers. This change in attitude opened the door in the 1960s and 1970s for the discovery of the first human tumor viruses--EBV, hepatitis B virus, and the papillomaviruses. Such knowledge proved instrumental to the development of the first cancer vaccines against cancers having an infectious etiology. Tumor virologists additionally recognized that viruses could serve as powerful discovery tools, leading to revolutionary breakthroughs in the 1970s and 1980s that included the concept of the oncogene, the identification of the p53 tumor suppressor, and the function of the retinoblastoma tumor suppressor. The subsequent availability of more advanced molecular technologies paved the way in the 1980s and 1990s for the identification of additional human tumor viruses--human T-cell leukemia virus type 1, hepatitis C virus, and Kaposi's sarcoma virus. In fact, current estimates suggest that viruses are involved in 15% to 20% of human cancers worldwide. Thus, viruses not only have been shown to represent etiologic agents for many human cancers but have also served as tools to reveal mechanisms that are involved in all human malignancies. This rich history promises that tumor virology will continue to contribute to our understanding of cancer and to the development of new therapeutic and preventive measures for this disease in the 21st century.

  10. The History of Tumor Virology

    PubMed Central

    Javier, Ronald T.; Butel, Janet S.

    2012-01-01

    In the century since its inception, the field of tumor virology has provided groundbreaking insights into the causes of human cancer. Peyton Rous founded this scientific field in 1911 by discovering an avian virus that induced tumors in chickens; however, it took 40 years for the scientific community to comprehend the effect of this seminal finding. Later identification of mammalian tumor viruses in the 1930s by Richard Shope and John Bittner, and in the 1950s by Ludwik Gross, sparked the first intense interest in tumor virology by suggesting the possibility of a similar causal role for viruses in human cancers. This change in attitude opened the door in the 1960s and 1970s for the discovery of the first human tumor viruses—EBV, hepatitis B virus, and the papillomaviruses. Such knowledge proved instrumental to the development of the first cancer vaccines against cancers having an infectious etiology. Tumor virologists additionally recognized that viruses could serve as powerful discovery tools, leading to revolutionary breakthroughs in the 1970s and 1980s that included the concept of the oncogene, the identification of the p53 tumor suppressor, and the function of the retinoblastoma tumor suppressor. The subsequent availability of more advanced molecular technologies paved the way in the 1980s and 1990s for the identification of additional human tumor viruses—human T-cell leukemia virus type 1, hepatitis C virus, and Kaposi’s sarcoma virus. In fact, current estimates suggest that viruses are involved in 15% to 20% of human cancers worldwide. Thus, viruses not only have been shown to represent etiologic agents for many human cancers but have also served as tools to reveal mechanisms that are involved in all human malignancies. This rich history promises that tumor virology will continue to contribute to our understanding of cancer and to the development of new therapeutic and preventive measures for this disease in the 21st century. PMID:18829521

  11. [Clinical algorithms in the treatment of status epilepticus in children].

    PubMed

    Zubcević, S; Buljina, A; Gavranović, M; Uzicanin, S; Catibusić, F

    1999-01-01

    The clinical algorithm is a text format that is specially suited for presenting a sequence of clinical decisions, for teaching clinical decision making, and for guiding patient care. Clinical algorithms are compared as to their clinical usefulness with decision analysis. We have tried to make clinical algorithm for managing status epilepticus in children that can be applicable to our conditions. Most of the algorithms that are made on this subject include drugs and procedures that are not available at our hospital. We identified performance requirement, defined the set of problems to be solved as well as who would solve them, developed drafts in several versions and put them in the discussion with experts in this field. Algorithm was tested and revised and graphical acceptability was achieved. In the algorithm we tried to clearly define how the clinician should make the decision and to be provided with appropriate feedback. In one year period of experience in working we found this algorithm very useful in managing status epilepticus in children, as well as in teaching young doctors the specifities of algorithms and this specific issue. Their feedback is that they find that it provides the framework for facilitating thinking about clinical problems. Sometimes we hear objection that algorithms may not apply to a specific patient. This objection is based on misunderstanding how algorithms are used and should be corrected by a proper explanation of their use. We conclude that methods should be sought for writing clinical algorithms that represent expert consensus. A clinical algorithm can then be written for many areas of medical decision making that can be standardized. Medical practice would then be presented to students more effectively, accurately and understood better.

  12. Clinical Status of Adolescents with Perinatal HIV at Transfer to Adult Care in the UK/Ireland.

    PubMed

    Collins, Intira Jeannie; Foster, Caroline; Tostevin, Anna; Tookey, Pat; Riordan, Andrew; Dunn, David; Gibb, D M; Judd, Ali

    2017-04-15

    Increasing numbers of children infected perinatally with human immunodeficiency virus (HIV) are surviving to adolescence and transitioning to adult care, yet there are scarce data on their clinical status at transfer. We analyzed prospective cohort data from the UK/Ireland national Collaborative HIV Pediatric Study (CHIPS). Clinical status at last pediatric clinic visit prior to transfer was described. Factors associated with higher CD4 cell count and viral load (VL) suppression<400 c/mL among patients on antiretroviral therapy (ART) at transfer were assessed using linear and logistic regression, respectively. Data were matched with the UK HIV Drug Resistance Database (UKHIVDRB) to assess cumulative resistance profiles at transfer. Of 1,907 children followed in CHIPS from 1996 to November 2014, 644 (34%) transferred to adult care: 53% were female, 62% born outside the UK/Ireland, 75% black African. At last pediatric follow-up, median age was 17.4 years [interquartile range 16.5,18.1], 27% had previous AIDS diagnosis, CD4 was 444 cells/mm3 [280, 643], 76% were on ART, 13% off-ART, and 11% ART-naive. Among patients on ART, 74% had VL<400 c/mL. In multivariable analysis, higher CD4 at transfer was associated with younger age, higher CD4 at ART initiation and lower VL at transfer (P ≤ .001). Predictors of viral suppression include no AIDS diagnosis and later year of transfer (P ≤ .05). Of 291 patients with resistance data, 82% had resistance to ≥1 drug class, 56% to ≥2 classes and 12% had triple-class resistance. Three-quarters of adolescents were on stable ART at transfer, of whom 74% were virologically suppressed. The prevalence of triple-class resistance was relatively low at 12%.

  13. Smoking Status Influences Clinical Outcome in Collagenous Colitis.

    PubMed

    Münch, Andreas; Tysk, Curt; Bohr, Johan; Madisch, Ahmed; Bonderup, Ole K; Mohrbacher, Ralf; Mueller, Ralph; Greinwald, Roland; Ström, Magnus; Miehlke, Stephan

    2016-04-01

    The relationship between clinical and histological parameters in collagenous colitis (CC) is poorly understood. Smoking is a risk factor for CC, whereas its impact on clinical activity and outcome is not well known. In a post hoc analysis of pooled data from two randomized controlled trials we assessed the association between demographic data (gender, age, smoking habits, family history of inflammatory bowel disease), clinical variables (duration of symptoms, mean number of stools/watery stools per day, abdominal pain, clinical remission) and histological data (thickness of the collagen band, inflammation of the lamina propria, total numbers of intraepithelial lymphocytes, degeneration). Moreover, we analysed the predictive value of baseline parameters for clinical outcome in a logistic regression model. Pooled data were available from 202 patients with active CC, of whom 36% were current smokers, 29% former smokers and 35% non-smokers. Smoking status was associated with decreased ability to achieve clinical remission (current smokers vs non-smokers: odds ratio [OR] 0.31, 95% confidence interval [CI] 0.10-0.98, p = 0.045; former smokers vs non-smokers: OR 0.19, 95% CI 0.05-0.73, p = 0.016). Current smokers had an increased mean number of watery stools at baseline compared with non-smokers (p = 0.051) and increased mean number of watery stools per se was associated with decreased likelihood of obtaining clinical remission (OR 0.63, 95% CI 0.47-0.86, p = 0.003). Patient characteristics and histology at baseline had no association with clinical parameters and no predictive value for clinical outcome. Smoking worsens clinical symptoms in CC and is associated with an increased number of watery stools and decreased likelihood of achieving clinical remission. There is no significant association between histology and clinical data. Copyright © 2015 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For

  14. Comparative study on the clinical and virological characteristics among patients with single occult hepatitis B virus (HBV), single occult hepatitis C virus (HCV) and occult HBV and HCV dual infection.

    PubMed

    Castillo, Inmaculada; Rodríguez-Iñigo, Elena; López-Alcorocho, Juan Manuel; Bartolomé, Javier; Pardo, Margarita; Carreño, Vicente

    2007-03-01

    Occult hepatitis B virus (HBV) and occult hepatitis C virus (HCV) infection are two recently described different forms of HBV and HCV infections. This work compares the clinical, virologic, and histologic characteristics of patients with occult dual infection to those of patients with single occult HBV or HCV infection. Seventy-six patients with abnormal liver function tests of unknown etiology (serum HBsAg, anti-HCV, HBV-DNA, and HCV-RNA negative) were included in the study. Viral genomes were tested in liver by real-time PCR and confirmed by in situ hybridization. Of the 76 patients, 17 had occult HBV infection (intrahepatic HBV-DNA positive, HCV-RNA negative), 35 had occult HCV infection (intrahepatic HCV-RNA positive, HBV-DNA negative) and 24 occult dual infection (intrahepatic HCV-RNA and HBV-DNA). No differences among the three groups were found regarding clinical and epidemiologic data. The median load of intrahepatic genomic and antigenomic HCV-RNA strands was similar between single occult HCV infection and occult HBV and HCV dual infection. The percentage of HCV-infected hepatocytes did not differ between these groups. In occult single HBV infection, intrahepatic levels of HBV-DNA and percentage of HBV-infected hepatocytes were similar to the group of patients with occult dual infection. Finally, no differences were found in histological liver damage among the three groups. In conclusion, liver disease in patients with occult dual infection was not more severe than in patients with single occult HBV or occult HCV infection. Moreover, in occult dual infection there is no a reciprocal inhibition of the viral genomes.

  15. 42 CFR 493.831 - Standard; Virology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Standard; Virology. 493.831 Section 493.831 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Tests § 493.831 Standard; Virology. (a) Failure to attain an overall testing event score of at least...

  16. 42 CFR 493.831 - Standard; Virology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard; Virology. 493.831 Section 493.831 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Tests § 493.831 Standard; Virology. (a) Failure to attain an overall testing event score of at least...

  17. 42 CFR 493.831 - Standard; Virology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Standard; Virology. 493.831 Section 493.831 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Tests § 493.831 Standard; Virology. (a) Failure to attain an overall testing event score of at least...

  18. 42 CFR 493.831 - Standard; Virology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Standard; Virology. 493.831 Section 493.831 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Tests § 493.831 Standard; Virology. (a) Failure to attain an overall testing event score of at least...

  19. 42 CFR 493.1265 - Standard: Virology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Standard: Virology. 493.1265 Section 493.1265 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1265 Standard: Virology. (a) When using cell culture to isolate or identify viruses,...

  20. 42 CFR 493.831 - Standard; Virology.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 5 2011-10-01 2011-10-01 false Standard; Virology. 493.831 Section 493.831 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... Tests § 493.831 Standard; Virology. (a) Failure to attain an overall testing event score of at least...

  1. 42 CFR 493.1265 - Standard: Virology.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 5 2014-10-01 2014-10-01 false Standard: Virology. 493.1265 Section 493.1265 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1265 Standard: Virology. (a) When using cell culture to isolate or identify viruses,...

  2. 42 CFR 493.1265 - Standard: Virology.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 5 2013-10-01 2013-10-01 false Standard: Virology. 493.1265 Section 493.1265 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1265 Standard: Virology. (a) When using cell culture to isolate or identify viruses,...

  3. 42 CFR 493.1265 - Standard: Virology.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 5 2012-10-01 2012-10-01 false Standard: Virology. 493.1265 Section 493.1265 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1265 Standard: Virology. (a) When using cell culture to isolate or identify viruses,...

  4. 42 CFR 493.1265 - Standard: Virology.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 5 2010-10-01 2010-10-01 false Standard: Virology. 493.1265 Section 493.1265 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES... Systems § 493.1265 Standard: Virology. (a) When using cell culture to isolate or identify viruses,...

  5. Integrative Virology for Senior Medical Students.

    ERIC Educational Resources Information Center

    Koment, Roger W.

    1991-01-01

    The article describes a senior elective in virology developed at the University of South Dakota School of Medicine. Students work independently through a series of course units, selecting 12 study topics from a catalog of 35 topics in medical virology and discussing their reading daily with the professor. (DB)

  6. Integrative Virology for Senior Medical Students.

    ERIC Educational Resources Information Center

    Koment, Roger W.

    1991-01-01

    The article describes a senior elective in virology developed at the University of South Dakota School of Medicine. Students work independently through a series of course units, selecting 12 study topics from a catalog of 35 topics in medical virology and discussing their reading daily with the professor. (DB)

  7. Impact of CD4 and CD8 dynamics and viral rebounds on loss of virological control in HIV controllers

    PubMed Central

    Chereau, Fanny; Madec, Yoann; Sabin, Caroline; Obel, Niels; Ruiz-Mateos, Ezequiel; Chrysos, Georgios; Fidler, Sarah; Lehmann, Clara; Zangerle, Robert; Wittkop, Linda; Reiss, Peter; Hamouda, Osamah; Estrada Perez, Vicente; Leal, Manuel; Mocroft, Amanda; Garcia De Olalla, Patricia; Ammassari, Adriana; D’Arminio Monforte, Antonella; Mussini, Cristina; Segura, Ferran; Castagna, Antonella; Cavassini, Matthias; Grabar, Sophie; Morlat, Philippe; De Wit, Stéphane; Lambotte, Olivier; Meyer, Laurence

    2017-01-01

    Objective HIV controllers (HICs) spontaneously maintain HIV viral replication at low level without antiretroviral therapy (ART), a small number of whom will eventually lose this ability to control HIV viremia. The objective was to identify factors associated with loss of virological control. Methods HICs were identified in COHERE on the basis of ≥5 consecutive viral loads (VL) ≤500 copies/mL over ≥1 year whilst ART-naive, with the last VL ≤500 copies/mL measured ≥5 years after HIV diagnosis. Loss of virological control was defined as 2 consecutive VL >2000 copies/mL. Duration of HIV control was described using cumulative incidence method, considering loss of virological control, ART initiation and death during virological control as competing outcomes. Factors associated with loss of virological control were identified using Cox models. CD4 and CD8 dynamics were described using mixed-effect linear models. Results We identified 1067 HICs; 86 lost virological control, 293 initiated ART, and 13 died during virological control. Six years after confirmation of HIC status, the probability of losing virological control, initiating ART and dying were 13%, 37%, and 2%. Current lower CD4/CD8 ratio and a history of transient viral rebounds were associated with an increased risk of losing virological control. CD4 declined and CD8 increased before loss of virological control, and before viral rebounds. Discussion Expansion of CD8 and decline of CD4 during HIV control may result from repeated low-level viremia. Our findings suggest that in addition to superinfection, other mechanisms, such as low grade viral replication, can lead to loss of virological control in HICs. PMID:28380038

  8. Relationship between clinical and BK virological response in patients with late hemorrhagic cystitis treated with cidofovir: a retrospective study from the European Group for Blood and Marrow Transplantation.

    PubMed

    Cesaro, S; Pillon, M; Tridello, G; Aljurf, M; Martino, R; Schroyens, W; Nozzoli, C; Barba, P; Faraci, M; Fagioli, F; Cappelli, B; Cordonnier, C; Al-Mohareb, F; Floisand, Y; Greil, J; Panizzolo, I S; Santarone, S

    2013-06-01

    To investigate the relationship between clinical response and modification of BK viremia, we assessed retrospectively 32 cases of hemorrhagic cystitis (HC) after allogeneic hematopoietic SCT that were treated with i.v. cidofovir (CDV). They were 22 men (69%) and 10 women (31%) with a median age of 24 years, range 3-62. The median number of CDV doses was 3, range 1-8, and the treatment lasted for a median of 3 weeks, range 1-10. Clinical improvement of HC was observed in 27 patients (84%). In 12 of 32 episodes (37.5%), BK viremia was determined before every CDV administration and a complete clinical response was observed in 10 of 12 patients (83%), the reduction of BK viremia load being 1 log by 2 weeks after starting CDV. Nephrotoxicity related to CDV was observed in nine patients. Among 26 patients with 100-day follow-up, 4 of 4 patients who had a complete clinical response by 30 days were alive vs 16 of 22 (73%) who did not have the resolution of HC in this time frame. We conclude that in patients with HC, the response to CDV treatment is usually associated with a significant reduction of BK viremia load.

  9. Virological, serological and epidemiological study of 255 consecutive cases of genital herpes in a sexually transmitted disease clinic of Paris (France): a prospective study.

    PubMed

    Janier, M; Scieux, C; Méouchi, R; Tournoux, C; Porcher, R; Maillard, A; Fouéré, S; Taquin, Y; Lassau, F; Morel, P

    2006-01-01

    Some studies (mostly retrospective) have pointed to an increasing frequency (up to 60%) of herpes simplex virus type 1 (HSV-1) in genital herpes (GH), but they were biased towards severe or atypical cases. We wished to evaluate the frequency of HSV-1 in patients attending our clinic for both first and recurrent episodes of GH. All patients (men and women) with genital lesions compatible with GH were included in a prospective study between May 1999 and April 2002. For all patients a standardized questionnaire, clinical examination, MRC5 culture (Dade Behring), polymerase chain reaction (PCR)-herpes consensus (Argène Biosoft) in case of negative culture and type-specific herpes serology HSV-1 and HSV-2 (Elisa Eurobio) were obtained. Predictive factors associated with HSV-1 and HSV-2 GH were studied by uni- and multivariable analyses. In all, 255 patients had a positive culture (n = 216) or PCR (n = 39). A total of 248 patients had typable herpes (148 men and 100 women). Median age was 33 (27-43); 20% had anal herpes; 48% had clinically recurrent lesions; 21% were HIV +; 20% of men were homosexual; 77% practised oral sex. In all, 36 were HSV-1 (14.5%): more in women, 25/100 (25%), than in men, 11/148 (7.5%) (odds ratio [OR]: 4 [1.8-9.1], P = 0.008). HSV-1 accounted for 23% of cases of first clinical episodes (women: 31.5%; men: 14.7%) (P = 0.02) and 6% of clinically recurrent episodes (women: 15%; men: 1.2%) (OR: 3.8 [1.6-9.1], P = 0.0033). Serological study was done in 239: primary infection was disclosed in 33 (HSV-1: 61%), HSV-2 non-primary first episode in 22 and recurrence in 184 (HSV-1: 8%). In all, 37% of recurrent episodes presented as a first clinical episode. HSV-1 was linked in men with homosexuality (P<0.01) and anilingus (P<0.01), in women with younger age (P<0.01), more sexual intercourses (P<0.0001) and more oral sex (P<0.001). Although HSV-1 is frequent in first clinical (23%) and primary (61%) episodes of GH, recurrent GH remains mostly due to HSV-2

  10. Nonconvulsive Status Epilepticus Resembling Clinical Absence with Atypical EEG Pattern

    PubMed Central

    Mysore, Channaiah Srikanth; Zabad, Rana; Bertoni, John

    2017-01-01

    Objective. We are reporting two cases: a patient with steroid responsive encephalopathy associated with autoimmune thyroiditis (SREAT) and another patient with secondary progressive multiple sclerosis (SPMS), both presenting with altered mental status (AMS) and later diagnosed with nonconvulsive atypical absence status epilepticus (AS), with atypical EEG changes. Methods. A report of two cases. Results. A patient with history of SREAT and the other with SPMS had multiple admissions due to AMS. For both, EEG revealed the presence of a high voltage generalized sharply contoured theta activity. A diagnosis of NCSE with clinical features of AS was made based on both clinical and EEG features. There was significant clinical and electrographic improvement with administration of levetiracetam for both patients in addition to sodium valproate and Solumedrol for the SREAT patient. Both patients continued to be seizure free on follow-up few months later. Conclusions. This is a report of two cases of atypical AS, with atypical EEG, in patients with different neurological conditions. Prompt clinical and EEG recovery occurred following appropriate medical treatment. We think that this condition might be underreported and could significantly benefit from prompt treatment when appropriately diagnosed. PMID:28203468

  11. Virologic, Clinical, and Immune Response Outcomes of Patients With Hepatitis C Virus-Associated Cryoglobulinemia Treated With Direct-Acting Antivirals.

    PubMed

    Bonacci, Martín; Lens, Sabela; Londoño, María-Carlota; Mariño, Zoe; Cid, Maria C; Ramos-Casals, Manuel; Sánchez-Tapias, Jose María; Forns, Xavier; Hernández-Rodríguez, José

    2017-04-01

    Cryoglobulins (circulating immune complexes of polyclonal IgG, monoclonal IgM, and rheumatoid factor) are detected in the circulation of 40% to 60% of patients with chronic hepatitis C virus infection, and cryoglobulinemic vasculitis (CV) is observed in approximately 10% of patients. We aimed to assess the clinical and immune effects of direct-acting antiviral treatment. We performed a prospective study of 64 patients with HCV infection with circulating cryoglobulins receiving direct-acting antiviral therapy at a single center in Barcelona, Spain, from January 2014 through April 2016. Patients were classified as having CV (n = 35) or asymptomatic circulating cryoglobulins (ACC, n = 29). Clinical response was considered complete if a patient's Birmingham Vasculitis Activity Score (version 3) was 0, or if all affected organs improved 12 weeks after the end of therapy. A complete immunologic response (CIR) was defined as no detection of circulating cryoglobulins and normalized levels of complement and/or rheumatoid factor. Clinical manifestations of CV included purpura (65%), weakness (70%), arthralgia (31%), myalgia (20%), peripheral neuropathy (50%), and renal involvement (20%). At baseline, patients with CV had significantly higher levels of rheumatoid factor and lower levels of C4 complement than patients with ACC, whereas cryocrits were similar between groups (3.2% vs 2.6%). Overall, 60 patients (94%) had a sustained viral response 12 weeks after therapy. Among patients with CV, the median Birmingham Vasculitis Activity Score (version 3) decreased from 9 (range, 2-31) to 3 (range, 0-12) (P < .001). Twenty-five patients with CV (71%) achieved a complete clinical response. Immune-suppressive therapy was reduced for 4 of 13 patients and withdrawn for 6 of 13. Overall, 48% of patients achieved a CIR. A low baseline cryocrit level (<2.7%) was the only factor associated with CIR (odds ratio, 9.8; 95% confidence interval, 2.2-44; P = .03). Viral eradication was

  12. Vaccination of ponies with the IE gene of EHV-1 in a recombinant modified live vaccinia vector protects against clinical and virological disease.

    PubMed

    Soboll, G; Breathnach, C C; Kydd, J H; Hussey, S B; Mealey, R M; Lunn, D P

    2010-05-15

    The control of EHV-1 infection by cytotoxic T-cell responses (CTL) via a reduction in cell associated viremia remains an important goal in horses. Unfortunately, current vaccines are inefficient at inducing these responses. We have identified the immediate early (IE) gene of EHV-1 as a potent stimulator of virus-specific CTL responses in ponies expressing a specific MHC class I serological haplotype (A3/B2). This study was designed to determine if vaccination of A3/B2 MHC I positive ponies with the IE gene could induce protection and immune responses associated with cell mediated immunity. Ponies expressing the MHC-I A3/B2 haplotype (A3/B2 vaccinates) and ponies with a different MHC I haplotype (either non-A3 vaccinates or A3-non-B2 vaccinates) were vaccinated with a recombinant modified vaccinia Ankara (rMVA) vector expressing the IE gene on 3 occasions and vaccinates and unvaccinated controls were challenge infected 8 weeks after the last vaccination. Interferon gamma (IFN-gamma) mRNA and antibody titers were determined throughout the study and clinical signs, nasal virus shedding and viremia were determined following challenge infection. Vaccination of A3/B2 vaccinates conferred significant clinical protection and a significant reduction in EHV-1 viremia. IFN-gamma mRNA increased significantly following vaccination in the A3/B2 vaccinates. Antibody titers remained low until after challenge infection, indicating that no accidental field acquired or recrudescent EHV-1 infection had occurred. In summary, this is an important study showing that vaccination of ponies with the EHV-1 IE protein provides not only reduction in clinical disease but also reduction of cell associated viremia, which is a prerequisite for the prevention of abortion and neurological disease. Copyright 2009 Elsevier B.V. All rights reserved.

  13. CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients

    PubMed Central

    Lu, Wei; Mehraj, Vikram; Vyboh, Kishanda; Cao, Wei; Li, Taisheng; Routy, Jean-Pierre

    2015-01-01

    Introduction Absolute CD4 T cell count and plasma viral load have been established as predictors of HIV disease progression, and CD4 T cell count is used as an indicator for initiation of antiretroviral therapy. Following long-term therapy, patients generally present with significant CD4 T cell recovery contrasting with persistently elevated CD8 T cell counts, which leads to a partial restoration of CD4:CD8 ratio. This review focuses on the relevance of the CD4:CD8 ratio on clinical outcomes, immune dysfunction and HIV reservoir size in long-term treated patients. Method We conducted a comprehensive literature review of publications in English language using major electronic databases. Our search was focused on factors contributing to CD4:CD8 T cell ratio and clinical outcome in adult HIV-positive patients in the context of treated infection. Discussion Low CD4:CD8 ratio has been linked to ageing and acts as a predictor of mortality in the general population. This ratio may represent the combined effects of inflammation and immunological changes called “inflammaging.” Although the mechanisms underlying partial correction of the CD4:CD8 ratio and persistently elevated CD8 T cell count in long-term treated patients remain poorly understood, it has been recently indicated that patients with optimal CD4 T cell recovery and low CD4:CD8 ratio still harbour increased immune activation, an immune senescent phenotype and have a higher risk of non-AIDS morbidity and mortality. This review reconsiders CD4:CD8 ratio in the light of advances in the understanding of immune dysfunction and examines its pathophysiological features and implications on clinical outcome and HIV reservoir size in long-term treated HIV-positive adults. Conclusion The CD4:CD8 ratio can contribute to the immunological evaluation of treated patients in a long-term follow-up and may be applied for monitoring both immune dysfunction and viral reservoir size in immune-based clinical trials. PMID:26130226

  14. The origin of phage virology.

    PubMed

    Pennazio, Sergio

    2006-01-01

    The history of bacteriophage (phage) had its start in 1915, when Twort isolated an unusual filterable and infectious agent from excrete of patients struck by diarrhoea; this discovery was followed by an analogous, and probably independent, finding of d'Hérelle in 1917. For several years phage research made scant progress but great attention was paid to the question of phage nature, which saw the contrast between d'Hérelle and Bordet's views (living against chemical nature, respectively). This situation changed with the independent discovery of lysogeny, in 1925, thanks to Bordet and Bail: this phenomenon was considered of genetical origin, a view that Wollman interpreted by assimilating the properties of phage to those of gene (according to a previous idea of Muller). In the 1930s, Burnet's work opened a new era by demonstrating the occurrence of several species of phages and their antigenic property. In the same period, the physical and chemical characteristics of these viruses were disclosed thanks, in particular, to the work of Schlesinger, who first demonstrated that a virus (phage) was constituted of nucleoproteins. The peculiarity of phage was finally shown after the invention of electron microscope: H. Ruska, in 1940, and Anderson and Luria in the next years, obtained the first images of tailed phages, a finding that strongly helped the investigation on the first steps of the infection process. The decisive impulse to phage virology came from Delbrück, a physicist who entered biology giving it a new arrangement. The so-called "phage group" assembled brilliant minds (Luria, Hershey and Delbrück himself, and later a dozen of other scientists): this group faced three fundamental questions of phage virology, i.e., the mechanisms of attack, multiplication and lysis. In ten years' time, phage virology became an integrant part of molecular biology, also thanks to the discovery of the genetical properties of DNA: in such scientific context, Delbrück, Luria and

  15. Clinical, virological and serological response of the West African dwarf sheep to experimental infection with different strains of Rift Valley fever virus.

    PubMed

    Tomori, O

    1979-03-01

    West African dwarf sheep were inoculated with three different strains of Rift Valley fever virus (RVFV). Using infective mouse serum as the source of virus classical RVFV disease characterised by sudden onset, a sharp but transient febrile response, viraemia, abortions and the development of specific RVFV antibodies in surviving animals was observed. The severity of clinical response was, however, dependent on the strain of virus used, with animals inoculated with Smithburn's neuroadapted strain showing a milder response than those inoculated with either the Nigerian or Lunyo strain. The inoculation of sheep with RVFV infective mouse brain material of the three different strains resulted in a mild febrile response with low level viraemia. Immune sera from sheep inoculated with both the Nigerian and Smithburn's neurotropic strains did not neutralise the Lunyo virus strain in a mouse intracerebral neutralisation test; the reverse, however, was not the case. The findings indicate that the West African dwarf sheep is highly susceptible to RVFV infection and that previous reports of only a mild clinical response following inoculation with the Nigerian strain were due to infective mouse brain rather than infective mouse serum.

  16. Raltegravir use prospectively assessed in a major HIV outpatient clinic in Italy: sample population, virological-immunological activity, and tolerability profile.

    PubMed

    Manfredi, Roberto; Calza, Leonardo; Marinacci, Ginevra; Cascavilla, Alessandra; Colangeli, Vincenzo; Salvadori, Caterina; Martelli, Giulia; Appolloni, Lucia; Puggioli, Cristina; Viale, Pierluigi

    2014-12-01

    Raltegravir, as the first HIV integrase inhibitor, has been used and prospectively monitored since 2010 in our HIV outpatient centre, where over 1,200 patients are monitored. The aim of our report is to perform an interim assessment of the background, the safety profile and the clinical-laboratory monitoring of all patients treated with a combination antiretroviral therapy (cART) including raltegravir, for at least 12 months. In all, 109 pretreated patients started a raltegravir-containing cART when aged 44.8 plus or minus 19.2 years, with a history of HIV infection lasting 13.4 plus or minus 9.7 years. All subjects were monitored for at least 12 months (mean 17.2 plus or minus 10.3 months). In the vast majority of cases (93 of 109: 85.3%), multiple (3-16) prior cART changes prompted raltegravir introduction in advanced-salvage lines: 72 of 109 (66.1%) patients had even developed a concurrent triple-class resistance to anti-HIV compounds. The most frequent companion antiretroviral agents were: darunavir/ritonavir (75 cases), maraviroc (47 subjects), and etravirine (38 cases). The most common underlying conditions were: AIDS (46 patients), liver cirrhosis (31 cases), AIDS-related or other malignancies (23 cases), and major cardio-cerebro-vascular events (18 cases). A chronic HCV and HBV hepatitis were of concern in 48 and 23 patients, respectively. The adjunct of raltegravir favourably affected all clinical-laboratory markers of HIV disease progression, and those of the broad spectrum of comorbidities, except for two patients who failed the raltegravir-containing cART due to insufficient adherence. Despite the already compromised clinical situation, a minority of subjects experienced mild-transient clinical-laboratory untoward events possibly attributable to raltegravir, such that no patients discontinued raltegravir during the observation period. Only three AIDS-defining conditions became apparent during raltegravir-based cART; chemotherapy and/or radiotherapy

  17. Clinical outcomes and virology of equine influenza in a naïve population and in horses infected soon after receiving one dose of vaccine.

    PubMed

    Kannegieter, N J; Frogley, A; Crispe, E; Kirkland, P D

    2011-07-01

    As part of the control measures of the equine influenza (EI) outbreak, in addition to the strategic use of vaccination to provide buffer zones around infected populations, approval was obtained to vaccinate Thoroughbred racing horses. We review the clinical expression of the disease and virus excretion in a population of racehorses that were exposed to EI approximately 7 days after administration of a single dose of the canarypox-vectored recombinant compared with a similar unvaccinated population of horses at a nearby racetrack. Although this study was undertaken opportunistically and under the difficult field conditions that prevailed during the outbreak, our observations demonstrate that an appropriate vaccine can be effectively used as a disease control measure, even in the face of an outbreak, and therefore should be rapidly implemented as soon as there is evidence of infection in a naïve population.

  18. Virologic and clinical features of primary infection with human parvovirus 4 in subjects with hemophilia: frequent transmission by virally inactivated clotting factor concentrates.

    PubMed

    Sharp, Colin P; Lail, Alice; Donfield, Sharyne; Gomperts, Edward D; Simmonds, Peter

    2012-07-01

    Human parvovirus 4 (PARV4) is a newly discovered parvovirus prevalent in injecting drug users and other groups with histories of parenteral exposure including persons with hemophilia exposed to non-virally inactivated clotting factor concentrates. To investigate its potential ongoing transmission to persons with hemophilia treated with plasma-derived, virally inactivated clotting factors, we screened a large cohort of persons with hemophilia for antibody seroconversion to PARV4 over a 5-year observation period. Samples from 195 persons with hemophilia enrolled in the Hemophilia Growth and Development Study cohort were screened for PARV4 antibodies at the start and end of a 5-year period of treatment with exclusively virally inactivated clotting factor concentrates. Samples collected at intermediate time points from subjects seroconverting over the study period were screened to narrow down the seroconversion time and investigate immunoglobulin (Ig)M responses, duration of acute viremia, and clinical presentations. PARV4 seroprevalence at the outset of the study was 44%. Over the observation period, nine subjects (seven human immunodeficiency virus positive) seroconverted for anti-PARV4 (incidence, 1.7%/year). Infected subjects showed relatively prolonged durations of viremia (mean, 7 months) and weak, transient IgM responses during acute infections. Clotting factors inactivated by solvent/detergent or by wet or dry heat were infectious. The most common clinical presentations were rashes and exacerbation of hepatitis. This study identifies PARV4 as a transfusion-transmissible agent that is resistant to viral inactivation. Of concern, infections may still regularly occur in those exposed to plasma-derived blood products. Urgent evaluation of the incidence of PARV4 in treated individuals and disease associations of PARV4 infections is required. © 2011 American Association of Blood Banks.

  19. Diversity of 1,213 hepatitis C virus NS3 protease sequences from a clinical virology laboratory database in Marseille university hospitals, southeastern France.

    PubMed

    Hajji, Hind; Aherfi, Sarah; Motte, Anne; Ravaux, Isabelle; Mokhtari, Saadia; Ruiz, Jean-Marie; Poizot-Martin, Isabelle; Tourres, Christian; Tivoli, Natacha; Gérolami, René; Tamalet, Catherine; Colson, Philippe

    2015-11-01

    Infection with hepatitis C virus (HCV) represents a major public health concern worldwide. Recent therapeutic advances have been considerable, HCV genotype continuing to guide therapeutic management. Since 2008, HCV genotyping in our clinical microbiology laboratory at university hospitals of Marseille, Southeastern France, has been based on NS3 protease gene population sequencing, to allow concurrent HCV genotype and protease inhibitor (PI) genotypic resistance determinations. We aimed, first, to analyze the genetic diversity of HCV NS3 protease obtained from blood samples collected between 2003 and 2013 from patients monitored at university hospitals of Marseille and detect possible atypical sequences; and, second, to identify NS3 protease amino acid patterns associated with decreased susceptibility to HCV PIs. A total of 1,213 HCV NS3 protease sequences were available in our laboratory sequence database. We implemented a strategy based on bioinformatic tools to determine whether HCV sequences are representative of our local HCV genetic diversity, or divergent. In our 2003-2012 HCV NS3 protease sequence database, we delineated 32 clusters representative of the majority HCV genetic diversity, and 61 divergent sequences. Five of these divergent sequences showed less than 85% nucleotide identity with their top GenBank hit. In addition, among the 294 sequences obtained in 2013, three were divergent relative to these 32 previously delineated clusters. Finally, we detected both natural and on-treatment genotypic resistance to HCV NS3 PIs, including a substantial prevalence of Q80K substitutions associated with decreased susceptibility to simeprevir, a second generation PI.

  20. Anal and penile condylomas in HIV-negative and HIV-positive men: clinical, histological and virological characteristics correlated to therapeutic outcome.

    PubMed

    von Krogh, G; Wikström, A; Syrjänen, K; Syrjänen, S

    1995-11-01

    Clinical, histological and HPV DNA hybridization findings were analyzed for 73 homosexual and 38 heterosexual men attending for anal warts; therapy results were evaluated retrospectively for 76 of these patients. Concurrent anal and penile warts occurred most commonly in the heterosexual men (p < 0.001). While perianal warts were most common in heterosexuals (p < 0.05), intraanal warts were most common in homosexuals (p < 0.001). Altogether 23 homosexual men were HIV-infected; 13 HIV-positive men followed regarding therapeutic outcome were immunologically relatively intact with mean CD4 counts of 524/mm3. Of 136 biopsy specimens 70% revealed benign hyperplasia, 27% AIN I, 2% AIN II and none AIN III. Of ISH positive samples 94% contained HPV 6/11 and 6% HPV 16/18/31/33. Anal warts were cured after an average of 2.5 (mean 1-10) therapy sessions in 64% of heterosexual, in 84% of HIV-negative homosexual and in 62% of HIV-positive homosexual men. The mean number of therapy sessions against anal warts was highest (p < 0.001) and the time for accomplishing cure for anal and penile warts was longest (p < 0.001) in the heterosexual study group.

  1. Correlation of clinical and virologic responses to antiviral treatment and regulatory T cell evolution in patients with hepatitis C virus-induced mixed cryoglobulinemia vasculitis.

    PubMed

    Landau, Dan-Avi; Rosenzwajg, Michelle; Saadoun, David; Trébeden-Negre, Hélène; Klatzmann, David; Cacoub, Patrice

    2008-09-01

    Mixed cryoglobulinemia (MC) vasculitis is an autoimmune disorder associated with chronic hepatitis C virus (HCV) infection. We previously reported that MC vasculitis is associated with a quantitative defect of peripheral blood regulatory T cells. The aim of this study was to prospectively evaluate the evolution of this defect during the course of antiviral treatment. Treg cell frequencies and numbers were analyzed in 131 patients with chronic HCV infection (including 66 with MC vasculitis) and 20 healthy volunteer donors. Measurements were taken before, during, and after treatment with PEGylated interferon alfa-2b plus ribavirin. At baseline, patients with MC vasculitis had a significantly lower frequency and number of Treg cells than did patients without MC vasculitis. Complete remission of MC vasculitis following antiviral treatment was associated with a significant increase in Treg cell levels compared with baseline. In contrast, Treg cell levels in nonresponders or partial responders, which did not differ from those in complete responders at baseline, remained unchanged over the course of the study. The strong positive correlation between clinical responses and Treg cell levels provides further support for the central role of Treg cells in the pathogenesis of HCV-induced MC vasculitis and emphasizes the dual role of Treg cells in chronic HCV infection: while Treg cells may hinder viral elimination, they also limit autoimmune injury.

  2. Comparative evaluation of the QIAGEN QIAsymphony® SP system and bioMérieux NucliSens easyMAG automated extraction platforms in a clinical virology laboratory.

    PubMed

    Lee, Adele V; Atkinson, Claire; Manuel, Rohini J; Clark, Duncan A

    2011-12-01

    The QIAGEN QIAsymphony(®) SP is an automated system that can process a variety of different sample types for nucleic acid extraction. To compare this system against the bioMérieux NucliSens easyMAG using a range of common clinical sample types. Nucleic acid extracts were tested on 6 in-house real time viral PCR assays: quantitative cytomegalovirus (CMV); respiratory and enteric multiplex (10 viruses); influenza A H1N1 2009 specific H1 and N1 assays (sH1/N1); herpes simplex virus (HSV) 1, HSV 2 and varicella zoster virus (VZV) multiplex; norovirus genogroups I and II (Noro GI/II) multiplex. Extraction of the clinical sample by either QIAsymphony(®) SP or NucliSens easyMAG gave similar results for each PCR; CMV viral loads, 52 plasma samples had a mean difference (easyMAG-QIAsymphony(®)) of 0.002 log(10)copies/ml (s.d. 0.536), 52 whole blood samples had a mean difference of -0.232 log(10)copies/ml (s.d. 0.490). Concordance for the qualitative assays were; 64/67 (95.5%) for the respiratory and enteric multiplex, all 28 (100%) for the sH1, sN1 and influenza A matrix multiplex, 33/34 (97%) for the HSV1/HSV2/VZV multiplex and all 15 (100%) for the Noro GI/II. Inter- and intra-run variation, determined for a 10-fold dilution series of CMV (5.20-3.20 log(10)copies/ml), was less than 0.63 log(10)copies/ml. Our evaluation found the performance of the QIAsymphony(®) SP comparable to the NucliSens easyMAG for a range of sample types commonly extracted in a clinical virology laboratory. In total, 331/343 (96.5%) PCR results were concordant on samples extracted by both platforms. Copyright © 2011 Elsevier B.V. All rights reserved.

  3. Finding our roots and celebrating our shoots: Plant virology in Virology, 1955-1964.

    PubMed

    Scholthof, Karen-Beth G

    2015-05-01

    To celebrate the sixtieth anniversary of Virology a survey is made of the plant viruses, virologists and their institutions, and tools and technology described in the first decade of plant virus publications in Virology. This was a period when plant viruses increasingly became tools of discovery as epistemic objects and plant virology became a discipline discrete from plant pathology and other life sciences. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. Computer network for a diagnostic virology laboratory.

    PubMed

    Stokes, K J; Morris, D J; Klapper, P E; Semple, A D; Crosdale, E; Corbitt, G

    1993-12-31

    A data base for a large diagnostic virology laboratory is described. The system uses a network of personal computers. It allows the entry, long-term storage, and subsequent retrieval of specimen and patient records (comprising personal identifiers and specimen and result information), and hard-copy results reporting. Sited entirely within the laboratory, the network is not connected to a modem. Within the laboratory there is restricted access to human immunodeficiency virus test results to guarantee patient confidentiality. Retention of a hard-copy of specimen request cards ensures the availability of the original clinical information. The data base is copied on a second file server to facilitate searches, and daily streaming onto magnetic tape provides system protection in the event of hard disc failure. Matching of old and new patient records is done by surname, date of birth, and sex, and therefore duplicate records accumulate when patient names are misspelt on specimen request forms. The system requires further development to speed searches of the data base and to achieve automatic generation of laboratory worksheets. Future goals are the replacement of hard-copy records of clinical information and hard-copy reporting with on-line access to hospital data bases and on-line requesting by and reporting to the clinician.

  5. Oxidant and antioxidant status in neonatal proven and clinical sepsis according to selenium status.

    PubMed

    Asci, Ali; Surmeli-Onay, Ozge; Erkekoglu, Pinar; Yigit, Sule; Yurdakok, Murat; Kocer-Gumusel, Belma

    2015-12-01

    Selenium is a trace element required for the functioning of the immune system. Neonatal sepsis is a serious condition leading to morbidity and mortality in neonates worldwide. The purpose of this study was to measure selenium and plasma selenoprotein P (SePP), selenoenzyme activity, and alterations in oxidant/antioxidant status with immune biomarkers in neonates with clinical (n = 27) and proven neonatal sepsis (n = 25). Erythrocyte selenium and SePP; plasma lipid peroxidation (LP), protein oxidation and total antioxidant capacity and erythrocyte total glutathione (GSH) concentration; erythrocyte glutathione peroxidase (GPx), thioredoxin reductase (TrxR), catalase (CAT) and total superoxide dismutase (SOD) activity were measured spectrophotometrically/spectrofluorometrically. Plasma interleukin 2 and 6 were also measured. Erythrocyte selenium and SePP were markedly lower both in the clinical and proven sepsis groups versus control. Erythrocyte GPx activity was higher only in the clinical sepsis group. TrxR activity was markedly lower in proven sepsis. SOD activity and GSH were markedly higher both in clinical sepsis and in proven sepsis. CAT activity was significantly higher both in clinical sepsis and in proven sepsis. LP and protein oxidation were significantly higher in both of the sepsis groups. Both selenium-dependent and selenium-independent blood redox systems were altered in sepsis, suggesting that sepsis causes an imbalance between cellular antioxidant and oxidant states. © 2015 Japan Pediatric Society.

  6. USE OF BIOLOGICAL KNOWLEDGE TO INFORM THE ANALYSIS OF GENE-GENE INTERACTIONS INVOLVED IN MODULATING VIROLOGIC FAILURE WITH EFAVIRENZ-CONTAINING TREATMENT REGIMENS IN ART-NAÏVE ACTG CLINICAL TRIALS PARTICIPANTS

    PubMed Central

    Grady, Benjamin J.; Torstenson, Eric S.; Mclaren, Paul J.; De Bakker, Paul I.W.; Haas, David W.; Robbins, Gregory K.; Gulick, Roy M.; Haubrich, Richard; Ribaudo, Heather; Ritchie, Marylyn D.

    2011-01-01

    Personalized medicine is a high priority for the future of health care. The idea of tailoring an individual’s wellness plan to their unique genetic code is one which we hope to realize through the use of pharmacogenomics. There have been examples of tremendous success in pharmacogenomic associations however there are many such examples in which only a small proportion of trait variance has been explained by the genetic variation. Although the increased use of GWAS could help explain more of this variation, it is likely that a significant proportion of the genetic architecture of these pharmacogenomic traits are due to complex genetic effects such as epistasis, also known as gene-gene interactions, as well as gene-drug interactions. In this study, we utilize the Biofilter software package to look for candidate epistasis contributing to risk for virologic failure with efavirenz-containing antiretroviral therapy (ART) regimens in treatment-naïve participants of AIDS Clinical Trials Group (ACTG) randomized clinical trials. A total of 904 individuals from three ACTG trials with data on efavirenz treatment are analyzed after race-stratification into white, black, and Hispanic ethnic groups. Biofilter was run considering 245 candidate ADME (absorption, distribution, metabolism, and excretion) genes and using database knowledge of gene and protein interaction networks to produce approximately 2 million SNP-SNP interaction models within each ethnic group. These models were evaluated within the PLATO software package using pair wise logistic regression models. Although no interaction model remained significant after correction for multiple comparisons, an interaction between SNPs in the TAP1 and ABCC9 genes was one of the top models before correction. The TAP1 protein is responsible for intracellular transport of antigen to MHC class I molecules, while ABCC9 codes for a transporter which is part of the subfamily of ABC transporters associated with multi-drug resistance

  7. Use of biological knowledge to inform the analysis of gene-gene interactions involved in modulating virologic failure with efavirenz-containing treatment regimens in ART-naïve ACTG clinical trials participants.

    PubMed

    Grady, Benjamin J; Torstenson, Eric S; McLaren, Paul J; DE Bakker, Paul I W; Haas, David W; Robbins, Gregory K; Gulick, Roy M; Haubrich, Richard; Ribaudo, Heather; Ritchie, Marylyn D

    2011-01-01

    Personalized medicine is a high priority for the future of health care. The idea of tailoring an individual's wellness plan to their unique genetic code is one which we hope to realize through the use of pharmacogenomics. There have been examples of tremendous success in pharmacogenomic associations however there are many such examples in which only a small proportion of trait variance has been explained by the genetic variation. Although the increased use of GWAS could help explain more of this variation, it is likely that a significant proportion of the genetic architecture of these pharmacogenomic traits are due to complex genetic effects such as epistasis, also known as gene-gene interactions, as well as gene-drug interactions. In this study, we utilize the Biofilter software package to look for candidate epistasis contributing to risk for virologic failure with efavirenz-containing antiretroviral therapy (ART) regimens in treatment-naïve participants of AIDS Clinical Trials Group (ACTG) randomized clinical trials. A total of 904 individuals from three ACTG trials with data on efavirenz treatment are analyzed after race-stratification into white, black, and Hispanic ethnic groups. Biofilter was run considering 245 candidate ADME (absorption, distribution, metabolism, and excretion) genes and using database knowledge of gene and protein interaction networks to produce approximately 2 million SNP-SNP interaction models within each ethnic group. These models were evaluated within the PLATO software package using pair wise logistic regression models. Although no interaction model remained significant after correction for multiple comparisons, an interaction between SNPs in the TAP1 and ABCC9 genes was one of the top models before correction. The TAP1 protein is responsible for intracellular transport of antigen to MHC class I molecules, while ABCC9 codes for a transporter which is part of the subfamily of ABC transporters associated with multi-drug resistance

  8. Introducing Virological Concepts Using an Insect Virus.

    ERIC Educational Resources Information Center

    Sheppard, Roger F.

    1980-01-01

    A technique is presented which utilizes wax moth larvae in a laboratory investigation of an insect virus. Describes how an insect virus can be used to introduce undergraduate biology students to laboratory work on viruses and several virological concepts. (SA)

  9. Introducing Virological Concepts Using an Insect Virus.

    ERIC Educational Resources Information Center

    Sheppard, Roger F.

    1980-01-01

    A technique is presented which utilizes wax moth larvae in a laboratory investigation of an insect virus. Describes how an insect virus can be used to introduce undergraduate biology students to laboratory work on viruses and several virological concepts. (SA)

  10. Protein bioinformatics applied to virology.

    PubMed

    Mohabatkar, Hassan; Keyhanfar, Mehrnaz; Behbahani, Mandana

    2012-09-01

    Scientists have united in a common search to sequence, store and analyze genes and proteins. In this regard, rapidly evolving bioinformatics methods are providing valuable information on these newly-discovered molecules. Understanding what has been done and what we can do in silico is essential in designing new experiments. The unbalanced situation between sequence-known proteins and attribute-known proteins, has called for developing computational methods or high-throughput automated tools for fast and reliably predicting or identifying various characteristics of uncharacterized proteins. Taking into consideration the role of viruses in causing diseases and their use in biotechnology, the present review describes the application of protein bioinformatics in virology. Therefore, a number of important features of viral proteins like epitope prediction, protein docking, subcellular localization, viral protease cleavage sites and computer based comparison of their aspects have been discussed. This paper also describes several tools, principally developed for viral bioinformatics. Prediction of viral protein features and learning the advances in this field can help basic understanding of the relationship between a virus and its host.

  11. Clinical status of comorbid bipolar disorder and borderline personality disorder.

    PubMed

    Parker, Gordon; Bayes, Adam; McClure, Georgia; Del Moral, Yolanda Romàn Ruiz; Stevenson, Janine

    2016-09-01

    The status and differentiation of comorbid borderline personality disorder and bipolar disorder is worthy of clarification. To determine whether comorbid borderline personality disorder and bipolar disorder are interdependent or independent conditions. We interviewed patients diagnosed with either a borderline personality disorder and/or a bipolar condition. Analyses of participants grouped by DSM diagnoses established that those with comorbid conditions scored similarly to those with a borderline personality disorder alone on all key variables (i.e. gender, severity of borderline personality scores, developmental stressors, illness correlates, self-injurious behaviour rates) and differed from those with a bipolar disorder alone on nearly all non-bipolar item variables. Similar findings were returned for groups defined by clinical diagnoses. Comorbid bipolar disorder and borderline personality disorder is consistent with the formal definition of comorbidity in that, while coterminous, individuals meeting such criteria have features of two independent conditions. © The Royal College of Psychiatrists 2016.

  12. Incomplete immune reconstitution despite virologic suppression in HIV-1 infected children and adolescents.

    PubMed

    Krogstad, Paul; Patel, Kunjal; Karalius, Brad; Hazra, Rohan; Abzug, Mark J; Oleske, James; Seage, George R; Williams, Paige L; Borkowsky, William; Wiznia, Andrew; Pinto, Jorge; Van Dyke, Russell B

    2015-03-27

    Some perinatally infected children do not regain normal CD4(+) T-cell counts despite suppression of HIV-1 plasma viremia by antiretroviral therapy (ART). The frequency, severity and significance of these discordant treatment responses remain unclear. We examined the persistence of CD4(+) lymphocytopenia despite virologic suppression in 933 children (≥ 5 years of age) in the USA, Latin America and the Caribbean. CD4(+) T-cell trajectories were examined and Kaplan-Meier methods used to estimate median time to CD4(+) T-cell count at least 500 cells/μl. After 1 year of virologic suppression, most (99%) children achieved a CD4(+) T-cell count of at least 200 cells/μl, but CD4(+) T-cell counts remained below 500 cells/μl after 1 and 2 years of virologic suppression in 14 and 8% of children, respectively. Median times to first CD4(+) T-cell count at least 500 cells/μl were 1.29, 0.78 and 0.46 years for children with less than 200, 200-349 and 350-499 cells/μl at the start of virologic suppression. New AIDS-defining events occurred in nine children, including four in the first 6 months of virologic suppression. Other infectious and HIV-related diagnoses occurred more frequently and across a wide range of CD4(+) cell counts. ART improved CD4(+) cell counts in most children, but the time to CD4(+) cell count of at least 500 cells was highly dependent upon baseline immunological status. Some children did not reach a CD4(+) T-cell count of 500 cells/μl despite 2 years of virologic suppression. AIDS-defining events occurred in 1% of the population, including children in whom virologic suppression and improved CD4(+) T-cell counts were achieved.

  13. Determinants of virological failure and antiretroviral drug resistance in Mozambique.

    PubMed

    Rupérez, María; Pou, Christian; Maculuve, Sonia; Cedeño, Samandhy; Luis, Leopoldina; Rodríguez, Judith; Letang, Emilio; Moltó, José; Macete, Eusébio; Clotet, Bonaventura; Alonso, Pedro; Menéndez, Clara; Naniche, Denise; Paredes, Roger

    2015-09-01

    The objective of this study was to inform public health actions to limit first-line ART failure and HIV drug resistance in Mozambique. This was a cross-sectional study. HIV-1-infected adults on first-line ART for at least 1 year attending routine visits in the Manhiça District Hospital, in a semi-rural area in southern Mozambique with no HIV-1 RNA monitoring available, were evaluated for clinical, socio-demographic, therapeutic, immunological and virological characteristics. Factors associated with HIV-1 RNA ≥1000 copies/mL and HIV drug resistance were determined using multivariate logistic regression. The study included 334 adults on first-line ART for a median of 3 years, of which 65% (214/332) had suppressed viraemia, 11% (37/332) had low-level viraemia (HIV-1 RNA 150-999 copies/mL) and 24% (81/332) had overt virological failure (HIV-1 RNA ≥1000 copies/mL). HIV drug resistance was detected in 89% of subjects with virological failure, but in none with low-level viraemia. Younger age [OR = 0.97 per additional year (95% CI = 0.94-1.00), P = 0.039], ART initiation at WHO stage III/IV [OR = 2.10 (95% CI = 1.23-3.57), P = 0.003] and low ART adherence [OR = 2.69 (95% CI = 1.39-5.19), P = 0.003] were associated with virological failure. Longer time on ART [OR = 1.55 per additional year (95% CI = 1.00-2.43), P = 0.052] and illiteracy [OR = 0.24 (95% CI = 0.07-0.89), P = 0.033] were associated with HIV drug resistance. Compared with HIV-1 RNA, clinician's judgement of ART failure, based on clinical and immunological outcomes, only achieved 29% sensitivity and misdiagnosed 1 out of every 4.5 subjects. Public health programmes in Mozambique should focus on early HIV diagnosis, early ART initiation and adherence support. Virological monitoring drastically improves the diagnosis of ART failure, enabling a better use of resources. © The Author 2015. Published by Oxford University Press on behalf of the British

  14. The educational and professional status of clinical embryology and clinical embryologists in Europe.

    PubMed

    Kovačič, B; Plas, C; Woodward, B J; Verheyen, G; Prados, F J; Hreinsson, J; De los Santos, M J; Magli, M C; Lundin, K; Plancha, C E

    2015-08-01

    What is the recognition of clinical embryology and the current status of clinical embryologists in European countries, regarding educational levels, responsibilities and workload, and need for a formal education in assisted reproductive technology (ART)? It is striking that the profession of clinical embryology, almost 40 years after the introduction of IVF, is still not officially recognized in most European countries. Reproductive medicine has developed into a sophisticated multidisciplinary medical branch since the birth of Louise Brown 37 years ago. The European Board & College of Obstetrics and Gynaecology (EBCOG) has recognized reproductive medicine as a subspeciality and has developed a subspeciality training for gynaecologists in collaboration with the European Society for Human Reproduction and Embryology (ESHRE). However, nothing similar exists for the field of clinical embryology or for clinical embryologists. A questionnaire about the situation in clinical embryology in the period of 2012-2013 in the respective European country was sent to ESHRE National representatives (basic scientists only) in December 2013. At this time, 28 European countries had at least one basic scientist in the ESHRE Committee of National Representatives. The survey consisted of 46 numeric, dichotomous (yes/no) or descriptive questions. Answers were obtained from 27 out of 28 countries and the data were tabulated. Data about the numbers of 'ESHRE Certified Embryologists' were taken from the ESHRE Steering Committee for Embryologist Certification. In 2012, more than 7000 laboratory staff from 1349 IVF clinics in 27 European countries performed over 700 000 fresh and frozen ART cycles. Despite this, clinical embryology is only recognized as an official profession in 3 out of 27 national health systems. In most countries clinical embryologists need to be registered under another profession, and have limited possibilities for organized education in clinical embryology. Mostly they

  15. Epidemiological and virological investigations of equine influenza outbreaks in Ireland (2010-2012).

    PubMed

    Gildea, Sarah; Fitzpatrick, David A; Cullinane, Ann

    2013-12-01

    Outbreaks of equine influenza (EI) in endemic populations cause disruption and economic loss. To identify (i) factors involved in the spread of EI (ii) virus strains responsible for outbreaks (iii) single radial haemolysis (SRH) antibody levels correlating with protection against current virus strains (iv) evidence of vaccination breakdown. RT-PCR, virus isolation and SRH were carried out on nasopharyngeal swabs and blood samples collected from horses, ponies and donkeys on affected premises. Data relating to 629 samples from 135 equidae were analysed. Outbreaks were sporadic, self limiting and associated with the movement of horses. Vaccination status and age influenced clinical signs of disease while housing and fomites contributed to virus spread. Subclinical infection as defined as a horse which tested positive by one or more of the following; RT-PCR, virus isolation and seroconversion in the absence of clinical signs, was identified in 9% of animals. Of the horses with up to date vaccination records 32% developed clinical signs. Vaccine breakdown occurred among horses vaccinated with all four commercially available vaccines. Analysis of HA1 sequence data generated for 26 viruses indicated that they all belonged to clade 2 of the Florida sublineage. Higher SRH antibody levels were required for both clinical and virological protection than reported in studies where vaccine strains were antigenically and genetically similar to those circulating in the field. The results of this study therefore support the OIE recommendations that vaccines be updated to include representatives of both clades of the Florida sublineage. © 2013 Blackwell Publishing Ltd.

  16. Nutritional Risk, Micronutrient Status and Clinical Outcomes: A Prospective Observational Study in an Infectious Disease Clinic.

    PubMed

    Dizdar, Oguzhan Sıtkı; Baspınar, Osman; Kocer, Derya; Dursun, Zehra Bestepe; Avcı, Deniz; Karakükcü, Cigdem; Çelik, İlhami; Gundogan, Kursat

    2016-02-29

    Malnutrition has been associated with increased morbidity and mortality. The objective of this study was to determine the nutritional status and micronutrient levels of hospitalized patients in an infectious disease clinic and investigate their association with adverse clinical outcomes. The nutritional status of the study participants was assessed using the Nutritional Risk Screening 2002 (NRS 2002) and micronutrient levels and routine biochemical parameters were tested within the first 24 h of the patient's admission. The incidence of zinc, selenium, thiamine, vitamin B6, vitamin B12 deficiency were 66.7% (n = 40), 46.6% (n = 29), 39.7% (n = 27), 35.3% (n = 24), 14.1% (n = 9), respectively. Selenium levels were significantly higher in patients with urinary tract infections, but lower in soft tissue infections. Copper levels were significantly higher in patients with soft tissue infections. In the Cox regression models, lower albumin, higher serum lactate dehydrogenase levels and higher NRS-2002 scores were associated with increased death. Thiamine, selenium, zinc and vitamin B6 deficiencies but not chromium deficiencies are common in infectious disease clinics. New associations were found between micronutrient levels and infection type and their adverse clinical outcomes. Hypoalbuminemia and a high NRS-2002 score had the greatest accuracy in predicting death, systemic inflammatory response syndrome and sepsis on admission.

  17. Nutritional Risk, Micronutrient Status and Clinical Outcomes: A Prospective Observational Study in an Infectious Disease Clinic

    PubMed Central

    Dizdar, Oguzhan Sıtkı; Baspınar, Osman; Kocer, Derya; Dursun, Zehra Bestepe; Avcı, Deniz; Karakükcü, Cigdem; Çelik, İlhami; Gundogan, Kursat

    2016-01-01

    Malnutrition has been associated with increased morbidity and mortality. The objective of this study was to determine the nutritional status and micronutrient levels of hospitalized patients in an infectious disease clinic and investigate their association with adverse clinical outcomes. The nutritional status of the study participants was assessed using the Nutritional Risk Screening 2002 (NRS 2002) and micronutrient levels and routine biochemical parameters were tested within the first 24 h of the patient’s admission. The incidence of zinc, selenium, thiamine, vitamin B6, vitamin B12 deficiency were 66.7% (n = 40), 46.6% (n = 29), 39.7% (n = 27), 35.3% (n = 24), 14.1% (n = 9), respectively. Selenium levels were significantly higher in patients with urinary tract infections, but lower in soft tissue infections. Copper levels were significantly higher in patients with soft tissue infections. In the Cox regression models, lower albumin, higher serum lactate dehydrogenase levels and higher NRS-2002 scores were associated with increased death. Thiamine, selenium, zinc and vitamin B6 deficiencies but not chromium deficiencies are common in infectious disease clinics. New associations were found between micronutrient levels and infection type and their adverse clinical outcomes. Hypoalbuminemia and a high NRS-2002 score had the greatest accuracy in predicting death, systemic inflammatory response syndrome and sepsis on admission. PMID:26938553

  18. Clinical periodontal status and inflammatory cytokines in gestational diabetes mellitus.

    PubMed

    Özçaka, Özgün; Ceyhan-Öztürk, Banu; Gümüş, Pınar; Akcalı, Aliye; Nalbantsoy, Ayşe; Buduneli, Nurcan

    2016-12-01

    The aim of the present cross-sectional study was to compare clinical periodontal findings as well as gingival crevicular fluid (GCF) and serum levels of tumour necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), and IL-33 between women with and without gestational diabetes mellitus (GDM). Serum and GCF samples were collected, full-mouth recordings comprising plaque index, bleeding on probing and probing depth were performed in 96 females with GDM (cases) and 65 non-diabetic pregnant females (controls). Age, smoking status, pre-pregnancy body mass index, pregnancy outcomes were recorded. Serum and GCF IL-10, IL-33, TNF-α levels were determined. The GDM group was significantly older than the control group with an age difference of 3.27 years (mean ages were 32.05 and 28.78 years, respectively) (p<0.0001). Plaque Index (50.0 and 30.0 p=0.005), bleeding on probing (50.0 and 30.0 p=0.003) values were significantly higher in the GDM group. Serum TNF-α concentrations were significantly higher in the nonGDM group than the GDM group (p=0.001). GCF IL-10 concentrations and total amounts were significantly higher in the GDM group than the controls (p=0.004 and p<0.0001, respectively). Elevated GCF IL-10 levels may be a consequence of higher levels of inflammation as indicated by higher PI and BOP in the GDM group. However, the investigated clinical parameters may not have prominent effects on TNF-α and IL-33 levels. These findings provide further support for the importance of periodontal health during pregnancy. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Predictive factors of virological success to salvage regimens containing protease inhibitors in HIV-1 infected children

    PubMed Central

    Larru, Beatriz; de Mendoza, Carmen; Bellón, José Ma; de José, Ma Isabel; Mellado, Ma José; Soriano, Vincent; Muñoz-Fernandez, Ma Angeles; Ramos, José T

    2007-01-01

    Background The impact of HIV drug resistance mutations in salvage therapy has been widely investigated in adults. By contrast, data available of predictive value of resistance mutations in pediatric population is scarce. Methods A multicenter, retrospective, observational study was conducted in children who received rescue salvage antiretroviral therapy after virologic failure. CD4 counts and viral load were determined at baseline and 6 months after rescue intervention. Genotypic HIV-1 resistance test and virtual phenotype were assessed at baseline. Results A total of 33 children met the inclusion criteria and were included in the analysis. The median viral load (VL) and median percentage of CD4+ at baseline was 4.0 HIV-RNA log copies/ml and 23.0% respectively. The median duration that children were taking the new rescue regimen was 24.3 weeks (23.8–30.6). Overall, 47% of the 33 children achieved virological response at 24 weeks. When we compared the group of children who achieved virological response with those who did not, we found out that mean number of PI related mutations among the group of responders was 3.8 vs. 5.4 (p = 0.115). Moreover, the mean number of susceptible drugs according to virtual phenotype clinical cut-off for maximal virologic response was 1.7 vs. 0.8 and mean number of susceptible drugs according to virtual phenotype cut-off for minimal virlologic response was 2.7 vs. 1.3 (p < 0.01 in all cases). Eighteen children were rescued with a regimen containing a boosted-PI and virological response was significantly higher in those subjects compared with the others (61.1% vs. 28.6%, p < 0.01). Conclusion Salvage treatment containing ritonavir boosted-PIs in children with virological failure was very efficient. The use of new tools as virtual phenotype could help to improve virologic success in pediatric population. PMID:17559687

  20. Magnitude of virologic blips is associated with a higher risk for virologic rebound in HIV-infected individuals: a recurrent events analysis.

    PubMed

    Grennan, J Troy; Loutfy, Mona R; Su, DeSheng; Harrigan, P Richard; Cooper, Curtis; Klein, Marina; Machouf, Nima; Montaner, Julio S G; Rourke, Sean; Tsoukas, Christos; Hogg, Bob; Raboud, Janet

    2012-04-15

    The importance of human immunodeficiency virus (HIV) blip magnitude on virologic rebound has been raised in clinical guidelines relating to viral load assays. Antiretroviral-naive individuals initiating combination antiretroviral therapy (cART) after 1 January 2000 and achieving virologic suppression were studied. Negative binomial models were used to identify blip correlates. Recurrent event models were used to determine the association between blips and rebound by incorporating multiple periods of virologic suppression per individual. 3550 participants (82% male; median age, 40 years) were included. In a multivariable negative binomial regression model, the Amplicor assay was associated with a lower blip rate than branched DNA (rate ratio, 0.69; P < .01), controlling for age, sex, region, baseline HIV-1 RNA and CD4 count, AIDS-defining illnesses, year of cART initiation, cART type, and HIV-1 RNA testing frequency. In a multivariable recurrent event model controlling for age, sex, intravenous drug use, cART start year, cART type, assay type, and HIV-1 RNA testing frequency, blips of 500-999 copies/mL were associated with virologic rebound (hazard ratio, 2.70; P = .002), whereas blips of 50-499 were not. HIV-1 RNA assay was an important determinant of blip rates and should be considered in clinical guidelines. Blips ≥500 copies/mL were associated with increased rebound risk.

  1. Estimates of global research productivity in virology.

    PubMed

    Falagas, Matthew E; Karavasiou, Antonia I; Bliziotis, Ioannis A

    2005-06-01

    The quantity and quality of published research in the field of Virology by different world regions was estimated in this study. Using the PubMed database, articles from journals included in the "Virology" category of the "Journal Citation Reports" database of the Institute for Scientific Information for the period 1995-2003 were retrieved. The world was divided into nine regions based on geographic, economic, and scientific criteria. Data on the country of origin of the research was available for 33,425 out of 33,712 articles (99.2% of all articles from the included journals). USA exceeds all other world regions in research production for the period studied (42% of total articles), with Western Europe ranking second (35.7%). The mean impact factor in articles published in Virology journals was highest for the USA (4.60), while it was 3.90 for Western Europe and 3.22 for the rest of the world (seven regions combined). USA and Canada ranked first in research productivity when both gross national income per capita (GNIPC) and population were taken into account. The results of this analysis show a distressing fact; the absolute and relative production of research in the field of Virology by the developing regions is very low, although viral diseases cause considerable morbidity and mortality in these areas. It is evident from this study that developing regions need more help from the developed regions to enhance research infrastructure.

  2. Single-Cell Genomics for Virology.

    PubMed

    Ciuffi, Angela; Rato, Sylvie; Telenti, Amalio

    2016-05-04

    Single-cell sequencing technologies, i.e., single cell analysis followed by deep sequencing investigate cellular heterogeneity in many biological settings. It was only in the past year that single-cell sequencing analyses has been applied in the field of virology, providing new ways to explore viral diversity and cell response to viral infection, which are summarized in the present review.

  3. Highlights from the 5th Annual Meeting of the Italian Society of Virology.

    PubMed

    Salata, Cristiano; Calistri, Arianna; Palù, Giorgio

    2006-07-01

    The 5th National Congress of the Italian Society of Virology (SIV) was attended by junior- and senior-level virologists to promote interactions and scientific collaborations among the different areas of Virology and allied sciences. The invited and selected lecturers covered the following topics: General Virology and Viral Genetics; Virus-host Interaction and Pathogenesis; Viral Oncogenesis; Viral Immunology and Vaccines; Anti-viral Therapy; Innovative Diagnostics; Viral Biotechnologies and Cell and Gene Therapy. As in the previous editions (Salata and Palù, 2004; Salata et al., 2005), a specific topic was thoroughly covered in a roundtable. This year the elected subject was "HIV: determinants of pathogenicity and clinical implications." The final program and the abstract book can be found at the web site http://www.siv-virologia.it. This report summarizes the lessons learned from the plenary lectures and the selected oral presentations of the 2005 meeting.

  4. Promoting translational research in human and veterinary medical virology.

    PubMed

    Tang, Yi-Wei

    2013-07-26

    Translational research serves as a bench-to-field "translation" of basic scientific research into practical diagnostic procedures and therapies useful in human and veterinary clinical services. The productivity of translational research involving infectious diseases relevant to both human and animal health (e.g., influenza diagnosis and epidemiology using emerging molecular detection and identification methods) can be maximized when both human and veterinary medical virology disciplines are integrated. Influenza viruses are continually evolving through site-specific mutation and segment reassortment, and these processes occur in all potential carrier species - including birds, humans, and many agriculturally important animals. This evolutionary plasticity occasionally allows "novel" influenzas to move from animal hosts to humans, potentially causing destructive pandemics; therefore, a rapid laboratory technique that can detect and identify "novel" influenza viruses is clinically and epidemiologically desirable. A technique-focused translational research approach is pursued to enhance detection and characterization of emerging influenza viruses circulating in both humans and other animal hosts. The PLEX-ID System, which incorporates multi-locus PCR and electrospray ionization/mass spectrometry, uses deliberately nonspecific primers that amplify all known variants (all H/N subtypes) of influenza virus, including human, other mammalian, and avian influenzas, and is therefore likely to generate analyzable amplicons from any novel influenza that might emerge in any host. Novel technology development and implementation such as the PLEX-ID System forms a key component of human and veterinary medical virology translational research.

  5. Clinical, virological and biochemical evidence supporting the association of HIV-1 reverse transcriptase polymorphism R284K and thymidine analogue resistance mutations M41L, L210W and T215Y in patients failing tenofovir/emtricitabine therapy

    PubMed Central

    2012-01-01

    Background Thymidine analogue resistance mutations (TAMs) selected under treatment with nucleoside analogues generate two distinct genotypic profiles in the HIV-1 reverse transcriptase (RT): (i) TAM1: M41L, L210W and T215Y, and (ii) TAM2: D67N, K70R and K219E/Q, and sometimes T215F. Secondary mutations, including thumb subdomain polymorphisms (e.g. R284K) have been identified in association with TAMs. We have identified mutational clusters associated with virological failure during salvage therapy with tenofovir/emtricitabine-based regimens. In this context, we have studied the role of R284K as a secondary mutation associated with mutations of the TAM1 complex. Results The cross-sectional study carried out with >200 HIV-1 genotypes showed that virological failure to tenofovir/emtricitabine was strongly associated with the presence of M184V (P < 10-10) and TAMs (P < 10-3), while K65R was relatively uncommon in previously-treated patients failing antiretroviral therapy. Clusters of mutations were identified, and among them, the TAM1 complex showed the highest correlation coefficients. Covariation of TAM1 mutations and V118I, V179I, M184V and R284K was observed. Virological studies showed that the combination of R284K with TAM1 mutations confers a fitness advantage in the presence of zidovudine or tenofovir. Studies with recombinant HIV-1 RTs showed that when associated with TAM1 mutations, R284K had a minimal impact on zidovudine or tenofovir inhibition, and in their ability to excise the inhibitors from blocked DNA primers. However, the mutant RT M41L/L210W/T215Y/R284K showed an increased catalytic rate for nucleotide incorporation and a higher RNase H activity in comparison with WT and mutant M41L/L210W/T215Y RTs. These effects were consistent with its enhanced chain-terminated primer rescue on DNA/DNA template-primers, but not on RNA/DNA complexes, and can explain the higher fitness of HIV-1 having TAM1/R284K mutations. Conclusions Our study shows the association

  6. Virological Response after Short-Term CCR5 Antagonist Exposure in HIV-Infected Patients: Frequency of Subjects with Virological Response and Associated Factors▿

    PubMed Central

    Ruiz-Mateos, Ezequiel; González-Serna, Alejandro; Genebat, Miguel; Machmach, Kawthar; Vidal, Francesc; Muñoz-Fernández, Ángeles; Ferrando-Martinez, Sara; Leal, Manuel

    2011-01-01

    The virological response after an 8-day maraviroc monotherapy has been proposed to be an alternative method to determine whether an CCR5 antagonist should be prescribed to HIV-infected patients. The frequency of patients eligible for a combined antiretroviral therapy which includes maraviroc on the basis of the result of this clinical test is not well-known at the moment. In the same way, clinical and immunovirological factors associated with the virological response after antagonist exposure need to be determined. Ninety consecutive HIV-infected patients were exposed to an 8-day maraviroc monotherapy. The virological response was considered positive if either a reduction of ≥1-log10 HIV RNA copies/ml or an undetectable viral load (<40 HIV RNA copies/ml) was achieved. CXCR4- and CCR5-tropic virus levels were determined by using patients' viral isolates and multiple rounds of infection of indicator cell lines (U87-CXCR4 and U87-CCR5). The frequency of patients with a positive virological response was 72.2% (94.7% and 66.2% for treatment-naïve and pretreated patients, respectively). The positive response rates dramatically decreased in patients with lower CD4+ T-cell counts. The CXCR4-tropic virus level was the only variable independently associated with the virological response after short-term maraviroc exposure. Lower CD4+ T-cell strata were associated with higher CXCR4-tropic virus levels. These results support the suggestion that CCR5 antagonists should be an early treatment option before the expansion of CXCR4-tropic strains. PMID:21807977

  7. Lopinavir Plasma Concentrations and Virological Outcome with Lopinavir-Ritonavir Monotherapy in HIV-1-Infected Patients

    PubMed Central

    Ruiz-Valderas, Rosa; Sánchez-Rivas, Elena; Lluch, Amparo; Gutierrez-Valencia, Alicia; Torres-Cornejo, Almudena; BenMarzouk-Hidalgo, Omar J.; Viciana, Pompeyo

    2013-01-01

    There is significant intra- and intersubject variability in lopinavir (LPV) plasma concentrations after standard dosing; thus, this prospective study was conducted to determine whether low plasma LPV concentrations could be associated with virological outcome throughout lopinavir-ritonavir maintenance monotherapy (mtLPVr) in the clinical practice setting. If this hypothesis would be confirmed, LPV drug monitoring could improve the efficacy of mtLPVr regimens. Patients with previous virological failure (VF) on protease inhibitor-based regimens were also included if the genotypic resistance tests showed no major resistance mutation associated with reduced susceptibility to lopinavir-ritonavir. VF was defined as 2 consecutive determinations of HIV RNA levels of >200 copies/ml. Efficacy was analyzed by per-protocol analysis. Plasma LPV trough concentrations were measured by high-performance liquid chromatography using a UV detector. A total of 127 patients were included (22% with previous failure on protease inhibitors). After 96 weeks, the efficacy rate was 82.3% (95% confidence interval [CI95], 75.3 to 89.3%). Virological efficacy was independent of LPV plasma concentrations even when LPVr was given once daily. An adherence of <90% (HR, 4.4 [CI95, 1.78 to 10.8; P = 0.001]) and the presence of blips in the preceding 12 months (HR, 3.06 [CI95, 1.17 to 8.01; P = 0.022]) were the only variables independently associated with time to VF. These findings suggest that the LPV concentrations achieved with the standard doses of LPVr are sufficient to maintain virological control during monotherapy and that measurement of LPV concentrations is not useful for predicting virological outcome. Tight control of viral replication in the previous months and strict adherence throughout the mtLPVr regimen could improve the virological efficacy of this maintenance regimen. PMID:23716055

  8. The origin of modern plant virology.

    PubMed

    Pennazio, S; Conti, M

    2002-10-01

    Plant virology, born with Mayer's work, saw a first (embryonic) phase of development during two decades (1900-1920) with outstanding contributions from Dimitri Ivanovski, Martinus Beijerinck, Erwin Baur and Harry Allard. Between 1920 and 1930 a second phase saw the elaboration of surprising hypotheses concerning the enigmatic nature of viruses and experimental evidence of great stress was obtained. Revolutionary renewal began from the mid-1930s on the basis of a body of knowledge which was organically assembled into the first textbook of plant virology published by Kenneth Smith in 1933. In 1922, the geneticist Hermann Muller put forward the hypothesis that considered viruses as possible genes. The theory was resumed in an apparently independent way by Benjamin Duggar and Joanne Karrer Armstrong in 1923, who considered TMV a biocolloidal self-reproducing protein, like genes appeared to be. This hypothesis, even if neglected by virologists, anticipated by some decades the functional nature of viruses and represented the first conceptual response to virus enigma. Considerable experimental results were obtained by James Johnson, who showed that plants could be infected by different viruses and who introduced a first rational system of plant virus classification. Harold McKinney showed that TMV could mutate. Harold Storey, Kenneth Smith and Harry Severin demonstrated that several viruses could be transmitted by insects and supplied the first interpretation of the relationship between virus and insect. Mayme Dvorak and Helen Purdy obtained the first experimental evidence of the antigenic power of plant viruses. Virus purification, first tentatively accomplished with physical methods, was brilliantly performed by chemical means. Finally, Francis Holmes elaborated the first suitable test to estimate virus infectivity. The evolution of plant virology from an empirical discipline to a biological science took place thanks to the work of one group of American and English

  9. Paediatric Virology: A rapidly increasing educational challenge.

    PubMed

    Mammas, Ioannis N; Theodoridou, Maria; Kramvis, Anna; Thiagarajan, Prakash; Gardner, Sharryn; Papaioannou, Georgia; Melidou, Angeliki; Koutsaki, Maria; Kostagianni, Georgia; Achtsidis, Vassilis; Koutsaftiki, Chryssie; Calachanis, Marcos; Zaravinos, Apostolos; Greenough, Anne; Spandidos, Demetrios A

    2017-02-01

    The '2nd Workshop on Paediatric Virology', which took place on Saturday the 8th of October 2016 in Athens, Greece, provided an overview on recent views and advances on Paediatric Virology. Emphasis was given to HIV-1 management in Greece, a country under continuous financial crisis, hepatitis B vaccination in Africa, treatment options for hepatitis C virus in childhood, Zika virus in pregnancy and infancy, the burden of influenza on childhood, hand-foot-mouth disease and myocarditis associated with Coxsackie viruses. Other general topics covered included a critical evaluation of Paediatric Accident and Emergency viral infections, multimodality imaging of viral infections in children, surgical approaches of otolaryngologists to complex viral infections, new advances in the diagnosis and treatment of viral conjunctivitis and novel molecular diagnostic methods for HPV in childhood. A brief historical overview of the anti-vaccination movement was also provided, as well as presentations on the educational challenge of Paediatric Virology as a new subspecialty of Paediatrics. This review highlights selected lectures and discussions of the workshop.

  10. Oral Health Status and Behaviour of Mauritians Visiting Private Dental Clinics

    ERIC Educational Resources Information Center

    Gunsam, P. Pugo; Banka, S.

    2011-01-01

    Purpose: This paper seeks to assess the oral health status and behaviour of a sample of the Mauritian population visiting private dental clinics. Design/methodology/approach: Oral health status was determined using the World Health Organization (Decayed, Missing, Filled Teeth (DMFT) index indicating the prevalence of caries, and factors associated…

  11. Oral Health Status and Behaviour of Mauritians Visiting Private Dental Clinics

    ERIC Educational Resources Information Center

    Gunsam, P. Pugo; Banka, S.

    2011-01-01

    Purpose: This paper seeks to assess the oral health status and behaviour of a sample of the Mauritian population visiting private dental clinics. Design/methodology/approach: Oral health status was determined using the World Health Organization (Decayed, Missing, Filled Teeth (DMFT) index indicating the prevalence of caries, and factors associated…

  12. Simplification to dual therapy (atazanavir/ritonavir + lamivudine) versus standard triple therapy [atazanavir/ritonavir + two nucleos(t)ides] in virologically stable patients on antiretroviral therapy: 96 week results from an open-label, non-inferiority, randomized clinical trial (SALT study).

    PubMed

    Perez-Molina, J A; Rubio, R; Rivero, A; Pasquau, J; Suárez-Lozano, I; Riera, M; Estébanez, M; Palacios, R; Sanz-Moreno, J; Troya, J; Mariño, A; Antela, A; Navarro, J; Esteban, H; Moreno, S

    2017-01-01

    We evaluated whether maintenance therapy with atazanavir/ritonavir plus lamivudine (ATV/r + 3TC) was non-inferior to ATV/r plus two nucleosides (ATV/r + 2NUCs) at 96 weeks of follow-up. SALT is a multicentre, open-label, non-inferiority clinical trial in HIV-1-infected virologically suppressed patients. Hepatitis B virus surface antigen-negative subjects with no previous treatment failure/resistance mutations and HIV-1-RNA <50 copies/mL for ≥6 months were randomized (1 : 1) to ATV/r + 3TC or ATV/r + 2NUCs. The primary endpoint was HIV-1-RNA <50 copies/mL in the PP population. Non-inferiority was demonstrated if the lower bound of the 95% CI for the difference was not below -12%. Some 286 patients were analysed. At week 96, 74.4% had HIV-1-RNA <50 copies/mL in the ATV/r + 3TC arm versus 73.9% in the ATV/r + 2NUCs arm (95% CI for the difference, -9.9%-11.0%). In both groups, similar values were observed for patients with confirmed virological failure in ATV/r + 3TC versus ATV/r + 2NUCs (9 versus 5), death (1 versus 0), discontinuation due to ART-related toxicity (7 versus 11), withdrawal from the study (7 versus 9) and loss to follow-up (6 versus 6). One patient taking ATV/r + 2NUCs developed resistance mutations (M184V and L63P). Similar values were obtained for change in mean CD4 count [19 versus 18 cells/mm(3) (95% CI for the difference, -49.3-50.7), grade 3-4 adverse events (70.7% versus 70.2%) and changes in the global deficit score, -0.3 (95% CI, -0.5 to -0.1) for ATV/r + 3TC, versus -0.2 (95% CI, -0.4 to -0.1) for ATV/r + 2NUCs]. The long-term results of switching to ATV/r + 3TC show that this strategy is effective, safe and non-inferior to ATV + 2NUCs in virologically suppressed HIV-infected patients. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Current Status and Future Prospects of Clinical Psycholog

    PubMed Central

    Baker, Timothy B.; McFall, Richard M.; Shoham, Varda

    2010-01-01

    SUMMARY The escalating costs of health care and other recent trends have made health care decisions of great societal import, with decision-making responsibility often being transferred from practitioners to health economists, health plans, and insurers. Health care decision making increasingly is guided by evidence that a treatment is efficacious, effective–disseminable, cost-effective, and scientifically plausible. Under these conditions of heightened cost concerns and institutional–economic decision making, psychologists are losing the opportunity to play a leadership role in mental and behavioral health care: Other types of practitioners are providing an increasing proportion of delivered treatment, and the use of psychiatric medication has increased dramatically relative to the provision of psychological interventions. Research has shown that numerous psychological interventions are efficacious, effective, and cost-effective. However, these interventions are used infrequently with patients who would benefit from them, in part because clinical psychologists have not made a convincing case for the use of these interventions (e.g., by supplying the data that decision makers need to support implementation of such interventions) and because clinical psychologists do not themselves use these interventions even when given the opportunity to do so. Clinical psychologists’ failure to achieve a more significant impact on clinical and public health may be traced to their deep ambivalence about the role of science and their lack of adequate science training, which leads them to value personal clinical experience over research evidence, use assessment practices that have dubious psychometric support, and not use the interventions for which there is the strongest evidence of efficacy. Clinical psychology resembles medicine at a point in its history when practitioners were operating in a largely prescientific manner. Prior to the scientific reform of medicine in the

  14. Clinical research within the chiropractic profession: status, needs and recommendations.

    PubMed

    Sawyer, C; Haas, M; Nelson, C; Elkington, W

    1997-01-01

    In the current climate of accountability, health care financing reform and the demand on all health professions for evidence, there is an urgent need to expand clinical research activity within the profession. Those randomized clinical trials that have been reported in the literature have focused primarily on low back and headache pain. Only recently have studies been initiated to investigate the effectiveness of chiropractic interventions for conditions other than back pain. The ability of chiropractic colleges to develop research infrastructures and productive clinical research programs depends on removing or minimizing a number of impediments. A shortage of chiropractic clinicians who have the experience and training to conduct clinical research is compounded by a dependency on tuition revenue, limited external funding and a lack of institutional emphasis on research. The profession generally, and chiropractic colleges specifically, must address the impediments that limit the growth of research capacity. We present several recommendations and the action steps required to achieve specific outcomes.

  15. CLINICAL CORRELATIONS AND SYSTEMIC STATUS IN PERIODONTAL DISEASE

    DTIC Science & Technology

    Generally speaking, the method is suitable only for the diagnosis of established diabetes mellitus and should not be used to study less marked alterations in carbohydrate metabolism. (Author)...Clinical and laboratory studies were carried out on 59 experimental and 64 control subjects. In the clinical evaluation, the periodontal score was...particularly since no steroid differences were found that could be correlated with the degree of periodontal breakdown. Results obtained in tests of oral

  16. Feasibility of Automatic Extraction of Electronic Health Data to Evaluate a Status Epilepticus Clinical Protocol.

    PubMed

    Hafeez, Baria; Paolicchi, Juliann; Pon, Steven; Howell, Joy D; Grinspan, Zachary M

    2016-05-01

    Status epilepticus is a common neurologic emergency in children. Pediatric medical centers often develop protocols to standardize care. Widespread adoption of electronic health records by hospitals affords the opportunity for clinicians to rapidly, and electronically evaluate protocol adherence. We reviewed the clinical data of a small sample of 7 children with status epilepticus, in order to (1) qualitatively determine the feasibility of automated data extraction and (2) demonstrate a timeline-style visualization of each patient's first 24 hours of care. Qualitatively, our observations indicate that most clinical data are well labeled in structured fields within the electronic health record, though some important information, particularly electroencephalography (EEG) data, may require manual abstraction. We conclude that a visualization that clarifies a patient's clinical course can be automatically created using the patient's electronic clinical data, supplemented with some manually abstracted data. Future work could use this timeline to evaluate adherence to status epilepticus clinical protocols. © The Author(s) 2015.

  17. Representation of Functional Status Concepts from Clinical Documents and Social Media Sources by Standard Terminologies.

    PubMed

    Kuang, Jinqiu; Mohanty, April F; Rashmi, V H; Weir, Charlene R; Bray, Bruce E; Zeng-Treitler, Qing

    2015-01-01

    Patient-reported functional status is widely recognized as an important patient-centered outcome that adds value to medical care, research, and quality improvement. Functional status outcomes are, however, not routinely or uniformly collected in the medical record, except in certain small patient populations (e.g. geriatrics, nursing home residents). To utilize patient reported functional status for clinical research and practice, we manually collected 2,763 terms from clinical records and social media sites and modeled them on the widely used Short Form-36 Health Survey. We then examined the coverage of the Unified Medical Language System (UMLS) for these functional status terms through automated mapping. Most terms (85.9%) did not have exact matches in the UMLS. The partial matches were prevalent, however, they typically did not capture the terms' exact semantics. Our study suggests that there is a need to extend existing standard terminologies to incorporate functional status terms used by patients and clinicians.

  18. “Risk factors associated with virologic failure in HIV-infected patients receiving antiretroviral therapy at a public hospital in Peru”

    PubMed Central

    Jorge, Alave R; Jorge, Paz B; Elsa, Gonzalez L; Miguel, Campos S; Rodriguez, Martin; Willig, James; Juan, Echevarría Z

    2013-01-01

    OBJECTIVE To describe clinical and biological characteristics of subjects with virologic failure who participated in the sexually transmitted diseases HIV/AIDS National Program from a Peruvian public hospital. MATERIALS AND METHODS An exploratory descriptive study was performed with data from subjects older than 18 who started high activity antiretroviral therapy (HAART) between May 2004 and December 2009 and who had a viral load control after 24 weeks of HAART. Virologic failure was defined as a viral load value above 1000 copies/mL on follow up after 24 weeks on HAART. RESULTS Of 1 478 records of patients on HAART analized, the median age was 35 years [IQR, 29-41] and 69.6% were male. Also, virologic failure occurred in 24% and 3.7% died. Of subjects with virologic failure, 9.5% died. On multivariate analysis, age, history of antiretroviral use before starting HAART, change of antiretroviral therapy due to toxicity, opportunistic infections during HAART, level of CD4 + lymphocytes below 100 cells/ml at start of HAART, adherence and clinical stage were independently associated with virologic failure. In the group of patient with no history of antiretroviral use before starting HAART, age, opportunistic infections during HAART were associated with virologic failure. CONCLUSION This study identified factors associated with virologic failure. Further studies are needed to evaluate whether the use of these factors can help to identify prospectively patients at high risk of failure, and to design interventions aimed to reduce this risk. PMID:23450408

  19. Virological diagnosis of Ebolavirus infection.

    PubMed

    Smith, D W; Rawlinson, W D; Kok, J; Dwyer, D E; Catton, M

    2015-08-01

    Ebolaviruses, and the other viral causes of haemorrhagic fevers (VHF) have always posed special problems for diagnostic laboratories. These arise from the rarity of human infections, minimal documented experience with test delivery and interpretation, the paucity of established commercial or in-house assays, the lack of clinical material for test development and validation, the high level containment required for handling live virus, the ongoing evolution of the viruses, and the high personal and public health requirements for accurate diagnosis. This article addresses the current situation and the ongoing challenges associated with delivering timely, high quality and safe testing within Australia for people exposed as part of the current major outbreak of Ebolavirus disease (EVD) in Western Africa. The members of the Public Health Laboratory Network have developed deliverable and reliable nucleic acid detection tests, and also have the laboratory capacity to handle the live viruses if necessary. However delivering and maintaining these services necessitates high levels of experience in developing and applying tests for exotic and emerging infections, strong national and international links and collaborations, ongoing monitoring and reassessment of test design and performance, innovative approaches to generation of positive control material, and a regular quality assurance program.

  20. Virological diagnosis of Ebolavirus infection

    PubMed Central

    Smith, D. W.; Rawlinson, W. D.; Kok, J.; Dwyer, D. E.; Catton, M.

    2015-01-01

    Summary Ebolaviruses, and the other viral causes of haemorrhagic fevers (VHF) have always posed special problems for diagnostic laboratories. These arise from the rarity of human infections, minimal documented experience with test delivery and interpretation, the paucity of established commercial or in-house assays, the lack of clinical material for test development and validation, the high level containment required for handling live virus, the ongoing evolution of the viruses, and the high personal and public health requirements for accurate diagnosis. This article addresses the current situation and the ongoing challenges associated with delivering timely, high quality and safe testing within Australia for people exposed as part of the current major outbreak of Ebolavirus disease (EVD) in Western Africa. The members of the Public Health Laboratory Network have developed deliverable and reliable nucleic acid detection tests, and also have the laboratory capacity to handle the live viruses if necessary. However delivering and maintaining these services necessitates high levels of experience in developing and applying tests for exotic and emerging infections, strong national and international links and collaborations, ongoing monitoring and reassessment of test design and performance, innovative approaches to generation of positive control material, and a regular quality assurance program. PMID:26126050

  1. Socio-economic factors and virological suppression among people diagnosed with HIV in the United Kingdom: results from the ASTRA study.

    PubMed

    Burch, Lisa; Smith, Colette; Anderson, Jane; Sherr, Lorraine; Rodger, Alison; O'Connell, Rebecca; Gilson, Richard; Elford, Jonathan; Phillips, Andrew; Speakman, Andrew; Johnson, Margaret; Lampe, Fiona

    2014-01-01

    In the United Kingdom, rates of virological suppression on antiretroviral therapy (ART) are very high, but there remain a small but significant number of people on ART with detectable viraemia. The impact of socio-economic factors on virological suppression has been little studied. We used data from ASTRA, a cross-sectional, questionnaire study of >3000 individuals from 8 clinics in the United Kingdom in 2011-2012, linked to clinical records to address this question. Included participants had received ART for >6 months with a recorded current viral load (VL) (latest at the time of questionnaire). Participants provided data on demographic factors: gender, sexual orientation, ethnicity and age; and socio-economic factors: UK birth/English reading ability, employment, housing, education and financial hardship. To assess non-adherence, participants were asked if in the past 3 months, they had missed ART for ≥2 days at a time. Virological suppression was defined as VL≤50 cps/mL. For each socio-economic factor, we calculated prevalence ratios using modified Poisson regression, first adjusting for demographic factors, then also for non-adherence. A total of 2445 people fulfilled the inclusion criteria (80% male, 69% MSM, median age: 46 years, median CD4 count: 556 cells/mm(3)); 10% (234/2445) had VL>50 cps/mL. After adjusting for demographic factors, non-fluent English, not being employed, not home owning, education below university level and increasing financial hardship were each associated with higher prevalence of VL>50 cps/mL. Additional adjustment for non-adherence largely attenuated each association, but did not fully explain them (see Table 1). After adjustment for non-adherence and demographic factors, younger age was also associated with VL>50 cps/mL: for each additional 10 years an individual was 0.80 (95% CI 0.70-0.92) times as likely to have VL>50 cps/mL (p=0.0019). Adjusted prevalence ratios for VL>50cps/mL were 0.91 (0.62-1.34) for women and 1.25 (0

  2. Current status and prospects of HIV treatment.

    PubMed

    Cihlar, Tomas; Fordyce, Marshall

    2016-06-01

    Current antiviral treatments can reduce HIV-associated morbidity, prolong survival, and prevent HIV transmission. Combination antiretroviral therapy (cART) containing preferably three active drugs from two or more classes is required for durable virologic suppression. Regimen selection is based on virologic efficacy, potential for adverse effects, pill burden and dosing frequency, drug-drug interaction potential, resistance test results, comorbid conditions, social status, and cost. With prolonged virologic suppression, improved clinical outcomes, and longer survival, patients will be exposed to antiretroviral agents for decades. Therefore, maximizing the safety and tolerability of cART is a high priority. Emergence of resistance and/or lack of tolerability in individual patients require availability of a range of treatment options. Development of new drugs is focused on improving safety (e.g. tenofovir alafenamide) and/or resistance profile (e.g. doravirine) within the existing drug classes, combination therapies with improved adherence (e.g. single-tablet regimens), novel mechanisms of action (e.g. attachment inhibitors, maturation inhibitors, broadly neutralizing antibodies), and treatment simplification with infrequent dosing (e.g. long-acting injectables). In parallel with cART innovations, research and development efforts focused on agents that target persistent HIV reservoirs may lead to prolonged drug-free remission and HIV cure.

  3. Simplified Assessment of Antiretroviral Adherence and Prediction of Virological Efficacy in HIV-Infected Patients in Cambodia

    PubMed Central

    Segeral, Olivier; Madec, Yoann; Ban, Boroath; Ouk, Vara; Hak, Chan Roeurn; Le Tiec, Clotilde; Nerrienet, Eric; Goujard, Cécile; Taburet, Anne Marie; Delfraissy, Jean Francois; Fontanet, Arnaud

    2010-01-01

    Background. Adherence to antiviral therapy is important for HIV-infected people living in low- and middle-income countries, because of poor access to alternative regimens. Methods. We conducted a cross-sectional survey of adherence in Cambodian patients enrolled in the ESTHER program and treated with WHO first-line regimen for at least 6 months. The survey was based on a self-report questionnaire, drug assay, MCV measurement, visual analog scale, and viral load HIV RNA. Results. Two hundred fifty-nine patients treated for a median of 16 months participated in the survey. At inclusion in the program, 158 patients (61%) were ARV-naïve. The virological success rate was 71% overall and 81% in previously ARV-naive patients. Considered individually, the measures suggested perfect adherence in 71% to 93% of patients. In multivariate analysis adjusted for sex and therapeutic status before HAART initiation, only the biological markers were associated with virological efficacy. Self-funded treatment before entry to the program was highly predictive of virological failure. Conclusion. Adherence was excellent in these Cambodian patients. Biological markers were predictive of virological efficacy. MCV might thus serve as a simple alternative for assessing adherence and predicting virological efficacy among patients receiving AZT- or d4T-based regimens. PMID:21490902

  4. Computerized clinical guidelines: current status & principles for future research.

    PubMed

    Kondylakis, Haridimos; Tsiknakis, Manolis

    2012-01-01

    Although it is widely accepted that the adoption of computerized clinical guidelines would improve the quality of the provided health care, their influence in the daily practice is limited. In this paper we provide insights on the core topics related to computer interpretable clinical guidelines and we present shortly the main approaches in the area. Then we discuss the current limitations, and we present three simple principles that according to our view should be adopted to enhance the penetration of computerized clinical guidelines in the health care organizations. The overall goal of this paper is not only to give readers a quick overview of the works in the area, but also to provide necessary insights for the practical understanding of the issues involved and draw directions for future research and development activities.

  5. Current status of functional gastrointestinal evaluation in clinical practice

    PubMed Central

    Ang, Daphne; Fock, Kwong Ming; Law, Ngai Moh; Ang, Tiing Leong

    2015-01-01

    Neurogastroenterology and motility disorders of the gastrointestinal (GI) tract encompass a broad spectrum of diseases involving the GI tract and central nervous system. They have varied pathophysiology, clinical presentation and management, and make up a substantial proportion of outpatient clinic visits. Typically, patients experience persistent symptoms referable to the GI tract despite normal endoscopic and radiologic findings. An appropriate evaluation is thus important in the patient’s care. Advances in technology and understanding of the disease pathophysiology have provided better insight into the physiological basis of disease and a more rational approach to patient management. While technological advances serve to explain patients’ persistent symptoms, they should be balanced against the costs of diagnostic tests. This review highlights the GI investigative modalities employed to evaluate patients with persistent GI symptoms in the absence of a structural lesion, with particular emphasis on investigative modalities available locally and the clinical impact of such tools. PMID:25715853

  6. Current status of functional gastrointestinal evaluation in clinical practice.

    PubMed

    Ang, Daphne; Fock, Kwong Ming; Law, Ngai Moh; Ang, Tiing Leong

    2015-02-01

    Neurogastroenterology and motility disorders of the gastrointestinal (GI) tract encompass a broad spectrum of diseases involving the GI tract and central nervous system. They have varied pathophysiology, clinical presentation and management, and make up a substantial proportion of outpatient clinic visits. Typically, patients experience persistent symptoms referable to the GI tract despite normal endoscopic and radiologic findings. An appropriate evaluation is thus important in the patient's care. Advances in technology and understanding of the disease pathophysiology have provided better insight into the physiological basis of disease and a more rational approach to patient management. While technological advances serve to explain patients' persistent symptoms, they should be balanced against the costs of diagnostic tests. This review highlights the GI investigative modalities employed to evaluate patients with persistent GI symptoms in the absence of a structural lesion, with particular emphasis on investigative modalities available locally and the clinical impact of such tools.

  7. Pathologic and virologic study of fatal Lassa fever in man.

    PubMed

    Walker, D H; McCormick, J B; Johnson, K M; Webb, P A; Komba-Kono, G; Elliott, L H; Gardner, J J

    1982-06-01

    Postmortem examination of 21 virologically documented cases of Lassa fever, including 6 complete autopsies, was performed as part of a field study of community-acquired Lassa fever in Sierra Leone. The most consistently observed lesions were hepatocellular, adrenal, and splenic necrosis and adrenal cytoplasmic inclusions. Neither these lesions, nor other milder and less constantly observed lesions such as myocarditis, renal tubular injury, and interstitial pneumonia, appeared severe enough to explain the cause of death in Lassa fever. The central nervous system (CNS) contained no specific lesions. Viral titrations demonstrated high viral content in liver, lung, spleen, kidney, heart, placenta, and mammary gland. Clinical laboratory data included elevation of hepatic enzymes, creatine phosphokinase (CPK), and blood urea nitrogen (BUN). Because of the paucity of pathologic lesions in spite of widely disseminated viral infection, further investigation of humoral inflammatory mechanisms is indicated.

  8. Genotypic resistance tests in the management of the HIV-infected patient at virological failure.

    PubMed

    Aceti, Antonio; Carosi, Giampiero

    2003-01-01

    Witness for the prosecution: The IAS-USA and Euro-Resistance Group HIV guidelines recommend the use of resistance testing for all patients experiencing treatment failure for whom therapy change is being considered. However, these assays suffer from several limitations (problems in sensitivity, specificity, complexity of interpretation, cost) and the results of the prospective studies evaluating genotype-guided treatment in HIV patients failing antiretroviral treatment are inconclusive and partially contrasting (virological benefit is short-term). On this basis, incorporating genotypic resistance assays into the clinical management of HIV patients experiencing first treatment failure is not a sufficiently evidence-based practice. Witness for the defence: Highly active antiretroviral therapy (HAART) has markedly improved the prognosis of HIV-infected patients by controlling HIV replication. However, HAART fails to control HIV replication in an increasing number of patients as a result of a complex array of causes. There is now substantial evidence that the emergence of drug resistance is a leading cause (as well as consequence) of antiretroviral therapy failure. Moreover, HIV drug resistance can be transmitted and this can favour initial treatment failure. Several retrospective and prospective studies have indicated that both genotypic and phenotypic HIV-1 drug resistance testing results are associated with, or predictive of, the virological outcome. As a consequence, international guidelines have soundly recommended the use of resistance testing to guide treatment choices after virological failure. The rationale and advantages of using such testing after first virological failure will be discussed.

  9. A Survey on Clinical Research Training Status and Needs in Public Hospitals from Shenzhen

    ERIC Educational Resources Information Center

    Ji, Ping; Wang, Haibo; Zhang, Chao; Liu, Min; Zhou, Liping; Xiao, Ping; Wang, Yanfang; Wu, Yangfeng

    2017-01-01

    Objective: To obtain information on the current clinical research training status and evaluate the training needs comprehensively for medical staff in hospitals. Methods: This survey was initiated and conducted by the Health and Family Planning Commission of Shenzhen in conjunction with the Peking University Clinical Research Institute (Shenzhen)…

  10. Profile of the Academic Status of Clinical Faculty in Schools of Pharmacy--1974

    ERIC Educational Resources Information Center

    Cardoni, Alex A.; Chow, Moses

    1975-01-01

    A survey of administrative structure and academic status of clinical faculty in accredited schools of pharmacy showed that all responding schools (70 per cent return) have a full-time clinical faculty category with most having part-time and unsalaried as well. Information on departmental power, promotion, tenure, and reappointment are included.…

  11. Weight Status of Children and Adolescents in a Telepsychiatry Clinic

    PubMed Central

    Shaikh, Ulfat; Hilty, Donald M.; Cole, Stacey

    2009-01-01

    Abstract The prevalence of overweight and obesity is approximately 32% among children and adolescents in the United States. Comorbid conditions associated with pediatric overweight and obesity include psychiatric conditions. The purpose of this study was to determine the prevalence of overweight and obesity among children and adolescents presenting for consultation from rural communities to the UC Davis Telemedicine Program (UCDTP), as well as to collect preliminary data to design an integrated disease management program for children and adolescents with obesity and mental illness. Patients aged 21 and under seen for psychiatric consultation at the UCDTP between 2004 and 2006 were included. Retrospective medical record review was conducted to determine the major psychiatric diagnoses, height, weight, body–mass index, and weight status (underweight/at risk for underweight, normal weight, overweight, or obese) for each patient. Of the 230 patients referred, a total of 121 patients had both height and weight values documented. Three patients were underweight; 51 were normal weight; 28 were overweight; 39 were obese. The most common psychiatric diagnoses in the 121 patients were attention deficit/hyperactivity disorder (ADHD; n = 40), bipolar disorder (n = 36), and depression (n = 31). The most common psychiatric diagnoses in patients with available weight and height data who were overweight and obese were bipolar disorder (n = 20), depression (n = 18), and ADHD (n = 17). Approximately 55% of child and adolescent patients seen for telepsychiatry consultation whose charts documented height and weight measurements were overweight or obese. Psychiatric diagnoses in overweight youngsters need to be researched further to determine whether the weight change is primary or secondary to mood and/or to treatments, such as medication. At such a high rate of comorbidity, monitoring the weight status of young psychiatric patients in this population is

  12. Weight status of children and adolescents in a telepsychiatry clinic.

    PubMed

    Marks, Shayna; Shaikh, Ulfat; Hilty, Donald M; Cole, Stacey

    2009-12-01

    The prevalence of overweight and obesity is approximately 32% among children and adolescents in the United States. Comorbid conditions associated with pediatric overweight and obesity include psychiatric conditions. The purpose of this study was to determine the prevalence of overweight and obesity among children and adolescents presenting for consultation from rural communities to the UC Davis Telemedicine Program (UCDTP), as well as to collect preliminary data to design an integrated disease management program for children and adolescents with obesity and mental illness. Patients aged 21 and under seen for psychiatric consultation at the UCDTP between 2004 and 2006 were included. Retrospective medical record review was conducted to determine the major psychiatric diagnoses, height, weight, body-mass index, and weight status (underweight/at risk for underweight, normal weight, overweight, or obese) for each patient. Of the 230 patients referred, a total of 121 patients had both height and weight values documented. Three patients were underweight; 51 were normal weight; 28 were overweight; 39 were obese. The most common psychiatric diagnoses in the 121 patients were attention deficit/hyperactivity disorder (ADHD; n = 40), bipolar disorder (n = 36), and depression (n = 31). The most common psychiatric diagnoses in patients with available weight and height data who were overweight and obese were bipolar disorder (n = 20), depression (n = 18), and ADHD (n = 17). Approximately 55% of child and adolescent patients seen for telepsychiatry consultation whose charts documented height and weight measurements were overweight or obese. Psychiatric diagnoses in overweight youngsters need to be researched further to determine whether the weight change is primary or secondary to mood and/or to treatments, such as medication. At such a high rate of comorbidity, monitoring the weight status of young psychiatric patients in this population is indicated.

  13. Current status of quality in Japanese clinical trials.

    PubMed

    Saito, Kazuyuki; Kodama, Yasuo; Ono, Shunsuke; Mutoh, Mizue; Kawashima, Susumu; Fujimura, Akio

    2005-08-01

    The changes in the quality of Japanese clinical trials were evaluated by comparing the results of Good Clinical Practice (GCP) audits conducted from April 1997 to March 2000 (fiscal year (FY) 1997-1999) with those from April 2001 to March 2002 (FY2001). During both of the periods inspections were undertaken by the Organization for Pharmaceutical Safety and Research (OPSR). The audit findings in the former period were based on the audits that covered 331 hospitals and 775 trials conducted under the old GCP guideline. The audits in the latter period targeted 147 hospitals and 238 trials conducted under the old or new GCP guideline. The total number of deficiencies detected by GCP audits in the former three-year period (FY 1997-1999) was 1529, and the corresponding number in the latter single year (FY 2001) was 912. Two remarkable changes in OPSR's findings were observed between FY 1997-1999 and FY 2001 as follows; the proportion of protocol deviations increased from 14.7% (225/1529) to 53.1% (484/912), while the proportion of errors in case report forms (CRFs) decreased from 43.6% (666/1529) to 15.4% (140/912). The new GCP guideline sets very high standards for a hospital's qualification: to have sufficient equipment and hospital resources, to have capacity for promptly responding to urgent trial-related problems, to have an IRB, and to have appropriate staff including clinical research coordinators (CRCs) assigned to the clinical trial. Our results suggest that the impact of the regulatory changes of applicable standard is large for a hospital's qualification for conducting clinical trials in Japan.

  14. [Cognitive impairment, nutritional status and clinical profile in chronic obstructive pulmonary disease].

    PubMed

    López Torres, Isabel; Torres-Sánchez, Irene; Martín Salvador, Adelina; Ortiz Rubio, Araceli; Rodríguez Alzueta, Elisabeth; Valenza, Marie Carmen

    2014-11-01

    Chronic obstructive pulmonary disease (COPD) is a progressive disease with a prevalence that increases with the aging of the subject. It presents a high prevalence of comorbidities, such as cognitive decline, which is gaining great clinical relevance in recent years. Factors such as pulmonary function, hypoxemia, hypercapnia or exacerbations contribute to the decline of cognitive functions. The nutritional status has been added to these factors as contributing to cognitive function decline when presenting in COPD. To evidence the relationship between cognitive decline, nutritional status and the clinical profile of patients admitted because of an acute exacerbation of COPD (AECOPD). 110 subjects hospitalized because of COPD, divided in two groups according to their nutritional status and assessment of cognitive decline at admittance, nutritional status and clinical profile. Significant differences between groups concerning nutritional status in anthropometric variables (sex and IMC), functional ability (Barthel index and Daily Life Activities Scale), quality of life (Euroqol- 5D y SGRQ), sleep quality (Pittsburgh), mood (HAD) and cognitive decline (MoCa attention, MoCa abstraction). (p<0.05). Cognitive function is affected in COPD patients with an altered nutritional status when compared to those with a normal nutritional status. The nutritional decline is a factor contributing to the impairment of cognitive functions in this kind of patients, particularly a decline in attention and abstraction ability. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

  15. Rabies molecular virology, diagnosis, prevention and treatment

    PubMed Central

    2012-01-01

    Rabies is an avertable viral disease caused by the rabid animal to the warm blooded animals (zoonotic) especially human. Rabies occurs in more than 150 countries and territories. According to an estimation by WHO, almost 55,000 people die because of rabies every year. The Dogs are the major reason behind this, approximately 99% human deaths caused by dog's bites. Developing and under developing countries, both are the victims of rabies. With the post-exposure preventive regimes, 327,000 people can prevent this disease annually. The current article mainly covers the genome, virology, symptoms, epidemiology, diagnostic methods, and the high risk countries around the globe. PMID:22348291

  16. Molecular Virology of Hepatitis E Virus

    PubMed Central

    Ahmad, Imran; Holla, R. Prasida; Jameel, Shahid

    2011-01-01

    This review details the molecular virology of the hepatitis E virus (HEV). While replicons and in vitro infection systems have recently become available, a lot of information on HEV has been generated through comparisons with better-studied positive-strand RNA viruses and through subgenomic expression of viral open reading frames. These models are now being verified with replicon and infection systems. We provide here the current knowledge on the HEV genome and its constituent proteins - ORF1, ORF2 and ORF3. Based on the available information, we also modify the existing model of the HEV life cycle. PMID:21345356

  17. Dolutegravir monotherapy as treatment de-escalation in HIV-infected adults with virological control: DoluMono cohort results.

    PubMed

    Oldenbuettel, Celia; Wolf, Eva; Ritter, Ayla; Noe, Sebastian; Heldwein, Silke; Pascucci, Rita; Wiese, Carmen; Von Krosigk, Ariane; Jaegel-Guedes, Eva; Jaeger, Hans; Balogh, Annamaria; Koegl, Christine; Spinner, Christoph D

    2017-01-01

    The potential toxicity of long-term antiretroviral therapy (ART) requires ongoing investigation of novel strategies for treatment of HIV-infected patients. Monotherapy with the integrase inhibitor (INSTI) dolutegravir (DTG) may offer a favourable safety profile. Additionally, DTG has a high barrier of resistance, crucial for successful maintenance of virological control. However, published data is sparse. Retrospective, single-centre cohort study. We enrolled patients on suppressive ART who were switched to DTG monotherapy in routine clinical practice and fulfilled the following inclusion criteria: HIV RNA level <50 copies/ml for ≥6 months at time of switch (one blip <200 copies/ml with re-suppression accepted), no known INSTI resistance or prior INSTI failure, no replicative HBV infection and no history of AIDS. We identified 31 patients with 24-weeks of follow-up data. Previous ART included a non-nucleoside reverse transcriptase inhibitor, a boosted protease inhibitor or an INSTI in 32%, 6% and 61% of patients, respectively. At week 24, HIV RNA remained <50 copies/ml in all but two patients (94%). One patient chose to discontinue DTG monotherapy and another developed confirmed virological failure (HIV RNA 538 copies/ml) with new INSTI mutations (Q148H/G140S). Immune status and renal and metabolic function showed no statistically significant changes, apart from a significant decrease in gamma-glutamyl transferase. De-escalating to DTG monotherapy in selected patients might be a safe and feasible option. However, in one case evolution of INSTI resistance was observed. Further studies should assess particular risk factors for DTG monotherapy failure. In the meanwhile, caution is warranted.

  18. Magnitude of Virologic Blips Is Associated With a Higher Risk for Virologic Rebound in HIV-Infected Individuals: A Recurrent Events Analysis

    PubMed Central

    Grennan, J. Troy; Loutfy, Mona R.; Su, DeSheng; Harrigan, P. Richard; Cooper, Curtis; Klein, Marina; Machouf, Nima; Montaner, Julio S. G.; Rourke, Sean; Tsoukas, Christos; Hogg, Bob

    2012-01-01

    (See the editorial commentary by Taiwo and Bosch, on pages 1189–91.) Background. The importance of human immunodeficiency virus (HIV) blip magnitude on virologic rebound has been raised in clinical guidelines relating to viral load assays. Methods. Antiretroviral-naive individuals initiating combination antiretroviral therapy (cART) after 1 January 2000 and achieving virologic suppression were studied. Negative binomial models were used to identify blip correlates. Recurrent event models were used to determine the association between blips and rebound by incorporating multiple periods of virologic suppression per individual. Results. 3550 participants (82% male; median age, 40 years) were included. In a multivariable negative binomial regression model, the Amplicor assay was associated with a lower blip rate than branched DNA (rate ratio, 0.69; P < .01), controlling for age, sex, region, baseline HIV-1 RNA and CD4 count, AIDS-defining illnesses, year of cART initiation, cART type, and HIV-1 RNA testing frequency. In a multivariable recurrent event model controlling for age, sex, intravenous drug use, cART start year, cART type, assay type, and HIV-1 RNA testing frequency, blips of 500–999 copies/mL were associated with virologic rebound (hazard ratio, 2.70; P = .002), whereas blips of 50–499 were not. Conclusions. HIV-1 RNA assay was an important determinant of blip rates and should be considered in clinical guidelines. Blips ≥500 copies/mL were associated with increased rebound risk. PMID:22438396

  19. CSF-1R Inhibitor Development: Current Clinical Status.

    PubMed

    Peyraud, Florent; Cousin, Sophie; Italiano, Antoine

    2017-09-05

    Colony-stimulating factor 1 receptor (CSF-1R) and its ligands, CSF-1 and interleukin 34 (IL-34), regulate the function and survival of tumor-associated macrophages, which are involved in tumorigenesis and in the suppression of antitumor immunity. Moreover, the CSF-1R/CSF-1 axis has been implicated in the pathogenesis of pigmented villonodular synovitis (PVNS), a benign tumor of the synovium. As advanced or metastatic malignant solid tumors and relapsed/refractory PVNS remain unresolved therapeutic problems, new approaches are needed to improve the outcome of patients with these conditions. In solid tumors, targeting CSF-1R via either small molecules or antibodies has shown interesting results in vitro but limited antitumor activity in vivo. Concerning PVNS, clinical trials assessing CSF-1R inhibitors have revealed promising initial outcomes. Blocking CSF-1/CSF-1R signaling represents a promising immunotherapy approach and several new potential combination therapies for future clinical testing.

  20. Cell Therapies in Cardiomyopathy: Current Status of Clinical Trials

    PubMed Central

    Wang, Richard

    2017-01-01

    Because the human heart has limited potential for regeneration, the loss of cardiomyocytes during cardiac myopathy and ischaemic injury can result in heart failure and death. Stem cell therapy has emerged as a promising strategy for the treatment of dead myocardium, directly or indirectly, and seems to offer functional benefits to patients. The ideal candidate donor cell for myocardial reconstitution is a stem-like cell that can be easily obtained, has a robust proliferation capacity and a low risk of tumour formation and immune rejection, differentiates into functionally normal cardiomyocytes, and is suitable for minimally invasive clinical transplantation. The ultimate goal of cardiac repair is to regenerate functionally viable myocardium after myocardial infarction (MI) to prevent or heal heart failure. This review provides a comprehensive overview of treatment with stem-like cells in preclinical and clinical studies to assess the feasibility and efficacy of this novel therapeutic strategy in ischaemic cardiomyopathy. PMID:28194324

  1. Ligand-targeted particulate nanomedicines undergoing clinical evaluation: current status.

    PubMed

    van der Meel, Roy; Vehmeijer, Laurens J C; Kok, Robbert J; Storm, Gert; van Gaal, Ethlinn V B

    2013-10-01

    Since the introduction of Doxil® on the market nearly 20years ago, a number of nanomedicines have become part of treatment regimens in the clinic. With the exception of antibody-drug conjugates, these nanomedicines are all devoid of targeting ligands and rely solely on their physicochemical properties and the (patho)physiological processes in the body for their biodistribution and targeting capability. At the same time, many preclinical studies have reported on nanomedicines exposing targeting ligands, or ligand-targeted nanomedicines, yet none of these have been approved at this moment. In the present review, we provide a concise overview of 13 ligand-targeted particulate nanomedicines (ligand-targeted PNMs) that have progressed into clinical trials. The progress of each ligand-targeted PNM is discussed based on available (pre)clinical data. Main conclusions of these analyses are that (a) ligand-targeted PNMs have proven to be safe and efficacious in preclinical models; (b) the vast majority of ligand-targeted PNMs is generated for the treatment of cancer; (c) contribution of targeting ligands to the PNM efficacy is not unambiguously proven; and (d) targeting ligands do not cause localization of the PNM within the target tissue, but rather provide benefits in terms of target cell internalization and target tissue retention once the PNM has arrived at the target site. Increased understanding of the in vivo fate and interactions of the ligand-targeted PNMs with proteins and cells in the human body is mandatory to rationally advance the clinical translation of ligand-targeted PNMs. Future perspectives for ligand-targeted PNM approaches include the delivery of drugs that are unable or inefficient in passing cellular membranes, treatment of drug resistant tumors, targeting of the tumor blood supply, the generation of targeted vaccines and nanomedicines that are able to cross the blood-brain barrier.

  2. [Clinical research training in dentistry: analysis of the current status].

    PubMed

    Sosa Martínez, J; Deister Mateos, E

    1990-06-01

    The collegiate and university realms--which include lectures, students, clinical and scientific sessions--is open to growth. Furthermore, it has opened gates for new currents of thought and planted hopes for the growth and development of professors who, apart from mastering their specialty, may be familiar with didactics and directly or indirectly engage in full-time research, so that their lecturing and promotions may partially depend on the number and quality of their published works, preferably on scientific research.

  3. The Clinical Status of Stem Cell Therapy for Ischemic Cardiomyopathy.

    PubMed

    Wang, Xianyun; Zhang, Jun; Zhang, Fan; Li, Jing; Li, Yaqi; Tan, Zirui; Hu, Jie; Qi, Yixin; Li, Quanhai; Yan, Baoyong

    2015-01-01

    Ischemic cardiomyopathy (ICM) is becoming a leading cause of morbidity and mortality in the whole world. Stem cell-based therapy is emerging as a promising option for treatment of ICM. Several stem cell types including cardiac-derived stem cells (CSCs), bone marrow-derived stem cells, mesenchymal stem cells (MSCs), skeletal myoblasts (SMs), and CD34(+) and CD 133(+) stem cells have been applied in clinical researches. The clinical effect produced by stem cell administration in ICM mainly depends on the transdifferentiation and paracrine effect. One important issue is that low survival and residential rate of transferred stem cells in the infracted myocardium blocks the effective advances in cardiac improvement. Many other factors associated with the efficacy of cell replacement therapy for ICM mainly including the route of delivery, the type and number of stem cell infusion, the timing of injection, patient's physical condition, the particular microenvironment onto which the cells are delivered, and clinical condition remain to be addressed. Here we provide an overview of the pros and cons of these transferred cells and discuss the current state of their therapeutic potential. We believe that stem cell translation will be an ideal option for patients following ischemic heart disease in the future.

  4. Current status of verification practices in clinical biochemistry in Spain.

    PubMed

    Gómez-Rioja, Rubén; Alvarez, Virtudes; Ventura, Montserrat; Alsina, M Jesús; Barba, Núria; Cortés, Mariano; Llopis, María Antonia; Martínez, Cecilia; Ibarz, Mercè

    2013-09-01

    Verification uses logical algorithms to detect potential errors before laboratory results are released to the clinician. Even though verification is one of the main processes in all laboratories, there is a lack of standardization mainly in the algorithms used and the criteria and verification limits applied. A survey in clinical laboratories in Spain was conducted in order to assess the verification process, particularly the use of autoverification. Questionnaires were sent to the laboratories involved in the External Quality Assurance Program organized by the Spanish Society of Clinical Biochemistry and Molecular Pathology. Seven common biochemical parameters were included (glucose, cholesterol, triglycerides, creatinine, potassium, calcium, and alanine aminotransferase). Completed questionnaires were received from 85 laboratories. Nearly all the laboratories reported using the following seven verification criteria: internal quality control, instrument warnings, sample deterioration, reference limits, clinical data, concordance between parameters, and verification of results. The use of all verification criteria varied according to the type of verification (automatic, technical, or medical). Verification limits for these parameters are similar to biological reference ranges. Delta Check was used in 24% of laboratories. Most laboratories (64%) reported using autoverification systems. Autoverification use was related to laboratory size, ownership, and type of laboratory information system, but amount of use (percentage of test autoverified) was not related to laboratory size. A total of 36% of Spanish laboratories do not use autoverification, despite the general implementation of laboratory information systems, most of them, with autoverification ability. Criteria and rules for seven routine biochemical tests were obtained.

  5. Does gender or mode of HIV acquisition affect virological response to modern antiretroviral therapy (ART)?

    PubMed

    Saunders, P; Goodman, A L; Smith, C J; Marshall, N; O'Connor, J L; Lampe, F C; Johnson, M A

    2016-01-01

    Previous UK studies have reported disparities in HIV treatment outcomes for women. We investigated whether these differences persist in the modern antiretroviral treatment (ART) era. A single-centre cohort analysis was carried out. We included in the study all previously ART-naïve individuals at our clinic starting triple ART from 1 January 2006 onwards with at least one follow-up viral load (VL). Time to viral suppression (VS; first viral load < 50 HIV-1 RNA copies/mL), virological failure (VF; first of two consecutive VLs > 200 copies/mL more than 6 months post-ART) and treatment modification were estimated using standard survival methods. Of 1086 individuals, 563 (52%) were men whose risk for HIV acquisition was sex with other men (MSM), 207 (19%) were men whose risk for HIV acquisition was sex with women (MSW) and 316 (29%) were women. Median pre-ART CD4 count and time since HIV diagnosis in these groups were 298, 215 and 219 cells/μL, and 2.3, 0.3 and 0.3 years, respectively. Time to VS was comparable between groups, but women [adjusted hazard ratio (aHR) 2.32; 95% confidence interval (CI) 1.28-4.22] and MSW (aHR 3.28; 95% CI 1.91-5.64) were at considerably higher risk of VF than MSM. Treatment switches and complete discontinuation were also more common among MSW [aHR 1.38 (95% CI 1.04-1.81) and aHR 1.73 (95% CI 0.97-3.16), respectively] and women [aHR 1.87 (95% CI 1.43-2.46) and aHR 3.20 (95% CI 2.03-5.03), respectively] than MSM. Although response rates were good in all groups, poorer virological outcomes for women and MSW have persisted into the modern ART era. Factors that might influence the differences include socioeconomic status and mental health disorders. Further interventions to ensure excellent response rates in women and MSW are required. © 2015 British HIV Association.

  6. Virologic Failure among Children Taking Lopinavir/Ritonavir-Containing First-Line Antiretroviral Therapy in South Africa

    PubMed Central

    Meyers, Tammy; Sawry, Shobna; Wong, Jessica Y.; Moultrie, Harry; Pinillos, Francoise; Fairlie, Lee; van Zyl, Gert

    2014-01-01

    Objective To report the outcomes, clinical management decisions and results of resistance testing among a group of children who developed virologic failure on first line lopinavir/ritonavir (LPV/r)-based therapy from a large cohort of ART-treated children in Soweto. Design Historical cohort study Methods Children with virologic failure were identified from a group of 1692 children <3 years who had initiated first-line LPV/r-containing therapy since 2000 up to end November 2011. Genotyping was conducted in some children and outcomes, management decisions and resistance results were described. Results 152 children with virologic failure on first-line LPV/r-containing ART were included. Resistance testing was performed in 75/152 (49%) and apart from a younger age (11.1 vs 15.1 months, p=0.04), the children with vs those without resistance testing were similar for baseline characteristics (weight, CD4, VL and time to failure). Genotyping revealed that 8/75 (10.7%) had significant LPV/r-associated resistance mutations, including 2 with intermediate DRV resistance. Among 63/75 (84%) children remaining on LPV/r-based therapy, 32/63 (51%) achieved virologic suppression, 2 of these children with significant LPV mutations. 12/152 (8%) children were switched to NNRTI-based therapy in accordance with local guidelines at the time. Of these, 4/12 (33%) resuppressed, and the rest did not achieve virologic suppression including the 2 with LPV mutations. Conclusions Virologic failure of LPV/r-containing first line regimens is associated with accumulation of LPV/r mutations in children. The implications are unclear and surveillance at selected sites is warranted for long-term virologic outcomes and development of resistance. PMID:25741970

  7. Current Status of Xenotransplantation and Prospects for Clinical Application

    PubMed Central

    Pierson, Richard N.; Dorling, Anthony; Ayares, David; Rees, Michael A.; Seebach, Jörg D.; Fishman, Jay A.; Hering, Bernhard J.; Cooper, David K.C.

    2010-01-01

    Xenotransplantation is one promising approach to bridge the gap between available human cells, tissues, and organs and the needs of patients with diabetes or end-stage organ failure. Based on recent progress using genetically-modified source pigs, improving results with conventional and experimental immunosuppression, and expanded understanding of residual physiologic hurdles, xenotransplantation appears likely to be evaluated in clinical trials in the near future for some select applications. This review offers a comprehensive overview of known mechanisms of xenograft injury, a contemporary assessment of preclinical progress and residual barriers, and our opinions regarding where breakthroughs are likely to occur. PMID:19796067

  8. Current status of clinical particle radiotherapy at Lawrence Berkeley Laboratory

    SciTech Connect

    Castro, J.R.; Quivey, J.M.; Lyman, J.T.; Chen, G.T.Y.; Phillips, T.L.; Tobias, C.A.; Alpen, E.L.

    1980-08-15

    Clinical experience with charged particle irradiation of human cancers has been underway at the University of California Lawrence Berkeley Laboratory. Over 150 patients have been irradiated with heavy charged particle beams including helium, carbon, neon, and argon ions. Pilot studies have included such tumor sites as glioma of the brain, carcinoma of the esophagus, carcinoma of the pancreas, carcinoma of the stomach, ocular melanoma, and carcinoma of the uterine cervix. Prospective studies are planned to investigate the improved dose localization potential (helium) and the enhanced biologic and physical dose potential (carbon, neon) in a controlled trial against the best available megavoltage irradiation techniques.

  9. Behavior problems of clinic children: relation to parental marital status, age and sex of child.

    PubMed

    Brady, C P; Bray, J H; Zeeb, L

    1986-07-01

    Behavior problems of 703 children seen in a clinical setting were examined for interactions between and effects of family type (i.e., parental marital status) and age and sex of child. Significant differences were found based on family type, with children of separated, divorced, and remarried parents having more problems. Expected interactions between marital status and age and sex of child were not obtained, although results support prior research with regard to the effects of age and sex.

  10. Synthetic virology: engineering viruses for gene delivery.

    PubMed

    Guenther, Caitlin M; Kuypers, Brianna E; Lam, Michael T; Robinson, Tawana M; Zhao, Julia; Suh, Junghae

    2014-01-01

    The success of gene therapy relies heavily on the performance of vectors that can effectively deliver transgenes to desired cell populations. As viruses have evolved to deliver genetic material into cells, a prolific area of research has emerged over the last several decades to leverage the innate properties of viruses as well as to engineer new features into them. Specifically, the field of synthetic virology aims to capitalize on knowledge accrued from fundamental virology research in order to design functionally enhanced gene delivery vectors. The enhanced viral vectors, or 'bionic' viruses, feature engineered components, or 'parts', that are natural (intrinsic to viruses or from other organisms) and synthetic (such as man-made polymers or inorganic nanoparticles). Various design strategies--rational, combinatorial, and pseudo-rational--have been pursued to create the hybrid viruses. The gene delivery vectors of the future will likely criss-cross the boundaries between natural and synthetic domains to harness the unique strengths afforded by the various functional parts that can be grafted onto virus capsids. Such research endeavors will further expand and enable enhanced control over the functional capacity of these nanoscale devices for biomedicine. © 2014 Wiley Periodicals, Inc.

  11. Raman spectroscopy: the gateway into tomorrow's virology

    PubMed Central

    Lambert, Phelps J; Whitman, Audy G; Dyson, Ossie F; Akula, Shaw M

    2006-01-01

    In the molecular world, researchers act as detectives working hard to unravel the mysteries surrounding cells. One of the researchers' greatest tools in this endeavor has been Raman spectroscopy. Raman spectroscopy is a spectroscopic technique that measures the unique Raman spectra for every type of biological molecule. As such, Raman spectroscopy has the potential to provide scientists with a library of spectra that can be used to unravel the makeup of an unknown molecule. However, this technique is limited in that it is not able to manipulate particular structures without disturbing their unique environment. Recently, a novel technology that combines Raman spectroscopy with optical tweezers, termed Raman tweezers, evades this problem due to its ability to manipulate a sample without physical contact. As such, Raman tweezers has the potential to become an incredibly effective diagnostic tool for differentially distinguishing tissue, and therefore holds great promise in the field of virology for distinguishing between various virally infected cells. This review provides an introduction for a virologist into the world of spectroscopy and explores many of the potential applications of Raman tweezers in virology. PMID:16805914

  12. Raman spectroscopy: the gateway into tomorrow's virology.

    PubMed

    Lambert, Phelps J; Whitman, Audy G; Dyson, Ossie F; Akula, Shaw M

    2006-06-28

    In the molecular world, researchers act as detectives working hard to unravel the mysteries surrounding cells. One of the researchers' greatest tools in this endeavor has been Raman spectroscopy. Raman spectroscopy is a spectroscopic technique that measures the unique Raman spectra for every type of biological molecule. As such, Raman spectroscopy has the potential to provide scientists with a library of spectra that can be used to unravel the makeup of an unknown molecule. However, this technique is limited in that it is not able to manipulate particular structures without disturbing their unique environment. Recently, a novel technology that combines Raman spectroscopy with optical tweezers, termed Raman tweezers, evades this problem due to its ability to manipulate a sample without physical contact. As such, Raman tweezers has the potential to become an incredibly effective diagnostic tool for differentially distinguishing tissue, and therefore holds great promise in the field of virology for distinguishing between various virally infected cells. This review provides an introduction for a virologist into the world of spectroscopy and explores many of the potential applications of Raman tweezers in virology.

  13. Synthetic Virology: Engineering Viruses for Gene Delivery

    PubMed Central

    Guenther, Caitlin M.; Kuypers, Brianna E.; Lam, Michael T.; Robinson, Tawana M.; Zhao, Julia; Suh, Junghae

    2014-01-01

    The success of gene therapy relies heavily on the performance of vectors that can effectively deliver transgenes to desired cell populations. As viruses have evolved to deliver genetic material into cells, a prolific area of research has emerged over the last several decades to leverage the innate properties of viruses as well as to engineer new features into them. Specifically, the field of synthetic virology aims to capitalize on knowledge accrued from fundamental virology research in order to design functionally enhanced gene delivery vectors. The enhanced viral vectors, or “bionic” viruses, feature engineered components, or “parts”, that are natural (intrinsic to viruses or from other organisms) and synthetic (such as man-made polymers or inorganic nanoparticles). Various design strategies – rational, combinatorial, and pseudo-rational – have been pursued to create the hybrid viruses. The gene delivery vectors of the future will likely criss-cross the boundaries between natural and synthetic domains to harness the unique strengths afforded by the various functional parts that can be grafted onto virus capsids. Such research endeavours will further expand and enable enhanced control over the functional capacity of these nanoscale devices for biomedicine. PMID:25195922

  14. Paediatric Virology in the Hippocratic Corpus

    PubMed Central

    Mammas, Ioannis N.; Spandidos, Demetrios A.

    2016-01-01

    Hippocrates (Island of Kos, 460 B.C.-Larissa, 370 B.C.) is the founder of the most famous Medical School of the classical antiquity. In acknowledgement of his pioneering contribution to the new scientific field of Paediatric Virology, this article provides a systematic analysis of the Hippocratic Corpus, with particular focus on viral infections predominating in neonates and children. A mumps epidemic, affecting the island of Thasos in the 5th century B.C., is described in detail. ‘Herpes’, a medical term derived from the ancient Greek word ‘ἕρπειν’, meaning ‘to creep’ or ‘crawl’, is used to describe the spreading of cutaneous lesions in both childhood and adulthood. Cases of children with exanthema ‘resembling mosquito bites’ are presented in reference to varicella or smallpox infection. A variety of upper and lower respiratory tract viral infections are described with impressive accuracy, including rhinitis, pharyngitis, tonsillitis, laryngitis, bronchiolitis and bronchitis. The ‘cough of Perinthos’ epidemic, an influenza-like outbreak in the 5th century B.C., is also recorded and several cases complicated with pneumonia or fatal outcomes are discussed. Hippocrates, moreover, describes conjunctivitis, otitis, lymphadenitis, meningoencephalitis, febrile convulsions, gastroenteritis, hepatitis, poliomyelitis and skin warts, along with proposed treatment directions. Almost 2,400 years later, Hippocrates' systematic approach and methodical innovations can inspire paediatric trainees and future Paediatric Virology subspecialists. PMID:27446241

  15. Paediatric Virology: A rapidly increasing educational challenge

    PubMed Central

    Mammas, Ioannis N.; Theodoridou, Maria; Kramvis, Anna; Thiagarajan, Prakash; Gardner, Sharryn; Papaioannou, Georgia; Melidou, Angeliki; Koutsaki, Maria; Kostagianni, Georgia; Achtsidis, Vassilis; Koutsaftiki, Chryssie; Calachanis, Marcos; Zaravinos, Apostolos; Greenough, Anne; Spandidos, Demetrios A.

    2017-01-01

    The ‘2nd Workshop on Paediatric Virology’, which took place on Saturday the 8th of October 2016 in Athens, Greece, provided an overview on recent views and advances on Paediatric Virology. Emphasis was given to HIV-1 management in Greece, a country under continuous financial crisis, hepatitis B vaccination in Africa, treatment options for hepatitis C virus in childhood, Zika virus in pregnancy and infancy, the burden of influenza on childhood, hand-foot-mouth disease and myocarditis associated with Coxsackie viruses. Other general topics covered included a critical evaluation of Paediatric Accident and Emergency viral infections, multimodality imaging of viral infections in children, surgical approaches of otolaryngologists to complex viral infections, new advances in the diagnosis and treatment of viral conjunctivitis and novel molecular diagnostic methods for HPV in childhood. A brief historical overview of the anti-vaccination movement was also provided, as well as presentations on the educational challenge of Paediatric Virology as a new subspecialty of Paediatrics. This review highlights selected lectures and discussions of the workshop. PMID:28352303

  16. Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052.

    PubMed

    Palumbo, Philip J; Wilson, Ethan A; Piwowar-Manning, Estelle; McCauley, Marybeth; Gamble, Theresa; Kumwenda, Newton; Makhema, Joseph; Kumarasamy, Nagalingeswaran; Chariyalertsak, Suwat; Hakim, James G; Hosseinipour, Mina C; Melo, Marineide G; Godbole, Sheela V; Pilotto, Jose H; Grinsztejn, Beatriz; Panchia, Ravindre; Chen, Ying Q; Cohen, Myron S; Eshleman, Susan H; Fogel, Jessica M

    2017-01-01

    Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350-550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.

  17. Measurement equivalence of the Toronto Structured Interview for Alexithymia across language, gender, and clinical status.

    PubMed

    Keefer, Kateryna V; Taylor, Graeme J; Parker, James D A; Inslegers, Ruth; Michael Bagby, R

    2015-08-30

    The Toronto Structured Interview for Alexithymia (TSIA) has been translated into Dutch, German, and Italian and validated in clinical and nonclinical populations. In order to make valid comparisons across different population groups, it is important to establish measurement equivalence across variables such as language, gender, and clinical status. Our objective in this study was to establish measurement equivalence in relation to language (English, Dutch, German, and Italian), gender, and clinical status (non-clinical, psychiatric, and medical) using differential item functioning (DIF). The sample was composed of 842 adults representing the four language groups, all of whom had undergone the TSIA assessment as part of several earlier studies. Ordinal Logistic Regression was employed to explore DIF of the TSIA items. Although several items were found to exhibit DIF for language, gender, or clinical status, all of these effects were within an acceptable range. These findings provide support for the measurement equivalence of the TSIA, and allow researchers to reliably compare results from studies using the TSIA across the four language groups, gender, and clinical status. Copyright © 2015. Published by Elsevier Ireland Ltd.

  18. Virologic Response to Tipranavir-Ritonavir or Darunavir-Ritonavir Based Regimens in Antiretroviral Therapy Experienced HIV-1 Patients: A Meta-Analysis and Meta-Regression of Randomized Controlled Clinical Trials

    PubMed Central

    Berhan, Asres; Berhan, Yifru

    2013-01-01

    Background The development of tipranavir and darunavir, second generation non-peptidic HIV protease inhibitors, with marked improved resistance profiles, has opened a new perspective on the treatment of antiretroviral therapy (ART) experienced HIV patients with poor viral load control. The aim of this study was to determine the virologic response in ART experienced patients to tipranavir-ritonavir and darunavir-ritonavir based regimens. Methods and Findings A computer based literature search was conducted in the databases of HINARI (Health InterNetwork Access to Research Initiative), Medline and Cochrane library. Meta-analysis was performed by including randomized controlled studies that were conducted in ART experienced patients with plasma viral load above 1,000 copies HIV RNA/ml. The odds ratios and 95% confidence intervals (CI) for viral loads of <50 copies and <400 copies HIV RNA/ml at the end of the intervention were determined by the random effects model. Meta-regression, sensitivity analysis and funnel plots were done. The number of HIV-1 patients who were on either a tipranavir-ritonavir or darunavir-ritonavir based regimen and achieved viral load less than 50 copies HIV RNA/ml was significantly higher (overall OR = 3.4; 95% CI, 2.61– 4.52) than the number of HIV-1 patients who were on investigator selected boosted comparator HIV-1 protease inhibitors (CPIs-ritonavir). Similarly, the number of patients with viral load less than 400 copies HIV RNA/ml was significantly higher in either the tipranavir-ritonavir or darunavir-ritonavir based regimen treated group (overall OR = 3.0; 95% CI, 2.15 – 4.11). Meta-regression showed that the viral load reduction was independent of baseline viral load, baseline CD4 count and duration of tipranavir-ritonavir or darunavir-ritonavir based regimen. Conclusions Tipranavir and darunavir based regimens were more effective in patients who were ART experienced and had poor viral load control. Further studies are

  19. Status and future concerns of clinical and environmental aluminum toxicology

    SciTech Connect

    Flaten, T.P.; Alfrey, A.C.; Birchall, J.D.

    1996-08-30

    A wide range of toxic effects of aluminum (Al) have been demonstrated in plants and aquatic animals in nature, in experimental animals by several routes of exposure, and under different clinical conditions in humans. Aluminum toxicity is a major problem in agriculture, affecting perhaps as much as 40% of arable soils in the world. In fresh waters acidified by acid rain, Al toxicity has led to fish extinction. Aluminum is a very potent neurotoxicant. In humans with chronic renal failure on dialysis, Al causes encephalopathy, osteomalacia, and anemia. There are also reports of such effects in certain patient groups without renal failure. Subtle neurocognitive and psychomotor effects and electroncephalograph (EEG) abnormalities have been reported at plasma Al levels as low as 50 {mu}g/L. Infants could be particularly susceptible to Al accumulation and toxicity, reduced renal function being one contributory cause. Recent reports clearly show that Al accumulation occurs in the tissues of workers with long-term occupational exposure to Al dusts or fumes, and also indicate that such exposure may cause subtle neurological effects increased efforts should be directed toward defining the full range of potentially harmful effects in humans. To this end, multidisciplinary collaborative research efforts are encouraged, involving scientists from many different specialities. Emphasis should be placed on increasing our understanding of the chemistry of Al in biological systems, and on determining the cellular and molecular mechanisms of Al toxicity. 95 refs.

  20. Self-Esteem, Oral Health Behaviours, and Clinical Oral Health Status in Chinese Adults: An Exploratory Study

    ERIC Educational Resources Information Center

    Chin, Luzy Siu-Hei; Chan, Joanne Chung-Yan

    2013-01-01

    Objectives: This is an exploratory study to examine the relations among self-esteem, oral health behaviours and clinical oral health status in Chinese adults. In addition, gender differences in clinical oral health status and oral health behaviours were explored. Methods: Participants were 192 patients from a private dental clinic in Hong Kong…

  1. Self-Esteem, Oral Health Behaviours, and Clinical Oral Health Status in Chinese Adults: An Exploratory Study

    ERIC Educational Resources Information Center

    Chin, Luzy Siu-Hei; Chan, Joanne Chung-Yan

    2013-01-01

    Objectives: This is an exploratory study to examine the relations among self-esteem, oral health behaviours and clinical oral health status in Chinese adults. In addition, gender differences in clinical oral health status and oral health behaviours were explored. Methods: Participants were 192 patients from a private dental clinic in Hong Kong…

  2. Immunotherapy for Cervical Cancer: Research Status and Clinical Potential

    PubMed Central

    Su, Jun-Han; Wu, Anjui; Scotney, Elizabeth; Ma, Barbara; Monie, Archana; Hung, Chien-Fu; Wu, T.-C.

    2010-01-01

    The high-risk types of human papillomavirus (HPV) have been found to be associated with most cervical cancers and play an essential role in the pathogenesis of the disease. Despite recent advances in preventive HPV vaccine development, such preventive vaccines are unlikely to reduce the prevalence of HPV infections within the next few years, due to their cost and limited availability in developing countries. Furthermore, preventive HPV vaccines may not be capable of treating established HPV infections and HPV-associated lesions, which account for high morbidity and mortality worldwide. Thus, it is important to develop therapeutic HPV vaccines for the control of existing HPV infection and associated malignancies. Therapeutic vaccines are quite different from preventive vaccines in that they require the generation of cell-mediated immunity, particularly T cell-mediated immunity, instead of the generation of neutralizing antibodies. The HPV-encoded early proteins, E6 and E7 oncoproteins, form ideal targets for therapeutic HPV vaccines since they are consistently expressed in HPV-associated cervical cancer and its precursor lesions and thus play crucial roles in the generation and maintenance of HPV-associated disease. Our review will cover the various therapeutic HPV vaccines for cervical cancer, including live vector-based, peptide or protein-based, nucleic acid-based, and cell-based vaccines targeting the HPV E6 and/or E7 antigens. Furthermore, we will review the studies using therapeutic HPV vaccines in combination with other therapeutic modalities and review the latest clinical trials on therapeutic HPV vaccines. PMID:20199126

  3. Elbasvir plus grazoprevir in patients with hepatitis C virus infection and stage 4-5 chronic kidney disease: clinical, virological, and health-related quality-of-life outcomes from a phase 3, multicentre, randomised, double-blind, placebo-controlled trial.

    PubMed

    Bruchfeld, Annette; Roth, David; Martin, Paul; Nelson, David R; Pol, Stanislas; Londoño, Maria-Carlota; Monsour, Howard; Silva, Marcelo; Hwang, Peggy; Arduino, Jean-Marie; Robertson, Michael; Nguyen, Bach-Yen; Wahl, Janice; Barr, Eliav; Greaves, Wayne

    2017-08-01

    In the C-SURFER study, therapy with the all-oral elbasvir plus grazoprevir regimen for 12 weeks in patients with chronic hepatitis C virus (HCV) infection and stage 4-5 chronic kidney disease resulted in a high rate of virological cure compared with placebo. Here, we report sustained virological response (SVR), safety data, health-related quality-of-life (HRQOL), and virological resistance analyses in patients in C-SURFER who received immediate antiviral therapy or who received placebo before therapy. In this phase 3, multicentre, randomised, placebo-controlled study, we randomly assigned adults with HCV genotype 1 infection and stage 4-5 chronic kidney disease enrolled at 68 centres worldwide to either elbasvir 50 mg plus grazoprevir 100 mg once per day for 12 weeks (immediate treatment group) or placebo for 12 weeks followed by elbasvir 50 mg plus grazoprevir 100 mg once per day for 12 weeks beginning at week 16 (deferred treatment group). The primary safety and efficacy endpoints for the immediate treatment group and placebo phase of the deferred treatment group have been reported previously. Here, we report safety and efficacy data for the treatment phase of the deferred treatment group, as well as HRQOL assessed using the 36-Item Short Form Health Survey for all groups, and baseline and treatment-emergent resistance-associated substitutions (RASs). SVR at 12 weeks (SVR12) was assessed in the modified full analysis set (FAS), defined as all patients excluding those who did not receive at least one dose of study drug, who died, or who discontinued the study before the end of treatment for reasons determined to be unrelated to HCV treatment. This trial is registered with ClinicalTrials.gov, Number NCT02092350. Between March 30 and Nov 28, 2014, 235 patients were enrolled and received at least one dose of study drug. The modified FAS included 116 patients assigned to immediate treatment and 99 assigned to deferred treatment. 115 (99·1%; 95% CI 95·3-100·0) of

  4. Design rules for nanomedical engineering: from physical virology to the applications of virus-based materials in medicine.

    PubMed

    Wen, Amy M; Rambhia, Pooja H; French, Roger H; Steinmetz, Nicole F

    2013-03-01

    Physical virology seeks to define the principles of physics underlying viral infections, traditionally focusing on the fundamental processes governing virus assembly, maturation, and disassembly. A detailed understanding of virus structure and assembly has facilitated the development and analysis of virus-based materials for medical applications. In this Physical Virology review article, we discuss the recent developments in nanomedicine that help us to understand how physical properties affect the in vivo fate and clinical impact of (virus-based) nanoparticles. We summarize and discuss the design rules that need to be considered for the successful development and translation of virus-based nanomaterials from bench to bedside.

  5. The current status and trend of clinical pharmacology in developing countries

    PubMed Central

    2013-01-01

    Background Several international forums for promoting clinical pharmacology in developing countries have been held since 1980, and several clinical pharmacology programmes targeting developing countries were instituted such that the status of clinical pharmacology in developing countries is not where it was 50 years ago. Therefore, a survey and an appraisal of the literature on the current status of clinical pharmacology in developing countries were undertaken with a hope that it would enable development of appropriate strategies for further promotion of clinical pharmacology in these countries. Methods First, nine determinants (or enabling factors) for running a successful clinical pharmacology programme were identified, i.e., disease burden, drug situation, economic growth, clinical pharmacology activities, recognition, human capital, government support, international collaboration, and support for traditional/alternative medicines. These factors were then evaluated with regard to their current status in the developing countries that responded to an electronic questionnaire, and their historical perspective, using the literature appraisal. From these, a projected trend was constructed with recommendations on the way forward. Results Clinical pharmacology services, research and teaching in developing countries have improved over the past 50 years with over 90% of countries having the appropriate policies for regulation and rational use of medicines in place. Unfortunately, policy implementation remains a challenge, owing to a worsening disease burden and drug situation, versus fewer clinical pharmacologists and other competing priorities for the national budgets. This has led to a preference for training ‘a physician clinical pharmacologist’ in programmes emphasizing local relevancy and for a shorter time, and the training of other professionals in therapeutics for endemic diseases (task shifting), as the most promising strategies of ensuring rational use of

  6. Virological outcomes of antiretroviral therapy in Zomba central prison, Malawi; a cross-sectional study

    PubMed Central

    Mpawa, Happy; Kwekwesa, Aunex; Amberbir, Alemayehu; Garone, Daniela; Divala, Oscar H.; Kawalazira, Gift; van Schoor, Vanessa; Ndindi, Henry; van Oosterhout, Joep J.

    2017-01-01

    Abstract Introduction: Antiretroviral therapy (ART) outcomes that include viral suppression rates are rarely reported among African prison populations. Prisoners deal with specific challenges concerning adherence to ART. We aimed to describe virological outcomes of ART in a large prison in Malawi. Methods: A cross-sectional study of ART outcomes was conducted at the Zomba Central Prison HIV clinic, Malawi, following the introduction of routine viral load monitoring. All prisoners on ART for at least 6 months were eligible for a viral load test. Patients with ≥1,000 copies/ml received adherence support for 3 months, after which a second VL sample was taken. Patients with ≥5,000 copies/ml on the second sample had virological failure and started 2nd line ART. We describe demographics and patient characteristics and report prevalence of potential- and documented virological failure. In the potential virological failure rate, those who could not be sampled after 3 months adherence support are included as virological failures. Logistic regression analysis was used to determine factors associated with potential ART failure. Results and discussion: Viral load testing was started at the end of 2014, when 1054 patients had ever registered on ART. Of those, 501 (47.5%) had transferred out to another clinic, 96 (9.1%) had died, 11 defaulted (1.0%) and 3 (0.3%) stopped ART. Of 443 (42.0%) remaining alive in care, an estimated 322 prisoners were on ART >6 months, of whom 262 (81.4%) were sampled. Their median age was 35 years (IQR 31–40) and 257 (98.1%) were male. Self-reported adherence was good in 258 (98.5%). The rate of potential ART failure was 8.0%, documented ART failure was 4.6% and documented HIV suppression 95.0%. No patient characteristics were independently associated with potential ART failure, possibly due to low numbers with this outcome. Conclusions: Good virological suppression rates can be achieved among Malawian prisoners on ART, under challenging

  7. Virological and serological features of acute hepatitis B in adults

    PubMed Central

    Du, Xiaofei; Liu, Yali; Ma, Lina; Lu, Junfeng; Jin, Yi; Ren, Shan; He, Zhimin; Chen, Xinyue

    2017-01-01

    Abstract Various viral kinetics among patients with acute hepatitis B (AHB) have been observed in clinical practice. This study investigated the virological, biochemical, and serological characteristics of AHB in adults. A total of 192 adult patients with AHB were recruited between December 2010 and January 2014. The quantification of biochemical and serologic markers for hepatitis B virus (HBV) infection was monitored from the onset. Of the 192 patients, 113 patients were followed up. One patient died due to acute liver failure, 2 developed chronic HBV infection. Clinical recovery was observed in 110 patients; 92.7% (102/110) achieved clinical recovery within 24 weeks, and 7.3% (8/110) between 24 and 44 weeks. There were 3 different viral kinetics patterns among the patients with AHB: the clearance of HBV DNA preceded hepatitis B e antigen (HBeAg) and hepatitis B surface antigen (HBsAg), the clearance of HBeAg preceded HBV DNA and HBsAg, the clearance of HBsAg preceded HBV DNA and HBeAg. In the absence of HBV DNA clearance within 13 weeks, the risk of development of chronic HBV infection increased. The serologic HBV markers clearance occurred between 24 and 44 weeks (6–11 months) from the onset in 8 of the AHB patients, which was longer than 6 months. Thus, AHB may be redefined as HBV DNA undetectable, HBsAg and HBeAg seroconversion within 44 weeks. PMID:28207518

  8. Hepatitis C virus: virology and life cycle.

    PubMed

    Kim, Chang Wook; Chang, Kyong-Mi

    2013-03-01

    Hepatitis C virus (HCV) is a positive sense, single-stranded RNA virus in the Flaviviridae family. It causes acute hepatitis with a high propensity for chronic infection. Chronic HCV infection can progress to severe liver disease including cirrhosis and hepatocellular carcinoma. In the last decade, our basic understanding of HCV virology and life cycle has advanced greatly with the development of HCV cell culture and replication systems. Our ability to treat HCV infection has also been improved with the combined use of interferon, ribavirin and small molecule inhibitors of the virally encoded NS3/4A protease, although better therapeutic options are needed with greater antiviral efficacy and less toxicity. In this article, we review various aspects of HCV life cycle including viral attachment, entry, fusion, viral RNA translation, posttranslational processing, HCV replication, viral assembly and release. Each of these steps provides potential targets for novel antiviral therapeutics to cure HCV infection and prevent the adverse consequences of progressive liver disease.

  9. Entomologic and Virologic Investigation of Chikungunya, Singapore

    PubMed Central

    Tan, Li-Kiang; Tan, Cheong-Huat; Tan, Sharon S.Y.; Hapuarachchi, Hapuarachchige C.; Pok, Kwoon-Yong; Lai, Yee-Ling; Lam-Phua, Sai-Gek; Bucht, Göran; Lin, Raymond T.P.; Leo, Yee-Sin; Tan, Boon-Hian; Han, Hwi-Kwang; Ooi, Peng-Lim S; James, Lyn; Khoo, Seow-Poh

    2009-01-01

    Local transmission of chikungunya, a debilitating mosquito-borne viral disease, was first reported in Singapore in January 2008. After 3 months of absence, locally acquired Chikungunya cases resurfaced in May 2008, causing an outbreak that resulted in a total of 231 cases by September 2008. The circulating viruses were related to East, Central, and South African genotypes that emerged in the Indian Ocean region in 2005. The first local outbreak was due to a wild-type virus (alanine at codon 226 of the envelope 1 gene) and occurred in an area where Aedes aegypti mosquitoes were the primary vector. Strains isolated during subsequent outbreaks showed alanine to valine substitution (A226V) and largely spread in areas predominated by Ae. albopictus mosquitoes. These findings led to a revision of the current vector control strategy in Singapore. This report highlights the use of entomologic and virologic data to assist in the control of chikungunya in disease-endemic areas. PMID:19751586

  10. VIPERdb: a relational database for structural virology

    PubMed Central

    Shepherd, Craig M.; Borelli, Ian A.; Lander, Gabriel; Natarajan, Padmaja; Siddavanahalli, Vinay; Bajaj, Chandrajit; Johnson, John E.; Brooks, Charles L.; Reddy, Vijay S.

    2006-01-01

    VIPERdb () is a database for icosahedral virus capsid structures. Our aim is to provide a comprehensive resource specific to the needs of the structural virology community, with an emphasis on the description and comparison of derived data from structural and energetic analyses of capsids. A relational database implementation based on a schema for macromolecular structure makes the data highly accessible to the user, allowing detailed queries at the atomic level. Together with curation practices that maintain data uniformity, this will facilitate structural bioinformatics studies of virus capsids. User friendly search, visualization and educational tools on the website allow both structural and derived data to be examined easily and extensively. Links to relevant literature, sequence and taxonomy databases are provided for each entry. PMID:16381893

  11. VIPERdb: a relational database for structural virology.

    PubMed

    Shepherd, Craig M; Borelli, Ian A; Lander, Gabriel; Natarajan, Padmaja; Siddavanahalli, Vinay; Bajaj, Chandrajit; Johnson, John E; Brooks, Charles L; Reddy, Vijay S

    2006-01-01

    VIPERdb (http://viperdb.scripps.edu) is a database for icosahedral virus capsid structures. Our aim is to provide a comprehensive resource specific to the needs of the structural virology community, with an emphasis on the description and comparison of derived data from structural and energetic analyses of capsids. A relational database implementation based on a schema for macromolecular structure makes the data highly accessible to the user, allowing detailed queries at the atomic level. Together with curation practices that maintain data uniformity, this will facilitate structural bioinformatics studies of virus capsids. User friendly search, visualization and educational tools on the website allow both structural and derived data to be examined easily and extensively. Links to relevant literature, sequence and taxonomy databases are provided for each entry.

  12. Levels of uninvolved immunoglobulins predict clinical status and progression-free survival for multiple myeloma patients.

    PubMed

    Harutyunyan, Nika M; Vardanyan, Suzie; Ghermezi, Michael; Gottlieb, Jillian; Berenson, Ariana; Andreu-Vieyra, Claudia; Berenson, James R

    2016-07-01

    Multiple myeloma (MM) is characterized by the enhanced production of the same monoclonal immunoglobulin (M-Ig or M protein). Techniques such as serum protein electrophoresis and nephelometry are routinely used to quantify levels of this protein in the serum of MM patients. However, these methods are not without their shortcomings and problems accurately quantifying M proteins remain. Precise quantification of the types and levels of M-Ig present is critical to monitoring patient response to therapy. In this study, we investigated the ability of the HevyLite (HLC) immunoassay to correlate with clinical status based on levels of involved and uninvolved antibodies. In our cohort of MM patients, we observed that significantly higher ratios and greater differences of involved HLC levels compared to uninvolved HLC levels correlated with a worse clinical status. Similarly, higher absolute levels of involved HLC antibodies and lower levels of uninvolved HLC antibodies also correlated with a worse clinical status and a shorter progression-free survival. These findings suggest that the HLC assay is a useful and a promising tool for determining the clinical status and survival time for patients with multiple myeloma. © 2016 John Wiley & Sons Ltd.

  13. T cell virological synapses and HIV-1 pathogenesis.

    PubMed

    Chen, Benjamin K

    2012-12-01

    Human immunodeficiency virus type 1 is the cause of a modern global pandemic associated with progressive acquired immune deficiency. The infection is characterized by the loss of the primary target of viral infection, the CD4+ T cell. The measurement of plasma viremia in patients can predict the rate of CD4+ cell decline; however, it is not clear whether this cell-free plasma virus represents the engine that drives viral spread. Active viral replication is mainly observed within lymphoid tissues that are hotbeds of cell-cell interactions that initiate and organize immune responses. It is well established that cell-cell interactions enhance viral spread in vitro. Dendritic cell-T cell interactions, which lie at the heart of adaptive immune responses, enhance viral infection in vitro. Interactions between infected and uninfected CD4+ T cells are a dominant route of viral spread in vitro and are likely to play a central role in viral dissemination in vivo. Future studies will test existing paradigms of HIV-1 dissemination to determine whether virus-transmitting contacts between infected and uninfected T cells called virological synapses are the dominant mode of viral spread in vivo. Here, we review the status of our understanding of this mode of infection with a focus on T cell-T cell interactions and examine how it may explain resistance to neutralizing antibodies and or the generation of genetic diversity of HIV.

  14. Research in the field of antiviral chemotherapy performed in the "Stefan S. Nicolau" Institute of Virology.

    PubMed

    Eşanu, V

    1984-01-01

    A brief review is made of the research in the field of antiviral chemotherapy performed in the "Stefan S. Nicolau" Institute of Virology during the 35 years since its foundation. The investigations have mainly focused on influenza and herpes virus, but the chemotherapy of other viral infections (mumps, vaccinia, Coxsackie, etc.) has also been approached. Most of the chemotherapy agents assayed have been represented by natural preparations: immunoglobulins, interferon, hormones, vitamins, plant extracts (garlic, horse radish), bee products (propolis, royal jelly); attempts have also been made with numerous synthetic compounds. Stress is laid on the preparations already tested with a view to application in human clinic, and the prospects of chemotherapy research in the Institute of Virology are discussed.

  15. Antiretroviral Treatment Interruptions Induced by the Kenyan Postelection Crisis Are Associated With Virological Failure

    PubMed Central

    Kemboi, Emmanuel; Mambo, Fidelis; Rono, Mary; Injera, Wilfred; Delong, Allison; Schreier, Leeann; Kaloustian, Kara W.; Sidle, John; Buziba, Nathan; Kantor, Rami

    2014-01-01

    Background Antiretroviral treatment interruptions (TIs) cause suboptimal clinical outcomes. Data on TIs during social disruption are limited. Methods We determined effects of unplanned TIs after the 2007–2008 Kenyan postelection violence on virological failure, comparing viral load (VL) outcomes in HIV-infected adults with and without conflict-induced TI. Results Two hundred and one patients were enrolled, median 2.2 years after conflict and 4.3 years on treatment. Eighty-eight patients experienced conflict-related TIs and 113 received continuous treatment. After adjusting for preconflict CD4, patients with TIs were more likely to have detectable VL, VL >5,000 and VL >10,000. Conclusions Unplanned conflict-related TIs are associated with increased likelihood of virological failure. PMID:24047971

  16. Current views and advances on Paediatric Virology: An update for paediatric trainees.

    PubMed

    Mammas, Ioannis N; Greenough, Anne; Theodoridou, Maria; Kramvis, Anna; Christaki, Iliana; Koutsaftiki, Chryssie; Koutsaki, Maria; Portaliou, Dimitra M; Kostagianni, Georgia; Panagopoulou, Paraskevi; Sourvinos, George; Spandidos, Demetrios A

    2016-01-01

    Paediatric Virology is a bold new scientific field, which combines Paediatrics with Virology, Epidemiology, Molecular Medicine, Evidence-based Medicine, Clinical Governance, Quality Improvement, Pharmacology and Immunology. The Workshop on Paediatric Virology, which took place on Saturday October 10, 2015 in Athens, Greece, provided an overview of recent views and advances on viral infections occurring in neonates and children. It was included in the official programme of the 20th World Congress on Advances in Oncology and the 18th International Symposium on Molecular Medicine, which attracted over 500 delegates from the five continents. During the Workshop, the topics covered included the challenges of vaccine implementation against human papillomaviruses in countries under financial crisis, strategies for eradicating poliomyelitis and its 60th vaccine anniversary, as well as the debate on the association between autism and vaccination against measles, mumps and rubella. Among the non-vaccine related topics, emphasis was given to viral infections in prematurely born infants and their long-term outcomes, new paediatric intensive care management options for bronchiolitis related to respiratory syncytial virus, the clinical implications of hepatitis B virus and cytomegalovirus genotyping, the Ebola virus threat and preparedness in Paediatric Emergency Departments, oral, oropharynx, laryngeal, nasal and ocular viral infections and Merkel cell polyomavirus as a novel emerging virus of infancy and childhood. In this review, we provide selected presentations and reports discussed at the Workshop.

  17. Current views and advances on Paediatric Virology: An update for paediatric trainees

    PubMed Central

    MAMMAS, IOANNIS N.; GREENOUGH, ANNE; THEODORIDOU, MARIA; KRAMVIS, ANNA; CHRISTAKI, ILIANA; KOUTSAFTIKI, CHRYSSIE; KOUTSAKI, MARIA; PORTALIOU, DIMITRA M.; KOSTAGIANNI, GEORGIA; PANAGOPOULOU, PARASKEVI; SOURVINOS, GEORGE; SPANDIDOS, DEMETRIOS A.

    2016-01-01

    Paediatric Virology is a bold new scientific field, which combines Paediatrics with Virology, Epidemiology, Molecular Medicine, Evidence-based Medicine, Clinical Governance, Quality Improvement, Pharmacology and Immunology. The Workshop on Paediatric Virology, which took place on Saturday October 10, 2015 in Athens, Greece, provided an overview of recent views and advances on viral infections occurring in neonates and children. It was included in the official programme of the 20th World Congress on Advances in Oncology and the 18th International Symposium on Molecular Medicine, which attracted over 500 delegates from the five continents. During the Workshop, the topics covered included the challenges of vaccine implementation against human papillomaviruses in countries under financial crisis, strategies for eradicating poliomyelitis and its 60th vaccine anniversary, as well as the debate on the association between autism and vaccination against measles, mumps and rubella. Among the non-vaccine related topics, emphasis was given to viral infections in prematurely born infants and their long-term outcomes, new paediatric intensive care management options for bronchiolitis related to respiratory syncytial virus, the clinical implications of hepatitis B virus and cytomegalovirus genotyping, the Ebola virus threat and preparedness in Paediatric Emergency Departments, oral, oropharynx, laryngeal, nasal and ocular viral infections and Merkel cell polyomavirus as a novel emerging virus of infancy and childhood. In this review, we provide selected presentations and reports discussed at the Workshop. PMID:26889211

  18. Illness Representations of HIV Positive Patients Are Associated with Virologic Success

    PubMed Central

    Leone, Daniela; Borghi, Lidia; Lamiani, Giulia; Barlascini, Luca; Bini, Teresa; d’Arminio Monforte, Antonella; Vegni, Elena

    2016-01-01

    Introduction: It is important for HIV positive patients to be engaged in their care and be adherent to treatment in order to reduce disease progression and mortality. Studies found that illness representations influence adherence through the mediating role of coping behaviors. However, no study has ever tested if patient engagement to the visits mediate the relationship between illness perceptions and adherence. This study aimed to explore illness representations of HIV positive patients and test the hypothesis that illness representations predict adherence through the mediating role of a component of behavioral engagement. Methods: HIV-positive patients treated with highly active antiretroviral therapy (HAART) for at least one year and presenting to a check-up visit were eligible to participate in the study. Patients completed the Illness Perception Questionnaire-Revised. Behavioral engagement was measured based on the patients’ clinical attendance to the check-up visits; adherence to HAART was measured by viral load. Undetectable viral load or HIV-RNA < 40 copies/ml were considered indexes of virologic success. Results: A total of 161 patients participated in the study. Most of them coherently attributed the experienced symptoms to HIV/HAART; perceived their condition as chronic, stable, coherent, judged the therapy as effective, and attributed their disease to the HIV virus and to their behavior or bad luck. The majority of patients (80.1%) regularly attended check-up visits and 88.5% of them reached virologic success. The mediation model did not show good fit indexes. However, a significant direct effect of two independent variables on virologic success was found. Specifically, the perception that the disease does not have serious consequences on patient’s life and the prevalence of negative emotions toward HIV were associated with virologic success. On the contrary, the patient’s perception that the disease has serious consequences on his/her life and

  19. Illness Representations of HIV Positive Patients Are Associated with Virologic Success.

    PubMed

    Leone, Daniela; Borghi, Lidia; Lamiani, Giulia; Barlascini, Luca; Bini, Teresa; d'Arminio Monforte, Antonella; Vegni, Elena

    2016-01-01

    Introduction: It is important for HIV positive patients to be engaged in their care and be adherent to treatment in order to reduce disease progression and mortality. Studies found that illness representations influence adherence through the mediating role of coping behaviors. However, no study has ever tested if patient engagement to the visits mediate the relationship between illness perceptions and adherence. This study aimed to explore illness representations of HIV positive patients and test the hypothesis that illness representations predict adherence through the mediating role of a component of behavioral engagement. Methods: HIV-positive patients treated with highly active antiretroviral therapy (HAART) for at least one year and presenting to a check-up visit were eligible to participate in the study. Patients completed the Illness Perception Questionnaire-Revised. Behavioral engagement was measured based on the patients' clinical attendance to the check-up visits; adherence to HAART was measured by viral load. Undetectable viral load or HIV-RNA < 40 copies/ml were considered indexes of virologic success. Results: A total of 161 patients participated in the study. Most of them coherently attributed the experienced symptoms to HIV/HAART; perceived their condition as chronic, stable, coherent, judged the therapy as effective, and attributed their disease to the HIV virus and to their behavior or bad luck. The majority of patients (80.1%) regularly attended check-up visits and 88.5% of them reached virologic success. The mediation model did not show good fit indexes. However, a significant direct effect of two independent variables on virologic success was found. Specifically, the perception that the disease does not have serious consequences on patient's life and the prevalence of negative emotions toward HIV were associated with virologic success. On the contrary, the patient's perception that the disease has serious consequences on his/her life and the

  20. Riboflavin status and its association with serum hs-CRP levels among clinical nurses with depression.

    PubMed

    Naghashpour, Mahshid; Amani, Reza; Nutr, R; Nematpour, Sorur; Haghighizadeh, Mohammad Hosein

    2011-10-01

    The objective of present study was to assess the relationship between the dietary intake and blood status of riboflavin and the prevalence of systemic inflammation among both depressed and nondepressed nurses. This was a cross-sectional study on 98 female clinical nurses (45 depressed and 53 nondepressed subjects). Depression status was assessed using the Beck Depression Inventory. We assessed dietary intake of riboflavin using 3-day 24-hour recalls. The serum concentrations of high-sensitive C-reactive protein (hs-CRP) were also measured. Riboflavin status was assessed as the erythrocyte glutathione reductase activity coefficient (EGRAC). Marginal riboflavin deficiency was more prevalent in depressed subjects (P = 0.028). The results of the dietary intake and status of riboflavin were classified to 3 tertiles of serum hs-CRP levels. In both nondepressed and depressed subjects, there was no significant difference between hs-CRP tertiles in dietary intakes of riboflavin, EGRAC, or riboflavin deficiencies. This study showed a higher prevalence of marginal riboflavin deficiency in depressed subjects. We found no association between dietary intake and status of riboflavin with low-grade systematic inflammation in nondepressed and depressed clinical nurses.

  1. Nutritional status of older patients with oropharyngeal dysphagia in a chronic versus an acute clinical situation.

    PubMed

    Carrión, Silvia; Roca, Maria; Costa, Alicia; Arreola, Viridiana; Ortega, Omar; Palomera, Elisabet; Serra-Prat, Mateu; Cabré, Mateu; Clavé, Pere

    2017-08-01

    Oropharyngeal dysphagia (OD) is a prevalent risk factor for malnutrition (MN) in older patients and both conditions are related to poor outcome. To explore the nutritional status in older patients with OD in a chronic and an acute clinical situation. We examined 95 older (≥70 years) patients with OD associated to chronic neurological diseases or aging, and 23 older patients with OD and acute community-acquired pneumonia (CAP) with videofluoroscopy; and 15 older people without OD. We collected nutritional status, measured with the Mini Nutritional Assessment (MNA(®)), anthropometric measurements, and biochemistry and bioimpedance for body composition. Functional status was assessed with the Barthel index. 1) Taking into consideration patients with OD with chronic conditions, 51.1% presented a MNA(®) ≤23.5; 16.7%, sarcopenia and a) reduced visceral and muscular protein compartments and fat compartment; b) muscular weakness c) intracellular water depletion, and d) reduced body weight. Patients with OD and MNA(®) ≤23 needed higher levels of nectar viscosity for a safe swallow and had increased oropharyngeal residue at spoon-thick viscosity. 2) Patients with OD and CAP, 69.5%, presented an MNA(®) ≤23.5 and 29.4% sarcopenia, the inflammatory response of the pneumonia adding to the more severe depletion in visceral protein and muscular mass. Prevalence of impaired nutritional status (malnutrition risk, and sarcopenia) among older patients with OD associated with either chronic or acute conditions is very high. In patients with OD and chronic diseases, poor nutritional status further impairs OD with an increase in oropharyngeal residue at spoon-thick viscosity. In the acute setting there is inflammation and an additional protein deficiency. These findings will help develop specific products both for OD and nutritional status in each specific clinical situation. Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights

  2. Are clinical decisions in endodontics influenced by the patient's fee-paying status?

    PubMed

    Walker, I; Gilbert, D; Asimakopoulou, K

    2015-12-01

    We explored whether the fee status of a UK patient influences clinical decision-making in endodontics. In a randomised-controlled vignette study describing either an 'NHS-funded', 'Privately-funded' or undisclosed fee-status patient, we examined the importance vocational trainer dentists placed on a series of factors normally considered when deciding whether to offer patients endodontic treatment as opposed to extracting the tooth. N = 119 experienced (M years post qualification = 20.01) dentists participated. Having read a vignette describing a hypothetical patient who could potentially be treated either endodontically or through an extraction, dentists rated a series of factors they would normally consider (for example, poor oral hygiene, the rest of their mouth is unfilled and caries-free), before recommending either endodontic treatment or an extraction. The patient's funding status had no influence on these dentists' clinical decision-making when considering endodontic treatment as an option (p >0.05) with the exception of a single item relating to infrequent attendance where the NHS patient was more likely than the 'undisclosed-fee' patient, to be offered extractions (F (2, 116) 3.43, p <0.04). We have found no strong evidence to suggest that the fee-status of a patient influences clinical decision-making in endodontic treatment by experienced dentists.

  3. The influence of individual socioeconomic status on the clinical outcomes in ischemic stroke patients with different neighborhood status in Shanghai, China.

    PubMed

    Yan, Han; Liu, Baoxin; Meng, Guilin; Shang, Bo; Jie, Qiqiang; Wei, Yidong; Liu, Xueyuan

    2017-01-01

    Objective: Socioeconomic status (SES) is being recognized as an important factor in both social and medical problems. The aim of present study is to examine the relationship between SES and ischemic stroke and investigate whether SES is a predictor of clinical outcomes among patients with different neighborhood status from Shanghai, China. Methods: A total of 471 first-ever ischemic stroke patients aged 18-80 years were enrolled in this retrospective study. The personal SES of each patient was evaluated using a summed score derived from his or her educational level, household income, occupation, and medical reimbursement rate. Clinical adverse events and all-cause mortality were analyzed to determine whether SES was a prognostic factor, its prognostic impact was then assessed based on different neighborhood status using multivariable Cox proportional hazard models after adjusting for other covariates. Results: The individual SES showed a significant positive correlation with neighborhood status (r = 0.370; P < 0.001). The incidence of clinical adverse events and mortality were significantly higher in low SES patients compared with middle and high SES patients (P = 0.001 and P = 0.037, respectively). After adjusting other risk factors and neighborhood status, Kaplan-Meier analysis showed clinical adverse events and deaths were still higher in the low SES patients (all P < 0.05). Multivariate Cox regression analysis demonstrated that both personal SES and neighborhood status are independent prognostic factors for ischemic stroke (all P < 0.05). Besides, among patients with low and middle neighborhood status, lower individual SES was significantly associated with clinical adverse events and mortality (all P < 0.05). Conclusion: Both individual SES and neighborhood status are significantly associated with the prognosis after ischemic stroke. A lower personal SES as well as poorer neighborhood status may significantly increase risk for adverse clinical outcomes among

  4. The influence of individual socioeconomic status on the clinical outcomes in ischemic stroke patients with different neighborhood status in Shanghai, China

    PubMed Central

    Yan, Han; Liu, Baoxin; Meng, Guilin; Shang, Bo; Jie, Qiqiang; Wei, Yidong; Liu, Xueyuan

    2017-01-01

    Objective: Socioeconomic status (SES) is being recognized as an important factor in both social and medical problems. The aim of present study is to examine the relationship between SES and ischemic stroke and investigate whether SES is a predictor of clinical outcomes among patients with different neighborhood status from Shanghai, China. Methods: A total of 471 first-ever ischemic stroke patients aged 18-80 years were enrolled in this retrospective study. The personal SES of each patient was evaluated using a summed score derived from his or her educational level, household income, occupation, and medical reimbursement rate. Clinical adverse events and all-cause mortality were analyzed to determine whether SES was a prognostic factor, its prognostic impact was then assessed based on different neighborhood status using multivariable Cox proportional hazard models after adjusting for other covariates. Results: The individual SES showed a significant positive correlation with neighborhood status (r = 0.370; P < 0.001). The incidence of clinical adverse events and mortality were significantly higher in low SES patients compared with middle and high SES patients (P = 0.001 and P = 0.037, respectively). After adjusting other risk factors and neighborhood status, Kaplan-Meier analysis showed clinical adverse events and deaths were still higher in the low SES patients (all P < 0.05). Multivariate Cox regression analysis demonstrated that both personal SES and neighborhood status are independent prognostic factors for ischemic stroke (all P < 0.05). Besides, among patients with low and middle neighborhood status, lower individual SES was significantly associated with clinical adverse events and mortality (all P < 0.05). Conclusion: Both individual SES and neighborhood status are significantly associated with the prognosis after ischemic stroke. A lower personal SES as well as poorer neighborhood status may significantly increase risk for adverse clinical outcomes among

  5. Current Status of Electronic Medical Record Systems in Hospitals and Clinics in Korea.

    PubMed

    Park, Young-Taek; Han, Dongwoon

    2017-07-01

    Many healthcare organizations and professionals have had interests in healthcare information and communication technology (ICT). The objective of this study was to investigate the current status of overall healthcare ICT, especially focusing on Electronic Medical Record (EMR) systems in Korea. This study used a part of the nationwide survey collected for the OECD benchmarking ICT study. The Health Insurance Review and Assessment Service conducted the survey from November 19, 2013 to January 10, 2014. This study followed the methodological guidelines of the OECD. A total of 2,093 hospitals and clinics, including long-term care hospitals, participated in the survey. Among them, 554 hospitals and 906 clinics were included in this study for the generalization of the results. The adoption rates of EMR systems were 96.3% in hospitals and 95.7% in clinics. Most of the hospitals and clinics had high rates of healthcare information exchange (HIE) within the organization; however, there were extremely low HIE rates among external organizations. Most of the hospitals and clinics had EMR systems with clinical-decision-supporting functionalities. Ninety-six percent of the EMR systems of the hospitals and 89.2% of the clinic systems had checking functions, such as alerts or reminders, on contraindications of drug-drug and drug-age interaction. Korea has maintained a high healthcare ICT status compared to countries in the European Union. The EMR systems of hospitals and clinics in Korea had sophisticated functionalities; however, their HIE status was extremely low, which indicates the need for healthcare ICT standardization.

  6. Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya.

    PubMed

    Chung, Michael H; Beck, Ingrid A; Dross, Sandra; Tapia, Kenneth; Kiarie, James N; Richardson, Barbra A; Overbaugh, Julie; Sakr, Samah R; John-Stewart, Grace C; Frenkel, Lisa M

    2014-11-01

    Transmitted drug resistance (TDR) is increasing in some areas of Africa. Detection of TDR may predict virologic failure of first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART). We evaluated the utility of a relatively inexpensive oligonucleotide ligation assay (OLA) to detect clinically relevant TDR at the time of ART initiation. Pre-ART plasmas from ART-naive Kenyans initiating an NNRTI-based fixed-dose combination ART in a randomized adherence trial conducted in 2006 were retrospectively analyzed by OLA for mutations conferring resistance to NNRTI (K103N, Y181C, and G190A) and lamivudine (M184V). Post-ART plasmas were analyzed for virologic failure (≥1000 copies/mL) at 6-month intervals over 18-month follow-up. Pre-ART plasmas of those with virologic failure were evaluated for drug resistance by consensus and 454-pyrosequencing. Among 386 participants, TDR was detected by OLA in 3.89% (95% confidence interval: 2.19 to 6.33) and was associated with a 10-fold higher rate of virologic failure (hazard ratio: 10.39; 95% confidence interval: 3.23 to 32.41; P < 0.001) compared with those without TDR. OLA detected 24 TDR mutations (K103N: n = 13; Y181C: n = 5; G190A: n = 3; M184V: n = 3) in 15 subjects (NNRTI: n = 15; 3TC: n = 3). Among 51 participants who developed virologic failure, consensus sequencing did not detect additional TDR mutations conferring high-level resistance, and pyrosequencing only detected additional mutations at frequencies <2%. Mutant frequencies <2% at ART initiation were significantly less likely to be found at the time of virologic failure compared with frequencies ≥2% (22% vs. 63%; P < 0.001). Detection of TDR by a point mutation assay may prevent the use of suboptimal ART.

  7. Oligonucleotide Ligation Assay Detects HIV Drug Resistance Associated with Virologic Failure among Antiretroviral-Naïve Adults in Kenya

    PubMed Central

    Chung, Michael H.; Beck, Ingrid A.; Dross, Sandra; Tapia, Kenneth; Kiarie, James N.; Richardson, Barbra A.; Overbaugh, Julie; Sakr, Samah R.; John-Stewart, Grace C.; Frenkel, Lisa M.

    2014-01-01

    Background Transmitted drug resistance (TDR) is increasing in some areas of Africa. Detection of TDR may predict virologic failure of first-line non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART). We evaluated the utility of a relatively inexpensive oligonucleotide ligation assay (OLA) to detect clinically relevant TDR at time of ART initiation. Methods Pre-ART plasmas from ART-naive Kenyans initiating an NNRTI-based fixed-dose combination ART in a randomized adherence trial conducted in 2006 were retrospectively analyzed by OLA for mutations conferring resistance to NNRTI (K103N, Y181C, and G190A) and lamivudine (M184V). Post-ART plasmas were analyzed for virologic failure (≥1,000 copies/mL) at 6 month intervals over 18-month follow-up. Pre-ART plasmas of those with virologic failure were evaluated for drug resistance by consensus and 454-pyrosequencing. Results Among 386 participants, TDR was detected by OLA in 3.89% [95% Confidence Interval (CI), 2.19-6.33], and was associated with a 10-fold higher rate of virologic failure [Hazard Ratio (HR), 10.39; 95% CI, 3.23-32.41; p<0.001) compared to those without TDR. OLA detected 24 TDR mutations (K103N, n=13; Y181C, n=5; G190A, n=3; M184V, n=3) in 15 subjects (NNRTI, n=15; 3TC, n=3). Among 51 participants who developed virologic failure, consensus sequencing did not detect additional TDR mutations conferring high-level resistance, and pyrosequencing only detected additional mutations at frequencies <2%. Mutant frequencies <2% at ART initiation were significantly less likely to be found at the time of virologic failure compared to frequencies ≥2% (22% vs. 63%; p<0.001). Conclusions Detection of TDR by a point mutation assay may prevent use of sub-optimal ART. PMID:25140907

  8. 1st Workshop of the Canadian Society for Virology

    PubMed Central

    McCormick, Craig; Grandvaux, Nathalie

    2017-01-01

    The 1st Workshop of the Canadian Society for Virology (CSV2016) was a Special Workshop of the 35th Annual Meeting for the American Society for Virology, held on 18 June 2016 on the beautiful Virginia Tech campus in Blacksburg, Virginia. The workshop provided a forum for discussion of recent advances in the field, in an informal setting conducive to interaction with colleagues. CSV2016 featured two internationally-renowned Canadian keynote speakers who discussed translational virology research; American Society for Virology President Grant McFadden (then from University of Florida, now relocated to Arizona State University) who presented his studies of oncolytic poxviruses, while Matthew Miller (McMaster University) reviewed the prospects for a universal influenza vaccine. The workshop also featured a variety of trainee oral and poster presentations, and a panel discussion on the topic of the future of the CSV and virus research in Canada. PMID:28335511

  9. 1st Workshop of the Canadian Society for Virology.

    PubMed

    McCormick, Craig; Grandvaux, Nathalie

    2017-03-20

    The 1st Workshop of the Canadian Society for Virology (CSV2016) was a Special Workshop of the 35th Annual Meeting for the American Society for Virology, held on 18 June 2016 on the beautiful Virginia Tech campus in Blacksburg, Virginia. The workshop provided a forum for discussion of recent advances in the field, in an informal setting conducive to interaction with colleagues. CSV2016 featured two internationally-renowned Canadian keynote speakers who discussed translational virology research; American Society for Virology President Grant McFadden (then from University of Florida, now relocated to Arizona State University) who presented his studies of oncolytic poxviruses, while Matthew Miller (McMaster University) reviewed the prospects for a universal influenza vaccine. The workshop also featured a variety of trainee oral and poster presentations, and a panel discussion on the topic of the future of the CSV and virus research in Canada.

  10. [Comments on influence of different functional status of the body on clinical effects of acupuncture therapy].

    PubMed

    Li, Zheng-Jie; Zeng, Fang; Yang, Jie; Ren, Yu-Lan; Liang, Fan-Rang

    2013-10-01

    Functional status is an important factor affecting clinical therapeutic effect of acupuncture therapy. Authors of the present article make an analysis on the related descriptions of ancient classical books about the patient's body constitution, age, duration of disease, type of disease or clinical conditions, psychological state, etc. which determine the functional state of patients. Moreover, the authors also make some comments on the results of modern clinical trials and experimental studies. However, till now, the results of many related modern studies were lower in reliability due to unreliable methodology. Fewer clinical trials involve the patient's psychological state, and constitution from the viewpoint of Chinese medicine. Correspondingly, the related experimental studies are fewer. The authors suggest that in the coming days clinical trials should be greatly improved in quality and the mutual interference among the influential factors should be excluded. At the same time, experimental studies on the related biochemical mechanisms should be strengthened.

  11. The role, responsibilities and status of the clinical medical physicist in AFOMP.

    PubMed

    Ng, K H; Cheung, K Y; Hu, Y M; Inamura, K; Kim, H J; Krisanachinda, A; Leung, J; Pradhan, A S; Round, H; van Doomo, T; Wong, T J; Yi, B Y

    2009-12-01

    This document is the first of a series of policy statements being issued by the Asia-Oceania Federation of Organizations for Medical Physics (AFOMP). The document was developed by the AFOMP Professional Development Committee (PDC) and was endorsed for official release by AFOMP Council in 2006. The main purpose of the document was to give guidance to AFOMP member organizations on the role and responsibilities of clinical medical physicists. A definition of clinical medical physicist has also been provided. This document discusses the following topics: professional aspects of education and training; responsibilities of the clinical medical physicist; status and organization of the clinical medical physics service and the need for clinical medical physics service.

  12. Adherence to Drug-Refill Is a Useful Early Warning Indicator of Virologic and Immunologic Failure among HIV Patients on First-Line ART in South Africa

    PubMed Central

    El-Khatib, Ziad; Katzenstein, David; Marrone, Gaetano; Laher, Fatima; Mohapi, Lerato; Petzold, Max; Morris, Lynn; Ekström, Anna Mia

    2011-01-01

    Background Affordable strategies to prevent treatment failure on first-line regimens among HIV patients are essential for the long-term success of antiretroviral therapy (ART) in sub-Saharan Africa. WHO recommends using routinely collected data such as adherence to drug-refill visits as early warning indicators. We examined the association between adherence to drug-refill visits and long-term virologic and immunologic failure among non-nucleoside reverse transcriptase inhibitor (NNRTI) recipients in South Africa. Methods In 2008, 456 patients on NNRTI-based ART for a median of 44 months (range 12–99 months; 1,510 person-years) were enrolled in a retrospective cohort study in Soweto. Charts were reviewed for clinical characteristics before and during ART. Multivariable logistic regression and Kaplan-Meier survival analysis assessed associations with virologic (two repeated VL>50 copies/ml) and immunologic failure (as defined by WHO). Results After a median of 15 months on ART, 19% (n = 88) and 19% (n = 87) had failed virologically and immunologically respectively. A cumulative adherence of <95% to drug-refill visits was significantly associated with both virologic and immunologic failure (p<0.01). In the final multivariable model, risk factors for virologic failure were incomplete adherence (OR 2.8, 95%CI 1.2–6.7), and previous exposure to single-dose nevirapine or any other antiretrovirals (adj. OR 2.1, 95%CI 1.2–3.9), adjusted for age and sex. In Kaplan-Meier analysis, the virologic failure rate by month 48 was 19% vs. 37% among adherent and non-adherent patients respectively (logrank p value = 0.02). Conclusion One in five failed virologically after a median of 15 months on ART. Adherence to drug-refill visits works as an early warning indicator for both virologic and immunologic failure. PMID:21408071

  13. Nationwide survey for current clinical status of amniocentesis and maternal serum marker test in Japan.

    PubMed

    Miyake, Hidehiko; Yamada, Shigehito; Fujii, Yosuke; Sawai, Hideaki; Arimori, Naoko; Yamanouchi, Yasuko; Ozasa, Yuka; Kanai, Makoto; Sago, Haruhiko; Sekizawa, Akihiko; Takada, Fumio; Masuzaki, Hideaki; Matsubara, Yoichi; Hirahara, Fumiki; Kugu, Koji

    2016-10-01

    Prenatal testing has been provided in Japan over the past several decades. However, it is difficult to assess the clinical status of amniocentesis (AC) and maternal serum markers (MSM) because obstetricians can perform these tests without registration. This study aims to investigate the current clinical status of AC and MSM in Japan. We conducted a questionnaire study that was intended for a total of 5622 Japanese obstetrics/gynecology facilities during October 2013 to January 2014. The response rate was 40.8% (2295/5622). Of the 2295 facilities, 864 performed MSM (37.7%), 619 performed AC (27.0%) and 412 performed both (18.0%). The average number of MSM tests was 2.0 per month (range 0-52), and the average number of AC tests was 2.4 per month (range 0-30). Involvement of genetic professionals, such as clinical geneticists (CGs) and certified genetic counselors (CGCs), contribute to a content-rich explanation and management of difficult issues and lengthened the explanation time. Nevertheless, relatively few facilities employed these specialists (MSM: 96/864 and AC: 128/619). This is the first study to highlight the current clinical status of AC and MSM tests in Japan. Active involvement of CGs and CGCs can provide more appropriate genetic counseling for prenatal tests.

  14. The impact of educational status on the clinical features of major depressive disorder among Chinese women.

    PubMed

    Gan, Zhaoyu; Li, Yihan; Xie, Dong; Shao, Chunhong; Yang, Fuzhong; Shen, Yuan; Zhang, Ning; Zhang, Guanghua; Tian, Tian; Yin, Aihua; Chen, Ce; Liu, Jun; Tang, Chunling; Zhang, Zhuoqiu; Liu, Jia; Sang, Wenhua; Wang, Xumei; Liu, Tiebang; Wei, Qinling; Xu, Yong; Sun, Ling; Wang, Sisi; Li, Chang; Hu, Chunmei; Cui, Yanping; Liu, Ying; Li, Ying; Zhao, Xiaochuan; Zhang, Lan; Sun, Lixin; Chen, Yunchun; Zhang, Yueying; Ning, Yuping; Shi, Shenxun; Chen, Yiping; Kendler, Kenneth S; Flint, Jonathan; Zhang, Jinbei

    2012-02-01

    Years of education are inversely related to the prevalence of major depressive disorder (MDD), but the relationship between the clinical features of MDD and educational status is poorly understood. We investigated this in 1970 Chinese women with recurrent MDD identified in a clinical setting. Clinical and demographic features were obtained from 1970 Han Chinese women with DSM-IV major depression between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models were used to determine the association between educational level and clinical features of MDD. Subjects with more years of education are more likely to have MDD, with an odds ratio of 1.14 for those with more than ten years. Low educational status is not associated with an increase in the number of episodes, nor with increased rates of co-morbidity with anxiety disorders. Education impacts differentially on the symptoms of depression: lower educational attainment is associated with more biological symptoms and increased suicidal ideation and plans to commit suicide. Findings may not generalize to males or to other patient populations. Since the threshold for treatment seeking differs as a function of education there may an ascertainment bias in the sample. The relationship between symptoms of MDD and educational status in Chinese women is unexpectedly complex. Our findings are inconsistent with the simple hypothesis from European and US reports that low levels of educational attainment increase the risk and severity of MDD. Copyright © 2011 Elsevier B.V. All rights reserved.

  15. The impact of educational status on the clinical features of major depressive disorder among Chinese women

    PubMed Central

    Gan, Zhaoyu; Li, Yihan; Xie, Dong; Shao, Chunhong; Yang, Fuzhong; Shen, Yuan; Zhang, Ning; Zhang, Guanghua; Tian, Tian; Yin, Aihua; Chen, Ce; Liu, Jun; Tang, Chunling; Zhang, Zhuoqiu; Liu, Jia; Sang, Wenhua; Wang, Xumei; Liu, Tiebang; Wei, Qinling; Xu, Yong; Sun, Ling; Wang, Sisi; Li, Chang; Hu, Chunmei; Cui, Yanping; Liu, Ying; Li, Ying; Zhao, Xiaochuan; Zhang, Lan; Sun, Lixin; Chen, Yunchun; Zhang, Yueying; Ning, Yuping; Shi, Shenxun; Chen, Yiping; Kendler, Kenneth S.; Flint, Jonathan; Zhang, Jinbei

    2012-01-01

    Background Years of education are inversely related to the prevalence of major depressive disorder (MDD), but the relationship between the clinical features of MDD and educational status is poorly understood. We investigated this in 1970 Chinese women with recurrent MDD identified in a clinical setting. Methods Clinical and demographic features were obtained from 1970 Han Chinese women with DSM-IV major depression between 30 and 60 years of age across China. Analysis of linear, logistic and multiple logistic regression models were used to determine the association between educational level and clinical features of MDD. Results Subjects with more years of education are more likely to have MDD, with an odds ratio of 1.14 for those with more than ten years. Low educational status is not associated with an increase in the number of episodes, nor with increased rates of co-morbidity with anxiety disorders. Education impacts differentially on the symptoms of depression: lower educational attainment is associated with more biological symptoms and increased suicidal ideation and plans to commit suicide. Limitations Findings may not generalize to males or to other patient populations. Since the threshold for treatment seeking differs as a function of education there may an ascertainment bias in the sample. Conclusions The relationship between symptoms of MDD and educational status in Chinese women is unexpectedly complex. Our findings are inconsistent with the simple hypothesis from European and US reports that low levels of educational attainment increase the risk and severity of MDD. PMID:21824664

  16. An overview of the current status of clinical trials on endometriosis: issues and concerns.

    PubMed

    Guo, Sun-Wei

    2014-01-01

    To examine and compare differences, if any, between industry- and nonindustry-sponsored clinical trials on endometriosis and to evaluate the effect of prior published positive preclinical results, or lack thereof, on trial status. Cross-sectional study of clinical trials on endometriosis that evaluate drugs/biologicals registered at ClinicalTrials.gov as of July 3, 2013. University-affiliated hospital. None. None. Trial status, size, phase, and duration; use of comparator groups; drug classes, number of arms, targeting conditions; and presence or absence of prior positive preclinical results before the launch of the trial. Eighty trials were identified. The trials sponsored by industry and non-industry have distinct features, differing in trial status, phase, comparator, drug classes, number of arms, trial size, and duration. The phase II/III trials are predominantly industry supported, but these trials frequently use placebo as the comparator. Trials launched without prior published preclinical results do not seem to fare well, although the presence of such studies is no guarantee for success. Questions as to whether the drug on trial is truly superior to the best available drug or of its cost-benefit profile are overlooked in most cases. There seems to be a deluge of "me-too" drugs with equivocal superiority over existing drugs and cost-benefit profiles. Because clinical trials are time-consuming, no blockbuster drug for endometriosis seems to be on the horizon yet. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  17. Defining the clinical outcome status (COS) in sarcoidosis: results of WASOG Task Force.

    PubMed

    Baughman, R P; Nagai, S; Balter, M; Costabel, U; Drent, M; du Bois, R; Grutters, J C; Judson, M A; Lambiri, I; Lower, E E; Muller-Quernheim, J; Prasse, A; Rizzato, G; Rottoli, P; Spagnolo, P; Teirstein, A

    2011-07-01

    The clinical outcome of sarcoidosis is quite variable. Several scoring systems have been used to assess the level of disease and clinical outcome. The definition of clinical phenotypes has become an important goal as genetic studies have identified distinct genotypes associated with different clinical phenotypes. In addition, treatment strategies have been developed for patients with resolving versus non resolving disease. A task force was established by the World Association of Sarcoidosis and Other Granulomatous diseases (WASOG) to define clinical phenotypes of the disease based on the clinical outcome status (COS). The committee chose to examine patients five years after diagnosis to determine the COS. Several features of the disease were incorporated into the final nine categories of the disease. These included the current or past need for systemic therapy, the resolution of the disease, and current status of the condition. Sarcoidosis patients who were African American or older were likely to have a higher COS, indicating more chronic disease. The COS may be useful in future studies of sarcoidosis.

  18. Virological diagnosis of African swine fever--comparative study of available tests.

    PubMed

    Oura, C A L; Edwards, L; Batten, C A

    2013-04-01

    The rapid and reliable detection of African swine fever virus (ASFV) is essential both for timely implementation of control measures to prevent the spread of disease, and to differentiate African swine fever (ASF) from other pig disease with similar clinical presentations. Many virological tests are currently available for the detection of ASFV (live virus), antigen and genome, including virus isolation, ELISA, fluorescent antibody, polymerase chain reaction (PCR) and isothermal assays. In recent years real-time PCR (rPCR) has become one of the most widely used formats for virological diagnosis providing sensitive, specific and swift detection and quantification of ASFV DNA. The ability to integrate rPCR into automated platforms increases sample throughput and decreases the potential for cross-contamination. In more recent years isothermal assays, which are a lower-cost alternative to PCR more suitable for use in non-specialised or mobile laboratories, have been developed for the detection of ASFV, however these assays have not been fully validated for routine use in the field. The performance of all virological detection assays in ASF diagnostics, as well as prospects for improving diagnostic strategies in the future, are discussed and reviewed in this chapter.

  19. [Virological diagnosis and follow-up of HIV infection. State of the art and situation in Tunisia].

    PubMed

    Ben Mamou, Myriam; Slim, Amine; Garbouj, Mounira; Ben Redjeb, Saida

    2006-07-01

    Human immunodeficiency virus (HIV) is a retrovirus infecting approximatively 40 million people worldwide. HIV is characterized by a great variability with epidemiological, diagnostic and therapeutic implications. The course of infection goes through three stages (acute infection, clinical latency and AIDS) with the evolution of virological markers (anti-HIV antibodies, p24 antigenemia, plasma RNA and proviral DNA). Direct virological diagnosis is mainly based on molecular tools allowing viral genome detection and amplification with specific primers and nucleic probes besides p24 antigenemia detection, and more rarely viral culture. Antigenic properties of viral proteins elicit in infected patients antibody synthesis, which is detected using serology (ELISA and Western blot tests). The follow-up of infected patients is carried out with plasma HIV-1 RNA quantitation and phenotypic or genotypic characterization of variant isolates. Virological tests are prescribed according to clinical presentation (screening, acute infection, newborn from HIV-infected mother). Most of these virological tools are available in Tunisia, allowing both diagnosis of HIV infection and monitoring of infected individuals. Regarding diagnostic tests indication and interpretation, multidisciplinary concertation is hopeful in order to optimize patient management.

  20. Clinical Variables Associated with Hydration Status in Acute Ischemic Stroke Patients with Dysphagia.

    PubMed

    Crary, Michael A; Carnaby, Giselle D; Shabbir, Yasmeen; Miller, Leslie; Silliman, Scott

    2016-02-01

    Acute stroke patients with dysphagia are at increased risk for poor hydration. Dysphagia management practices may directly impact hydration status. This study examined clinical factors that might impact hydration status in acute ischemic stroke patients with dysphagia. A retrospective chart review was completed on 67 ischemic stroke patients who participated in a prior study of nutrition and hydration status during acute care. Prior results indicated that patients with dysphagia demonstrated elevated BUN/Cr compared to non-dysphagia cases during acute care and that BUN/Cr increased selectively in dysphagic patients. This chart review evaluated clinical variables potentially impacting hydration status: diuretics, parenteral fluids, tube feeding, oral diet, and nonoral (NPO) status. Exposure to any variable and number of days of exposure to each variable were examined. Dysphagia cases demonstrated significantly more NPO days, tube fed days, and parenteral fluid days, but not oral fed days, or days on diuretics. BUN/Cr values at discharge were not associated with NPO days, parenteral fluid days, oral fed days, or days on diuretics. Patients on modified solid diets had significantly higher mean BUN/Cr values at discharge (27.12 vs. 17.23) as did tube fed patients (28.94 vs. 18.66). No difference was noted between these subgroups at baseline (regular diet vs. modified solids diets). Any modification of solid diets (31.11 vs. 17.23) or thickened liquids (28.50 vs. 17.81) resulted in significantly elevated BUN/Cr values at discharge. Liquid or diet modifications prescribed for acute stroke patients with dysphagia may impair hydration status in these patients.

  1. The clinical impact of HPV tumor status upon head and neck squamous cell carcinomas

    PubMed Central

    Benson, Eleni; Li, Ryan; Eisele, David; Fakhry, Carole

    2015-01-01

    SUMMARY Human papillomavirus (HPV) is etiologically responsible for a distinct subset of head and neck squamous cell cancers (HNSCCs). HPV-positive HNSCCs (HPV-HNSCCs) most commonly arise from the oropharynx and are responsible for the increasing incidence of oropharyngeal SCC (OSCC) in the United States (US) and abroad. HPV-positive OSCC (HPV-OSCC) has a unique demographic and risk factor profile and tumor biology. HPV-OSCC patients tend to be white, younger, and have a higher cumulative exposure to sexual behaviors as compared with HPV-negative OSCC patients. HPV-positive tumor status also significantly improves survival, and is indeed the single strongest prognostic factor for OSCC. The mechanisms that underlie the improved prognosis conferred by HPV-positive disease are unknown. The purpose of this review is to describe the clinical impact of HPV status in HNSCC, particularly in OSCC, both in terms of the unique clinic-demographic profile and prognostic implications. PMID:24134947

  2. Functional health status of persons with diabetes in a nurse-managed clinic.

    PubMed

    Hartley, Lou Ann

    2002-01-01

    The purpose of this psychometric analysis was to (1) describe the functional health status of medically underserved persons with diabetes participating in an exercise program; (2) examine the relationships between functional health status scores and physiologic measures for blood pressure, heart rate, and blood glucose levels; and (3) examine the reliability and validity of the Medical Outcomes Study SF-36 survey. Data were collected from 31 men and women receiving diabetes disease management in a community-based nurse-managed clinic. The SF-36 survey was used to measure functional health status. Blood pressure, heart rate, and blood glucose also were measured (pretest/posttest). The SF-36 survey had good internal consistency in the total sample. Blood pressure and blood glucose levels decreased significantly and heart rate increased significantly from pretest to posttest. Functional health status was negatively associated with physiological parameters. Further research is needed on the use of the SF-36 survey in medically underserved persons with diabetes because this instrument lacked construct validity as a measure of functional health status in this population.

  3. EBV infection and MSI status significantly influence the clinical outcomes of gastric cancer patients.

    PubMed

    Shen, Hua; Zhong, Meizuo; Wang, Weili; Liao, Ping; Yin, Xianli; Rotroff, Daniel; Knepper, Todd C; Mcleod, Howard L; Zhou, Chengfang; Xie, Shangchen; Li, Wei; Xu, Biaobo; He, Yijing

    2017-08-01

    Epstein-Barr virus (EBV) and microsatellite instability (MSI) are associated with the carcinogenesis of many kinds of tumors, including gastric cancer (GC). However, the impact of EBV and MSI status on the prognosis of stage II and III GC is still unclear. The aim of this study was to find out the prognostic value of EBV and MSI status in a population of GC patients from Southern China. Patients were genotyped for EBV infection based on the detection of EBV DNA from the formalin-fixed paraffin-embedded (FFPE) specimens. Sequentially, MSI status was measured by direct sequencing. Clinical characteristics and overall survival (OS) were analyzed in 202 GC patients. Additionally, the association of EBV and MSI status with chemotherapy-based toxicity was analyzed in 324 GC patients. The survival analysis revealed EBV+ patients had a poorer OS than EBV- patients (HR=1.75, 95% CI: 1.08-2.82, FDR p=0.04). This survival advantage for EBV- patients was also found in patients <60y (FDR p=0.04) and patient with stage III disease (FDR p=0.04). EBV infection and MSI status are associated with overall survival of gastric cancer patients. However, traditional chemotherapy showed no difference on outcome of patients in EBV and MSI subgroups. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. New-onset refractory status epilepticus: Etiology, clinical features, and outcome.

    PubMed

    Gaspard, Nicolas; Foreman, Brandon P; Alvarez, Vincent; Cabrera Kang, Christian; Probasco, John C; Jongeling, Amy C; Meyers, Emma; Espinera, Alyssa; Haas, Kevin F; Schmitt, Sarah E; Gerard, Elizabeth E; Gofton, Teneille; Kaplan, Peter W; Lee, Jong W; Legros, Benjamin; Szaflarski, Jerzy P; Westover, Brandon M; LaRoche, Suzette M; Hirsch, Lawrence J

    2015-11-03

    The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus. Retrospective review of patients with refractory status epilepticus without etiology identified within 48 hours of admission between January 1, 2008, and December 31, 2013, in 13 academic medical centers. The primary outcome measure was poor functional outcome at discharge (defined as a score >3 on the modified Rankin Scale). Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies were autoimmune (19%) and paraneoplastic (18%) encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor outcome included duration of status epilepticus, use of anesthetics, and medical complications. Among the 63 patients with available follow-up data (median 9 months), functional status improved in 36 (57%); 79% had good or fair outcome at last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medications. Immune therapies were used less frequently in cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes. Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation. © 2015 American Academy of Neurology.

  5. [Epilepsies with electric status epilepticus in sleep: peculiarities of clinical course and rational approaches to treatment].

    PubMed

    Ermolenko, N A; Ermakov, A Iu; Buchneva, I A; Zakharova, E I; Kalikina, T A

    2011-01-01

    We studied 52 patients with electric status epilepticus in slow sleep (EESSS) during 3-5 years. Age-dependent peculiarities of clinical course of the disease, risk factors for EESSS and rational approaches to antiepileptic treatment for these cases were singled out. Symptomatic and idiopathic EESSS variants were revealed. Combinations of valproates, levetiracetam and ethosuximidum were the most effective antiepileptic drugs in the treatment of EESSS.

  6. [Linking Nef with the immunological and virological determinants of AIDS].

    PubMed

    Gómez-Icazbalceta, Guillermo; Larralde, Carlos

    2009-01-01

    Nef is an accessory protein from HIV-1 involved in viral replication, depletion of CD4 + T cells and progression to AIDS. The participation of Nef in altering several of the cellular and subcellular components has been studied in detail. The finding that infected patients over 15 years with HIV-1 variants that expressed a defective nef gene had not progressed to AIDS, suggested that Nef played a decisive role in the outcome of AIDS, through the regulation of different virological and immunological components. In addition, the mere expression of Nef is able to induce AIDS in transgenic mice and alter the kinetics of replication of the virus in infected monkeys. This review examines the relationship between the expression of Nef and the ultimate consequences of HIV-1 infection, taking into account the most relevant clinical parameters: viral load, counting of CD4 + T cells and progression to AIDS. Under this approach, it is emphasized the role of Nef as immunomodulator and also as independent mediator of damage to the immune system.

  7. Hepatitis C virus and atherosclerosis: A legacy after virologic cure?

    PubMed

    Bassendine, M F; Nielsen, S U; Bridge, S H; Felmlee, D J; Sheridan, D A; Packard, C J; Neely, R D

    2017-02-01

    Hepatitis C virus (HCV) is a major pathogen with approximately 3% of the world's population (over 170 million) infected. Epidemiological studies have shown HCV is associated with an increased risk of cardiovascular and cerebrovascular mortality as well as peripheral arterial disease. This is despite HCV inducing an ostensibly favourable lipid profile with accompanying low classical risk score for atherosclerosis (AS). We discuss possible factors involved in the aetiopathogenesis of atherosclerosis in chronic HCV and hypothesise that an important mechanism underlying the development of AS is the presence of circulating low-density immune complexes that induce an inflammatory response. We suggest that HCV particles may be inducing an antibody response to lipoproteins present in the lipoviral particles and sub-viral particles - a concept similar to the more general 'autoantibody' response to modified LDL. After virologic cure some AS risk factors will recede but an increase in serum cholesterol could result in progression of early atherosclerotic lesions, leaving a legacy from persistent HCV infection that has clinical and therapeutic implications. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  8. [The history and current status of clinical applications of stem cells].

    PubMed

    Yamato, Masayuki; Okano, Teruo

    2011-12-01

    Here, we summarize the history and current status of clinical applications of stem cells for regenerative medicine. Cultured autologous epidermal cells were successfully applied to treat human severe burn patients in 1980 for the first time ever. Then, several commercial tissue engineered products including skin and cartilage have been approved by the regulatory agencies, and many clinical trials are ongoing now in Europe and United States. Regenerative medicine achieved by tissue engineering with autologous and allogeneic stem cells including ES and iPS cells are highly promising, and more and more products are expected to come on the market in the near future.

  9. Is zidovudine first-line therapy virologically comparable to tenofovir in resource-limited settings?

    PubMed

    Labhardt, Niklaus D; Bader, Joëlle; Lejone, Thabo Ismael; Ringera, Isaac; Puga, Daniel; Glass, Tracy R; Klimkait, Thomas

    2015-07-01

    To compare virologic success between adult patients on tenofovir (TDF) and zidovudine (AZT)-containing first-line antiretroviral (ART) regimens in 10 rural clinics in Lesotho, Southern Africa. Multicentre cross-sectional study, patients ≥16 years, on first-line ART ≥6 months, receiving AZT/lamivudine (3TC) or TDF/3TC combined with efavirenz (EFV) or nevirapine (NVP). Patient characteristics and clinical/therapeutic history were collected on the day of blood draw for viral load (VL). Analysis was stratified for non-nucleoside reverse transcriptase inhibitor (EFV or NVP). A logistic regression model weighted for patients' baseline characteristics was used to assess the likelihood of virologic success (<80 copies/ml) in patients with TDF- as compared to AZT-backbones. In total 1539 patients were included in the analysis. Most were clinically and immunologically stable (clinical failure: 2.7% (AZT) and 2.8% (TDF); immunological failure: 4.6% (AZT) and 4.8% (TDF)). In EFV-based regimens (n = 1162), TDF was significantly associated with higher rates of virologic suppression than AZT (93.8% vs. 88.1%; weighted odds ratio: 2.15 (95% CI: 1.29-3.58; P = 0.003)). In NVP-based regimens, a similar trend was observed, but not significant (89.4% vs. 86.7%; 1.99 (0.83-4.75, P = 0.121)). These findings support the WHO recommendation to use TDF/3TC/EFV as first-line regimen. They do, however, not support the recommendation that patients who are clinically stable on AZT should continue on this first-line regimen. © 2015 John Wiley & Sons Ltd.

  10. Gastrointestinal stromal tumors: clinical significance of p53 expression, MDM2 amplification, and KIT mutation status.

    PubMed

    Wallander, Michelle L; Layfield, Lester J; Tripp, Sheryl R; Schmidt, Robert L

    2013-07-01

    Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor of the gastrointestinal tract. Clinical behavior is best predicted by size and mitotic count (risk index). KIT and platelet-derived growth factor receptor α (PDGFRA) mutations have therapeutic and prognostic value but few other prognostically significant molecular markers have been identified. We investigated the prognostic value of p53 protein expression and MDM2 gene amplification in a series of GISTs. Thirty-five GISTs were tested for KIT and PDGFRA mutations, p53 protein expression (high >10% positive by immunohistochemistry) and MDM2 gene amplification (ratio >1.8). Mitotic index (>5/50 HPF), MDM2 amplification status, p53 protein expression, tumor size, and KIT/PDGFRA mutational status were correlated with clinical outcome. Only a single (3%) GIST was amplified for MDM2. p53 protein expression, mitotic index, and KIT/PDGFRA mutations did not correlate with recurrence or metastasis (P=0.20, 0.50, and 0.08, respectively) but tumor size did (P=0.04). Risk assessment (size and mitotic index) showed a weak association with clinical behavior (P=0.19). MDM2 amplification is uncommon in GISTs. Although high p53 expression occurred in 35% of cases, it did not correlate with clinical behavior. Only GIST size predicted clinical outcome.

  11. Botswana's progress toward achieving the 2020 UNAIDS 90-90-90 antiretroviral therapy and virological suppression goals: a population-based survey.

    PubMed

    Gaolathe, Tendani; Wirth, Kathleen E; Holme, Molly Pretorius; Makhema, Joseph; Moyo, Sikhulile; Chakalisa, Unoda; Yankinda, Etienne Kadima; Lei, Quanhong; Mmalane, Mompati; Novitsky, Vlad; Okui, Lillian; van Widenfelt, Erik; Powis, Kathleen M; Khan, Nealia; Bennett, Kara; Bussmann, Hermann; Dryden-Peterson, Scott; Lebelonyane, Refeletswe; El-Halabi, Shenaaz; Mills, Lisa A; Marukutira, Tafireyi; Wang, Rui; Tchetgen, Eric J Tchetgen; DeGruttola, Victor; Essex, M; Lockman, Shahin

    2016-05-01

    HIV programmes face challenges achieving high rates of HIV testing and treatment needed to optimise health and to reduce transmission. We used data from the Botswana Combination Prevention Project study survey to assess Botswana's progress toward achieving UNAIDS targets for 2020: 90% of all people living with HIV knowing their status, 90% of these receiving sustained antiretroviral therapy (ART), and 90% of those having virological suppression (90-90-90). A population-based sample of individuals was recruited and interviewed in 30 rural and periurban communities from Oct 30, 2013, to Nov 24, 2015, as part of a large, ongoing community-randomised trial designed to assess the effect of a combination prevention package on HIV incidence. A random sample of about 20% of households in each community was selected. Consenting household residents aged 16-64 years who were Botswana citizens or spouses of citizens responded to a questionnaire and had blood drawn for HIV testing in the absence of documentation of positive HIV status. Viral load testing was done in all HIV-infected participants, irrespective of treatment status. We used modified Poisson generalised estimating equations to obtain prevalence ratios, corresponding Huber robust SEs, and 95% Wald CIs to examine associations between individual sociodemographic factors and a binary outcome indicating achievement of the three individual and combined overall 90-90-90 targets. The study is registered at ClinicalTrials.gov, number NCT01965470. 81% of enumerated eligible household members took part in the survey (10% refused and 9% were absent). Among 12 610 participants surveyed, 3596 (29%) were infected with HIV, and 2995 (83·3%, 95% CI 81·4-85·2) of these individuals already knew their HIV status. Among those who knew their HIV status, 2617 (87·4%, 95% CI 85·8-89·0) were receiving ART (95% of those eligible by national guidelines, and 73% of all infected people). Of the 2609 individuals receiving ART with a

  12. No clear association between ultrasound remission and health status in rheumatoid arthritis patients in clinical remission.

    PubMed

    van der Ven, Myrthe; Kuijper, T Martijn; Gerards, Andreas H; Tchetverikov, Ilja; Weel, Angelique E; van Zeben, Jendé; Hazes, Johanna M; Luime, Jolanda J

    2017-08-01

    Although RA patients achieve clinical remission, risk of flare still exists. Given the association between US synovitis and increased risk of flare, it is of clinical interest whether these patients report a different health status. Therefore, our aim was to evaluate the frequency of US remission in RA patients in clinical remission and to compare the health status of RA patients in clinical remission with those who were also in US remission. In a prospective study, we included 89 RA patients (aged >17 years) treated with a synthetic DMARD and a TNF inhibitor who were in remission (DAS in 44 joints ⩽2.4 and swollen joint count ⩽1). Demographic characteristics, swollen and tender joints, laboratory variables, US (MCP2-5, PIP2-5, wrists and MTP2-5) and patient-reported outcomes (general health, functional ability, fatigue, depression and anxiety, pain and morning stiffness) were recorded at two consecutive visits (3 months apart). US remission was defined as grey scale grade ⩽1 and power Doppler = 0. At visit 1, 39% of patients were in US remission. At visit 2, 32% of patients were in US remission. At visit 1, functional ability (HAQ) was scored lower by patients in US remission (P = 0.029). At visit 2, HAQ scores were similar (P = 0.928). At visit 2, Hospital Anxiety and Depression Scale anxiety score and visual analog scale pain were significantly higher in patients in US remission. Similar levels were found for the other patient-reported outcomes. One-third of RA patients in clinical remission were in US remission. In our study population, we could not find a clear association between health status of RA patients and being in US remission.

  13. Lorazepam vs diazepam for pediatric status epilepticus: a randomized clinical trial.

    PubMed

    Chamberlain, James M; Okada, Pamela; Holsti, Maija; Mahajan, Prashant; Brown, Kathleen M; Vance, Cheryl; Gonzalez, Victor; Lichenstein, Richard; Stanley, Rachel; Brousseau, David C; Grubenhoff, Joseph; Zemek, Roger; Johnson, David W; Clemons, Traci E; Baren, Jill

    Benzodiazepines are considered first-line therapy for pediatric status epilepticus. Some studies suggest that lorazepam may be more effective or safer than diazepam, but lorazepam is not Food and Drug Administration approved for this indication. To test the hypothesis that lorazepam has better efficacy and safety than diazepam for treating pediatric status epilepticus. This double-blind, randomized clinical trial was conducted from March 1, 2008, to March 14, 2012. Patients aged 3 months to younger than 18 years with convulsive status epilepticus presenting to 1 of 11 US academic pediatric emergency departments were eligible. There were 273 patients; 140 randomized to diazepam and 133 to lorazepam. Patients received either 0.2 mg/kg of diazepam or 0.1 mg/kg of lorazepam intravenously, with half this dose repeated at 5 minutes if necessary. If status epilepticus continued at 12 minutes, fosphenytoin was administered. The primary efficacy outcome was cessation of status epilepticus by 10 minutes without recurrence within 30 minutes. The primary safety outcome was the performance of assisted ventilation. Secondary outcomes included rates of seizure recurrence and sedation and times to cessation of status epilepticus and return to baseline mental status. Outcomes were measured 4 hours after study medication administration. Cessation of status epilepticus for 10 minutes without recurrence within 30 minutes occurred in 101 of 140 (72.1%) in the diazepam group and 97 of 133 (72.9%) in the lorazepam group, with an absolute efficacy difference of 0.8% (95% CI, -11.4% to 9.8%). Twenty-six patients in each group required assisted ventilation (16.0% given diazepam and 17.6% given lorazepam; absolute risk difference, 1.6%; 95% CI, -9.9% to 6.8%). There were no statistically significant differences in secondary outcomes except that lorazepam patients were more likely to be sedated (66.9% vs 50%, respectively; absolute risk difference, 16.9%; 95% CI, 6.1% to 27.7%). Among

  14. Clinical and virological evaluation of the efficacy of an inactivated EHV1 and EHV4 whole virus vaccine (Duvaxyn EHV1,4). Vaccination/challenge experiments in foals and pregnant mares.

    PubMed

    Heldens, J G; Hannant, D; Cullinane, A A; Prendergast, M J; Mumford, J A; Nelly, M; Kydd, J H; Weststrate, M W; van den Hoven, R

    2001-07-20

    Pregnant mares and young foals were vaccinated with Duvaxyn EHV1,4, an inactivated and adjuvanted vaccine containing both the EHV-1 and 4 antigens. SN and CF antibody titres were induced two weeks after first vaccination. Antibody levels were boosted after second vaccination, however they never reached the levels induced after virus challenge. Young foals were challenged with virulent EHV-1 and EHV-4 field viruses. Pregnant mares were challenged with the highly abortigenic EHV-1 strain Ab4. Vaccinated animals showed a clear reduction in clinical signs and virus excretion compared to unvaccinated control animals. Log transformed antibody levels could be correlated to duration of virus excretion. The incidence of EHV-1 induced abortions was drastically reduced in vaccinated mares. Therefore, although vaccinated animals are not fully protected against disease, Duvaxyn EHV1,4 clearly reduces clinical symptoms, the duration of virus shedding and the quantity of virus shed. It can be concluded that vaccination of foals and pregnant mares with Duvaxyn EHV1,4 significantly reduces the risk of abortions and outbreaks of respiratory disease caused by circulating field viruses.

  15. Clinical evolution and nutritional status in asthmatic children and adolescents enrolled in Primary Health Care

    PubMed Central

    Morishita, Rosinha Yoko Matsubayaci; Strufaldi, Maria Wany Louzada; Puccini, Rosana Fiorini

    2015-01-01

    Objective: To evaluate the clinical evolution and the association between nutritional status and severity of asthma in children and adolescents enrolled in Primary Health Care. Methods: A retrospective cohort study of 219 asthmatic patients (3-17 years old) enrolled in Primary Care Services (PCSs) in Embu das Artes (SP), from 2007 to 2011. Secondary data: gender, age, diagnosis of asthma severity, other atopic diseases, family history of atopy, and body mass index. To evaluate the clinical outcome of asthma, data were collected on number of asthma exacerbations, number of emergency room consultations and doses of inhaled corticosteroids at follow-up visits in the 6th and 12th months. The statistical analysis included chi-square and Kappa agreement index, with 5% set as the significance level. Results: 50.5% of patients started wheezing before the age of 2 years, 99.5% had allergic rhinitis and 65.2% had a positive family history of atopy. Regarding severity, intermittent asthma was more frequent (51.6%) and, in relation to nutritional status, 65.8% of patients had normal weight. There was no association between nutritional status and asthma severity (p=0.409). After 1 year of follow-up, 25.2% of patients showed reduction in exacerbations and emergency room consultations, and 16.2% reduced the amount of inhaled corticosteroids. Conclusions: The monitoring of asthmatic patients in Primary Care Services showed improvement in clinical outcome, with a decreased number of exacerbations, emergency room consultations and doses of inhaled corticosteroids. No association between nutritional status and asthma severity was observed in this study. PMID:26316387

  16. Craniopharyngioma Clinical Status Scale: a standardized metric of preoperative function and posttreatment outcome.

    PubMed

    Elliott, Robert E; Sands, Stephen A; Strom, Russell G; Wisoff, Jeffrey H

    2010-04-01

    Controversy persists concerning the optimal treatment of craniopharyngiomas in children, and no standard outcome metric exists for comparison across treatment modalities, nor is there one that adequately reflects the multisystem dysfunction that may arise. The authors retrospectively analyzed the records of 86 consecutive children who underwent a uniform treatment paradigm of attempted radical resection performed by a single surgeon. Excluding 3 perioperative deaths and 3 patients with inadequate follow-up, 80 children (34 girls and 46 boys; mean age 9.56 years; mean follow-up 9.6 years) composed the study group (53 primary and 27 previously treated/recurrent tumors). Building on existing classification schemes proposed by De Vile for hypothalamic dysfunction and Wen for overall functional outcome, the authors devised a more nuanced classification system (Craniopharyngioma Clinical Status Scale [CCSS]) that assesses outcome across 5 axes, including neurological examination, visual status, pituitary function, hypothalamic dysfunction, and educational/occupational status at last follow-up (there is a 4-tiered grading scale in each domain, with increasing values reflecting greater dysfunction). There was a significant increase in pituitary dysfunction following treatment-consistent with the high rates of diabetes insipidus and hypopituitarism common to the surgical management of craniopharyngiomas-and less dramatic deterioration in hypothalamic function or cognitive domains. Significant improvement in vision was also demonstrated, with no significant overall change in neurological status. Preoperative CCSS scores predicted postoperative outcome better than clinical characteristics like patient age, sex, tumor size, and the location or presence of hydrocephalus. Preoperative CCSS scores predicted outcome with higher accuracy than clinical or imaging characteristics. In lieu of randomized trials, the CCSS may provide a useful outcome assessment tool for comparison

  17. [Clinical evolution and nutritional status in asthmatic children and adolescents enrolled in Primary Health Care].

    PubMed

    Morishita, Rosinha Yoko Matsubayaci; Strufaldi, Maria Wany Louzada; Puccini, Rosana Fiorini

    2015-12-01

    To evaluate the clinical evolution and the association between nutritional status and severity of asthma in children and adolescents enrolled in Primary Health Care. A retrospective cohort study of 219 asthmatic patients (3 to 17 years old) enrolled in primary care services (PCSs) in Embu das Artes (SP), from 2007 to 2011. Secondary data: gender, age, diagnosis of asthma severity, other atopic diseases, family history of atopy, and body mass index. To evaluate the clinical outcome of asthma, data were collected on number of asthma exacerbations, number of emergency room consultations and doses of inhaled corticosteroids at follow-up visits in the 6th and 12th months. The statistical analysis included chi-square and Kappa agreement index, with 5% set as the significance level. 50.5% of patients started wheezing before the age of two years, 99.5% had allergic rhinitis and 65.2% had a positive family history of atopy. Regarding severity, intermittent asthma was more frequent (51.6%) and, in relation to nutritional status, 65.8% of patients had normal weight. There was no association between nutritional status and asthma severity (p=0,409). After one year of follow-up, 25.2% of patients showed reduction in exacerbations and emergency room consultations, and 16.2% reduced the amount of inhaled corticosteroids. The monitoring of asthmatic patients in PCSs showed improvement in clinical outcome, with a decreased number of exacerbations, emergency room consultations and doses of inhaled corticosteroids. No association between nutritional status and asthma severity was observed in this study. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  18. Impact of postoperative glycemic control and nutritional status on clinical outcomes after total pancreatectomy.

    PubMed

    Shi, Hao-Jun; Jin, Chen; Fu, De-Liang

    2017-01-14

    To evaluate the impact of glycemic control and nutritional status after total pancreatectomy (TP) on complications, tumor recurrence and overall survival. Retrospective records of 52 patients with pancreatic tumors who underwent TP were collected from 2007 to 2015. A series of clinical parameters collected before and after surgery, and during the follow-up were evaluated. The associations of glycemic control and nutritional status with complications, tumor recurrence and long-term survival were determined. Risk factors for postoperative glycemic control and nutritional status were identified. High early postoperative fasting blood glucose (FBG) levels (OR = 4.074, 95%CI: 1.188-13.965, P = 0.025) and low early postoperative prealbumin levels (OR = 3.816, 95%CI: 1.110-13.122, P = 0.034) were significantly associated with complications after TP. Postoperative HbA1c levels over 7% (HR = 2.655, 95%CI: 1.299-5.425, P = 0.007) were identified as one of the independent risk factors for tumor recurrence. Patients with postoperative HbA1c levels over 7% had much poorer overall survival than those with HbA1c levels less than 7% (9.3 mo vs 27.6 mo, HR = 3.212, 95%CI: 1.147-8.999, P = 0.026). Patients with long-term diabetes mellitus (HR = 15.019, 95%CI: 1.278-176.211, P = 0.031) and alcohol history (B = 1.985, SE = 0.860, P = 0.025) tended to have poor glycemic control and lower body mass index levels after TP, respectively. At least 3 mo are required after TP to adapt to diabetes and recover nutritional status. Glycemic control appears to have more influence over nutritional status on long-term outcomes after TP. Improvement in glycemic control and nutritional status after TP is important to prevent early complications and tumor recurrence, and improve survival.

  19. Application perspectives of localization microscopy in virology.

    PubMed

    Cremer, C; Kaufmann, R; Gunkel, M; Polanski, F; Müller, P; Dierkes, R; Degenhard, S; Wege, C; Hausmann, M; Birk, U

    2014-07-01

    Localization microscopy approaches allowing an optical resolution down to the single-molecule level in fluorescence-labeled biostructures have already found a variety of applications in cell biology, as well as in virology. Here, we focus on some perspectives of a special localization microscopy embodiment, spectral precision distance/position determination microscopy (SPDM). SPDM permits the use of conventional fluorophores or fluorescent proteins together with standard sample preparation conditions employing an aqueous buffered milieu and typically monochromatic excitation. This allowed superresolution imaging and studies on the aggregation state of modified tobacco mosaic virus particles on the nanoscale with a single-molecule localization accuracy of better than 8 nm, using standard fluorescent dyes in the visible spectrum. To gain a better understanding of cell entry mechanisms during influenza A virus infection, SPDM was used in conjunction with algorithms for distance and cluster analyses to study changes in the distribution of virus particles themselves or in the distribution of infection-related proteins, the hepatocyte growth factor receptors, in the cell membrane on the single-molecule level. Not requiring TIRF (total internal reflection) illumination, SPDM was also applied to study the molecular arrangement of gp36.5/m164 glycoprotein (essentially associated with murine cytomegalovirus infection) in the endoplasmic reticulum and the nuclear membrane inside cells with single-molecule resolution. On the basis of the experimental evidence so far obtained, we finally discuss additional application perspectives of localization microscopy approaches for the fast detection and identification of viruses by multi-color SPDM and combinatorial oligonucleotide fluorescence in situ hybridization, as well as SPDM techniques for optimization of virus-based nanotools and biodetection devices.

  20. Long-term Virologic Response and Genotypic Resistance Mutations in HIV-1 Infected Kenyan Children on Combination Antiretroviral Therapy

    PubMed Central

    Wamalwa, Dalton; Lehman, Dara A; Benki-Nugent, Sarah; Gasper, Melanie; Gichohi, Richard; Maleche-Obimbo, Elizabeth; Farquhar, Carey; John-Stewart, Grace; Overbaugh, Julie

    2012-01-01

    Background HIV-infected children may require the use of combination antiretroviral treatment (cART) into adulthood. However, regimens are limited to first- and second-line in many African settings. Therefore, understanding the long-term rate of virologic failure and drug resistance during prolonged antiretroviral treatment is important for establishing treatment strategies in African pediatric cohorts. Methods Children ages 18 months to 12 years initiated first-line cART and were followed every 1–3 months, for up to 5.5 years. Treatment was switched to second-line based on clinical and immunologic criteria according to national guidelines. Virologic failure was determined retrospectively as defined by ≥2 viral loads >5000 copies/mL. Drug resistance was assessed during viral failure by population-based sequencing. Results Among 100 children on first-line cART followed for a median 49 months, 34% experienced virologic failure. Twenty-three (68%) of the 34 children with viral failure had detectable resistance mutations, of whom 14 (61%) had multi-class resistance. Fourteen (14%) children were switched to second-line regimens and followed for a median of 28 months. Retrospective analysis revealed that virologic failure had occurred a median of 12 months prior to the switch to second-line. During prolonged first-line treatment in the presence of viral failure, additional resistance mutations accumulated, however, only 1 (7%) of 14 children had persistent viremia during second-line treatment. Discussion Virologic suppression was maintained on first-line cART in two-thirds of HIV-infected children for up to 5 years. Switch to second-line based on clinical/immunologic criteria occurred ~1 year after viral failure, but the delay did not consistently compromise second-line treatment. PMID:23196827

  1. Gender-specific risk factors for virologic failure in KwaZulu-Natal: Automobile ownership and financial insecurity

    PubMed Central

    HARE, Anna Q.; ORDÓÑEZ, Claudia E.; JOHNSON, Brent A.; RIO, Carlos DEL; KEARNS, Rachel A.; WU, Baohua; HAMPTON, Jane; WU, Peng; SUNPATH, Henry; MARCONI, Vincent C.

    2014-01-01

    We sought to examine which socioeconomic indicators are risk factors for virologic failure among HIV-1 infected patients receiving antiretroviral therapy in KwaZulu-Natal, South Africa. A case-control study of virologic failure was conducted among patients recruited from the outpatient clinic at McCord Hospital in Durban, South Africa between October 1, 2010 and June 30, 2012. Cases were those failing first-line antiretroviral therapy (ART), defined as viral load > 1000 copies/mL. Univariate logistic regression was performed on sociodemographic data for the outcome of virologic failure. Variables found significant (p<.05) were used in multivariate models and all models were stratified by gender. Of 158 cases and 300 controls, 35% were male and median age was 40 years. Gender stratification of models revealed automobile ownership was a risk factor among males, while variables of financial insecurity (unemployment, non-spouse family paying for care, staying with family) were risk factors for women. In this cohort, financial insecurity among women and automobile ownership among men were risk factors for virologic failure. Risk factor differences between genders demonstrate limitations of generalized risk factor analysis. PMID:25037488

  2. Gender-specific risk factors for virologic failure in KwaZulu-Natal: automobile ownership and financial insecurity.

    PubMed

    Hare, Anna Q; Ordóñez, Claudia E; Johnson, Brent A; Del Rio, Carlos; Kearns, Rachel A; Wu, Baohua; Hampton, Jane; Wu, Peng; Sunpath, Henry; Marconi, Vincent C

    2014-11-01

    We sought to examine which socioeconomic indicators are risk factors for virologic failure among HIV-1 infected patients receiving antiretroviral therapy (ART) in KwaZulu-Natal, South Africa. A case-control study of virologic failure was conducted among patients recruited from the outpatient clinic at McCord Hospital in Durban, South Africa between October 1, 2010 and June 30, 2012. Cases were those failing first-line ART, defined as viral load >1,000 copies/mL. Univariate logistic regression was performed on sociodemographic data for the outcome of virologic failure. Variables found significant (p < 0.05) were used in multivariate models and all models were stratified by gender. Of 158 cases and 300 controls, 35 % were male and median age was 40 years. Gender stratification of models revealed automobile ownership was a risk factor among males, while variables of financial insecurity (unemployment, non-spouse family paying for care, staying with family) were risk factors for women. In this cohort, financial insecurity among women and automobile ownership among men were risk factors for virologic failure. Risk factor differences between genders demonstrate limitations of generalized risk factor analysis.

  3. Preoperative Nutritional Status and Clinical Complications in the Postoperative Period of Cardiac Surgeries

    PubMed Central

    Gonçalves, Luciana de Brito; de Jesus, Natanael Moura Teixeira; Gonçalves, Maiara de Brito; Dias, Lidiane Cristina Gomes; Deiró, Tereza Cristina Bomfim de Jesus

    2016-01-01

    Objective This study aims to assess the preoperative nutritional status of patients and the role it plays in the occurrence of clinical complications in the postoperative period of major elective cardiac surgeries. Methods Cross-sectional study comprising 72 patients aged 20 years or older, who underwent elective cardiac surgery. The preoperative nutritional assessment consisted of nutritional screening, anthropometry (including the measurement of the adductor pollicis muscle thickness) and biochemical tests. The patients were monitored for up to 10 days after the surgery in order to control the occurrence of postoperative complications. The R software, version 3.0.2, was used to statistically analyze the data. Results Clinical complications were found in 62.5% (n=42) of the studied samples and complications of non-infectious nature were most often found. Serum albumin appeared to be associated with renal complications (P=0.026) in the nutritional status indicators analyzed herein. The adductor pollicis muscle thickness was associated with infectious complications and presented mean of 9.39±2.32 mm in the non-dominant hand (P=0.030). No significant correlation was found between the other indicators and the clinical complications. Conclusion The adductor pollicis muscle thickness and the serum albumin seemed be associated with clinical complications in the postoperative period of cardiac surgeries. PMID:27982346

  4. The recording of Aboriginal and Torres Strait Islander status in general practice clinical records: a cross-sectional study.

    PubMed

    Thomson, Allison; Morgan, Simon; O'Mara, Peter; Tapley, Amanda; Henderson, Kim; van Driel, Mieke; Oldmeadow, Christopher; Ball, Jean; Scott, John; Spike, Neil; McArthur, Lawrie; Magin, Parker

    2016-04-01

    To document the frequency of recording of Aboriginal and Torres Strait Islander status in general practice (GP) clinical records and to establish associations of this recording. Cross-sectional analysis of recording of patients' Aboriginal and Torres Strait Islander status in GP clinical records from GP training practices in four Australian states. Of the 9,704 clinical records examined, the patients' Aboriginal and Torres Strait Islander status had been documented in 5,165 (53.2%). Higher rates of recording were associated with older patient age, practices outside a major city, patients who were not new to the practice and the patient being Aboriginal and Torres Strait Islander. In encounters with Aboriginal and Torres Strait Islander patients, the patient's status had been documented in 82% of records. Those attending larger practices were less likely to have had their status recorded. This is the first report of Aboriginal and Torres Strait Islander status recording in GP clinical records. Almost 20% of Aboriginal and Torres Strait Islander patients did not have their status recorded in the clinical record, with indications that recording may be unsystematic. Our findings reinforce the need for a systematic approach to identification of Aboriginal and Torres Strait Islander status in general practice and will inform policy and practice in this important area. © 2015 The Authors.

  5. Salzburg Consensus Criteria for Non-Convulsive Status Epilepticus--approach to clinical application.

    PubMed

    Leitinger, M; Beniczky, S; Rohracher, A; Gardella, E; Kalss, G; Qerama, E; Höfler, J; Hess Lindberg-Larsen, A; Kuchukhidze, G; Dobesberger, J; Langthaler, P B; Trinka, E

    2015-08-01

    Salzburg Consensus Criteria for diagnosis of Non-Convulsive Status Epilepticus (SCNC) were proposed at the 4th London-Innsbruck Colloquium on status epilepticus in Salzburg (2013). We retrospectively analyzed the EEGs of 50 consecutive nonhypoxic patients with diagnoses of nonconvulsive status epilepticus (NCSE) at discharge and 50 consecutive controls with abnormal EEGs in a large university hospital in Austria. We implemented the American Clinical Neurophysiology Society's Standardized Critical Care EEG Terminology, 2012 version (ACNS criteria) to increase the test performance of SCNC. In patients without preexisting epileptic encephalopathy, the following criteria were applied: (1) more than 25 epileptiform discharges (ED) per 10-second epoch, i.e., >2.5/s and (2) patients with EDs ≤ 2.5/s or rhythmic delta/theta activity (RDT) exceeding 0.5/s AND at least one of the additional criteria: (2a) clinical and EEG improvements from antiepileptic drugs (AEDs), (2b) subtle clinical phenomena, or (2c) typical spatiotemporal evolution. In case of fluctuation without evolution or EEG improvement without clinical improvement, "possible NCSE" was diagnosed. For identification of RDT, the following criteria were compared: (test condition A) continuous delta-theta activity without further rules, (B) ACNS criterion for rhythmic delta activity (RDA), and (C) ACNS criteria for RDA and fluctuation. False positive rate in controls dropped from 28% (condition A) to 2% (B) (p = 0.00039) and finally to 0% (C) (p = 0.000042). Application of test condition C in the group with NCSE gives one false negative (2%). Various EEG patterns were found in patients with NCSE: (1) 8.2%, (2a) 2%, (2b) 12.2%, and (2c) 32.7%. Possible NCSE was diagnosed based on fluctuations in 57.1% and EEG improvement without clinical improvement in 14.2%. The modified SCNC with refined definitions including the ACNS terminology leads to clinically relevant and statistically significant reduction of false

  6. Socioeconomic Status of Counties Where Dialysis Clinics Are Located Is an Important Factor in Comparing Dialysis Providers.

    PubMed

    Almachraki, Fadi; Tuffli, Michael; Lee, Paul; Desmarais, Mark; Shih, Huai-Che; Nissenson, Allen R; Krishnan, Mahesh

    2016-02-01

    This study assessed the hypothesis that the clinic site of service socioeconomic status (SES) represents an unmeasured confounder for clinical outcome comparisons between dialysis clinics and provider types, using data from the federal pay-for-performance program for end-stage renal disease. A total of 6506 dialysis facilities were categorized by clinic SES status (rurality and poverty status). Clinics were then grouped by provider type (chain size and tax status). Lastly, performance penalties were determined by each of these classifications. Findings were that 7.4% of dialysis clinics could be classified as being in rural locations, and 20.6% could be classified as being in high-poverty locations. Large dialysis organizations served more rural (65%) and high-poverty areas (metropolitan, 69%; micropolitan, 75%; rural, 75%) compared to other providers (medium, small, hospital/university). For-profit providers accounted for a majority of dialysis clinics in rural areas (78%) and high poverty areas (metropolitan, 84%; micropolitan, 85%; rural, 90%). This study found that dialysis clinic performance penalties did vary by SES, with poorer outcomes observed for clinic locations with lower SES. This finding, along with the nonrandom distribution of provider types by SES status, suggests that clinic and provider location SES may need to be considered when comparing providers.

  7. Assessment of demographic and clinical characteristics on functional status and disability of patients with stroke

    PubMed Central

    Memis, Derya; Kozanoglu, Erkan; Kelle, Bayram; Goncu, Mustafa K.

    2016-01-01

    Objective: To determine the effects of demographic and clinical characteristics on mobility, disability, and activities of daily life of patients with stroke. Methods: This cross-sectional clinical study was performed in the Department of Physical Medicine and Rehabilitation in Cukurova University Faculty of Medicine in Adana, Turkey, between February 2011 and December 2011. The study included 126 patients with stroke. The Brunnstrom recovery scale (BRS), functional ambulation classification scale (FACS), modified Barthel index (MBI), modified Rankin scale (MRS), and Rivermead mobility index (RMI) were used in the evaluation of the functional status of stroke patients. Correlations between each scale and parameters including age, etiology, and duration of hemiplegia were assessed. Results: The major etiology of stroke was found as ischemic (77%). Hypertension was a major risk factor in both genders (72% for males, 85% for females). Statistically significant differences were found between ischemic and hemorrhagic stroke patients regarding the RMI, MBI, BRS, and the FACS (p<0.001). Age had a poor negative correlation with the FACS and RMI. Conclusion: It is suggested that age is an important risk factor for the development of stroke, but it has no strong effect on functional status and disability in patients with stroke. The BRS, FACS, MBI, MRS, and RMI scales can be used in stroke patients whether they are under or over 65 years old in order to evaluate functional status and disability. PMID:27744465

  8. Investigating the genetic background of bovine digital dermatitis using improved definitions of clinical status.

    PubMed

    Schöpke, K; Gomez, A; Dunbar, K A; Swalve, H H; Döpfer, D

    2015-11-01

    Bovine digital dermatitis (DD) is an increasing claw health problem in all cattle production systems worldwide. The objective of this study was to evaluate the use of an improved scoring of the clinical status for DD via M-scores accounting for the dynamics of the disease; that is, the transitions from one stage to another. The newly defined traits were then subjected to a genetic analysis to determine the genetic background for susceptibility to DD. Data consisted of 6,444 clinical observations from 729 Holstein heifers in a commercial dairy herd, collected applying the M-score system. The M-score system is a classification scheme for stages of DD that allows a macroscopic scoring based on clinical inspections of the bovine foot, thus it describes the stages of lesion development. The M-scores were used to define new DD trait definitions with different complexities. Linear mixed models and logistic models were used to identify fixed environmental effects and to estimate variance components. In total, 68% of all observations showed no DD status, whereas 11% were scored as infectious for and affected by DD, and 21% of all observations exhibited an affected but noninfectious status. For all traits, the probability of occurrence and clinical status were associated with age at observation and period of observation. Risk of becoming infected increased with age, and month of observation significantly affected all traits. Identification of the optimal month concerning DD herd status was consistent for all trait definitions; the last month of the trial was identified. In contrast, months exhibiting the highest least squares means of transformed scores differed depending on trait definition. In this respect, traits that can distinguish between healthy, infectious, and noninfectious stages of DD can account for the infectious potential of the herd and can serve as an alert tool. Estimates of heritabilities of traits studied ranged between 0.19 (±0.11) and 0.52 (±0

  9. Smoking status and its relationship to demographic and clinical characteristics in first episode psychosis.

    PubMed

    Grossman, Michael; Bowie, Christopher R; Lepage, Martin; Malla, Ashok K; Joober, Ridha; Iyer, Srividya N

    2017-02-01

    Elevated rates of cigarette smoking are observed prior to the onset of psychosis and remain stable early in the illness. Cannabis use frequently co-occurs with cigarette smoking and is independently associated with distinct clinical outcomes. However, past research has not controlled for cannabis use in cigarette smokers with first episode psychosis (FEP), limiting conclusions on the unique relationship of cigarette smoking to the demographic and clinical profiles of these patients. The present study therefore aimed to: (1) Determine the prevalence and patterns of cigarette smoking and its co-use with cannabis in FEP, and (2) Examine the demographic, clinical, cognitive, and functional characteristics associated with cigarette smoking status, after adjusting for frequency of cannabis use. Patients entering specialized treatment for FEP (N = 140) were divided into groups according to their current smoking status: 66 non-smokers (0 cigarettes/day), 47 light/moderate smokers (1-19 cigarettes/day; M = 9.81, SD = 3.93), and 27 heavy smokers (≥20 cigarettes/day; M = 26.39, SD = 6.31). The prevalence of cigarette smoking was 53% and smoking status was highly associated with frequency of cannabis use. After adjusting for cannabis use, significant between-group differences emerged. Heavy smokers were older at program entry and had a later age of onset of psychosis than light/moderate and non-smokers. Non-smokers had more education, better neurocognitive performance, and higher levels of functioning than light/moderate and heavy smokers. Prospective, longitudinal studies are needed to better understand the clinical significance of tobacco use and factors that contribute to the initiation and continuation of smoking behaviours in FEP. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Clinical patterns and outcomes of status epilepticus in patients with tuberous sclerosis complex

    PubMed Central

    Shehata, Hatem S; AbdelGhaffar, Hadeer Mahmoud; Nasreldin, Mohammed; Elmazny, Alaa; Abdelalim, Ahmed; Sabbah, Asmaa; Shalaby, Nevin M

    2017-01-01

    Introduction Refractory epilepsy is a common clinical manifestation in patients with tuberous sclerosis complex (TSC), which can be complicated by many life-threatening conditions, such as status epilepticus (SE). However, very few reports mention the patterns and semiology of SE in those patients. Objective To study the clinical characteristics and outcomes of SE in TSC patients. Materials and methods This observational, prospective study was carried out on 36 Egyptian children with definite TSC. Clinical history, general and neurological examination and psychometric evaluation by standard questionnaires were used to explore characteristics of epileptic manifestations and clinical patterns of SE. All included patients were required to have long-term video electroencephalograms (EEGs) and brain MRI performed. Results A total of 32 attacks of SE were recorded in 21 patients (58.3%) in our cohort during a follow-up period of 2.8±1.1 years; of those patients, 15 had convulsive status, 7 had non-convulsive SE, 6 had refractory/super-refractory SE and 14 patients had a history of infantile spasms (epileptic spasms). The duration of status ranged from 40 to 150 min (mean ± standard deviation: 90±15). Fourteen patients with SE had severe mental retardation, 9 had autistic spectrum disorder and 22 had severe epileptogenic EEG findings. Patients with SE had higher tuber numbers (mean: 9.6), 5 patients had subependymal giant cell astrocytomas and 2 patients had their SE after receiving everolimus. Conclusions The incidence of SE in our patient sample is high (>50%); severe mental retardation, autistic features, history of infantile spasm (epileptic spasms) and high tuber burden are risk factors for developing SE. PMID:28721058

  11. Current status and perspectives of interventional clinical trials for glioblastoma - analysis of ClinicalTrials.gov.

    PubMed

    Cihoric, Nikola; Tsikkinis, Alexandros; Minniti, Giuseppe; Lagerwaard, Frank J; Herrlinger, Ulrich; Mathier, Etienne; Soldatovic, Ivan; Jeremic, Branislav; Ghadjar, Pirus; Elicin, Olgun; Lössl, Kristina; Aebersold, Daniel M; Belka, Claus; Herrmann, Evelyn; Niyazi, Maximilian

    2017-01-03

    The records of 208.777 (100%) clinical trials registered at ClinicalTrials.gov were downloaded on the 19th of February 2016. Phase II and III trials including patients with glioblastoma were selected for further classification and analysis. Based on the disease settings, trials were classified into three groups: newly diagnosed glioblastoma, recurrent disease and trials with no differentiation according to disease setting. Furthermore, we categorized trials according to the experimental interventions, the primary sponsor, the source of financial support and trial design elements. Trends were evaluated using the autoregressive integrated moving average model. Two hundred sixteen (0.1%) trials were selected for further analysis. Academic centers (investigator initiated trials) were recorded as primary sponsors in 56.9% of trials, followed by industry 25.9%. Industry was the leading source of monetary support for the selected trials in 44.4%, followed by 25% of trials with primarily academic financial support. The number of newly initiated trials between 2005 and 2015 shows a positive trend, mainly through an increase in phase II trials, whereas phase III trials show a negative trend. The vast majority of trials evaluate forms of different systemic treatments (91.2%). In total, one hundred different molecular entities or biologicals were identified. Of those, 60% were involving drugs specifically designed for central nervous system malignancies. Trials that specifically address radiotherapy, surgery, imaging and other therapeutic or diagnostic methods appear to be rare. Current research in glioblastoma is mainly driven or sponsored by industry, academic medical oncologists and neuro-oncologists, with the majority of trials evaluating forms of systemic therapies. Few trials reach phase III. Imaging, radiation therapy and surgical procedures are underrepresented in current trials portfolios. Optimization in research portfolio for glioblastoma is needed.

  12. Variation in serum biomarkers with sex and female hormonal status: implications for clinical tests

    PubMed Central

    Ramsey, Jordan M.; Cooper, Jason D.; Penninx, Brenda W. J. H.; Bahn, Sabine

    2016-01-01

    Few serum biomarker tests are implemented in clinical practice and recent reports raise concerns about poor reproducibility of biomarker studies. Here, we investigated the potential role of sex and female hormonal status in this widespread irreproducibility. We examined 171 serum proteins and small molecules measured in 1,676 participants from the Netherlands Study of Depression and Anxiety. Concentrations of 96 molecules varied with sex and 66 molecules varied between oral contraceptive pill users, postmenopausal females, and females in the follicular and luteal phases of the menstrual cycle (FDR-adjusted p-value <0.05). Simulations of biomarker studies yielded up to 40% false discoveries when patient and control groups were not matched for sex and up to 41% false discoveries when premenopausal females were not matched for oral contraceptive pill use. High accuracy (over 90%) classification tools were developed to label samples with sex and female hormonal status where this information was not collected. PMID:27240929

  13. A commitment contract to achieve virologic suppression in poorly adherent patients with HIV/AIDS.

    PubMed

    Alsan, Marcella; Beshears, John; Armstrong, Wendy S; Choi, James J; Madrian, Brigitte C; Nguyen, Minh Ly T; Del Rio, Carlos; Laibson, David; Marconi, Vincent C

    2017-07-31

    Assess whether a commitment contract informed by behavioral economics leads to persistent virologic suppression among HIV-positive patients with poor antiretroviral therapy (ART) adherence. Single-center pilot randomized clinical trial and a nonrandomized control group. Publicly funded HIV clinic in Atlanta, Georgia, USA. The study involved three arms. First, participants in the provider visit incentive (PVI) arm received $30 after attending each scheduled provider visit. Second, participants in the incentive choice arm were given a choice between the above arrangement and a commitment contract that made the $30 payment conditional on both attending the provider visit and meeting an ART adherence threshold. Third, the passive control arm received routine care and no incentives. A total of 110 HIV-infected adults with a recent plasma HIV-1 viral load more than 200 copies/ml despite ART. The sample sizes of the three groups were as follows: PVI, n = 21; incentive choice, n = 19; and passive control, n = 70. Virologic suppression (plasma HIV-1 viral load ≤200 copies/ml) at the end of the incentive period and at an unanticipated postincentive study visit approximately 3 months later. The odds of suppression were higher in the incentive choice arm than in the passive control arm at the postincentive visit (adjusted odds ratio 3.93, 95% confidence interval 1.19-13.04, P = 0.025). The differences relative to the passive control arm at the end of the incentive period and relative to the PVI arm at both points in time were not statistically significant. Commitment contracts can improve ART adherence and virologic suppression. ClinicalTrials.gov identifier NCT01455740.

  14. Relationship between radiological grading and clinical status in knee osteoarthritis. a multicentric study

    PubMed Central

    2012-01-01

    Background Controversy exists regarding the relationship between radiographic findings and clinical status in knee osteoarthritis. Although the surgical indication for total knee arthroplasty (TKA) should be based on pain, clinical status, and the deterioration of quality of life, the radiographic study is the most commonly used criterion for preoperative evaluation. The objective of this study is to find out the relationship between the Ahlbäck classification and clinical status in patients undergoing TKA. Methods 1329 protocols were collected from preoperative studies in four multicentric working groups (the Interax, Duracon, Scorpio, and Triathlon Spanish groups) in 30 Spanish hospitals. Mean age was 70.4 years (SD: 6.8; range: 35 to 98); 76.3% of patients were women. Patients entered the study whenever the surgeon found that medical treatment was insufficient to control pain and functional limitation. Data were collected using electronic Case Report Forms, and included Ahlbäck grading scores, Hospital for Special Surgery Knee Score (HSS), SF-12, and other clinical and epidemiologic variables. Results According to the Ahlbäck grading system, patients were divided as follows: 243 grade I (18.3%), 358 grade II (26.9%), 416 grade III (31.3%), 241 grade IV (18.1%), and 71 grade V (5.3%). As for HSS, the following scores were obtained: <60 points in 925 patients (69.6%), 60 to 69 points in 286 patients (21.5%), 70 to 84 points in 112 patients (8.4%) and 85 to 100 points in 6 patients (0.5%). Scores showed a statistically significant difference depending on Ahlbäck grade, with a clear tendency towards decrease in HSS scores as the Ahlbäck grade increases (p<0.001). However, the HSS score difference between Ahlbäck grades I and V was of 9.56 points only. Comparing the status of the patients at the start (1994) and at the end (2010) of the data collection process, we observed that patients who underwent surgery in the last years were older and showed a lower Ahlb

  15. Sexual Risk Behavior Among Virologically Detectable Human Immunodeficiency Virus-Infected Young Men Who Have Sex With Men.

    PubMed

    Wilson, Patrick A; Kahana, Shoshana Y; Fernandez, Maria Isabel; Harper, Gary W; Mayer, Kenneth; Wilson, Craig M; Hightow-Weidman, Lisa B

    2016-02-01

    Human immunodeficiency virus (HIV) diagnoses continue to increase among young men who have sex with men (YMSM). Many YMSM living with HIV engage in sexual risk behaviors, and those who have a detectable viral load can transmit HIV to sex partners. Understanding factors that are related to sexual risk taking among virologically detectable (VL+) YMSM can inform prevention and treatment efforts. To describe differences between virologically suppressed (VL-) and VL+ YMSM living with HIV and to identify correlates of condomless anal intercourse (CAI) and serodiscordant CAI among VL+ YMSM. In this cross-sectional survey conducted from December 1, 2009, through June 30, 2012, we studied 991 HIV-infected YMSM 15 to 26 years of age at 20 adolescent HIV clinics in the United States. Data analysis was conducted December 1, 2013, through July 31, 2015. Demographic, behavioral, and psychosocial assessments obtained using audio computer-assisted self-interviews. Viral load information was obtained via blood draw or medical record abstraction. Of the 991 participants, 688 (69.4%) were VL+ and 458 (46.2%) reported CAI, with 310 (31.3%) reporting serodiscordant CAI in the past 3 months. The VL+ YMSM were more likely than the VL- YMSM to report CAI (detectable, 266 [54.7%]; suppressed, 91 [44.4%]; P = .01) and serodiscordant CAI (detectable, 187 [34.9%]; suppressed, 57 [25.0%]; P < .01). Multivariable analyses indicated that among VL+ YMSM, those reporting problematic substance use were more likely to report CAI (adjusted odds ratio [AOR], 1.46; 95% CI, 1.02-2.10) and serodiscordant CAI (AOR, 1.45; 95% CI, 1.06-1.99). Black VL+ YMSM were less likely to report CAI (AOR, 0.63; 95% CI, 0.44-0.90) or serodiscordant CAI (AOR, 0.66; 95% CI, 0.46-0.94) compared with other VL+ YMSM. In addition, VL+ YMSM who disclosed their HIV status to sex partners were more likely to report CAI compared with nondisclosing YMSM (AOR, 1.35; 95% CI, 1.01-1.81). Transgender participants were less likely

  16. Sexual Risk Behavior Among Virologically Detectable Human Immunodeficiency Virus–Infected Young Men Who Have Sex With Men

    PubMed Central

    Wilson, Patrick A.; Kahana, Shoshana Y.; Fernandez, Maria Isabel; Harper, Gary W.; Mayer, Kenneth; Wilson, Craig M.; Hightow-Weidman, Lisa B.

    2016-01-01

    Importance Human immunodeficiency virus (HIV) diagnoses continue to increase among young men who have sex with men (YMSM). Many YMSM living with HIV engage in sexual risk behaviors, and those who have a detectable viral load can transmit HIV to sex partners. Understanding factors that are related to sexual risk taking among virologically detectable (VL+) YMSM can inform prevention and treatment efforts. Objectives To describe differences between virologically suppressed (VL−) and VL+ YMSM living with HIV and to identify correlates of condomless anal intercourse (CAI) and serodiscordant CAI among VL+ YMSM. Design, Setting, and Participants In this cross-sectional survey conducted from December 1, 2009, through June 30, 2012, we studied 991 HIV-infected YMSM 15 to 26 years of age at 20 adolescent HIV clinics in the United States. Data analysis was conducted December 1, 2013, through July 31, 2015. Main Outcomes and Measures Demographic, behavioral, and psychosocial assessments obtained using audio computer-assisted self-interviews. Viral load information was obtained via blood draw or medical record abstraction. Results Of the 991 participants, 688 (69.4%) were VL+ and 458 (46.2%) reported CAI, with 310 (31.3%) reporting serodiscordant CAI in the past 3 months. The VL+ YMSM were more likely than the VL− YMSM to report CAI (detectable, 266 [54.7%]; suppressed, 91 [44.4%]; P = .01) and serodiscordant CAI (detectable, 187 [34.9%]; suppressed, 57 [25.0%]; P < .01). Multivariable analyses indicated that among VL+ YMSM, those reporting problematic substance use were more likely to report CAI (adjusted odds ratio [AOR], 1.46; 95% CI, 1.02-2.10) and serodiscordant CAI (AOR, 1.45; 95% CI, 1.06-1.99). Black VL+ YMSM were less likely to report CAI (AOR, 0.63; 95% CI, 0.44-0.90) or serodiscordant CAI (AOR, 0.66; 95% CI, 0.46-0.94) compared with other VL+ YMSM. In addition, VL+ YMSM who disclosed their HIV status to sex partners were more likely to report CAI compared with

  17. Impact of smoking status on clinical outcome in oral cavity cancer patients.

    PubMed

    Kawakita, Daisuke; Hosono, Satoyo; Ito, Hidemi; Oze, Isao; Watanabe, Miki; Hanai, Nobuhiro; Hasegawa, Yasuhisa; Tajima, Kazuo; Murakami, Shingo; Tanaka, Hideo; Matsuo, Keitaro

    2012-02-01

    The association between smoking status and survival in oral cavity squamous cell carcinoma (OSCC) patients remains unclear. Therefore, we evaluated the association between smoking status before treatment and clinical outcome in OSCC patients. We conducted a retrospective cohort study of 222 OSCC patients who were treated at Aichi Cancer Center in Japan. Of these, 82 patients (36.9%) were non-smokers, 65 (29.3%) were light smokers (pack-years smoking (PY) <30), 54 (24.3%) were moderate smokers (30≤PY<60), and 21 (9.5%) were heavy smokers (60≤PY). The survival impact of pre-treatment smoking status was evaluated using multivariate proportional hazard models. Five-year overall survival for non-, light, moderate, and heavy smokers was 72.9% (95% confidence interval CI): (61.4-81.5), 85.5% (74.0-92.2), 59.9% (44.3-72.4) and 69.0% (42.8-85.0). Adjusted hazard ratios (HRs) for moderate and heavy smokers in comparison with light smokers were 2.44 (1.07-5.57, P=0.034) and 2.66 (0.97-7.33, P=0.058) and the dose-response relationship among smokers was statistically significance (P(trend)=0.024). In addition, adjusted HR for non-smokers relative to light smokers was 2.27 (0.84-6.15, P=0.108). We observed a suggestive heterogeneity in the impact of smoking status by treatment method (P for heterogeneity=0.069). Effect of smoking was evident only among the chemoradiotherapy or radiotherapy group. In this study, we found the significant positive dose-response relationship among smokers on clinical outcome in OSCC patients and that non-smokers were worse prognosis than light smokers. In addition, this effect might differ by treatment method.

  18. Impact of IDH1 mutation status on outcome in clinical trials for recurrent glioblastoma.

    PubMed

    Mandel, Jacob J; Cachia, David; Liu, Diane; Wilson, Charmaine; Aldape, Ken; Fuller, Greg; de Groot, John F

    2016-08-01

    IDH1 mutated glioblastoma (GB) has a better prognosis than IDH1 wildtype GB. However, it remains unknown whether patients (pts) with IDH1 mutated GB have a higher 6-month progression free survival (PFS6) or radiographic response (RR) rate on clinical trials for recurrence. Retrospective review of GB pts at MDACC between 2006 and 2012 identified 330 patients in recurrent GB trials. 93 patients (28 %) had either PFS6 or a complete/partial RR per RANO criteria. 49/93 (53 %) patients with PFS6 or a complete/partial RR had tumor tissue for IDH1 testing. A matched cohort of 49 patients on recurrent GB clinical trials that failed to achieve PFS6 or RR (also with tissue for IDH1 testing) was identified for comparison. IDH1 status was obtained in 92/98 (94 %) patients of which 17 (18 %) had an IDH1 mutation. PFS6 was seen in 26/49 (53 %) patients. IDH status was unknown in two of these patients. 5/24 (21 %) were IDH1 mutated compared to 5/24 (21 %) of their matched cohort without PFS6. RR was found in 47/49 (94 %) patients. IDH status was unknown in four of these patients. IDH1 mutation was present in 7/43 (16 %) patients with RR compared to 10/43 (23 %) in the matched cohort without RR (p = 0.48). Median OS for trials at first recurrence was 9.8 months for IDH1 wildtype GB vs. 19.32 months for IDH1 mutated GB (p = 0.14). IDH1 mutation status was not predictive of PFS6 or RR in recurrent GB trials for this data set. However, further examination in larger randomized prospective studies is needed.

  19. Effect of socioeconomic status as measured by education level on survival in breast cancer clinical trials.

    PubMed

    Herndon, James E; Kornblith, Alice B; Holland, Jimmie C; Paskett, Electra D

    2013-02-01

    This paper aims to investigate the effect of socioeconomic status, as measured by education, on the survival of breast cancer patients treated on 10 studies conducted by the Cancer and Leukemia Group B. Sociodemographic data, including education, were reported by the patient at trial enrollment. Cox proportional hazards model stratified by treatment arm/study was used to examine the effect of education on survival among patients with early stage and metastatic breast cancer, after adjustment for known prognostic factors. The patient population included 1020 patients with metastatic disease and 5146 patients with early stage disease. Among metastatic patients, factors associated with poorer survival in the final multivariable model included African American race, never married, negative estrogen receptor status, prior hormonal therapy, visceral involvement, and bone involvement. Among early stage patients, significant factors associated with poorer survival included African American race, separated/widowed, post/perimenopausal, negative/unknown estrogen receptor status, negative progesterone receptor status, >4 positive nodes, tumor diameter >2 cm, and education. Having not completed high school was associated with poorer survival among early stage patients. Among metastatic patients, non-African American women who lacked a high school degree had poorer survival than other non-African American women, and African American women who lacked a high school education had better survival than educated African American women. Having less than a high school education is a risk factor for death among patients with early stage breast cancer who participated in a clinical trial, with its impact among metastatic patients being less clear. Post-trial survivorship plans need to focus on women with low social status, as measured by education. Copyright © 2011 John Wiley & Sons, Ltd.

  20. Non-convulsive status epilepticus: usefulness of clinical features in selecting patients for urgent EEG

    PubMed Central

    Husain, A; Horn, G; Jacobson, M

    2003-01-01

    Background: Non-convulsive status epilepticus (NCSE) is status epilepticus without obvious tonic–clonic activity. Patients with NCSE have altered mental state. An EEG is needed to confirm the diagnosis, but obtaining an EEG on every patient with altered mental state is not practical. Objective: To determine whether clinical features could be used to predict which patients were more likely to be in NCSE and thus in need of an urgent EEG. Methods: Over a six month period, all patients for whom an urgent EEG was ordered to identify NCSE were enrolled. Neurology residents examined the patients and filled out a questionnaire without knowledge of the EEG results. The patients were divided into two groups, NCSE and non-NCSE, depending on the EEG result. The clinical features were compared between the two groups. The sensitivity and specificity of the features were calculated. Results: 48 patients were enrolled, 12 in NCSE and 36 not in NCSE. Remote risk factors for seizures, severely impaired mental state, and ocular movement abnormalities were seen significantly more often in the NCSE group. The combined sensitivity of remote risk factors for seizures and ocular movement abnormalities was 100%. Conclusions: There are certain clinical features that are more likely to be present in patients in NCSE compared with other types of encephalopathy. Either remote risk factors for seizures or ocular movement abnormalities were seen in all patients in NCSE. These features may be used to select which patients should have an urgent EEG. PMID:12531946

  1. Leukogram Profile and Clinical Status in vivax and falciparum Malaria Patients from Colombia

    PubMed Central

    Tobón-Castaño, Alberto; Mesa-Echeverry, Esteban; Miranda-Arboleda, Andrés Felipe

    2015-01-01

    Introduction. Hematological alterations are frequent in malaria patients; the relationship between alterations in white blood cell counts and clinical status in malaria is not well understood. In Colombia, with low endemicity and unstable transmission for malaria, with malaria vivax predominance, the hematologic profile in malaria patients is not well characterized. The aim of this study was to characterize the leukogram in malaria patients and to analyze its alterations in relation to the clinical status. Methods. 888 leukogram profiles of malaria patients from different Colombian regions were studied: 556 with P. falciparum infection (62.6%), 313 with P. vivax infection (35.2%), and 19 with mixed infection by these species (2.1%). Results. Leukocyte counts at diagnosis were within normal range in 79% of patients and 18% had leucopenia; the most frequent alteration was lymphopenia (54%) followed by monocytosis (11%); the differential granulocyte count in 298 patients revealed eosinophilia (15%) and high basophil counts (8%). Leukocytosis, eosinopenia, and neutrophilia were associated with clinical complications. The utility of changes in leukocyte counts as markers of severity should be explored in depth. A better understanding of these hematological parameters will allow their use in prompt diagnosis of malaria complications and monitoring treatment response. PMID:26664413

  2. Leukogram Profile and Clinical Status in vivax and falciparum Malaria Patients from Colombia.

    PubMed

    Tobón-Castaño, Alberto; Mesa-Echeverry, Esteban; Miranda-Arboleda, Andrés Felipe

    2015-01-01

    Introduction. Hematological alterations are frequent in malaria patients; the relationship between alterations in white blood cell counts and clinical status in malaria is not well understood. In Colombia, with low endemicity and unstable transmission for malaria, with malaria vivax predominance, the hematologic profile in malaria patients is not well characterized. The aim of this study was to characterize the leukogram in malaria patients and to analyze its alterations in relation to the clinical status. Methods. 888 leukogram profiles of malaria patients from different Colombian regions were studied: 556 with P. falciparum infection (62.6%), 313 with P. vivax infection (35.2%), and 19 with mixed infection by these species (2.1%). Results. Leukocyte counts at diagnosis were within normal range in 79% of patients and 18% had leucopenia; the most frequent alteration was lymphopenia (54%) followed by monocytosis (11%); the differential granulocyte count in 298 patients revealed eosinophilia (15%) and high basophil counts (8%). Leukocytosis, eosinopenia, and neutrophilia were associated with clinical complications. The utility of changes in leukocyte counts as markers of severity should be explored in depth. A better understanding of these hematological parameters will allow their use in prompt diagnosis of malaria complications and monitoring treatment response.

  3. Thank you to Virology Journal's peer reviewers in 2013

    PubMed Central

    2014-01-01

    The editors of Virology Journal would like to thank all our reviewers who have contributed to the journal in Volume 10 (2013). The success of any scientific journal depends on an effective and strict peer review process and Virology Journal could not operate without your contribution. We are grateful to the large number of reviewers (1026 to be exact!), who have done a great job in not only lifting the quality of the journal’s scientific peer reviewing process, but also helped us to achieve our goal of a median time to first decision of just 35 days. Our record time from submission to online, open access, publication in 2013 was 22 days for a Research Article [1] and 28 days for a Review [2]. This is a great achievement by any standard. We look forward to your continuous support of Virology Journal either as an invited reviewer or a contributing author in the years to come.

  4. How the American Society for Virology was founded.

    PubMed

    Joklik, Wolfang K; Grossberg, Sidney E

    2006-01-05

    The American Society for Virology, the very first such Society to be formed anywhere, was founded at a meeting of some 40 virologists at Chicago O'Hare International airport on June 9, 1981. They met after a decade and a half of intense discussion that originated at the 9th International Congress of Microbiology in Moscow in 1966 when a small group of virologists requested the International Association of Microbiological Societies to form a Virology Section within IAMS, and this request was rejected. Virologists therefore held their own First International Congress of Virology in Helsinki in 1968 which was very successful and generated intense informal discussion among leading virologists in this country as to the desirability of founding an American society for virologists. Proposals were circulated and discussed which resulted in the informal Chicago meeting that created the mechanism for founding the ASV and organizing its 1st Annual Meeting at Cornell in Ithaca in August 1982.

  5. Immunological/virological peripheral blood biomarkers and distinct patterns of sleeping quality in chronic hepatitis C patients.

    PubMed

    de Almeida, C M O; de Lima, T A; Castro, D B; Torres, K L; da Silva Braga, W; Peruhype-Magalhães, V; Teixeira-Carvalho, A; Martins-Filho, O A; Malheiro, A

    2011-05-01

    The rational of this study we intended to investigate whether the peripheral blood immunological/virological biomarkers were associated with distinct patterns of sleeping quality in patients with chronic hepatitis C-(HCV). Distinct well-established indexes/scores were used to categorize the sleeping quality of HCV patients, including the Pittsburgh Sleep Quality Index (PSQI), Epworth Sleepiness Scale and Fatigue Severity Scores. Our findings demonstrated that HCV patients classified as 'good sleeper' displayed an enhanced frequency of circulating CD8(+) T cells, lower frequency of activated (CD69(+)) neutrophils and eosinophils but enhanced frequency of activated lymphocytes besides lower seric levels of IL-4/IL-8/IL-10 but higher levels of IL-12, besides lower HCV virus load and lower anti-HCV IgG levels. In contrast, HCV patients classified as 'poor sleeper' displayed enhanced levels of activated neutrophils and eosinophils but lower frequency of activated lymphocytes, higher seric levels of IL-6/TNF-α/IL-10 but lower levels of IL-12 besides higher HCV virus load and increased anti-HCV IgG levels. Positive correlation was further confirmed by the relationship between the leucocyte activation status, the cytokine levels, the HCV viral load and the anti-HCV IgG reactivity with the PSQI indexes. Analysis of cytokine signature curves demonstrated that lower frequency of IL-10 was observed in HCV patients classified as 'good sleepers', whereas enhanced frequency of IL-6 was found HCV patients classified as 'poor sleepers'. In conclusion, our data suggest that immunological biomarkers (leucocytes activation status and seric cytokines levels) are likely to be associated with sleeping quality patterns in HCV patients, suggesting their putative use for clinical monitoring purposes.

  6. A text mining approach to the prediction of disease status from clinical discharge summaries.

    PubMed

    Yang, Hui; Spasic, Irena; Keane, John A; Nenadic, Goran

    2009-01-01

    OBJECTIVE The authors present a system developed for the Challenge in Natural Language Processing for Clinical Data-the i2b2 obesity challenge, whose aim was to automatically identify the status of obesity and 15 related co-morbidities in patients using their clinical discharge summaries. The challenge consisted of two tasks, textual and intuitive. The textual task was to identify explicit references to the diseases, whereas the intuitive task focused on the prediction of the disease status when the evidence was not explicitly asserted. DESIGN The authors assembled a set of resources to lexically and semantically profile the diseases and their associated symptoms, treatments, etc. These features were explored in a hybrid text mining approach, which combined dictionary look-up, rule-based, and machine-learning methods. MEASUREMENTS The methods were applied on a set of 507 previously unseen discharge summaries, and the predictions were evaluated against a manually prepared gold standard. The overall ranking of the participating teams was primarily based on the macro-averaged F-measure. RESULTS The implemented method achieved the macro-averaged F-measure of 81% for the textual task (which was the highest achieved in the challenge) and 63% for the intuitive task (ranked 7(th) out of 28 teams-the highest was 66%). The micro-averaged F-measure showed an average accuracy of 97% for textual and 96% for intuitive annotations. CONCLUSIONS The performance achieved was in line with the agreement between human annotators, indicating the potential of text mining for accurate and efficient prediction of disease statuses from clinical discharge summaries.

  7. Clinical Relevance of Telomere Status and Telomerase Activity in Colorectal Cancer.

    PubMed

    Fernández-Marcelo, Tamara; Sánchez-Pernaute, Andrés; Pascua, Irene; De Juan, Carmen; Head, Jacqueline; Torres-García, Antonio-José; Iniesta, Pilar

    2016-01-01

    The role of telomeres and telomerase in colorectal cancer (CRC) is well established as the major driving force in generating chromosomal instability. However, their potential as prognostic markers remains unclear. We investigated the outcome implications of telomeres and telomerase in this tumour type. We considered telomere length (TL), ratio of telomere length in cancer to non-cancer tissue (T/N ratio), telomerase activity and TERT levels; their relation with clinical variables and their role as prognostic markers. We analyzed 132 CRCs and paired non-cancer tissues. Kaplan-Meier curves for disease-free survival were calculated for TL, T/N ratio, telomerase activity and TERT levels. Overall, tumours had shorter telomeres than non-tumour tissues (P < 0.001) and more than 80% of CRCs displayed telomerase activity. Telomere lengths of non-tumour tissues and CRCs were positively correlated (P < 0.001). Considering telomere status and clinical variables, the lowest degree of telomere shortening was shown by tumours located in the rectum (P = 0.021). Regarding prognosis studies, patients with tumours showing a mean TL < 6.35 Kb experienced a significantly better clinical evolution (P < 0.001) and none of them with the highest degree of tumour telomere shortening relapsed during the follow-up period (P = 0.043). The mean TL in CRCs emerged as an independent prognostic factor in the Cox analysis (P = 0.017). Telomerase-positive activity was identified as a marker that confers a trend toward a poor prognosis. In CRC, our results support the use of telomere status as an independent prognostic factor. Telomere status may contribute to explaining the different molecular identities of this tumour type.

  8. Clinical presentation and visual status of retinitis pigmentosa patients: a multicenter study in southwestern Nigeria

    PubMed Central

    Onakpoya, Oluwatoyin Helen; Adeoti, Caroline Olufunlayo; Oluleye, Tunji Sunday; Ajayi, Iyiade Adeseye; Majengbasan, Timothy; Olorundare, Olayemi Kolawole

    2016-01-01

    Background To review the visual status and clinical presentation of patients with retinitis pigmentosa (RP). Methodology Multicenter, retrospective, and analytical review was conducted of the visual status and clinical characteristics of patients with RP at first presentation from January 2007 to December 2011. Main outcome measure was the World Health Organization’s visual status classification in relation to sex and age at presentation. Data analysis by SPSS (version 15) and statistical significance was assumed at P<0.05. Results One hundred and ninety-two eyes of 96 patients with mean age of 39.08±18.5 years and mode of 25 years constituted the study population; 55 (57.3%) were males and 41 (42.7%) females. Loss of vision 67 (69.8%) and night blindness 56 (58.3%) were the leading symptoms. Twenty-one (21.9%) patients had a positive family history, with RP present in their siblings 15 (71.4%), grandparents 11 (52.3%), and parents 4 (19.4%). Forty (41.7%) were blind at presentation and 23 (24%) were visually impaired. Blindness in six (15%) patients was secondary to glaucoma. Retinal vascular narrowing and retinal pigmentary changes of varying severity were present in all patients. Thirty-five (36.5%) had maculopathy, 36 (37.5%) refractive error, 19 (20%) lenticular opacities, and eleven (11.5%) had glaucoma. RP was typical in 85 patients (88.5%). Older patients had higher rates of blindness at presentation (P=0.005); blindness and visual impairment rate at presentation were higher in males than females (P=0.029). Conclusion Clinical presentation with advanced diseases, higher blindness rate in older patients, sex-related difference in blindness/visual impairment rates, as well as high glaucoma blindness in RP patients requires urgent attention in southwestern Nigeria. PMID:27601870

  9. Clinical presentation and visual status of retinitis pigmentosa patients: a multicenter study in southwestern Nigeria.

    PubMed

    Onakpoya, Oluwatoyin Helen; Adeoti, Caroline Olufunlayo; Oluleye, Tunji Sunday; Ajayi, Iyiade Adeseye; Majengbasan, Timothy; Olorundare, Olayemi Kolawole

    2016-01-01

    To review the visual status and clinical presentation of patients with retinitis pigmentosa (RP). Multicenter, retrospective, and analytical review was conducted of the visual status and clinical characteristics of patients with RP at first presentation from January 2007 to December 2011. Main outcome measure was the World Health Organization's visual status classification in relation to sex and age at presentation. Data analysis by SPSS (version 15) and statistical significance was assumed at P<0.05. One hundred and ninety-two eyes of 96 patients with mean age of 39.08±18.5 years and mode of 25 years constituted the study population; 55 (57.3%) were males and 41 (42.7%) females. Loss of vision 67 (69.8%) and night blindness 56 (58.3%) were the leading symptoms. Twenty-one (21.9%) patients had a positive family history, with RP present in their siblings 15 (71.4%), grandparents 11 (52.3%), and parents 4 (19.4%). Forty (41.7%) were blind at presentation and 23 (24%) were visually impaired. Blindness in six (15%) patients was secondary to glaucoma. Retinal vascular narrowing and retinal pigmentary changes of varying severity were present in all patients. Thirty-five (36.5%) had maculopathy, 36 (37.5%) refractive error, 19 (20%) lenticular opacities, and eleven (11.5%) had glaucoma. RP was typical in 85 patients (88.5%). Older patients had higher rates of blindness at presentation (P=0.005); blindness and visual impairment rate at presentation were higher in males than females (P=0.029). Clinical presentation with advanced diseases, higher blindness rate in older patients, sex-related difference in blindness/visual impairment rates, as well as high glaucoma blindness in RP patients requires urgent attention in southwestern Nigeria.

  10. Oxidative stress status in Chinese women with different clinical phenotypes of polycystic ovary syndrome.

    PubMed

    Zhang, Renjiao; Liu, Hongwei; Bai, Huai; Zhang, Yujin; Liu, Qingqing; Guan, Linbo; Fan, Ping

    2017-01-01

    To determine oxidative stress status and its association with clinical and metabolic parameters in Chinese women with different clinical phenotypes of polycystic ovary syndrome (PCOS). A cross-sectional study. A total of 544 patients with PCOS and 468 control women were included. The total oxidant status (TOS) was determined using a microplate colorimetric method. Total antioxidant capacity (T-AOC), oxidative stress index (OSI, the ratios of TOS to T-AOC) and clinical, hormonal and metabolic parameters were also analysed. TOS and OSI were significantly higher in each of the four PCOS phenotypes based on the Rotterdam criteria than in the control women and higher in patients with hyperandrogenism (HA) than in those without HA (P < 0·05). TOS, T-AOC and OSI were higher in lean patients than in lean controls (P < 0·05). These values, except OSI, were also higher in overweight/obese patients than in lean patients, and lean or overweight/obese controls (P < 0·05). Multivariate regression analysis demonstrated that apolipoprotein (apo)A1, the Ferriman-Gallwey score, triglyceride (TG), oestradiol (E2 ), high-density lipoprotein cholesterol (HDL-C) and 2-h glucose levels were the main predictors of TOS; the Ferriman-Gallwey score, E2 , apoA1, TG and HDL-C levels were the main predictors of OSI. Patients with PCOS with HA have higher oxidative stress levels compared with those without HA. The increased oxidative stress in PCOS is related to HA status, increased plasma glucose, TG, HDL-C and E2 levels, decreased apoA1 concentrations and a relative shortage of antioxidant capacity. © 2016 John Wiley & Sons Ltd.

  11. Genetics of Autism Spectrum Disorder: Current Status and Possible Clinical Applications

    PubMed Central

    2015-01-01

    Autism spectrum disorder (ASD) is one of the most complex behavioral disorders with a strong genetic influence. The objectives of this article are to review the current status of genetic research in ASD, and to provide information regarding the potential candidate genes, mutations, and genetic loci possibly related to pathogenesis in ASD. Investigations on monogenic causes of ASD, candidate genes among common variants, rare de novo mutations, and copy number variations are reviewed. The current possible clinical applications of the genetic knowledge and their future possibilities are highlighted. PMID:26713075

  12. Thermal biology and physiology in clinical hyperthermia: current status and future needs.

    PubMed

    Li, G C

    1984-10-01

    The current status and needs of thermal biology and physiology as related to clinical hyperthermia are summarized. Emphasis is placed on heat-induced modification of blood flow and microenvironment in tissues, on the biological effects of heat and X-rays, and on the relationship between drug resistance, heat resistance, and thermotolerance in thermochemotherapy. Results from recent studies investigating the relationships between thermotolerance and heat shock proteins in tissue culture cell lines, in rodent tumors, and in normal tissues are presented. These data strongly suggest that the levels of Mr 70,000 heat shock protein can be used as an assay to predict the thermal sensitivity of tissues during fractionated hyperthermia.

  13. Rates of switching to second-line antiretroviral therapy and impact of delayed switching on immunologic, virologic, and mortality outcomes among HIV-infected adults with virologic failure in Rakai, Uganda.

    PubMed

    Ssempijja, Victor; Nakigozi, Gertrude; Chang, Larry; Gray, Ron; Wawer, Maria; Ndyanabo, Anthony; Kasule, Jingo; Serwadda, David; Castelnuovo, Barbara; Hoog, Anja Van't; Reynolds, Steven James

    2017-08-22

    Switch from first to second-line ART is recommended by WHO for patients with virologic failure. Delays in switching may contribute to accumulated drug resistance, advanced immunosuppression, increased morbidity and mortality. The 3rd 90' of UNAIDS 90:90:90 targets 90% viral suppression for persons on ART. We evaluated the rate of switching to second-line antiretroviral therapy (ART), and the impact of delayed switching on immunologic, virologic, and mortality outcomes in the Rakai Health Sciences Program (RHSP) Clinical Cohort Study which started providing ART in 2004 and implemented 6 monthly routine virologic monitoring beginning in 2005. Retrospective cohort study of HIV-infected adults on first-line ART who had two consecutive viral loads (VLs) >1000 copies/ml after 6 months on ART between June 2004 and June 2011 was studied for switching to second-line ART. Immunologic decline after virologic failure was defined as decrease in CD4 count of ≥50 cells/ul and virologic increase was defined as increase of 0.5 log 10 copies/ml. Competing risk models were used to summarize rates of switching to second-line ART while cox proportional hazard marginal structural models were used to assess the risk of virologic increase or immunologic decline associated with delay to switch first line ART failing patients. The cumulative incidence of switching at 6, 12, and 24 months following virologic failure were 30.2%, 44.6%, and 65.0%, respectively. The switching rate was increased with higher VL at the time of virologic failure; compared to those with VLs ≤ 5000 copies/ml, patients with VLs = 5001-10,000 copies/ml had an aHR = 1.81 (95% CI = 0.9-3.6), and patients with VLs > 10,000 copies/ml had an aHR = 3.38 (95%CI = 1.9-6.2). The switching rate was also increased with CD4 < 100 cells/ul at ART initiation, compared to those with CD4 ≥ 100 cells/ul (aHR = 2.30, 95% CI = 1.5-3.6). Mortality in patients not switched to second-line ART was 11

  14. [The virological supervision of drinking water quality--a review].

    PubMed

    Schulze, E

    1990-01-01

    Drinking-water must be free of pathogenic organisms; this challenge refers to pathogenic viruses too. In order to control virological aspects of water quality realistic and practicable monitoring procedures, esp. practical microbial assays, must be performed. They should include in all cases standard plate counts and counts of total or faecal coliform bacteria. Counts of coliphages in combination with standard plate counts and counts of coliform bacteria offer a practical and reliable indicator system for evaluating the virological safety of treated drinking-water supplies in the case of drinking-water reclaimed from contaminated raw water, esp. surface water.

  15. Serum DNA Motifs Predict Disease and Clinical Status in Multiple Sclerosis

    PubMed Central

    Beck, Julia; Urnovitz, Howard B.; Saresella, Marina; Caputo, Domenico; Clerici, Mario; Mitchell, William M.; Schütz, Ekkehard

    2010-01-01

    Using recently available mass sequencing and assembly technologies, we have been able to identify and quantify unique cell-free DNA motifs in the blood of patients with multiple sclerosis (MS). The most common MS clinical syndrome, relapsing-remitting MS (RRMS), is accompanied by a unique fingerprint of both inter- and intragenic cell-free circulating nucleic acids as specific DNA sequences that provide significant clinical sensitivity and specificity. Coding genes that are differentially represented in MS serum encode cytoskeletal proteins, brain-expressed regulators of growth, and receptors involved in nervous system signal transduction. Although coding genes distinguish RRMS and its clinical activity, several repeat sequences, such as the L1M family of LINE elements, are consistently different in all MS patients and clinical status versus the normal database. These data demonstrate that DNA motifs observed in serum are characteristic of RRMS and disease activity and are promising as a clinical tool in monitoring patient responses to treatment modalities. PMID:20228264

  16. Clinical pharmacology and therapeutics in undergraduate medical education in the UK: current status.

    PubMed Central

    Walley, T; Bligh, J; Orme, M; Breckenridge, A

    1994-01-01

    1. Medical undergraduate education is currently undergoing major changes in the UK in response to calls for the development of a core curriculum. Teaching in clinical pharmacology and therapeutics will also change to meet these demands. A postal survey was conducted to assess the current status of teaching in these subjects. 2. A questionnaire based on previous similar surveys conducted elsewhere was sent to departments or individuals in 27 medical schools in the UK; 22 (81%) replied. 3. Departmental priorities were defined as (in order): clinical research, undergraduate teaching, basic scientific research and clinical service provision. No change in these priorities in the future was foreseen by respondents. 4. Teaching methods were for the most part traditional, with the lecture as the most widely used and important technique. Specific clinical teaching was conducted by some and was considered very important by them. Teaching by problem solving was much less common. 5. Respondents were asked for free text comments; many of the remarks suggested dissatisfaction with the resources and time currently available for teaching in clinical pharmacology and therapeutics. Some expressed significant concerns that their teaching commitment would be reduced further by the development of the core curriculum. PMID:8186059

  17. Context: An Algorithm for Determining Negation, Experiencer, and Temporal Status from Clinical Reports

    PubMed Central

    Harkema, Henk; Dowling, John N.; Thornblade, Tyler; Chapman, Wendy W.

    2009-01-01

    In this paper we describe an algorithm called ConText for determining whether clinical conditions mentioned in clinical reports are negated, hypothetical, historical, or experienced by someone other than the patient. The algorithm infers the status of a condition with regard to these properties from simple lexical clues occurring in the context of the condition. The discussion and evaluation of the algorithm presented in this paper address the questions of whether a simple surface-based approach which has been shown to work well for negation can be successfully transferred to other contextual properties of clinical conditions, and to what extent this approach is portable among different clinical report types. In our study we find that ConText obtains reasonable to good performance for negated, historical, and hypothetical conditions across all report types that contain such conditions. Conditions experienced by someone other than the patient are very rarely found in our report set. A comprehensive solution to the problem of determining whether a clinical condition is historical or recent requires knowledge above and beyond the surface clues picked up by ConText. PMID:19435614

  18. Role of the virology laboratory in diagnosis and management of patients with central nervous system disease.

    PubMed Central

    Chonmaitree, T; Baldwin, C D; Lucia, H L

    1989-01-01

    A number of viruses cause acute central nervous system disease. The two major clinical presentations are aseptic meningitis and the less common meningoencephalitis. Clinical virology laboratories are now more widely available than a decade ago; they can be operated on a modest scale and can be tailored to the needs of the patients they serve. Most laboratories can provide diagnostic information on diseases caused by enteroviruses, herpesviruses, and human immunodeficiency virus. Antiviral therapy for herpes simplex virus is now available. By providing a rapid diagnostic test or isolation of the virus or both, the virology laboratory plays a direct role in guiding antiviral therapy for patients with herpes simplex encephalitis. Although there is no specific drug available for enteroviruses, attention needs to be paid to these viruses since they are the most common cause of nonbacterial meningitis and the most common pathogens causing hospitalization for suspected sepsis in young infants in the United States during the warm months of the year. When the virology laboratory maximizes the speed of viral detection or isolation, it can make a significant impact on management of these patients. Early viral diagnosis benefits patients with enteroviral meningitis, most of whom are hospitalized and treated for bacterial sepsis or meningitis or both; these patients have the advantage of early withdrawal of antibiotics and intravenous therapy, early hospital discharge, and avoidance of the risks and costs of unnecessary tests and treatment. Enteroviral infection in young infants also is a risk factor for possible long-term sequelae. For compromised patients, the diagnostic information helps in selecting specific immunoglobulin therapy. Good communication between the physician and the laboratory will result in the most benefit to patients with central nervous system viral infection. PMID:2644021

  19. Baseline clinical status as a predictor of methylprednisolone response in multiple sclerosis relapses.

    PubMed

    Ramo-Tello, Cristina; Tintoré, Mar; Rovira, Alex; Ramió-Torrenta, Luis; Brieva, Luis; Saiz, Albert; Cano, Antonio; Carmona, Olga; Hervás, Jose V; Grau-López, Laia

    2016-01-01

    To date, there are no available factors to predict the outcome after multiple sclerosis relapse. To investigate factors that may be useful for predicting response to methylprednisolone treatment, following a relapse of multiple sclerosis (MS). The study included 48 MS patients enrolled in a double-blind multicenter trial to receive intravenous versus oral high-dose methylprednisolone treatment. Associations were sought between the disability status prior to relapse and the relapse severity, determined by changes in the Expanded Disability Status Scale (EDSS) score, as well as the improvements after treatment. We also analyzed the relationships between the number of magnetic resonance imaging (MRI) gadolinium-enhancing lesions (Gd+) and improvement. A higher EDSS score before relapse was associated with more severe relapses (p = 0.04) and less marked improvement (odds ratio (OR) 1.8; 95% CI (1.2-2.2); p = 0.05) after methylprednisolone treatment. Relapse severity (p = 0.29) and the number of Gd+ lesions at relapse (p = 0.41) were not related with improvement. Clinical baseline status prior to MS relapse is a predictor of response to methylprednisolone treatment. © The Author(s), 2015.

  20. The Theory and Fundamentals of Bioimpedance Analysis in Clinical Status Monitoring and Diagnosis of Diseases

    PubMed Central

    Khalil, Sami F.; Mohktar, Mas S.; Ibrahim, Fatimah

    2014-01-01

    Bioimpedance analysis is a noninvasive, low cost and a commonly used approach for body composition measurements and assessment of clinical condition. There are a variety of methods applied for interpretation of measured bioimpedance data and a wide range of utilizations of bioimpedance in body composition estimation and evaluation of clinical status. This paper reviews the main concepts of bioimpedance measurement techniques including the frequency based, the allocation based, bioimpedance vector analysis and the real time bioimpedance analysis systems. Commonly used prediction equations for body composition assessment and influence of anthropometric measurements, gender, ethnic groups, postures, measurements protocols and electrode artifacts in estimated values are also discussed. In addition, this paper also contributes to the deliberations of bioimpedance analysis assessment of abnormal loss in lean body mass and unbalanced shift in body fluids and to the summary of diagnostic usage in different kinds of conditions such as cardiac, pulmonary, renal, and neural and infection diseases. PMID:24949644

  1. Vitamin D Status – A Clinical Review with Implications for the Pelvic Floor

    PubMed Central

    PARKER-AUTRY, Candace Y.; BURGIO, Kathryn L.; RICHTER, Holly E.

    2013-01-01

    Vitamin D is a micronutrient vital in calcium homeostasis and musculoskeletal health. Vitamin D insufficiency is a common variant of vitamin D deficiency which has clinical signs of rickets and osteomalacia. The clinical significance of vitamin D insufficiency is being explored in several medical conditions. However, the most robust work suggests a role in musculoskeletal disease. The pelvic floor is a unique part of the body whose function is dependent on interrelationships between muscle, nerve, connective tissue, and bone. Pelvic floor disorders result when these relationships are disrupted. This paper reviews current knowledge regarding insufficient vitamin D nutritional status, the importance of vitamin D in muscle function, and how insufficient or deficient vitamin D levels may play a role in the function of the female pelvic floor. PMID:22415704

  2. The theory and fundamentals of bioimpedance analysis in clinical status monitoring and diagnosis of diseases.

    PubMed

    Khalil, Sami F; Mohktar, Mas S; Ibrahim, Fatimah

    2014-06-19

    Bioimpedance analysis is a noninvasive, low cost and a commonly used approach for body composition measurements and assessment of clinical condition. There are a variety of methods applied for interpretation of measured bioimpedance data and a wide range of utilizations of bioimpedance in body composition estimation and evaluation of clinical status. This paper reviews the main concepts of bioimpedance measurement techniques including the frequency based, the allocation based, bioimpedance vector analysis and the real time bioimpedance analysis systems. Commonly used prediction equations for body composition assessment and influence of anthropometric measurements, gender, ethnic groups, postures, measurements protocols and electrode artifacts in estimated values are also discussed. In addition, this paper also contributes to the deliberations of bioimpedance analysis assessment of abnormal loss in lean body mass and unbalanced shift in body fluids and to the summary of diagnostic usage in different kinds of conditions such as cardiac, pulmonary, renal, and neural and infection diseases.

  3. Virologic testing in bronchiolitis: does it change management decisions and predict outcomes?

    PubMed

    Stollar, Fabiola; Alcoba, Gabriel; Gervaix, Alain; Argiroffo, Constance Barazzone

    2014-11-01

    The aim of this study was to evaluate the clinical, therapeutic, laboratory, and radiological differences between respiratory syncytial virus (RSV) and non-RSV bronchiolitis in order to assess if the prior knowledge of viral etiology changed management decisions and would be able to predict outcomes. Medical charts of children <1 year admitted to the emergency department with bronchiolitis during two RSV seasons (2010-2012) were reviewed. We analyzed 221 episodes of bronchiolitis. The percentage of exams performed (95 % confidence interval (CI) 0.74-2.52), abnormal laboratory and radiological findings (95 % CI 0.53-16.89) did not differ between groups. RSV bronchiolitis had a more severe clinical course. However, virologic testing for RSV had low specificity in identifying at-risk patients for hospitalization, longer hospital length of stay, and need of oxygen therapy and nasogastric tube (44, 40, 42, and 35 %, respectively), and while statistically significant, the positive likelihood ratios were only slightly greater than 1. Although RSV bronchiolitis has a more severe clinical course, virologic testing does not help in management decisions, and at an individual level, as a performance test, it seems insufficient to precisely predict outcomes.

  4. Comparison of Diffusion Tensor Tractography and Motor Evoked Potentials for the Estimation of Clinical Status in Subacute Stroke.

    PubMed

    Chun, Kwang-Soo; Lee, Yong-Taek; Park, Jong-Wan; Lee, Joon-Youn; Park, Chul-Hyun; Yoon, Kyung Jae

    2016-02-01

    To compare diffusion tensor tractography (DTT) and motor evoked potentials (MEPs) for estimation of clinical status in patients in the subacute stage of stroke. Patients with hemiplegia due to stroke who were evaluated using both DTT and MEPs between May 2012 and April 2015 were recruited. Clinical assessments investigated upper extremity motor and functional status. Motor status was evaluated using Medical Research Council grading and the Fugl-Meyer Assessment of upper limb and hand (FMA-U and FMA-H). Functional status was measured using the Modified Barthel Index (MBI). Patients were classified into subgroups according to DTT findings, MEP presence, fractional anisotropy (FA) value, FA ratio (rFA), and central motor conduction time (CMCT). Correlations of clinical assessments with DTT parameters and MEPs were estimated. Fifty-five patients with hemiplegia were recruited. In motor assessments (FMA-U), MEPs had the highest sensitivity and negative predictive value (NPV) as well as the second highest specificity and positive predictive value (PPV). CMCT showed the highest specificity and PPV. Regarding functional status (MBI), FA showed the highest sensitivity and NPV, whereas CMCT had the highest specificity and PPV. Correlation analysis showed that the resting motor threshold (RMT) ratio was strongly associated with motor status of the upper limb, and MEP parameters were not associated with MBI. DTT and MEPs could be suitable complementary modalities for analyzing the motor and functional status of patients in the subacute stage of stroke. The RMT ratio was strongly correlated with motor status.

  5. Clinical and neuropsychiatric status in children with Williams-Beuren Syndrome in Upper Egypt.

    PubMed

    Saad, Khaled; Abdelrahman, Ahmed A; Abdallah, Alameldin M; Othman, Hisham A K; Badry, Reda

    2013-12-01

    The aim of this study was to evaluate and explore the clinical, neuropsychiatric status and EEG pattern in a series of children with Williams-Beuren syndrome (WBS) in Assiut, Upper Egypt. We aimed to provide a comprehensive data comparable to what has been published, to enable us to make comparisons across different cultural areas. This will contribute to a better definition of the neuropsychiatric features that may be specific to WBS that allows early and better detection and management of those children. A series of 17 WBS children patients who consulted at our hospital were evaluated. The patients were assessed mainly for clinical, neurological, psychiatric and EEG status. We performed FISH for all patients. All patients had a deletion of the long arm of chromosome 7 (7q 11.23). All had elfin facies. Neurological examination revealed hypotonia in 25% of patients and rigidity (12.50%), brisk deep tendon reflexes (25%), abnormal plantar response (12.50%). Cerebellar and extrapyramidal signs were frequent: dysmetria (31.25%), dysdiadochokinesia (31.25%) and ataxia (18.75%). Epileptic seizures were present in 31.25% of patients and ADHD (37.5%). Autism was present in one patient. EEG abnormalities were present in 31.25%. Congenital cardiopathies were present in 62.50%. Our data showed that WBS children had multi-systemic clinical complications and the management of those patients requires the pediatrician to understand the natural course of this condition, awareness of potential medical problems, and periodic baseline clinical, neuropsychiatric evaluations, monitoring, and rapid intervention to improve the medical care for patients who have WBS. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. The status of vaccine availability and associated factors in Tshwane government clinics.

    PubMed

    Ngcobo, Ntombenhle Judith; Kamupira, Mercy G

    2017-05-24

    Vaccines have greatly contributed to the control of vaccine-preventable diseases and to human development. Efforts by many countries to introduce new vaccines are a significant move towards achieving the sustainable development goal for health. However, effective vaccine supply chains that ensure an uninterrupted supply of vaccines are pivotal to attaining universal access to life-saving vaccines and sustainable development. The introduction of new vaccines puts a strain on supply chains; South Africa (SA) is no exception, as there are indications of vaccine stock-outs in clinics. To establish the status of vaccine availability and associated factors in government health facilities of Tshwane Health District in Gauteng Province, SA. A cross-sectional study was conducted in a sample of randomly selected government clinics in the Tshwane health district of Gauteng Province. Data were collected using a structured measurement instrument in participating clinics. Data were analysed using Excel-based software (Microsoft, USA). A total of 31 clinics participated. In the preceding 12 months, clinics had experienced vaccine stock-outs, especially of the three newer vaccines: pneumococcal conjugate vaccine, rotavirus and Pentaxim. These were also out of stock for a long duration; for over 2 weeks in a majority of clinics. The causes of vaccine stock-outs were: poor management of stock, district depot out of stock, unreliable deliveries, lack of pharmacy assistants and limited fridge capacity. Further burdening the situation is the ineffective emergency-ordering system. Significant shortages of vaccines, which are essential drugs, occur in Tshwane government clinics. Vaccine supply chain issues and vaccine shortages should be treated as a priority at all levels of the healthcare system; therefore, a similar study should be conducted at national level. It is recommended that the vaccine supply chain should be restructured and overhauled with the use of advances in technology

  7. Vitamin D Status of Clinical Practice Populations at Higher Latitudes: Analysis and Applications

    PubMed Central

    Genuis, Stephen J.; Schwalfenberg, Gerry K.; Hiltz, Michelle N.; Vaselenak, Sharon A.

    2009-01-01

    Background: Inadequate levels of vitamin D (VTD) throughout the life cycle from the fetal stage to adulthood have been correlated with elevated risk for assorted health afflictions. The purpose of this study was to ascertain VTD status and associated determinants in three clinical practice populations living in Edmonton, Alberta, Canada - a locale with latitude of 53°30’N, where sun exposure from October through March is often inadequate to generate sufficient vitamin D. Methods: To determine VTD status, 1,433 patients from three independent medical offices in Edmonton had levels drawn for 25(OH)D as part of their medical assessment between Jun 2001 and Mar 2007. The relationship between demographic data and lifestyle parameters with VTD status was explored. 25(OH)D levels were categorized as follows: (1) Deficient: <40 nmol/L; (2) Insufficient (moderate to mild): 40 to <80 nmol/L; and (3) Adequate: 80–250 nmol/L. Any cases <25 nmol/L were subcategorized as severely deficient for purposes of further analysis. Results: 240 (16.75% of the total sample) of 1,433 patients were found to be VTD ‘deficient’ of which 48 (3.35% of the overall sample) had levels consistent with severe deficiency. 738 (51.5% of the overall sample) had ‘insufficiency’ (moderate to mild) while only 31.75% had ‘adequate’ 25(OH)D levels. The overall mean for 25(OH) D was 68.3 with SD=28.95. VTD status was significantly linked with demographic and lifestyle parameters including skin tone, fish consumption, milk intake, sun exposure, tanning bed use and nutritional supplementation. Conclusion: A high prevalence of hypovitaminosis-D was found in three clinical practice populations living in Edmonton. In view of the potential health sequelae associated with widespread VTD inadequacy, strategies to facilitate translation of emerging epidemiological information into clinical intervention need to be considered in order to address this public health issue. A suggested VTD supplemental

  8. Improved virologic suppression with HIV subspecialty care in a large prison system using telemedicine: an observational study with historical controls.

    PubMed

    Young, Jeremy D; Patel, Mahesh; Badowski, Melissa; Mackesy-Amiti, Mary Ellen; Vaughn, Pyrai; Shicker, Louis; Puisis, Michael; Ouellet, Lawrence J

    2014-07-01

    Correctional populations have an elevated human immunodeficiency virus (HIV) prevalence, yet many individuals lack access to subspecialty care. Our study showed that HIV-infected inmates had significantly greater virologic suppression and higher CD4 T-lymphocyte counts when managed by a multidisciplinary team of subspecialists conducting clinics via telemedicine. In other studies, these outcomes have been associated with reductions on HIV-related morbidity and mortality, as well as HIV transmission.

  9. Impact of postoperative glycemic control and nutritional status on clinical outcomes after total pancreatectomy

    PubMed Central

    Shi, Hao-Jun; Jin, Chen; Fu, De-Liang

    2017-01-01

    AIM To evaluate the impact of glycemic control and nutritional status after total pancreatectomy (TP) on complications, tumor recurrence and overall survival. METHODS Retrospective records of 52 patients with pancreatic tumors who underwent TP were collected from 2007 to 2015. A series of clinical parameters collected before and after surgery, and during the follow-up were evaluated. The associations of glycemic control and nutritional status with complications, tumor recurrence and long-term survival were determined. Risk factors for postoperative glycemic control and nutritional status were identified. RESULTS High early postoperative fasting blood glucose (FBG) levels (OR = 4.074, 95%CI: 1.188-13.965, P = 0.025) and low early postoperative prealbumin levels (OR = 3.816, 95%CI: 1.110-13.122, P = 0.034) were significantly associated with complications after TP. Postoperative HbA1c levels over 7% (HR = 2.655, 95%CI: 1.299-5.425, P = 0.007) were identified as one of the independent risk factors for tumor recurrence. Patients with postoperative HbA1c levels over 7% had much poorer overall survival than those with HbA1c levels less than 7% (9.3 mo vs 27.6 mo, HR = 3.212, 95%CI: 1.147-8.999, P = 0.026). Patients with long-term diabetes mellitus (HR = 15.019, 95%CI: 1.278-176.211, P = 0.031) and alcohol history (B = 1.985, SE = 0.860, P = 0.025) tended to have poor glycemic control and lower body mass index levels after TP, respectively. CONCLUSION At least 3 mo are required after TP to adapt to diabetes and recover nutritional status. Glycemic control appears to have more influence over nutritional status on long-term outcomes after TP. Improvement in glycemic control and nutritional status after TP is important to prevent early complications and tumor recurrence, and improve survival. PMID:28127200

  10. Comprehensive Determination of Prostate Tumor ETS Gene Status in Clinical Samples Using the CLIA Decipher Assay.

    PubMed

    Torres, Alba; Alshalalfa, Mohammed; Tomlins, Scott A; Erho, Nicholas; Gibb, Ewan A; Chelliserry, Jijumon; Lim, Lony; Lam, Lucia L C; Faraj, Sheila F; Bezerra, Stephania M; Davicioni, Elai; Yousefi, Kasra; Ross, Ashley E; Netto, George J; Schaeffer, Edward M; Lotan, Tamara L

    2017-05-01

    ETS family gene fusions are common in prostate cancer and molecularly define a tumor subset. ERG is the most commonly rearranged, leading to its overexpression, followed by ETV1, ETV4, and ETV5, and these alterations are generally mutually exclusive. We validated the Decipher prostate cancer assay to detect ETS alterations in a Clinical Laboratory Improvement Amendments-accredited laboratory. Benchmarking against ERG immunohistochemistry and ETV1/4/5 RNA in situ hybridization, we examined the accuracy, precision, and reproducibility of gene expression ETS models using formalin-fixed, paraffin-embedded samples. The m-ERG model achieved an area under curve of 95%, with 93% sensitivity and 98% specificity to predict ERG immunohistochemistry status. The m-ETV1, -ETV4, and -ETV5 models achieved areas under curve of 98%, 88%, and 99%, respectively. The models had 100% robustness for ETS status, and scores were highly correlated across sample replicates. Models predicted 41.5% of a prospective radical prostatectomy cohort (n = 4036) to be ERG(+), 6.3% ETV1(+), 1% ETV4(+), and 0.4% ETV5(+). Of prostate tumor biopsy samples (n = 509), 41.2% were ERG(+), 8.6% ETV1(+), 0.4% ETV4(+), and none ETV5(+). Higher Decipher risk status tumors were more likely to be ETS(+) (ERG or ETV1/4/5) in the radical prostatectomy and the biopsy cohorts (P < 0.05). These results support the utility of microarray-based ETS status prediction models for molecular classification of prostate tumors. Copyright © 2017 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  11. Children's marking of verbal -s by nonmainstream English dialect and clinical status.

    PubMed

    Cleveland, Lesli H; Oetting, Janna B

    2013-11-01

    Children's marking of verbal -s was examined by their dialect (African American English [AAE] vs. Southern White English [SWE]) and clinical status (specific language impairment [SLI] vs. typically developing [TD]) and as a function of 4 linguistic variables (verb regularity, negation, expression of a habitual activity, and expression of historical present tense). The data were language samples from 57 six-year-olds who varied by their dialect and clinical status (AAE: SLI = 14, TD = 12; SWE: SLI = 12, TD = 19). The AAE groups produced lower rates of marking than did the SWE groups, and the SWE SLI group produced lower rates of marking than did the SWE TD group. Although low numbers of verb contexts made it difficult to evaluate the linguistic variables, there was evidence of their influence, especially for verb regularity and negation. The direction and magnitude of the effects were often (but not always) consistent with what has been described in the adult dialect literature. Verbal -s can be used to help distinguish children with and without SLI in SWE but not in AAE. Clinicians can apply these findings to other varieties of AAE and SWE and other dialects by considering rates of marking and the effects of linguistic variables on marking.

  12. Children’s Marking of Verbal –s by Nonmainstream English Dialect and Clinical Status

    PubMed Central

    Cleveland, Lesli H.; Oetting, Janna B.

    2015-01-01

    Purpose Children’s marking of verbal –s was examined by their dialect (African American English [AAE] vs. Southern White English [SWE]) and clinical status (specific language impairment [SLI] vs. typically developing [TD]) and as a function of 4 linguistic variables (verb regularity, negation, expression of a habitual activity, and expression of historical present tense). Method The data were language samples from 57 six-year-olds who varied by their dialect and clinical status (AAE: SLI = 14, TD = 12; SWE: SLI = 12, TD = 19). Results The AAE groups produced lower rates of marking than did the SWE groups, and the SWE SLI group produced lower rates of marking than did the SWE TD group. Although low numbers of verb contexts made it difficult to evaluate the linguistic variables, there was evidence of their influence, especially for verb regularity and negation. The direction and magnitude of the effects were often (but not always) consistent with what has been described in the adult dialect literature. Conclusion Verbal –s can be used to help distinguish children with and without SLI in SWE but not in AAE. Clinicians can apply these findings to other varieties of AAE and SWE and other dialects by considering rates of marking and the effects of linguistic variables on marking. PMID:23813205

  13. Predicting Cognitive Function from Clinical Measures of Physical Function and Health Status in Older Adults

    PubMed Central

    Bolandzadeh, Niousha; Kording, Konrad; Salowitz, Nicole; Davis, Jennifer C.; Hsu, Liang; Chan, Alison; Sharma, Devika; Blohm, Gunnar; Liu-Ambrose, Teresa

    2015-01-01

    Introduction Current research suggests that the neuropathology of dementia—including brain changes leading to memory impairment and cognitive decline—is evident years before the onset of this disease. Older adults with cognitive decline have reduced functional independence and quality of life, and are at greater risk for developing dementia. Therefore, identifying biomarkers that can be easily assessed within the clinical setting and predict cognitive decline is important. Early recognition of cognitive decline could promote timely implementation of preventive strategies. Methods We included 89 community-dwelling adults aged 70 years and older in our study, and collected 32 measures of physical function, health status and cognitive function at baseline. We utilized an L1–L2 regularized regression model (elastic net) to identify which of the 32 baseline measures were strongly predictive of cognitive function after one year. We built three linear regression models: 1) based on baseline cognitive function, 2) based on variables consistently selected in every cross-validation loop, and 3) a full model based on all the 32 variables. Each of these models was carefully tested with nested cross-validation. Results Our model with the six variables consistently selected in every cross-validation loop had a mean squared prediction error of 7.47. This number was smaller than that of the full model (115.33) and the model with baseline cognitive function (7.98). Our model explained 47% of the variance in cognitive function after one year. Discussion We built a parsimonious model based on a selected set of six physical function and health status measures strongly predictive of cognitive function after one year. In addition to reducing the complexity of the model without changing the model significantly, our model with the top variables improved the mean prediction error and R-squared. These six physical function and health status measures can be easily implemented in a

  14. Clinical and Virological Outcome of European Patients Infected With HIV

    ClinicalTrials.gov

    2016-02-29

    HIV; Hepatitis B; Hepatitis C; AIDS; Coinfection; Cardiovascular Diseases; Diabetes Mellitus; Acidosis, Lactic; Renal Insufficiency; Fractures, Bone; End Stage Liver Disease; Kidney Failure, Chronic; Proteinuria

  15. [Virological and clinical features of patients with sporadic hepatitis C].

    PubMed

    Tang, Z; Wang, Y; Yu, Z; Yang, D; Hao, L

    1997-06-01

    In this study, the transmission route in 16 sporadic hepatitis C (SHC) patients was investigated. Three of them were surgeons who had often had occupational needlestick accidents, another 3 had close household contact with their spouses who had been diagnosed as chronic posttransfusion viral hepatitis C (PTHC), and the remaining 5 had potential parenteral exposure such as tooth extraction, injection or inoculation and so on. Five patients with SHC didn't have such history, their transmission route was not determined. Our result showed a lower viremia level in patients with SHC when compared to PTHC patients (the serum dilutions for HCV RNA detection was 10-100 times in the former and 100-10000 times in the latter. P<0.01). Only 1 patient with SHC was anti-HCV positive. Comparing to PTHC, the patients with SHC in our study had milder liver demage and lower ALT levels, and most of them (10/16) were symptomless.

  16. [Anogenital warts: a clinical, pathological and virological study].

    PubMed

    Mataix Díaz, J; Betlloch Mas, I; Pastor Tomás, N; Bañuls Roca, J; Martínez, M T

    2008-12-01

    The objective of this study was to investigate the possible relationship between the presence of anogenital warts (AGW) in children and the sexual abuse as mode of transmission. Our series includes 8 patients with AGW who were treated in our hospital during the year 2007. A complete physical examination was carried out, including colposcopy or anoscopy, and samples were taken for histopathological examination and human papiloma virus (HPV) subtyping. We considered perinatal transmission as a possible route in two cases. Although sexual abuse was definitively confirmed in only one case, we observed some findings in four cases that led us to consider the possibility of sexual abuse. We did not consider the possibility of heteroinoculation or autoinoculation from common warts in any case. Our results have demonstrated the difficulty in assessing with certainty the source of HPV contamination in children with AGW.

  17. Concise Review: The Clinical Application of Mesenchymal Stem Cells for Musculoskeletal Regeneration: Current Status and Perspectives

    PubMed Central

    Steinert, Andre F.; Rackwitz, Lars; Gilbert, Fabian; Nöth, Ulrich

    2012-01-01

    Regenerative therapies in the musculoskeletal system are based on the suitable application of cells, biomaterials, and/or factors. For an effective approach, numerous aspects have to be taken into consideration, including age, disease, target tissue, and several environmental factors. Significant research efforts have been undertaken in the last decade to develop specific cell-based therapies, and in particular adult multipotent mesenchymal stem cells hold great promise for such regenerative strategies. Clinical translation of such therapies, however, remains a work in progress. In the clinical arena, autologous cells have been harvested, processed, and readministered according to protocols distinct for the target application. As outlined in this review, such applications range from simple single-step approaches, such as direct injection of unprocessed or concentrated blood or bone marrow aspirates, to fabrication of engineered constructs by seeding of natural or synthetic scaffolds with cells, which were released from autologous tissues and propagated under good manufacturing practice conditions (for example, autologous chondrocyte implantation). However, only relatively few of these cell-based approaches have entered the clinic, and none of these treatments has become a “standard of care” treatment for an orthopaedic disease to date. The multifaceted reasons for the current status from the medical, research, and regulatory perspectives are discussed here. In summary, this review presents the scientific background, current state, and implications of clinical mesenchymal stem cell application in the musculoskeletal system and provides perspectives for future developments. PMID:23197783

  18. Pseudomonas aeruginosa quorum sensing molecules correlate with clinical status in cystic fibrosis

    PubMed Central

    Halliday, Nigel; Cámara, Miguel; Barrett, David A.; Williams, Paul; Forrester, Douglas L.; Simms, Rebecca; Smyth, Alan R.; Honeybourne, David; Whitehouse, Joanna L.; Nash, Edward F.; Dewar, Jane; Clayton, Andrew; Knox, Alan J.; Fogarty, Andrew W.

    2015-01-01

    Pseudomonas aeruginosa produces quorum sensing signal molecules that are potential biomarkers for infection. A prospective study of 60 cystic fibrosis patients with chronic P. aeruginosa, who required intravenous antibiotics for pulmonary exacerbations, was undertaken. Clinical measurements and biological samples were obtained at the start and end of the treatment period. Additional data were available for 29 of these patients when they were clinically stable. Cross-sectionally, quorum sensing signal molecules were detectable in the sputum, plasma and urine of 86%, 75% and 83% patients, respectively. They were positively correlated between the three biofluids. Positive correlations were observed for most quorum sensing signal molecules in sputum, plasma and urine, with quantitative measures of pulmonary P. aeruginosa load at the start of a pulmonary exacerbation. Plasma concentrations of 2-nonyl-4-hydroxy-quinoline (NHQ) were significantly higher at the start of a pulmonary exacerbation compared to clinical stability (p<0.01). Following the administration of systemic antibiotics, plasma 2-heptyl-4-hydroxyquinoline (p=0.02) and NHQ concentrations (p<0.01) decreased significantly. In conclusion, quorum sensing signal molecules are detectable in cystic fibrosis patients with pulmonary P. aeruginosa infection and are positively correlated with quantitative measures of P. aeruginosa. NHQ correlates with clinical status and has potential as a novel biomarker for P. aeruginosa infection. PMID:26022946

  19. Pseudomonas aeruginosa quorum sensing molecules correlate with clinical status in cystic fibrosis.

    PubMed

    Barr, Helen L; Halliday, Nigel; Cámara, Miguel; Barrett, David A; Williams, Paul; Forrester, Douglas L; Simms, Rebecca; Smyth, Alan R; Honeybourne, David; Whitehouse, Joanna L; Nash, Edward F; Dewar, Jane; Clayton, Andrew; Knox, Alan J; Fogarty, Andrew W

    2015-10-01

    Pseudomonas aeruginosa produces quorum sensing signal molecules that are potential biomarkers for infection.A prospective study of 60 cystic fibrosis patients with chronic P. aeruginosa, who required intravenous antibiotics for pulmonary exacerbations, was undertaken. Clinical measurements and biological samples were obtained at the start and end of the treatment period. Additional data were available for 29 of these patients when they were clinically stable.Cross-sectionally, quorum sensing signal molecules were detectable in the sputum, plasma and urine of 86%, 75% and 83% patients, respectively. They were positively correlated between the three biofluids. Positive correlations were observed for most quorum sensing signal molecules in sputum, plasma and urine, with quantitative measures of pulmonary P. aeruginosa load at the start of a pulmonary exacerbation. Plasma concentrations of 2-nonyl-4-hydroxy-quinoline (NHQ) were significantly higher at the start of a pulmonary exacerbation compared to clinical stability (p<0.01). Following the administration of systemic antibiotics, plasma 2-heptyl-4-hydroxyquinoline (p=0.02) and NHQ concentrations (p<0.01) decreased significantly.In conclusion, quorum sensing signal molecules are detectable in cystic fibrosis patients with pulmonary P. aeruginosa infection and are positively correlated with quantitative measures of P. aeruginosa. NHQ correlates with clinical status and has potential as a novel biomarker for P. aeruginosa infection.

  20. Comparison of Clinical and Radiographic Periodontal Status Between Habitual Water-Pipe Smokers and Cigarette Smokers.

    PubMed

    Javed, Fawad; Al-Kheraif, Abdulaziz A; Rahman, Irfan; Millan-Luongo, Lorena Teresa; Feng, Changyong; Yunker, Michael; Malmstrom, Hans; Romanos, Georgios E

    2016-02-01

    There is a dearth of studies that have compared clinical and radiologic markers of periodontal inflammation between water-pipe smokers (WPs) and cigarette smokers (CSs). The aim of the present study is to compare the clinical and radiographic periodontal status between habitual WPs and CSs. In total, 200 males (50 WPs, 50 CSs, and 100 controls) with comparable mean age and education were included. Demographic information was recorded using a questionnaire. Periodontal parameters (plaque index [PI], bleeding on probing [BOP], probing depth [PD], clinical attachment loss [AL], and marginal bone loss [MBL]) and numbers of missing teeth (MT) were recorded. The duration of each smoking session for WPs and CSs was 50.2 ± 6.7 and 15.3 ± 0.4 minutes, respectively. Number of MT [P <0.0001], PI [P <0.0001], AL [P <0.0001], PD ≥4 mm [P <0.0001], and MBL [P <0.0001]) was significantly higher among WPs and CSs than controls. BOP was significantly higher among controls than WPs (P <0.0001) and CSs (P <0.0001). There was no statistically significant difference in the aforementioned parameters between WPs and CSs. Males in a Saudi Arabian community who were CSs or WPs had more MT and poorer periodontal condition than never smokers. The periodontal condition of WPs was equally as poor as CSs. Additional clinical observational studies with emphasis on sex and sociodemographic characteristics are needed.

  1. Is long-term virological response related to CCR5 Δ32 deletion in HIV-1-infected patients started on highly active antiretroviral therapy?

    PubMed Central

    Laurichesse, Jean-Jacques; Taieb, Audrey; Capoulade-Metay, Corinne; Katlama, Christine; Villes, Virginie; Drobacheff-Thiebaud, Marie-Christine; Raffi, François; Chêne, Genevieve; Theodorou, Ioannis; Leport, Catherine

    2010-01-01

    Objective To examine whether CCR5 Δ32 deletion is associated with long-term response to combination antiretroviral treatment (cART) in HIV-1 infected patients. Methods The genetic sub-study of ANRS CO8 APROCO-COPILOTE cohort included 609 patients who started a protease inhibitor-containing cART in 1997–99. Patients were considered to have a sustained virological response if all plasma HIV-RNA measurements between month 4 and years 3–5 were <500 copies/ml, allowing for a single blip. Virological response was compared between patients heterozygous for CCR5 Δ32 (Δ32/wt) and wild-type patients (wt/wt) from month 4 to year 3 and month 4 to year 5. Logistic regression analysis was used to adjust for baseline demographical data, HIV-RNA, CD4 cell counts, antiretroviral naive status, time spent on antiretroviral therapy at year 3 and 5 and adherence to treatment (month 4 to year 3 and 5). Results Sustained virological response was better in Δ32/wt than in wt/wt patients: 66% versus 52% up to year 3 (p=0.02), nearly significant after adjustment to potential cofounders (p=0.07). Δ32/wt patients had a better virological response, up to year 5, 48% versus 35% (p=0.01), and remained significantly better, after adjustment, associated with a better virological response up to 5 years post initiation of cART (p=0.04). There was no association with CD4 response. Conclusion Δ32/wt deletion is associated with a beneficial virological response to cART on the long-term. Whether this association can be a direct effect of Δ32/wt deletion remains questionable and needs confirmation in other observational studies. PMID:20050936

  2. SMOKING STATUS IS A CLINICAL INDICATOR FOR ALCOHOL MISUSE IN US ADULTS

    PubMed Central

    McKee, Sherry A.; Falba, Tracy; O’Malley, Stephanie S.; Sindelar, Jody; O’Connor, Patrick G.

    2010-01-01

    Context Screening for alcohol use in primary care settings is recommended by clinical care guidelines, but is not adhered to as strongly as screening for smoking. It has been proposed that smoking status could be used to enhance the identification of alcohol misuse in primary and other medical settings but national data are lacking. Objective To investigate smoking status as a clinical indicator for alcohol misuse in a national sample of US adults, following clinical care guidelines for the assessment of these behaviors. Design, Setting, and Participants Analyses are based on a sample of 42,565 US adults from the National Epidemiological Survey on Alcohol and Related Conditions (Wave I, 2001–2002). Main Outcome Measures Odds ratios (O.R.) and test characteristics (sensitivity, specificity, positive and negative predictive value [PPV, NPV], and likelihood ratio [LR] of smoking behavior (daily, occasional, former) were determined for the detection of hazardous drinking behavior and alcohol-related diagnoses, assessed by the Alcohol Use Disorder and Associated Disabilities Interview Schedule-IV. Results Daily, occasional, and ex-smokers were more likely than never smokers to be hazardous drinkers (O.R.3.23 [95% CI 3.02–3.46]; O.R.5.33 [95% CI 4.70–6.04]; O.R.1.19 [95% CI 1.10–1.28], respectively). Daily and occasional smokers were more likely to meet criteria for alcohol diagnoses (O.R.3.52 [95% CI 3.19–3.90], O.R.5.39 [95% CI 4.60–6.31]; respectively). For the detection of hazardous drinking by current smoking (occasional + daily), sensitivity was 42.5%; specificity 81.9%, PPV 45.3% (vs. population rate of 26.1%), and LR+ 2.34. For the detection of alcohol diagnoses by current smoking; sensitivity was 51.4%; specificity 78.0%, PPV 17.8% (vs. population rate of 8.5%), and LR+ 2.33. Conclusions Occasional and daily smokers were at heightened risk for hazardous drinking and alcohol use diagnoses. Smoking status can be used as a clinical indicator for alcohol

  3. Integrated Design of a Virology Course Develops Lifelong Learners

    ERIC Educational Resources Information Center

    Mester, Joseph C.

    2009-01-01

    This article describes the author's first attempt at integrated course design. Students in the author's virology course helped set the learning goals, and the design and content of the exams, and developed rubrics for individual and group projects. The result was that they learned how to direct their own learning. Integrated course design and…

  4. Integrated Design of a Virology Course Develops Lifelong Learners

    ERIC Educational Resources Information Center

    Mester, Joseph C.

    2009-01-01

    This article describes the author's first attempt at integrated course design. Students in the author's virology course helped set the learning goals, and the design and content of the exams, and developed rubrics for individual and group projects. The result was that they learned how to direct their own learning. Integrated course design and…

  5. Immune status at presentation for human immunodeficiency virus clinical care in Rio de Janeiro and Baltimore

    PubMed Central

    Moreira, Ronaldo I.; Luz, Paula M.; Struchiner, Claudio J.; Morgado, Mariza; Veloso, Valdilea G.; Keruly, Jeanne C.; Grinsztejn, Beatriz; Moore, Richard D.

    2011-01-01

    Introduction Late presentation to HIV clinical care increases individual risk of (multiple) clinical events and death, and decreases successful response to highly active antiretroviral therapy (HAART). In Brazil, provision of HAART free of charge to all HIV-infected individuals could lead to increased testing and linkage to care. Methods We assessed the immune status of 2,555 patients who newly presented for HIV clinical care between 1997 and 2009 at the Johns Hopkins Clinical Cohort, in Baltimore, USA and at the Instituto de Pesquisa Clinica Evandro Chagas Clinical Cohort, in Rio de Janeiro, Brazil. The mean change in the CD4 cell count per year was estimated using multivariate linear regression models. Results Overall, from 1997 to 2009, 56% and 54% of the patients presented for HIV clinical care with CD4 count ≤ 350 cells/mm3 in Baltimore and Rio de Janeiro, respectively. On average, 75% of the patients presented with viral load > 10,000 copies/mL. In Rio de Janeiro only, the overall adjusted per year increase in the mean CD4 cell count was statistically significant [5 cells/mm3 (95% CI 1, 10 cells/mm3)]. Discussion We found that, over years, the majority of patients presented late, that is, with a CD4 count < 350 cells/mm3. Our findings indicate that, despite the availability of HAART for more than a decade, and mass media campaigns stimulating HIV testing in both countries, the proportion of patients who start therapy at an advanced stage of the disease is still high. PMID:21857314

  6. Immune status at presentation for HIV clinical care in Rio de Janeiro and Baltimore.

    PubMed

    Moreira, Ronaldo I; Luz, Paula M; Struchiner, Claudio J; Morgado, Mariza; Veloso, Valdilea G; Keruly, Jeanne C; Grinsztejn, Beatriz; Moore, Richard D

    2011-08-01

    Late presentation to HIV clinical care increases individual risk for (multiple) clinical events and death, and decreases successful response to highly active antiretroviral therapy (HAART). In Brazil, provision of HAART free of charge to all individuals infected with HIV could lead to increased testing and linkage to care. We assessed the immune status of 2555 patients who newly presented for HIV clinical care between 1997 and 2009 at the Johns Hopkins Clinical Cohort, in Baltimore, Md, and at the Instituto de Pesquisa Clinica Evandro Chagas Clinical Cohort, in Rio de Janeiro, Brazil. The mean change in the CD4 cell count per year was estimated using multivariate linear regression models. Overall, from 1997 to 2009, 56% and 54% of the patients presented for HIV clinical care with CD4 count ≤350 cells per cubic millimeter in Baltimore and Rio de Janeiro, respectively. On average, 75% of the patients presented with viral load >10,000 copies per millimeter. In Rio de Janeiro only, the overall adjusted per year increase in the mean CD4 cell count was statistically significant (5 cells/mm, 95% confidence interval: 1 to 10 cells/mm). We found that, over years, the majority of patients presented late, that is, with a CD4 count <350 cells per cubic millimeter. Our findings indicate that, despite the availability of HAART for more than a decade, and mass media campaigns stimulating HIV testing in both countries, the proportion of patients who start therapy at an advanced stage of the disease is still high.

  7. A Serious Game for Clinical Assessment of Cognitive Status: Validation Study.

    PubMed

    Tong, Tiffany; Chignell, Mark; Tierney, Mary C; Lee, Jacques

    2016-05-27

    We propose the use of serious games to screen for abnormal cognitive status in situations where it may be too costly or impractical to use standard cognitive assessments (eg, emergency departments). If validated, serious games in health care could enable broader availability of efficient and engaging cognitive screening. The objective of this work is to demonstrate the feasibility of a game-based cognitive assessment delivered on tablet technology to a clinical sample and to conduct preliminary validation against standard mental status tools commonly used in elderly populations. We carried out a feasibility study in a hospital emergency department to evaluate the use of a serious game by elderly adults (N=146; age: mean 80.59, SD 6.00, range 70-94 years). We correlated game performance against a number of standard assessments, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Confusion Assessment Method (CAM). After a series of modifications, the game could be used by a wide range of elderly patients in the emergency department demonstrating its feasibility for use with these users. Of 146 patients, 141 (96.6%) consented to participate and played our serious game. Refusals to play the game were typically due to concerns of family members rather than unwillingness of the patient to play the game. Performance on the serious game correlated significantly with the MoCA (r=-.339, P <.001) and MMSE (r=-.558, P <.001), and correlated (point-biserial correlation) with the CAM (r=.565, P <.001) and with other cognitive assessments. This research demonstrates the feasibility of using serious games in a clinical setting. Further research is required to demonstrate the validity and reliability of game-based assessments for clinical decision making.

  8. A Serious Game for Clinical Assessment of Cognitive Status: Validation Study

    PubMed Central

    Chignell, Mark; Tierney, Mary C.; Lee, Jacques

    2016-01-01

    Background We propose the use of serious games to screen for abnormal cognitive status in situations where it may be too costly or impractical to use standard cognitive assessments (eg, emergency departments). If validated, serious games in health care could enable broader availability of efficient and engaging cognitive screening. Objective The objective of this work is to demonstrate the feasibility of a game-based cognitive assessment delivered on tablet technology to a clinical sample and to conduct preliminary validation against standard mental status tools commonly used in elderly populations. Methods We carried out a feasibility study in a hospital emergency department to evaluate the use of a serious game by elderly adults (N=146; age: mean 80.59, SD 6.00, range 70-94 years). We correlated game performance against a number of standard assessments, including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Confusion Assessment Method (CAM). Results After a series of modifications, the game could be used by a wide range of elderly patients in the emergency department demonstrating its feasibility for use with these users. Of 146 patients, 141 (96.6%) consented to participate and played our serious game. Refusals to play the game were typically due to concerns of family members rather than unwillingness of the patient to play the game. Performance on the serious game correlated significantly with the MoCA (r=–.339, P <.001) and MMSE (r=–.558, P <.001), and correlated (point-biserial correlation) with the CAM (r=.565, P <.001) and with other cognitive assessments. Conclusions This research demonstrates the feasibility of using serious games in a clinical setting. Further research is required to demonstrate the validity and reliability of game-based assessments for clinical decision making. PMID:27234145

  9. Pulp bleeding color is an indicator of clinical and histohematologic status of primary teeth.

    PubMed

    Aaminabadi, Naser Asl; Parto, Marziyeh; Emamverdizadeh, Parya; Jamali, Zahra; Shirazi, Sajjad

    2017-06-01

    This study was carried out to investigate whether the changes in hematologic characteristic and color of pulpal bleeding is associated with clinical and histologic status of the pulp in primary teeth. A total of 211 primary molars in 103 patients, 3-6 years old, were treated. One hundred eight teeth had pulpectomy, 57 teeth had pulpotomy after pulp exposure during caries excavation, and 46 teeth had pulpotomy after accidental pulp exposure in sound dentin. After pulpal exposure, pulpal blood was collected in capillary tubes for blood color and hematologic assessment. Coronal and radicular pulp tissues were amputated for histologic assessment. Blood color was significantly darker in pulpectomy cases and samples with severe inflammation. The differences were clinically perceptible by the human eye. A significant negative correlation was detected between white blood cell (WBC) count and blood color. The counts of neutrophils and lymphocytes were significantly different between treatment groups. In addition, WBC, eosinophil, monocyte, neutrophil, and basophils counts were significantly different between degrees of inflammation in coronal pulp. Moreover, severe inflammation was higher in pulpectomy group versus pulpotomy groups. Pulp tissue calcification was also significantly higher in the pulpectomy cases. Considering the significant difference in pulpal blood color between the pulpectomy and pulpotomy cases, and between the different levels of pulpal inflammation; blood color can be a valid clinical diagnostic criterion of pulpal status and can be used for the selection of appropriate pulp treatment strategy. This study shows that pulp bleeding color can be used for selection of an appropriate pulp treatment method in primary teeth.

  10. Relationships of clinical, psychologic, and individual factors with the functional status of neck pain patients.

    PubMed

    Luo, Xuemei; Edwards, Christopher L; Richardson, William; Hey, Lloyd

    2004-01-01

    The objective of this study was to use both generic and disease-specific functional measures examining relationships of clinical, psychologic, and individual factors with the functional status of neck pain patients. Patients who visited a university-based spine clinic and reported neck pain were included in this study. A comprehensive computerized survey questionnaire was used to collect the information related to this study. The questionnaire also contained a generic measure, short form 12-item survey (SF-12), and a disease-specific measure, neck disability index (NDI). Correlation and multiple regression analysis were conducted to examine the relationships. A range of clinical, psychologic, and individual factors emerged to be significant predictors of the NDI or physical component of the SF-12 (PCS). The predictors of higher NDI included higher levels of neck pain, higher levels of back pain, higher levels of pain in arm or shoulder areas, not working, lower education, higher stress, the presence of depression or anxiety, and smoking. The predictors of lower PCS included not working, higher levels of back pain, higher levels of neck pain, lower education, female sex, the presence of cardiovascular disorders, the absence of cervical disk disorders, and older age. The predictors of the NDI or PCS appear to be multidimensional. Interventions designed to maximally improve the functional status of neck pain patients should be multifaceted and involve multidisciplinary teams. Selection of the most appropriate functional measures for an intervention study should consider differences between the generic and disease-specific measures in terms of their respective relationships with targeted factors. Prospective studies are needed to confirm the relationships observed in this study.

  11. Factors Influencing Antiretroviral Adherence and Virological Outcomes in People Living with HIV in the Highlands of Papua New Guinea.

    PubMed

    Gare, Janet; Kelly-Hanku, Angela; Ryan, Claire E; David, Matthew; Kaima, Petronia; Imara, Ulato; Lote, Namarola; Crowe, Suzanne M; Hearps, Anna C

    2015-01-01

    Adherence to antiretroviral therapy (ART) is paramount for virological suppression and positive treatment outcomes. ART has been rapidly scaled up in Papua New Guinea (PNG) in recent years, however clinical monitoring of HIV+ individuals on ART is limited. A cross-sectional study was conducted at two major sexual health clinics in high HIV prevalence provinces in the Highlands Region of PNG to assess ART adherence, factors affecting adherence and the relationship between ART adherence and virological outcomes. Ninety-five HIV+ individuals were recruited and administered a questionnaire to gather demographic and ART adherence information whilst clinical data and pill counts were extracted from patient charts and blood was collected for viral load testing. Bivariate analysis was performed to identify independent predictors of ART adherence. Fourteen percent (n = 12) of participants showed evidence of virological failure. Although the majority of participants self-reported excellent ART adherence in the last seven days (78.9%, 75/91), pill count measurements indicated only 40% (34/84) with >95% adherence in the last month. Taking other medications while on ART (p = 0.01) and taking ART for ≥1 year (p = 0.037) were positively associated with adherence by self-report and pill count, respectively. Participants who had never heard of drug resistance were more likely to show virological failure (p = 0.033). Misconception on routes of HIV transmission still persists in the studied population. These findings indicate that non-adherence to ART is high in this region of PNG and continued education and strategies to improve adherence are required to ensure the efficacy of ART and prevent HIV drug resistance.

  12. Factors Influencing Antiretroviral Adherence and Virological Outcomes in People Living with HIV in the Highlands of Papua New Guinea

    PubMed Central

    Gare, Janet; Kelly-Hanku, Angela; Ryan, Claire E.; David, Matthew; Kaima, Petronia; Imara, Ulato; Lote, Namarola; Crowe, Suzanne M.; Hearps, Anna C.

    2015-01-01

    Adherence to antiretroviral therapy (ART) is paramount for virological suppression and positive treatment outcomes. ART has been rapidly scaled up in Papua New Guinea (PNG) in recent years, however clinical monitoring of HIV+ individuals on ART is limited. A cross-sectional study was conducted at two major sexual health clinics in high HIV prevalence provinces in the Highlands Region of PNG to assess ART adherence, factors affecting adherence and the relationship between ART adherence and virological outcomes. Ninety-five HIV+ individuals were recruited and administered a questionnaire to gather demographic and ART adherence information whilst clinical data and pill counts were extracted from patient charts and blood was collected for viral load testing. Bivariate analysis was performed to identify independent predictors of ART adherence. Fourteen percent (n = 12) of participants showed evidence of virological failure. Although the majority of participants self-reported excellent ART adherence in the last seven days (78.9%, 75/91), pill count measurements indicated only 40% (34/84) with >95% adherence in the last month. Taking other medications while on ART (p = 0.01) and taking ART for ≥1 year (p = 0.037) were positively associated with adherence by self-report and pill count, respectively. Participants who had never heard of drug resistance were more likely to show virological failure (p = 0.033). Misconception on routes of HIV transmission still persists in the studied population. These findings indicate that non-adherence to ART is high in this region of PNG and continued education and strategies to improve adherence are required to ensure the efficacy of ART and prevent HIV drug resistance. PMID:26244516

  13. Predictors of late virologic failure after initial successful suppression of HIV replication on efavirenz-based antiretroviral therapy.

    PubMed

    Singini, Isaac; Campbell, Thomas B; Smeaton, Laura M; Kumarasamy, Nagalingeswaran; La Rosa, Alberto; Taejareonkul, Sineenart; Safren, Steven A; Flanigan, Timothy P; Hakim, James G; Hughes, Michael D

    2016-07-29

    Practical issues, including cost, hinder implementing virologic monitoring of patients on antiretroviral therapy (ART) in resource-limited settings. We evaluated factors that might guide monitoring frequency and efforts to prevent treatment failure after initial virologic suppression. Participants were the 911 HIV-infected antiretroviral-naïve adults with CD4 count <300 cells/μL who started efavirenz-based ART in the international A5175/PEARLS trial and achieved HIV-1 RNA <1000 copies/mL at 24 weeks. Participant report of ART adherence was evaluated using a structured questionnaire in monthly interviews. Adherence and readily available clinical and laboratory measures were evaluated as predictors of late virologic failure (late VF: confirmed HIV-1 RNA ≥1000 copies/mL after 24 weeks). During median follow-up of 3.5 years, 82/911 participants (9%) experienced late VF. Of 516 participants reporting missed doses during the first 24 weeks of ART, 55 (11%) experienced late VF, compared with 27 (7%) of 395 participants reporting no missed doses (hazard ratio: 1.73; 95% CI: 1.08, 2.73). This difference persisted in multivariable analysis, in which lower pre-ART hemoglobin and absence of Grade ≥3 laboratory results prior to week 24 were also associated with higher risk of late VF. In this clinical trial, the late VF rate after successful suppression was very low. If achievable in routine clinical practice, virologic monitoring involving infrequent (e.g. annual) measurements might be considered; the implications of this for development of resistance need evaluating. Patients reporting missed doses early after ART initiation, despite achieving initial suppression, might require more frequent measurement and/or strategies for promoting adherence.

  14. Impact of baseline plasma HIV-1 RNA and time to virological suppression on virological rebound according to first-line antiretroviral regimen.

    PubMed

    Raffi, François; Hanf, Matthieu; Ferry, Tristan; Khatchatourian, Lydie; Joly, Véronique; Pugliese, Pascal; Katlama, Christine; Robineau, Olivier; Chirouze, Catherine; Jacomet, Christine; Delobel, Pierre; Poizot-Martin, Isabelle; Ravaux, Isabelle; Duvivier, Claudine; Gagneux-Bugnon, Amandine; Rey, David; Reynes, Jacques; May, Thierry; Bani-Sadr, Firouzé; Hoen, Bruno; Morrier, Marine; Cabie, André; Allavena, Clotilde

    2017-09-06

    We investigated the risk of virological rebound in HIV-1-infected patients achieving virological suppression on first-line combined ART (cART) according to baseline HIV-1 RNA, time to virological suppression and type of regimen. Subjects were 10 836 adults who initiated first-line cART (two nucleoside or nucleotide reverse transcriptase inhibitors + efavirenz, a ritonavir-boosted protease inhibitor or an integrase inhibitor) from 1 January 2007 to 31 December 2014. Cox proportional hazards models with multiple adjustment and propensity score matching were used to investigate the effect of baseline HIV-1 RNA and time to virological suppression on the occurrence of virological rebound. During 411 436 patient-months of follow-up, risk of virological rebound was higher in patients with baseline HIV-1 RNA ≥100 000 copies/mL versus <100 000 copies/mL, in those achieving virological suppression in > 6 months versus <6 months, and lower with efavirenz or integrase inhibitors than with ritonavir-boosted protease inhibitors. Baseline HIV-1 RNA >100 000 copies/mL was associated with virological rebound for ritonavir-boosted protease inhibitors but not for efavirenz or integrase inhibitors. Time to virological suppression >6 months was strongly associated with virological rebound for all regimens. In HIV-1-infected patients starting cART, risk of virological rebound was lower with efavirenz or integrase inhibitors than with ritonavir-boosted protease inhibitors. These data, from a very large observational cohort, in addition to the more rapid initial virological suppression obtained with integrase inhibitors, reinforce the positioning of this class as the preferred one for first-line therapy.

  15. Natural peste des petits ruminants virus infection in Black Bengal goats: virological, pathological and immunohistochemical investigation.

    PubMed

    Chowdhury, Emdadul Haque; Bhuiyan, Ataur Rahman; Rahman, Mohammad Mushfiqur; Siddique, Mohammad Sahinur Alam; Islam, Mohammad Rafiqul

    2014-11-14

    Peste des Petits Ruminants (PPR), also known as Goat Plague, occurs in goats, sheep and related species. It is caused by a morbillivirus in the family Paramyxoviridae. In Bangladesh PPR is endemic and it causes serious economic losses. Pathology of PPR has been reported in different goat and sheep breeds from natural and experimental infections. Field results are better indicators of pathogenicity of the circulating virus. The severity of the disease varies with species, breed and immune status of the host. Pathological investigations of natural outbreaks of PPR in Balck Bengal goats are very limited. The current investigation was aimed at describing pathology and antigen localization in natural PPR infections in Black Bengal goats. A total of 28 outbreaks were investigated clinically and virologically. Average flock morbidity and mortality were 75% and 59%, respectively, with case fatality rate of 74%. Necropsy was conducted on 21 goats from 15 outbreaks. The major gross lesions were congestion of gastrointestinal tract, pneumonia, engorged spleen, and oedematous lymphnodes. Histopathological examination revealed severe enteritis with denudation of intestinal epithelium, severe broncho-interstitial pneumonia with macrophages within lung alveoli and extensive haemorrhages with depletion of lymphoid cells and infiltration of macrophages in the sinuses of spleen. In lymph nodes, the cortical nodules were replaced by wide sinusoids with severe depletion of lymphocytes, infiltration of mononuclear cells and some giant cells in sub-capsular areas and medullary sinuses. PPR virus antigen was found in pneumocytes and alveolar macrophages in lungs. Viral RNA could be detected by RT-PCR in 69 out of 84 nasal swab, 59 out of 84 blood and 21 out of 21 lymph node samples. Sequence analyses revealed closeness of Bangladeshi strains with other recent Asian isolates. Natural outbreaks of PPR in Black Bengal goats in Bangladesh resulted in 75% and 59% flock morbidity and mortality

  16. Are three generations of quantitative molecular methods sufficient in medical virology? Brief review.

    PubMed

    Clementi, Massimo; Bagnarelli, Patrizia

    2015-10-01

    In the last two decades, development of quantitative molecular methods has characterized the evolution of clinical virology more than any other methodological advancement. Using these methods, a great deal of studies has addressed efficiently in vivo the role of viral load, viral replication activity, and viral transcriptional profiles as correlates of disease outcome and progression, and has highlighted the physio-pathology of important virus diseases of humans. Furthermore, these studies have contributed to a better understanding of virus-host interactions and have sharply revolutionized the research strategies in basic and medical virology. In addition and importantly from a medical point of view, quantitative methods have provided a rationale for the therapeutic intervention and therapy monitoring in medically important viral diseases. Despite the advances in technology and the development of three generations of molecular methods within the last two decades (competitive PCR, real-time PCR, and digital PCR), great challenges still remain for viral testing related not only to standardization, accuracy, and precision, but also to selection of the best molecular targets for clinical use and to the identification of thresholds for risk stratification and therapeutic decisions. Future research directions, novel methods and technical improvements could be important to address these challenges.

  17. Current status, challenges and the way forward for clinical pharmacy service in Ethiopian public hospitals.

    PubMed

    Bilal, Arebu Issa; Tilahun, Zelalem; Gebretekle, Gebremedhin Beedemariam; Ayalneh, Belete; Hailemeskel, Bisrat; Engidawork, Ephrem

    2017-05-19

    Clinical pharmacy service has evolved steadily over the past few decades and is now contributing to the 'patient care journey' at all stages. It is improving the safety and effectiveness of medicines and has made a significant contribution to the avoidance of medication errors. In Ethiopia, clinical pharmacy service is in its initial phase, being started in July 2013. This study therefore aimed at assessing the status, challenges and way forward of clinical pharmacy service in the country. A cross-sectional survey was conducted in six regional states and one city- administration in September 2014. A total of 51 hospitals were included in the study. Both qualitative and quantitative methods were employed for data collection. A total of 160 pharmacy graduates, and 51 pharmacy heads participated in the study. Internal Medicine and Pediatric wards were the major wards where the graduates provide clinical pharmacy service. Almost 94% of the new graduates were found to be involved in clinical pharmacy service, but 47% of them rated their service as poor. The overall satisfaction of the graduates was close to 36%. Thirteen hospitals discontinued and two hospitals not even initiated the service largely due to shortage of pharmacists and lack of management support. About 44% of the surveyed hospitals documented the clinical pharmacy service provided using either developed or adopted formats. Lack of awareness by the medical fraternity, high attrition rate, lack of support from the management as well as from the health care team, readiness of the graduates to deliver the service, and shortage of pharmacists were identified by the key informants as the major stumbling block to deliver clinical pharmacy service. Clinical pharmacy service is initiated in most of the surveyed hospitals and a large proportion of the graduates were involved in the service. Although there is a great enthusiasm to promote clinical pharmacy service in the surveyed hospitals, efforts made to

  18. Super-refractory nonconvulsive status epilepticus secondary to fat embolism: A clinical, electrophysiological, and pathological study.

    PubMed

    Fernández-Torre, José L; Burgueño, Paula; Ballesteros, María A; Hernández-Hernández, Miguel A; Villagrá-Terán, Nuria; de Lucas, Enrique Marco

    2015-08-01

    Fat embolism syndrome (FES) is a rare complication of long-bone fractures and joint reconstruction surgery. To the best of our knowledge, we describe the clinical, electrophysiological, neuroimaging, and neuropathological features of the first case of super-refractory nonconvulsive status epilepticus (sr-NCSE) secondary to fat embolism. An 82-year-old woman was transferred to our intensive care unit because of a sudden decrease of consciousness level, right hemiparesis, and acute respiratory failure in the early postoperative period of knee prosthesis surgery. Brain computed tomography (TC) including angio-CT and CT perfusion was normal. An urgent video-electroencephalography (v-EEG) evaluation showed continuous sharp-and slow-wave at 2.0-2.5 Hz in keeping with the diagnosis of generalized NCSE. Epileptiform discharges ceased after the administration of 5mg of intravenous diazepam, and background activity constituted by diffuse theta waves was observed without clinical improvement. Treatment with levetiracetam (1000 mg/day) and sedation with propofol and midazolam were initiated. Moreover, continuous v-EEG monitoring was also started. Despite antiepileptic therapy, epileptiform activity recurred after the interruption of profound sedation, and valproate and lacosamide were added during the ensuing days. Magnetic resonance imaging (MRI) disclosed small scattered foci of acute ischemic infarcts and diffuse petechiae involving the basal ganglia and pons and centrum semiovale in keeping with fat embolism. Super-refractory nonconvulsive status epilepticus remained without control for 2 weeks. Finally, the patient died. The clinical autopsy revealed a bilateral lung fat embolism associated with a hemorrhagic infarction in the left lower lobe. Fatty lesions were also seen in the intestine and pancreas. Scattered microscopic cerebral infarcts associated with fat emboli in the capillaries were noticed, affecting both supra- and infratentorial structures. In addition

  19. Factors Associated With Smoking Status among HIV-Positive Patients in Routine Clinical Care

    PubMed Central

    Zyambo, Cosmas M; Willig, James H; Cropsey, Karen L; Carson, April P; Wilson, Craig; Tamhane, Ashutosh R; Westfall, Andrew O; Burkholder, Greer A

    2015-01-01

    Background Treatment-related reductions in morbidity and mortality among human immunodeficiency virus (HIV)-positive patients have been attenuated by cigarette smoking, which increases risk of cardiovascular, respiratory, and neoplastic diseases. This study investigated factors associated with smoking status among HIV-positive patients. Methods This cross-sectional study included 2,464 HIV-positive patients attending the HIV Clinic at the University of Alabama at Birmingham between April 2008 and December 2013. Smoking status (current, former, never), psychosocial factors, and clinical characteristics were assessed. Multinomial logistic regression was used to obtain unadjusted and adjusted odds ratios (OR) and 95% confidence intervals (CI) for the association of the various factors with smoking status. Results Among HIV-positive patients (mean age 45 years, 75% male, 55% African-American), the majority reported a history of smoking (39% current and 22% former smokers). In adjusted models, patient characteristics associated with increased odds of current smoking were male gender (OR for heterosexual men, 1.8 [95% CI: 1.3–2.6]; for men who have sex with men, 1.5 [1.1–1.9]), history of respiratory diseases (1.5 [1.2–1.9]), unsuppressed HIV viral load (>50 copies/mL) (1.5 [1.1–1.9]), depression (1.6 [1.3–2.0]), anxiety (1.6 [1.2–2.1]), and prior and current substance abuse (4.7 [3.6–6.1] and 8.3 [5.3–13.3] respectively). Male gender, anxiety, and substance abuse were also associated with being a former smoker. Conclusions Smoking was common among HIV-positive patients, with several psychosocial factors associated with current and former smoking. This suggests smoking cessation programs in HIV clinic settings may achieve greater impact by integrating interventions that also address illicit substance abuse and mental health. PMID:26767146

  20. Current Clinical Status of Telehealth in Korea: Categories, Scientific Basis, and Obstacles

    PubMed Central

    Kim, Hun-Sung; Kim, Hyunah; Lee, Suehyun; Lee, Kye Hwa

    2015-01-01

    Objectives Through telehealth, medical services have expanded beyond spatial boundaries and are now available in living spaces outside of hospitals. It can also contribute to patient medical knowledge improvement because patients can access their hospital records and data from home. However, concepts of telehealth are rather vague in Korea. Methods We refer to several clinical reports to determine the current clinical status of and obstacles to telehealth in Korea. Results Patients' health conditions are now reported regularly to doctors remotely, and patients can receive varied assistance. Self-improvement based on minute details that are beyond medical staff's reach is another possible benefit that may be realized with the help of a variety of medical equipment (sensors). The feasibility, clinical effect, and cost-benefit of telehealth have been verified by scientific evidence. Conclusions Patients will be able to improve their treatment adherence by receiving help from various professionals, such as doctors, nurses, nutritionists, and sports therapists. This means that the actual treatment time per patient will increase as well. Ultimately, this will increase the quality of patients' self-administration of care to impede disease progression and prevent complications. PMID:26618030

  1. [Research on application status of Chinese herbal decoction pieces based on clinical survey].

    PubMed

    Fan, Yu-Hao; Wang, Peng-Li; Fan, Xin-Sheng; Yu, Jiang-Yong; Li, Jun; Duan, Jin-Ao

    2016-08-01

    Chinese herbal decoction pieces are the basic approaches for clinical traditional Chinese medicine (TCM), reflecting the features and advantages of TCM. In order to investigate the clinical application status and features of Chinese herbal decoction pieces, the questionnaire on application of commonly used Chinese herbal decoction pieces was designed in this study for analysis of the application situations of Chinese herbal decoction pieces from 56 medical institutions in 10 provinces. The results showed 549 varieties of Chinese herbs and 801 varieties of decoction pieces were used on clinic. They can be classified into 19 categories according to their effects. The varieties of Gancao (Glycyrrhizae Radix et Rhizoma), Huangqi (Astragali Radix), Dihuang (Rehmanniae Radix), Chuanxiong (Chuanxiong Rhizoma), Baizhu (Atractylodis Macrocephale Rhizima), Huangqin (Scutellariae Radix), Danggui (Angelicae Sinenses Radix), Baishao (Paeoniae Radix Alba) and Maidong (Ophiopogonis Radix) were most common ones; the application of Chinese herbal decoction pieces from different medical institutions was differentiated from areas to areas. The survey results reflected the general situation about application of decoction pieces, providing the basic data for recording and completing Chinese herbal decoction pieces in essential drug system, with certain reference significance for the production of Chinese medicinal materials and the allocation of the varieties of Chinese herbal decoction pieces. Copyright© by the Chinese Pharmaceutical Association.

  2. Low socioeconomic status, adverse gene expression profiles, and clinical outcomes in hematopoietic stem cell transplant recipients

    PubMed Central

    Knight, Jennifer M.; Rizzo, J. Douglas; Logan, Brent R.; Wang, Tao; Arevalo, Jesusa M.G.; Ma, Jeffrey; Cole, Steve W.

    2015-01-01

    Purpose Low socioeconomic status (SES) is associated with adverse outcomes among unrelated donor hematopoietic stem cell transplant (HCT) recipients, but the biological mechanisms contributing to this health disparity are poorly understood. Therefore, we examined whether social environment affects expression of a stress-related gene expression profile known as the conserved transcriptional response to adversity (CTRA), which involves up-regulation of pro-inflammatory genes and down-regulation of genes involved in type I IFN response and antibody synthesis. Experimental Design We compared pre-transplant leukocyte CTRA gene expression between a group of 78 high vs. low SES recipients of unrelated donor HCT for acute myelogenous leukemia in first remission. Post hoc exploratory analyses also evaluated whether CTRA gene expression was associated with poor clinical outcomes. Results Peripheral blood mononuclear cells collected pre-HCT from low SES individuals demonstrated significant CTRA up-regulation compared to matched HCT recipients of high SES. Promoter-based bioinformatics implicated distinct patterns of transcription factor activity including increased CREB signaling and decreased IRF and GR signaling. High expression of the CTRA gene profile was also associated with increased relapse risk and decreased leukemia-free survival. Conclusions Low SES is associated with increased expression of the CTRA gene profile, and CTRA gene expression is associated with adverse HCT clinical outcomes. These findings provide a biologic framework within which to understand how social environmental conditions may influence immune function and clinical outcomes in allogeneic HCT. PMID:26286914

  3. Clinical and Taxonomic Status of Pathogenic Nonpigmented or Late-Pigmenting Rapidly Growing Mycobacteria

    PubMed Central

    Brown-Elliott, Barbara A.; Wallace, Richard J.

    2002-01-01

    The history, taxonomy, geographic distribution, clinical disease, and therapy of the pathogenic nonpigmented or late-pigmenting rapidly growing mycobacteria (RGM) are reviewed. Community-acquired disease and health care-associated disease are highlighted for each species. The latter grouping includes health care-associated outbreaks and pseudo-outbreaks as well as sporadic disease cases. Treatment recommendations for each species and type of