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Sample records for antiviral treatment initiation

  1. Predictors of antiviral treatment initiation in hepatitis C virus-infected patients: a Danish cohort study

    DEFF Research Database (Denmark)

    Hansen, N; Obel, N; Christensen, P B

    2009-01-01

    Predictive factors for initiation of antiviral therapy in chronically infected hepatitis C virus (HCV) patients are not fully elucidated. The aim of this study was to determine predictive factors for initiation of treatment with standard or pegylated interferon either alone or combined...... with ribavirin. A Danish cohort of individuals chronically infected with HCV was used and observation time was calculated from the date of inclusion in the cohort to date of death, last clinical observation, 1 January 2007, or start of HCV antiviral treatment in treatment-naïve patients. Kaplan-Meier survival...... analysis was used to construct time to event curves. Cox regression was used to determine the incidence rate ratios as estimates of relative risk (RR) and 95% confidence intervals (CI). A total of 1780 patients were enrolled in the study. The cumulative chance of treatment initiation over 5 years was 33...

  2. WITHDRAWN. Antiviral treatment for Bell's palsy (idiopathic facial paralysis).

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    Gagyor, Ildiko; Madhok, Vishnu B; Daly, Fergus; Somasundara, Dhruvashree; Sullivan, Michael; Gammie, Fiona; Sullivan, Frank

    2015-05-04

    Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but the effectiveness of additional treatment with an antiviral agent is uncertain. Significant morbidity can be associated with severe cases of Bell's palsy. To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy. On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, DARE, NHS EED, and HTA. We also reviewed the bibliographies of the identified trials and contacted trial authors and known experts in the field and relevant drug companies to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies. We considered randomised controlled trials or quasi-randomised controlled trials of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy. We excluded trials that had a high risk of bias in several domains. Pairs of authors independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures. Eleven trials, including 2883 participants, met the inclusion criteria and are included in the final analysis. We added four studies to the previous review for this update. Some of the trials were small, and a number were at high or unclear risk of bias. Other trials did not meet current best standards in allocation concealment and blinding. Incomplete recoveryWe found no significant benefit from adding antivirals to corticosteroids in comparison with corticosteroids alone for people with Bell's palsy (risk ratio (RR) 0.69, 95% confidence interval (CI) 0.47 to 1.02, n = 1715). For people with severe Bell's palsy (House-Brackmann scores of 5 and 6 or the equivalent in other scales), we found a reduction in the rate of incomplete recovery at month six when antivirals plus corticosteroids were used (RR 0.64, 95% CI 0.41 to 0

  3. Bell's Palsy: Treatment with Steroids and Antiviral Drugs

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    ... Drooping of a corner of the mouth • Difficulty smiling, frowning, or making other facial expressions • Twitching or ... no definite added improvement. If there is any benefit to adding an antiviral to steroid treatment, it ...

  4. Antiviral treatment for Bell's palsy (idiopathic facial paralysis).

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    Gagyor, Ildiko; Madhok, Vishnu B; Daly, Fergus; Somasundara, Dhruvashree; Sullivan, Michael; Gammie, Fiona; Sullivan, Frank

    2015-11-09

    Corticosteroids are widely used in the treatment of idiopathic facial paralysis (Bell's palsy), but the effectiveness of additional treatment with an antiviral agent is uncertain. Significant morbidity can be associated with severe cases of Bell's palsy. This review was first published in 2001 and revised several times, most recently in 2009. This version replaces an update of the review in Issue 7 of the Cochrane Library subsequently withdrawn because of an ongoing investigation into the reliability of data from an included study. To assess the effects of antiviral treatments alone or in combination with any other therapy for Bell's palsy. On 7 October 2014 we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL, MEDLINE, EMBASE, LILACS, DARE, NHS EED, and HTA. We also reviewed the bibliographies of the identified trials and contacted trial authors and known experts in the field and relevant drug companies to identify additional published or unpublished data. We searched clinical trials registries for ongoing studies. We considered randomised controlled trials or quasi-randomised controlled trials of antivirals with and without corticosteroids versus control therapies for the treatment of Bell's palsy. We excluded trials that had a high risk of bias in several domains. Pairs of authors independently assessed trials for relevance, eligibility, and risk of bias, using standard Cochrane procedures. Ten trials, including 2280 participants, met the inclusion criteria and are included in the final analysis. Some of the trials were small, and a number were at high or unclear risk of bias. Other trials did not meet current best standards in allocation concealment and blinding. Incomplete recoveryWe found a significant benefit from adding antivirals to corticosteroids in comparison with corticosteroids alone for people with Bell's palsy (risk ratio (RR) 0.61, 95% confidence interval (CI) 0.39 to 0.97, n = 1315). For people with severe Bell

  5. Antiviral treatment among older adults hospitalized with influenza, 2006-2012.

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    Mary Louise Lindegren

    Full Text Available To describe antiviral use among older, hospitalized adults during six influenza seasons (2006-2012 in Davidson County, Tennessee, USA.Among adults ≥50 years old hospitalized with symptoms of respiratory illness or non-localizing fever, we collected information on provider-initiated influenza testing and nasal/throat swabs for influenza by RT-PCR in a research laboratory, and calculated the proportion treated with antivirals.We enrolled 1753 adults hospitalized with acute respiratory illness. Only 26% (457/1753 of enrolled patients had provider-initiated influenza testing. Thirty-eight patients had a positive clinical laboratory test, representing 2.2% of total patients and 8.3% of tested patients. Among the 38 subjects with clinical laboratory-confirmed influenza, 26.3% received antivirals compared to only 4.5% of those with negative clinical influenza tests and 0.7% of those not tested (p<0.001. There were 125 (7.1% patients who tested positive for influenza in the research laboratory. Of those with research laboratory-confirmed influenza, 0.9%, 2.7%, and 2.8% received antivirals (p=.046 during pre-pandemic, pandemic, and post-pandemic influenza seasons, respectively. Both research laboratory-confirmed influenza (adjusted odds ratio [AOR] 3.04 95%CI 1.26-7.35 and clinical laboratory-confirmed influenza (AOR 3.05, 95%CI 1.07-8.71 were independently associated with antiviral treatment. Severity of disease, presence of a high-risk condition, and symptom duration were not associated with antiviral use.In urban Tennessee, antiviral use was low in patients recognized to have influenza by the provider as well as those unrecognized to have influenza. The use of antivirals remained low despite recommendations to treat all hospitalized patients with confirmed or suspected influenza.

  6. Prophylactic Antiviral Treatment in Recurrent Herpes Zoster: A Case Report

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    Hatice Gamze Bayram

    2011-06-01

    Full Text Available Herpes zoster (HZ occurs in older ages with activation of varicella-zoster virus (VZV which persists in a dormant phase within the dorsal root ganglia. The incidence of HZ in immunosuppressed patients is 20-100 times higher and the clinical progress is more severe than in immunocompetent individuals. A 48-year-old man who had been diagnosed with acute myelocytic leukemia type M3 and had been treated with immunosuppressive agents was admitted to our clinic. The patient was clinically diagnosed as having HZ. He was treated with acyclovir 800 mg five times daily for 7 days. In the consecutive three months, he attended our clinic again with similar complaints. The left cervical (C5, C6 dermatomes were involved at the fourth attack of HZ. Multinucleated giant cells were determined on the Tzanck smear. VZV DNA was detected by polymerase chain reaction (PCR. Treatment with valacyclovir 1 g three times daily for 14 days was prescribed and then, prophylactic treatment with valacyclovir 500 mg two times a day was administered. Although immunosuppressive treatment was continued, no new attacks of herpes zoster occurred. We think that prophylactic antiviral therapy should be initiated in immunosuppressive individuals who have recurrent herpes zoster attacks.

  7. Herpesvirus infections in immunocompromised patients : treatment, treatment failure and antiviral resistance

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    Beek, Martha Trijntje van der

    2012-01-01

    The research described in this thesis aims to study determinants of the course and outcome of treatment of herpesvirus infections in immunocompromised patients. Both viral factors, such as antiviral resistance, and patient factors, including immunological parameters, were investigated. Techniques to

  8. New antivirals for the treatment of chronic hepatitis B.

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    Soriano, Vincent; Barreiro, Pablo; Benitez, Laura; Peña, Jose M; de Mendoza, Carmen

    2017-07-01

    Current treatment with oral nucleos(t)ides entecavir or tenofovir provide sustained suppression of HBV replication and clinical benefit in most chronic hepatitis B virus (HBV) infected persons. However, HBV rebound generally occurs upon drug discontinuation due to persistence of genomic HBV reservoirs as episomic cccDNA and chromosomic integrated HBV-DNA. There is renewed enthusiasm on HBV drug discovery following recent successes with antivirals for hepatitis C and immunotherapies for some cancers. Areas covered: New drugs that target distinct steps of the HBV life cycle are been developed, including inhibitors of viral entry, new polymerase inhibitors, capsid and assembly inhibitors, virus release blockers, and disruptors of cccDNA formation and transcription. Alongside these antivirals, agents that enhance anti-HBV specific immune responses are being tested, including TLR agonists, checkpoint inhibitors and therapeutic vaccines. Expert opinion: The achievement of a 'functional cure' for chronic HBV infection, with sustained HBsAg clearance and undetectable viremia once medications are stopped, represents the next step in the pace towards HBV elimination. Hopefully, the combination of new drugs that eliminate or functionally inactivate the genomic HBV reservoirs (cccDNA and integrated HBV-DNA) along with agents that enhance or activate immune responses against HBV will lead to a 'definitive cure' for chronic HBV infection.

  9. Antiviral stockpiles for influenza pandemics from the household perspective: treatment alone versus treatment with prophylaxis.

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    Kwok, Kin On; Leung, Gabriel M; Mak, Peter; Riley, Steven

    2013-06-01

    Model-based studies of antiviral use to mitigate the impact of moderate and severe influenza pandemics implicitly take the viewpoint of a central public health authority. However, it seems likely that the key decision of when to use antivirals will be made at the household level. We used a stochastic compartmental model of the transmission of influenza within and between households to evaluate the expected mortality under two strategies: households saving available antivirals for treatment only and households implementing prophylaxis as well as treatment. Given that every individual in the population was allocated a single course of antivirals, we investigated the impact of these two strategies for a wide range of AVED, the efficacy of antivirals in preventing death in severe cases (AVED=1 for complete protection). We found a cross-over point for our baseline parameter values in a regime where antivirals were still highly effective in reducing the chance of death: below AVED=0.9 the optimal strategy was for households to use both treatment and prophylaxis. We also considered the possibility that a small number of households might "cheat" by choosing to follow the treatment-only strategy when other households were following treatment with prophylaxis. The cross-over point for cheating households was considerably lower, at AVED=0.6, but substantially above 0. These results suggest that unless antivirals are almost completely effective in reducing the chance of death in serious cases, households will likely be better served implementing prophylaxis as well as treatment. More generally, our study illustrates the potential value of considering viewpoints other than a central authority when conducting model-based analysis of interventions against infectious disease. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Antiviral treatment for chronic hepatitis C in patients with human immunodeficiency virus

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    Iorio, Alfonso; Marchesini, Emanuela; Awad, Tahany

    2010-01-01

    Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV).......Antiviral treatment for chronic hepatitis C may be less effective if patients are co-infected with human immunodeficiency virus (HIV)....

  11. Corticosteroids vs corticosteroids plus antiviral agents in the treatment of Bell palsy: a systematic review and meta-analysis.

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    Goudakos, John K; Markou, Konstantinos D

    2009-06-01

    To review systematically and meta-analyze the results of all randomized controlled trials (RCTs) for the treatment of patients with Bell palsy with corticosteroids vs corticosteroids plus antiviral agents. A MEDLINE, EMBASE, Cochrane Library, and CENTRAL database search, followed by extensive hand-searching for the identification of relevant studies. No time and language limitations were applied. Prospective RCTs on the treatment of patients with Bell palsy. Odds ratios (ORs), 95% confidence intervals (CIs), and tests for heterogeneity were reported. Five studies were eventually identified and systematically reviewed. Meta-analysis was performed for 4 studies. Regarding the complete recovery rate of facial nerve paralysis 3 months after initiation of therapy, the current systematic review and meta-analysis suggests that the addition of an antiviral agent does not provide any benefit (OR, 1.03 [95% CI, 0.74-1.42]; P = .88). The same conclusion emerged at posterior (fourth, sixth, and ninth) months of assessment. Subgroup analysis, conducted on the basis of time point of therapy initiation, type of antiviral agent, and blindness of assessments did not change the results obtained. The occurrence rate of adverse effects attributable to therapy choice was not significantly different between patients receiving corticosteroids and those following combined treatment. The present systematic review and meta-analysis, based on the currently available evidence, suggests that the addition of an antiviral agent to corticosteroids for the treatment of Bell palsy is not associated with an increase in the complete recovery rate of the facial motor function.

  12. Viral Response to Specifically Targeted Antiviral Therapy for Hepatitis C and the Implications for Treatment Success

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    Curtis L Cooper

    2010-01-01

    Full Text Available Currently, hepatitis C virus (HCV antiviral therapy is characterized by long duration, a multitude of side effects, difficult administration and suboptimal success; clearly, alternatives are needed. Collectively, specifically targeted antiviral therapy for HCV (STAT-C molecules achieve rapid viral suppression and very high rapid virological response rates, and improve sustained virological response rates. The attrition rate of agents within this class has been high due to various toxicities. Regardless, several STAT-C molecules are poised to become the standard of care for HCV treatment in the foreseeable future. Optimism must be tempered with concerns related to the rapid development of drug resistance with resulting HCV rebound. Strategies including induction dosing with interferon and ribavirin, use of combination high-potency STAT-C molecules and an intensive emphasis on adherence to HCV antiviral therapy will be critical to the success of this promising advance in HCV therapy.

  13. Use of competitive polymerase chain reaction to determine HIV-1 levels in response to antiviral treatments

    NARCIS (Netherlands)

    Bruisten, S. M.; Koppelman, M. H.; Roos, M. T.; Loeliger, A. E.; Reiss, P.; Boucher, C. A.; Huisman, H. G.

    1993-01-01

    OBJECTIVE: To develop a competitive polymerase chain reaction technique with which to evaluate the usefulness of HIV-1 level as a marker of response to antiviral treatment. DESIGN: HIV-1 sequences were assessed by competitive polymerase chain reaction in four subjects participating in a double-blind

  14. Chronic Hepatitis C and Antiviral Treatment Regimens: Where Can Psychology Contribute?

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    Evon, Donna M.; Golin, Carol E.; Fried, Michael W.; Keefe, Francis J.

    2013-01-01

    Objective: Our goal was to evaluate the existing literature on psychological, social, and behavioral aspects of chronic hepatitis C viral (HCV) infection and antiviral treatment; provide the state of the behavioral science in areas that presently hinder HCV-related health outcomes; and make recommendations for areas in which clinical psychology…

  15. Cost-effectiveness of hepatitis C treatment using generic direct-acting antivirals available in India.

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    Rakesh Aggarwal

    Full Text Available Availability of directly-acting antivirals (DAAs has changed the treatment landscape of hepatitis C virus (HCV infection. The high price of DAAs has restricted their use in several countries. However, in some countries such as India, generic DAAs are available at much cheaper price. This study examined whether generic DAAs could be cost-saving and how long it would take for the treatment to become cost-saving/effective.A previously-validated, mathematical model was adapted to the HCV-infected population in India to compare the outcomes of no treatment versus treatment with DAAs. Model parameters were estimated from published studies. Cost-effectiveness of HCV treatment using available DAAs was calculated, using a payer's perspective. We estimated quality-adjusted life years (QALYs, disability-adjusted life years (DALYs, total costs, and incremental cost-effectiveness ratio of DAAs versus no treatment. One-way and probabilistic sensitivity analyses were conducted.Compared with no treatment, the use of generic DAAs in Indian HCV patients would increase the life expectancy by 8.02 years, increase QALYs by 3.89, avert 19.07 DALYs, and reduce the lifetime healthcare costs by $1,309 per-person treated. Treatment became cost-effective within 2 years, and cost-saving within 10 years of its initiation overall and within 5 years in persons with cirrhosis. Treating 10,000 HCV-infected persons could prevent 3400-3850 decompensated cirrhosis, 1800-2500 HCC, and 4000-4550 liver-related deaths. The results were sensitive to the costs of DAAs, pre- and post-treatment diagnostic tests and management of cirrhosis, and quality of life after sustained virologic response.Treatment with generic DAAs available in India will improve patient outcomes, provide a good value for money within 2 years, and be ultimately cost-saving. Therefore, in this and similar settings, HCV treatment should be a priority from a public health as well an economic perspective.

  16. Clinical case of Successful Treatment by Antiviral Preparations of a Patient with Guillain — Barre Syndrome

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    E.Yu. Vinnyk

    2015-11-01

    Full Text Available There is described a clinical case of treatment of patients with acute Guillain — Barre syndrome of significant viral etiology. It was used the complex therapy with antiviral drugs according to the recommendations of the infectious disease specialist. In addition to basic therapy and plasma depletion, there were prescribed the preparation of acyclic nucleosides group, interferon and normal human immunoglobulin. The age of the latter significantly reduced the period of recovery of the patient and allow avoid complications.

  17. Effect of a short-term HAART on SIV load in macaque tissues is dependent on time of initiation and antiviral diffusion

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    Durand-Gasselin Lucie

    2010-09-01

    Full Text Available Abstract Background HIV reservoirs are rapidly established after infection, and the effect of HAART initiated very early during acute infection on HIV reservoirs remains poorly documented, particularly in tissue known to actively replicate the virus. In this context, we used the model of experimental infection of macaques with pathogenic SIV to assess in different tissues: (i the effect of a short term HAART initiated at different stages during acute infection on viral dissemination and replication, and (ii the local concentration of antiviral drugs. Results Here, we show that early treatment with AZT/3TC/IDV initiated either within 4 hours after intravenous infection of macaques with SIVmac251 (as a post exposure prophylaxis or before viremia peak (7 days post-infection [pi], had a strong impact on SIV production and dissemination in all tissues but did not prevent infection. When treatment was initiated after the viremia peak (14 days pi or during early chronic infection (150 days pi, significant viral replication persists in the peripheral lymph nodes and the spleen of treated macaques despite a strong effect of treatment on viremia and gut associated lymphoid tissues. In these animals, the level of virus persistence in tissues was inversely correlated with local concentrations of 3TC: high concentrations of 3TC were measured in the gut whereas low concentrations were observed in the secondary lymphoid tissues. IDV, like 3TC, showed much higher concentration in the colon than in the spleen. AZT concentration was below the quantification threshold in all tissues studied. Conclusions Our results suggest that limited antiviral drug diffusion in secondary lymphoid tissues may allow persistent viral replication in these tissues and could represent an obstacle to HIV prevention and eradication.

  18. [A new challenge in clinical practice: resistance to directly acting antivirals in hepatitis C treatment].

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    Chen, Z W; Hu, P; Ren, H

    2016-03-20

    Directly acting antivirals (DAAs) is a major treatment of hepatitis C virus (HCV) overseas. But DAAs resistance is getting more and more clinicians' attention. DAAs have not been approved in China to date, even though some of them are in clinical trials. However, a good knowledge of DAAs resistance is important on optimizing HCV treatment regimens, increasing sustained virological response (SVR) and decreasing treatment failure in clinical. In this review, DAAs resistance mechanism and virologic barrier to resistance, the prevalence of pre-existing DAAs resistance-associated variants (RAVs), the impact of RAVs on treatment outcome, the options of treatment regimens after resistance and drug resistance testing are discussed, hoping to provide some help for DAAs' standardized treatment in China in the future.

  19. Mechanism of action of direct-acting antiviral agents in treatment of chronic hepatitis C

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    WEN Xiaoyu

    2016-09-01

    Full Text Available With the development and launch of direct-acting antiviral agents (DAAs in the world in recent years, therapeutic regimens for chronic hepatitis C are constantly evolving. DAAs will also be launched in China in the near future. DAAs mainly target at the non-structural proteins of HCV and can inhibit HCV RNA replication. This article introduces the targets, mechanism of action, and resistance characteristics of different DAAs, as well as their current research and development in China and the results of phase Ⅲ clinical studies, in order to provide a reference for combined therapeutic strategies with DAAs in the treatment for chronic hepatitis C.

  20. Study of Preoperative Antiviral Treatment of Patients with HCC Negative for HBV-DNA.

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    Liu, Xiao-Fang; Zhang, Tong; Tang, Kun; Sui, Lu-Lu; Xu, Gang; Liu, Qiang

    2017-08-01

    To study preoperative HBV-DNA negative HBV-related hepatocellular carcinoma (HCC) which was reactivated after surgery and could influence liver function and HCC recurrence. Patients were divided into two groups according to preoperative antiviral therapy status. The control group comprised of 102 preoperative HBV-DNA-negative patients who had not undergone antiviral therapy before surgery. In the treatment group, all HBV-DNA-negative patients (n=63) received entecavir 3-5 days before surgery and for 12 months after surgery. Patients were followed-up regularly, during the preoperative period, and at 1, 3, 6, 12, 18, 24, 30 and 36 months postoperatively. The data for the two groups were analyzed including the level of HBV-DNA and HBV-DNA activation; liver function; 1-, 2- and 3-year survival rate; cumulative survival time; and tumor recurrence. Liver function in the treatment group was better than that of the control group12 months after surgery. Compared to the control group, total bilirubin in the treatment group was significantly better at 6 and 12 months after surgery (pHBV-DNA activation while there were 13 cases (12.75%) with HBV-DNA activation in the control group (pHBV-related HCC with negative HBV-DNA is beneficial to liver function, coagulation function, disease control, prevention of tumor recurrence, improvement of patient quality of life, reduces the death rate and prolongs survival duration. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

  1. Antiviral RNA silencing initiated in the absence of RDE-4, a double-stranded RNA binding protein, in Caenorhabditis elegans.

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    Guo, Xunyang; Zhang, Rui; Wang, Jeffrey; Lu, Rui

    2013-10-01

    Small interfering RNAs (siRNAs) processed from double-stranded RNA (dsRNA) of virus origins mediate potent antiviral defense through a process referred to as RNA interference (RNAi) or RNA silencing in diverse organisms. In the simple invertebrate Caenorhabditis elegans, the RNAi process is initiated by a single Dicer, which partners with the dsRNA binding protein RDE-4 to process dsRNA into viral siRNAs (viRNAs). Notably, in C. elegans this RNA-directed viral immunity (RDVI) also requires a number of worm-specific genes for its full antiviral potential. One such gene is rsd-2 (RNAi spreading defective 2), which was implicated in RDVI in our previous studies. In the current study, we first established an antiviral role by showing that rsd-2 null mutants permitted higher levels of viral RNA accumulation, and that this enhanced viral susceptibility was reversed by ectopic expression of RSD-2. We then examined the relationship of rsd-2 with other known components of RNAi pathways and established that rsd-2 functions in a novel pathway that is independent of rde-4 but likely requires the RNA-dependent RNA polymerase RRF-1, suggesting a critical role for RSD-2 in secondary viRNA biogenesis, likely through coordinated action with RRF-1. Together, these results suggest that RDVI in the single-Dicer organism C. elegans depends on the collective actions of both RDE-4-dependent and RDE-4-independent mechanisms to produce RNAi-inducing viRNAs. Our study reveals, for the first time, a novel siRNA-producing mechanism in C. elegans that bypasses the need for a dsRNA-binding protein.

  2. Co-infection with HIV associated with reduced vulnerability to symptoms of depression during antiviral treatment for hepatitis C.

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    Fialho, Renata; Pereira, Marco; Harrison, Neil; Rusted, Jennifer; Whale, Richard

    2017-07-01

    In this prospective study, we examined new-onset major depressive disorder (MDD) and the differential expression of depressive symptoms in a sample of 132 HCV mono-infected and 40 HIV/HCV co-infected patients initiating pegylated interferon-based treatment, including protease inhibitor therapy. The semi-structured clinical interview (SCID-I) was used to assess MDD. Severity of depressive symptoms was assessed using the Hamilton Depression Rating Scale. Of the total sample, 60 patients (34.9%) developed SCID-I defined MDD during antiviral treatment. The proportion of HCV mono- and HIV/HCV patients developing MDD during treatment was not significantly different (37.9% vs. 25%; p=0.185). In both groups, there was a significant increase in HAMD total score from baseline to week 4, and a significant decrease between week 24 and 6 months post-treatment cessation. The greatest increase was observed in the symptoms of the neurovegetative syndrome. HCV mono-infected patients reported higher scores than co-infected patients, particularly impaired activity and somatic symptoms, but the differences were only significant at week 12. The finding that co-infected patients appear less vulnerable to the development of depressive symptoms during HCV treatment than HCV mono-infected patients warrants further exploration, including a thorough analysis of the biological and psychosocial factors associated with this emergence. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

  3. Retreatment of patients with treatment failure of direct-acting antivirals: Focus on hepatitis C virus genotype 1b.

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    Kanda, Tatsuo; Nirei, Kazushige; Matsumoto, Naoki; Higuchi, Teruhisa; Nakamura, Hitomi; Yamagami, Hiroaki; Matsuoka, Shunichi; Moriyama, Mitsuhiko

    2017-12-14

    The recent development of direct-acting antiviral agents (DAAs) against hepatitis C virus (HCV) infection could lead to higher sustained virological response (SVR) rates, with shorter treatment durations and fewer adverse events compared with regimens that include interferon. However, a relatively small proportion of patients cannot achieve SVR in the first treatment, including DAAs with or without peginterferon and/or ribavirin. Although retreatment with a combination of DAAs should be conducted for these patients, it is more difficult to achieve SVR when retreating these patients because of resistance-associated substitutions (RASs) or treatment-emergent substitutions. In Japan, HCV genotype 1b (GT1b) is founded in 70% of HCV-infected individuals. In this minireview, we summarize the retreatment regimens and their SVR rates for HCV GT1b. It is important to avoid drugs that target the regions targeted by initial drugs, but next-generation combinations of DAAs, such as sofosbuvir/velpatasvir/voxilaprevir for 12 wk or glecaprevir/pibrentasvir for 12 wk, are proposed to be potential solution for the HCV GT1b-infected patients with treatment failure, mainly on a basis of targeting distinctive regions. Clinicians should follow the new information and resources for DAAs and select the proper combination of DAAs for the retreatment of HCV GT1b-infected patients with treatment failure.

  4. Bay laurel (Laurus nobilis) as potential antiviral treatment in naturally BQCV infected honeybees.

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    Aurori, Adriana C; Bobiş, Otilia; Dezmirean, Daniel S; Mărghitaş, Liviu A; Erler, Silvio

    2016-08-15

    Viral diseases are one of the multiple factors associated with honeybee colony losses. Apart from their innate immune system, including the RNAi machinery, honeybees can use secondary plant metabolites to reduce or fully cure pathogen infections. Here, we tested the antiviral potential of Laurus nobilis leaf ethanolic extracts on forager honeybees naturally infected with BQCV (Black queen cell virus). Total viral loads were reduced even at the lowest concentration tested (1mg/ml). Higher extract concentrations (≥5mg/ml) significantly reduced virus replication. Measuring vitellogenin gene expression as an indicator for transcript homeostasis revealed constant RNA levels before and after treatment, suggesting that its expression was not impacted by the L. nobilis treatment. In conclusion, plant secondary metabolites can reduce virus loads and virus replication in naturally infected honeybees. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Health-related quality of life in patients with chronic hepatitis B during antiviral treatment and off-treatment

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    Xue X

    2017-01-01

    Full Text Available Xiulan Xue,1,* Shaohang Cai,1–3,* Hongjie Ou,1 Caixia Zheng,1 Xiaolu Wu1 1Department of Infectious Diseases, First Affiliated Hospital of Xiamen University, Xiamen, Fujian Province, 2Department of Pathology, Sun Yat-sen University Cancer Center, 3State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong Province, People’s Republic of China *These authors contributed equally to this work Introduction: Health-related quality of life (HRQoL has emerged as an important consideration in the care of patients with chronic hepatitis B (CHB. However, whether benefits from the improved HRQoL that occurs after antiviral treatment or drug discontinuation outweigh the risks of viral relapse is an unanswered question. The aim of this study was to evaluate the HRQoL among patients with CHB during antiviral treatment and withdrawal of treatment. Patients and methods: There were 102 patients who met the enrollment criteria with 54 patients in the treatment group and 48 patients in the discontinuation group. Sociodemographic information was collected. The 36-Item Short-Form Health Survey (SF-36, European Quality of Life-5 Dimensions, and Beck Depression Inventory (BDI were adopted to evaluate life quality and mental health. Results: In the treatment group, SF-36 showed that the physical functions were significantly increased. In the discontination group, the psychological functions showed improvement. A multivariate regression analysis indicated that baseline SF-36 score was a predictor for improvement in HRQoL (odds ratio =1.17, P=0.003 and baseline BDI score was a factor for remission of depression (odds ratio =0.75, P=0.005 after medical intervention. When the cutoff value of SF-36 score was set at 79.5, the sensitivity and specificity to predict improvement in HRQoL were 82.8% and 74.0%, respectively. When the cutoff value of BDI was found as 8.5, the sensitivity and specificity to predict

  6. Antiviral Efficacy and Host Innate Immunity Associated with SB 9200 Treatment in the Woodchuck Model of Chronic Hepatitis B.

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    Kyle E Korolowicz

    Full Text Available SB 9200, an oral prodrug of the dinucleotide SB 9000, is being developed for the treatment of chronic hepatitis B virus (HBV infection and represents a novel class of antivirals. SB 9200 is thought to activate the viral sensor proteins, retinoic acid-inducible gene 1 (RIG-I and nucleotide-binding oligomerization domain-containing protein 2 (NOD2 resulting in interferon (IFN mediated antiviral immune responses in virus-infected cells. Additionally, the binding of SB 9200 to these sensor proteins could also sterically block the ability of the viral polymerase to access pre-genomic RNA for nucleic acid synthesis. The immune stimulating and direct antiviral properties of SB 9200 were evaluated in woodchucks chronically infected with woodchuck hepatitis virus (WHV by daily, oral dosing at 15 and 30 mg/kg for 12 weeks. Prolonged treatment resulted in 2.2 and 3.7 log10 reductions in serum WHV DNA and in 0.5 and 1.6 log10 declines in serum WHV surface antigen from pretreatment level with the lower or higher dose of SB 9200, respectively. SB 9200 treatment also resulted in lower hepatic levels of WHV nucleic acids and antigen and reduced liver inflammation. Following treatment cessation, recrudescence of viral replication was observed but with dose-dependent delays in viral relapse. The antiviral effects were associated with dose-dependent and long-lasting induction of IFN-α, IFN-β and IFN-stimulated genes in blood and liver, which correlated with the prolonged activation of the RIG-I/NOD2 pathway and hepatic presence of elevated RIG-I protein levels. These results suggest that in addition to a direct antiviral activity, SB 9200 induces antiviral immunity during chronic hepadnaviral infection via activation of the viral sensor pathway.

  7. The effectiveness of different antiviral treatment regimens in patients with chronic hepatitis C infected with genotype 3 virus

    Directory of Open Access Journals (Sweden)

    E.V. Riabokon

    2018-02-01

    Full Text Available Background. Chronic hepatitis C (CHC remains one of the most urgent problems of modern infectology. In recent years, the principles of antiviral therapy have substantially changed due to the emergence of new drugs with a direct mechanism of action and the development of non-interferon treatment regimens. Two regimens included HCV NS5B polymerase inhibitors were available in Ukraine for treating CHC patients infected with genotype 3 virus. Objective: to analyze the effectiveness of different schemes of antiviral treatment in patients with chronic hepatitis C infected with genotype 3 virus. Materials and methods. The study included 66 patients with CHC infected with genotype 3 virus. All patients underwent study of liver fibrosis degree by the method of fibrotest; in the dynamics, we have tested viral load, liver tests, indicators of complete blood count, functional kidney tests. Antiviral treatment and analysis of its effectiveness were carried out in accordance with the Unified Protocol of the Ministry of Health of Ukraine. Results. According to the results of treating CHC patients infected with genotype 3 virus, high efficacy of both applied schemes of antiviral therapy in clinical practice is shown. A rapid virologic response occurred in 93.5 % of CHC patients treated with peginterferon (peg-IFN α2a + sofosbuvir (SOF + ribavirin (RBV regimen, and in 82.9 % of patients receiving non-interferon therapy with SOF + RBV. The immediate response to treatment was achieved according to treatment regimens in 90.3 and 94.3 % of patients. Sustained virological response at week 24 after antiviral treatment was noted in 87.5 and 91.4 % of patients, respectively. The frequency of virological response to antiviral treatment in CHC patients infected with genotype 3 virus did not depend on the stage of liver fibrosis, either in the use of non-interferon treatment by SOF + RBV scheme, or in the treatment with interferon-containing scheme included the drug with

  8. Neurological outcomes in symptomatic congenital cytomegalovirus-infected infants after introduction of newborn urine screening and antiviral treatment.

    Science.gov (United States)

    Nishida, Kosuke; Morioka, Ichiro; Nakamachi, Yuji; Kobayashi, Yoko; Imanishi, Takamitsu; Kawano, Seiji; Iwatani, Sota; Koda, Tsubasa; Deguchi, Masashi; Tanimura, Kenji; Yamashita, Daisuke; Nibu, Ken-Ichi; Funakoshi, Toru; Ohashi, Masanobu; Inoue, Naoki; Iijima, Kazumoto; Yamada, Hideto

    2016-02-01

    Newborn screening for urinary cytomegalovirus (CMV) and early introduction of antiviral treatment are expected to improve neurological outcomes in symptomatic congenital CMV-infected infants. This cohort study prospectively evaluated neurological outcomes in symptomatic congenital CMV-infected infants following the introduction of hospital-based newborn urinary CMV screening and antiviral treatment. Following institutional review board approval and written informed consent from their parents, newborns were prospectively screened from 2009 to 2014 for urinary CMV-DNA by PCR within 1 week after birth at Kobe University Hospital and affiliated hospitals. CMV-positive newborns were further examined at Kobe University Hospital, and those diagnosed as symptomatic were treated with valganciclovir for 6 weeks plus immunoglobulin. Clinical neurological outcomes were evaluated at age ⩾12 months and categorized by the presence and severity of neurologic sequelae. Urine samples of 6348 newborns were screened, with 32 (0.50%) positive for CMV. Of these, 16 were diagnosed with symptomatic infection and 12 received antiviral treatment. Four infants developed severe impairment (33%), three developed mild impairment (25%), and five developed normally (42%). This is the first Japanese report of neurological assessments in infants with symptomatic congenital CMV infection who received early diagnosis and antiviral treatment. Urinary screening, resulting in early diagnosis and treatment, may yield better neurological outcomes in symptomatic congenital CMV-infected infants. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  9. Initial treatment of Parkinson's disease.

    Science.gov (United States)

    Tarsy, Daniel

    2006-05-01

    Initial treatment of early idiopathic Parkinson's disease (PD) begins with diagnosis based on clinical evaluation supplemented by laboratory studies and brain imaging to exclude causes of secondary parkinsonism. In most cases, testing is normal and the diagnosis of PD rests on clinical criteria. In patients with mild symptoms and signs, the diagnosis of PD may not initially be apparent, and follow-up evaluation is needed to arrive at a diagnosis. Once the diagnosis is made, pharmacologic treatment may not be the first step. First, patient education is essential, especially because PD is a high-profile disease for which information and misinformation are readily available to patients and families. Counseling concerning prognosis, future symptoms, future disability, and treatment must be provided. Questions from patients concerning diet, lifestyle, and exercise are especially common at this point. The decision of when to initiate treatment is the next major consideration. Much controversy but relatively little light has been brought to bear on this issue. L-dopa was the first major antiparkinson medication to be introduced and remains the "gold standard" of treatment. Next in efficacy are the dopamine agonists (DAs). A debate has raged concerning whether initial dopaminergic treatment should be with L-dopa or DAs. Physicians have been concerned about forestalling the appearance of dyskinesias and motor fluctuations, whereas patients have incorrectly understood that L-dopa and possibly other antiparkinson drugs have a finite duration of usefulness, making it important to defer treatment for as long as possible. This has created "L-dopa phobia," which may stand in the way of useful treatment. In spite of this controversy, there is uniform agreement that the appropriate time to treat is when the patient is beginning to be disabled. This varies from patient to patient and depends on age, employment status, nature of job, level of physical activity, concern about

  10. 75 FR 11189 - Expanded Access to Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C...

    Science.gov (United States)

    2010-03-10

    ... viral hepatitis and from 70 to 90 percent of all cases of hepatocellular carcinoma. An estimated 3.2...] Expanded Access to Direct-Acting Antiviral Agents for the Treatment of Chronic Hepatitis C Infection in... hepatitis C (CHC) infection in patients with unmet medical need. This public hearing is being held to obtain...

  11. HIV-1 reverse transcription initiation: a potential target for novel antivirals?

    NARCIS (Netherlands)

    Abbink, Truus E. M.; Berkhout, Ben

    2008-01-01

    Reverse transcription is an essential step in the retroviral life cycle, as it converts the genomic RNA into DNA. In this review, we describe recent developments concerning the initiation step of this complex, multi-step reaction. During initiation of reverse transcription, a cellular tRNA primer is

  12. Treatment of chronic hepatitis C with direct-acting antivirals: The role of resistance.

    Science.gov (United States)

    Jiménez-Pérez, Miguel; González-Grande, Rocío; España Contreras, Pilar; Pinazo Martínez, Isabel; de la Cruz Lombardo, Jesús; Olmedo Martín, Raúl

    2016-08-07

    The use of direct-acting antivirals (DAAs) to treat chronic hepatitis C has resulted in a significant increase in rates of sustained viral response (around 90%-95%) as compared with the standard treatment of peginterferon/ribavirin. Despite this, however, the rates of therapeutic failure in daily clinical practice range from 10%-15%. Most of these cases are due to the presence of resistant viral variants, resulting from mutations produced by substitutions of amino acids in the viral target protein that reduce viral sensitivity to DAAs, thus limiting the efficacy of these drugs. The high genetic diversity of hepatitis C virus has resulted in the existence of resistance-associated variants (RAVs), sometimes even before starting treatment with DAAs, though generally at low levels. These pre-existing RAVs do not appear to impact on the sustained viral response, whereas those that appear after DAA therapy could well be determinant in virological failure with future treatments. As well as the presence of RAVs, virological failure to treatment with DAAs is generally associated with other factors related with a poor response, such as the degree of fibrosis, the response to previous therapy, the viral load or the viral genotype. Nonetheless, viral breakthrough and relapse can still occur in the absence of detectable RAVs and after the use of highly effective DAAs, so that the true clinical impact of the presence of RAVs in therapeutic failure remains to be determined.

  13. Depletion of elongation initiation factor 4E binding proteins by CRISPR/Cas9 genome editing enhances antiviral response in porcine cells

    Science.gov (United States)

    Type I interferons (IFN) are key mediators of the innate antiviral response in mammalian cells. Elongation initiation factor 4E binding proteins (4E-BPs) are translational controllers of interferon regulatory factor 7 (IRF7), the master regulator of IFN transcription. The role of 4EBPs in the negat...

  14. Treatment of Decompensated Cirrhosis Secondary to Hepatitis C with Antiviral Therapy

    International Nuclear Information System (INIS)

    Khokhar, N.; Qureshi, M.O.; Niazi, T.K.

    2013-01-01

    Objective: To treat decompensated hepatitis C patient with interferon, ribavirin and amantidine to ascertain the sustained viral response. Study Design: Descriptive study. Place and Duration of Study: Shifa International Hospital, Islamabad, from January 2007 to January 2012. Methodology: HCV PCR patients with decompensated hepatitis C, who had developed a complication like ascites, encephalopathy or variceal bleeding were included in the study. Those with uncontrolled ascites or other complications were excluded. Treatment with standard interferon 3 miU subcutaneously three times a week along with ribavirin 800 mg to 1200 mg and amantidine 100 mg b.i.d. was administered for 12 months. Patients were followed every month with CBC and ALT and HCV PCR was performed after 3 months to document early viral response. They had HCV PCR at the end of the treatment to document end of treatment response. All were further followed for another 6 months at monthly intervals and HCV PCR was performed at the end of this period to document sustained viral response. Results: In all, 165 patients were treated. Treatment had to be discontinued in 42 (26%) patients. Out of these, 16 patients died. Thus, 123 completed treatment. Sustained viral response was documented in 58 out of the 123 (47%) patients. Hepatic encephalopathy, gastrointestinal bleeding, sepsis and development of ascites were the major complications during treatment. Conclusion: Forty seven percent of patients with decompensated hepatitis C cirrhosis were able to achieve sustained viral response after one year treatment with anti-viral therapy. However, complications developed during treatment and, therefore, frequent and close monitoring is necessary in these patients. (author)

  15. Antiviral Stilbene 1,2-Diamines Prevent Initiation of Hepatitis C Virus RNA Replication at the Outset of Infection▿

    Science.gov (United States)

    Gastaminza, Pablo; Pitram, Suresh M.; Dreux, Marlene; Krasnova, Larissa B.; Whitten-Bauer, Christina; Dong, Jiajia; Chung, Josan; Fokin, Valery V.; Sharpless, K. Barry; Chisari, Francis V.

    2011-01-01

    The recent development of a cell culture model of hepatitis C virus (HCV) infection based on the JFH-1 molecular clone has enabled discovery of new antiviral agents. Using a cell-based colorimetric screening assay to interrogate a 1,200-compound chemical library for anti-HCV activity, we identified a family of 1,2-diamines derived from trans-stilbene oxide that prevent HCV infection at nontoxic, low micromolar concentrations in cell culture. Structure-activity relationship analysis of ∼300 derivatives synthesized using click chemistry yielded compounds with greatly enhanced low nanomolar potency and a >1,000:1 therapeutic ratio. Using surrogate models of HCV infection, we showed that the compounds selectively block the initiation of replication of incoming HCV RNA but have no impact on viral entry, primary translation, or ongoing HCV RNA replication, nor do they suppress persistent HCV infection. Selection of an escape variant revealed that NS5A is directly or indirectly targeted by this compound. In summary, we have identified a family of HCV inhibitors that target a critical step in the establishment of HCV infection in which NS5A translated de novo from an incoming genomic HCV RNA template is required to initiate the replication of this important human pathogen. PMID:21430055

  16. TMC125 exerts similar initial antiviral potency as a five-drug, triple class antiretroviral regimen

    NARCIS (Netherlands)

    Sankatsing, Sanjay U. C.; Weverling, Gerrit J.; Peeters, Monika; van't Klooster, Gerben; Gruzdev, Boris; Rakhmanova, Aza; Danner, Sven A.; Jurriaans, Suzanne; Prins, Jan M.; Lange, Joep M. A.

    2003-01-01

    Objective: TMC125, a next generation, non-nucleoside reverse transcriptase inhibitor (NNRTI), demonstrated a remarkable decline of plasma HIV-1 RNA during a phase IIa study. We compared the initial rate of decline of plasma HIV-1 RNA achieved by TMC125 monotherapy with that of a triple class,

  17. The value of some genetic factors for prediction of chronic hepatitis C antiviral treatment effectiveness

    Directory of Open Access Journals (Sweden)

    V. M. Mitsura

    2014-01-01

    Full Text Available Aim: To determine the value of gene polymorphisms of interleukin-28B (IL28B, RNase L, HLA DRB1*1101 and HLADQB1*03 alleles as predictors of antiviral treatment efficacy in patients with chronic hepatitis C (CHC.Material and methods. A total of 156 in-patients with chronic hepatitis C (65.4% men, 62.4% had genotype 1 hepatitis C virus – HCV were studied. The results of treatment with interferon (IFN and ribavirin (RBV were analyzed in 74 patients. Polymerase chain reaction identified single nucleotide polymorphisms (SNP of the gene IL28B 39743165T>G (rs8099917, SNP 39738787C> T (rs12979860, RNase L gene (1385G>A, HLA DRB1*1101 and HLA-DQB1*03 alleles.Results. In patients with HCV genotype 1 mutant alleles were more common in SNP 39743165T>G (p=0.001 and 39738787C>T (p=0.0002 than in patients with other genotypes. Response to therapy IFN/RBV was higher in those with “favorable” TT variant (SNP 39743165T>G and CC (SNP 39738787C>T, in those with their combination virologic response ffect were found according to genes IL28B and RNase L SNP variants, DRB1*1101 and HLA-DQB1*03 alleles.Conclusion. Testing for SNP 39738787C>T of IL28B gene is recommended before starting therapy IFN / RBV for all patients with genotype 1 HCV as a predictor of treatment response. Testing SNP 1385G>A gene RNase L and DRB1*1101, HLA-DQB1*03 alleles has no apparent prognostic value for patients with CHC antiviral therapy.

  18. Future of liver disease in the era of direct acting antivirals for the treatment of hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Francesca Romana Ponziani; Francesca Mangiola; Cecilia Binda; Maria Assunta Zocco; Massimo Siciliano; Antonio Grieco; Gian Lodovico Rapaccini; Maurizio Pompili; Antonio Gasbarrini

    2017-01-01

    Hepatitis C virus(HCV) infection has been a global health problem for decades, due to the high number of infected people and to the lack of effective and welltolerated therapies. In the last 3 years, the approval of new direct acting antivirals characterized by high rates of virological clearance and excellent tolerability has dramatically improved HCV infection curability, especially for patients with advanced liver disease and for liver transplant recipients. Long-term data about the impact of the new direct acting antivirals on liver fibrosis and liver disease-related outcomes are not yet available, due to their recent introduction. However, previously published data deriving from the use of pegylatedinterferon and ribavirin lead to hypothesizing that we are going to observe, in the future, a reduction in mortality and in the incidence of hepatocellular carcinoma, as well as a regression of fibrosis for people previously affected by hepatitis C. In the liver transplant setting, clinical improvement has already been described after treatment with the new direct acting antivirals, which has often led to patients delisting. In the future, this may hopefully reduce the gap between liver organ request and availability, probably expanding liver transplant indications to other clinical conditions. Therefore, these new drugs are going to change the natural history of HCV-related liver disease and the epidemiology of HCV infection worldwide. However, the global consequences will depend on treatment accessibility and on the number of countries that could afford the use of the new direct acting antivirals.

  19. Initiation of Antiviral B Cell Immunity Relies on Innate Signals from Spatially Positioned NKT Cells.

    Science.gov (United States)

    Gaya, Mauro; Barral, Patricia; Burbage, Marianne; Aggarwal, Shweta; Montaner, Beatriz; Warren Navia, Andrew; Aid, Malika; Tsui, Carlson; Maldonado, Paula; Nair, Usha; Ghneim, Khader; Fallon, Padraic G; Sekaly, Rafick-Pierre; Barouch, Dan H; Shalek, Alex K; Bruckbauer, Andreas; Strid, Jessica; Batista, Facundo D

    2018-01-25

    B cells constitute an essential line of defense from pathogenic infections through the generation of class-switched antibody-secreting cells (ASCs) in germinal centers. Although this process is known to be regulated by follicular helper T (TfH) cells, the mechanism by which B cells initially seed germinal center reactions remains elusive. We found that NKT cells, a population of innate-like T lymphocytes, are critical for the induction of B cell immunity upon viral infection. The positioning of NKT cells at the interfollicular areas of lymph nodes facilitates both their direct priming by resident macrophages and the localized delivery of innate signals to antigen-experienced B cells. Indeed, NKT cells secrete an early wave of IL-4 and constitute up to 70% of the total IL-4-producing cells during the initial stages of infection. Importantly, the requirement of this innate immunity arm appears to be evolutionarily conserved because early NKT and IL-4 gene signatures also positively correlate with the levels of neutralizing antibodies in Zika-virus-infected macaques. In conclusion, our data support a model wherein a pre-TfH wave of IL-4 secreted by interfollicular NKT cells triggers the seeding of germinal center cells and serves as an innate link between viral infection and B cell immunity. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  20. Nanomedicine formulations for the delivery of antiviral drugs: a promising solution for the treatment of viral infections.

    Science.gov (United States)

    Lembo, David; Donalisio, Manuela; Civra, Andrea; Argenziano, Monica; Cavalli, Roberta

    2018-01-01

    Viral infections represent a public health problem and one of the leading causes of global mortality. Nanomedicine strategies can be considered a powerful tool to enhance the effectiveness of antiviral drugs, often associated with solubility and bioavailability issues. Consequently, high doses and frequent administrations are required, resulting in adverse side effects. To overcome these limitations, various nanomedicine platforms have been designed. Areas covered: This review focuses on the state of the art of organic-based nanoparticles for the delivery of approved antivirals. A brief description of the main characteristics of nanocarriers is followed by an overview of the most promising research addressing the treatment of most important viral infections. Expert opinion: The activity of antiviral drugs could be improved with nanomedicine formulations. Indeed, nanoparticles can affect the fate of the encapsulated drugs, allowing controlled release kinetics, enhanced bioavailability, modified pharmacokinetics, and reduced side effects. In addition, the physicochemical properties of nanocarriers can enable their capability to target specific sites and to interact with virus structures. In this regard, nanomedicines can be considered an opportunity to enhance the therapeutic index of antivirals. Efficacy, safety, and manufacturing issues need to be carefully assessed to bring this promising approach to the clinic.

  1. Direct-Acting Antivirals for the Treatment of Chronic Hepatitis C: Open Issues and Future Perspectives

    Directory of Open Access Journals (Sweden)

    Hee Bok Chae

    2013-01-01

    Full Text Available Currently, two direct-acting antivirals (DAAs show well-established efficacy against hepatitis C virus (HCV, namely, first-wave protease inhibitors telaprevir and boceprevir. Most clinical trials have examined DAAs in combination with standard of care (SOC regimens. Future therapeutic drugs were divided into three categories. They are second-wave protease inhibitors, second-generation protease inhibitors, and polymerase inhibitors. Second-wave protease inhibitors are more improved form and can be administered once a day. Oral drug combinations can be favored because interferon (IFN not only has to be given as intradermal injection, but also can cause several serious side effects. Combination of drugs with different mechanisms shows a good sustained virological response (SVR. But several mutations are associated with viral resistance to DAAs. Therefore, genotypic resistance data may provide insights into strategies aimed at maximizing SVR rates and minimizing resistance. Combined drug regimens are necessary to prevent the emergence of drug-resistant HCV. Many promising DAA candidates have been identified. Of these, a triple regimen containing sofosbuvir shows promise, and treatment with daclatasvir plus asunaprevir yields a high SVR rate (95%. Oral drug combinations will be standard of care in the near future.

  2. Inducible protein-10 as a predictive marker of antiviral hepatitis C treatment

    DEFF Research Database (Denmark)

    Neesgaard, Bastian; Ruhwald, Morten; Weis, Nina

    2017-01-01

    AIM: To investigate interferon-γ-inducible protein-10's (IP-10) potential to anticipate rapid (RVR)- and sustained virological responses (SVR) to chronic hepatitis C (CHC) treatment. METHODS: We included case series examining RVR or SVR in relation to 24 or 48 wk treatment for CHC, in patients...... treatment free for at least six months, with genotype 1 or 4, and in relation to 24 wk treatment for genotype 2 and 3, with pegylated interferon in combination with ribavirin. Patients had to have both a baseline IP-10 level as well as a hepatitis C virus (HCV)-RNA determination 4 wk after treatment...... initiation or 24 wk after end of treatment. Studies including patients with liver diseases other than CHC, human immunodeficiency virus-infection, treatment with immunosuppresents or cytostatica, alcohol dependency or active intravenous drug-use were excluded. We found 81 articles by searching the MEDLINE...

  3. HBV reactivation in patients with HCV/HBV cirrhosis on treatment with direct-acting antivirals.

    Science.gov (United States)

    Calvaruso, V; Ferraro, D; Licata, A; Bavetta, M G; Petta, S; Bronte, F; Colomba, G; Craxì, A; Di Marco, V

    2018-01-01

    Anecdotal reports suggest that patients with chronic hepatitis C virus (HCV) hepatitis and overt or occult hepatitis B virus (HBV) coinfection may reactivate HBV when HCV is suppressed or cleared by direct-acting antivirals (DAAs). We assessed the prevalence of overt or previous HBV coinfection and the risk of HBV reactivation in patients with HCV cirrhosis treated with DAAs. This was a retrospective cohort of 104 consecutive patients with HCV cirrhosis treated with DAAs. Serum HCV-RNA and HBV-DNA were tested at weeks 4, 8 and 12 of DAAs therapy and at week 12 of follow-up. At the start of DAAs, eight patients (7.7%) were HBsAg positive/HBeAg negative with undetectable HBV-DNA and low levels of quantitative HBsAg (four on nucleos(t)ide analogues [NUCs] and four inactive carriers), 37 patients (35.6%) had markers of previous HBV infection (25 anti-HBc positive, 12 anti-HBc/anti-HBs positive) and 59 (56.7%) had no evidence of HBV infection. Sixty-seven patients (64.4%) were HCV-RNA negative at week 4 and 98 (94.2%) achieved sustained virological response. All four HBsAg-positive patients treated with NUCs remained HBV-DNA negative, but three of four untreated patients showed an increase in HBV-DNA of 2-3 log without a biochemical flare and achieved HBV-DNA suppression when given NUCs. During or after DAAs, by conventional assay, HBV-DNA remained not detectable in all 37 anti-HBc-positive patients but in three of them (8.1%) HBV-DNA became detectable with a highly sensitive PCR. HBV reactivation is likely to occur in untreated HBV/HCV-coinfected cirrhotic patients when they undergo HCV treatment with DAAs. Pre-emptive therapy with NUCs should be considered in this setting. Anti-HBc-positive patients rarely reactivate HBV without clinical or virological outcomes. © 2017 John Wiley & Sons Ltd.

  4. Clinical impact of non-organ-specific autoantibodies on the response to combined antiviral treatment in patients with hepatitis C.

    Science.gov (United States)

    Muratori, Paolo; Muratori, Luigi; Guidi, Marcello; Granito, Alessandro; Susca, Micaela; Lenzi, Marco; Bianchi, Francesco B

    2005-02-15

    Hepatitis C virus (HCV)-related chronic hepatitis is frequently associated with non-organ-specific autoantibodies (NOSAs), but available data about the relationship between NOSA positivity and the effect of antiviral therapy in persons with hepatitis C are few and controversial. Our aim was to evaluate the impact of NOSA positivity on the outcome of combined antiviral therapy in HCV-positive patients. A total of 143 consecutive adult patients with hepatitis C were studied. Antinuclear antibody (ANA), anti-smooth muscle antibody (SMA), and anti-liver/kidney microsomal antibody type 1 (LKM1) were detected by indirect immunofluorescence. All patients were treatment naive and received combined antiviral therapy (interferon [IFN]-ribavirin) after enrollment in the study. Patients were classified as nonresponders if HCV RNA was detectable after 6 months of therapy, as relapsers if abnormal transaminase levels and reactivation of HCV replication were observed after the end of treatment, and as long-term responders if transaminase levels were persistently normal and HCV RNA was undetectable 6 months after the end of treatment. Thirty-seven patients (25%) were NOSA positive (SMA was detected in 19 patients, ANA in 10, ANA and SMA in 4, LKM1 in 3, and SMA and LKM1 in 1). The prevalence of long-term response was similar between NOSA-positive patients and NOSA-negative patients (48.6% vs. 56.6%; P=not significant). Compared with HCV genotype 1 (HCV-1), HCV genotypes other than 1 were more often associated with long-term response among NOSA-positive patients (93.3% vs. 30%; P=.0017). The overall rate of long-term response, irrespective of NOSA status, was 54.5%. Detection of HCV-1 and elevated gamma-glutamyl transpeptidase serum levels were independent negative prognostic factors of treatment response (P=.007 and P=.026, respectively). Combined antiviral treatment (IFN-ribavirin) is safe and effective in NOSA-positive patients with hepatitis C, even if long-term response is

  5. The Denver Tube Combined with Antiviral Drugs In the Treatment of HBV-related Cirrhosis with Refractory Ascites: A Report of Three Cases

    Directory of Open Access Journals (Sweden)

    Wang Xiao-jin

    2014-03-01

    Full Text Available Treatment of nucleos(tide antiviral drugs for decompensated HBV-related cirrhosis can significantly improve the prognosis. But those patients with refractory ascites possibly deteriorate due to the complications of ascites before any benefit from anti-viral drugs could be observed. Therefore, it is important to find a way to help the patients with HBV-related cirrhosis and refractory ascites to receive the full benefits from antiviral therapy. Peritoneovenous shunt (PVS using Denver tube enables ascites to continuously bypass into systemic circulation, thereby reducing ascites and albumin input and improving quality of life. We report herein 3 cases of decompensated HBV-related cirrhosis with refractory ascites, PVS using Denver tube was combined with lamivudine for antiviral treatment before and after. Then, ascites was alleviated significantly or disapeared and viral responsed well. All patients achieved a satisfactory long-term survival from 6.7 to 14.7 years. It was suggested that the Denver shunt could be used as an adjuvant method to antiviral drugs for decompensated HBV-related cirrhosis with refractory ascites to help the patients reap the full benefits and maximize efficacy of antiviral treatment.

  6. New antiviral agents and new treatments on the horizon for the management of viral hepatitis

    Directory of Open Access Journals (Sweden)

    M. Sönmezoğlu

    2011-12-01

    Full Text Available Transfusion dependant patients are at risk of acquiring transfusiontransmitted viral infections including Hepatitis B virus (HBV and Hepatitis C (HCV. These infections can lead to cirrhosis and hepatic cancer. Standard treatment, although with improved therapeutic results still exhibits resistance and relapses. New antiviral agents have been developed to further improve results and reduce adverse events. For hepatitis B, along with pegylated interferon a-2a, other drugs that have been approved include lamivudine, adefovir, entecavir, telbivudine and tenofovir, while emtricitabine and clevudine are awaiting FDA approval. Possible combination drug therapy may improve efficacy without engendering resistance. For hepatitis C, standard therapy has been the combination of Peg-IFN/Ribavarin. Genotype 1 of the virus, which is widespread in the USA and Europe, can be resistant to treatment especially with high viral load. Directly acting antiviral agents (DAAs, are being developed. These are: i HCV NS3 protease inhibitors, such as telaprevir and boceprevir, which are currently approved by the FDA. Several other compounds are in phase I-II development; ii NS5B polymerase inhibitors, which target HCV replication. These include mericitabine (a nucleoside analogue inhibitor currently in phase III trials, and nonnucleiside inhibitors; iii New intreferons such as pgylated interferonl, which are also on trial. Triple therapy using pegylated IFNa/ Ribavarin along with telaprevir or boceprevir are also under trial. 输血依赖型患者面临输血传播病毒感染的风险,包括乙型肝炎病毒(HBV)和丙型肝炎病毒(HCV)。 这些感染可导致肝硬化和肝癌。 标准治疗,尽管具有改善的治疗效果,但是仍然表现出抗病性和复发性 已研发出新的抗病毒药物,进一步完善结果和降低不良事件。 关于乙型肝炎,和聚乙二醇化干扰素a-2a一起,其他已获批准的药物包括拉米夫

  7. Antiviral Agents Added to Corticosteroids for Early Treatment of Adults With Acute Idiopathic Facial Nerve Paralysis (Bell Palsy).

    Science.gov (United States)

    Sullivan, Frank; Daly, Fergus; Gagyor, Ildiko

    Compared with oral corticosteroids alone, are oral antiviral drugs associated with improved outcomes when combined with oral corticosteroids in patients presenting within 72 hours of the onset of Bell palsy? Compared with oral corticosteroids alone, the addition of acyclovir, valacyclovir, or famcyclovir to oral corticosteroids for treatment of Bell palsy was associated with a higher proportion of people who recovered at 3- to 12-month follow-up. The quality of evidence is limited by heterogeneity, imprecision of the result estimates, and risk of bias.

  8. Antiviral treatment of feline immunodeficiency virus-infected cats with (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine.

    Science.gov (United States)

    Taffin, Elien; Paepe, Dominique; Goris, Nesya; Auwerx, Joeri; Debille, Mariella; Neyts, Johan; Van de Maele, Isabel; Daminet, Sylvie

    2015-02-01

    Feline immunodeficiency virus (FIV), the causative agent of an acquired immunodeficiency syndrome in cats (feline AIDS), is a ubiquitous health threat to the domestic and feral cat population, also triggering disease in wild animals. No registered antiviral compounds are currently available to treat FIV-infected cats. Several human antiviral drugs have been used experimentally in cats, but not without the development of serious adverse effects. Here we report on the treatment of six naturally FIV-infected cats, suffering from moderate to severe disease, with the antiretroviral compound (R)-9-(2-phosphonylmethoxypropyl)-2,6-diaminopurine ([R]-PMPDAP), a close analogue of tenofovir, a widely prescribed anti-HIV drug in human medicine. An improvement in the average Karnofsky score (pretreatment 33.2 ± 9.4%, post-treatment 65±12.3%), some laboratory parameters (ie, serum amyloid A and gammaglobulins) and a decrease of FIV viral load in plasma were noted in most cats. The role of concurrent medication in ameliorating the Karnofsky score, as well as the possible development of haematological side effects, are discussed. Side effects, when noted, appeared mild and reversible upon cessation of treatment. Although strong conclusions cannot be drawn owing to the small number of patients and lack of a placebo-treated control group, the activity of (R)-PMPDAP, as observed here, warrants further investigation. © ISFM and AAFP 2014.

  9. Identification of transformation products of antiviral drugs formed during biological wastewater treatment and their occurrence in the urban water cycle.

    Science.gov (United States)

    Funke, Jan; Prasse, Carsten; Ternes, Thomas A

    2016-07-01

    The fate of five antiviral drugs (abacavir, emtricitabine, ganciclovir, lamivudine and zidovudine) was investigated in biological wastewater treatment. Investigations of degradation kinetics were accompanied by the elucidation of formed transformation products (TPs) using activated sludge lab experiments and subsequent LC-HRMS analysis. Degradation rate constants ranged between 0.46 L d(-1) gSS(-1) (zidovudine) and 55.8 L d(-1) gSS(-1) (abacavir). Despite these differences of the degradation kinetics, the same main biotransformation reaction was observed for all five compounds: oxidation of the terminal hydroxyl-moiety to the corresponding carboxylic acid (formation of carboxy-TPs). In addition, the oxidation of thioether moieties to sulfoxides was observed for emtricitabine and lamivudine. Antiviral drugs were detected in influents of municipal wastewater treatment plants (WWTPs) with concentrations up to 980 ng L(-1) (emtricitabine), while in WWTP effluents mainly the TPs were found with concentration levels up to 1320 ng L(-1) (carboxy-abacavir). Except of zidovudine none of the original antiviral drugs were detected in German rivers and streams, whereas the concentrations of the TPs ranged from 16 ng L(-1) for carboxy-lamivudine up to 750 ng L(-1) for carboxy-acyclovir. These concentrations indicate an appreciable portion from WWTP effluents present in rivers and streams, as well as the high environmental persistence of the carboxy-TPs. As a result three of the carboxylic TPs were detected in finished drinking water. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Whole genome HBV deletion profiles and the accumulation of preS deletion mutant during antiviral treatment

    Science.gov (United States)

    2012-01-01

    Background Hepatitis B virus (HBV), because of its error-prone viral polymerase, has a high mutation rate leading to widespread substitutions, deletions, and insertions in the HBV genome. Deletions may significantly change viral biological features complicating the progression of liver diseases. However, the clinical conditions correlating to the accumulation of deleted mutants remain unclear. In this study, we explored HBV deletion patterns and their association with disease status and antiviral treatment by performing whole genome sequencing on samples from 51 hepatitis B patients and by monitoring changes in deletion variants during treatment. Clone sequencing was used to analyze preS regions in another cohort of 52 patients. Results Among the core, preS, and basic core promoter (BCP) deletion hotspots, we identified preS to have the highest frequency and the most complex deletion pattern using whole genome sequencing. Further clone sequencing analysis on preS identified 70 deletions which were classified into 4 types, the most common being preS2. Also, in contrast to the core and BCP regions, most preS deletions were in-frame. Most deletions interrupted viral surface epitopes, and are possibly involved in evading immuno-surveillance. Among various clinical factors examined, logistic regression showed that antiviral medication affected the accumulation of deletion mutants (OR = 6.81, 95% CI = 1.296 ~ 35.817, P = 0.023). In chronic carriers of the virus, and individuals with chronic hepatitis, the deletion rate was significantly higher in the antiviral treatment group (Fisher exact test, P = 0.007). Particularly, preS2 deletions were associated with the usage of nucleos(t)ide analog therapy (Fisher exact test, P = 0.023). Dynamic increases in preS1 or preS2 deletions were also observed in quasispecies from samples taken from patients before and after three months of ADV therapy. In vitro experiments demonstrated that preS2 deletions alone

  11. [Clinical significance of drug resistance-associated mutations in treatment of hepatitis C with direct-acting antiviral agents].

    Science.gov (United States)

    Li, Z; Chen, Z W; Ren, H; Hu, P

    2017-03-20

    Direct-acting antiviral agents (DAAs) achieve a high sustained virologic response rate in the treatment of chronic hepatitis C virus infection. However, drug resistance-associated mutations play an important role in treatment failure and have attracted more and more attention. This article elaborates on the clinical significance of drug resistance-associated mutations from the aspects of their definition, association with genotype, known drug resistance-associated mutations and their prevalence rates, the impact of drug resistance-associated mutations on treatment naive and treatment-experienced patients, and the role of clinical detection, in order to provide a reference for clinical regimens with DAAs and help to achieve higher sustained virologic response rates.

  12. Formal hepatitis C education enhances HCV care coordination, expedites HCV treatment and improves antiviral response.

    Science.gov (United States)

    Lubega, Samali; Agbim, Uchenna; Surjadi, Miranda; Mahoney, Megan; Khalili, Mandana

    2013-08-01

    Formal Hepatitis C virus (HCV) education improves HCV knowledge but the impact on treatment uptake and outcome is not well described. We aimed to evaluate the impact of formal HCV patient education on primary provider-specialist HCV comanagement and treatment. Primary care providers within the San Francisco safety-net health care system were surveyed and the records of HCV-infected patients before and after institution of a formal HCV education class by liver specialty (2006-2011) were reviewed retrospectively. Characteristics of 118 patients who received anti-HCV therapy were: mean age 51, 73% males and ~50% White and uninsured. The time to initiation of HCV treatment was shorter among those who received formal education (median 136 vs 284 days, P non-1 genotype (OR 6.17, 95% CI 2.3-12.7, P = 0.0003) and receipt of HCV education (OR 3.0, 95% CI 1.1-7.9, P = 0.03) were associated with sustained virologic treatment response. Among 94 provider respondents (response rate = 38%), mean age was 42, 62% were White, and 63% female. Most providers agreed that the HCV education class increased patients' HCV knowledge (70%), interest in HCV treatment (52%), and provider-patient communication (56%). A positive provider attitude (Coef 1.5, 95% CI 0.1-2.9 percent, P = 0.039) was independently associated with referral rate to education class. Formal HCV education expedites HCV therapy and improves virologic response rates. As primary care provider attitude plays a significant role in referral to HCV education class, improving provider knowledge will likely enhance access to HCV specialty services in the vulnerable population. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Cabozantinib for Initial Treatment of Kidney Cancer

    Science.gov (United States)

    FDA has approved cabozantinib (Cabometyx®) as an initial treatment for patients with advanced renal cell carcinoma. The approval adds another tyrosine kinase inhibitor to the available options for patients with advanced kidney cancer.

  14. Emergence of antiviral resistance during oral valganciclovir treatment of an infant with congenital cytomegalovirus (CMV) infection.

    Science.gov (United States)

    Choi, K Yeon; Sharon, B; Balfour, H H; Belani, K; Pozos, T C; Schleiss, M R

    2013-08-01

    Congenital infection with human cytomegalovirus (CMV) is a major cause of morbidity, including sensorineural hearing loss (SNHL), in newborns. Antiviral therapy with ganciclovir (GCV) and its oral prodrug, valganciclovir (VAL-GCV) are increasingly being administered to infected infants, toward the goal of improving neurodevelopmental and auditory outcomes. In this case report, we describe a symptomatic congenitally infected infant treated with VAL-GCV in whom GCV resistance was suspected, based on a 50-fold increase in viral load after 6 weeks of oral therapy. Analyses of CMV sequences from both blood and urine demonstrated populations of viruses with M460V and L595F mutations in the UL97 phosphotransferase gene. In contrast, analysis of viral DNA retrieved from the newborn dried blood spot demonstrated wild-type UL97 sequences. DNAemia resolved after the discontinuation of VAL-GCV. Long-term VAL-GCV therapy in congenitally infected infants can select for resistant viral variants, and anticipatory virological monitoring may be warranted. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Real-world outcomes of unrestricted direct-acting antiviral treatment for hepatitis C in Australia: The South Australian statewide experience.

    Science.gov (United States)

    Haridy, James; Wigg, Alan; Muller, Kate; Ramachandran, Jeyamani; Tilley, Emma; Waddell, Victoria; Gordon, David; Shaw, David; Huynh, Dep; Stewart, Jeffrey; Nelson, Renjy; Warner, Morgyn; Boyd, Mark; Chinnaratha, Mohamed A; Harding, Damian; Ralton, Lucy; Colman, Anton; Liew, Danny; Iyngkaran, Guru; Tse, Edmund

    2018-06-11

    In March 2016, the Australian government offered unrestricted access to direct-acting antiviral (DAA) therapy for chronic hepatitis C (HCV) to the entire population. This included prescription by any medical practitioner in consultation with specialists until sufficient experience was attained. We sought to determine the outcomes and experience over the first twelve-months for the entire state of South Australia. We performed a prospective, observational study following outcomes of all treatments associated with the state's four main tertiary centres. 1909 subjects initiating DAA therapy were included, representing an estimated 90% of all treatments in the state. Overall, SVR12 was 80.4% in all subjects intended for treatment and 95.7% in those completing treatment and follow-up. 14.2% were lost to follow-up (LTFU) and did not complete SVR12 testing. LTFU was independently associated with community treatment via remote consultation (OR 1.50, 95% CI 1.04-2.18, p=0.03), prison-based treatment (OR 2.02, 95% CI 1.08-3.79, p=0.03) and younger age (OR 0.98, 95% CI 0.97-0.99, p=0.05). Of the 1534 subjects completing treatment and follow-up, decreased likelihood of SVR12 was associated with genotype 2 (OR 0.23,95% CI 0.07-0.74, p=0.01) and genotype 3 (OR 0.23 95% CI 0.12-0.43, p=<0.01). A significant decrease in treatment initiation was observed over the twelve-month period in conjunction with a shift from hospital to community-based treatment. Our findings support the high responses observed in clinical trials, however a significant gap exists in SVR12 in our real-world cohort due to LTFU. A declining treatment initiation rate and shift to community-based treatment highlights the need to explore additional strategies to identify, treat and follow-up remaining patients in order to achieve elimination targets. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  16. Metabolic syndrome is associated with poor treatment response to antiviral therapy in chronic hepatitis C genotype 3 patients.

    Science.gov (United States)

    Aziz, Hafsa; Gill, Uzma; Raza, Abida; Gill, Muzaffar L

    2014-05-01

    Hepatitis C viral (HCV) infection is caused by an RNA virus. HCV infection is considered to induce systemic disease that causes steatosis, alters lipid metabolism, and results in metabolic syndrome. This study aimed to investigate the therapeutic outcome in HCV genotype 3 patients with metabolic syndrome. A total of 621 HCV-positive patients who visited the hospital for treatment were screened. Among these, 441 patients were enrolled for antiviral therapy. These enrolled patients were assessed for metabolic syndrome according to the International Diabetes Federation criteria. Group A included patients with metabolic syndrome and group B included patients without metabolic syndrome. All patients received peginterferon-α2a (180 μg/week) and ribavirin (10 mg/kg/day) for 6 months. The prevalence of metabolic syndrome in chronic HCV patients was 37.9%. We observed that metabolic syndrome was more common among female compared with male participants (43.9 vs. 28.8%, P=0.005). It was found that sustained virologic response (SVR) rates were significantly higher in the patients in group B (without metabolic syndrome) compared with the patients in group A who had metabolic syndrome (72.2 vs. 43.7%, Pmetabolic syndrome and a correlation of metabolic syndrome with nonresponse to antiviral therapy was observed. An interesting correlation among metabolic syndrome, age, and SVR was found: with age, SVR decreases, while metabolic syndrome increases. Metabolic syndrome has an influence on therapeutic outcomes in terms of SVR. Moreover, this information can identify patients who might have a low chance of attaining an SVR and a timely decision may protect the patients from the adverse effects of therapy.

  17. Access to direct-acting antivirals for the treatment of hepatitis C in a country with limited resources.

    Science.gov (United States)

    Marciano, S; Haddad, L; Borzi, S M; D'Amico, C; Gaite, L A; Aubone, M V; Sirotinsky, M E; Ratusnu, N; Frola, M S; Aparicio, M C; Ríos, B; Anselmo, M N; Hansen, R; De Filippi, S; Dans, C García; de Labra, L; Peche, M A; Strella, T M; Ibáñez Duran, M; García Rosales, M B; Dirchwolf, M; Galdame, O A; Gadano, A C

    2018-04-12

    To estimate the proportion of patients who access to direct-acting antivirals agents (DAAs) for the treatment of hepatitisC in Argentina and to evaluate factors associated with failure to access to treatment. We performed a cross-sectional study of DAAs prescriptions written by centers participating in the telemedicine project ECHO TM -Hospital Italiano of Buenos Aires between January 2016 and February 2017. A total of 143 consecutive prescriptions were evaluated; the global access was 70% (95% CI: 62%-77%). The only factor independently associated with failure to access to treatment was belonging to the public healthcare system [OR 4.98 (95% CI: 2.05- 12.09)] in comparison to belonging to private insurance or HMOs. Patients with hepatitisC who belong to the public healthcare system are 4 times more likely to fail to access to treatment of hepatitisC than patients with private insurance or other kind of insurance. Copyright © 2018 Asociación Mexicana de Gastroenterología. Publicado por Masson Doyma México S.A. All rights reserved.

  18. Veritable antiviral capacity of natural killer cells in chronic HBV infection: an argument for an earlier anti-virus treatment

    Directory of Open Access Journals (Sweden)

    Xiaoyan Li

    2017-10-01

    Full Text Available Abstract Background There is limited information on innate immunity, especially natural killer (NK cell function, in different chronic hepatitis B (CHB stages. Therefore, we examined whether the clinical staging strategy accurately reflects veritable NK cell immunity. Methods A total of 237 eligible CHB patients and 22 healthy controls were enrolled in our study. Demographic and clinical data were collected, and the CHB phases (immune active-IA, immune tolerant phase-IT, inactive CHB-IC, and grey zone-GZ were classified according to the latest American Association for the Study of Liver Disease guidelines. Peripheral blood mononuclear cells from patients and healthy controls were tested for NK cell frequency, phenotype and function using flow cytometry. Results A significant decrease in activating receptor NKp44 and NKp46 expression and significant increase of exhaustion molecule Tim-3 expression were observed in NK cells from CHB patients. Reduced cytokine secretion and preserved or elevated cytotoxic function were also observed. Patients in the IT group exhibited comparable cytokine secretion and cytolytic capacity as age-matched IA patients. NK cell anti-viral functions were preserved in GZ patients. Some of the NK cell function in patients who were excluded from treatment by the current treatment guidelines was less compromised than patients who qualified for treatment. Conclusion Our findings provide evidence of veritable NK cell immunity during different natural history phases in treatment-naïve patients with chronic HBV Infection. Chronic HBV infection hindered NK cell function in CHB patients. However, the presumed IT and GZ statuses of CHB patients based on the clinical parameters may not accurately reflect the inner immune status of these patients and should be reconsidered. Some patients excluded from treatment by the current treatment guidelines may be able to be selected as candidates for treatment.

  19. Potential risk of HBV reactivation in patients with resolved HBV infection undergoing direct-acting antiviral treatment for HCV.

    Science.gov (United States)

    Ogawa, Eiichi; Furusyo, Norihiro; Murata, Masayuki; Toyoda, Kazuhiro; Hayashi, Takeo; Ura, Kazuya

    2018-01-01

    Despite a known risk of hepatitis B virus (HBV) reactivation during direct-acting antiviral (DAA) treatment for patients with hepatitis C virus (HCV)-HBV coinfection, it remains unclear whether patients with past HBV infection are at risk for reactivation. This study evaluated the risk of HBV reactivation during treatment with sofosbuvir (SOF)-based regimens, focusing on patients with resolved HBV infection. This study analyzes the data of 183 consecutive patients treated with SOF-based regimens. From these patients, 63 with resolved HBV infection (negative for hepatitis B surface antigen [HBsAg] and undetectable HBV DNA but positive for hepatitis B core antibody) were eligible for this study. HBV reactivation was defined as a quantifiable HBV DNA level >20 IU/mL. Among the patients antibody to HBsAg (anti-HBs) positive (10-500 mIU/mL) (n = 30), the titre of anti-HBs was significantly decreased with time, as shown by the results of repeated-measures analysis of variance (P = .0029). Overall, four patients (6.3%) with resolved HBV infection came to have detectable HBV DNA during treatment, including one who had HBV reactivation at week 4 (HBV DNA 80 IU/mL). However, none developed hepatic failure. Among four patients who had detectable HBV DNA during treatment, all were negative or had very low-titre (HBV infection and negative or very low-titre anti-HBs at baseline are at risk for having detectable HBV DNA transiently during treatment. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  20. Effect of Qianggan Pills combined with antiviral treatment on the fibrosis indexes, immune and inflammatory response in patients with compensated hepatitis b cirrhosis

    Directory of Open Access Journals (Sweden)

    Hong-Gang Huang

    2017-04-01

    Full Text Available Objective: To study the effect of Qianggan Pills combined with antiviral treatment on the fibrosis indexes, immune and inflammatory response in patients with compensated hepatitis b cirrhosis. Methods: A total of 88 patients with compensated hepatitis b cirrhosis treated in our hospital between April 2013 and March 2016 were collected and divided into observation group and control group according to single blind randomized control. Observation group of patients accepted Qianggan Pills combined with antiviral treatment and control group of patients received antiviral treatment alone. After 6 months of treatment, chemiluminescence method was used to detect serum fibrosis indexes, flow cytometer was used to detect peripheral blood T lymphocyte subset levels, and enzyme-linked immunosorbent assay (ELISA was used to detect serum levels of inflammatory factors. Results: Before treatment, differences in fibrosis indexes, immune and inflammatory response indexes were not statistically significant between two groups of patients; after 6 months of treatment, serum LN, HA and Ⅳ-C levels of observation group were lower than those of control group, peripheral blood CD3+ and CD4+ T lymphocyte levels as well as CD4+/CD8+ ratio were higher than those of control group, and CD8+ T lymphocyte level was lower than that of control group; serum PCT and CRP levels were lower than those of control group while IL-10 and IL-13 levels were higher than those of control group. Conclusion: Qianggan Pills combined with antiviral treatment can inhibit the fibrosis process, strengthen the body's immune function and also relieve systemic inflammatory response in patients with compensated hepatitis b cirrhosis.

  1. Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults: 2016 Recommendations of the International Antiviral Society-USA Panel.

    Science.gov (United States)

    Günthard, Huldrych F; Saag, Michael S; Benson, Constance A; del Rio, Carlos; Eron, Joseph J; Gallant, Joel E; Hoy, Jennifer F; Mugavero, Michael J; Sax, Paul E; Thompson, Melanie A; Gandhi, Rajesh T; Landovitz, Raphael J; Smith, Davey M; Jacobsen, Donna M; Volberding, Paul A

    2016-07-12

    New data and therapeutic options warrant updated recommendations for the use of antiretroviral drugs (ARVs) to treat or to prevent HIV infection in adults. To provide updated recommendations for the use of antiretroviral therapy in adults (aged ≥18 years) with established HIV infection, including when to start treatment, initial regimens, and changing regimens, along with recommendations for using ARVs for preventing HIV among those at risk, including preexposure and postexposure prophylaxis. A panel of experts in HIV research and patient care convened by the International Antiviral Society-USA reviewed data published in peer-reviewed journals, presented by regulatory agencies, or presented as conference abstracts at peer-reviewed scientific conferences since the 2014 report, for new data or evidence that would change previous recommendations or their ratings. Comprehensive literature searches were conducted in the PubMed and EMBASE databases through April 2016. Recommendations were by consensus, and each recommendation was rated by strength and quality of the evidence. Newer data support the widely accepted recommendation that antiretroviral therapy should be started in all individuals with HIV infection with detectable viremia regardless of CD4 cell count. Recommended optimal initial regimens for most patients are 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus an integrase strand transfer inhibitor (InSTI). Other effective regimens include nonnucleoside reverse transcriptase inhibitors or boosted protease inhibitors with 2 NRTIs. Recommendations for special populations and in the settings of opportunistic infections and concomitant conditions are provided. Reasons for switching therapy include convenience, tolerability, simplification, anticipation of potential new drug interactions, pregnancy or plans for pregnancy, elimination of food restrictions, virologic failure, or drug toxicities. Laboratory assessments are recommended before treatment, and

  2. Pandemic pharmaceutical dosing effects on wastewater treatment: no adaptation of activated sludge bacteria to degrade the antiviral drug oseltamivir (Tamiflu®) and loss of nutrient removal performance.

    Science.gov (United States)

    Slater, Frances R; Singer, Andrew C; Turner, Susan; Barr, Jeremy J; Bond, Philip L

    2011-02-01

    The 2009-2010 influenza pandemic saw many people treated with antivirals and antibiotics. High proportions of both classes of drugs are excreted and enter wastewater treatment plants (WWTPs) in biologically active forms. To date, there has been no study into the potential for influenza pandemic-scale pharmaceutical use to disrupt WWTP function. Furthermore, there is currently little indication as to whether WWTP microbial consortia can degrade antiviral neuraminidase inhibitors when exposed to pandemic-scale doses. In this study, we exposed an aerobic granular sludge sequencing batch reactor, operated for enhanced biological phosphorus removal (EBPR), to a simulated influenza-pandemic dosing of antibiotics and antivirals for 8 weeks. We monitored the removal of the active form of Tamiflu(®), oseltamivir carboxylate (OC), bacterial community structure, granule structure and changes in EBPR and nitrification performance. There was little removal of OC by sludge and no evidence that the activated sludge community adapted to degrade OC. There was evidence of changes to the bacterial community structure and disruption to EBPR and nitrification during and after high-OC dosing. This work highlights the potential for the antiviral contamination of receiving waters and indicates the risk of destabilizing WWTP microbial consortia as a result of high concentrations of bioactive pharmaceuticals during an influenza pandemic. © 2010 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  3. BCX4430 - A broad-spectrum antiviral adenosine nucleoside analog under development for the treatment of Ebola virus disease.

    Science.gov (United States)

    Taylor, Raymond; Kotian, Pravin; Warren, Travis; Panchal, Rekha; Bavari, Sina; Julander, Justin; Dobo, Sylvia; Rose, Angela; El-Kattan, Yahya; Taubenheim, Brian; Babu, Yarlagadda; Sheridan, William P

    2016-01-01

    The adenosine nucleoside analog BCX4430 is a direct-acting antiviral drug under investigation for the treatment of serious and life-threatening infections from highly pathogenic viruses, such as the Ebola virus. Cellular kinases phosphorylate BCX4430 to a triphosphate that mimics ATP; viral RNA polymerases incorporate the drug's monophosphate nucleotide into the growing RNA chain, causing premature chain termination. BCX4430 is active in vitro against many RNA viral pathogens, including the filoviruses and emerging infectious agents such as MERS-CoV and SARS-CoV. In vivo, BCX4430 is active after intramuscular, intraperitoneal, and oral administration in a variety of experimental infections. In nonclinical studies involving lethal infections with Ebola virus, Marburg virus, Rift Valley fever virus, and Yellow Fever virus, BCX4430 has demonstrated pronounced efficacy. In experiments conducted in several models, both a reduction in the viral load and an improvement in survival were found to be related to the dose of BCX4430. A Phase 1 clinical trial of intramuscular administration of BCX4430 in healthy subjects is currently ongoing. Copyright © 2016 King Saud Bin Abdulaziz University for Health Sciences. All rights reserved.

  4. Antiviral treatment of a boy with EBV-associated hydroa vacciniforme

    DEFF Research Database (Denmark)

    Mose, Anja Pahlow; Fisker, Niels; Clemmensen, Ole

    2014-01-01

    Hydroa vacciniforme is one of the rarest forms of photosensitivity disorders of the skin. Effective treatment options are scarce and mainly constitute of strict sun protection. Lately, hydroa vacciniforme has been associated with Epstein-Barr virus infection. We present a patient with hydroa vacc...

  5. Impact of hepatitis C virus polymorphisms on direct-acting antiviral treatment efficacy: Regulatory analyses and perspectives.

    Science.gov (United States)

    Harrington, Patrick R; Komatsu, Takashi E; Deming, Damon J; Donaldson, Eric F; O'Rear, Julian J; Naeger, Lisa K

    2018-06-01

    Several highly effective, interferon-free, direct-acting antiviral (DAA)-based regimens are available for the treatment of chronic hepatitis C virus (HCV) infection. Despite impressive efficacy overall, a small proportion of patients in registrational trials experienced treatment failure, which in some cases was associated with the detection of HCV resistance-associated substitutions (RASs) at baseline. In this article, we describe methods and key findings from independent regulatory analyses investigating the impact of baseline nonstructural (NS) 3 Q80K and NS5A RASs on the efficacy of current United States Food and Drug Administration (FDA)-approved regimens for patients with HCV genotype (GT) 1 or GT3 infection. These analyses focused on clinical trials that included patients who were previously naïve to the DAA class(es) in their investigational regimen and characterized the impact of baseline RASs that were enriched in the viral population as natural or transmitted polymorphisms (i.e., not drug-selected RASs). We used a consistent approach to optimize comparability of results across different DAA regimens and patient populations, including the use of a 15% sensitivity cutoff for next-generation sequencing results and standardized lists of NS5A RASs. These analyses confirmed that detection of NS3 Q80K or NS5A baseline RASs was associated with reduced treatment efficacy for multiple DAA regimens, but their impact was often minimized with the use of an intensified treatment regimen, such as a longer treatment duration and/or addition of ribavirin. We discuss the drug resistance-related considerations that contributed to pretreatment resistance testing and treatment recommendations in drug labeling for FDA-approved DAA regimens. Independent regulatory analyses confirmed that baseline HCV RASs can reduce the efficacy of certain DAA-based regimens in selected patient groups. However, highly effective treatment options are available for patients with or without

  6. Direct-acting Antivirals in Kidney Transplant Patients: Successful Hepatitis C Treatment and Short Term Reduction in Urinary Protein/Creatinine Ratios

    Directory of Open Access Journals (Sweden)

    Michael R. Goetsch

    2017-09-01

    Full Text Available Introduction: The role of Hepatitis C Virus (HCV clearance in long-term kidney graft survival is unknown. In this study, we examined short-term trends of urinary protein/creatinine (P/C ratios in a cohort of HCV-infected kidney transplant recipients with stable graft function and treated with direct-acting antivirals (DAAs. Methods: We conducted a retrospective study of 19 kidney transplant patients with chronic HCV infection treated with DAAs at the University of Alabama at Birmingham 1917 Viral Hepatitis Clinic between January 2013 and June 2016. Markers of glomerular damage were assessed using average protein/creatinine (P/C ratios measured pre- and post-treatment. We also described treatment efficacy using sustained virologic response at 12 weeks post-HCV treatment (SVR12. Results: The median age of the 19 patients included was 59 years (Q1=58, Q3=64 at completion of treatment. Of these patients, 68% were African American, 32% were White and 63% were male. The median time between kidney transplant and initiation of DAA therapy was 2.25 years (Q1=0.79, Q3=3.79. Post-treatment P/C ratios (median=0.127, Q1=0.090, Q3=0.220 were significantly lower (p=0.01 than pre-treatment ratios (median=0.168, Q1=0.118, Q3=0.385. P/C ratios decreased in 14 of 19 patients (74% with median change of -0.072 (median percent change= -40%. Post-treatment eGFRs (median=58.9, Q1=48.9, Q3=72.3 were not significantly different (p=0.82 than the pre-treatment values (median=57.0, Q1=48.8, Q3=67.8. Conclusions: In this preliminary study, there was a statistically significant decrease in P/C ratios associated with HCV clearance, suggesting a potential role for DAAs in improving kidney graft survival. Larger cohort studies will be needed to assess the clinical and long-term benefits of DAAs in this special population of HCV infected patients.

  7. YMDD motif mutations in chronic hepatitis B antiviral treatment naïve patients: a multi-center study

    Directory of Open Access Journals (Sweden)

    You-Wen Tan

    Full Text Available OBJECTIVE: This study aimed to determine the natural prevalence of variants of tyrosine-methionine-aspartic acid-aspartic acid (YMDD motif in patients with chronic hepatitis B (CHB, and to explore its relation with demographic and clinical features, hepatitis B virus (HBV genotypes, and HBV DNA levels. METHODS: A total of 1,042 antiviral treatment naïve CHB patients (including with lamivudine [LAM] in the past year were recruited from outpatient and inpatient departments of six centers from December 2008 to June 2010. YMDD variants were analyzed using the HBV drug resistance line probe assay (Inno-Lipa HBV-DR. HBV genotypes were detected with polymerase chain reaction (PCR microcosmic nucleic acid cross-ELISA, and HBV deoxyribonucleic acid (DNA was quantitated with real-time PCR. All serum samples underwent tests for HBV, HCV, and HDV with ELISA. RESULTS: YMDD variants were detected in 23.3% (243/1042 of CHB patients. YMDD mutation was accompanied by L180M mutation in 154 (76.9% patients. Both wild-type HBV and YMDD variant HBV were present in 231 of 243 patients. Interestingly, 12 patients had only YIDD and/or YVDD variants without wild YMDD motif. In addition, 27.2% (98/359 of HbeAg-positive patients had YMDD mutations, which was higher than that in HbeAg-negative patients (21.2%, 145/683. The incidence of YMDD varied among patients with different HBV genotypes, but the difference was not significant. Moreover, the incidence of YMDD in patients with high HBV DNA level was significantly higher than that in those with low HBV DNA level. CONCLUSION: Mutation of YMDD motif was detectable at a high rate in CHB patients in this study. The incidence of YMDD may be correlated with HBeAg and HBV DNA level.

  8. A hematopoietic contribution to microhemorrhage formation during antiviral CD8 T cell-initiated blood-brain barrier disruption

    Directory of Open Access Journals (Sweden)

    Johnson Holly L

    2012-03-01

    Full Text Available Abstract Background The extent to which susceptibility to brain hemorrhage is derived from blood-derived factors or stromal tissue remains largely unknown. We have developed an inducible model of CD8 T cell-initiated blood-brain barrier (BBB disruption using a variation of the Theiler's murine encephalomyelitis virus (TMEV model of multiple sclerosis. This peptide-induced fatal syndrome (PIFS model results in severe central nervous system (CNS vascular permeability and death in the C57BL/6 mouse strain, but not in the 129 SvIm mouse strain, despite the two strains' having indistinguishable CD8 T-cell responses. Therefore, we hypothesize that hematopoietic factors contribute to susceptibility to brain hemorrhage, CNS vascular permeability and death following induction of PIFS. Methods PIFS was induced by intravenous injection of VP2121-130 peptide at 7 days post-TMEV infection. We then investigated brain inflammation, astrocyte activation, vascular permeability, functional deficit and microhemorrhage formation using T2*-weighted magnetic resonance imaging (MRI in C57BL/6 and 129 SvIm mice. To investigate the contribution of hematopoietic cells in this model, hemorrhage-resistant 129 SvIm mice were reconstituted with C57BL/6 or autologous 129 SvIm bone marrow. Gadolinium-enhanced, T1-weighted MRI was used to visualize the extent of CNS vascular permeability after bone marrow transfer. Results C57BL/6 and 129 SvIm mice had similar inflammation in the CNS during acute infection. After administration of VP2121-130 peptide, however, C57BL/6 mice had increased astrocyte activation, CNS vascular permeability, microhemorrhage formation and functional deficits compared to 129 SvIm mice. The 129 SvIm mice reconstituted with C57BL/6 but not autologous bone marrow had increased microhemorrhage formation as measured by T2*-weighted MRI, exhibited a profound increase in CNS vascular permeability as measured by three-dimensional volumetric analysis of

  9. Bioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophores

    KAUST Repository

    O'Rourke, Aubrie

    2015-05-01

    Natural products offer many possibilities for the treatment of disease. More than 70% of the Earth’s surface is ocean, and recent exploration and access has allowed for new additions to this catalog of natural treasures. The Central Red Sea off the coast of Saudi Arabia serves as a newly accessible location, which provides the opportunity to bioprospect marine sponges with the purpose of identifying novel antiviral scaffolds. Antivirals are underrepresented in present day clinical trials, as well as in the academic screens of marine natural product libraries. Here a high-throughput pipeline was initiated by prefacing the antiviral screen with an Image-based High-Content Screening (HCS) technique in order to identify candidates with antiviral potential. Prospective candidates were tested in a biochemical or cell-based assay for the ability to inhibit the NS3 protease of the West Nile Virus (WNV NS protease) as well as replication and reverse transcription of the Human Immunodeficiency Virus 1 (HIV-1). The analytical chemistry techniques of High-Performance Liquid Chromatograpy (HPLC), Liquid Chromatography-Mass Spectrometry (LC-MS), and Nuclear Magnetic Resonance (NMR) where used in order to identify the compounds responsible for the characteristic antiviral activity of the selected sponge fractions. We have identified a 3-alkyl pyridinium from Amphimedon chloros as the causative agent of the observed WNV NS3 protease inhibition in vitro. Additionally, we identified debromohymenialdisine, hymenialdisine, and oroidin from Stylissa carteri as prospective scaffolds capable of HIV-1 inhibition.

  10. Retinoblastoma: concerning its initiation and treatment

    Directory of Open Access Journals (Sweden)

    Ying-Ping Deng

    2013-06-01

    Full Text Available Retinoblastoma (RB is the most common intraocular cancer of infancy and childhood. This cancer is initiated by mutation on RB1, the tumor suppressor gene that is responsible for the regulation of both cell cycle and gnome stability in retinal cells. Patients with a constitutional mutation on RB1 can be inherited. RB occurs approximately 1 in every 15 000-20 000 live births. The worldwide mortality for this cancer is about 5%-11%. However, this rate rises to about 40%-70% in developing countries due to a delay in diagnosis. A wide variety of options are available for the treatment, but often a combination of therapies is adopted to optimize individualized care.

  11. TIARA: treatment initiatives after radiological accidents

    International Nuclear Information System (INIS)

    Menetrier, F.; Berard, Ph.; Joussineau, S.; Stradling, N.; Hodgson, A.; List, V.; Morcillo, M.A.; Paile, W.; Holt, D.C.B.; Eriksson, T.

    2007-01-01

    This paper describes the objectives, and reviews the progress, of the European project 'Treatment Initiatives After Radiological Accidents' (TIARA). TIARA forms part of the 'Preparatory Action for Security Research' (PASR) launched by the European Commission in 2004. The Preparatory Action is intended to reach preliminary conclusions on the needs for the security of EU citizens. It prepared a comprehensive Security Research Programme as part of the Commission's Seventh Framework Programme proposal, which was adopted in 2006 and launched in 2007. The principal purpose of TIARA is to constitute a European network that will participate in facilitating the management of a crisis in the event of the malevolent dispersal of radionuclides into the public environment. (authors)

  12. The future of antiviral immunotoxins

    DEFF Research Database (Denmark)

    Spiess, K.; Høy Jakobsen, Mette; Kledal, Thomas N

    2016-01-01

    There is a constant need for new therapeutic interventions in a wide range of infectious diseases. Over the past few years, the immunotoxins have entered the stage as promising antiviral treatments. Immunotoxins have been extensively explored in cancer treatment and have achieved FDA approval in ...

  13. Intra- and inter-pandemic variations of antiviral, antibiotics and decongestants in wastewater treatment plants and receiving rivers.

    Directory of Open Access Journals (Sweden)

    Andrew C Singer

    Full Text Available The concentration of eleven antibiotics (trimethoprim, oxytetracycline, ciprofloxacin, azithromycin, cefotaxime, doxycycline, sulfamethoxazole, erythromycin, clarithromycin, ofloxacin, norfloxacin, three decongestants (naphazoline, oxymetazoline, xylometazoline and the antiviral drug oseltamivir's active metabolite, oseltamivir carboxylate (OC, were measured weekly at 21 locations within the River Thames catchment in England during the month of November 2009, the autumnal peak of the influenza A[H1N1]pdm09 pandemic. The aim was to quantify the pharmaceutical response to the pandemic and compare this to drug use during the late pandemic (March 2010 and the inter-pandemic periods (May 2011. A large and small wastewater treatment plant (WWTP were sampled in November 2009 to understand the differential fate of the analytes in the two WWTPs prior to their entry in the receiving river and to estimate drug users using a wastewater epidemiology approach. Mean hourly OC concentrations in the small and large WWTP's influent were 208 and 350 ng/L (max, 2070 and 550 ng/L, respectively. Erythromycin was the most concentrated antibiotic measured in Benson and Oxford WWTPs influent (max=6,870 and 2,930 ng/L, respectively. Napthazoline and oxymetazoline were the most frequently detected and concentrated decongestant in the Benson WWTP influent (1650 and 67 ng/L and effluent (696 and 307 ng/L, respectively, but were below detection in the Oxford WWTP. OC was found in 73% of November 2009's weekly river samples (max=193 ng/L, but only in 5% and 0% of the late- and inter-pandemic river samples, respectively. The mean river concentration of each antibiotic during the pandemic largely fell between 17-74 ng/L, with clarithromycin (max=292 ng/L and erythromycin (max=448 ng/L yielding the highest single measure. In general, the concentration and frequency of detecting antibiotics in the river increased during the pandemic. OC was uniquely well-suited for the wastewater

  14. Hepatitis C Virus and Antiviral Drug Resistance.

    Science.gov (United States)

    Kim, Seungtaek; Han, Kwang-Hyub; Ahn, Sang Hoon

    2016-11-15

    Since its discovery in 1989, hepatitis C virus (HCV) has been intensively investigated to understand its biology and develop effective antiviral therapies. The efforts of the previous 25 years have resulted in a better understanding of the virus, and this was facilitated by the development of in vitro cell culture systems for HCV replication. Antiviral treatments and sustained virological responses have also improved from the early interferon monotherapy to the current all-oral regimens using direct-acting antivirals. However, antiviral resistance has become a critical issue in the treatment of chronic hepatitis C, similar to other chronic viral infections, and retreatment options following treatment failure have become important questions. Despite the clinical challenges in the management of chronic hepatitis C, substantial progress has been made in understanding HCV, which may facilitate the investigation of other closely related flaviviruses and lead to the development of antiviral agents against these human pathogens.

  15. La respuesta inmune antiviral

    Directory of Open Access Journals (Sweden)

    Rainel Sánchez de la Rosa

    1998-02-01

    Full Text Available Se expone que los virus son parásitos intracelulares obligados, puesto que no tienen metabolismo propio; esto obliga al sistema inmune a poner en marcha sus mecanismos más especializados para reconocer y eliminar, tanto a los virus libres, como a las células infectadas. Se señala que las células presentadoras de antígenos, los linfocitos B y los T unidos al complejo mayor de histocompatibilidad, forman parte de la organización de la respuesta inmune antiviral; la inducción de esta respuesta con proteínas, péptidos y ADN desnudo, son alternativas actuales tanto en la prevención como en el tratamiento de las infecciones viralesIt is explained that viruses are compulsory intracellular parasites, since they don't have their own metabolism, which makes the immune system to start its mest specialized mechanisms to recognize and eliminate the free viruses and the infected cells. It is stated that the cells presenting antigens, and the B and T lymphocytes together with the major histocompatibility complex, are part of the organization of the immune antiviral response. The induction of this response with proteins, peptides and naked DNA are the present alternatives for the prevention and treatment of viral infections

  16. Complementarity-Determining Region 3 Size Spectratypes of T Cell Receptor β Chains in CD8+ T Cells following Antiviral Treatment of Chronic Hepatitis B▿

    Science.gov (United States)

    Ma, Shi-Wu; Li, Yong-Yin; Zhang, Guang-Wen; Huang, Xuan; Sun, Jian; Li, Chris; Abbott, William G. H.; Hou, Jin-Lin

    2011-01-01

    An increased CD8+ T cell response to hepatitis B virus (HBV) peptides occurs between 12 and 24 weeks after starting antiviral therapy for chronic hepatitis B. It is not known whether these cells have antiviral function. The aim of this study was to determine whether clonal expansions of CD8+ T cells at these time points predict the virological response to therapy. Peripheral blood CD8+ T cells were obtained from 20 patients treated with lamivudine or telbivudine for chronic hepatitis B at baseline, 12 weeks, and 24 weeks. The CDR3 spectratype of each T cell receptor (TCR) β chain variable region (Vβ) gene family was analyzed, and the changes in the numbers of Vβ families with clonal expansions were compared in subjects with (n = 12) and without (n = 8) a virological response (52 week HBV DNA < 300 copies/ml). The number of CD8+ TCR Vβ families with clonal expansions at 12 weeks relative to baseline (median [10th to 90th percentile], +2.5 [0 to +7] versus +1 [0 to +2], P = 0.03) and at 24 weeks relative to 12 weeks (+1 [0 to +2] versus −1 [−3 to +4], P = 0.006) was higher in subjects with a virological response versus subjects without a virological response, as were interleukin-2 (IL-2) but not IL-21 mRNA levels in peripheral blood mononuclear cells. The duration of new expansions at 12 weeks was higher (P < 0.0001) in responders. Increased numbers of CD8+ T cell expansions after antiviral therapy are associated with a virological response to treatment. These CD8+ T cells are a potential target for a therapeutic vaccine for chronic hepatitis B. PMID:21098256

  17. USE OF HEMATOPOIETIC GROWTH FACTOR IN THE MANAGEMENT OF HEMATOLOGICAL SIDE EFFECTS ASSOCIATED TO ANTIVIRAL TREATMENT FOR HCV HEPATITIS

    Directory of Open Access Journals (Sweden)

    Paola Mancino

    2010-03-01

    Full Text Available Haematological abnormalities are common during combination antiviral therapy for chronic hepatitis C. Although dose reduction or discontinuation can easily treat these side effects, they can adversely affect the efficacy of combination antiviral therapy reducing the likelihood of a sustained viral response (SVR. To avoid potentially diminishing a patient’s chance of response, many physicians have begun using growth factors off-label to manage anaemia and neutropenia in hepatitis C. Haematopoietic growth factors are generally well tolerated and they may be useful for managing haematological side effects of anti-HCV therapy improving patients’ quality of life. To date, the role and benefit of these agents during anti-HCV therapy and their positive impact on SVR have not conclusively determined in the published studies. However, the possibility of a benefit to individual outpatients remains, and an individualized approach is recommended. This review explores the incidence, clinical significance, and management of anaemia, neutropenia and thrombocytopenia associated with combination therapy for HCV infection.

  18. Development and evaluation of aerosol delivery of antivirals for the treatment of equine virus induced respiratory infections

    International Nuclear Information System (INIS)

    Martens, J.G.

    1985-01-01

    An aerosol delivery system incorporating the DeVilbiss ultrasonic nebulizer was developed for antiviral chemotherapy of equine viral respiratory infections. The system's delivery capabilities were proven effective by two modes of analysis: (a) a non-destructive, non-invasive radioactive tracer method utilizing a saline solution of DTPA labelled 99mTc and, (b) an invasive-terminal study using fluorescent polystyrene monodispersed latex particles. Particles were efficiently distributed throughout the lung parenchyma with deposition more heavily concentrated in the tracheobronchial region. Amantadine HCl was administered to the lungs of a yearling horse and three yearling Shetland ponies over a single 15-30 minute period with no untoward side effects. Likewise, ribavirin was aerosolized into the respiratory trace of an adult pony and a yearling horse for 15-30 minutes twice a day for three and seven days respectively. Neither the horse nor pony demonstrated signs of clinical illness or other signs of ribavirin toxicity. Attempts to produce a reproducible equine influenza disease model were made. During these studies, the authors were unsuccessful in developing a consistent respiratory disease model. Without this model the efficacy of antiviral compounds cannot be assessed. From the data generated in these studies, the implication of equine influenza viruses as the major single etiological agents responsible for equine respiratory disease is brought into question. Further, the author proposed that equine respiratory disease is a multiple agent-induced disease, which needs extensive investigation

  19. Results of a multinational study suggest the need for rapid diagnosis and early antiviral treatment at the onset of herpetic meningoencephalitis

    DEFF Research Database (Denmark)

    Erdem, Hakan; Cag, Yasemin; Ozturk-Engin, Derya

    2015-01-01

    survived, with sequelae. Age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.02 to 1.05), Glasgow Coma Scale score (OR, 0.84; 95% CI, 0.77 to 0.93), and symptomatic periods of 2 to 7 days (OR, 1.80; 95% CI, 1.16 to 2.79) and >7 days (OR, 3.75; 95% CI, 1.72 to 8.15) until the commencement...... of treatment predicted unfavorable outcomes. The outcome in HME patients is related to a combination of therapeutic and host factors. This study suggests that rapid diagnosis and early administration of antiviral treatment in HME patients are keys to a favorable outcome....

  20. Use of Direct-Acting Antivirals for the Treatment of Hepatitis C Virus-Associated Oral Lichen Planus: A Case Report

    Directory of Open Access Journals (Sweden)

    Kenji Misaka

    2016-10-01

    Full Text Available Hepatitis C virus (HCV is frequently associated with various extrahepatic manifestations such as autoimmune features and immune complex deposit diseases. Oral lichen planus (OLP is one of the representative extrahepatic manifestations of HCV infection. Direct-acting antivirals (DAA are highly effective and safe for the eradication of HCV. However, there is a lack of information regarding the association between HCV-associated OLP and interferon (IFN-free DAA therapy. Herein, we present the case of a 60-year-old female who was diagnosed with OLP during routine periodontal treatment by a dentist. The patient was referred for hepatitis C treatment using IFN-free DAA, which resulted in the improvement of the symptoms of OLP. This case represents the safety and efficacy of IFN-free DAAs in patients with HCV-associated OLP. However, long-term follow-up studies are required to elucidate the therapeutic effects of this therapy in these patients.

  1. Semiclassical initial value treatment of wave functions

    International Nuclear Information System (INIS)

    Kay, Kenneth G.

    2010-01-01

    A semiclassical initial value approximation for time-independent wave functions, previously derived for integrable systems, is rederived in a form which allows it to be applied to more general systems. The wave function is expressed as an integral over a Lagrangian manifold that is constructed by propagating trajectories from an initial manifold formed on a Poincare surface. Even in the case of bound, integrable systems, it is unnecessary to identify action-angle variables or construct quantizing tori. The approximation is numerically tested for separable and highly chaotic two-dimensional quartic oscillator systems. For the separable (but highly anharmonic) system, the accuracy of the approximation is found to be excellent: overlaps of the semiclassical wave functions with the corresponding quantum wave functions exceed 0.999. For the chaotic system, semiclassical-quantum overlaps are found to range from 0.989 to 0.994, indicating accuracy that is still very good, despite the short classical trajectories used in the calculations.

  2. Naturally Occurring Resistance-Associated Variants to Hepatitis C Virus Direct-Acting Antiviral Agents in Treatment-Naive HCV Genotype 6a-Infected Patients

    Directory of Open Access Journals (Sweden)

    Zhanyi Li

    2017-01-01

    Full Text Available Background and Objective. The direct-acting antiviral agents (DAAs antiviral therapy has drastically improved the prognosis of hepatitis C virus (HCV patients. However, the viral drug resistance-associated variants (RAVs can limit the efficacy of DAAs. For the HCV-6a is not the predominant prevalent genotype; the data on the prevalence of naturally occurring RAVs in it is scarce. Our study aims to assess the prevalence of RAVs in treatment-naive HCV-6a patients. Methods. Nested PCR assays were performed on 95 HCV-6a patients to amplify HCV viral regions of NS3, NS5A, and NS5B. Results. In NS3/4A region, we detected Q80K in 95.5% isolates (84/88 and D168E in 2.3% isolates (2/88. In NS5A region, we detected Q30R in 93.2% isolates (82/88, L31M in 4.6% isolates (4/88, and H58P in 6.8% isolates (6/88. In NS5B region, we detected A15G in 2.3% isolates (2/88, S96T in 1.1% isolates (1/88, and S282T in 20.7% isolates (17/88 and we detected I482L in 100% isolates (4/4, V494A in 50% isolates (2/4, and V499A in 100% isolates (4/4. Conclusions. RAVs to DAAs preexist in treatment-naive HCV-6a patients. Further studies should address the issue of the impact of RAVs in response to DAA therapies for HCV-6a patients.

  3. Nanoparticulate delivery systems for antiviral drugs.

    Science.gov (United States)

    Lembo, David; Cavalli, Roberta

    2010-01-01

    Nanomedicine opens new therapeutic avenues for attacking viral diseases and for improving treatment success rates. Nanoparticulate-based systems might change the release kinetics of antivirals, increase their bioavailability, improve their efficacy, restrict adverse drug side effects and reduce treatment costs. Moreover, they could permit the delivery of antiviral drugs to specific target sites and viral reservoirs in the body. These features are particularly relevant in viral diseases where high drug doses are needed, drugs are expensive and the success of a therapy is associated with a patient's adherence to the administration protocol. This review presents the current status in the emerging area of nanoparticulate delivery systems in antiviral therapy, providing their definition and description, and highlighting some peculiar features. The paper closes with a discussion on the future challenges that must be addressed before the potential of nanotechnology can be translated into safe and effective antiviral formulations for clinical use.

  4. Absence of HIV-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection.

    Directory of Open Access Journals (Sweden)

    Teresa H Evering

    2012-02-01

    Full Text Available Mucosal mononuclear (MMC CCR5+CD4+ T cells of the gastrointestinal (GI tract are selectively infected and depleted during acute HIV-1 infection. Despite early initiation of combination antiretroviral therapy (cART, gut-associated lymphoid tissue (GALT CD4+ T cell depletion and activation persist in the majority of HIV-1 positive individuals studied. This may result from ongoing HIV-1 replication and T-cell activation despite effective cART. We hypothesized that ongoing viral replication in the GI tract during cART would result in measurable viral evolution, with divergent populations emerging over time. Subjects treated during early HIV-1 infection underwent phlebotomy and flexible sigmoidoscopy with biopsies prior to and 15-24 months post initiation of cART. At the 2(nd biopsy, three GALT phenotypes were noted, characterized by high, intermediate and low levels of immune activation. A representative case from each phenotype was analyzed. Each subject had plasma HIV-1 RNA levels <50 copies/ml at 2(nd GI biopsy and CD4+ T cell reconstitution in the peripheral blood. Single genome amplification of full-length HIV-1 envelope was performed for each subject pre- and post-initiation of cART in GALT and PBMC. A total of 280 confirmed single genome sequences (SGS were analyzed for experimental cases. For each subject, maximum likelihood phylogenetic trees derived from molecular sequence data showed no evidence of evolved forms in the GALT over the study period. During treatment, HIV-1 envelope diversity in GALT-derived SGS did not increase and post-treatment GALT-derived SGS showed no substantial genetic divergence from pre-treatment sequences within transmitted groups. Similar results were obtained from PBMC-derived SGS. Our results reveal that initiation of cART during acute/early HIV-1 infection can result in the interruption of measurable viral evolution in the GALT, suggesting the absence of de-novo rounds of HIV-1 replication in this compartment

  5. Absence of HIV-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection.

    Science.gov (United States)

    Evering, Teresa H; Mehandru, Saurabh; Racz, Paul; Tenner-Racz, Klara; Poles, Michael A; Figueroa, Amir; Mohri, Hiroshi; Markowitz, Martin

    2012-02-01

    Mucosal mononuclear (MMC) CCR5+CD4+ T cells of the gastrointestinal (GI) tract are selectively infected and depleted during acute HIV-1 infection. Despite early initiation of combination antiretroviral therapy (cART), gut-associated lymphoid tissue (GALT) CD4+ T cell depletion and activation persist in the majority of HIV-1 positive individuals studied. This may result from ongoing HIV-1 replication and T-cell activation despite effective cART. We hypothesized that ongoing viral replication in the GI tract during cART would result in measurable viral evolution, with divergent populations emerging over time. Subjects treated during early HIV-1 infection underwent phlebotomy and flexible sigmoidoscopy with biopsies prior to and 15-24 months post initiation of cART. At the 2(nd) biopsy, three GALT phenotypes were noted, characterized by high, intermediate and low levels of immune activation. A representative case from each phenotype was analyzed. Each subject had plasma HIV-1 RNA levels <50 copies/ml at 2(nd) GI biopsy and CD4+ T cell reconstitution in the peripheral blood. Single genome amplification of full-length HIV-1 envelope was performed for each subject pre- and post-initiation of cART in GALT and PBMC. A total of 280 confirmed single genome sequences (SGS) were analyzed for experimental cases. For each subject, maximum likelihood phylogenetic trees derived from molecular sequence data showed no evidence of evolved forms in the GALT over the study period. During treatment, HIV-1 envelope diversity in GALT-derived SGS did not increase and post-treatment GALT-derived SGS showed no substantial genetic divergence from pre-treatment sequences within transmitted groups. Similar results were obtained from PBMC-derived SGS. Our results reveal that initiation of cART during acute/early HIV-1 infection can result in the interruption of measurable viral evolution in the GALT, suggesting the absence of de-novo rounds of HIV-1 replication in this compartment during

  6. HOMA, BMI, and Serum Leptin Levels Variations during Antiviral Treatment Suggest Virus-Related Insulin Resistance in Noncirrhotic, Nonobese, and Nondiabetic Chronic Hepatitis C Genotype 1 Patients

    Directory of Open Access Journals (Sweden)

    Alessandro Grasso

    2015-01-01

    Full Text Available Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders. Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment. Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline (P=0.033 and 0.048, resp. in patients who achieved an early viral load decay (EVR, a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR. Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype.

  7. HOMA, BMI, and Serum Leptin Levels Variations during Antiviral Treatment Suggest Virus-Related Insulin Resistance in Noncirrhotic, Nonobese, and Nondiabetic Chronic Hepatitis C Genotype 1 Patients.

    Science.gov (United States)

    Grasso, Alessandro; Malfatti, Federica; Andraghetti, Gabriella; Marenco, Simona; Mazzucchelli, Chiara; Labanca, Sara; Cordera, Renzo; Testa, Roberto; Picciotto, Antonino

    2015-01-01

    Objective. To investigate the relationship between insulin resistance and viral load decay in nondiabetic and noncirrhotic genotype 1 chronic HCV patients during peginterferon and ribavirin treatment and the possible influence of BMI and leptin as metabolic confounders. Methods. 75 consecutive noncirrhotic, nonobese, and nondiabetic patients with genotype 1 chronic hepatitis C treated with peginterferon alpha 2a plus ribavirin were evaluated. HOMA-IR, serum leptin, and BMI were measured in all patients at baseline and at weeks 12 and 48, whereas viral load was measured at the same time points and then 24 weeks after the end of treatment. Results. HOMA-IR was significantly associated with both BMI and leptin at baseline. During peginterferon plus ribavirin treatment, there was a significant reduction of HOMA-IR at weeks 12 and 48 from baseline (P = 0.033 and 0.048, resp.) in patients who achieved an early viral load decay (EVR), a trend not observed in patients who not achieved EVR. No variations during treatment were observed regarding BMI and leptin irrespective of EVR. Conclusion. The early reduction of HOMA-IR but not of BMI and leptin during antiviral treatment in noncirrhotic, chronic hepatitis C genotype 1 patients who achieved EVR suggests a viral genesis of insulin resistance in patients with nonmetabolic phenotype.

  8. Antiviral therapy: a perspective

    Directory of Open Access Journals (Sweden)

    Shahidi Bonjar AH

    2016-02-01

    s recovery to a large extent depends on their general health status. EVAC would be for single use and appropriately disposed of after each detoxification procedure. When sufficient research has yielded positive results in animal models, EVAC could be used as a supportive treatment in humans along with conventional antiviral therapies. EVAC would not be suitable for all viral infections, but could be expected to decrease the casualties resulting from blood-borne viral infections. The EVAC approach would be efficient in terms of time, effort, and expenditure in the research and treatment of blood-borne viral infections. Keywords: blood, virus, infection, antiviral, sepsis, HIV, Ebola

  9. Impact of antiviral treatment and hospital admission delay on risk of death associated with 2009 A/H1N1 pandemic influenza in Mexico

    Directory of Open Access Journals (Sweden)

    Chowell Gerardo

    2012-04-01

    Mexican Social Security system, April-December 2009. We considered a spectrum of disease severity encompassing outpatient visits, hospitalizations, and deaths, and recorded demographic and geographic information on individual patients. We assessed the impact of neuraminidase inhibitor treatment and hospital admission delay (≤ > 2 days after disease onset on the risk of death by multivariate logistic regression. Results Approximately 50% of all A/H1N1-positive patients received antiviral medication during the Spring and Summer 2009 pandemic waves in Mexico while only 9% of A/H1N1 cases received antiviral medications during the fall wave (P  Conclusions Our findings underscore the potential impact of decreasing admission delays and increasing antiviral use to mitigate the mortality burden of future influenza pandemics.

  10. Cost-effectiveness analysis of two treatment strategies for chronic hepatitis C before and after access to direct-acting antivirals in Spain.

    Science.gov (United States)

    Turnes, Juan; Domínguez-Hernández, Raquel; Casado, Miguel Ángel

    To evaluate the cost-effectiveness of a strategy based on direct-acting antivirals (DAAs) following the marketing of simeprevir and sofosbuvir (post-DAA) versus a pre-direct-acting antiviral strategy (pre-DAA) in patients with chronic hepatitis C, from the perspective of the Spanish National Health System. A decision tree combined with a Markov model was used to estimate the direct health costs (€, 2016) and health outcomes (quality-adjusted life years, QALYs) throughout the patient's life, with an annual discount rate of 3%. The sustained virological response, percentage of patients treated or not treated in each strategy, clinical characteristics of the patients, annual likelihood of transition, costs of treating and managing the disease, and utilities were obtained from the literature. The cost-effectiveness analysis was expressed as an incremental cost-effectiveness ratio (incremental cost per QALY gained). A deterministic sensitivity analysis and a probabilistic sensitivity analysis were performed. The post-DAA strategy showed higher health costs per patient (€30,944 vs. €23,707) than the pre-DAA strategy. However, it was associated with an increase of QALYs gained (15.79 vs. 12.83), showing an incremental cost-effectiveness ratio of €2,439 per QALY. The deterministic sensitivity analysis and the probabilistic sensitivity analysis showed the robustness of the results, with the post-DAA strategy being cost-effective in 99% of cases compared to the pre-DAA strategy. Compared to the pre-DAA strategy, the post-DAA strategy is efficient for the treatment of chronic hepatitis C in Spain, resulting in a much lower cost per QALY than the efficiency threshold used in Spain (€30,000 per QALY). Copyright © 2017 Elsevier España, S.L.U., AEEH y AEG. All rights reserved.

  11. Modelling how reversal of immune exhaustion elicits cure of chronic hepatitis C after the end of treatment with direct-acting antiviral agents.

    Science.gov (United States)

    Baral, Subhasish; Roy, Rahul; Dixit, Narendra M

    2018-05-09

    A fraction of chronic hepatitis C patients treated with direct-acting antivirals (DAAs) achieved sustained virological responses (SVR), or cure, despite having detectable viremia at the end of treatment (EOT). This observation, termed EOT + /SVR, remains puzzling and precludes rational optimization of treatment durations. One hypothesis to explain EOT + /SVR, the immunologic hypothesis, argues that the viral decline induced by DAAs during treatment reverses the exhaustion of cytotoxic T lymphocytes (CTLs), which then clear the infection after treatment. Whether the hypothesis is consistent with data of viral load changes in patients who experienced EOT + /SVR is unknown. Here, we constructed a mathematical model of viral kinetics incorporating the immunologic hypothesis and compared its predictions with patient data. We found the predictions to be in quantitative agreement with patient data. Using the model, we unraveled an underlying bistability that gives rise to EOT + /SVR and presents a new avenue to optimize treatment durations. Infected cells trigger both activation and exhaustion of CTLs. CTLs in turn kill infected cells. Due to these competing interactions, two stable steady states, chronic infection and viral clearance, emerge, separated by an unstable steady state with intermediate viremia. When treatment during chronic infection drives viremia sufficiently below the unstable state, spontaneous viral clearance results post-treatment, marking EOT + /SVR. The duration to achieve this desired reduction in viremia defines the minimum treatment duration required for ensuring SVR, which our model can quantify. Estimating parameters defining the CTL response of individuals to HCV infection would enable the application of our model to personalize treatment durations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  12. Pegylated-interferon plus ribavirin treatment does not alter the prevalence of resistance-associated substitutions to direct-acting antivirals in HCV genotype 1a patients

    Directory of Open Access Journals (Sweden)

    Chen Z

    2017-08-01

    Full Text Available Zhi-wei Chen,* Xi-chen Pang,* Zhao Li, Hong Ren, Peng Hu Department of Infectious Diseases, Institute for Viral Hepatitis, The Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China *These authors contributed equally to this work Background: Direct-acting antiviral (DAA resistance-associated substitutions (RASs can jeopardize the effectiveness of DAAs in patients with hepatitis C virus (HCV. The selection pressure by pegylated-interferon (Peg-IFN plus ribavirin (P/R treatment may enhance HCV genome variation. However, whether P/R treatment alters the rate of change of RASs is still unclear. Materials and methods: We retrieved the genomic sequences of HCV genotype (GT 1a patients from GenBank, which included patients naïve to P/R (pre-IFN group and those previously treated with P/R (post-IFN group. The sequences were aligned and analyzed by using MEGA 6.0 software. Clinically relevant RASs were summarized from the current medical literature. Results: In the cross-sectional study, the total prevalence of clinically relevant RASs was high, independent of the treatment group (pre-IFN: 219/403 [54.34%] vs post-IFN: 67/131 [51.15%]. The high prevalence was mainly detected in the NS3 region RAS at Q80 (40.69% vs 36.64%. The RASs in the NS5A region, such as M28, Q30, L31 and Y93, were uncommon (0%–5%. Similarly, all RASs showed no difference between the two groups. One exception was the RAS at I170 in the NS3 region, which was significantly higher in the post-IFN group than in the pre-IFN group. In the longitudinal study, similar results were observed. However, no difference in RAS at I170 was observed between the two groups. Finally, no clinically relevant RASs were detected in response to the DAA regimens approved for GT 1a patients treated with P/R. Conclusion: Our results suggest that previous P/R treatment failure was not

  13. Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1-6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance.

    Science.gov (United States)

    Cuypers, Lize; Li, Guangdi; Libin, Pieter; Piampongsant, Supinya; Vandamme, Anne-Mieke; Theys, Kristof

    2015-09-16

    Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, the diversity of the HCV genome is a major obstacle for the development of antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide diversity and selective pressure was mapped, focusing on positions important for treatment, drug resistance, and resistance testing. A dataset of 1415 full-genome sequences, including genotypes 1-6 from the Los Alamos database, was analyzed. In 44% of all full-genome positions, the consensus amino acid was different for at least one genotype. Focusing on positions sharing the same consensus amino acid in all genotypes revealed that only 15% was defined as pan-genotypic highly conserved (≥99% amino acid identity) and an additional 24% as pan-genotypic conserved (≥95%). Despite its large genetic diversity, across all genotypes, codon positions were rarely identified to be positively selected (0.23%-0.46%) and predominantly found to be under negative selective pressure, suggesting mainly neutral evolution. For NS3, NS5A, and NS5B, respectively, 40% (6/15), 33% (3/9), and 14% (2/14) of the resistance-related positions harbored as consensus the amino acid variant related to resistance, potentially impeding treatment. For example, the NS3 variant 80K, conferring resistance to simeprevir used for treatment of HCV1 infected patients, was present in 39.3% of the HCV1a strains and 0.25% of HCV1b strains. Both NS5A variants 28M and 30S, known to be associated with resistance to the pan-genotypic drug daclatasvir, were found in a significant proportion of HCV4 strains (10.7%). NS5B variant 556G, known to confer resistance to non-nucleoside inhibitor dasabuvir, was observed in 8.4% of the HCV1b strains. Given the large HCV genetic diversity, sequencing efforts for resistance testing purposes may need to be

  14. Smallpox Antiviral Drug

    Science.gov (United States)

    2007-01-01

    Candida albicans] A G1L (590 aa) Flag VV(WR) 30/ENDIDEILGIAHLLEHLLISF/50 107/HIKELENEYYFRNEVFH/123 H41A 30/ENDIDEILGIAALLEHLLISF/50 107...RSV) (Table 1). Additional antiviral drug examples include the use of interferon for human papilloma virus ( HPV ) [Cantell, 1995]. Antivirals are most...low oral bioavailability, and quick elimination from plasma [Ghosn et al., 2004; Hostetler et al., 1994; Kempf et al., 1991; Matsumoto et al., 2001

  15. Efficacy of Antiviral Drugs against Feline Immunodeficiency Virus

    Directory of Open Access Journals (Sweden)

    Katrin Hartmann

    2015-12-01

    Full Text Available Feline immunodeficiency virus (FIV is one of the most common infectious agents affecting cats worldwide .FIV and human immunodeficiency virus (HIV share many properties: both are lifelong persistent lentiviruses that are similar genetically and morphologically and both viruses propagate in T-lymphocytes, macrophages, and neural cells. Experimentally infected cats have measurable immune suppression, which sometimes progresses to an acquired immunodeficiency syndrome. A transient initial state of infection is followed by a long latent stage with low virus replication and absence of clinical signs. In the terminal stage, both viruses can cause severe immunosuppression. Thus, FIV infection in cats has become an important natural model for studying HIV infection in humans, especially for evaluation of antiviral compounds. Of particular importance for chemotherapeutic studies is the close similarity between the reverse transcriptase (RT of FIV and HIV, which results in high in vitro susceptibility of FIV to many RT-targeted antiviral compounds used in the treatment of HIV-infected patients. Thus, the aim of this article is to provide an up-to-date review of studies on antiviral treatment of FIV, focusing on commercially available compounds for human or animal use.

  16. The cost-effectiveness, health benefits, and financial costs of new antiviral treatments for hepatitis C virus.

    Science.gov (United States)

    Rein, David B; Wittenborn, John S; Smith, Bryce D; Liffmann, Danielle K; Ward, John W

    2015-07-15

    New hepatitis C virus (HCV) treatments deliver higher cure rates with fewer contraindications, increasing demand for treatment and healthcare costs. The cost-effectiveness of new treatments is unknown. We conducted a microsimulation of guideline testing followed by alternative treatment regimens for HCV among the US population aged 20 and older to estimate cases identified, treated, sustained viral response, deaths, medical costs, quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER) of different treatment options expressed as discounted lifetime costs and benefits from the healthcare perspective. Compared to treatment with pegylated interferon and ribavirin (PR), and a protease inhibitor for HCV genotype (G) 1 and PR alone for G2/3, treatment with PR and Sofosbuvir (PRS) for G1/4 and treatment with Sofosbuvir and ribavirin (SR) for G2/3 increased QALYs by 555 226, reduced deaths by 80 682, and increased costs by $26.2 billion at an ICER of $47 304 per QALY gained. As compared to PRS/SR, treating with an all oral regimen of Sofosbuvir and Simeprevir (SS) for G1/4 and SR for G2/3, increased QALYs by 1 110 451 and reduced deaths by an additional 164 540 at an incremental cost of $80.1 billion and an ICER of $72 169. In sensitivity analysis, where treatment with SS effectiveness was set to the list price of Viekira Pak and then Harvoni, treatment cost $24 921 and $25 405 per QALY gained as compared to PRS/SR. New treatments are cost-effectiveness per person treated, but pent-up demand for treatment may create challenges for financing. © 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.

  17. Non-invasive tests in prediction of liver fibrosis in chronic hepatitis B and comparison with post-antiviral treatment results.

    Science.gov (United States)

    Başar, Omer; Yimaz, Bariş; Ekiz, Fuat; Giniş, Zeynep; Altinbaş, Akif; Aktaş, Bora; Tuna, Yaşar; Çoban, Sahin; Delibaş, Namik; Yüksel, Osman

    2013-04-01

    The aim of this study was to assess and compare the performance of a series of non-invasive tests to detect fibrosis in patients with chronic hepatitis B (CHB). Seventy-six patients with CHB, whose blood samples were collected and biopsies were done on the same day, were included in this study. Pre-treatment calculations of aspartate aminotransferase to platelet ratio index (APRI), Forn's index, FIB-4, S-index, Shanghai Liver Fibrosis Group's index (SLFG) and Hepascore(®) were done and relations with mild and advanced fibrosis and cirrhosis were assessed. Post-treatment values of APRI, Forn's index, FIB-4, S-index with oral antiviral agents were also investigated. APRI, S-index, SLFG, FIB-4, Forn's index and Hepascore(®) had 0.669, 0.669, 0.739, 0.741, 0.753, 0.780; retrospectively Area Under the Receiver Operating Characteristic Curve (AUROC) for significant fibrosis. APRI, Forn's index, S-index, FIB-4, SLFG, and Hepascore(®) had 0.681, 0.714, 0.715, 0.738, 0.747, 0.777 retrospectively AUROC for advanced fibrosis. APRI, SLFG, FIB-4, Forn's index, S-index, and Hepascore(®) had 0.741, 0.742, 0.768, 0.779, 0.792, 0.824 retrospectively AUROC for cirrhosis. APRI, Forn's index, FIB-4 and S-index were significantly lower in post-treatment group compared with pre-treatment group (P-values: fibrosis. Our study also suggests that the use of non-invasive test to predict fibrosis in patients with CHB may reduce the need for liver biopsy and may help to monitor the efficacy of treatment. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  18. Research priorities to achieve universal access to hepatitis C prevention, management and direct-acting antiviral treatment among people who inject drugs.

    Science.gov (United States)

    Grebely, Jason; Bruneau, Julie; Lazarus, Jeffrey V; Dalgard, Olav; Bruggmann, Philip; Treloar, Carla; Hickman, Matthew; Hellard, Margaret; Roberts, Teri; Crooks, Levinia; Midgard, Håvard; Larney, Sarah; Degenhardt, Louisa; Alho, Hannu; Byrne, Jude; Dillon, John F; Feld, Jordan J; Foster, Graham; Goldberg, David; Lloyd, Andrew R; Reimer, Jens; Robaeys, Geert; Torrens, Marta; Wright, Nat; Maremmani, Icro; Norton, Brianna L; Litwin, Alain H; Dore, Gregory J

    2017-09-01

    Globally, it is estimated that 71.1 million people have chronic hepatitis C virus (HCV) infection, including an estimated 7.5 million people who have recently injected drugs (PWID). There is an additional large, but unquantified, burden among those PWID who have ceased injecting. The incidence of HCV infection among current PWID also remains high in many settings. Morbidity and mortality due to liver disease among PWID with HCV infection continues to increase, despite the advent of well-tolerated, simple interferon-free direct-acting antiviral (DAA) HCV regimens with cure rates >95%. As a result of this important clinical breakthrough, there is potential to reverse the rising burden of advanced liver disease with increased treatment and strive for HCV elimination among PWID. Unfortunately, there are many gaps in knowledge that represent barriers to effective prevention and management of HCV among PWID. The Kirby Institute, UNSW Sydney and the International Network on Hepatitis in Substance Users (INHSU) established an expert round table panel to assess current research gaps and establish future research priorities for the prevention and management of HCV among PWID. This round table consisted of a one-day workshop held on 6 September, 2016, in Oslo, Norway, prior to the International Symposium on Hepatitis in Substance Users (INHSU 2016). International experts in drug and alcohol, infectious diseases, and hepatology were brought together to discuss the available scientific evidence, gaps in research, and develop research priorities. Topics for discussion included the epidemiology of injecting drug use, HCV, and HIV among PWID, HCV prevention, HCV testing, linkage to HCV care and treatment, DAA treatment for HCV infection, and reinfection following successful treatment. This paper highlights the outcomes of the roundtable discussion focused on future research priorities for enhancing HCV prevention, testing, linkage to care and DAA treatment for PWID as we strive

  19. Gastrointestinal events and association with initiation of treatment for osteoporosis

    Directory of Open Access Journals (Sweden)

    Modi A

    2015-11-01

    Full Text Available Ankita Modi,1 Ethel S Siris,2 Jackson Tang,3 Shiva Sajjan,1 Shuvayu S Sen1 1Center for Observational and Real-World Evidence, Merck & Co., Inc, Kenilworth, NJ, 2Toni Stabile Osteoporosis Center, Columbia University Medical Center, NY Presbyterian Hospital, New York, NY, 3Asclepius Analytics Ltd, Brooklyn, NY, USA Background: Preexisting gastrointestinal (GI events may deter the use of pharmacologic treatment in patients diagnosed with osteoporosis (OP. The objective of this study was to examine the association between preexisting GI events and OP pharmacotherapy initiation among women diagnosed with OP. Methods: The study utilized claims data from a large US managed care database to identify women aged ≥55 years with a diagnosis code for OP (index date during 2002–2009. Patients with a claim for pharmacologic OP treatment in the 12-month pre-index period (baseline were excluded. OP treatment initiation in the post-index period was defined as a claim for bisphosphonates (alendronate, ibandronate, risedronate, zoledronic acid, calcitonin, raloxifene, or teriparatide. During the post-index period (up to 12 months, GI events were identified before treatment initiation. A time-dependent Cox regression model was used to investigate the likelihood of initiating any OP treatment. Among patients initiating OP treatment, a discrete choice model was utilized to assess the relationship between post-index GI events and likelihood of initiating with a bisphosphonate versus a non-bisphosphonate. Results: In total, 65,344 patients (mean age 66 years were included; 23.7% had a GI event post diagnosis and before treatment initiation. Post-index GI events were associated with a 75% lower likelihood of any treatment initiation (hazard ratio 0.25; 95% confidence interval 0.24–0.26. Among treated patients (n=23,311, those with post-index GI events were 39% less likely to receive a bisphosphonate versus a non-bisphosphonate (odds ratio 0.61; 95% confidence

  20. Cost trend analysis of initial cancer treatment in Taiwan.

    Directory of Open Access Journals (Sweden)

    Tsai-Yun Li

    Full Text Available BACKGROUND: Despite the high cost of initial cancer care, that is, care in the first year after diagnosis, limited information is available for specific categories of cancer-related costs, especially costs for specific services. This study purposed to identify causes of change in cancer treatment costs over time and to perform trend analyses of the percentage of cancer patients who had received a specific treatment type and the mean cost of care for patients who had received that treatment. METHODOLOGY/PRINCIPAL FINDINGS: The analysis of trends in initial treatment costs focused on cancer-related surgery, chemotherapy, radiation therapy, and treatments other than active treatments. For each cancer-specific trend, slopes were calculated for regression models with 95% confidence intervals. Analyses of patients diagnosed in 2007 showed that the National Health Insurance (NHI system paid, on average, $10,780 for initial care of a gastric cancer patient and $10,681 for initial care of a lung cancer patient, which were inflation-adjusted increases of $6,234 and $5,522, respectively, over the 1996 care costs. During the same interval, the mean NHI payment for initial care for the five specific cancers increased significantly (p<0.05. Hospitalization costs comprised the largest portion of payments for all cancers. During 1996-2007, the use of chemotherapy and radiation therapy significantly increased in all cancer types (p<0.05. In 2007, NHI payments for initial care for these five cancers exceeded $12 billion, and gastric and lung cancers accounted for the largest share. CONCLUSIONS/SIGNIFICANCE: In addition to the growing number of NHI beneficiaries with cancer, treatment costs and the percentage of patients who undergo treatment are growing. Therefore, the NHI must accurately predict the economic burden of new chemotherapy agents and radiation therapies and may need to develop programs for stratifying patients according to their potential benefit

  1. Is sustained virological response a marker of treatment efficacy in patients with chronic hepatitis C viral infection with no response or relapse to previous antiviral intervention?

    DEFF Research Database (Denmark)

    Gurusamy, Kurinchi S; Wilson, Edward; Koretz, Ronald L

    2013-01-01

    Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs.......Randomised clinical trials (RCTs) of antiviral interventions in patients with chronic hepatitis C virus (HCV) infection use sustained virological response (SVR) as the main outcome. There is sparse information on long-term mortality from RCTs....

  2. Interferon alpha treatment stimulates interferon gamma expression in type I NKT cells and enhances their antiviral effect against hepatitis C virus.

    Science.gov (United States)

    Miyaki, Eisuke; Hiraga, Nobuhiko; Imamura, Michio; Uchida, Takuro; Kan, Hiromi; Tsuge, Masataka; Abe-Chayama, Hiromi; Hayes, C Nelson; Makokha, Grace Naswa; Serikawa, Masahiro; Aikata, Hiroshi; Ochi, Hidenori; Ishida, Yuji; Tateno, Chise; Ohdan, Hideki; Chayama, Kazuaki

    2017-01-01

    Interferon (IFN) inhibits hepatitis C virus (HCV) replication through up-regulation of intrahepatic IFN-stimulated gene expression but also through activation of host immune cells. In the present study, we analyzed the immune cell-mediated antiviral effects of IFN-α using HCV-infected mice. Urokinase-type plasminogen activator (uPA)-severe combined immunodeficiency (SCID) mice with transplanted human hepatocytes were infected with genotype 1b HCV and injected with human peripheral blood mononuclear cells (PBMCs). IFN-α treatment following human PBMC transplantation resulted in a significant reduction in serum HCV RNA titers and a higher human CD45-positive mononuclear cell chimerism compared to mice without human PBMC transplantation. In mice with human PBMCs treated with IFN-α, serum concentrations of IFN-γ increased, and natural killer T (NKT) cells, especially type I NKT cells, produced IFN-γ. Mice in which IFN-γ signaling was blocked using antibody or in which transplanted PBMCs were depleted for type I NKT cells showed similar levels of anti-HCV effect compared with mice treated only with IFN-α. These results show that IFN-α stimulates IFN-γ expression in type 1 NKT cells and enhances the inhibition of HCV replication. We propose that type 1 NKT cells might represent a new therapeutic target for chronic hepatitis C patients.

  3. Anti-viral drug treatment along with immune activator IL-2: a control-based mathematical approach for HIV infection

    Science.gov (United States)

    Nath Chatterjee, Amar; Roy, Priti Kumar

    2012-02-01

    Recent development in antiretroviral treatment against HIV can help AIDS patients to fight against HIV. But the question that whether the disease is to be partially or totally eradicated from HIV infected individuals still remains unsolved. Usually, the most effective treatment for the disease is HAART which can only control the disease progression. But as the immune system becomes weak, the patients can not fight against other diseases. Immune cells are activated and proliferated by IL-2 after the identification of antigen. IL-2 production is impaired in HIV positive patients and intermitted administration of immune activator IL-2 together with HAART which is a more effective treatment to fight against the disease. Thus, its expediency is essential and is yet to be explored. In this article we anticipated a mathematical model of the effect of IL-2 together with RTIs therapy in HIV positive patients. Our analytical as well as numerical study shows that the optimal schedule of treatment for best result is to be obtained by systematic drug therapy. But at the last stage of treatment, the infection level raises again due to minimisation of drug dosage. Thus we study the perfect adherence of the drugs and found out if RTIs are taken with sufficient interval then for fixed interval of IL-2 therapy, certain amount of drug dosages may be able to sustain the immune system at pre-infection stage and the infected CD4+T cells are going towards extinction.

  4. The Clinical Interpretation of Viral Blips in HIV Patients Receiving Antiviral Treatment: Are We Ready to Infer Poor Adherence?

    NARCIS (Netherlands)

    Chun-Hai Fung, Isaac; Gambhir, Manoj; van Sighem, Ard; de Wolf, Frank; Garnett, Geoffrey P.

    2012-01-01

    Objectives: Viral blips may be an indication of poor adherence to antiretroviral treatment. This article studies how the variations of the definitions of viral blips and that of the choice of sampling frame in studies investigating viral blips may contribute to the uncertainty of the associations

  5. Antiviral therapy: a perspective.

    Science.gov (United States)

    Shahidi Bonjar, Amir Hashem

    2016-01-01

    research has yielded positive results in animal models, EVAC could be used as a supportive treatment in humans along with conventional antiviral therapies. EVAC would not be suitable for all viral infections, but could be expected to decrease the casualties resulting from blood-borne viral infections. The EVAC approach would be efficient in terms of time, effort, and expenditure in the research and treatment of blood-borne viral infections.

  6. Self-interest versus group-interest in antiviral control

    NARCIS (Netherlands)

    Boven, M. van; Klinkenberg, D.; Pen, I.; Weissing, F.J.; Heesterbeek, J.A.P.

    2008-01-01

    Antiviral agents have been hailed to hold considerable promise for the treatment and prevention of emerging viral diseases like H5N1 avian influenza and SARS. However, antiviral drugs are not completely harmless, and the conditions under which individuals are willing to participate in a

  7. Ophthalmic antiviral chemotherapy : An overview

    Directory of Open Access Journals (Sweden)

    Athmanathan Sreedharan

    1997-01-01

    Full Text Available Antiviral drug development has been slow due to many factors. One such factor is the difficulty to block the viral replication in the cell without adversely affecting the host cell metabolic activity. Most of the antiviral compounds are analogs of purines and pyramidines. Currently available antiviral drugs mainly inhibit viral nucleic acid synthesis, hence act only on actively replicating viruses. This article presents an overview of some of the commonly used antiviral agents in clinical ophthalmology.

  8. Antiviral Drugs: Seasonal Flu

    Centers for Disease Control (CDC) Podcasts

    2010-09-29

    In this podcast, Dr. Joe Bresee explains the nature of antiviral drugs and how they are used for seasonal flu.  Created: 9/29/2010 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 9/29/2010.

  9. Antiviral properties of photosensitizers

    International Nuclear Information System (INIS)

    Hudson, J.B.; Towers, G.H.N.

    1988-01-01

    We have studied the antiviral properties of three different groups of photo-sensitizers, viz. (i) various furyl compounds; (ii) β-carboline alkaloids; (iii) thiophenes and their acetylene derivatives. In general the antiviral potency of the furyl compounds correlated with their ability to produce DNA photoadducts. Among the naturally occurring β-carboline alkaloids, harmine was considerably more potent (in the presence of long wavelength UV radiation, UVA) than several other harmane-related compounds. Slight alterations in chemical structure had profound effects on their antiviral activities. Harmine was shown to inactivate the DNA-virus murine cytomegalovirus (MCMV) by inhibiting viral gene expression, although other targets may also exist. Several eudistomins, carboline derivatives isolated from a tunicate, were also photoactive against viruses. Various plant thiophenes and polyacetylenes were studied in detail. These compounds also required UVA for antiviral activity, and some of them were extremely potent against viruses with membranes, e.g. α-terthienyl, which showed significant activity at only 10 -5 μg/ml. When MCMV had been treated with α-terthienyl plus UVA, the virus retained its integrity and penetrated cells normally; but the virus did not replicate. (author)

  10. Adverse cardiac events in out-patients initiating clozapine treatment

    DEFF Research Database (Denmark)

    Rohde, C; Polcwiartek, C; Kragholm, K

    2018-01-01

    OBJECTIVE: Using national Danish registers, we estimated rates of clozapine-associated cardiac adverse events. Rates of undiagnosed myocarditis were estimated by exploring causes of death after clozapine initiation. METHOD: Through nationwide health registers, we identified all out-patients initi......OBJECTIVE: Using national Danish registers, we estimated rates of clozapine-associated cardiac adverse events. Rates of undiagnosed myocarditis were estimated by exploring causes of death after clozapine initiation. METHOD: Through nationwide health registers, we identified all out...... the maximum rate of clozapine-associated fatal myocarditis to 0.28%. CONCLUSION: Cardiac adverse effects in Danish out-patients initiating clozapine treatment are extremely rare and these rates appear to be comparable to those observed for other antipsychotic drugs....

  11. Research progress in antiviral therapy for chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    YU Guoying

    2015-04-01

    Full Text Available Antiviral therapy is the most important treatment for chronic hepatitis C. This paper reviews the progress in antiviral treatment over recent years, including the combination therapy with polyethylene glycol-Interferon (PEG-IFN and ribavirin (RBV, specific target therapy, and gene therapy. The paper believes that the anti-hepatitis C virus treatment needs more effective drug combination therapies, shorter courses, less side effect, higher drug resistance threshold, etc.

  12. Treatment initiatives after radiological accidents: TIARA first step

    International Nuclear Information System (INIS)

    Menetrier, F.; Berard, P.; Joussineau, S.; Stradling, N.; Hodgson, V.; List, MA.; Morcillo, W.; Paile, D.; Holt, T.; Eriksson

    2006-01-01

    Full text of publication follows: T.I.A.R.A. [Treatment Initiatives After Radiological Accidents] project is a consortium of 8 European partners. This project is part of the Preparatory Action on Security Research recently launched by the European Commission. The Preparatory Action is intended to reach preliminary conclusions on the needs for the security of European Union citizens before the launch of the Security Research Programme in 2007. The principal purpose of T.I.A.R.A. is to constitute a European network which will participate in enhancing the management of a crisis in the hypothesis of a malevolent dispersal of radionuclides in a public place. The main concern is to identify and define effective medical treatments for internal radioactive contamination. A preview of the state of treatment of contamination by radionuclides (especially actinides) in Europe highlights the following points: a decrease in the number of physicians with experience of treatment, a need for generalised agreement on treatment decisions and protocols, unanticipated operational issues and research into new treatments. If treatment is to be effective then several factors must be addressed and these include: firstly, the availability of effective specific treatment for the radionuclides involved, their rapid transport to and distribution of the drugs at the place of the malevolent dispersal and the easy administration of the drug even if numerous people are contaminated. The objectives of T.I.A.R.A. are threefold. First to provide straightforward guidance on dose assessment and efficacy of treatment which is readily understood by health physicists and physicians who do not have detailed knowledge and experience in radiological protection matters. Second, to foresee the operational needs for treating persons when there are mass casualties. Third, to monitor scientific and technological development on research into new treatments. Progress in all these aspects of the project will be

  13. Antiviral Resistance to Influenza Viruses: Clinical and Epidemiological Aspects

    NARCIS (Netherlands)

    van der Vries, E.

    2017-01-01

    There are three classes of antiviral drugs approved for the treatment of influenza: the M2 ion channel inhibitors (amantadine, rimantadine), neuraminidase (NA) inhibitors (laninamivir, oseltamivir, peramivir, zanamivir), and the protease inhibitor (favipiravir); some of the agents are only available

  14. Osteoporosis in the Women's Health Initiative: Another Treatment Gap?

    Science.gov (United States)

    Sattari, Maryam; Cauley, Jane A; Garvan, Cynthia; Johnson, Karen C; LaMonte, Michael J; Li, Wenjun; Limacher, Marian; Manini, Todd; Sarto, Gloria E; Sullivan, Shannon D; Wactawski-Wende, Jean; Beyth, Rebecca J

    2017-08-01

    Osteoporotic fractures are associated with high morbidity, mortality, and cost. We performed a post hoc analysis of the Women's Health Initiative (WHI) clinical trials data to assess osteoporosis treatment and identify participant characteristics associated with utilization of osteoporosis medication(s) after new diagnoses of osteoporosis or fracture. Information from visits prior to and immediately subsequent to the first fracture event or osteoporosis diagnosis were evaluated for medication use. A full logistic regression model was used to identify factors predictive of osteoporosis medication use after a fracture or a diagnosis of osteoporosis. The median length of follow-up from enrollment to the last WHI clinic visit for the study cohort was 13.9 years. Among the 13,990 women who reported new diagnoses of osteoporosis or fracture between enrollment and their final WHI visit, and also had medication data available, 21.6% reported taking an osteoporosis medication other than estrogen. Higher daily calcium intake, diagnosis of osteoporosis alone or both osteoporosis and fracture (compared with diagnosis of fracture alone), Asian or Pacific Islander race/ethnicity (compared with White/Caucasian), higher income, and hormone therapy use (past or present) were associated with significantly higher likelihood of osteoporosis pharmacotherapy. Women with Black/African American race/ethnicity (compared with White/Caucasian), body mass index ≥30 (compared with body mass index of 18.5-24.9), current tobacco use (compared with past use or lifetime nonusers), and history of arthritis were less likely to use osteoporosis treatment. Despite well-established treatment guidelines in postmenopausal women with osteoporosis or history of fractures, pharmacotherapy use was suboptimal in this study. Initiation of osteoporosis treatment after fragility fracture may represent an opportunity to improve later outcomes in these high-risk women. Specific attention needs to be paid to

  15. Importance of proper initial treatment of moderate and major burns

    Directory of Open Access Journals (Sweden)

    Vulović Dejan

    2008-01-01

    Full Text Available Background/Aim. Burns are common injuries with frequency depending on human factors, development of protection, industry and traffic, eventual wars. Organized treatment of major burn injuries has tremendous medical, social and economic importance. The aim of this study was to analyze initial treatment of major and moderate burns, to compare it with the current recommendations and to signify the importance of organized management of burns. Methods. In a prospective study 547 adult patients with major burns were analyzed, covering a period of eight years, with the emphasis on the initial hospital admission and emergency care for burns greater than 10% of total body surface area (TBSA. Results. In the different groups of major burns, the percentage of hospital admission was: 81.5 in burns greater than 10% TBSA, 37.7 in burns of the functional areas, 54.5 in the III degree burns, 81.6 in electrical burns, 55.9 in chemical burns, 61.9 in inhalation injury, 41.0 in burns in patients with the greater risk and 100 in burns with a concomitant trauma. In the group of 145 patients with burns greater than 10% TBSA, intravenous fluids were given in 87 patients, analgesics in 45, corticosteroids in 29, antibiotics in 23 and oxygen administration in 14. In the same group, wound irrigation was done in 14.4%, removing of the clothing and shoes in 29.6%, elevation of the legs in 8.9% and prevention of hypothermia in 7.6% of the victims. There were no initial estimations of burn extent (percentage of a burn, notes about the patient and injury and tetanus immunizations. Conclusion. Based on these findings, it is concluded that there should be much more initial hospital admissions of major burns, and also, necessary steps in the emergency care of burns greater than 10% TBSA should be taken more frequently. On the other side, unnecessary or wrong steps should be avoided in the initial burn treatment.

  16. Management of hepatitis C infection in the era of direct-acting antiviral therapy

    Science.gov (United States)

    Zain, L. H.; Sungkar, T.

    2018-03-01

    Hepatitis C viral infection globally affects millions of people and commonly results in debilitating complications and mortality. Initial mainstay therapy consisted of pegylated interferon α (pegIFNα) with additional ribavirin that showed unsatisfactory cure rate, common side effects and complicated dosing, contributing to high discontinuation rate. Over the last few years, newer antivirals have been extensively studied, that are Direct-Acting Antivirals (DAAs). Specifically targeting viral protein mainly during replication phase, DAAs showed greater cure rate (commonly measured as sustained virologic response), improved safety profile and shorter treatment duration compared to traditional interferon-ribavirin therapy. Current guidelines have also included Interferon-free, often ribavirin-free, DAAs combinations that suggest promising outcomes. The current review highlights development of rapidly growing hepatitis C treatment including DAAs recommendations.

  17. La respuesta inmune antiviral

    OpenAIRE

    Sánchez de la Rosa, Rainel; Sánchez de la Rosa, Ernesto; Rodríguez Hernández, Néstor

    1998-01-01

    Se expone que los virus son parásitos intracelulares obligados, puesto que no tienen metabolismo propio; esto obliga al sistema inmune a poner en marcha sus mecanismos más especializados para reconocer y eliminar, tanto a los virus libres, como a las células infectadas. Se señala que las células presentadoras de antígenos, los linfocitos B y los T unidos al complejo mayor de histocompatibilidad, forman parte de la organización de la respuesta inmune antiviral; la inducción de esta respuesta c...

  18. Liver stiffness becomes stable in patients with chronic hepatitis C three months after ALT normalization due to antiviral therapy

    Directory of Open Access Journals (Sweden)

    CHEN Feikai

    2013-10-01

    Full Text Available ObjectiveTo investigate the time for liver stiffness measurement (LSM to become stable in chronic hepatitis C (CHC patients with elevated alanine aminotransferase (ALT levels after ALT normalization due to antiviral therapy. MethodsCHC patients who sought initial treatment at Peking University People′s Hospital were screened for elevated ALT levels from May 2011. Liver stiffness was determined by FibroScan. A total of 29 patients had been included in the study by September 2012, who were followed up regularly after antiviral treatment. ALT tests were repeated every four weeks and LSM every eight weeks until their medians did not change significantly. Comparisons of matched data at two adjacent time points were made with the non-parametric Wilcoxon test, while multiple comparisons of repeated measurements were performed using Bonferroni correction. Correlation between two variables was analyzed with the Spearman rank test. ResultsPatients were followed up until 24 weeks after antiviral treatment, and 24 patients were included in analysis. The median ALT levels were 64, 26, 21, 20, and 22 U/L at baseline and 4, 8, 12, and 24 weeks, respectively (P= 0.000, 0.006, 0.337, and 0.109 for comparisons between two adjacent values. ALT decreased significantly below 1 ULN at 4 weeks after antiviral therapy and stabilized at 8 weeks. The median LSM values were 8.7, 7.8, 6.8, and 6.7 kPa at baseline and 8, 16, and 24 weeks, respectively (P= 0.009, 0.001, and 0188 for comparisons between two adjacent values. LSM decreased significantly within 16 weeks after antiviral therapy and stabilized afterwards. LSM stabilized 12 weeks after ALT normalization. ConclusionLSM becomes stable in CHC patients with elevated ALT levels three months after ALT normalization due to antiviral therapy.

  19. 'Crisis' and 'everyday' initiators: A qualitative study of coercion and agency in the context of methadone maintenance treatment initiation.

    Science.gov (United States)

    Damon, Will; Small, Will; Anderson, Solanna; Maher, Lisa; Wood, Evan; Kerr, Thomas; McNeil, Ryan

    2017-03-01

    Patient attrition is common among people enrolled in methadone maintenance treatment (MMT) programs and most pronounced during the first year of treatment. However, the experiences of patients initiating MMT have been overlooked in the literature. This study explores experiences of MMT initiation among MMT patients, focusing on contextual influences on MMT initiation and perceptions of MMT and their subsequent influence on treatment retention. Semi-structured qualitative interviews were conducted with 39 MMT patients in Vancouver, Canada. Individuals reporting enrolment in MMT were recruited from within two ongoing cohort studies comprised of people who use drugs. Interview transcripts were analysed using an inductive and iterative approach. Two groups of MMT initiators were identified: (i) 'crisis initiators' prescribed methadone following critical transition events, such as incarceration or pregnancy; and (ii) 'everyday initiators' enrolled in MMT as part of routine healthcare utilisation. While most 'crisis initiators' and some 'everyday initiators' described experiencing coercion during MMT initiation, 'crisis initiators' were further subjected to the coercive leveraging of their vulnerability to motivate 'consent' for MMT. 'Crisis initiators' developed negative views towards MMT and were more likely to discontinue treatment. Long-standing patient-provider relationships and open dialogue were associated with more positive views regarding MMT, regardless of the circumstances of initiation. Findings underscore the need for clear and effective communication regarding treatment regimens and expectations during MMT initiation. Furthermore, training in trauma-informed care may help reduce perceptions of coercion and rates of early treatment termination. [Damon W, Small W, Anderson S, Maher L, Wood E, Kerr T, McNeil R. Crisis' and 'everyday' initiators: A qualitative study of coercion and agency in the context of methadone maintenance treatment initiation. Drug

  20. Brachytherapy as sole treatment modality in initial cervix carcinoma

    International Nuclear Information System (INIS)

    Heredia Z, A.

    1993-01-01

    The aim of this study was to evaluate brachytherapy as the only treatment modality in inoperable early cervix carcinoma patients (carcinoma in situ, IA and IBocc). In a retrospective analysis 36 patients were treated with intracavitary irradiation between 1984 and 1988 in the Radiotherapy Department of the National Institute of Neoplasmic Diseases. Distribution by stage was; carcinoma in situ: one patient (2,47%), IA: six patients (16,6%), IBooc: twenty-nine patients (80,7%). Histology revealed epidermoid carcinoma in all cases. Mean age 55 years (range: 32-78). Treatment consisted in: two intracavitary applications of Radium, for 120 hours each, with a month interval, in 30 patients (carcinoma in situ: one, IA: four, IBocc: twenty-five patients), two applications of 72 hours each, with 15 days interval in four patients (IA: one, IBocc: 3) and one single intracavitary radium application in two patients (IA and IBocc). Local control was complete in all carcinoma in situ and IA patients. Only 1 of 29 patients with IBocc stage failed to respond, in spite of having received two applications, this shows that local response is independent of the number of insertions. Incidence of complications was low, and resolved with medical treatment. One patient had rectal adenocarcinoma 3 years after treatment -it was considered as radio induced neoplasm, since time of appearance was more than two years and localization was within irradiated area. Two patients died form intercurrent diseases, one (IBocc) from persistent diseases. Two patients were lost to follow-up. Three years survival was: 100% for carcinoma in situ and IA 86,2% for IBocc. Five years survival was 80% for IA and IBocc. Brachytherapy as unique modality of treatment is highly effective in initial cervix carcinoma stages. (author). 41 refs., 14 tabs., 2 figs., 1 ill

  1. Radiologic and clinical observation of tuberculous cavity in initial treatment

    International Nuclear Information System (INIS)

    Huh, Jin Do

    1986-01-01

    Tuberculous cavity is important in diagnosis and observation in the course of pulmonary tuberculosis. Author analyzed the radiologic findings of cavity and average months of negative conversion in AFB culture in 89 cases of initial treatment. The results were as follows: 1. The more number of cavities, the longer period in negative conversion of AFB culture. 2. No relation between sums of diameter and thickness of cavity and average months of negative conversion in AFB culture. 3. In the cases of cavity with air-fluid level took longer period in negative conversion og AFB culture than those of cavity without air-fluid level, significantly. 4. No relation between radiologic findings of cavity and results of chemotherapy for pulmonary tuberculosis.

  2. Aciclovir: nuevo antiviral

    Directory of Open Access Journals (Sweden)

    G. Repetto

    2017-05-01

    Full Text Available El aciclovir es un antiviral útil en infecciones graves causadas por el virus varicela-zoster. Es bien tolerado con escasas reacciones adversas. En pacientes deshidratados, en insuficiencia renal o si la infusión endovenosa es muy rápida, puede ocacionar una "nefropatía obstructiva" transitoria. Existen preparados de uso tópico, oftálmico, endovenoso y oral; esta última vía constituye una ventaja sobre la vidarabina con la que tiene en común el espectro de actividad. En razón de su selectividad, riesgo de resistencia y número reducido de antivirales, su prescripción debe restringirse a infecciones graves causadas por los agentes inmunodeprimidos; excluyendo por lo tanto las comunes y autolimitadas, frecuentes en el individuo normal.

  3. Decision Making with Regard to Antiviral Intervention during an Influenza Pandemic

    Science.gov (United States)

    Shim, Eunha; Chapman, Gretchen B.; Galvani, Alison P.

    2012-01-01

    Background Antiviral coverage is defined by the proportion of the population that takes antiviral prophylaxis or treatment. High coverage of an antiviral drug has epidemiological and evolutionary repercussions. Antivirals select for drug resistance within the population, and individuals may experience adverse effects. To determine optimal antiviral coverage in the context of an influenza outbreak, we compared 2 perspectives: 1) the individual level (the Nash perspective), and 2) the population level (utilitarian perspective). Methods We developed an epidemiological game-theoretic model of an influenza pandemic. The data sources were published literature and a national survey. The target population was the US population. The time horizon was 6 months. The perspective was individuals and the population overall. The interventions were antiviral prophylaxis and treatment. The outcome measures were the optimal coverage of antivirals in an influenza pandemic. Results At current antiviral pricing, the optimal Nash strategy is 0% coverage for prophylaxis and 30% coverage for treatment, whereas the optimal utilitarian strategy is 19% coverage for prophylaxis and 100% coverage for treatment. Subsidizing prophylaxis by $440 and treatment by $85 would bring the Nash and utilitarian strategies into alignment. For both prophylaxis and treatment, the optimal antiviral coverage decreases as pricing of antivirals increases. Our study does not incorporate the possibility of an effective vaccine and lacks probabilistic sensitivity analysis. Our survey also does not completely represent the US population. Because our model assumes a homogeneous population and homogeneous antiviral pricing, it does not incorporate heterogeneity of preference. Conclusions The optimal antiviral coverage from the population perspective and individual perspectives differs widely for both prophylaxis and treatment strategies. Optimal population and individual strategies for prophylaxis and treatment might

  4. Apolipoprotein B-associated cholesterol is a determinant of treatment outcome in patients with chronic hepatitis C virus infection receiving anti-viral agents interferon-alpha and ribavirin.

    Science.gov (United States)

    Sheridan, D A; Price, D A; Schmid, M L; Toms, G L; Donaldson, P; Neely, D; Bassendine, M F

    2009-06-15

    Hepatitis C virus (HCV) co-opts very-low-density lipoprotein (VLDL) pathways for replication, secretion and entry into hepatocytes and associates with apolipoprotein B (apoB) in plasma. Each VLDL contains apoB-100 and variable amounts of apolipoproteins E and C, cholesterol and triglycerides. To determine whether baseline lipid levels predicted treatment outcome. Retrospective analysis was performed of 250 chronic hepatitis C (CHC) patients who had received anti-viral agents interferon-alpha and ribavirin; 165 had a sustained virological response (SVR). Pre- and post-treatment nonfasting lipid profiles were measured and non-high-density lipoprotein (non-HDL) cholesterol (i.e. apoB-associated) was calculated. Binary logistic regression analysis assessed factors independently associated with treatment outcome. There was an independent association between higher apoB-associated cholesterol (non-HDL-C) and increased odds of SVR (odds ratio 2.09, P = 0.042). In multivariate analysis, non-HDL-C was significantly lower in HCV genotype 3 (g3) than genotype 1 (P = 0.007); this was reversible upon eradication of HCVg3 (pre-treatment non-HDL-C = 2.8 mmol/L, SVR = 3.6 mmol/L, P < 0.001). Higher apoB-associated cholesterol is positively associated with treatment outcome in CHC patients receiving anti-viral therapy, possibly due to competition between apoB-containing lipoproteins and infectious low-density HCV lipo-viral particles for hepatocyte entry via shared lipoprotein receptors.

  5. Antiviral agents for infectious mononucleosis (glandular fever).

    Science.gov (United States)

    De Paor, Muireann; O'Brien, Kirsty; Fahey, Tom; Smith, Susan M

    2016-12-08

    Infectious mononucleosis (IM) is a clinical syndrome, usually caused by the Epstein Barr virus (EPV), characterised by lymphadenopathy, fever and sore throat. Most cases of symptomatic IM occur in older teenagers or young adults. Usually IM is a benign self-limiting illness and requires only symptomatic treatment. However, occasionally the disease course can be complicated or prolonged and lead to decreased productivity in terms of school or work. Antiviral medications have been used to treat IM, but the use of antivirals for IM is controversial. They may be effective by preventing viral replication which helps to keep the virus inactive. However, there are no guidelines for antivirals in IM. To assess the effects of antiviral therapy for infectious mononucleosis (IM). We searched the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, March 2016), which contains the Cochrane Acute Respiratory Infections (ARI) Group's Specialised Register, MEDLINE (1946 to 15 April 2016), Embase (1974 to 15 April 2016), CINAHL (1981 to 15 April 2016), LILACS (1982 to 15 April 2016) and Web of Science (1955 to 15 April 2016). We searched the World Health Organization (WHO) International Clinical Trials Registry Platform and ClinicalTrials.gov for completed and ongoing trials. We included randomised controlled trials (RCTs) comparing antivirals versus placebo or no treatment in IM. We included trials of immunocompetent participants of any age or sex with clinical and laboratory-confirmed diagnosis of IM, who had symptoms for up to 14 days. Our primary outcomes were time to clinical recovery and adverse events and side effects of medication. Secondary outcomes included duration of abnormal clinical examination, complications, viral shedding, health-related quality of life, days missing from school or work and economic outcomes. Two review authors independently assessed studies for inclusion, assessed the included studies' risk of bias and extracted data using a

  6. Antiviral Drug Research Proposal Activity

    Directory of Open Access Journals (Sweden)

    Lisa Injaian

    2011-03-01

    Full Text Available The development of antiviral drugs provides an excellent example of how basic and clinical research must be used together in order to achieve the final goal of treating disease. A Research Oriented Learning Activity was designed to help students to better understand how basic and clinical research can be combined toward a common goal. Through this project students gained a better understanding of the process of scientific research and increased their information literacy in the field of virology. The students worked as teams to research the many aspects involved in the antiviral drug design process, with each student becoming an "expert" in one aspect of the project. The Antiviral Drug Research Proposal (ADRP culminated with students presenting their proposals to their peers and local virologists in a poster session. Assessment data showed increased student awareness and knowledge of the research process and the steps involved in the development of antiviral drugs as a result of this activity.

  7. Treatment of initially metastatic small-cell lung cancer

    International Nuclear Information System (INIS)

    Kohutek, F.; Bystricky, B.; Tamasova, M.

    2013-01-01

    Lung cancer (LC) is the most common cause of death associated with neoplasms. The incidence of LC in 2007 was 71.3/100,000 men and 18.6/100,000 women in Slovakia. Small-cell lung cancer (SCLC) includes 15 - 18% of all cases. The diagnosis of LC is based on patient's history, physical examination, basic laboratory tests, x-ray imaging and computed tomography (CT) imaging and histology. The material required for histology can be obtained by means of endoscopy or surgery. Ultrasonography (USG) and/or CT of abdomen is commonly performed as a part of staging process, along with CT or MRI of brain. Bone scan is performed in case of suspicion of bone involvement. According to TNM classification, seventh edition, the same classification can be used for SCLC and non-small cell lung cancer (NSCLC). Chemotherapy and radiotherapy are available for treatment of initially metastatic SCLC. First-line chemotherapy regimen should be based on combination of cisplatin or carboplatin with etoposide (PE). Alternatively, CAV regimen (cyclophosphamide, doxorubicin, vincristine) can be used. Newer regimens did not provide benefit when compared to standard regimens. If progression occurs later than 3 months after finishing first-line chemotherapy, the same regimen may be used in second-line chemotherapy. If progression occurs earlier than 3 months after finishing first-line chemotherapy, topotecan-based regimen is an option for second-line line chemotherapy. Despite promising outcomes of amrubicin-based second-line chemotherapy in Japan, amrubicin is not available in countries of E U. Standard therapy schedules do not include radiotherapy targeted on primary tumor and affected lymph-nodes. According to American and European guidelines, prophylactic cranial irradiation is recommended for patients with extensive disease-SCLC with good performance status after achieving complete or partial response to first-line chemotherapy. (author)

  8. Antiviral lead compounds from marine sponges

    KAUST Repository

    Sagar, Sunil

    2010-10-11

    Marine sponges are currently one of the richest sources of pharmacologically active compounds found in the marine environment. These bioactive molecules are often secondary metabolites, whose main function is to enable and/or modulate cellular communication and defense. They are usually produced by functional enzyme clusters in sponges and/or their associated symbiotic microorganisms. Natural product lead compounds from sponges have often been found to be promising pharmaceutical agents. Several of them have successfully been approved as antiviral agents for clinical use or have been advanced to the late stages of clinical trials. Most of these drugs are used for the treatment of human immunodeficiency virus (HIV) and herpes simplex virus (HSV). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due to the discovery of new types of viruses and emergence of drug resistant strains, it is necessary to develop new antiviral lead compounds continuously. Several sponge derived antiviral lead compounds which are hopedto be developed as future drugs are discussed in this review. Supply problems are usually the major bottleneck to the development of these compounds as drugs during clinical trials. However advances in the field of metagenomics and high throughput microbial cultivation has raised the possibility that these techniques could lead to the cost-effective large scale production of such compounds. Perspectives on biotechnological methods with respect to marine drug development are also discussed. 2010 by the authors; licensee MDPI.

  9. Perspective of Use of Antiviral Peptides against Influenza Virus

    Directory of Open Access Journals (Sweden)

    Sylvie Skalickova

    2015-10-01

    Full Text Available The threat of a worldwide influenza pandemic has greatly increased over the past decade with the emergence of highly virulent avian influenza strains. The increased frequency of drug-resistant influenza strains against currently available antiviral drugs requires urgent development of new strategies for antiviral therapy, too. The research in the field of therapeutic peptides began to develop extensively in the second half of the 20th century. Since then, the mechanisms of action for several peptides and their antiviral prospect received large attention due to the global threat posed by viruses. Here, we discussed the therapeutic properties of peptides used in influenza treatment. Peptides with antiviral activity against influenza can be divided into three main groups. First, entry blocker peptides such as a Flupep that interact with influenza hemagglutinin, block its binding to host cells and prevent viral fusion. Second, several peptides display virucidal activity, disrupting viral envelopes, e.g., Melittin. Finally, a third set of peptides interacts with the viral polymerase complex and act as viral replication inhibitors such as PB1 derived peptides. Here, we present a review of the current literature describing the antiviral activity, mechanism and future therapeutic potential of these influenza antiviral peptides.

  10. Antiviral resistance and the control of pandemic influenza.

    Directory of Open Access Journals (Sweden)

    Marc Lipsitch

    2007-01-01

    Full Text Available The response to the next influenza pandemic will likely include extensive use of antiviral drugs (mainly oseltamivir, combined with other transmission-reducing measures. Animal and in vitro studies suggest that some strains of influenza may become resistant to oseltamivir while maintaining infectiousness (fitness. Use of antiviral agents on the scale anticipated for the control of pandemic influenza will create an unprecedented selective pressure for the emergence and spread of these strains. Nonetheless, antiviral resistance has received little attention when evaluating these plans.We designed and analyzed a deterministic compartmental model of the transmission of oseltamivir-sensitive and -resistant influenza infections during a pandemic. The model predicts that even if antiviral treatment or prophylaxis leads to the emergence of a transmissible resistant strain in as few as 1 in 50,000 treated persons and 1 in 500,000 prophylaxed persons, widespread use of antivirals may strongly promote the spread of resistant strains at the population level, leading to a prevalence of tens of percent by the end of a pandemic. On the other hand, even in circumstances in which a resistant strain spreads widely, the use of antivirals may significantly delay and/or reduce the total size of the pandemic. If resistant strains carry some fitness cost, then, despite widespread emergence of resistance, antivirals could slow pandemic spread by months or more, and buy time for vaccine development; this delay would be prolonged by nondrug control measures (e.g., social distancing that reduce transmission, or use of a stockpiled suboptimal vaccine. Surprisingly, the model suggests that such nondrug control measures would increase the proportion of the epidemic caused by resistant strains.The benefits of antiviral drug use to control an influenza pandemic may be reduced, although not completely offset, by drug resistance in the virus. Therefore, the risk of resistance

  11. Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes

    Energy Technology Data Exchange (ETDEWEB)

    Komatsu, Tetsuro [Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux 33076 (France); Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575 (Japan); Will, Hans [Department of Tumor Biology, University Hospital Hamburg-Eppendorf, 20246 Hamburg (Germany); Nagata, Kyosuke [Department of Infection Biology, Faculty of Medicine, University of Tsukuba, Tsukuba 305-8575 (Japan); Wodrich, Harald, E-mail: harald.wodrich@u-bordeaux.fr [Microbiologie Fondamentale et Pathogénicité, MFP CNRS UMR 5234, Université de Bordeaux, Bordeaux 33076 (France)

    2016-04-22

    Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. - Highlights: • Host nuclear antiviral factors were analyzed upon adenovirus genome delivery. • Interferon treatments fail to permit PML nuclear bodies to target adenoviral genomes. • Neither Sp100A nor B targets adenoviral genomes despite potentially opposite roles. • The nuclear DNA sensor IFI16 does not target incoming adenoviral genomes. • PHF13/SPOC1 targets neither incoming adenoviral genomes nor genome-bound protein VII.

  12. Imaging analysis of nuclear antiviral factors through direct detection of incoming adenovirus genome complexes

    International Nuclear Information System (INIS)

    Komatsu, Tetsuro; Will, Hans; Nagata, Kyosuke; Wodrich, Harald

    2016-01-01

    Recent studies involving several viral systems have highlighted the importance of cellular intrinsic defense mechanisms through nuclear antiviral proteins that restrict viral propagation. These factors include among others components of PML nuclear bodies, the nuclear DNA sensor IFI16, and a potential restriction factor PHF13/SPOC1. For several nuclear replicating DNA viruses, it was shown that these factors sense and target viral genomes immediately upon nuclear import. In contrast to the anticipated view, we recently found that incoming adenoviral genomes are not targeted by PML nuclear bodies. Here we further explored cellular responses against adenoviral infection by focusing on specific conditions as well as additional nuclear antiviral factors. In line with our previous findings, we show that neither interferon treatment nor the use of specific isoforms of PML nuclear body components results in co-localization between incoming adenoviral genomes and the subnuclear domains. Furthermore, our imaging analyses indicated that neither IFI16 nor PHF13/SPOC1 are likely to target incoming adenoviral genomes. Thus our findings suggest that incoming adenoviral genomes may be able to escape from a large repertoire of nuclear antiviral mechanisms, providing a rationale for the efficient initiation of lytic replication cycle. - Highlights: • Host nuclear antiviral factors were analyzed upon adenovirus genome delivery. • Interferon treatments fail to permit PML nuclear bodies to target adenoviral genomes. • Neither Sp100A nor B targets adenoviral genomes despite potentially opposite roles. • The nuclear DNA sensor IFI16 does not target incoming adenoviral genomes. • PHF13/SPOC1 targets neither incoming adenoviral genomes nor genome-bound protein VII.

  13. Qualitative analysis of patient-centered decision attributes associated with initiating hepatitis C treatment.

    Science.gov (United States)

    Zuchowski, Jessica L; Hamilton, Alison B; Pyne, Jeffrey M; Clark, Jack A; Naik, Aanand D; Smith, Donna L; Kanwal, Fasiha

    2015-10-01

    In this era of a constantly changing landscape of antiviral treatment options for chronic viral hepatitis C (CHC), shared clinical decision-making addresses the need to engage patients in complex treatment decisions. However, little is known about the decision attributes that CHC patients consider when making treatment decisions. We identify key patient-centered decision attributes, and explore relationships among these attributes, to help inform the development of a future CHC shared decision-making aid. Semi-structured qualitative interviews with CHC patients at four Veterans Health Administration (VHA) hospitals, in three comparison groups: contemplating CHC treatment at the time of data collection (Group 1), recently declined CHC treatment (Group 2), or recently started CHC treatment (Group 3). Participant descriptions of decision attributes were analyzed for the entire sample as well as by patient group and by gender. Twenty-nine Veteran patients participated (21 males, eight females): 12 were contemplating treatment, nine had recently declined treatment, and eight had recently started treatment. Patients on average described eight (range 5-13) decision attributes. The attributes most frequently reported overall were: physical side effects (83%); treatment efficacy (79%), new treatment drugs in development (55%); psychological side effects (55%); and condition of the liver (52%), with some variation based on group and gender. Personal life circumstance attributes (such as availability of family support and the burden of financial responsibilities) influencing treatment decisions were also noted by all participants. Multiple decision attributes were interrelated in highly complex ways. Participants considered numerous attributes in their CHC treatment decisions. A better understanding of these attributes that influence patient decision-making is crucial in order to inform patient-centered clinical approaches to care (such as shared decision-making augmented

  14. Hanford Site radioactive mixed waste thermal treatment initiative

    International Nuclear Information System (INIS)

    Place, B.G.; Riddelle, J.G.

    1993-03-01

    This paper is a progress report of current Westinghouse Hanford Company engineering activities related to the implementation of a program for the thermal treatment of the Hanford Site radioactive mixed waste. Topics discussed include a site-specific engineering study, the review of private sector capability in thermal treatment, and thermal treatment of some of the Hanford Site radioactive mixed waste at other US Department of Energy sites

  15. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy

    Directory of Open Access Journals (Sweden)

    Ninna Aggerholm-Pedersen

    2016-01-01

    Full Text Available Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal growth factor receptor (EGFR was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8. However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin.

  16. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy.

    Science.gov (United States)

    Aggerholm-Pedersen, Ninna; Demuth, Christina; Safwat, Akmal; Meldgaard, Peter; Kassem, Moustapha; Sandahl Sorensen, Boe

    2016-01-01

    Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI) treatment with or without doxorubicin was assessed by MTS assay. Results. Initial results showed that the hMSC-TERT4 was more doxorubicin-sensitive while hMSC-TERT20-CE8 was less doxorubicin-sensitive evidenced by monitoring cell viability in the presence of doxorubicin at different doses. The epidermal growth factor receptor (EGFR) was activated in both cell lines. However hMSC-TERT20-CE8 exhibited significantly higher expression of the EGFR ligands. EGFR inhibitors such as erlotinib and afatinib alone or in combination with doxorubicin failed to further decrease cell viability of hMSC-TERT20-CE8. However, inhibition with the TKI dasatinib in combination with doxorubicin decreased cell viability of the hMSC-TERT20-CE8 cell line. Conclusion. Our results demonstrate that dasatinib, but not EGFR-directed treatment, can decrease cell viability of stromal cancer stem cells less sensitive to doxorubicin.

  17. Utilizing the fluidized bed to initiate water treatment on site

    International Nuclear Information System (INIS)

    Ahmadvand, H.; Germann, G.; Gandee, J.P.; Buehler, V.T.

    1995-01-01

    Escalating wastewater disposal costs coupled with enforcement of stricter regulations push industrial sites previously without water treatment to treat on site. These sites, inexperienced in water treatment, require a treatment technology that is easily installed, operated, and maintained. The aerobic granular activated carbon (GAC) fluidized bed incorporates biological and adsorptive technologies into a simple, cost-effective process capable of meeting strict effluent requirements. Two case studies at industrial sites illustrate the installation and operation of the fluidized bed and emphasize the ability to use the fluidized bed singularly or as an integral component of a treatment system capable of achieving treatment levels that allow surface discharge and reinjection. Attention is focused on BTEX (benzene, toluene, ethylbenzene, and xylenes)

  18. Dasatinib and Doxorubicin Treatment of Sarcoma Initiating Cells: A Possible New Treatment Strategy

    DEFF Research Database (Denmark)

    Aggerholm-Pedersen, Ninna; Demouth, Christina; Safwat, Akmal

    2016-01-01

    Background. One of the major challenges affecting sarcoma treatment outcome, particularly that of metastatic disease, is resistance to chemotherapy. Cancer-initiating cells are considered a major contributor to this resistance. Methods. An immortalised nontransformed human stromal (mesenchymal......) stem cell line hMSC-TERT4 and a transformed cell line hMSC-TERT20-CE8, known to form sarcoma-like tumours when implanted in immune-deficient mice, were used as models. Receptor tyrosine kinase (RTK) activation was analysed by RTK arrays and cellular viability after tyrosine kinases inhibitor (TKI...

  19. Viral ancestors of antiviral systems.

    Science.gov (United States)

    Villarreal, Luis P

    2011-10-01

    All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the 'Big Bang' theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features.

  20. Viral Ancestors of Antiviral Systems

    Directory of Open Access Journals (Sweden)

    Luis P. Villarreal

    2011-10-01

    Full Text Available All life must survive their corresponding viruses. Thus antiviral systems are essential in all living organisms. Remnants of virus derived information are also found in all life forms but have historically been considered mostly as junk DNA. However, such virus derived information can strongly affect host susceptibility to viruses. In this review, I evaluate the role viruses have had in the origin and evolution of host antiviral systems. From Archaea through bacteria and from simple to complex eukaryotes I trace the viral components that became essential elements of antiviral immunity. I conclude with a reexamination of the ‘Big Bang’ theory for the emergence of the adaptive immune system in vertebrates by horizontal transfer and note how viruses could have and did provide crucial and coordinated features.

  1. Aminoadamantanes versus other antiviral drugs for chronic hepatitis C

    DEFF Research Database (Denmark)

    Lamers, Mieke H; Broekman, Mark; Drenth, Joost Ph

    2014-01-01

    months after the end of treatment) in approximately 40% to 80% of treated patients, depending on viral genotype. Recently, a new class of drugs have emerged for hepatitis C infection, the direct acting antivirals, which in combination with standard therapy or alone can lead to sustained virological...... response in 80% or more of treated patients. Aminoadamantanes, mostly amantadine, are antiviral drugs used for the treatment of patients with chronic hepatitis C. We have previously systematically reviewed amantadine versus placebo or no intervention and found no significant effects of the amantadine...... on all-cause mortality or liver-related morbidity and on adverse events in patients with hepatitis C. Overall, we did not observe a significant effect of amantadine on sustained virological response. In this review, we systematically review aminoadamantanes versus other antiviral drugs. OBJECTIVES...

  2. Prevalence of hepatitis C virus-resistant association substitutions to direct-acting antiviral agents in treatment-naïve hepatitis C genotype 1b-infected patients in western China

    Directory of Open Access Journals (Sweden)

    Li Z

    2017-10-01

    Full Text Available Zhao Li,* Zhi-wei Chen,* Hu Li, Hong Ren, Peng Hu Department of Infectious Diseases, Institute for Viral Hepatitis, Key Laboratory of Molecular Biology for Infectious Diseases, Chinese Ministry of Education, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China *These authors contributed equally to this work. Background: Direct-acting antivirals (DAAs against hepatitis C virus (HCV are potent and highly efficacious. However, resistance-associated substitutions (RASs relevant to DAAs can impair treatment effectiveness even at baseline. Moreover, the prevalence of baseline RASs in HCV genotype 1b-infected patients in western China is still unclear. Materials and methods: Direct sequencing of the HCV NS3, NS5A, and NS5B regions was performed in baseline serum samples of 70 DAAs treatment-naïve HCV 1b-infected patients in western China. The sequences were analyzed with MEGA version 5.05 software. Evolutionary patterns of RASs and amino-acid covariance patterns in the NS3, NS5A, and NS5B genes were analyzed by MEGA and Cytoscape (version 3.2.1, respectively.Results: The presence of at least one RAS in the NS3 region (C16S, T54S, Q80R/L, A87T, R117H, S122G, V132I, V170I was observed in 85.48% (53 of 62 of patients, RASs in the NS5A region (L28M, R30Q, Q54H, P58S/T, Q62H/R, Y93H were observed in 42.42% (28 of 66 of patients, and RASs in the NS5B region (N142S, A300T, C316N, A338V, S365A, L392I, M414L, I424V, A442T, V499A, S556G were observed in 100% (44 of 44 of patients. Evolutionary patterns of RASs and amino-acid covariance patterns for the NS3, NS5A, and NS5B genes are reported.Conclusion: The prevalence of RASs relevant to DAAs detected in the NS3, NS5A, and NS5B regions of HCV 1b from DAA treatment-naïve patients is high. Therefore, more attention should be paid to RASs associated with DAAs in the upcoming DAA-treatment era in China. Keywords: hepatitis C virus, unstructured proteins, resistance

  3. Experimental Simulation of the Effects of an Initial Antibiotic Treatment on a Subsequent Treatment after Initial Therapy Failure

    NARCIS (Netherlands)

    Feng, Yanfang; Händel, Nadine; de Groot, Marnix H. P.; Brul, Stanley; Schultsz, Constance; ter Kuile, Benno H.

    2014-01-01

    Therapy failure of empirical antibiotic treatments prescribed by primary care physicians occurs commonly. The effect of such a treatment on the susceptibility to second line antimicrobial drugs is unknown. Resistance to amoxicillin was rapidly induced or selected in E. coli at concentrations

  4. [Integrated intensive treatment of tinnitus: method and initial results].

    Science.gov (United States)

    Mazurek, B; Georgiewa, P; Seydel, C; Haupt, H; Scherer, H; Klapp, B F; Reisshauer, A

    2005-07-01

    In recent years, no major advances have been made in understanding the mechanisms underlying the development of tinnitus. Hence, the present therapeutic strategies aim at decoupling the subconscious from the perception of tinnitus. Mindful of the lessons drawn from existing tinnitus retraining and desensitisation therapies, a new integrated day hospital strategy of treatment lasting 7-14 days has been developed at the Charité Hospital and is presented in the present paper. The strategy for treating tinnitus in the proximity of patient domicile is designed for patients who feel disturbed in their world of perception and their efficiency due to tinnitus and give evidence of mental and physical strain. In view of the etiologically non-uniform and multiple events connected with tinnitus, consideration was also given to the fact that somatic and psychosocial factors are equally involved. Therefore, therapy should aim at diagnosing and therapeutically influencing those psychosocial factors that reduce the hearing impression to such an extent that the affected persons suffer from strain. The first results of therapy-dependent changes of 46 patients suffering from chronic tinnitus are presented. The data were evaluated before and after 7 days of treatment and 6 months after the end of treatment. Immediately after the treatment, the scores of both the tinnitus questionnaire (Goebel and Hiller) and the subscales improved significantly. These results were maintained during the 6-month post-treatment period and even improved.

  5. A Naval Postgraduate Dental School Analysis Of Initial Endodontic Treatment

    Science.gov (United States)

    2015-07-01

    location by quadrant Follow-up variables Pain location by tooth Permanent restoration History of orthodontic treatment Intracanal post History of external... resorption Open margin on restoration History of internal resorption Tooth location!type History of bleaching Follow-up time Presence of

  6. Arthrocentesis as initial treatment for temporomandibular joint arthropathy : A randomized controlled trial

    NARCIS (Netherlands)

    Vos, L. M.; Huddleston Slater, J. J. R.; Stegenga, B.

    Objective: To determine the effectiveness of arthrocentesis compared to conservative treatment as initial treatment with regard to temporomandibular joint pain and mandibular movement. Patients and methods: In this randomized controlled trial, 80 patients with arthralgia of the TMJ (classified

  7. Fat embolism syndrome in femoral shaft fractures: does the initial treatment make a difference?

    Directory of Open Access Journals (Sweden)

    Janio Jose Alves Bezerra Silva

    Full Text Available ABSTRACT Objective: To identify the risk factors correlated with the initial treatment performed. Methods: This is a retrospective study involving a total of 272 patients diagnosed with femoral shaft fractures. Of the patients, 14% were kept at rest until the surgical treatment, 52% underwent external fixation, 10% received immediate definitive treatment, and 23% remained in skeletal traction (23% until definitive treatment., Results: There were six cases of fat embolism syndrome (FES, which showed that , polytrauma is the main risk factor for its development and that initial therapy was not important. Conclusion: Polytrauma patients have a greater chance of developing FES and there was no influence from the initial treatment.

  8. Delay of Treatment Initiation Does Not Adversely Affect Survival Outcome in Breast Cancer.

    Science.gov (United States)

    Yoo, Tae-Kyung; Han, Wonshik; Moon, Hyeong-Gon; Kim, Jisun; Lee, Jun Woo; Kim, Min Kyoon; Lee, Eunshin; Kim, Jongjin; Noh, Dong-Young

    2016-07-01

    Previous studies examining the relationship between time to treatment and survival outcome in breast cancer have shown inconsistent results. The aim of this study was to analyze the overall impact of delay of treatment initiation on patient survival and to determine whether certain subgroups require more prompt initiation of treatment. This study is a retrospective analysis of stage I-III patients who were treated in a single tertiary institution between 2005 and 2008. Kaplan-Meier survival analysis and Cox proportional hazards regression model were used to evaluate the impact of interval between diagnosis and treatment initiation in breast cancer and various subgroups. A total of 1,702 patients were included. Factors associated with longer delay of treatment initiation were diagnosis at another hospital, medical comorbidities, and procedures performed before admission for surgery. An interval between diagnosis and treatment initiation as a continuous variable or with a cutoff value of 15, 30, 45, and 60 days had no impact on disease-free survival (DFS). Subgroup analyses for hormone-responsiveness, triple-negative breast cancer, young age, clinical stage, and type of initial treatment showed no significant association between longer delay of treatment initiation and DFS. Our results show that an interval between diagnosis and treatment initiation of 60 days or shorter does not appear to adversely affect DFS in breast cancer.

  9. A Naval Postgraduate Dental School Analysis of Initial Endodontic Treatment

    Science.gov (United States)

    2013-06-01

    to prevent or heal disease , i.e. apical periodontitis . Accordingly, endodontic treatment outcomes can better be defined in reference to healing and...Janket S, Baird AE, Chuang S, Jones JA. Meta-analysis of periodontal disease risk and risk of coronary heart disease and stroke. Oral Surg Oral Med Oral...appointment endodontic therapy in dogs ’ teeth with apical periodontitis . J Endod 2003;29:121-4. 27. Penesis VA, Fitzgerald PI, Fayad MI, Wenckus

  10. Recent developments in antiviral agents against enterovirus 71 infection.

    Science.gov (United States)

    Tan, Chee Wah; Lai, Jeffrey Kam Fatt; Sam, I-Ching; Chan, Yoke Fun

    2014-02-12

    Enterovirus 71 (EV-71) is the main etiological agent of hand, foot and mouth disease (HFMD). Recent EV-71 outbreaks in Asia-Pacific were not limited to mild HFMD, but were associated with severe neurological complications such as aseptic meningitis and brainstem encephalitis, which may lead to cardiopulmonary failure and death. The absence of licensed therapeutics for clinical use has intensified research into anti-EV-71 development. This review highlights the potential antiviral agents targeting EV-71 attachment, entry, uncoating, translation, polyprotein processing, virus-induced formation of membranous RNA replication complexes, and RNA-dependent RNA polymerase. The strategies for antiviral development include target-based synthetic compounds, anti-rhinovirus and poliovirus libraries screening, and natural compound libraries screening. Growing knowledge of the EV-71 life cycle will lead to successful development of antivirals. The continued effort to develop antiviral agents for treatment is crucial in the absence of a vaccine. The coupling of antivirals with an effective vaccine will accelerate eradication of the disease.

  11. Exploiting Genetic Interference for Antiviral Therapy.

    Directory of Open Access Journals (Sweden)

    Elizabeth J Tanner

    2016-05-01

    Full Text Available Rapidly evolving viruses are a major threat to human health. Such viruses are often highly pathogenic (e.g., influenza virus, HIV, Ebola virus and routinely circumvent therapeutic intervention through mutational escape. Error-prone genome replication generates heterogeneous viral populations that rapidly adapt to new selection pressures, leading to resistance that emerges with treatment. However, population heterogeneity bears a cost: when multiple viral variants replicate within a cell, they can potentially interfere with each other, lowering viral fitness. This genetic interference can be exploited for antiviral strategies, either by taking advantage of a virus's inherent genetic diversity or through generating de novo interference by engineering a competing genome. Here, we discuss two such antiviral strategies, dominant drug targeting and therapeutic interfering particles. Both strategies harness the power of genetic interference to surmount two particularly vexing obstacles-the evolution of drug resistance and targeting therapy to high-risk populations-both of which impede treatment in resource-poor settings.

  12. [Reporting initiatives. An update on treatment in radiology].

    Science.gov (United States)

    Hempel, J-M; Pinto dos Santos, D; Kloeckner, R; Dueber, C; Mildenberger, P

    2014-07-01

    The written radiological report is the most important means of communication between the radiologist and the referring medical doctor. There is no universal definition of a radiological report concerning its structure and content. The majority of clinicians and radiologists prefer structured reporting rather than free text reports of findings. Structured reporting does not increase the quality of a radiological report but has many advantages in research, teaching and quality management. Using standard RadLex terms facilitates translation and ontological assignment of a report. The Reporting Initiative of the Radiological Society of North America (RSNA) offers free and freely available extensively validated best practices radiology report templates in the new management of radiology report templates (MRRT) format according to the guidelines of the Integrating the Healthcare Enterprise (IHE).

  13. From genome to antivirals: SARS as a test tube.

    Science.gov (United States)

    Kliger, Yossef; Levanon, Erez Y; Gerber, Doron

    2005-03-01

    The severe acute respiratory syndrome (SARS) epidemic brought into the spotlight the need for rapid development of effective anti-viral drugs against newly emerging viruses. Researchers have leveraged the 20-year battle against AIDS into a variety of possible treatments for SARS. Most prominently, based solely on viral genome information, silencers of viral genes, viral-enzyme blockers and viral-entry inhibitors were suggested as potential therapeutic agents for SARS. In particular, inhibitors of viral entry, comprising therapeutic peptides, were based on the recently launched anti-HIV drug enfuvirtide. This could represent one of the most direct routes from genome sequencing to the discovery of antiviral drugs.

  14. Favipiravir elicits antiviral mutagenesis during virus replication in vivo.

    Science.gov (United States)

    Arias, Armando; Thorne, Lucy; Goodfellow, Ian

    2014-10-21

    Lethal mutagenesis has emerged as a novel potential therapeutic approach to treat viral infections. Several studies have demonstrated that increases in the high mutation rates inherent to RNA viruses lead to viral extinction in cell culture, but evidence during infections in vivo is limited. In this study, we show that the broad-range antiviral nucleoside favipiravir reduces viral load in vivo by exerting antiviral mutagenesis in a mouse model for norovirus infection. Increased mutation frequencies were observed in samples from treated mice and were accompanied with lower or in some cases undetectable levels of infectious virus in faeces and tissues. Viral RNA isolated from treated animals showed reduced infectivity, a feature of populations approaching extinction during antiviral mutagenesis. These results suggest that favipiravir can induce norovirus mutagenesis in vivo, which in some cases leads to virus extinction, providing a proof-of-principle for the use of favipiravir derivatives or mutagenic nucleosides in the clinical treatment of noroviruses.

  15. The Antiviral Effect of Baicalin on Enterovirus 71 In Vitro

    Directory of Open Access Journals (Sweden)

    Xiang Li

    2015-08-01

    Full Text Available Baicalin is a flavonoid compound extracted from Scutellaria roots that has been reported to possess antibacterial, anti-inflammatory, and antiviral activities. However, the antiviral effect of baicalin on enterovirus 71 (EV71 is still unknown. In this study, we found that baicalin showed inhibitory activity on EV71 infection and was independent of direct virucidal or prophylactic effect and inhibitory viral absorption. The expressions of EV71/3D mRNA and polymerase were significantly blocked by baicalin treatment at early stages of EV71 infection. In addition, baicalin could decrease the expressions of FasL and caspase-3, as well as inhibit the apoptosis of EV71-infected human embryonal rhabdomyosarcoma (RD cells. Altogether, these results indicate that baicalin exhibits potent antiviral effect on EV71 infection, probably through inhibiting EV71/3D polymerase expression and Fas/FasL signaling pathways.

  16. Treatment outcomes after initiation of exenatide twice daily or insulin in clinical practice

    DEFF Research Database (Denmark)

    Ostenson, Claes-Göran; Matthaei, Stephan; Reaney, Matthew

    2013-01-01

    OBJECTIVE: The CHanges to treatment and Outcomes in patients with type 2 diabetes initiating InjeCtablE therapy (CHOICE) study assessed time to, and reasons for, significant treatment change after patients with type 2 diabetes (T2DM) initiated their first injectable glucose-lowering therapy (exen...

  17. Cost effectiveness of arthrocentesis as initial treatment for temporomandibular joint arthralgia: A randomized controlled trial

    NARCIS (Netherlands)

    Vos, L.M.; Stant, A.D.; Quik, E.H.; Huddleston Slater, J.J.R.; Stegenga, B.

    2013-01-01

    Objective: To determine the cost effectiveness of arthrocentesis as initial treatment compared to care as usual (CAU) for temporomandibular joint (TMJ) arthralgia. Materials and methods: 80 patients were randomly allocated to arthrocentesis as initial treatment (n = 40) or CAU (n = 40).

  18. Initial treatment results using cyberknife for head and neck tumor

    International Nuclear Information System (INIS)

    Himei, Kengo; Katsui, Kuniaki; Yoshida, Atsushi; Takemoto, Mitsuhiro; Kobayashi, Mitsuru; Kuroda, Masahiro; Hiraki, Yoshio

    2002-01-01

    The CyberKnife, a medical device for stereotactic radiotherapy, is composed of a combination of a robot manipulator and LINAC. For the treatment of head and neck tumors, this system has been applied. Between June 2000 and January 2001, 18 patients with head and neck tumor were treated with this system because of tumor recurrence, difficulty in surgery or additional increase after external radiotherapy. The median age was 64 years. Primary lesions were skull base (4), nasopharynx (3), paranasal sinus (3), nasal cavity (2), lacrimal gland (1), oropharynx (1), oral floor (1), and buccul mucosa (1), metastatic lymph nodes were found in three. The prescribed dose was 12-38 Gy as for marginal dose. The response rate (CR+PR) was 44.4% and local control rate (CR+PR+NC) was 77.8%. The adverse effects were assessed by the NCI-CTC Version 2.0 and observed grade 3 in two cases. Our early experience indicates that this system could to be feasible for the treatment of locally advanced or recurrent head and neck tumor, and for the reduction of adverse effect and maintenance of useful QOL of patients. (author)

  19. Therapeutic Erythrocytapheresis in the Initial Treatment of Hereditary Hemochromatosis

    Directory of Open Access Journals (Sweden)

    Vít Řeháček

    2012-01-01

    Full Text Available Background: The current treatment of hereditary hemochromatosis (HH consists of performing periodic whole blood phlebotomies. Erythrocytapheresis (EA can remove up to three times more red blood cells per single procedure and could thus have a clinical benefit. A prospective study of 30 consecutive cases of HH were included in a periodic EA program. Methods and patients: EA were performed using a discontinuous flow cell separators. The protocol consisted of a bimonthly EA until normalization of the serum ferritin was reached. The aim was to reduce the total erythrocyte volume by 25–35%, eventually, to adjust the amount so that hematocrit would not drop below 0.25. Results: 530 ± 101 ml of erythrocytes were removed (median 517, range 116–761 ml. Iron depletion (ferritin < 20 μg/l was achieved in all patients after a mean 6.9 ± 7.6 months, median 5 months, range 1–36 months and a mean 14 EA sessions. The procedures were well tolerated and there were no severe side-effects. Conclusions: We conclude that HH patients treated with EA achieved iron depletion quickly under good conditions of tolerance. The efficacy, speed, tolerability, and more favorable schedule of an EA program facilitate treatment of HH.

  20. Antiviral activity of the extracts of Rhodophyceae from Morocco

    African Journals Online (AJOL)

    Administrator

    2010-11-15

    Nov 15, 2010 ... replication of HSV-1 in vitro at an EC50 (Effective Concentration 50%) ranging from <2.5 to 75.9 µg mL-1. No cytotoxic effect ... Keywords: Antiviral, Aqueous extracts, Organic extracts, Rhodophyceae, Herpes simplex virus. INTRODUCTION ... from a species of Bryopsis as a possible treatment of lung cancer ...

  1. Towards a global initiative for fibrosis treatment (GIFT

    Directory of Open Access Journals (Sweden)

    Maria Molina-Molina

    2017-12-01

    Full Text Available Idiopathic pulmonary fibrosis (IPF is a progressive lung disease characterised by increased scarring of lung tissue. Despite the recent introduction of novel drugs that slow disease progression, IPF remains a deadly disease, and the benefits of these new drugs differ markedly between patients. Human diseases arise due to alterations in an almost limitless network of interconnected genes, proteins, metabolites, cells and tissues, in direct relationship with a continuously changing macro- or microenvironment. Systems biology is a novel research strategy that seeks to understand the structure and behaviour of the so-called “emergent properties” of complex systems, such as those involved in disease pathogenesis, which are most often overlooked when just one element of disease pathogenesis is observed in isolation. This article summarises the debate that took place during a European Respiratory Society research seminar in Barcelona, Spain on December 15–16, 2016, which focused on how systems biology could generate new data by integrating the different IPF pathogenic levels of complexity. The main conclusion of the seminar was to create a global initiative to improve IPF outcomes by integrating cutting-edge international research that leverages systems biology to develop a precision medicine approach to tackle this devastating disease.

  2. Patterns of initial treatment failure of esophageal cancer following radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Sugahara, Shinji; Nakajima, Kotaro [Hitachi General Hospital, Ibaraki (Japan); Ohara, Kiyoshi; Okumura, Toshiyuki; Irie, Toshiyuki; Itai, Yuji

    1999-11-01

    Sixty patients with stage I-III esophageal squamous cell cancer treated by definitive radiotherapy (RT) were analyzed for patterns of treatment failure. Patients were treated by external RT alone (n=45) or in combination with intraluminal RT (N=15) when suitable, with prescribed total doses ranging from 59.4 to 104.4 Gy. Concurrent chemotherapy consisting of cisplatin and/or 5-fluorouracil was administered to 19 patients. The two-year actuarial survival rate and two year disease-free survival rate were 29.5% and 18.3%, respectively. Two-year failure rates were 66.5%, 36.9%, and 3.8%, for the esophagus, lymph nodes, and other sites, respectively. Two-year esophageal failure rates for patients with T1-2 (n=8), T3 (n=30), and T4 disease (n=22) were 14.3%, 64.7%, and 87.9%, respectively (p<0.05). A multivariate analysis of esophageal failure with descriptive variables of T classification, tumor length, and performance of intraluminal RT revealed that only T classification was an independent factor (p=0.021). Two-year lymph node failure rates were 24.8% and 33.6% for patients with N0 (n=36) and N1 disease (n=24), respectively (p=0.0035). Lymph node failure in N0 patients was found exclusively outside the treatment field. These results suggest that inclusion of potential lymph node metastases in the radiation field could lessen the lymph node failure rate in T1-3N0M0 patients. (author)

  3. Breast Cancer-Initiating Cells: Insights into Novel Treatment Strategies

    International Nuclear Information System (INIS)

    Santilli, Guido; Binda, Mara; Zaffaroni, Nadia; Daidone, Maria Grazia

    2011-01-01

    There is accumulating evidence that breast cancer may arise from mutated mammary stem/progenitor cells which have been termed breast cancer-initiating cells (BCIC). BCIC identified in clinical specimens based on membrane phenotype (CD44 + /CD24 −/low and/or CD133 + expression) or enzymatic activity of aldehyde dehydrogenase 1 (ALDH1 + ), have been demonstrated to have stem/progenitor cell properties, and are tumorigenic when injected in immunocompromized mice at very low concentrations. BCIC have also been isolated and in vitro propagated as non-adherent spheres of undifferentiated cells, and stem cell patterns have been recognized even in cancer cell lines. Recent findings indicate that aberrant regulation of self renewal is central to cancer stem cell biology. Alterations in genes involved in self-renewal pathways, such as Wnt, Notch, sonic hedgehog, PTEN and BMI, proved to play a role in breast cancer progression. Hence, targeting key elements mediating the self renewal of BCIC represents an attractive option, with a solid rationale, clearly identifiable molecular targets, and adequate knowledge of the involved pathways. Possible concerns are related to the poor knowledge of tolerance and efficacy of inhibiting self-renewal mechanisms, because the latter are key pathways for a variety of biological functions and it is unknown whether their interference would kill BCIC or simply temporarily stop them. Thus, efforts to develop BCIC-targeted therapies should not only be focused on interfering on self-renewal, but could seek to identify additional molecular targets, like those involved in regulating EMT-related pathways, in reversing the MDR phenotype, in inducing differentiation and controlling cell survival pathways

  4. Research priorities to achieve universal access to hepatitis C prevention, management and direct-acting antiviral treatment among people who inject drugs

    DEFF Research Database (Denmark)

    Grebely, Jason; Bruneau, Julie; Lazarus, Jeffrey V

    2017-01-01

    of HCV among PWID. The Kirby Institute, UNSW Sydney and the International Network on Hepatitis in Substance Users (INHSU) established an expert round table panel to assess current research gaps and establish future research priorities for the prevention and management of HCV among PWID. This round table......, gaps in research, and develop research priorities. Topics for discussion included the epidemiology of injecting drug use, HCV, and HIV among PWID, HCV prevention, HCV testing, linkage to HCV care and treatment, DAA treatment for HCV infection, and reinfection following successful treatment. This paper...

  5. Antiviral therapy of hepatitis C in 2014: do we need resistance testing?

    Science.gov (United States)

    Schneider, Maximilian David; Sarrazin, Christoph

    2014-05-01

    The treatment of chronic hepatitis C has fundamentally changed since the approval of the first direct-acting antivirals (DAA) in 2011. In addition to telaprevir and boceprevir, in 2014 two new NS3 protease inhibitors (simeprevir and faldaprevir), one non-nucleoside polymerase inhibitor (sofosbuvir) and one NS5a replication complex inhibitor (daclatasvir) have expanded the treatment options for chronic hepatitis C. Resistance-associated variants (RAV) are naturally produced during the HCV life cycle. The frequency of RAVs within HCV quasispecies mainly depends on their replicational fitness. Variants conferring resistance to nucleos(t)ide analogues have not been detected, and the majority of NS3 protease-resistant variants are present at low frequencies (0.1-3%) before initiation of DAA-based therapies. However, the Q80K variant conferring resistance to simeprevir has been observed in 9-48% of untreated HCV genotype 1a-infected patients, leading to reduced SVR rates. Resistant variants are detectable in the majority of patients with treatment failure to NS3 protease inhibitor- or NS5a inhibitor-based antiviral therapy. Long-term follow-up studies by population-based sequence analysis have shown the disappearance of resistant variants in the majority of patients, with median times to loss of mutations of 4-64weeks. For the nucleotide analogue sofosbuvir, the emergence of the S282T resistant variant has been observed only in single patients, with reversion to wild-type within several weeks. Data are sparse on retreatment of patients with the same DAA or the same class of DAAs. However, retreatment with a different class of DAAs after failure of NS3 protease inhibitor-based therapy has been successful in small studies. This article forms part of a symposium in Antiviral Research on "Hepatitis C: next steps toward global eradication." Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Development and initial evaluation of a treatment decision dashboard.

    Science.gov (United States)

    Dolan, James G; Veazie, Peter J; Russ, Ann J

    2013-04-21

    For many healthcare decisions, multiple alternatives are available with different combinations of advantages and disadvantages across several important dimensions. The complexity of current healthcare decisions thus presents a significant barrier to informed decision making, a key element of patient-centered care.Interactive decision dashboards were developed to facilitate decision making in Management, a field marked by similarly complicated choices. These dashboards utilize data visualization techniques to reduce the cognitive effort needed to evaluate decision alternatives and a non-linear flow of information that enables users to review information in a self-directed fashion. Theoretically, both of these features should facilitate informed decision making by increasing user engagement with and understanding of the decision at hand. We sought to determine if the interactive decision dashboard format can be successfully adapted to create a clinically realistic prototype patient decision aid suitable for further evaluation and refinement. We created a computerized, interactive clinical decision dashboard and performed a pilot test of its clinical feasibility and acceptability using a multi-method analysis. The dashboard summarized information about the effectiveness, risks of side effects and drug-drug interactions, out-of-pocket costs, and ease of use of nine analgesic treatment options for knee osteoarthritis. Outcome evaluations included observations of how study participants utilized the dashboard, questionnaires to assess usability, acceptability, and decisional conflict, and an open-ended qualitative analysis. The study sample consisted of 25 volunteers - 7 men and 18 women - with an average age of 51 years. The mean time spent interacting with the dashboard was 4.6 minutes. Mean evaluation scores on scales ranging from 1 (low) to 7 (high) were: mechanical ease of use 6.1, cognitive ease of use 6.2, emotional difficulty 2.7, decision-aiding effectiveness 5

  7. Learning from the Messengers: Innate Sensing of Viruses and Cytokine Regulation of Immunity — Clues for Treatments and Vaccines

    Directory of Open Access Journals (Sweden)

    Jesper Melchjorsen

    2013-01-01

    Full Text Available Virus infections are a major global public health concern, and only via substantial knowledge of virus pathogenesis and antiviral immune responses can we develop and improve medical treatments, and preventive and therapeutic vaccines. Innate immunity and the shaping of efficient early immune responses are essential for control of viral infections. In order to trigger an efficient antiviral defense, the host senses the invading microbe via pattern recognition receptors (PRRs, recognizing distinct conserved pathogen-associated molecular patterns (PAMPs. The innate sensing of the invading virus results in intracellular signal transduction and subsequent production of interferons (IFNs and proinflammatory cytokines. Cytokines, including IFNs and chemokines, are vital molecules of antiviral defense regulating cell activation, differentiation of cells, and, not least, exerting direct antiviral effects. Cytokines shape and modulate the immune response and IFNs are principle antiviral mediators initiating antiviral response through induction of antiviral proteins. In the present review, I describe and discuss the current knowledge on early virus–host interactions, focusing on early recognition of virus infection and the resulting expression of type I and type III IFNs, proinflammatory cytokines, and intracellular antiviral mediators. In addition, the review elucidates how targeted stimulation of innate sensors, such as toll-like receptors (TLRs and intracellular RNA and DNA sensors, may be used therapeutically. Moreover, I present and discuss data showing how current antimicrobial therapies, including antibiotics and antiviral medication, may interfere with, or improve, immune response.

  8. Is initial (24 hours) lavage necessary in treatment of CAPD peritonitis?

    DEFF Research Database (Denmark)

    Ejlersen, E; Brandi, L; Løkkegaard, H

    1991-01-01

    A randomized trial was conducted to examine the influence of initial lavage on treatment of CAPD peritonitis. Patients with hypotension and shock were excluded from the trial. Thirty-six CAPD patients with acute peritonitis were randomized to treatment with intraperitoneal antibiotics including...... benefit in treatment of CAPD peritonitis in patients without profound hypotension and shock....

  9. Initial Severity and Differential Treatment Outcome in the National Institute of Mental Health Treatment of Depression Collaborative Research Program.

    Science.gov (United States)

    Elkin, Irene; And Others

    1995-01-01

    Random regression models were used to investigate the role of initial severity in the outcome of four treatments for major depression: cognitive behavioral therapy, interpersonal psychotherapy, imipramine plus clinical management, and placebo plus clinical management. Initial severity of depression and impairment of functioning significantly…

  10. Initial development of a treatment adherence measure for cognitive-behavioral therapy for child anxiety

    OpenAIRE

    Southam-Gerow, MA; McLeod, BD; Arnold, CC; Rodríguez, A; Cox, JR; Reise, SP; Bonifay, WE; Weisz, JR; Kendall, PC

    2016-01-01

    © 2015 American Psychological Association.The measurement of treatment adherence (a component of treatment integrity defined as the extent to which a treatment is delivered as intended) is a critical element in treatment evaluation research. This article presents initial psychometric data for scores on the Cognitive-Behavioral Therapy Adherence Scale for Youth Anxiety (CBAY-A), an observational measure designed to be sensitive to common practice elements found in individual cognitive- behavio...

  11. Resistance mutations and CTL epitopes in archived HIV-1 DNA of patients on antiviral treatment: toward a new concept of vaccine.

    Directory of Open Access Journals (Sweden)

    Jennifer Papuchon

    Full Text Available Eleven patients responding successfully to first-line antiretroviral therapy (ART were investigated for proviral drug resistance mutations (DRMs in RT by ultra-deep pyrosequencing (UDPS. After molecular typing of the class I alleles A and B, the CTL epitopes in the Gag, Nef and Pol regions of the provirus were sequenced and compared to the reference HXB2 HIV-1 epitopes. They were then matched with the HLA alleles with determination of theoretical affinity (TA. For 3 patients, the results could be compared with an RNA sample of the circulating virus at initiation of therapy. Five out of 11 patients exhibited DRMs by UDPS. The issue is whether a therapeutic switch is relevant in these patients by taking into account the identity of the archived resistance mutations. When the archived CTL epitopes were determined on the basis of the HLA alleles, different patterns were observed. Some epitopes were identical to those reported for the reference with the same TA, while others were mutated with a decrease in TA. In 2 cases, an epitope was observed as a combination of subpopulations at entry and was retrieved as a single population with lower TA at success. With regard to immunological stimulation and given the variability of the archived CTL epitopes, we propose a new concept of curative vaccine based on identification of HIV-1 CTL epitopes after prior sequencing of proviral DNA and matching with HLA class I alleles.

  12. Sleep Hygiene and Melatonin Treatment for Children and Adolescents with ADHD and Initial Insomnia

    Science.gov (United States)

    Weiss, Margaret D.; Wasdell, Michael B.; Bomben, Melissa M.; Rea, Kathleen J.; Freeman, Roger D.

    2006-01-01

    Objective: To evaluate the efficacy of sleep hygiene and melatonin treatment for initial insomnia in children with attention-deficit/hyperactivity disorder (ADHD). Method: Twenty-seven stimulant-treated children (6-14 years of age) with ADHD and initial insomnia (greater than 60 minutes) received sleep hygiene intervention. Nonresponders were…

  13. RNAi: antiviral therapy against dengue virus.

    Science.gov (United States)

    Idrees, Sobia; Ashfaq, Usman A

    2013-03-01

    Dengue virus infection has become a global threat affecting around 100 countries in the world. Currently, there is no licensed antiviral agent available against dengue. Thus, there is a strong need to develop therapeutic strategies that can tackle this life threatening disease. RNA interference is an important and effective gene silencing process which degrades targeted RNA by a sequence specific process. Several studies have been conducted during the last decade to evaluate the efficiency of siRNA in inhibiting dengue virus replication. This review summarizes siRNAs as a therapeutic approach against dengue virus serotypes and concludes that siRNAs against virus and host genes can be next generation treatment of dengue virus infection.

  14. Serum albumin level predicts initial intravenous immunoglobulin treatment failure in Kawasaki disease.

    Science.gov (United States)

    Kuo, Ho-Chang; Liang, Chi-Di; Wang, Chih-Lu; Yu, Hong-Ren; Hwang, Kao-Pin; Yang, Kuender D

    2010-10-01

    Kawasaki disease (KD) is a systemic vasculitis primarily affecting children who are initial IVIG treatment. This study was conducted to investigate the risk factors for initial IVIG treatment failure in KD. Children who met KD diagnosis criteria and were admitted for IVIG treatment were retrospectively enrolled for analysis. Patients were divided into IVIG-responsive and IVIG-resistant groups. Initial laboratory data before IVIG treatment were collected for analysis. A total of 131 patients were enrolled during the study period. At 48 h after completion of initial IVIG treatment, 20 patients (15.3%) had an elevated body temperature. Univariate analysis showed that patients who had initial findings of high neutrophil count, abnormal liver function, low serum albumin level (≤2.9 g/dL) and pericardial effusion were at risk for IVIG treatment failure. Multivariate analysis with a logistic regression procedure showed that serum albumin level was considered the independent predicting factor of IVIG resistance in patients with KD (p = 0.006, OR = 40, 95% CI: 52.8-562). There was no significant correlation between age, gender, fever duration before IVIG treatment, haemoglobin level, total leucocyte and platelet counts, C-reactive protein level, or sterile pyuria and initial IVIG treatment failure. The specificity and sensitivity for prediction of IVIG treatment failure in this study were 96% and 34%, respectively. Pre-IVIG treatment serum albumin levels are a useful predictor of IVIG resistance in patients with KD. © 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.

  15. A qualitative study of determinants of PTSD treatment initiation in veterans.

    Science.gov (United States)

    Sayer, Nina A; Friedemann-Sanchez, Greta; Spoont, Michele; Murdoch, Maureen; Parker, Louise E; Chiros, Christine; Rosenheck, Robert

    2009-01-01

    Although there are effective treatments for Posttraumatic Stress Disorder (PTSD), many PTSD sufferers wait years to decades before seeking professional help, if they seek it at all. An understanding of factors affecting treatment initiation for PTSD can inform strategies to promote help-seeking. We conducted a qualitative study to identify determinants of PTSD treatment initiation among 44 U.S. military veterans from the Vietnam and Afghanistan/Iraq wars; half were and half were not receiving treatment. Participants described barriers to and facilitators of treatment initiation within themselves, the post-trauma socio-cultural environment, the health care and disability systems, and their social networks. Lack of knowledge about PTSD was a barrier that occurred at both the societal and individual levels. Another important barrier theme was the enduring effect of experiencing an invalidating socio-cultural environment following trauma exposure. In some cases, system and social network facilitation led to treatment initiation despite individual-level barriers, such as beliefs and values that conflicted with help-seeking. Our findings expand the dominant model of service utilization by explicit incorporation of factors outside the individual into a conceptual framework of PTSD treatment initiation. Finally, we offer suggestions regarding the direction of future research and the development of interventions to promote timely help-seeking for PTSD.

  16. New Inhibitors of the DENV-NS5 RdRp from Carpolepis laurifolia as Potential Antiviral Drugs for Dengue Treatment

    Directory of Open Access Journals (Sweden)

    Paul Coulerie

    2014-05-01

    Full Text Available Since a few decades the dengue virus became a major public health concern and no treatment is available yet. In order to propose potential antidengue compounds for chemotherapy we focused on DENV RNA polymerase (DENV-NS5 RdRp which is specific and essential for the virus replication. Carpolepis laurifolia belongs to the Myrtaceae and is used as febrifuge in traditional kanak medicine. Leaf extract of this plant has been identified as a hit against the DENV-NS5 RdRp. Here we present a bioguided fractionation of the leaf extract of C. laurifolia which is also the first phytochemical evaluation of this plant. Five flavonoids, namely quercetin (1, 6-methyl-7-methoxyapigenin (2, avicularin (3, quercitrin (4 and hyperoside (5, together with betulinic acid (6, were isolated from the leaf extract of C. laurifolia. All isolated compounds were tested individually against the DENV-NS5 RdRp and compared with four other commercial flavonoids: isoquercitrin (7, spiraeoside (8, quercetin-3,4’-di-O-glucoside (9 and rutine (10. Compounds 3, 4, 6, 8 and 10 displayed IC 50 ranging from 1.7 to 2.1 µM, and were the most active against the DENV-NS5 RdRp.

  17. Frequency of Natural Resistance within NS5a Replication Complex Domain in Hepatitis C Genotypes 1a, 1b: Possible Implication of Subtype-Specific Resistance Selection in Multiple Direct Acting Antivirals Drugs Combination Treatment

    Directory of Open Access Journals (Sweden)

    Sabrina Bagaglio

    2016-03-01

    Full Text Available Different HCV subtypes may naturally harbor different resistance selection to anti-NS5a inhibitors. 2761 sequences retrieved from the Los Alamos HCV database were analyzed in the NS5a domain 1, the target of NS5a inhibitors. The NS5a resistance-associated polymorphisms (RAPs were more frequently detected in HCV G1b compared to G1a. The prevalence of polymorphisms associated with cross-resistance to compounds in clinical use (daclatasvir, DCV, ledipasvir, LDV, ombitasvir, and OMV or scheduled to come into clinical use in the near future (IDX719, elbasvir, and ELV was higher in G1b compared to G1a (37/1552 (2.4% in 1b sequences and 15/1209 (1.2% in 1a isolates, p = 0.040. Interestingly, on the basis of the genotype-specific resistance pattern, 95 (6.1% G1b sequences had L31M RAP to DCV/IDX719, while 6 sequences of G1a (0.5% harbored L31M RAP, conferring resistance to DCV/LDV/IDX719/ELV (p < 0.0001. Finally, 28 (2.3% G1a and none of G1b isolates harbored M28V RAP to OMV (p < 0.0001. In conclusion, the pattern of subtype-specific resistance selection in the naturally occurring strains may guide the treatment option in association with direct acting antivirals (DAAs targeting different regions, particularly in patients that are difficult to cure, such as those with advanced liver disease or individuals who have failed previous DAAs.

  18. Innate and intrinsic antiviral immunity in skin.

    Science.gov (United States)

    Kawamura, Tatsuyoshi; Ogawa, Youichi; Aoki, Rui; Shimada, Shinji

    2014-09-01

    As the body's most exposed interface with the environment, the skin is constantly challenged by potentially pathogenic microbes, including viruses. To sense the invading viruses, various types of cells resident in the skin express many different pattern-recognition receptors (PRRs) such as C-type lectin receptors (CLRs), Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs), retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and cytosolic DNA sensors, that can detect the pathogen-associated molecular patterns (PAMPs) of the viruses. The detection of viral PAMPs initiates two major innate immune signaling cascades: the first involves the activation of the downstream transcription factors, such as interferon regulatory factors (IRFs), nuclear factor kappa B (NF-κB) and activator protein 1 (AP-1), which cooperate to induce the transcription of type I interferons and pro-inflammatory cytokines. The second signaling pathway involves the caspase-1-mediated processing of IL-1β and IL-18 through the formation of an inflammasome complex. Cutaneous innate immunity including the production of the innate cytokines constitutes the first line of host defence that limits the virus dissemination from the skin, and also plays an important role in the activation of adaptive immune response, which represents the second line of defence. More recently, the third immunity "intrinsic immunity" has emerged, that provides an immediate and direct antiviral defense mediated by host intrinsic restriction factors. This review focuses on the recent advances regarding the antiviral immune systems, highlighting the innate and intrinsic immunity against the viral infections in the skin, and describes how viral components are recognized by cutaneous immune systems. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  19. Antiviral activity of exopolysaccharides from Arthrospira platensis against koi herpesvirus.

    Science.gov (United States)

    Reichert, M; Bergmann, S M; Hwang, J; Buchholz, R; Lindenberger, C

    2017-10-01

    Although koi herpesvirus (KHV) has a history of causing severe economic losses in common carp and koi farms, there are still no treatments available on the market. Thus, the aim of this study was to test exopolysaccharides (EPS) for its antiviral activity against KHV, by monitoring inhibition and cytotoxic effects in common carp brain cells. These substances can be easily extracted from extracellular algae supernatant and were identified as groups of sulphated polysaccharides. In order to reach this aim, Arthrospira platensis, which is well known for its antiviral activity of intra- and extracellular compounds towards mammalian herpesviruses, was investigated as standard organism and compared to commercial antiviral drug, ganciclovir, which inhibits the viral DNA polymerization. The antiviral activity of polysaccharides of A. platensis against KHV was confirmed in vitro using qualitative assessment of KHV life cycle genes, and it was found by RT-PCR that EPS, applied at a concentration of >18 μg mL -1 and a multiplicity of infection (MOI) of 0.45 of KHV, suppressed the viral replication in common carp brain (CCB) cells even after 22 days post-infection, entirely. Further, this study presents first data indicating an enormous potential using polysaccharides as an additive for aquacultures to lower or hinder the spread of the KHV and koi herpesvirus disease (KHVD) in future. © 2017 John Wiley & Sons Ltd.

  20. Antihypertensive medication classes used among medicare beneficiaries initiating treatment in 2007-2010.

    Science.gov (United States)

    Kent, Shia T; Shimbo, Daichi; Huang, Lei; Diaz, Keith M; Kilgore, Meredith L; Oparil, Suzanne; Muntner, Paul

    2014-01-01

    After the 2003 publication of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) guidelines, there was a 5-10% increase in patients initiating antihypertensive medication with a thiazide-type diuretic, but most patients still did not initiate treatment with this class. There are few contemporary published data on antihypertensive medication classes filled by patients initiating treatment. We used the 5% random Medicare sample to study the initiation of antihypertensive medication between 2007 and 2010. Initiation was defined by the first antihypertensive medication fill preceded by 365 days with no antihypertensive medication fills. We restricted our analysis to beneficiaries ≥ 65 years who had two or more outpatient visits with a hypertension diagnosis and full Medicare fee-for-service coverage for the 365 days prior to initiation of antihypertensive medication. Between 2007 and 2010, 32,142 beneficiaries in the 5% Medicare sample initiated antihypertensive medication. Initiation with a thiazide-type diuretic decreased from 19.2% in 2007 to 17.9% in 2010. No other changes in medication classes initiated occurred over this period. Among those initiating antihypertensive medication in 2010, 31.3% filled angiotensin-converting enzyme inhibitors (ACE-Is), 26.9% filled beta blockers, 17.2% filled calcium channel blockers, and 14.4% filled angiotensin receptor blockers (ARBs). Initiation with >1 antihypertensive medication class decreased from 25.6% in 2007 to 24.1% in 2010. Patients initiated >1 antihypertensive medication class most commonly with a thiazide-type diuretic and either an ACE-I or ARB. These results suggest that JNC 7 had a limited long-term impact on the choice of antihypertensive medication class and provide baseline data prior to the publication of the 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults from the Panel Members Appointed to

  1. Resistance Mechanisms in Hepatitis C Virus: implications for Direct-Acting Antiviral Use.

    Science.gov (United States)

    Bagaglio, Sabrina; Uberti-Foppa, Caterina; Morsica, Giulia

    2017-07-01

    Multiple direct-acting antiviral (DAA)-based regimens are currently approved that provide one or more interferon-free treatment options for hepatitis C virus (HCV) genotypes (G) 1-6. The choice of a DAA regimen, duration of therapy, and use of ribavirin depends on multiple viral and host factors, including HCV genotype, the detection of resistance-associated amino acid (aa) substitutions (RASs), prior treatment experience, and presence of cirrhosis. In regard to viral factors that may guide the treatment choice, the most important is the infecting genotype because a number of DAAs are genotype-designed. The potency and the genetic barrier may also impact the choice of treatment. One important and debated possible virologic factor that may negatively influence the response to DAAs is the presence of baseline RASs. Baseline resistance testing is currently not routinely considered or recommended for initiating HCV treatment, due to the overall high response rates (sustained virological response >90%) obtained. Exceptions are patients infected by HCV G1a when initiating treatment with simeprevir and elbasvir/grazoprevir or in those with cirrhosis prior to daclatasvir/sofosbuvir treatment because of natural polymorphisms demonstrated in sites of resistance. On the basis of these observations, first-line strategies should be optimized to overcome treatment failure due to HCV resistance.

  2. Low molecular weight heparin versus unfractionated heparin in the initial treatment of venous thromboembolism

    NARCIS (Netherlands)

    Hettiarachchi, R. J.; Prins, M. H.; Lensing, A. W.; Buller, H. R.

    1998-01-01

    In this review, we analyze data from randomized trials in which low molecular weight heparin was compared with unfractionated heparin, both to estimate the treatment effect of low molecular weight heparin in the initial treatment of venous thromboembolism and to evaluate the effect of the varied

  3. Pontine abscess with initial treatment failure following infectious endocarditis with Streptococcus salivarius

    DEFF Research Database (Denmark)

    Knudtzen, Fredrikke Christie; Lynge, Maja; Gaini, Shahin

    2015-01-01

    for Streptococcus salivarius aortic valve endocarditis. The abscess was not suitable for surgery, and the patient received multidrug antibiotic treatment for 4 weeks. The patient initially responded well clinically, but was readmitted 4 weeks after discontinuation of treatment, with headache and dizziness. A new...

  4. Factors associated with delays in treatment initiation after tuberculosis diagnosis in two districts of India.

    Directory of Open Access Journals (Sweden)

    Durba Paul

    Full Text Available BACKGROUND: Excessive time between diagnosis and initiation of tuberculosis (TB treatment contributes to ongoing TB transmission and should be minimized. In India, Revised National TB Control Programme (RNTCP focuses on indicator start of treatment within 7 days of diagnosis for patients with sputum smear-positive PTB for monitoring DOTS implementation. OBJECTIVES: To determine length of time between diagnosis and initiation of treatment and factors associated with delays of more than 7 days in smear-positive pulmonary TB. METHODS: Using existing programme records such as the TB Register, treatment cards, and the laboratory register, we conducted a retrospective cohort study of all patients with smear-positive pulmonary TB registered from July-September 2010 in two districts in India. A random sample of patients with pulmonary TB who experienced treatment delay of more than 7 days was interviewed using structured questionnaire. RESULTS: 2027 of 3411 patients registered with pulmonary TB were smear-positive. 711(35% patients had >7 days between diagnosis and treatment and 262(13% had delays >15 days. Mean duration between TB diagnosis and treatment initiation was 8 days (range = 0-128 days. Odds of treatment delay >7 days was 1.8 times more likely among those who had been previously treated (95% confidence interval [CI] 1.5-2.3 and 1.6 (95% CI 1.3-1.8 times more likely among those diagnosed in health facilities without microscopy centers. The main factors associated with a delay >7 days were: patient reluctance to start a re-treatment regimen, patients seeking second opinions, delay in transportation of drugs to the DOT centers and delay in initial home visits. To conclude, treatment delay >7 days was associated with a number of factors that included history of previous treatment and absence of TB diagnostic services in the local health facility. Decentralized diagnostic facilities and improved referral procedures may reduce such treatment

  5. Epimedium koreanum Nakai Displays Broad Spectrum of Antiviral Activity in Vitro and in Vivo by Inducing Cellular Antiviral State

    Directory of Open Access Journals (Sweden)

    Won-Kyung Cho

    2015-01-01

    Full Text Available Epimedium koreanum Nakai has been extensively used in traditional Korean and Chinese medicine to treat a variety of diseases. Despite the plant’s known immune modulatory potential and chemical make-up, scientific information on its antiviral properties and mode of action have not been completely investigated. In this study, the broad antiviral spectrum and mode of action of an aqueous extract from Epimedium koreanum Nakai was evaluated in vitro, and moreover, the protective effect against divergent influenza A subtypes was determined in BALB/c mice. An effective dose of Epimedium koreanum Nakai markedly reduced the replication of Influenza A Virus (PR8, Vesicular Stomatitis Virus (VSV, Herpes Simplex Virus (HSV and Newcastle Disease Virus (NDV in RAW264.7 and HEK293T cells. Mechanically, we found that an aqueous extract from Epimedium koreanum Nakai induced the secretion of type I IFN and pro-inflammatory cytokines and the subsequent stimulation of the antiviral state in cells. Among various components present in the extract, quercetin was confirmed to have striking antiviral properties. The oral administration of Epimedium koreanum Nakai exhibited preventive effects on BALB/c mice against lethal doses of highly pathogenic influenza A subtypes (H1N1, H5N2, H7N3 and H9N2. Therefore, an extract of Epimedium koreanum Nakai and its components play roles as immunomodulators in the innate immune response, and may be potential candidates for prophylactic or therapeutic treatments against diverse viruses in animal and humans.

  6. Criminal charges prior to and after initiation of office-based buprenorphine treatment

    Directory of Open Access Journals (Sweden)

    Harris Elizabeth E

    2012-03-01

    Full Text Available Abstract Background There is little data on the impact of office-based buprenorphine therapy on criminal activity. The goal of this study was to determine the impact of primary care clinic-based buprenorphine maintenance therapy on rates of criminal charges and the factors associated with criminal charges in the 2 years after initiation of treatment. Methods We collected demographic and outcome data on 252 patients who were given at least one prescription for buprenorphine. We searched a public database of criminal charges and recorded criminal charges prior to and after enrollment. We compared the total number of criminal cases and drug cases 2 years before versus 2 years after initiation of treatment. Results There was at least one criminal charge made against 38% of the subjects in the 2 years after initiation of treatment; these subjects were more likely to have used heroin, to have injected drugs, to have had any prior criminal charges, and recent criminal charges. There was no significant difference in the number of subjects with any criminal charge or a drug charge before and after initiation of treatment. Likewise, the mean number of all cases and drug cases was not significantly different between the two periods. However, among those who were opioid-negative for 6 or more months in the first year of treatment, there was a significant decline in criminal cases. On multivariable analysis, having recent criminal charges was significantly associated with criminal charges after initiation of treatment (adjusted odds ratio 3.92; subjects who were on opioid maintenance treatment prior to enrollment were significantly less likely to have subsequent criminal charges (adjusted odds ratio 0.52. Conclusions Among subjects with prior criminal charges, initiation of office-based buprenorphine treatment did not appear to have a significant impact on subsequent criminal charges.

  7. What You Should Know about Flu Antiviral Drugs

    Science.gov (United States)

    ... Other What You Should Know About Flu Antiviral Drugs Language: English (US) Español Recommend on Facebook Tweet ... used to treat flu illness. What are antiviral drugs? Antiviral drugs are prescription medicines (pills, liquid, an ...

  8. Operational challenges in diagnosing multi-drug resistant TB and initiating treatment in Andhra Pradesh, India.

    Directory of Open Access Journals (Sweden)

    Sarabjit S Chadha

    Full Text Available BACKGROUND: Revised National TB Control Programme (RNTCP, Andhra Pradesh, India. There is limited information on whether MDR-TB suspects are identified, undergo diagnostic assessment and are initiated on treatment according to the programme guidelines. OBJECTIVES: To assess i using the programme definition, the number and proportion of MDR-TB suspects in a large cohort of TB patients on first-line treatment under RNTCP ii the proportion of these MDR-TB suspects who underwent diagnosis for MDR-TB and iii the number and proportion of those diagnosed as MDR-TB who were successfully initiated on treatment. METHODS: A retrospective cohort analysis, by reviewing RNTCP records and reports, was conducted in four districts of Andhra Pradesh, India, among patients registered for first line treatment during October 2008 to December 2009. RESULTS: Among 23,999 TB patients registered for treatment there were 559 (2% MDR-TB suspects (according to programme definition of which 307 (55% underwent diagnosis and amongst these 169 (55% were found to be MDR-TB. Of the MDR-TB patients, 112 (66% were successfully initiated on treatment. Amongst those eligible for MDR-TB services, significant proportions are lost during the diagnostic and treatment initiation pathway due to a variety of operational challenges. The programme needs to urgently address these challenges for effective delivery and utilisation of the MDR-TB services.

  9. New pathogenic viruses and novel antiviral drugs

    NARCIS (Netherlands)

    Berkhout, Ben; Eggink, Dirk

    2011-01-01

    The journal Antiviral Research was conceived and born in 1980, and launched in 1981, a time when very few antiviral drugs were around. This 30-year celebration meeting was convened by the publisher Elsevier and chaired by Eric de Clercq (Leuven University), who has acted as editor-in-chief for the

  10. Improving Substance Abuse Treatment: The National Treatment Plan Initiative. Changing the Conversation.

    Science.gov (United States)

    Substance Abuse and Mental Health Services Administration (DHHS/PHS), Rockville, MD. Center for Substance Abuse Treatment.

    This report is the result of five expert panels and six regional public hearings around the country that focused on key persistent issues that have characterized discussions of substance abuse over the years: closing the treatment gap; reducing stigma and changing attitudes; improving and strengthening treatment systems; connecting services and…

  11. Teachers' Knowledge of ADHD, Treatments for ADHD, and Treatment Acceptability: An Initial Investigation. Research Brief

    Science.gov (United States)

    Vereb, Rebecca L.; DiPerna, James C.

    2004-01-01

    The purpose of this study was to begin to explore the relationship among teachers' knowledge of Attention Deficit Hyperactivity Disorder (ADHD), knowledge of common treatments for ADHD, and acceptability of different approaches to treatment for ADHD (medication and behavior management). Relationships also were explored between these variables and…

  12. Impact of combination antiretroviral therapy initiation on adherence to antituberculosis treatment

    Directory of Open Access Journals (Sweden)

    Marlene Knight

    2015-10-01

    Full Text Available Background: Healthcare workers are often reluctant to start combination antiretroviral therapy (ART in patients receiving tuberculosis (TB treatment because of the fear of high pill burden, immune reconstitution inflammatory syndrome, and side-effects. Object: To quantify changes in adherence to tuberculosis treatment following ART initiation. Design: A prospective observational cohort study of ART-naïve individuals with baseline CD4 count between 50 cells/mm3 and 350 cells/mm3 at start of TB treatment at a primary care clinic in Johannesburg, South Africa. Adherence to TB treatment was measured by pill count,self-report, and electronic Medication Event Monitoring System (eMEMS before and after initiation of ART. Results: ART tended to negatively affect adherence to TB treatment, with an 8% – 10% decrease in the proportion of patients adherent according to pill count and an 18% – 22% decrease in the proportion of patients adherent according to eMEMS in the first month following ART initiation, independent of the cut-off used to define adherence (90%, 95% or 100%. Reasons for non-adherence were multi factorial, and employment was the only predictor for optimal adherence (adjusted odds ratio 4.11, 95% confidence interval 1.06–16.0. Conclusion: Adherence support in the period immediately following ART initiation could optimise treatment outcomes for people living with TB and HIV.

  13. Associations between timing of corticosteroid treatment initiation and clinical outcomes in Duchenne muscular dystrophy.

    Science.gov (United States)

    Kim, Sunkyung; Zhu, Yong; Romitti, Paul A; Fox, Deborah J; Sheehan, Daniel W; Valdez, Rodolfo; Matthews, Dennis; Barber, Brent J

    2017-08-01

    The long-term efficacy of corticosteroid treatment and timing of treatment initiation among Duchenne muscular dystrophy (DMD) patients is not well-understood. We used data from a longitudinal, population-based DMD surveillance program to examine associations between timing of treatment initiation (early childhood [before or at age 5 years], late childhood [after age 5 years], and naïve [not treated]) and five clinical outcomes (age at loss of ambulation; ages at onset of cardiomyopathy, scoliosis, and first fracture; and pulmonary function). Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using survival analysis. DMD patients who initiated corticosteroid treatment in early childhood had a higher risk of earlier onset cardiomyopathy compared to cases who initiated treatment in late childhood (HR = 2.0, 95% CI = [1.2, 3.4]) or treatment naïve patients (HR = 1.9, 95% CI = [1.1, 3.2]), and higher risk of suffering a fracture (HR = 2.3, 95% CI = [1.4, 3.7] and HR = 2.6, 95% CI = [1.6, 4.2], respectively). Patients with early childhood treatment had slightly decreased respiratory function compared with those with late childhood treatment. Ages at loss of ambulation or scoliosis diagnosis did not differ statistically among treatment groups. We caution that the results from our study are subject to several limitations, as they were based on data abstracted from medical records. Further investigations using improved reporting of disease onset and outcomes are warranted to obtain a more definitive assessment of the association between the timing of corticosteroid treatment and disease severity. Published by Elsevier B.V.

  14. First Contact: the intersection of demographics, knowledge, and appraisal of treatment at the initial infertility visit

    Science.gov (United States)

    CHILDRESS, Krista J.; LAWSON, Angela K.; GHANT, Marissa S.; MENDOZA, Gricelda; CARDOZO, Eden R.; CONFINO, Edmond; MARSH, Erica E.

    2015-01-01

    Objective To determine the impact of the initial infertility visit on treatment-related knowledge, patient anxiety, and appraisals of treatment. Study Design Prospective survey. Setting Academic medical center. Patients 234 English-speaking women, ages 18-50, attending their first infertility visit Intervention(s) Participants completed a survey assessing health literacy, knowledge, anxiety, and appraisals of the treatment process before and after their infertility visit. Main Outcome Measure(s) 1) Knowledge of infertility and treatment and, 2) Anxiety and appraisal scores. Results Most participants were white and earned >$100,000/year and had at least a college education. Baseline knowledge of reproductive anatomy, ART, and fertility factors was modest, but improved after the initial visit. Factors associated with higher knowledge included higher education and income, White or Asian ethnicity, and English as their primary language. Patient appraisals of treatment represented by the positive (Challenge) and negative (Threat and Loss) subscale scores on the Appraisal of Life Events (ALE) scale, changed from the pre-visit survey to the post-visit survey. Negative appraisals of treatment and anxiety scores decreased and positive appraisals of treatment increased after the initial visit. Lower knowledge was associated with higher positive appraisal scores lower health literacy was associated with higher anxiety and appraisal scores (positive and negative) post-visit. Black women had higher Challenge scores compared to White and Asian women. Hispanic women had higher anxiety scores than non-Hispanic women. Conclusions Infertility patients have modest baseline knowledge of fertility and infertility treatment. The initial infertility visit can improve this knowledge and decrease both negative appraisals of treatment and anxiety levels. Differences in knowledge and appraisal were seen across ethnic groups and other demographic variables. Physicians should individualize

  15. Acute kidney injury aggravated by treatment initiation with apixaban: Another twist of anticoagulant-related nephropathy

    Directory of Open Access Journals (Sweden)

    Sergey V. Brodsky

    2017-12-01

    Full Text Available Anticoagulant-related nephropathy (ARN was initially described in patients on warfarin (as warfarin-related nephropathy and recently in those using dabigatran. Herein, we report clinical history and kidney biopsy findings in a patient on apixaban (Eliquis. Initiation of treatment with apixaban resulted in aggravation of preexisting mild acute kidney injury (AKI. A few days after apixaban therapy, the patient became oligoanuric, and kidney biopsy showed severe acute tubular necrosis with numerous occlusive red blood cell casts. Only one out of 68 glomeruli with open capillary loops had small segmental cellular crescent. Therefore, there was major discrepancy between the degree of glomerular injury and the glomerular hematuria. Considering that the onset of this AKI was associated with apixaban treatment initiation, we propose that this patient had ARN associated with factor Xa inhibitor (apixaban, which has not previously been described. Monitoring of kidney function is recommended after initiation of anticoagulant therapy.

  16. Antiviral activity of an N-allyl acridone against dengue virus

    OpenAIRE

    Mazzucco, María Belén; Talarico, Laura Beatriz; Vatansever, Sezen; Carro, Ana Clara; Fascio, Mirta Liliana; D'Accorso, Norma Beatriz; Garcia, Cybele; Damonte, Elsa Beatriz

    2016-01-01

    Dengue virus (DENV), a member of the family Flaviviridae, is at present the most widespread causative agent of a human viral disease transmitted by mosquitoes. Despite the increasing incidence of this pathogen, there are no antiviral drugs or vaccines currently available for treatment or prevention. In a previous screening assay, we identified a group of N-allyl acridones as effective virus inhibitors. Here, the antiviral activity and mode of action targeted to viral RNA replication of one of...

  17. A randomized controlled trial of prison-initiated buprenorphine: prison outcomes and community treatment entry.

    Science.gov (United States)

    Gordon, Michael S; Kinlock, Timothy W; Schwartz, Robert P; Fitzgerald, Terrence T; O'Grady, Kevin E; Vocci, Frank J

    2014-09-01

    Buprenorphine is a promising treatment for heroin addiction. However, little is known regarding its provision to pre-release prisoners with heroin dependence histories who were not opioid-tolerant, the relative effectiveness of the post-release setting in which it is provided, and gender differences in treatment outcome in this population. This is the first randomized clinical trial of prison-initiated buprenorphine provided to male and female inmates in the US who were previously heroin-dependent prior to incarceration. A total of 211 participants with 3-9 months remaining in prison were randomized to one of four conditions formed by crossing In-Prison Treatment Condition (received buprenorphine vs. counseling only) and Post-release Service Setting (at an opioid treatment center vs. a community health center). Outcome measures were: entered prison treatment; completed prison treatment; and entered community treatment 10 days post-release. There was a significant main effect (p=.006) for entering prison treatment favoring the In-Prison buprenorphine Treatment Condition (99.0% vs. 80.4%). Regarding completing prison treatment, the only significant effect was Gender, with women significantly (pPrison buprenorphine Treatment Condition (47.5% vs. 33.7%). Buprenorphine appears feasible and acceptable to prisoners who were not opioid-tolerant and can facilitate community treatment entry. However, concerns remain with in-prison treatment termination due to attempted diversion of medication. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  18. Treatment patterns and clinical characteristics prior to initiating depot typical antipsychotics for nonadherent schizophrenia patients

    Directory of Open Access Journals (Sweden)

    Montgomery William

    2009-07-01

    Full Text Available Abstract Background Nonadherence with antipsychotic medication is an important clinical and economic problem in the treatment of schizophrenia. This study identified treatment patterns and clinical characteristics that immediately precede the initiation of depot typical antipsychotics in the usual treatment of schizophrenia patients with a recent history of nonadherence with oral antipsychotic regimens. Methods Data were drawn from a large, multisite, 3-year prospective noninterventional observational study of persons treated for schizophrenia in the United States, which was conducted between 7/1997 and 9/2003. The analytical sample included patients who, in the 6 months prior to enrollment, were considered nonadherent with oral antipsychotics and were not treated with depot antipsychotics (N = 314. Patients who were subsequently initiated on typical depots during the 3-year follow-up were compared with patients who continued therapy with only oral antipsychotic agents. Group comparisons were made on patient baseline characteristics and precedent variables that were assessed 1 to 6 months prior to depot initiation. Patient assessments were made at predetermined intervals throughout the 3-year study using standard psychiatric measures, a patient-reported questionnaire, and medical record information. Results A small proportion of patients (12.4% who were recently nonadherent with oral antipsychotics were subsequently initiated on depot therapy during the 3-year study. Compared to patients treated with only oral antipsychotics, those subsequently initiated on a depot were significantly more likely to be hospitalized at depot initiation or the previous 30 days, to have recent involvement with the criminal justice system (arrests, recent illicit drug use, recent switching or augmentation of oral antipsychotics, and recent treatment with oral typical antipsychotics. Conclusion Despite prior nonadherence with oral antipsychotic medication, only a

  19. Incidence and associated factors to adverse reactions of the initial antiretroviral treatment in patients with HIV

    OpenAIRE

    Astuvilca, Juan; Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú. Sociedad Científica de San Fernando. Lima, Perú. Estudiantes de medicina.; Arce-Villavicencio, Yanet; Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú. Sociedad Científica de San Fernando. Lima, Perú. Estudiantes de medicina.; Sotelo, Raúl; Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú. Sociedad Científica de San Fernando. Lima, Perú. Estudiantes de medicina.; Quispe, José; Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú. Sociedad Científica de San Fernando. Lima, Perú. Estudiantes de medicina.; Guillén, Regina; Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú. Estudiantes de medicina.; Peralta, Lillian; Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú. Estudiantes de medicina.; Huaringa, Jorge; Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima, Perú. Estudiantes de medicina.; Gutiérrez, César; Departamento Académico de Medicina Preventiva y Salud Pública, Facultad de Medicina, Universidad Nacional Mayor de San Marcos. Lima-Perú. Médico epidemiólogo.

    2007-01-01

    The high incidence of adverse reactions to the high activity antiretroviral treatment (HAART) in patients with HIV/AIDS, can affect their quality of life and adherence to the treatment. Objectives: To determinate the incidence of adverse reactions to the initial HAART and to identify the factors associated to the occurrence of adverse reactions when receiving this therapy. Material and methods: Historic cohort study. The population was conformed by all the HIV-infected adult patients (≥18...

  20. Cardiac Complications, Earlier Treatment, and Initial Disease Severity in Kawasaki Disease.

    Science.gov (United States)

    Abrams, Joseph Y; Belay, Ermias D; Uehara, Ritei; Maddox, Ryan A; Schonberger, Lawrence B; Nakamura, Yosikazu

    2017-09-01

    To assess if observed higher observed risks of cardiac complications for patients with Kawasaki disease (KD) treated earlier may reflect bias due to confounding from initial disease severity, as opposed to any negative effect of earlier treatment. We used data from Japanese nationwide KD surveys from 1997 to 2004. Receipt of additional intravenous immunoglobulin (IVIG) (data available all years) or any additional treatment (available for 2003-2004) were assessed as proxies for initial disease severity. We determined associations between earlier or later IVIG treatment (defined as receipt of IVIG on days 1-4 vs days 5-10 of illness) and cardiac complications by stratifying by receipt of additional treatment or by using logistic modeling to control for the effect of receiving additional treatment. A total of 48 310 patients with KD were included in the analysis. In unadjusted analysis, earlier IVIG treatment was associated with a higher risk for 4 categories of cardiac complications, including all major cardiac complications (risk ratio, 1.10; 95% CI, 1.06-1.15). Stratifying by receipt of additional treatment removed this association, and earlier IVIG treatment became protective against all major cardiac complications when controlling for any additional treatment in logistic regressions (OR, 0.90; 95% CI, 0.80-1.00). Observed higher risks of cardiac complications among patients with KD receiving IVIG treatment on days 1-4 of the illness are most likely due to underlying higher initial disease severity, and patients with KD should continue to be treated with IVIG as early as possible. Published by Elsevier Inc.

  1. Reasons for entering treatment reported by initially treatment-resistant patients with substance use disorders

    NARCIS (Netherlands)

    Meyers, Robert J.; Roozen, Hendrik G.; Smith, Jane Ellen; Evans, Brittany E.

    2014-01-01

    Many individuals with substance use disorders are resistant to entering formal treatment, despite the negative consequences that plague their own lives and the lives of concerned significant others (CSOs). Community Reinforcement and Family Training (CRAFT) has been developed as an effective

  2. Safety of BTZ retreatment for patients with low-grade peripheral neuropathy during the initial treatment.

    Science.gov (United States)

    Vidisheva, Aleksandra P; Wang, James; Spektor, Tanya M; Bitran, Jacob D; Lutzky, Jose; Tabbara, Imad A; Ye, Joseph Z; Ailawadhi, Sikander; Stampleman, Laura V; Steis, Ronald G; Moezi, Mehdi M; Swift, Regina A; Maluso, Tina M; Udd, Kyle A; Eshaghian, Shahrooz; Nassir, Youram; Berenson, James R

    2017-10-01

    Neuropathy is an important complication that may limit treatment options for patients with multiple myeloma. Previous studies have focused on treatment efficacy and have shown that retreatment with bortezomib (BTZ) is an effective treatment option. The goal of this study was to focus on the clinical manifestations of peripheral neuropathy (PN) and to retrospectively compare the incidence and severity of PN between the initial BTZ regimen and upon retreatment. Furthermore, this study evaluated how certain factors affect BIPN, which will help determine what conditions should be considered prior to retreatment. Charts were reviewed from 93 patients who were retreated with a BTZ-containing regimen after previously being treated with this drug. Among the patients who developed PN, most patients in the study had low-grade neuropathy during the initial BTZ treatment (n = 52, 68%). The results showed no evidence of cumulative toxicity, and there was no significant difference in the incidence and severity of PN upon retreatment. Factors such as the presence of baseline PN, number of prior treatments, dose of BTZ, and comorbidities did not increase the severity of PN upon retreatment. The lapse of time between the two regimens also did not affect the severity of PN. The results suggest that retreatment with BTZ may be a feasible option, without additional risks of PN, for MM patients even with peripheral neuropathy during their initial treatment with this drug.

  3. Antihypertensive medication classes used among medicare beneficiaries initiating treatment in 2007-2010.

    Directory of Open Access Journals (Sweden)

    Shia T Kent

    Full Text Available After the 2003 publication of the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7 guidelines, there was a 5-10% increase in patients initiating antihypertensive medication with a thiazide-type diuretic, but most patients still did not initiate treatment with this class. There are few contemporary published data on antihypertensive medication classes filled by patients initiating treatment.We used the 5% random Medicare sample to study the initiation of antihypertensive medication between 2007 and 2010. Initiation was defined by the first antihypertensive medication fill preceded by 365 days with no antihypertensive medication fills. We restricted our analysis to beneficiaries ≥ 65 years who had two or more outpatient visits with a hypertension diagnosis and full Medicare fee-for-service coverage for the 365 days prior to initiation of antihypertensive medication. Between 2007 and 2010, 32,142 beneficiaries in the 5% Medicare sample initiated antihypertensive medication. Initiation with a thiazide-type diuretic decreased from 19.2% in 2007 to 17.9% in 2010. No other changes in medication classes initiated occurred over this period. Among those initiating antihypertensive medication in 2010, 31.3% filled angiotensin-converting enzyme inhibitors (ACE-Is, 26.9% filled beta blockers, 17.2% filled calcium channel blockers, and 14.4% filled angiotensin receptor blockers (ARBs. Initiation with >1 antihypertensive medication class decreased from 25.6% in 2007 to 24.1% in 2010. Patients initiated >1 antihypertensive medication class most commonly with a thiazide-type diuretic and either an ACE-I or ARB.These results suggest that JNC 7 had a limited long-term impact on the choice of antihypertensive medication class and provide baseline data prior to the publication of the 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults from the Panel

  4. Revisión sistemática de evaluaciones económicas de fármacos antivirales para el tratamiento de la hepatitis B crónica Economic evaluation of antiviral treatment for chronic hepatitis B: a systematic review

    Directory of Open Access Journals (Sweden)

    Lely Solari

    2010-03-01

    Full Text Available Objetivo. Revisar la evidencia disponible acerca de la costo-efectividad de los regímenes antivirales en el tratamiento de la hepatitis B crónica. Material y Métodos. Se realizó una revisión sistemática de las bases de datos de MEDLINE, LILACS, NICE guidelines y COCHRANE sobre evaluaciones económicas de regímenes antivirales para el tratamiento de hepatitis B crónica. Se incluyó los estudios originales, revisiones sistemáticas y guías de manejo conteniendo información acerca de la costo-efectividad de dicho tratamiento. Se registró las características y resultados de los documentos obtenidos. Resultados. Se obtuvo 29 artículos originales, cuatro artículos de revisión y cuatro guías de manejo clínico. La mayoría de las publicaciones fueron hechas en los cinco últimos años. Los autores tenían conflicto de interés, por trabajar en la industria farmacéutica, en 73% de los artículos originales. El 93% de los artículos que evalúan costo-efectividad de brindar tratamiento para hepatitis B crónica frente a manejo de complicaciones, encuentran que es costo-efectivo el tratamiento antiviral; 3/6 estudios que evalúan lamivudina frente a otros esquemas la encuentran como estrategia dominante, 3/5 encuentran a entecavir como estrategia dominante, 1/1 a tenofovir como dominante, 1/4 a interferón convencional como dominante y ninguno encuentra a adefovir ni interferón pegilado como estrategia dominante. Conclusiones. Consideramos que la evidencia disponible sugiere que brindar tratamiento antiviral para hepatitis B crónica sea una intervención costo-efectiva para muchos sistemas de salud, incluyendo el nuestro, con índices variables de costo-efectividad de acuerdo con los esquemas evaluados. Idealmente, se debe realizar evaluaciones económicas locales en este aspecto.Objective. To revise the available evidence on the cost-effectiveness of antiviral regimens for treatment of chronic hepatitis B. Material and methods. We

  5. Treatment initiation in paediatric pulmonary hypertension: insights from a multinational registry.

    Science.gov (United States)

    Humpl, Tilman; Berger, Rolf M F; Austin, Eric D; Fasnacht Boillat, Margrit S; Bonnet, Damien; Ivy, Dunbar D; Zuk, Malgorzata; Beghetti, Maurice; Schulze-Neick, Ingram

    2017-08-01

    Different treatment options for pulmonary hypertension have emerged in recent years, and evidence-based management strategies have improved quality of life and survival in adults. In children with pulmonary vascular disease, therapeutic algorithms are not so clearly defined; this study determined current treatment initiation in children with pulmonary hypertension in participating centres of a registry. Through the multinational Tracking Outcomes and Practice in Pediatric Pulmonary Hypertension registry, patient demographics, diagnosis, and treatment as judged and executed by the local physician were collected. Inclusion criteria were >3 months and pulmonary hypertension (mean pulmonary arterial pressure ⩾25 mmHg, pulmonary vascular resistance index ⩾3 Wood units×m2, and mean pulmonary capillary wedge pressure ⩽12 mmHg). At diagnostic catheterisation, 217/244 patients (88.9%) were treatment naïve for pulmonary hypertension-targeted therapy. Targeted therapy was initiated after catheterisation in 170 (78.3%) treatment-naïve patients. A total of 19 patients received supportive therapy, 28 patients were not started on therapy, and 26 patients (10.7%) were on targeted treatment before catheterisation. Among treatment-naïve subjects, treatment was initiated with one targeted drug (n=112, 51.6%), dual therapy (n=39, 18%) or triple-therapy (n=5, 2.3%), and calcium channel blockers with one targeted medication in one patient (0.5%). Phosphodiesterase inhibitors type 5 were used frequently; some patients with pulmonary hypertension related to lung disease received targeted therapy. There is a diverse therapeutic approach for children with pulmonary hypertension with a need of better-defined treatment algorithms based on paediatric consensus for different aetiologies including the best possible diagnostic workup.

  6. "Salvage microbiology": detection of bacteria directly from clinical specimens following initiation of antimicrobial treatment.

    Directory of Open Access Journals (Sweden)

    John J Farrell

    Full Text Available PCR coupled with electrospray ionization mass spectrometry (ESI-MS is a diagnostic approach that has demonstrated the capacity to detect pathogenic organisms from culture negative clinical samples after antibiotic treatment has been initiated. [1] We describe the application of PCR/ESI-MS for detection of bacteria in original patient specimens that were obtained after administration of antibiotic treatment in an open investigation analysis.We prospectively identified cases of suspected bacterial infection in which cultures were not obtained until after the initiation of antimicrobial treatment. PCR/ESI-MS was performed on 76 clinical specimens that were submitted for conventional microbiology testing from 47 patients receiving antimicrobial treatment.In our series, 72% (55/76 of cultures obtained following initiation of antimicrobial treatment were non-diagnostic (45 negative cultures; and 10 respiratory specimens with normal flora (5, yeast (4, or coagulase-negative staphylococcus (1. PCR/ESR-MS detected organisms in 83% (39/47 of cases and 76% (58/76 of the specimens. Bacterial pathogens were detected by PCR/ESI-MS in 60% (27/45 of the specimens in which cultures were negative. Notably, in two cases of relapse of prosthetic knee infections in patients on chronic suppressive antibiotics, the previous organism was not recovered in tissue cultures taken during extraction of the infected knee prostheses, but was detected by PCR/ESI-MS.Molecular methods that rely on nucleic acid amplification may offer a unique advantage in the detection of pathogens collected after initiation of antimicrobial treatment and may provide an opportunity to target antimicrobial therapy and "salvage" both individual treatment regimens as well as, in select cases, institutional antimicrobial stewardship efforts.

  7. Nitrogen implantation of steels: A treatment which can initiate sustained oxidative wear

    International Nuclear Information System (INIS)

    Hale, E.B.; Reinbold, R.; Missouri Univ., Rolla; Kohser, R.A.

    1987-01-01

    Falex wear tests on mild (SAE 3135) steel samples treated by either nitrogen implantation (2.5x10 17 N 2 + cm -2 at 180 keV) or low temperature (about 315 0 C) oxidation are reported. The results show that both treatments lead to about an order-of-magnitude reduction in the long-term wear rate of the steel. In addition to the wear rate measurements, the wear member asymmetry behavior, scanning electron microscopy studies, Auger spectra and sputter profiles all indicate that the wear modes induced by both treatments are the same and are oxidative wear. These results confirm the previously proposed initiator-sustainer wear model in which implanted nitrogen simply acts as an initiator of favorable oxidative wear but is not directly involved in maintaining the sustained wear resistance. Possible mechanisms for both the initiation process and the sustained wear process are reviewed and discussed. (orig.)

  8. Novel drugs targeting Toll-like receptors for antiviral therapy.

    Science.gov (United States)

    Patel, Mira C; Shirey, Kari Ann; Pletneva, Lioubov M; Boukhvalova, Marina S; Garzino-Demo, Alfredo; Vogel, Stefanie N; Blanco, Jorge Cg

    2014-09-01

    Toll-like receptors (TLRs) are sentinel receptors of the host innate immune system that recognize conserved 'pathogen-associated molecular patterns' of invading microbes, including viruses. The activation of TLRs establishes antiviral innate immune responses and coordinates the development of long-lasting adaptive immunity in order to control viral pathogenesis. However, microbe-induced damage to host tissues may release 'danger-associated molecular patterns' that also activate TLRs, leading to an overexuberant inflammatory response and, ultimately, to tissue damage. Thus, TLRs have proven to be promising targets as therapeutics for the treatment of viral infections that result in inflammatory damage or as adjuvants in order to enhance the efficacy of vaccines. Here, we explore recent advances in TLR biology with a focus on novel drugs that target TLRs (agonists and antagonists) for antiviral therapy.

  9. Using the ferret as an animal model for investigating influenza antiviral effectiveness

    Directory of Open Access Journals (Sweden)

    Ding Yuan Oh

    2016-02-01

    Full Text Available The concern of the emergence of a pandemic influenza virus has sparked an increased effort towards the development and testing of novel influenza antivirals. Central to this is the animal model of influenza infection, which has played an important role in understanding treatment effectiveness and the effect of antivirals on host immune responses. Among the different animal models of influenza, ferrets can be considered the most suitable for antiviral studies as they display most of the human-like symptoms following influenza infections, they can be infected with human influenza virus without prior viral adaptation and have the ability to transmit influenza virus efficiently between one another. However, an accurate assessment of the effectiveness of an antiviral treatment in ferrets is dependent on three major experimental considerations encompassing firstly, the volume and titre of virus, and the route of viral inoculation. Secondly, the route and dose of drug administration, and lastly, the different methods used to assess clinical symptoms, viral shedding kinetics and host immune responses in the ferrets. A good understanding of these areas is necessary to achieve data that can accurately inform the human use of influenza antivirals. In this review, we discuss the current progress and the challenges faced in these three major areas when using the ferret model to measure influenza antiviral effectiveness.

  10. Translational control in plant antiviral immunity

    Directory of Open Access Journals (Sweden)

    João Paulo B. Machado

    Full Text Available Abstract Due to the limited coding capacity of viral genomes, plant viruses depend extensively on the host cell machinery to support the viral life cycle and, thereby, interact with a large number of host proteins during infection. Within this context, as plant viruses do not harbor translation-required components, they have developed several strategies to subvert the host protein synthesis machinery to produce rapidly and efficiently the viral proteins. As a countermeasure against infection, plants have evolved defense mechanisms that impair viral infections. Among them, the host-mediated translational suppression has been characterized as an efficient mean to restrict infection. To specifically suppress translation of viral mRNAs, plants can deploy susceptible recessive resistance genes, which encode translation initiation factors from the eIF4E and eIF4G family and are required for viral mRNA translation and multiplication. Additionally, recent evidence has demonstrated that, alternatively to the cleavage of viral RNA targets, host cells can suppress viral protein translation to silence viral RNA. Finally, a novel strategy of plant antiviral defense based on suppression of host global translation, which is mediated by the transmembrane immune receptor NIK1 (nuclear shuttle protein (NSP-Interacting Kinase1, is discussed in this review.

  11. Antiviral and Inflammatory Cellular Signaling Associated with Enterovirus 71 Infection

    Directory of Open Access Journals (Sweden)

    Yuefei Jin

    2018-03-01

    Full Text Available Enterovirus 71 (EV71 infection has become a major threat to global public health, especially in infants and young children. Epidemiological studies have indicated that EV71 infection is responsible for severe and even fatal cases of hand, foot, and mouth disease (HFMD. Accumulated evidence indicates that EV71 infection triggers a plethora of interactive signaling pathways, resulting in host immune evasion and inflammatory response. This review mainly covers the effects of EV71 infection on major antiviral and inflammatory cellular signal pathways. EV71 can activate cellular signaling networks including multiple cell surface and intracellular receptors, intracellular kinases, calcium flux, and transcription factors that regulate antiviral innate immunity and inflammatory response. Cellular signaling plays a critical role in the regulation of host innate immune and inflammatory pathogenesis. Elucidation of antiviral and inflammatory cellular signaling pathways initiated by EV71 will not only help uncover the potential mechanisms of EV71 infection-induced pathogenesis, but will also provide clues for the design of therapeutic strategies against EV71 infection.

  12. Quality of life among HIV-infected patients in Brazil after initiation of treatment

    Directory of Open Access Journals (Sweden)

    Lorenza Nogueira Campos

    2009-01-01

    Full Text Available INTRODUCTION: Despite improvement in clinical treatment for HIV-infected patients, the impact of antiretroviral therapy on the overall quality of life has become a major concern. OBJECTIVE: To identify factors associated with increased levels of self-reported quality of life among HIV-infected patients after four months of antiretroviral therapy. METHODS: Patients were recruited at two public health referral centers for AIDS, Belo Horizonte, Brazil, for a prospective adherence study. Patients were interviewed before initiating treatment (baseline and after one and four months. Quality of life was assessed using a psychometric instrument, and factors associated with good/very good quality of life four months after the initiation of antiretroviral therapy were assessed using a cross-sectional approach. Logistic regression was used for analysis. RESULTS: Overall quality of life was classified as 'very good/good' by 66.4% of the participants four months after initiating treatment, while 33.6% classified it as 'neither poor nor good/poor/very poor'. Logistic regression indicated that >8 years of education, none/mild symptoms of anxiety and depression, no antiretroviral switch, lower number of adverse reactions and better quality of life at baseline were independently associated with good/very good quality of life over four months of treatment. CONCLUSIONS: Our results highlight the importance of modifiable factors such as psychiatric symptoms and treatment-related variables that may contribute to a better quality of life among patients initiating treatment. Considering that poor quality of life is related to non-adherence to antiretroviral therapy, careful clinical monitoring of these factors may contribute to ensuring the long-term effectiveness of antiretroviral regimens.

  13. Viruses and Antiviral Immunity in Drosophila

    Science.gov (United States)

    Xu, Jie; Cherry, Sara

    2013-01-01

    Viral pathogens present many challenges to organisms, driving the evolution of a myriad of antiviral strategies to combat infections. A wide variety of viruses infect invertebrates, including both natural pathogens that are insect-restricted, and viruses that are transmitted to vertebrates. Studies using the powerful tools available in the model organism Drosophila have expanded our understanding of antiviral defenses against diverse viruses. In this review, we will cover three major areas. First, we will describe the tools used to study viruses in Drosophila. Second, we will survey the major viruses that have been studied in Drosophila. And lastly, we will discuss the well-characterized mechanisms that are active against these diverse pathogens, focusing on non-RNAi mediated antiviral mechanisms. Antiviral RNAi is discussed in another paper in this issue. PMID:23680639

  14. Antiviral lead compounds from marine sponges

    KAUST Repository

    Sagar, Sunil; Kaur, Mandeep; Minneman, Kenneth P.

    2010-01-01

    ). The most important antiviral lead of marine origin reported thus far is nucleoside Ara-A (vidarabine) isolated from sponge Tethya crypta. It inhibits viral DNA polymerase and DNA synthesis of herpes, vaccinica and varicella zoster viruses. However due

  15. Assessment of Inhibition of Ebola Virus Progeny Production by Antiviral Compounds.

    Science.gov (United States)

    Falzarano, Darryl

    2017-01-01

    Assessment of small molecule compounds against filoviruses, such as Ebola virus, has identified numerous compounds that appear to have antiviral activity and should presumably be further investigated in animal efficacy trials. However, despite the many compounds that are purported to have good antiviral activity in in vitro studies, there are few instances where any efficacy has been reported in nonhuman primate models. Many of the high-throughput screening assays use reporter systems that only recapitulate a portion of the virus life cycle, while other assays only assess antiviral activity at relatively early time points. Moreover, many assays do not assess virus progeny production. A more in-depth evaluation of small numbers of test compounds is useful to economize resources and to generate higher quality antiviral hits. Assessing virus progeny production as late as 5 days post-infection allows for the elimination of compounds that have initial antiviral effects that are not sustained or where the virus rapidly develops resistance. While this eliminates many potential lead compounds that may be worthy of further structure-activity relationship (SAR) development, it also quickly excludes compounds that in their current form are unlikely to be effective in animal models. In addition, the inclusion of multiple assays that assess both cell viability and cell cytotoxicity, via different mechanisms, provides a more thorough assessment to exclude compounds that are not direct-acting antivirals.

  16. The similar hexheimer reaction during initial treatment of pulmonary tuberculosis: CT appearances

    International Nuclear Information System (INIS)

    Lu Yan; Zhou Xinhua; Xie Ruming; Xu Jinping

    2009-01-01

    Objective: To investigate CT features of similar Hexheimer's reaction during initial treatment of active pulmonary tuberculosis. Methods: The similar Hexheimer's reaction in 44 patients diagnosed by clinic and follow-up CT scans were retrospectively reviewed by three radiologists. Results: During initial treatment of active pulmonary tuberculosis, development of radiographic progression were observed in 57 foci, including 28 pulmonary lesions increased at the site of their original lesion or new opacities elsewhere, ipsilateral or contralateral to the original lesion or both, 10 lesions related to the pleura (pleural effusion, pleural tuberculoma), 15 lymphadenectasis, 3 thymus reactions, and 1 cardiac pericardium thickening, respectively. These reactions appeared from the 20 days to 3.5 months, then with continuation of the initial chemotherapy for 1.0-3.0 months, the radiographic response was excellent with the areas of progression and the original lesions demonstrating resolution or improvement. Conclusion: The CT appearances of similar Hexheimer's reaction during initial treatment of active tuberculosis are specific to a certainty. (authors)

  17. Human influenza is more effective than avian influenza at antiviral suppression in airway cells.

    Science.gov (United States)

    Hsu, Alan Chen-Yu; Barr, Ian; Hansbro, Philip M; Wark, Peter A

    2011-06-01

    Airway epithelial cells are the initial site of infection with influenza viruses. The innate immune responses of airway epithelial cells to infection are important in limiting virus replication and spread. However, relatively little is known about the importance of this innate antiviral response to infection. Avian influenza viruses are a potential source of future pandemics; therefore, it is critical to examine the effectiveness of the host antiviral system to different influenza viruses. We used a human influenza (H3N2) and a low-pathogenic avian influenza (H11N9) to assess and compare the antiviral responses of Calu-3 cells. After infection, H3N2 replicated more effectively than the H11N9 in Calu-3 cells. This was not due to differential expression of sialic acid residues on Calu-3 cells, but was attributed to the interference of host antiviral responses by H3N2. H3N2 induced a delayed antiviral signaling and impaired type I and type III IFN induction compared with the H11N9. The gene encoding for nonstructural (NS) 1 protein was transfected into the bronchial epithelial cells (BECs), and the H3N2 NS1 induced a greater inhibition of antiviral responses compared with the H11N9 NS1. Although the low-pathogenic avian influenza virus was capable of infecting BECs, the human influenza virus replicated more effectively than avian influenza virus in BECs, and this was due to a differential ability of the two NS1 proteins to inhibit antiviral responses. This suggests that the subversion of human antiviral responses may be an important requirement for influenza viruses to adapt to the human host and cause disease.

  18. Acceleration of Intended Pozzolanic Reaction under Initial Thermal Treatment for Developing Cementless Fly Ash Based Mortar

    Directory of Open Access Journals (Sweden)

    Yang-Hee Kwon

    2017-02-01

    Full Text Available Without using strong alkaline solution or ordinary Portland cement, a new structural binder consisting of fly ash and hydrated lime was hardened through an intensified pozzolanic reaction. The main experimental variables are the addition of silica fume and initial thermal treatment (60 °C for 3 days. A series of experiments consisting of mechanical testing (compressive and flexural strength, modulus of elasticity, X-ray diffraction, and measurements of the heat of hydration, pore structure, and shrinkage were conducted. These tests show that this new fly ash-based mortar has a compressive strength of 15 MPa at 91 days without any silica fume addition or initial thermal treatment. The strength increased to over 50 MPa based on the acceleration of the intensified pozzolanic reaction from the silica fume addition and initial thermal treatment. This is explained by a significant synergistic effect induced by the silica fume. It intensifies the pozzolanic reaction under thermal treatment and provides a space filling effect. This improved material performance can open a new pathway to utilize the industrial by-product of fly ash in cementless construction materials.

  19. Caries preventive efficiency of therapeutic complex accomponying orthodontic treatment of children with initial dental caries

    Directory of Open Access Journals (Sweden)

    Denga A.E.

    2013-12-01

    Full Text Available The use of orthodontic non-removable appliance in orthodontic treatment inter¬feres with the process of teeth mineralization, worsens level of oral cavity hygiene, stimulates development of caries process. The situation is complicated when a patient has an initial tooth decay. The aim of this study was to determine genetic characteristics of children with initial caries and clinical evaluation of effectiveness of the developed caries preventive therapeutic complex accompanying treatment of jaw facial anomalies (JFA. 47 children aged 12-14 with initial tooth decay participated in the examination. Complex diagnostics, including molecular genetic studies was carried out. Therapeutic complex for children, of the main group included remineralizing, adaptogenic, biogenic agents, which increase non-specific resistance, as well as infiltration ICON therapy before fixing braces. Caries preventive complex accompanying JFA treatment in children with primary tooth decay developed with regard to revealed genetic disorders of amelogenesis, 2-nd of phase detoxification, collagen formation, functional responses in the oral cavity, state of hard tissues of teeth and periodontal tissues enabled to preserve existing carious process, normalize periodontal and hygienic indices at all stages of treatment.

  20. Loss-to-follow-up and delay to treatment initiation in Pakistan's national tuberculosis control programme.

    Science.gov (United States)

    Ali, Syed Mustafa; Naureen, Farah; Noor, Arif; Fatima, Irum; Viney, Kerri; Ishaq, Muhammad; Anjum, Naveed; Rashid, Aamna; Haider, Ghulam Rasool; Khan, Muhammad Aamir; Aamir, Javariya

    2018-03-09

    Researchers and policy-makers have identified loss to follow-up as a major programmatic problem. Therefore, the objective of this study is to quantify TB related pre-treatment loss to follow up and treatment delay in private sector health care facilities in Pakistan. This was a retrospective, descriptive cohort study using routinely collected programmatic data from TB referral, diagnosis and treatment registers. Data from 48 private healthcare facilities were collected using an online questionnaire prepared in ODK Collect, for the period October 2015 to March 2016. Data were analysed using SPSS. We calculated the: (1) number and proportion of patients who were lost to follow-up during the diagnostic period, (2) number and proportion of patients with pre-treatment loss to follow-up, and (3) the number of days between diagnosis and initiation of treatment. One thousand five hundred ninety-six persons with presumptive TB were referred to the laboratory. Of these, 96% (n = 1538) submitted an on-the-spot sputum sample. Of the 1538 people, 1462 (95%) people subsequently visited the laboratory to submit the early morning (i.e. the second) sample. Hence, loss to follow-up during the diagnostic process was 8% overall (n = 134). Of the 1462 people who submitted both sputum samples, 243 (17%) were diagnosed with sputum smear-positive pulmonary TB and 231 were registered for anti-TB treatment, hence, loss in the pre-treatment phase was 4.9% (n = 12). 152 persons with TB (66%) initiated TB treatment either on the day of TB diagnosis or the next day. A further 79 persons with TB (34%) commenced TB treatment within a mean time of 7 days (range 2 to 64 days). Concentrated efforts should be made by the National TB Control Programme to retain TB patients and innovative methods such as text reminders and behavior change communication may need to be used and tested.

  1. Initial and Middle-Term Outcome of Treatment for Spontaneous Isolated Dissection of Superior Mesenteric Artery.

    Science.gov (United States)

    Li, Zilun; Ding, Huanyu; Shan, Zhen; Du, Jianliang; Yao, Chen; Chang, Guangqi; Wang, Shenming

    2015-11-01

    Symptomatic isolated dissection of the superior mesenteric artery (SIDSMA) represents an extremely rare condition. Although various treatments including conservative treatment, endovascular stenting (ES), and surgical repair are currently available, consensus treatment guideline is absent due to scarce of SIDSMA cases. Thus, we present our experience in the treatment of SIDSMA at our single center.Fourteen cases of SIDSMA were treated with conservative treatment, catheter-directed thrombolysis (CDT), endovascular stenting (ES), or surgical repair at our center between January 2008 and January 2014. Demographics, clinical manifestations, coexisting medical conditions, imaging feature, treatments, and follow-up outcome of these patients were retrospectively collected and analyzed.For 13 patients without peritonitis, conservative treatment was given for 4 to 6 days initially. After the first observation cycle, symptoms and signs were alleviated in 8 patients, and conservative treatments were continued. The remaining 5 patients received technically and clinically successful ES (in 4) or CDT (in 1) due to worsening symptoms and signs during conservative treatment. One patient with peritonitis underwent emergency surgery, with the necrotic small intestine resected. However, the abdominal pain was not alleviated 17 days postoperatively, ES was thus performed and symptoms relieved immediately. Two weeks after ES, a new aneurysm and partial thrombosis in the distal part of the stent were found by computed tomography angiography in this patient. No intestinal infarction or mortality developed during hospitalization. Follow-up was accomplished in 11 cases, ranging from 4 to 74 months (23.5 ± 21.3). Except that one complained with mild abdominal pain, the other 10 achieved complete remission. All patients were free from new aneurysmal formation of SMA and all stents remained patent.For SIDSMA without peritonitis, conservative treatment can be provided with reasonable

  2. Probiotics as Antiviral Agents in Shrimp Aquaculture

    Directory of Open Access Journals (Sweden)

    Bestha Lakshmi

    2013-01-01

    Full Text Available Shrimp farming is an aquaculture business for the cultivation of marine shrimps or prawns for human consumption and is now considered as a major economic and food production sector as it is an increasingly important source of protein available for human consumption. Intensification of shrimp farming had led to the development of a number of diseases, which resulted in the excessive use of antimicrobial agents, which is finally responsible for many adverse effects. Currently, probiotics are chosen as the best alternatives to these antimicrobial agents and they act as natural immune enhancers, which provoke the disease resistance in shrimp farm. Viral diseases stand as the major constraint causing an enormous loss in the production in shrimp farms. Probiotics besides being beneficial bacteria also possess antiviral activity. Exploitation of these probiotics in treatment and prevention of viral diseases in shrimp aquaculture is a novel and efficient method. This review discusses the benefits of probiotics and their criteria for selection in shrimp aquaculture and their role in immune power enhancement towards viral diseases.

  3. Did our current initial treatment practice change after EAU/ESPU vesicoureteral reflux risk grouping?

    Science.gov (United States)

    Tokat, Eda; Gurocak, Serhat; Ure, Iyimser; Acar, Cenk; Sınık, Zafer; Tan, Mustafa Ozgur

    2018-06-02

    The "European Association of Urology (EAU) Guidelines on Vesicoureteral Reflux (VUR) in Children (September 2012)" established risk classification by analyzing and defining risk factors for each patient. In this study we aimed to investigate how our initial treatment procedures were affected by EAU/ESPU guideline vesicoureteral reflux risk grouping and to compare the early clinical results of treatments performed before and after the risk classification in our patients with VUR. 334 renal units with regular clinical follow-up who were treated owing to VUR (vesicoureteral reflux) between years 2009 and 2017 were retrospectively reviewed. Preoperative clinical parameters such as grade and laterality of reflux, presence of renal scar, initial and follow-up treatments, findings of medical treatment and surgical procedures were analyzed. The initial medical and surgical methods were compared by categorizing patients according to risk groups before and after 2013. Mean age and follow-up duration were 71.4(6-216) months and 47(4-141) months, respectively. Among the preoperative parameters, only high EAU risk group (p = 0.01) and treating lower urinary tract symptoms (p age, sex, and presence of renal scar at DMSA were not affecting the success of treatment significantly. While no significant difference in medical and surgical treatment rates is observed after risk grouping system in low risk group, the percentages of patients who are treated with surgical methods initially were significantly decreased in moderate and high risk groups (p = 0.002 and p = 0.012, respectively). We determined that VUR risk grouping did not change clinical success significantly in all risk groups. Despite the fact that EAU/ESPU VUR risk classification changed our current practice in terms of initial treatment method, this different approach did not seem to affect early clinical success positively. There is still an absolute need for studies with larger sample size and long

  4. Addressing the selectivity and toxicity of antiviral nucleosides.

    Science.gov (United States)

    Feng, Joy Y

    2018-01-01

    Nucleoside and nucleotide analogs have played significant roles in antiviral therapies and are valued for their impressive potency and high barrier to resistance. They have been approved for treatment of herpes simplex virus-1, HIV, HBV, HCV, and influenza, and new drugs are being developed for the treatment of RSV, Ebola, coronavirus MERS, and other emerging viruses. However, this class of compounds has also experienced a high attrition rate in clinical trials due to toxicity. In this review, we discuss the utility of different biochemical and cell-based assays and provide recommendations for assessing toxicity liability before entering animal toxicity studies.

  5. Parent perspectives on information about late effects of childhood cancer treatment and their role in initial treatment decision making.

    Science.gov (United States)

    Greenzang, Katie A; Dauti, Angela; Mack, Jennifer W

    2018-06-01

    Though most childhood cancer survivors experience late effects of treatment, we know little about parent preferences for late effects information during therapy, or how parents weigh late effects when making treatment decisions. Our objective was to explore how parents of children with cancer consider late effects in initial treatment decision making and during active cancer treatment. Semistructured interviews were conducted with 12 parents of children with cancer who were actively receiving treatment at Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Interviews were audio-recorded, transcribed verbatim, and qualitatively analyzed using thematic analysis. Ten of 12 parents reported that they had to decide between two or more treatment options for their child's cancer. Of those, 50% (5/10) considered late effects to be an important factor in their decision making. Most parents wanted early and detailed information about their child's risk of late effects to make treatment decisions and to feel prepared for the future. However, a few parents felt too overwhelmed to focus on late effects at diagnosis. While many recalled extensive late effects information in informed consent discussions, some parents felt these issues were minimally addressed. Parents desire detailed information about late effects to make informed treatment decisions and prepare for the future. Despite the role of late effects in treatment decision making, some parents feel that late effects are either inadequately addressed or too overwhelming to process at diagnosis. Parents may benefit from early assessment of their information needs and a return to these issues over time. © 2018 Wiley Periodicals, Inc.

  6. Practical aspects of treatment with target specific anticoagulants: initiation, payment and current market, transitions, and venous thromboembolism treatment.

    Science.gov (United States)

    Mahan, Charles E

    2015-04-01

    Target specific anticoagulants (TSOACs) have recently been introduced to the US market for multiple indications including venous thromboembolism (VTE) prevention in total hip and knee replacement surgeries, VTE treatment and reduction in the risk of stroke in patients with non-valvular atrial fibrillation (NVAF). Currently, three TSOACs are available including rivaroxaban, apixaban, and dabigatran with edoxaban currently under Food and Drug Administration review for VTE treatment and stroke prevention in NVAF. The introduction of these agents has created a paradigm shift in anticoagulation by considerably simplifying treatment and anticoagulant initiation for patients by giving clinicians the opportunity to use a rapid onset, rapid offset, oral agent. The availability of these rapid onset TSOACs is allowing for outpatient treatment of low risk pulmonary embolism and deep vein thrombosis which can greatly reduce healthcare costs by avoiding inpatient hospitalizations and treatment for the disease. Additionally with this practice, the complications of an inpatient hospitalization may also be avoided such as nosocomial infections. Single-agent approaches with TSOACs represent a paradigm shift in the treatment of VTE versus the complicated overlap of a parenteral agent with warfarin. Transitions between anticoagulants, including TSOACs, are a high-risk period for the patient, and clinicians must carefully consider patient characteristics such as renal function as well as the agents that are being transitioned. TSOAC use appears to be growing slowly with improved payment coverage throughout the US.

  7. The use of sofosbuvir for the treatment of recurrent hepatitis C after liver transplantation

    Directory of Open Access Journals (Sweden)

    M. Sh. Khubutiya

    2017-01-01

    Full Text Available The article presents the experience of direct-acting antiviral (DAA drug treatment for hepatitis C in the patients after liver transplantation. The end-stage liver disease caused by hepatitis C is the main indication for orthotopic liver transplantation (OLT. In 2013, the first agent in the class of antiviral drugs directly acting on hepatitis C virus (HCV was introduced into clinical practice. That was sofosbuvir, a HCV polymerase inhibitor, that could be used without interferon alfa.Materials and methods. The study enrolled 33 liver transplant recipients with recurrent hepatitis C. Thirty-five courses of antiviral therapy (AT were conducted with sofosbuvir being one of AT components.Results. By the time of analysis, 21 patients had completed the antiviral therapy. All the patients showed an initial response to the antiviral therapy, HCV aviremia was achieved. In 3 patients, with the evaluable sustained virologic response (SVR, a renewed HCV replication was observed in the first weeks after the AT completion.Conclusion. The new direct-acting antiviral drugs offer an effective antiviral therapy to all liver graft recipients with recurrent HCV.

  8. Cinnamon Bark, Water Soluble Cinnamon Extract, and Metformin as Initial Treatment for Type 2 Diabetes Mellitus: A Randomized, Controlled Trial

    Science.gov (United States)

    2016-12-14

    Cinnamon Extract, and Metformin as Initial Treatment for Type 2 Diabetes Mellitus : A Randomized, Controlled Trial. Paul Crawford, MD Clinical Investigation...Title: “Cinnamon Bark, Water-Soluble Cinnamon Extract, and Metformin as Initial Treatment for Type 2 Diabetes Mellitus : A Randomized, Controlled...as initial treatment for Type 2 diabetes mellitus : A randomized, controlled trial. IRB #: FWH20110004H Principal Investigator (PI) Rank / Civ

  9. Cost-effectiveness of emergency department-initiated treatment for opioid dependence.

    Science.gov (United States)

    Busch, Susan H; Fiellin, David A; Chawarski, Marek C; Owens, Patricia H; Pantalon, Michael V; Hawk, Kathryn; Bernstein, Steven L; O'Connor, Patrick G; D'Onofrio, Gail

    2017-11-01

    In a recent randomized trial, patients with opioid dependence receiving brief intervention, emergency department (ED)-initiated buprenorphine and ongoing follow-up in primary care with buprenorphine (buprenorphine) were twice as likely to be engaged in addiction treatment compared with referral to community-based treatment (referral) or brief intervention and referral (brief intervention). Our aim was to evaluate the relative cost-effectiveness of these three methods of intervening on opioid dependence in the ED. Measured health-care use was converted to dollar values. We considered a health-care system perspective and constructed cost-effectiveness acceptability curves that indicate the probability each treatment is cost-effective under different thresholds of willingness-to-pay for outcomes studied. An urban ED in the United States. Opioid-dependent patients aged 18 years or older. Self-reported 30-day assessment data were used to construct cost-effectiveness acceptability curves for patient engagement in formal addiction treatment at 30 days and the number of days illicit opioid-free in the past week. Considering only health-care system costs, cost-effectiveness acceptability curves indicate that at all positive willingness-to-pay values, ED-initiated buprenorphine treatment was more cost-effective than brief intervention or referral. For example, at a willingness-to-pay threshold of $1000 for 30-day treatment engagement, we are 79% certain ED-initiated buprenorphine is most cost-effective compared with other studied treatments. Similar results were found for days illicit opioid-free in the past week. Results were robust to secondary analyses that included patients with missing cost data, included crime and patient time costs in the numerator, and to changes in unit price estimates. In the United States, emergency department-initiated buprenorphine intervention for patients with opioid dependence provides high value compared with referral to community

  10. Pretreatment costs of care and time to initial treatment for patients with cancer of unknown primary.

    Science.gov (United States)

    Walker, Mark S; Weinstein, Laura; Luo, Roger; Marino, Ingrid

    2018-06-01

    Time to treatment and pretreatment costs may be affected by unknown primary tumor site. This retrospective study used electronic medical record data from patients in ten US community oncology practices. Eligible patients were ≥18 years, diagnosed with cancer of unknown primary (CUP) or known metastatic solid tumor, and presented between 1 January 2012 and 30 June 2014. Patients with CUP (n = 294) had a longer interval than non-CUP patients (n = 92) from presentation to treatment initiation (1.18 vs 0.49 months, p < 0.0001), and had higher pretreatment costs (US$27,882 vs US$20,449, p = 0.0075). When analyzed as monthly cost, the difference between groups in log-cost per month was nonsignificant. Higher pretreatment costs in CUP patients appeared attributable to significantly longer time to initiation of therapy.

  11. Age at the time of sulfonylurea initiation influences treatment outcomes in KCNJ11-related neonatal diabetes.

    Science.gov (United States)

    Thurber, Brian W; Carmody, David; Tadie, Elizabeth C; Pastore, Ashley N; Dickens, Jazzmyne T; Wroblewski, Kristen E; Naylor, Rochelle N; Philipson, Louis H; Greeley, Siri Atma W

    2015-07-01

    Individuals with heterozygous activating mutations of the KCNJ11 gene encoding a subunit of the ATP-sensitive potassium channel (KATP) can usually be treated with oral sulfonylurea (SU) pills in lieu of insulin injections. The aim of this study was to test our hypothesis that younger age at the time of initiation of SU therapy is correlated with lower required doses of SU therapy, shorter transition time and decreased likelihood of requiring additional diabetes medications. We performed a retrospective cohort study using data on 58 individuals with neonatal diabetes due to KCNJ11 mutations identified through the University of Chicago Monogenic Diabetes Registry ( http://monogenicdiabetes.uchicago.edu/registry ). We assessed the influence of age at initiation of SU therapy on treatment outcomes. HbA1c fell from an average of 8.5% (69 mmol/mol) before transition to 6.2% (44 mmol/mol) after SU therapy (p < 0.001). Age of initiation of SU correlated with the dose (mg kg(-1) day(-1)) of SU required at follow-up (r = 0.80, p < 0.001). Similar associations were observed across mutation subtypes. Ten participants required additional glucose-lowering medications and all had initiated SU at age 13 years or older. No serious adverse events were reported. Earlier age at initiation of SU treatment is associated with improved response to SU therapy. Declining sensitivity to SU may be due to loss of beta cell mass over time in those treated with insulin. Our data support the need for early genetic diagnosis and appropriate personalised treatment in all cases of neonatal diabetes.

  12. Clinical and Genetic Determinants of Warfarin Pharmacokinetics and Pharmacodynamics during Treatment Initiation

    Science.gov (United States)

    Gong, Inna Y.; Schwarz, Ute I.; Crown, Natalie; Dresser, George K.; Lazo-Langner, Alejandro; Zou, GuangYong; Roden, Dan M.; Stein, C. Michael; Rodger, Marc; Wells, Philip S.; Kim, Richard B.; Tirona, Rommel G.

    2011-01-01

    Variable warfarin response during treatment initiation poses a significant challenge to providing optimal anticoagulation therapy. We investigated the determinants of initial warfarin response in a cohort of 167 patients. During the first nine days of treatment with pharmacogenetics-guided dosing, S-warfarin plasma levels and international normalized ratio were obtained to serve as inputs to a pharmacokinetic-pharmacodynamic (PK-PD) model. Individual PK (S-warfarin clearance) and PD (Imax) parameter values were estimated. Regression analysis demonstrated that CYP2C9 genotype, kidney function, and gender were independent determinants of S-warfarin clearance. The values for Imax were dependent on VKORC1 and CYP4F2 genotypes, vitamin K status (as measured by plasma concentrations of proteins induced by vitamin K absence, PIVKA-II) and weight. Importantly, indication for warfarin was a major independent determinant of Imax during initiation, where PD sensitivity was greater in atrial fibrillation than venous thromboembolism. To demonstrate the utility of the global PK-PD model, we compared the predicted initial anticoagulation responses with previously established warfarin dosing algorithms. These insights and modeling approaches have application to personalized warfarin therapy. PMID:22114699

  13. Icotinib as initial treatment in lung adenocarcinoma patients with brain metastases.

    Science.gov (United States)

    Xu, Jian-Ping; Liu, Xiao-Yan; Yang, Sheng; Zhang, Chang-Gong; Wang, Lin; Shi, Yuan-Kai

    2016-07-01

    To evaluate the antitumor activity and toxicity of icotinib as initial treatment in lung adenocarcinoma patients with brain metastases. Twenty-one patients with histologically or pathologically documented brain metastatic lung cancer were administered icotinib as initial treatment from 2011 to 2015 at the Cancer Institute and Hospital, Chinese Academy of Medical Sciences. Chemotherapy response was assessed by Response Evaluation Criteria in Solid Tumors and toxicity was evaluated according to National Cancer Institute-Common Toxicity Criteria. Icotinib was administered three times per day at a dose of 125mg. The median overall and progression-free survival rates were 15.2 (1.2-31.5 months, 95% confidence interval [CI] 6.6-23.7 months) and 8.9 months (0.6-30.5 months, 95% CI 3.4-14.3 months), respectively. The overall response and disease control rates were 61.9% and 90.5%, respectively. Icotinib was well tolerated, and no grade 3/4 adverse events were observed. The most common grade 1/2 adverse events included acneiform eruptions (38.1%), diarrhea (19.0%), and stomatitis (9.5%). Icotinib is effective and well tolerated as initial treatment in lung adenocarcinoma patients with brain metastases.

  14. Impact of a new reimbursement program on hepatitis B antiviral medication cost and utilization in Beijing, China.

    Directory of Open Access Journals (Sweden)

    Qian Qiu

    Full Text Available BACKGROUND: Hepatitis B virus (HBV infection is a significant clinical and financial burden for chronic hepatitis B (CHB patients. In Beijing, China, partial reimbursement on antiviral agents was first implemented for the treatment of CHB patients in July 1, 2011. AIMS: In this study, we describe the medical cost and utilization rates of antiviral therapy for CHB patients to explore the impact of the new partial reimbursement policy on the medical care cost, the composition, and antivirals utilization. METHODS: Clinical and claims data of a retrospective cohort of 92,776 outpatients and 2,774 inpatients with non-cirrhotic CHB were retrieved and analyzed from You'an Hospital, Beijing between February 14, 2008 and December 31, 2012. The propensity score matching was used to adjust factors associated with the annual total cost, including age, gender, medical insurance type and treatment indicator. RESULTS: Compared to patients who paid out-of-pocket, medical cost, especially antiviral costs increased greater among patients with medical insurance after July 1, 2011, the start date of reimbursement policy. Outpatients with medical insurance had 16% more antiviral utilization; usage increased 3% among those who paid out-of-pocket after the new partial reimbursement policy was implemented. CONCLUSIONS: Direct medical costs and antiviral utilization rates of CHB patients with medical insurance were higher than those from paid out-of-pocket payments, even after adjusting for inflation and other factors. Thus, a new partial reimbursement program may positively optimize the cost and standardization of antiviral treatment.

  15. Initial Selection of Supplemental Treatment Technologies for Hanford's Low-Activity Tank Waste

    International Nuclear Information System (INIS)

    Raymond, Richard E.; Powell, Roger W.; Hamilton, Dennis W.; Kitchen, William A.; Mauss, Billie M.; Brouns, Thomas M.

    2004-01-01

    In 2002, the U.S. Department of Energy (DOE) documented a plan for accelerating cleanup of the Hanford Site, located in southeastern Washington State, by at least 35 years (DOE 2002). A key element of the accelerated cleanup plan was a strategic initiative for acceleration of the tank waste program and completion of ''tank waste treatment by 2028 by increasing the capacity of the planned Waste Treatment Plant (ETP) and using supplemental technologies for waste treatment and immobilization''. The plan identified specific technologies to be evaluated for supplemental treatment of as much as 70% of the low-activity waste (LAW). The objective was to complete required testing and evaluation that would ''...bring an appropriate combination of the above technologies to deployment to supplement LAW treatment and immobilization in the WTP to achieve the completion of tank waste treatment by 2028''. In concert with this acceleration plan, DOE, the U.S. Environmental Protection Agency, and the Washington State Department of Ecology have proposed to accelerate from 2012 to 2005 the Hanford Federal Facility Compliance Agreement (Tri-Party Agreement) milestone (M-62-08) associated with a final decision on treatment of the balance of tank waste that is beyond the capacity of the currently designed WTP

  16. Treatment of chronic hepatitis B virus infection - Dutch national guidelines

    NARCIS (Netherlands)

    Buster, E. H. C. J.; van Erpecum, K. J.; Schalm, S. W.; Zaaijer, H. L.; Brouwer, J. T.; Gelderblom, H. C.; de Knegt, R. J.; Minke Bakker, C.; Reesink, H. W.; Janssen, H. L. A.; Bakker, C. M.

    2008-01-01

    The development of this guideline was initiated and coordinated by the Netherlands Association of Gastroenterologists and Hepatologists (Nederlandse Vereniging van Maag-Darm-Leverartsen). The aim is the establishment of national standards in the evaluation and antiviral treatment of patients with

  17. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    International Nuclear Information System (INIS)

    Kim, Yoo-Shin; Lee, Tae Hoon; O'Neill, Brian E.

    2015-01-01

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy

  18. Non-lethal heat treatment of cells results in reduction of tumor initiation and metastatic potential

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yoo-Shin; Lee, Tae Hoon; O' Neill, Brian E., E-mail: BEOneill@houstonmethodist.org

    2015-08-14

    Non-lethal hyperthermia is used clinically as adjuvant treatment to radiation, with mixed results. Denaturation of protein during hyperthermia treatment is expected to synergize with radiation damage to cause cell cycle arrest and apoptosis. Alternatively, hyperthermia is known to cause tissue level changes in blood flow, increasing the oxygenation and radiosensitivity of often hypoxic tumors. In this study, we elucidate a third possibility, that hyperthermia alters cellular adhesion and mechanotransduction, with particular impact on the cancer stem cell population. We demonstrate that cell heating results in a robust but temporary loss of cancer cell aggressiveness and metastatic potential in mouse models. In vitro, this heating results in a temporary loss in cell mobility, adhesion, and proliferation. Our hypothesis is that the loss of cellular adhesion results in suppression of cancer stem cells and loss of tumor virulence and metastatic potential. Our study suggests that the metastatic potential of cancer is particularly reduced by the effects of heat on cellular adhesion and mechanotransduction. If true, this could help explain both the successes and failures of clinical hyperthermia, and suggest ways to target treatments to those who would most benefit. - Highlights: • Non-lethal hyperthermia treatment of cancer cells is shown to cause a reduction in rates of tumor initiation and metastasis. • Dynamic imaging of cells during heat treatment shows temporary changes in cell shape, cell migration, and cell proliferation. • Loss of adhesion may lead to the observed effect, which may disproportionately impact the tumor initiating cell fraction. • Loss or suppression of the tumor initiating cell fraction results in the observed loss of metastatic potential in vivo. • This result may lead to new approaches to synergizing hyperthermia with surgery, radiation, and chemotherapy.

  19. Outcomes among HIV-infected children initiating HIV care and antiretroviral treatment in Ethiopia.

    Science.gov (United States)

    Melaku, Zenebe; Lulseged, Sileshi; Wang, Chunhui; Lamb, Matthew R; Gutema, Yoseph; Teasdale, Chloe A; Ahmed, Solomon; Gadisa, Tsigereda; Habtamu, Zelalem; Bedri, Abubaker; Fayorsey, Ruby; Abrams, Elaine J

    2017-04-01

    To describe pediatric ART scale-up in Ethiopia, one of the 21 global priority countries for elimination of pediatric HIV infection. A descriptive analysis of routinely collected HIV care and treatment data on HIV-infected children (<15 years) enrolled at 70 health facilities in four regions in Ethiopia, January 2006-September 2013. Characteristics at enrollment and ART initiation are described along with outcomes at 1 year after enrollment. Among children who initiated ART, cumulative incidence of death and loss to follow-up (LTF) were estimated using survival analysis. 11 695 children 0-14 years were enrolled in HIV care and 6815 (58.3%) initiated ART. At enrollment, 31.2% were WHO stage III and 6.3% stage IV. The majority (87.9%) were enrolled in secondary or tertiary facilities. At 1 year after enrollment, 17.9% of children were LTF prior to ART initiation. Among children initiating ART, cumulative incidence of death was 3.4%, 4.1% and 4.8%, and cumulative incidence of LTF was 7.7%, 11.8% and 16.6% at 6, 12 and 24 months, respectively. Children <2 years had higher risk of LTF and death than older children (P < 0.0001). Children with more advanced disease and those enrolled in rural settings were more likely to die. Children enrolled in more recent years were less likely to die but more likely to be LTF. Over the last decade large numbers of HIV-infected children have been successfully enrolled in HIV care and initiated on ART in Ethiopia. Retention prior to and after ART initiation remains a major challenge. © 2017 John Wiley & Sons Ltd.

  20. African American women's experiences with the initial discovery, diagnosis, and treatment of breast cancer.

    Science.gov (United States)

    Lackey, N R; Gates, M F; Brown, G

    2001-04-01

    To describe the experiences of African American women living with breast cancer following the primary diagnosis and while undergoing initial treatment. Phenomenologic. 13 African American women (ages 30-66) purposefully selected from two oncology clinics in the mid-South. Phenomenologic interviews (transcribed verbatim) and field notes were analyzed using Colaizzi's method of phenomenologic description and analysis. Experience Trajectory, Femininity, and Spirituality were the three major themes. The Experience Trajectory subthemes were finding the lump, getting the diagnosis, undergoing surgery and adjuvant treatment. The Femininity subthemes were loss of all or part of the breast, loss of hair, and sexual attractiveness to a man. Spirituality was reflected as a reliance on God. Telling the story of their experience trajectory during their breast cancer experience is valuable in assessing African American women's feelings, emotions, and fears of body changes that occur during surgery and treatment. Their spirituality helps them through this experience. Research involving both African American women and their partners would provide greater insight into specific relationship patterns and communication related to sexuality during this experience. Nurses need to listen to the stories of African American women about the initial experience of discovery, diagnosis, and treatment of breast cancer so they can be more informed advocates for these women. African American women need more information from healthcare providers regarding the whole experience trajectory.

  1. Comparison of steroid pulse therapy and conventional oral steroid therapy as initial treatment for autoimmune pancreatitis

    International Nuclear Information System (INIS)

    Tomiyama, Takashi; Uchida, Kazushige; Matsushita, Mitsunobu; Ikeura, Tsukasa; Fukui, Toshiro; Takaoka, Makoto; Nishio, Akiyoshi; Okazaki, Kazuichi

    2011-01-01

    The efficacy of oral steroid therapy for autoimmune pancreatitis (AIP) is well known, and oral prednisolone treatment is most usually commenced at 30-40 mg/day, but there have been few reports about comparative studies of oral steroid therapy and steroid pulse therapy as the initial treatment for AIP. We studied the clinical course and image findings to estimate the utility of steroid pulse therapy for AIP, comparing it with oral steroid therapy. Laboratory and image findings were assessed retrospectively in 11 patients who received steroid pulse therapy, and the findings were compared to those in 10 patients who received conventional oral steroid therapy. Change in pancreatic size showed no significant difference between the therapies after 2 weeks of treatment. Significant improvement of lower bile duct strictures after 2 weeks of treatment and that of immunoglobulin values within 6 months were shown with both therapies. However, steroid pulse therapy showed significant improvement of γ-guanosine triphosphate (GTP) in 2 weeks and of alanine aminotransferase (ALT) in 2 and 8 weeks, compared with oral steroid therapy. Moreover, there was one patient in whom the lower bile duct stricture was not improved by oral steroid therapy, but it did show improvement with steroid pulse therapy. Initial steroid pulse therapy is a beneficial alternative to oral steroid therapy for the improvement of bile duct lesions. In future, the accumulation of a larger number of patients receiving steroid pulse therapy is needed, and prospective studies will be required. (author)

  2. Radiotherapy compared to chemotherapy as initial treatment of angiocentric centrofacial lymphoma (polymorphic reticulosis)

    International Nuclear Information System (INIS)

    Sobrevilla-Calvo, P.; Meneses, A.; Alfaro, P.; Bares, J.P.; Amador, J.; Reynoso, E.E.

    1993-01-01

    Polymorphic reticulosis has recently been characterized as an angiocentric lymphoproliferative disorder of the peripheral T-lymphocytes. However, its treatment is still a matter of controversy. In order to study efficacy and toxicity of the primary treatment, we reviewed clinical features and therapeutic results in 29 patients seen at the Instituto Nacional de Cancerologia de Mexico. Nineteen patients received primary local irradiation and 10 patients primary combination chemotherapy. In the radiotherapy group, 14 (74%) patients achieved complete response, but only 4 (40%) did so in the primary chemotherapy group. Five patients in the latter group died of treatment-related complications. The 5-year actuarial survival rate was 70% in the irradiation group, while the 1-year survival rate was only 15% in the chemotherapy group. These data strongly suggest that, in polymorphic reticulosis, initial chemotherapy may be very toxic. (orig.)

  3. Correlates of Initiation of Treatment for Chronic Hepatitis C Infection in United States Veterans, 2004-2009.

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    Adi V Gundlapalli

    Full Text Available We describe the rates and predictors of initiation of treatment for chronic hepatitis C (HCV infection in a large cohort of HCV positive Veterans seen in U.S. Department of Veterans Affairs (VA facilities between January 1, 2004 and December 31, 2009. In addition, we identify the relationship between homelessness among these Veterans and treatment initiation. Univariate and multivariable Cox Proportional Hazards regression models with time-varying covariates were used to identify predictors of initiation of treatment with pegylated interferon alpha plus ribavirin. Of the 101,444 HCV treatment-naïve Veterans during the study period, rates of initiation of treatment among homeless and non-homeless Veterans with HCV were low and clinically similar (6.2% vs. 7.4%, p<0.0001. For all U.S. Veterans, being diagnosed with genotype 2 or 3, black or other/unknown race, having Medicare or other insurance increased the risk of treatment. Veterans with age ≥50 years, drug abuse, diabetes, and hemoglobin < 10 g/dL showed lower rates of treatment. Initiation of treatment for HCV in homeless Veterans is low; similar factors predicted initiation of treatment. Additionally, exposure to treatment with medications for diabetes predicted lower rates of treatment. As newer therapies become available for HCV, these results may inform further studies and guide strategies to increase treatment rates in all U.S. Veterans and those who experience homelessness.

  4. Radiotherapy for locally recurrent rectal cancer treated with surgery alone as the initial treatment

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    Tanaka, Hidekazu; Yamaguchi, Takahiro; Hachiya, Kae; Okada, Sunaho; Kitahara, Masashi; Matsuyama, Katsuya; Matsuo, Masayuki [Gifu University, Gifu (Japan)

    2017-03-15

    Although the technical developments of radiotherapy have been remarkable, there are currently few reports on the treatment results of radiotherapy for local recurrence of rectal cancer treated with surgery alone as initial treatment in this three-dimensional conformal radiotherapy era. Thus, we retrospectively evaluated the treatment results of radiotherapy for local recurrence of rectal cancer treated with surgery alone as the initial treatment. Thirty-two patients who underwent radiotherapy were enrolled in this study. The dose per fraction was 2.0–3.5 Gy. Because the treatment schedule was variable, the biological effective dose (BED) was calculated. Local control (LC) and overall survival (OS) rates from the completion of radiotherapy were calculated. The 1-, 2-, 3-, 4-, and 5-year LC rates were 51.5%, 24.5%, 19.6%, 19.6%, and 13.1%, respectively. LC rates were significantly higher for the high BED group (≥75 Gy10) than for the lower BED group (<75 Gy10). All patients who reported pain achieved pain relief. The duration of pain relief was significantly higher for the high BED group than for the lower BED group. The 1-, 2-, 3-, 4-, and 5-year OS rates were 82.6%, 56.5%, 45.2%, 38.7%, and 23.2%, respectively. There was a trend toward higher OS rates in with higher BED group compared to lower BED group. For patients with unresectable locally recurrent rectal cancer treated with surgery alone, radiotherapy is effective treatment. The prescribed BED should be more than 75 Gy10, if the dose to the organ at risk is within acceptable levels.

  5. European evidence-based recommendations for diagnosis and treatment of paediatric antiphospholipid syndrome: the SHARE initiative.

    Science.gov (United States)

    Groot, Noortje; de Graeff, Nienke; Avcin, Tadej; Bader-Meunier, Brigitte; Dolezalova, Pavla; Feldman, Brian; Kenet, Gili; Koné-Paut, Isabelle; Lahdenne, Pekka; Marks, Stephen D; McCann, Liza; Pilkington, Clarissa A; Ravelli, Angelo; van Royen-Kerkhof, Annet; Uziel, Yosef; Vastert, Sebastiaan J; Wulffraat, Nico M; Ozen, Seza; Brogan, Paul; Kamphuis, Sylvia; Beresford, Michael W

    2017-10-01

    Antiphospholipid syndrome (APS) is rare in children, and evidence-based guidelines are sparse. Consequently, management is mostly based on observational studies and physician's experience, and treatment regimens differ widely. The Single Hub and Access point for paediatric Rheumatology in Europe (SHARE) initiative was launched to develop diagnostic and management regimens for children and young adults with rheumatic diseases. Here, we developed evidence-based recommendations for diagnosis and treatment of paediatric APS. Evidence-based recommendations were developed using the European League Against Rheumatism standard operating procedure. Following a detailed systematic review of the literature, a committee of paediatric rheumatologists and representation of paediatric haematology with expertise in paediatric APS developed recommendations. The literature review yielded 1473 articles, of which 15 were valid and relevant. In total, four recommendations for diagnosis and eight for treatment of paediatric APS (including paediatric Catastrophic Antiphospholipid Syndrome) were accepted. Additionally, two recommendations for children born to mothers with APS were accepted. It was agreed that new classification criteria for paediatric APS are necessary, and APS in association with childhood-onset systemic lupus erythematosus should be identified by performing antiphospholipid antibody screening. Treatment recommendations included prevention of thrombotic events, and treatment recommendations for venous and/or arterial thrombotic events. Notably, due to the paucity of studies on paediatric APS, level of evidence and strength of the recommendations is relatively low. The SHARE initiative provides international, evidence-based recommendations for diagnosis and treatment for paediatric APS, facilitating improvement and uniformity of care. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use

  6. Antiviral therapy and outcomes of patients with pneumonia caused by influenza A pandemic (H1N1 virus.

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    Shi-gui Yang

    Full Text Available BACKGROUND: There is limited data on the clinical outcome of patients with pandemic H1N1 (pH1N1 pneumonia who received oseltamivir treatment, especially when the treatment was administered more than 48 hours after symptom onset. METHODS: During the pandemic in 2009, a cohort of pH1N1 influenza pneumonia was built in China, and their clinical information was collected systematically, and analyzed with Cox models. RESULTS: 920 adults and 541 children with pneumonia who didn't receive corticosteroids were analyzed. In-hospital mortality was higher in adults who did not receive antiviral therapy (18.2% than those with who received oseltamivir ≤ 2 days (2.9%, between 2-5 days (4.6% and >5 days after illness onset (4.9%, p5 days, respectively. For males patients, aged ≥ 14 years and baseline PaO(2/FiO(23.8 mg/kg/d did not improve clinical outcome (mortality, higher dose 2.5% vs standard dose 2.8%, p>0.05. CONCLUSIONS: Antiviral therapy might reduce mortality of patients with pH1N1 pneumonia, even when initiated more than 48 hours after onset of illness. Greater protective effects might be in males, patients aged 14-60 years, and patients with PaO(2/FiO(2<200.

  7. Initial arch wires for tooth alignment during orthodontic treatment with fixed appliances.

    Science.gov (United States)

    Jian, Fan; Lai, Wenli; Furness, Susan; McIntyre, Grant T; Millett, Declan T; Hickman, Joy; Wang, Yan

    2013-04-30

    Initial arch wires are the first arch wires to be inserted into the fixed appliance at the beginning of orthodontic treatment and are used mainly for the alignment of teeth by correcting crowding and rotations. With a number of different types of orthodontic arch wires available for initial tooth alignment, it is important to understand which wire is most efficient, as well as which wires cause the least amount of root resorption and pain during the initial aligning stage of treatment. This is an update of the review 'Initial arch wires for alignment of crooked teeth with fixed orthodontic braces' first published in the Cochrane Database of Systematic Reviews 2010, Issue 4. To assess the effects of initial arch wires for alignment of teeth with fixed orthodontic braces in relation to alignment speed, root resorption and pain intensity. We searched the following electronic databases: the Cochrane Oral Health Group's Trials Register (to 2 August 2012), CENTRAL (The Cochrane Library 2012, Issue 7), MEDLINE via OVID (1950 to 2 August 2012) and EMBASE via OVID (1980 to 2 August 2012). We also searched the reference lists of relevant articles. There was no restriction with regard to publication status or language of publication. We contacted all authors of included studies to identify additional studies. We included randomised controlled trials (RCTs) of initial arch wires to align teeth with fixed orthodontic braces. Only studies involving participants with upper and/or lower full arch fixed orthodontic appliances were included. Two review authors were responsible for study selection, validity assessment and data extraction. All disagreements were resolved by discussion amongst the review team. Corresponding authors of included studies were contacted to obtain missing information. Nine RCTs with 571 participants were included in this review. All trials were at high risk of bias and a number of methodological limitations were identified. All trials had at least one

  8. Antiviral activity of viro care gz-08 against newcastle disease virus in poultry and its in-vitro cytotoxicity assay

    International Nuclear Information System (INIS)

    Rasool, M.H.; Afzal, A.M.

    2014-01-01

    Newcastle disease (ND), one of the most important disease of poultry throughout the World is caused by Newcastle Disease Virus (NDV). It is causing huge economic losses in poultry industry of Pakistan. Regardless of vaccination, other prevention and control measures are necessary to prevent ND outbreaks. Natural resources have been exploited to obtain antiviral compounds in several latest studies. In this study, the antiviral activity of Viro Care GZ-081 was checked up in-vitro, in-ovo and in-vivo. The cytotoxicity assay of the product was performed using Vero cell line. All the trials revealed that the stock solution and 1:2 dilution of GZ-08 had some antiviral activity as well as were cytotoxic. As the concentration decreased, cytotoxicity as well as antiviral activities were lost. Based on these findings, it was concluded that GZ-08 sanitizer or spray can be used as antiviral agent to clean or disinfect some non-living surfaces against different viruses in general and NDV in particular. However, in-vivo use of GZ-08 in poultry against NDV is recommended only as pre-treatment with ND vaccines as it significantly reduced morbidity and mortality as compared to the use of vaccines alone. However, further work is recommended in future on GZ-08 for its use as post-treatment of ND as well as on other antiviral compounds of natural origin to develop a novel antiviral drug against NDV in poultry. (author)

  9. Parent perspectives on the decision to initiate medication treatment of attention-deficit/hyperactivity disorder.

    Science.gov (United States)

    Coletti, Daniel J; Pappadopulos, Elizabeth; Katsiotas, Nikki J; Berest, Alison; Jensen, Peter S; Kafantaris, Vivian

    2012-06-01

    Despite substantial evidence supporting the efficacy of stimulant medication for children with attention-deficit/hyperactivity disorder (ADHD), adherence to stimulant treatment is often suboptimal. Applying social/cognitive theories to understanding and assessing parent attitudes toward initiating medication may provide insight into factors influencing parent decisions to follow ADHD treatment recommendations. This report describes results from formative research that used focus groups to obtain parent input to guide development of a provider-delivered intervention to improve adherence to stimulants. Participants were caregivers of children with ADHD who were given a stimulant treatment recommendation. Focus groups were recorded and transcribed verbatim. Data were analyzed by inductive, grounded theory methods as well as a deductive analytic strategy using an adapted version of the Unified Theory of Behavior Change to organize and understand parent accounts. Five groups were conducted with 27 parents (mean child age=9.35 years; standard deviation [SD]=2.00), mean time since diagnosis=3.33 years (SD=2.47). Most parents (81.5%) had pursued stimulant treatment. Inductive analysis revealed 17 attitudes facilitating adherence and 25 barriers. Facilitators included parent beliefs that medication treatment resulted in multiple functional gains and that treatment was imperative for their children's safety. Barriers included fears of personality changes and medication side effects. Complex patterns of parent adherence to medication regimens were also identified, as well as preferences for psychiatrists who were diagnostically expert, gave psychoeducation using multiple modalities, and used a chronic illness metaphor to explain ADHD. Theory-based analyses revealed conflicting expectancies about treatment risks and benefits, significant family pressures to avoid medication, guilt and concern that their children required medication, and distorted ideas about treatment risks

  10. Tobacco Dependence Treatment Grants: A Collaborative Approach to the Implementation of WHO Tobacco Control Initiatives

    Directory of Open Access Journals (Sweden)

    Margaret B. Nolan

    2018-01-01

    Full Text Available The number of global tobacco-related deaths is projected to increase from about 6 million to 8 million annually by 2030, with more than 80% of these occurring in low- and middle-income countries (LMICs. The World Health Organization Framework Convention on Tobacco Control (FCTC came into force in 2005 and Article 14 relates specifically to the treatment of tobacco dependence. However, LMICs, in particular, face several barriers to implementing tobacco dependence treatment. This paper is a descriptive evaluation of a novel grant funding mechanism that was initiated in 2014 to address these barriers. Global Bridges. Healthcare Alliance for Tobacco Dependence Treatment aims to create and mobilize a global network of healthcare professionals and organizations dedicated to advancing evidence-based tobacco dependence treatment and advocating for effective tobacco control policy. A 2014 request for proposals (RFP focused on these goals, particularly in LMICs, where funding for this work had been previously unavailable. 19 grants were awarded by Global Bridges to organizations in low- and middle-income countries across all six WHO regions. Virtually all focused on developing a tobacco dependence treatment curriculum for healthcare providers, while also influencing the political environment for Article 14 implementation. As a direct result of these projects, close to 9,000 healthcare providers have been trained in tobacco dependence treatment and an estimated 150,000 patients have been offered treatment. Because most of these projects are designed with a “train-the-trainer” component, two years of grant funding has been a tremendous catalyst for accelerating change in tobacco dependence treatment practices throughout the world. In order to foster such exponential growth and continue to maintain the impact of these projects, ongoing financial, educational, and professional commitments are required.

  11. Hemodilution after Initial Treatment in Patients with Acute Decompensated Heart Failure.

    Science.gov (United States)

    Fujita, Teppei; Inomata, Takayuki; Yazaki, Mayu; Iida, Yuichiro; Kaida, Toyoji; Ikeda, Yuki; Nabeta, Takeru; Ishii, Shunsuke; Maekawa, Emi; Yanagisawa, Tomoyoshi; Koitabashi, Toshimi; Takeuchi, Ichiro; Ako, Junya

    2018-05-09

    Decongestion is an important goal of heart failure (HF) management. Blood cell concentration is a recognized indicator for guiding decongestive treatment for HF. We aimed to assess the clinical impact of hemodilution and hemoconcentration after initial treatment in acute decompensated HF (ADHF) patients. We retrospectively evaluated hemoglobin levels and body weight obtained before admission, on admission, 3 days after admission, and at discharge in 102 consecutive patients admitted with ADHF. Patients were then stratified into hemodilution (n = 55) and hemoconcentration (n = 47) groups based on whether their hemoglobin levels decreased or increased, respectively, during the first 3 days after admission. From before admission to admission, hemoglobin levels decreased less in the hemodilution group (-0.16 ± 0.98 g/dL) than in the hemoconcentration group (-0.88 ± 1.11 g/dL) (P < 0.001); however, there was no significant difference in body weight (P≥ 0.05). More patients in the hemodilution group (85%) had grade III/IV pulmonary edema (Turner's criteria) compared with the hemoconcentration group (63%) (P < 0.01). Rate of readmission for HF within 180 days of discharge was higher in the hemodilution group (34%) compared with the hemoconcentration group (9%) (P < 0.01). Hemodilution after initial treatment for ADHF was associated with severe pulmonary edema at admission and higher readmission rates.

  12. Antiviral Defense Mechanisms in Honey Bees

    Science.gov (United States)

    Brutscher, Laura M.; Daughenbaugh, Katie F.; Flenniken, Michelle L.

    2015-01-01

    Honey bees are significant pollinators of agricultural crops and other important plant species. High annual losses of honey bee colonies in North America and in some parts of Europe have profound ecological and economic implications. Colony losses have been attributed to multiple factors including RNA viruses, thus understanding bee antiviral defense mechanisms may result in the development of strategies that mitigate colony losses. Honey bee antiviral defense mechanisms include RNA-interference, pathogen-associated molecular pattern (PAMP) triggered signal transduction cascades, and reactive oxygen species generation. However, the relative importance of these and other pathways is largely uncharacterized. Herein we review the current understanding of honey bee antiviral defense mechanisms and suggest important avenues for future investigation. PMID:26273564

  13. Antiviral Activity of Polyacrylic and Polymethacrylic Acids

    Science.gov (United States)

    De Somer, P.; De Clercq, E.; Billiau, A.; Schonne, E.; Claesen, M.

    1968-01-01

    Polyacrylic acid (PAA) and polymethacrylic acid (PMAA) were investigated for their antiviral properties in tissue culture. Compared to other related polyanions, as dextran sulfate, polystyrene sulfonate, polyvinyl sulfate, and polyphloroglucinol phosphate, PAA and PMAA were found to be significantly more antivirally active and less cytotoxic. PMAA added 24 hr prior to virus inoculation inhibited viral growth most efficiently but it was still effective when added 3 hr after infection. Neither a direct irreversible action on the virus nor inhibition of virus penetration into the cell could explain the antiviral activity of PMAA. PMAA inhibited the adsorption of the virus to the host cell and suppressed the one-cycle viral synthesis in tissue cultures inoculated with infectious RNA. PMID:4302187

  14. [Impact of care pathway on the delay for initiation of antituberculosis treatment in Conakry, Guinea].

    Science.gov (United States)

    Camara, A; Bah-Sow, O Y; Baldé, N M; Camara, L M; Barry, I S; Bah, B; Diallo, M; Chaperon, J; Riou, F

    2009-06-01

    Complex care pathways can result in detrimental treatment delay particularly in tuberculosis patients. The purpose of this retrospective study was to assess the care pathways followed by tuberculosis patients prior to diagnosis and to assess impact on the delay for initiation of treatment in Conakry, Guinea. A total of 112 patients were interviewed at the time of first admission for pulmonary tuberculosis with positive bacilloscopy. Based on interview data, pathways were classified as conventional (use of health care facilities only) and mixed (use of health care facilities, self-medication, and traditional medicine). The correlation between patient characteristics and type of pathway was assessed by univariate and multivariate analysis and the two groups, i.e., conventional vs. mixed, were compared with regard to delay for initiation of treatment. The care pathway was classified as mixed in two out of three patients. Multivariate analysis showed that this type of pathway was only correlated with schooling (p=0.02). The mean delay for treatment was similar, i.e., 13.4 and 12.8 weeks for conventional and mixed pathways respectively (p<0.68). The percentage of pathways including three consultations at health care facilities was significantly higher in the conventional than mixed group (72% vs. 30%, p<0.001). The main reasons given for delayed use of health care facilities were poor knowledge of tuberculosis symptoms (26%) and high cost of care (12%). The findings of this study indicate that tuberculosis patients follow a variety of care pathways that can lead to delayed treatment. An information campaign is needed to increase awareness among the population and care providers.

  15. Overall response rates to radiation therapy for patients with painful uncomplicated bone metastases undergoing initial treatment and retreatment

    International Nuclear Information System (INIS)

    Bedard, Gillian; Hoskin, Peter; Chow, Edward

    2014-01-01

    Introduction: Radiation therapy has been shown to successfully palliate bone metastases. A number of systematic reviews and large clinical trials have reported response rates for initial treatment and retreatment. Objective: To determine overall response rates of patients with painful uncomplicated bone metastases undergoing initial treatment and retreatment. Methods: Intent-to-treat and evaluable patient statistics from a systematic review of palliative radiotherapy trials for initial treatment of bone metastases and a randomized clinical trial of retreatment were pooled and analyzed to determine the overall response rates for patients receiving initial treatment and retreatment. Results: In the intent-to-treat calculation, 71–73% of patients had an overall response to radiation treatment and in the evaluable patient population; 85–87% of patients did so. Response rates varied slightly whether patients underwent single or multiple fractions in initial treatment or retreatment. Conclusions: Single and multiple fraction radiation treatment yielded very similar overall response rates. Patients treated with a single fraction for both initial and repeat radiation experience almost identical overall response to those patients treated with multiple fraction treatment. It is therefore recommended that patients with uncomplicated painful bone metastases be treated with a single 8 Gy fraction of radiation at both the initial treatment and retreatment

  16. Initiating antiretroviral therapy for HIV at a patient's first clinic visit: a cost-effectiveness analysis of the rapid initiation of treatment randomized controlled trial.

    Science.gov (United States)

    Long, Lawrence C; Maskew, Mhairi; Brennan, Alana T; Mongwenyana, Constance; Nyoni, Cynthia; Malete, Given; Sanne, Ian; Fox, Matthew P; Rosen, Sydney

    2017-07-17

    Determine the cost and cost-effectiveness of single-visit (same-day) antiretroviral treatment (ART) initiation compared to standard of care initiation. Cost-effectiveness analysis of individually randomized (1 : 1) pragmatic trial of single-visit initiation, which increased viral suppression at 10 months by 26% [relative risk (95% confidence interval) 1.26 (1.05-1.50)]. Primary health clinic in Johannesburg, South Africa. HIV positive, adult, nonpregnant patients not yet on ART or known to be eligible who presented at the clinic 8 May 2013 to 29 August 2014. Same-day ART initiation using point-of-care laboratory instruments and accelerated clinic procedures to allow treatment-eligible patients to receive antiretroviral medications at the same visit as testing HIV positive or having an eligible CD4 cell count. Comparison was to standard of care ART initiation, which typically required three to five additional clinic visits. Average cost per patient enrolled and per patient achieving the primary outcome of initiated 90 days or less and suppressed 10 months or less, and production cost per patient achieving primary outcome (all costs per primary outcome patients). The average cost per patient enrolled, per patient achieving the primary outcome, and production cost were $319, $487, and $738 in the standard arm and $451, $505, and $707 in the rapid arm. Same-day treatment initiation was more effective than standard initiation, more expensive per patient enrolled, and less expensive to produce a patient achieving the primary outcome. Omitting point-of-care laboratory tests at initiation and focusing on high-volume clinics have the potential to reduce costs substantially and should be evaluated in routine settings.

  17. Regulatory T cells predict the time to initial treatment in early stage chronic lymphocytic leukemia.

    Science.gov (United States)

    Weiss, Lukas; Melchardt, Thomas; Egle, Alexander; Grabmer, Christoph; Greil, Richard; Tinhofer, Inge

    2011-05-15

    Early stage chronic lymphocytic leukemia is characterized by a highly variable course of disease. Because it is believed that regulatory T cells (T(regs) ) are potent suppressors of antitumor immunity, the authors hypothesized that increased T(regs) may favor disease progression. T(reg) levels (cluster of differentiation 3 [CD3]-positive, [CD4]-positive, CD25-positive, and CD127-negative) in peripheral blood from 102 patients were analyzed by flow cytometry. Statistical analysis was used to evaluate correlations with clinical data. The relative T(reg) numbers in CD4-positive T cells were significantly greater in patients with chronic lymphocytic leukemia compared with the numbers in a control group of 170 healthy individuals (P = .001). Patients were divided into 2 groups using a median T(reg) value of 9.7% (the percentage of CD4-positive T cells). Patients with higher T(reg) levels had a significantly shorter time to initial treatment (median, 5.9 years) compared with patients who had lower T(reg) levels (median, 11.7 years; log-rank P = .019). Furthermore, T(reg) levels (the percentage of CD4-positive T cells) had significant prognostic power to predict the time to initial treatment in univariate analysis (P = .023) and in multivariate Cox regression analysis that included the variables Rai stage, immunoglobulin heavy-chain variable region gene mutational status, chromosomal aberrations, and CD38 expression (P = .028). Higher T(reg) levels had significant and independent prognostic power for predicting the time to initial treatment in patients with low to intermediate stage chronic lymphocytic leukemia. 2010 American Cancer Society.

  18. Removal of the antiviral agent oseltamivir and its biological activity by oxidative processes

    International Nuclear Information System (INIS)

    Mestankova, Hana; Schirmer, Kristin; Escher, Beate I.; Gunten, Urs von

    2012-01-01

    The antiviral agent oseltamivir acid (OA, the active metabolite of Tamiflu ® ) may occur at high concentrations in wastewater during pandemic influenza events. To eliminate OA and its antiviral activity from wastewater, ozonation and advanced oxidation processes were investigated. For circumneutral pH, kinetic measurements yielded second-order rate constants of 1.7 ± 0.1 × 10 5 and 4.7 ± 0.2 × 10 9 M −1 s −1 for the reaction of OA with ozone and hydroxyl radical, respectively. During the degradation of OA by both oxidants, the antiviral activity of the treated aqueous solutions was measured by inhibition of neuraminidase activity of two different viral strains. A transient, moderate (two-fold) increase in antiviral activity was observed in solutions treated up to a level of 50% OA transformation, while for higher degrees of transformation the activity corresponded to that caused exclusively by OA. OA was efficiently removed by ozonation in a wastewater treatment plant effluent, suggesting that ozonation can be applied to remove OA from wastewater. - Highlights: ► Oseltamivir acid (OA) is oxidized by ozone and hydroxyl radical. ► Kinetics: We determined rate constants for the reaction with these oxidants. ► The specific activity of OA as neuraminidase inhibitor disappeared during oxidation. ► Ozonation and advanced oxidation can effectively remove OA from wastewaters. - Ozone and hydroxyl radical treatment processes can degrade aqueous oseltamivir acid and remove its antiviral activity.

  19. Antiviral Activity of Lambda Interferon in Chickens

    Science.gov (United States)

    Reuter, Antje; Soubies, Sebastien; Härtle, Sonja; Schusser, Benjamin; Kaspers, Bernd

    2014-01-01

    Interferons (IFNs) are essential components of the antiviral defense system of vertebrates. In mammals, functional receptors for type III IFN (lambda interferon [IFN-λ]) are found mainly on epithelial cells, and IFN-λ was demonstrated to play a crucial role in limiting viral infections of mucosal surfaces. To determine whether IFN-λ plays a similar role in birds, we produced recombinant chicken IFN-λ (chIFN-λ) and we used the replication-competent retroviral RCAS vector system to generate mosaic-transgenic chicken embryos that constitutively express chIFN-λ. We could demonstrate that chIFN-λ markedly inhibited replication of various virus strains, including highly pathogenic influenza A viruses, in ovo and in vivo, as well as in epithelium-rich tissue and cell culture systems. In contrast, chicken fibroblasts responded poorly to chIFN-λ. When applied in vivo to 3-week-old chickens, recombinant chIFN-λ strongly induced the IFN-responsive Mx gene in epithelium-rich organs, such as lungs, tracheas, and intestinal tracts. Correspondingly, these organs were found to express high transcript levels of the putative chIFN-λ receptor alpha chain (chIL28RA) gene. Transfection of chicken fibroblasts with a chIL28RA expression construct rendered these cells responsive to chIFN-λ treatment, indicating that receptor expression determines cell type specificity of IFN-λ action in chickens. Surprisingly, mosaic-transgenic chickens perished soon after hatching, demonstrating a detrimental effect of constitutive chIFN-λ expression. Our data highlight fundamental similarities between the IFN-λ systems of mammals and birds and suggest that type III IFN might play a role in defending mucosal surfaces against viral intruders in most if not all vertebrates. PMID:24371053

  20. Early, patient-initiated treatment of herpes labialis with topical 10% acyclovir.

    Science.gov (United States)

    Spruance, S L; Crumpacker, C S; Schnipper, L E; Kern, E R; Marlowe, S; Arndt, K A; Overall, J C

    1984-01-01

    To determine whether topical acyclovir in polyethylene glycol could reduce the severity of herpes simplex labialis if applied immediately after onset of a recurrence, 10% acyclovir in polyethylene glycol ointment or polyethylene glycol alone was prospectively dispensed to 352 patients in a double-blind, randomized trial. Sixty-nine subjects initiated treatment in the prodrome (57%) or erythema (43%) stage and were followed by clinical and virological criteria. The healing time (6.0 days), maximum lesion area (42 mm2), vesicle or ulcer formation (91%), and maximum lesion virus titer (4.8 log10 PFU) in the drug recipients were not reduced in comparison with those who received the vehicle (5.2 days, 30 mm2, 75%, and 4.5 log10 PFU, respectively). Topical acyclovir in polyethylene glycol was ineffective for the treatment of herpes labialis despite an optimum therapeutic opportunity. PMID:6732224

  1. Lung Metastasis of Primary Alveolar Soft-Part Sarcoma Occurring 20 Years after Initial Treatment

    Directory of Open Access Journals (Sweden)

    R. F. Falkenstern-Ge

    2013-01-01

    Full Text Available A 30-year old woman was referred to our center because of suspicion of a primary lung tumor of the right upper lobe. Histological examination of the lung lesion revealed lung metastasis of a previously treated alveolar soft part sarcoma of the musculus vastus medialis of the right femur, which was resected 20 years ago. Alveolar soft-part sarcoma is a rare malignant tumor that occurs most often in the soft tissue of lower limbs. It is a slow-growing malignant soft tissue tumor arising in muscle tissue, usually in young adults. Due to pleural and extensive mediastinal infiltration with bilateral lung metastases, a systemic treatment with chemotherapy doxorubicin and ifosfamide was initiated. Late metastases from previously treated alveolar part sarcoma should be considered in patients with suspicious lung lesions even if surgical treatment was performed a long time ago.

  2. Initial cathode processing experiences and results for the treatment of spent fuel

    International Nuclear Information System (INIS)

    Westphal, B.R.; Laug, D.V.; Brunsvold, A.R.; Roach, P.D.

    1996-01-01

    As part of the spent fuel treatment demonstration at Argonne National Laboratory, a vacuum distillation process is being employed for the recovery of uranium following an electrorefining process. Distillation of a salt electrolyte, primarily consisting of a eutectic mixture of lithium and potassium chlorides, from uranium is achieved by a batch operation termed ''cathode processing.'' Cathode processing is performed in a retort furnace which enables the production of a stable uranium product that can be isotopically diluted and stored. To date, experiments have been performed with two distillation units; one for prototypical testing and the other for actual spent fuel treatment operations. The results and experiences from these initial experiments with both units will be discussed as well as problems encountered and their resolution

  3. Pubertal development among girls with classical congenital adrenal hyperplasia initiated on treatment at different ages

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    Bindu Kulshreshtha

    2012-01-01

    Full Text Available Introduction: Children with congenital adrenal hyperplasia (CAH provide us an opportunity to study the clinical effects of androgen excess in humans. We studied the sequence of pubertal development in girls with congenital adrenal hyperplasia initiated on treatment at different ages, to assess the effects of androgen exposure on the Hypothalamic-Pituitary-Ovarian (HPO axis. Materials and Methods: Girls more than 18 years of age, with CAH, on follow-up at this hospital were the subjects for this study. Details of history, physical findings, laboratory evaluation, and medication were noted from their case records and verified from the patients and their / parents, in addition to assessment of their present health status. Result: We studied 24 patients of classical CAH (SW-2, SV-22, average age - 24.5 ± 6.6 years. All had varying degrees of genital ambiguity (Prader stage 3 (n = 13, Prader stage 2 (n = 10, Prader stage 1 (n = 1. Among them were13 girls, who were started on steroids after eight years of age. Girls who received treatment from infancy and early childhood had normal pubertal development (mean age at menarche 11.4 ± 1.7 years. Hirsutism was not a problem among them. Untreated children had progressive clitoral enlargement throughout childhood, developed pubic hair at around three to six years of age, and facial hair between nine and eleven years. Plasma testosterone ranged from 3 to 6 ng / ml prior to treatment. Six of the 13 untreated CAH girls had subtle breast development starting at ages 11 - 16 years and three had spontaneous infrequent vaginal bleeding starting at ages 11 - 17. Steroid supplementation initiated pubertal changes in older girls in two-to-six months′ time. Conclusion: There was a delay in HPO axis maturation (as evidenced by delayed pubertal development in the absence of treatment in girls with CAH. This could be corrected with steroid supplementation.

  4. Antiviral Activity of Natural Products Extracted from Marine Organisms

    Directory of Open Access Journals (Sweden)

    Sobia Tabassum

    2011-11-01

    Full Text Available Many epidemics have broken out over the centuries. Hundreds and thousands of humans have died over a disease. Available treatments for infectious diseases have always been limited. Some infections are more deadly than the others, especially viral pathogens. These pathogens have continuously resisted all kinds of medical treatment, due to a need for new treatments to be developed. Drugs are present in nature and are also synthesized in vitro and they help in combating diseases and restoring health. Synthesizing drugs is a hard and time consuming task, which requires a lot of man power and financial aid. However, the natural compounds are just lying around on the earth, may it be land or water. Over a thousand novel compounds isolated from marine organisms are used as antiviral agents. Others are being pharmacologically tested. Today, over forty antiviral compounds are present in the pharmacological market. Some of these compounds are undergoing clinical and pre-clinical stages. Marine compounds are paving the way for a new trend in modern medicine.

  5. Bioprospecting of Red Sea Sponges for Novel Antiviral Pharmacophores

    KAUST Repository

    O'Rourke, Aubrie

    2015-01-01

    the coast of Saudi Arabia serves as a newly accessible location, which provides the opportunity to bioprospect marine sponges with the purpose of identifying novel antiviral scaffolds. Antivirals are underrepresented in present day clinical trials, as well

  6. The long-term prognosis for live birth in couples initiating fertility treatments.

    Science.gov (United States)

    Malchau, S S; Henningsen, A A; Loft, A; Rasmussen, S; Forman, J; Nyboe Andersen, A; Pinborg, A

    2017-07-01

    What are the long-term chances of having a child for couples starting fertility treatments and how many conceive with ART, IUI and without treatment? Total 5-year live birthrates were strongly influenced by female age and ranged from 80% in women under 35-26% in women ≥40 years, overall, 14% of couples conceived naturally and one-third of couples starting treatments with intrauterine insemination delivered from that treatment. Few studies report success rates in fertility treatments across a couple's complete fertility treatment history, across clinics, evaluating live births after insemination, ART and natural conceptions. This register-based national cohort study from Denmark includes all women initiating fertility treatments in public and private clinics with homologous gametes in 2007-2010. Women were identified in the Danish ART Registry and were cross-linked with the Medical Birth Registry to identify live births. Subfertile couples were followed 2 years (N = 19 884), 3 years (N = 14 445) and 5 years (N = 5165), or until their first live birth. Cumulative live birthrates were estimated 2, 3 and 5 years from the first treatment cycle, in all women, including drop-outs. Birthrates were stratified by type of first treatment (ART/IUI), mode of conception (ART/IUI/natural conception) and female age. Within 5 years, in women aged years (N = 3553), 35-39 years (N = 1156) and ≥40 years (N = 451), a total of 64%, 49% and 16% had a live birth due to treatment, respectively. Additionally, in women aged years, 35-39 years and ≥40 years, 16%, 11% and 10% delivered after natural conception, yielding total 5-year birthrates of 80%, 60% and 26%. In women starting treatments with IUI (N = 3028), 35% delivered after IUI within 5 years, 24% delivered after shift to ART treatments and 17% delivered after natural conception. Within 5 years from starting treatments with ART (N = 2137), 53% delivered after ART, 11% delivered after natural conception and 0.6% delivered after

  7. Initial development of a treatment adherence measure for cognitive-behavioral therapy for child anxiety.

    Science.gov (United States)

    Southam-Gerow, Michael A; McLeod, Bryce D; Arnold, Cassidy C; Rodríguez, Adriana; Cox, Julia R; Reise, Steven P; Bonifay, Wesley E; Weisz, John R; Kendall, Philip C

    2016-01-01

    The measurement of treatment adherence (a component of treatment integrity defined as the extent to which a treatment is delivered as intended) is a critical element in treatment evaluation research. This article presents initial psychometric data for scores on the Cognitive-Behavioral Therapy Adherence Scale for Youth Anxiety (CBAY-A), an observational measure designed to be sensitive to common practice elements found in individual cognitive-behavioral therapy (ICBT) for youth anxiety. Therapy sessions (N = 954) from 1 efficacy and 1 effectiveness study of ICBT for youth anxiety were independently rated by 2 coders. Interrater reliability (as gauged by intraclass correlation coefficients) for the item scores averaged 0.77 (SD = 0.15; range .48 to .80). The CBAY-A item and scale (skills, model, total) scores demonstrated evidence of convergent and discriminant validity with an observational measure of therapeutic interventions and an observational measure of the alliance. The CBAY-A item and scale scores also discriminated between therapists delivering ICBT in research and practice settings and therapists delivering nonmanualized usual clinical care. We discuss the importance of replicating these psychometric findings in different samples and highlight possible application of an adherence measure in testing integrity-outcome relations. (c) 2016 APA, all rights reserved).

  8. SOME ASPECTS OF THE MARKETING STUDIES FOR THE PHARMACEUTICAL MARKET OF ANTIVIRAL DRUGS

    Directory of Open Access Journals (Sweden)

    A. G. Salnikova

    2015-01-01

    Full Text Available Antiviral drugs are widely used in medicinal practice. They suppress the originator and stimulate the protection of an organism. The drugs are used for the treatment of flu and ARVI, herpetic infections, virus hepatitis, HIV-infection. Contemporary pharmaceutical market is represented by a wide range of antiviral drugs. Marketing studies are conducted to develop strategies, used for the enhancement of pharmacy organization activity efficiency. Conduction of the marketing researches of pharmaceutical market is the purpose of this study. We have used State Registry of Drugs, State Record of Drugs, List of vital drugs, questionnaires of pharmaceutical workers during our work. Historical, sociological, mathematical methods, and a method of expert evaluation were used in the paper. As the result of the study we have made the following conclusions. We have studied and generalized the literature data about classification and application of antiviral drugs, marketing, competition. The assortment of antiviral drugs on the pharmaceutical market of the Russian Federation was also studied. We have conducted an analysis for the obtainment of the information about antiviral drugs by pharmaceutical workers. We have determined the competitiveness of antiviral drugs, and on the basis of the research conducted we have submitted an offer for pharmaceutical organizations to form the range of antiviral drugs.

  9. Undesirable financial effects of head and neck cancer radiotherapy during the initial treatment period

    Directory of Open Access Journals (Sweden)

    Helen Egestad

    2015-01-01

    Full Text Available Background: Healthcare cost and reforms are at the forefront of international debates. One of the current discussion themes in oncology is whether and how patients’ life changes due to costs of cancer care. In Norway, the main part of the treatment costs is supported by general taxpayer revenues. Objectives: The objective of this study was to clarify whether head and neck cancer patients (n=67 in northern Norway experienced financial health-related quality of life (HRQOL deterioration due to costs associated with treatment. Design: HRQOL was examined by the European Organization for Research and Treatment of Cancer (EORTC QLQ-C30 in the beginning and in the end of radiation treatment in patients treated at the University Hospital in Northern Norway. Changes in financial HRQOL were calculated and compared by paired sample T-tests. Multiple regression analyses were used to examine correlations among gender, marital status, age and treatment with or without additional chemotherapy and changes in the HRQOL domain of financial difficulties. Results: The majority of score results at both time points were in the lower range (mean 15–25, indicating limited financial difficulties. We observed no statistically significant differences by gender, marital status and age. Increasing financial difficulties during treatment were reported by male patients and those younger than 65, that is, patients who were younger than retirement age. The largest effect was seen in singles. However, differences were not statistically significant. Conclusions: During the initial phase of the disease trajectory, no significant increase in financial difficulties was found. This is in line with the aims of the Norwegian public healthcare model. However, long-term longitudinal studies should be performed, especially with regard to the trends we observed in single, male and younger patients.

  10. Initiation and persistence with clopidogrel treatment after acute myocardial infarction: a nationwide study

    DEFF Research Database (Denmark)

    Sørensen, Rikke; Gislason, G H; Fosbøl, E L

    2008-01-01

    AIMS: To identify possible underuse by analysing initiation and persistence with clopidogrel treatment in an unselected population of patients admitted with myocardial infarction (MI) with or without subsequent percutaneous coronary intervention (PCI). METHODS: Patients admitted with first-time MI...... proportional hazard models. RESULTS: A total of 46,190 MI patients were included in the study, of whom 14,939 were treated with PCI. From 2000 to 2005 initiation of clopidogrel increased from 80.4 to 93.7% among MI patients with PCI and from 2.8 to 39.3% among MI patients without PCI. MI patients...... with concomitant heart failure received less treatment [odds ratio (OR) 0.49, confidence interval (CI) 0.43, 0.56 among patients with PCI and OR 0.90, CI 0.81, 0.99 among patients without PCI in 2002-2003, and OR 0.89, CI 0.80, 1.00 in 2004-2005, respectively]. Of MI patients with PCI, 77.5% completed 9 months...

  11. Spinal epidural neurostimulation for treatment of acute and chronic intractable pain: initial and long term results.

    Science.gov (United States)

    Richardson, R R; Siqueira, E B; Cerullo, L J

    1979-09-01

    Spinal epidural neurostimulation, which evolved from dorsal column stimulation, has been found to be effective in the treatment of acute and chronic intractable pain. Urban and Hashold have shown that it is a safe, simplified alternative to dorsal column stimulation, especially because laminectomy is not required if the electrodes are inserted percutaneously. Percutaneous epidural neurostimulation is also advantageous because there can be a diagnostic trial period before permanent internalization and implantation. This diagnostic and therapeutic modality has been used in 36 patients during the past 3 years at Northwestern Memorial Hospital. Eleven of these patients had acute intractable pain, which was defined as pain of less than 1 year in duration. Initial postimplantation results from the 36 patients indicate that spinal epidural neurostimulation is most effective in treating the intractable pain of diabetes, arachnoiditis, and post-traumatic and postamputation neuroma. Long term follow-up, varying from 1 year to 3 years postimplantation in the 20 initially responding patients, indicates that the neurostimulation continues to provide significant pain relief (50% or greater) in a majority of the patients who experienced initial significant pain relief.

  12. Initial Treatment for Nonsyndromic Early-Life Epilepsy: An Unexpected Consensus.

    Science.gov (United States)

    Shellhaas, Renée A; Berg, Anne T; Grinspan, Zachary M; Wusthoff, Courtney J; Millichap, John J; Loddenkemper, Tobias; Coryell, Jason; Saneto, Russell P; Chu, Catherine J; Joshi, Sucheta M; Sullivan, Joseph E; Knupp, Kelly G; Kossoff, Eric H; Keator, Cynthia; Wirrell, Elaine C; Mytinger, John R; Valencia, Ignacio; Massey, Shavonne; Gaillard, William D

    2017-10-01

    There are no evidence-based guidelines on the preferred approach to treating early-life epilepsy. We examined initial therapy selection in a contemporary US cohort of children with newly diagnosed, nonsyndromic, early-life epilepsy (onset before age three years). Seventeen pediatric epilepsy centers participated in a prospective cohort study of children with newly diagnosed epilepsy with onset under 36 months of age. Details regarding demographics, seizure types, and initial medication selections were obtained from medical records. About half of the 495 enrolled children with new-onset, nonsyndromic epilepsy were less than 12 months old at the time of diagnosis (n = 263, 53%) and about half (n = 260, 52%) had epilepsy with focal features. Of 464 who were treated with monotherapy, 95% received one of five drugs: levetiracetam (n = 291, 63%), oxcarbazepine (n = 67, 14%), phenobarbital (n = 57, 12%), topiramate (n = 16, 3.4%), and zonisamide (n = 13, 2.8%). Phenobarbital was prescribed first for 50 of 163 (31%) infants less than six months old versus seven of 300 (2.3%) of children six months or older (P epilepsy presentation (focal, generalized, mixed/uncertain). Between the first and second treatment choices, 367 (74%) of children received levetiracetam within the first year after diagnosis. Without any specific effort, the pediatric epilepsy community has developed an unexpectedly consistent approach to initial treatment selection for early-life epilepsy. This suggests that a standard practice is emerging and could be utilized as a widely acceptable basis of comparison in future drug studies. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Organized Chronic Subdural Hematomas Treated by Large Craniotomy with Extended Membranectomy as the Initial Treatment

    Science.gov (United States)

    Balevi, Mustafa

    2017-01-01

    Objective: The aim of this retrospective study is to evaluate the efficacy and incidence of complications of craniotomy and membranectomy in elderly patients for the treatment of organized chronic subdural hematoma (OCSH). Materials and Methods: We retrospectively reviewed a series of 28 consecutive patients suffering from OCSH, diagnosed by magnetic resonance imaging (MRI) or computer tomography (CT) to establish the degree of organization and determine the intrahematomal architecture including inner membrane ossification. The indication to perform a primary enlarged craniotomy as initial treatment for nonliquefied OCSH with multilayer loculations was based on the hematoma MRI appearance – mostly hyperintense in both T1- and T2-weighted images with a hypointense web- or net-like structure within the hematoma cavity or inner membrane calcification CT appearance - hyperdense. These cases have been treated by a large craniotomy with extended membranectomy as the initial treatment. However, the technique of a burr hole with closed system drainage for 24–72 h was chosen for cases of nonseptated and mostly liquefied Chronic Subdural Hematoma (CSDH). Results: Between 1998 and 2015, 148 consecutive patients were surgically treated for CSDH at our institution. Of these, 28 patients which have OSDH underwent a large craniotomy with extended membranectomy as the initial treatment. The average age of the patients was 69 (69.4 ± 12.1). Tension pneumocephalus (TP) has occurred in 22.8% of these patients (n = 28). Recurring subdural hemorrhage (RSH) in the operation area has occurred in 11.9% of these patients in the first 24 h. TP with RSH was seen in 4 of 8 TP patients (50%). Large epidural air was seen in one case. Postoperative seizures requiring medical therapy occurred in 25% of our patients. The average stay in the department of neurosurgery was 11 days, ranging from 7 to 28 days. Four patients died within 28 days after surgery; mortality rate was 14.28%. Conclusion

  14. Community-based MDR-TB care project improves treatment initiation in patients diagnosed with MDR-TB in Myanmar.

    Science.gov (United States)

    Wai, Pyae Phyo; Shewade, Hemant Deepak; Kyaw, Nang Thu Thu; Thein, Saw; Si Thu, Aung; Kyaw, Khine Wut Yee; Aye, Nyein Nyein; Phyo, Aye Mon; Maung, Htet Myet Win; Soe, Kyaw Thu; Aung, Si Thu

    2018-01-01

    The Union in collaboration with national TB programme (NTP) started the community-based MDR-TB care (CBMDR-TBC) project in 33 townships of upper Myanmar to improve treatment initiation and treatment adherence. Patients with MDR-TB diagnosed/registered under NTP received support through the project staff, in addition to the routine domiciliary care provided by NTP staff. Each township had a project nurse exclusively for MDR-TB and 30 USD per month (max. for 4 months) were provided to the patient as a pre-treatment support. To assess whether CBMDR-TBC project's support improved treatment initiation. In this cohort study (involving record review) of all diagnosed MDR-TB between January 2015 and June 2016 in project townships, CBMDR-TBC status was categorized as "receiving support" if date of project initiation in patient's township was before the date of diagnosis and "not receiving support", if otherwise. Cox proportional hazards regression (censored on 31 Dec 2016) was done to identify predictors of treatment initiation. Of 456 patients, 57% initiated treatment: 64% and 56% among patients "receiving support (n = 208)" and "not receiving support (n = 228)" respectively (CBMDR-TBC status was not known in 20 (4%) patients due to missing diagnosis dates). Among those initiated on treatment (n = 261), median (IQR) time to initiate treatment was 38 (20, 76) days: 31 (18, 50) among patients "receiving support" and 50 (26,101) among patients "not receiving support". After adjusting other potential confounders (age, sex, region, HIV, past history of TB treatment), patients "receiving support" had 80% higher chance of initiating treatment [aHR (0.95 CI): 1.8 (1.3, 2.3)] when compared to patients "not receiving support". In addition, age 15-54 years, previous history of TB and being HIV negative were independent predictors of treatment initiation. Receiving support under CBMDR-TBC project improved treatment initiation: it not only improved the proportion initiated but also

  15. Antiviral Prophylaxis and H1N1

    Centers for Disease Control (CDC) Podcasts

    2011-07-14

    Dr. Richard Pebody, a consultant epidemiologist at the Health Protection Agency in London, UK, discusses the use of antiviral post-exposure prophylaxis and pandemic H1N1.  Created: 7/14/2011 by National Center for Emerging Zoonotic and Infectious Diseases (NCEZID).   Date Released: 7/18/2011.

  16. Generation of antiviral transgenic chicken using spermatogonial ...

    African Journals Online (AJOL)

    This study was conducted in order to generate anti-viral transgenic chickens through transfected spermatogonial stem cell with fusion gene EGFP-MMx. After injecting fusion gene EGFP-MMx into testes, tissues frozen section, polymerase chain reaction (PCR) and dot blot of testes was performed at 30, 40, 50, 60, 70 and 80 ...

  17. Quantitative Analysis of a Parasitic Antiviral Strategy

    OpenAIRE

    Kim, Hwijin; Yin, John

    2004-01-01

    We extended a computer simulation of viral intracellular growth to study a parasitic antiviral strategy that diverts the viral replicase toward parasite growth. This strategy inhibited virus growth over a wide range of conditions, while minimizing host cell perturbations. Such parasitic strategies may inhibit the development of drug-resistant virus strains.

  18. Glioblastoma multiforme (GBM) in the elderly: initial treatment strategy and overall survival.

    Science.gov (United States)

    Glaser, Scott M; Dohopolski, Michael J; Balasubramani, Goundappa K; Flickinger, John C; Beriwal, Sushil

    2017-08-01

    The EORTC trial which solidified the role of external beam radiotherapy (EBRT) plus temozolomide (TMZ) in the management of GBM excluded patients over age 70. Randomized studies of elderly patients showed that hypofractionated EBRT (HFRT) alone or TMZ alone was at least equivalent to conventionally fractionated EBRT (CFRT) alone. We sought to investigate the practice patterns and survival in elderly patients with GBM. We identified patients age 65-90 in the National Cancer Data Base (NCDB) with histologically confirmed GBM from 1998 to 2012 and known chemotherapy and radiotherapy status. We analyzed factors predicting treatment with EBRT alone vs. EBRT plus concurrent single-agent chemotherapy (CRT) using multivariable logistic regression. Similarly, within the EBRT alone cohort we compared CFRT (54-65 Gy at 1.7-2.1 Gy/fraction) to HFRT (34-60 Gy at 2.5-5 Gy/fraction). Multivariable Cox proportional hazards model (MVA) with propensity score adjustment was used to compare survival. A total of 38,862 patients were included. Initial treatments for 1998 versus 2012 were: EBRT alone = 50 versus 10%; CRT = 6 versus 50%; chemo alone = 1.6% (70% single-agent) versus 3.2% (94% single-agent). Among EBRT alone patients, use of HFRT (compared to CFRT) increased from 13 to 41%. Numerous factors predictive for utilization of CRT over EBRT alone and for HFRT over CFRT were identified. Median survival and 1-year overall survival were higher in the CRT versus EBRT alone group at 8.6 months vs. 5.1 months and 36.0 versus 15.7% (p GBM patients in the United States, CRT is the most common initial treatment and appears to offer a survival advantage over EBRT alone. Adoption of hypofractionation has increased over time but continues to be low.

  19. Effect of initial treatment in the preparation of natural indigo dye from Indigofera tinctoria

    Science.gov (United States)

    Purnama, Herry; Hidayati, Nur; Safitri, Dyah S.; Rahmawati, Sofia

    2017-06-01

    The current tinting industries return to the use of natural dyes because of their characteristics including safe and environmentally friendly. Indonesia can widely promote the potential of natural colours due to the availability of abundant natural dye plants. One of the potential plants that generates blue colour is Indigofera tinctoria. This research was conducted to improve the quality and quantity of natural indigo dye for batik production that supports the environment sustainability. The indigo dark blue paste was produced by initial treatment of soaking in cold water for 48 hours. The 48 hours fermentation anaerobic conditions reached optimum temperature, due to time and pH were also met by nutrients. Aeration was done in ten minutes using an aquarium air pump to increase mixing in water immersion with solution of calcium oxide. Indoxyl in the fermented leaves of Indigofera tinctoria is easily oxidized by air in alkali solution that will form pigment indigo. In that condition, lime (CaO) can be used in the manufacture of indigo paste. In this study, the higher concentrated of blue colour was achieved by lesser amount of lime. The soaking treatment in cold water produced high amount of dyes rather than the initial treatment by both hot water and grounding the indigo leaves. Analysis were done by using UV-Vis Spectrophotometry which showed the value of absorbance. The sample that was soaked in 5 liters of water added by a kilogram of Indigofera tinctoria leaves and 15 grams of lime for 48 hours, obtained the highest absorbance or concentration level. The application of the indigo dyes with or without mordanting agent was also tested for colour fastness.

  20. An initial experience using concurrent paclitaxel and radiation in the treatment of head and neck malignancies

    International Nuclear Information System (INIS)

    Tishler, Roy B.; Busse, Paul M.; Norris, Charles M.; Rossi, Rene; Poulin, Mark; Thornhill, Lee; Costello, Rosemary; Peters, Edward S.; Colevas, A. Dimitrios; Posner, Marshall R.

    1999-01-01

    Background: Combined modality therapy plays a central role in the management of head and neck malignancies. This study examined the feasibility and preliminary results of treating a group of patients using concurrent bolus paclitaxel (Taxol TM ) and radiation therapy. Methods: Fourteen patients with a median age of 56 years (range 42-81) were treated. Paclitaxel was given every 3 weeks at a dose of 100 mg/m 2 concurrently with external beam radiation. The patients treated included those who had failed to achieve a complete response (CR) to induction chemotherapy with cisplatin, 5-fluorouracil, and leucovorin (PFL), or who had locally advanced disease not previously treated. Results: Median follow-up from the initiation of treatment is 40 months (range 23-48). The majority of patients (13/14) achieved clinical CRs at the primary site. The development of responses was characterized by a long time course. Three patients who were nonresponders (NRs) to induction PFL chemotherapy were treated. One was a clinical CR at the primary site, one did not achieve a CR, and the other had residual disease in the neck. Four patients have failed, one with local-regional disease, one with a marginal failure, one with distant metastases, and one was not rendered disease-free by the treatment. As expected, significant local toxicity was observed. Most patients were managed with the aid of a percutaneous endoscopic gastrostomy (PEG). Two patients experienced significant moist desquamation and required treatment breaks of greater than 1 week. Conclusion: Paclitaxel can be given on a 3-week schedule at 100 mg/m 2 concurrently with radiation. The preliminary results indicate good local responses and acceptable toxicity. This treatment approach merits further study in the treatment of head and neck malignancies, and should be considered as an option in other sites

  1. Avanafil for the treatment of erectile dysfunction: initial data and clinical key properties.

    Science.gov (United States)

    Kedia, George T; Uckert, Stefan; Assadi-Pour, Farhang; Kuczyk, Markus A; Albrecht, Knut

    2013-02-01

    Orally active, selective inhibitors of phosphodiesterase type 5 (PDE 5, cyclic GMP PDE), such as sildenafil, tadalafil and vardenafil, are currently the first-choice treatment options for the clinical management of erectile dysfunction (ED) of various etiologies and severities. However, a significant number of patients remain dissatisfied with the available therapies due a lack of efficacy or discomfort arising from adverse events. Several new PDE5 inhibitors, among which are avanafil (TA-1790), lodenafil, mirodenafil, udenafil, SLX-2101, JNJ-10280205 and JNJ-10287069, have recently been approved and introduced into the market or are in the final stages of their clinical development. Avanafil (marketed in the US under the brand name STENDRA(™)) has been developed by VIVUS Inc. (Mountain View, CA, USA) and has recently received approval from the US Food and Drug Administration (FDA) for use in the treatment of male ED. The drug has demonstrated improved selectivity for PDE5, is rapidly absorbed after oral administration with a fast onset of action and a plasma half-life that is comparable to sildenfil and vardenafil. In phase II and phase III clinical trials that included a large number of patients, avanafil has been shown to be effective and well tolerated. Owing to its favorable pharmacodynamic and pharmacokinetic profile, avanafil is considered as a promising new option in the treatment of ED. The present article summarizes the initial data and clinical key properties of avanafil.

  2. Cytotoxic, Virucidal, and Antiviral Activity of South American Plant and Algae Extracts

    Directory of Open Access Journals (Sweden)

    Paula Faral-Tello

    2012-01-01

    Full Text Available Herpes simplex virus type 1 (HSV-1 infection has a prevalence of 70% in the human population. Treatment is based on acyclovir, valacyclovir, and foscarnet, three drugs that share the same mechanism of action and of which resistant strains have been isolated from patients. In this aspect, innovative drug therapies are required. Natural products offer unlimited opportunities for the discovery of antiviral compounds. In this study, 28 extracts corresponding to 24 plant species and 4 alga species were assayed in vitro to detect antiviral activity against HSV-1. Six of the methanolic extracts inactivated viral particles by direct interaction and 14 presented antiviral activity when incubated with cells already infected. Most interesting antiviral activity values obtained are those of Limonium brasiliense, Psidium guajava, and Phyllanthus niruri, which inhibit HSV-1 replication in vitro with 50% effective concentration (EC50 values of 185, 118, and 60 μg/mL, respectively. For these extracts toxicity values were calculated and therefore selectivity indexes (SI obtained. Further characterization of the bioactive components of antiviral plants will pave the way for the discovery of new compounds against HSV-1.

  3. Phytochemical screening, cytotoxicity and antiviral activity of hexane fraction of Phaleria macrocarpa fruits

    Science.gov (United States)

    Ismaeel, Mahmud Yusef Yusef; Yaacob, Wan Ahmad; Tahir, Mariya Mohd.; Ibrahim, Nazlina

    2015-09-01

    Phaleria macrocarpa fruits have been widely used in the traditional medicine for the treatment of several infections. The current study was done to determine the phytochemical content, cytotoxicity and antiviral activity of the hexane fraction (HF) of P. macrocarpa fruits. In the hexane fraction of P. macarocarpa fruits, phytochemical screening showed the presence of terpenoids whereas saponins, alkaloids, tannins and anthraquinones were not present. Evaluation on Vero cell lines by using MTT assay showed that the 50% cytotoxic concentration (CC50) value was 0.48 mg/mL indicating that the fraction is not cytotoxic. Antiviral properties of the plant extracts were determined by plaque reduction assay. The effective concentration (EC50) was 0.18 mg/mL. Whereas the selective index (SI = CC50/EC50) of hexane fraction is 2.6 indicating low to moderate potential as antiviral agent.

  4. Antiviral activity and specific modes of action of bacterial prodigiosin against Bombyx mori nucleopolyhedrovirus in vitro.

    Science.gov (United States)

    Zhou, Wei; Zeng, Cheng; Liu, RenHua; Chen, Jie; Li, Ru; Wang, XinYan; Bai, WenWen; Liu, XiaoYuan; Xiang, TingTing; Zhang, Lin; Wan, YongJi

    2016-05-01

    Prodigiosin, the tripyrrole red pigment, is a bacterial secondary metabolite with multiple bioactivities; however, the antiviral activity has not been reported yet. In the present study, we found the antiviral activity of bacterial prodigiosin on Bombyx mori nucleopolyhedrovirus (BmNPV)-infected cells in vitro, with specific modes of action. Prodigiosin at nontoxic concentrations selectively killed virus-infected cells, inhibited viral gene transcription, especially viral early gene ie-1, and prevented virus-mediated membrane fusion. Under prodigiosin treatment, both progeny virus production and viral DNA replication were significantly inhibited. Fluorescent assays showed that prodigiosin predominantly located in cytoplasm which suggested it might interact with cytoplasm factors to inhibit virus replication. In conclusion, the present study clearly indicates that prodigiosin possesses significant antiviral activity against BmNPV.

  5. A small effect of adding antiviral agents in treating patients with severe Bell palsy.

    NARCIS (Netherlands)

    Veen, E.L. van der; Rovers, M.M.; Ru, J.A. de; Heijden, G.J. van der

    2012-01-01

    In this evidence-based case report, the authors studied the following clinical question: What is the effect of adding antiviral agents to corticosteroids in the treatment of patients with severe or complete Bell palsy? The search yielded 250 original research articles. The 6 randomized trials of

  6. Ganciclovir Antiviral Therapy in Advanced Idiopathic Pulmonary Fibrosis: An Open Pilot Study

    Directory of Open Access Journals (Sweden)

    J. J. Egan

    2011-01-01

    Conclusion. This audit outcome suggests that 2-week course of ganciclovir (iv may attenuate disease progression in a subgroup of advanced IPF patients. These observations do not suggest that anti-viral treatment is a substitute for the standard care, however, suggests the need to explore the efficacy of ganciclovir as adjunctive therapy in IPF.

  7. Evaluation of abdominal CT in the initial treatment of abdominal trauma

    International Nuclear Information System (INIS)

    Watanabe, Shinsuke; Ishii, Takashi; Kuwata, Katsuya; Yoneyama, Chihiro; Kitamura, Kazuya; Sasaki, Yoshifumi; Kamachi, Masahiro; Nishiguchi, Hiroyasu.

    1986-01-01

    During the last four years 102 patients with abdominal trauma were examined by CT for preoperative evaluation in our hospital. In 35 patients (34 %), the CT scans revealed no abnormal findings. They were all managed conservatively except for one case of perforated small bowel. In 67 patients (66 %) CT revealed evidences of substantial abdominal or retroperitoneal trauma. In 30 of them CT findings were confirmed by surgery. Hepatic injury is usually easily recognized by CT. CT is also useful for the detection of renal or splenic injuries. The majority of those parenchymatous organ injuries were successfully managed with conservative therapy, despite apparent traumatic lesions revealed by CT. Repeat CT scans is proved to be very useful to follow the changes of these traumatic lesions. In conclusion, application of abdominal CT is extremely useful for the initial decision making in treatment of patients with abdominal trauma and for the follow-up observation of injured lesions. (author)

  8. Initiation and persistence to statin treatment in patients with diabetes receiving glucose-lowering medications 1997- 2006

    DEFF Research Database (Denmark)

    Dominguez, H; Schramm, T K; Norgaard, M L

    2009-01-01

    AIMS: Since 2001 guidelines recommend statin treatment in most patients with diabetes. We investigated secular changes in initiation and persistence to statin treatment during a 10-year period in a nationwide cohort of patients initiating glucose-lowering medication (GLM). METHODS: All Danish...... citizens 30 years and older who claimed prescriptions of GLM between 1997 and 2006 were identified from nationwide registers of drug dispensing from pharmacies and hospitalizations, and followed until 2006. Statin treatment was registered if a prescription was claimed during the period. By logistic...... regression we analyzed factors related to initiation and persistence to statin treatment. RESULTS: In total 128,106 patients were included. In 1997 only 7% of the patients receiving GLM claimed statins within the first year after GLM initiation. Despite increasing statin prescriptions the following years...

  9. Total pancreatectomy with islet cell autotransplantation as the initial treatment for minimal-change chronic pancreatitis.

    Science.gov (United States)

    Wilson, Gregory C; Sutton, Jeffrey M; Smith, Milton T; Schmulewitz, Nathan; Salehi, Marzieh; Choe, Kyuran A; Brunner, John E; Abbott, Daniel E; Sussman, Jeffrey J; Ahmad, Syed A

    2015-03-01

    Patients with minimal-change chronic pancreatitis (MCCP) are traditionally managed medically with poor results. This study was conducted to review outcomes following total pancreatectomy with islet cell autotransplantation (TP/IAT) as the initial surgical procedure in the treatment of MCCP. All patients submitted to TP/IAT for MCCP were identified for inclusion in a single-centre observational study. A retrospective chart review was performed to identify pertinent preoperative, perioperative and postoperative data. A total of 84 patients with a mean age of 36.5 years (range: 15-60 years) underwent TP/IAT as the initial treatment for MCCP. The most common aetiology of chronic pancreatitis in this cohort was idiopathic (69.0%, n = 58), followed by aetiologies associated with genetic mutations (16.7%, n = 14), pancreatic divisum (9.5%, n = 8), and alcohol (4.8%, n = 4). The most common genetic mutations pertained to CFTR (n = 9), SPINK1 (n = 3) and PRSS1 (n = 2). Mean ± standard error of the mean preoperative narcotic requirements were 129.3 ± 18.7 morphine-equivalent milligrams (MEQ)/day. Overall, 58.3% (n = 49) of patients achieved narcotic independence and the remaining patients required 59.4 ± 10.6 MEQ/day (P < 0.05). Postoperative insulin independence was achieved by 36.9% (n = 31) of patients. The Short-Form 36-Item Health Survey administered postoperatively demonstrated improvement in all tested quality of life subscales. The present report represents one of the largest series demonstrating the benefits of TP/IAT in the subset of patients with MCCP. © 2014 International Hepato-Pancreato-Biliary Association.

  10. In vitro antiviral activity of plant extracts from Asteraceae medicinal plants.

    Science.gov (United States)

    Visintini Jaime, María F; Redko, Flavia; Muschietti, Liliana V; Campos, Rodolfo H; Martino, Virginia S; Cavallaro, Lucia V

    2013-07-27

    Due to the high prevalence of viral infections having no specific treatment and the constant appearance of resistant viral strains, the development of novel antiviral agents is essential. The aim of this study was to evaluate the antiviral activity against bovine viral diarrhea virus, herpes simplex virus type 1 (HSV-1), poliovirus type 2 (PV-2) and vesicular stomatitis virus of organic (OE) and aqueous extracts (AE) from: Baccharis gaudichaudiana, B. spicata, Bidens subalternans, Pluchea sagittalis, Tagetes minuta and Tessaria absinthioides. A characterization of the antiviral activity of B. gaudichaudiana OE and AE and the bioassay-guided fractionation of the former and isolation of one active compound is also reported. The antiviral activity of the OE and AE of the selected plants was evaluated by reduction of the viral cytopathic effect. Active extracts were then assessed by plaque reduction assays. The antiviral activity of the most active extracts was characterized by evaluating their effect on the pretreatment, the virucidal activity and the effect on the adsorption or post-adsorption period of the viral cycle. The bioassay-guided fractionation of B. gaudichaudiana OE was carried out by column chromatography followed by semipreparative high performance liquid chromatography fractionation of the most active fraction and isolation of an active compound. The antiviral activity of this compound was also evaluated by plaque assay. B. gaudichaudiana and B. spicata OE were active against PV-2 and VSV. T. absinthioides OE was only active against PV-2. The corresponding three AE were active against HSV-1. B. gaudichaudiana extracts (OE and AE) were the most selective ones with selectivity index (SI) values of 10.9 (PV-2) and > 117 (HSV-1). For this reason, both extracts of B. gaudichaudiana were selected to characterize their antiviral effects. Further bioassay-guided fractionation of B. gaudichaudiana OE led to an active fraction, FC (EC50 = 3.1 μg/ml; SI = 37

  11. APPROVAL OF WASTE TREATMENT AND IMMOBILIZATION PLANT CONTRACTOR-INITIATED AUTHORIZATION BASIS AMENDMENT REQUESTS (ABAR)

    International Nuclear Information System (INIS)

    JONES GL

    2008-01-01

    The objective is to describe the process used by the Office of River Protection (ORP) for evaluating and implementing Contractor-initiated changes to the Waste Treatment and Immobilization Plant (WTP) Authorization Basis (AB). The WTP Project's history has provided a unique challenge for establishing and maintaining an ORP-approved AB during design and construction. Until operations begin, the project cannot implement the classic Unreviewed Safety Question (USQ) process to determine when ORP approval of Contractor-initiated changes is required. A 'quasiUSQ' process has been implemented that defines when AB changes could occur. The three types of AB changes are (1) Limited Scope Changes, (2) Authorization Basis Deviations, and (3) Authorization Basis Amendment Request (ABAR). DOE RL/REG 97-13, 'Office of River Protection Position on Contractor-Initiated Changes to the Authorization Basis', describes the process the WTP Contractor must follow to make changes to the AB, with and without ORP approval. The process uses a 'safety evaluation' process that is similar to the USQ process but at a more qualitative level. The maturation of the WTP Contractor's facility design and activities, and other changing conditions, resulted in a process that allows the Contractor to make changes to the AB without ORP approval; however, those changes that may significantly affect nuclear safety do require ORP approval. This process balances the WTP regulatory principle of efficiency with assurance that adequate safety will not be compromised. The process has reduced the number of ABARs requiring ORP approval and reduced the potential for delays in design and procurement activities

  12. Force systems in the initial phase of orthodontic treatment -- a comparison of different leveling arch wires.

    Science.gov (United States)

    Fuck, Lars-Michael; Drescher, Dieter

    2006-01-01

    The determination of orthodontically-effective forces and moments places great demands on the technical equipment. Many patients report severe pain after fixed appliance insertion. Since it is assumed that pain from orthodontic appliances is associated with the force and moment levels applied to the teeth and since the occurrence of root resorption is a common therapeutic side effect, it would seem important to know the actual magnitudes of the components of the active orthodontic force systems. The aim of the present study was therefore to measure initial force systems produced by different leveling arch-wires in a complete multi-bracket appliance and to assess whether force and moment levels can be regarded as biologically acceptable or not. The actual bracket position in 42 patients was transferred onto a measurement model. Forces and moments produced by a super-elastic nickel-titanium (NiTi) archwire, a 6-strand stainless steel archwire, and a 7-strand super-elastic NiTi archwire were determined experimentally on different teeth. Average forces and moments produced by the super-elastic NiTi arch wires were found to be the highest. In spite if their larger diameter, the stranded arch wires' average force and moment levels were lower, especially that of the stranded super-elastic archwire. Nevertheless, maximum force levels sometimes exceeded recommended values in the literature and must be considered as too high. The measured arch wires' initial force systems differed significantly depending on the type of archwire and its material structure. Stranded arch wires produced lower force and moment levels, and we recommend their use in the initial phase of orthodontic treatment.

  13. The Correlation of Initial Sputum Smear Positivity on Treatment Failure of Category 1 Therapy for Pulmonary Tuberculosis

    Directory of Open Access Journals (Sweden)

    Puput Dyah Ayu

    2016-11-01

    Full Text Available Tuberculosis is an infectious disease and is an important public health problem. Based on data from East Java Province Health Department reported that number of tuberculosis patient in Surabaya is the highest in East Java on year 2014. Early identification and good treatment based on the result of sputum identification are the strategy use to control tuberculosis widespread. So that why, microscopic observation to identify acid fast bacilli (AFB is the fundamental stage to determine recovery treatment. Initial sputum smear positivity is necessary to determine infectious graded. The objectives of the study were to identify of initial sputum smear positivity on treatment failure of category 1 therapy for pulmonary tuberculosis in RS Paru Surabaya year 2011-2014. This study used case control method with quantitative approach. Forty two samples were taken from secondary data. Case group is 21 samples who have treatment failure and control group is 21 successful treatment. Samples were selected by simple random sampling. The chi square correlation showed that highly positive initial smear (p = 0,045; OR = 5,4 have correlated and risk factor to treatment failure on category 1 therapy for pulmonary tuberculosis. The conclusion is patient’s high positive sputum smear initially correlated to treatment failure on category 1 therapy for pulmonary tuberculosis in RS Paru Surabaya year 2011–2014. Keywords: initial sputum smear positivity, treatment failure,, category 1 therapy for pulmonary tuberculosis

  14. Future of external beam irradiation as initial treatment of rectal cancer

    Energy Technology Data Exchange (ETDEWEB)

    Papillon, J.

    1987-06-01

    The authors' protocol consists of a split-course regimen with a short course of cobalt-60 arc rotation (3000 c/Gy in 12 days). After 2 months rest, the second stage treatment depends upon the pressure of residual disease and the tumour site. It consists of either radical surgery (82 cases) or conservative treatment by intracavitary irradiation in the event of a favourable initial response or in the case of poor risk patients (73 cases). In the radiotherapy-surgical group, the subsequent operative specimens were tumour free in 17% of cases and assigned to Dukes' A category in 32% of cases. Of 91 patients with T/sub 2/ or T/sub 3/ tumour involving the lower third of the rectum (followed up for more than 3 years) 72(84%) had no recurrence. Thirty-three of these patients (46%) underwent a colostomy while 39 (54%) has normal anal function. These results demonstrate the major place that a properly planned external beam irradiation can have in the curative management of cancers of the low rectum.

  15. Craving and subsequent opioid use among opioid dependent patients who initiate treatment with buprenorphine

    Science.gov (United States)

    Tsui, Judith I.; Anderson, Bradley J.; Strong, David R.; Stein, Michael D.

    2016-01-01

    Background Few studies have directly assessed associations between craving and subsequent opioid use among treated patients. Our objective was to prospectively evaluate the relative utility of two craving questionnaires to predict opioid use among opioid dependent patients in treatment. Method Opioid dependent patients (n=147) initiating buprenorphine treatment were assessed for three months. Craving was measured using: 1) the Desires for Drug Questionnaire (DDQ) and 2) the Penn Alcohol-Craving Scale adapted for opioid craving (PCS) for this study. Multi-level logistic regression models estimated the effects of craving on the likelihood of opioid use after adjusting for gender, age, ethnicity, education, opioid of choice, frequency of use, pain and depression. In these analyses craving assessed at time t was entered as a time-varying predictor of opioid use at time t+1. Results In adjusted regression models, a 1-point increase in PCS scores (on a 7-point scale) was associated with a significant increase in the odds of opioid use at the subsequent assessment (OR = 1.27, 95% CI 1.08; 1.49, p .05) or DDQ control (OR = 0.97, 95%CI 0.85; 1.11, p > .05) scores. Conclusion Self-reported craving for opioids was associated with subsequent lapse to opioid use among a cohort of patients treated with buprenorphine. PMID:24521036

  16. CHOICE OF THE INITIAL TREATMENT FOR MILD TO MODERATE ARTERIAL HYPERTENSION IN MOSCOW PRIMARY PRACTICE

    Directory of Open Access Journals (Sweden)

    S. V. Gatsura

    2015-09-01

    Full Text Available Aim. To assess the choice of initial pharmacotherapy of uncomplicated mild to moderate arterial hypertension (HT in Moscow primary care as well as to clear up the influence of regulatory measures on this choice.Material and methods. Results of two similar surveys conducted in 2011-2012 (452 respondents and 2013-2014 (273 respondents were compared to estimate preferences of Moscow primary care physicians regarding initial antihypertensive agents for therapy of uncomplicated mild to moderate HT taking into consideration an influence of regulatory requirement to prescribe medicinal products by international nonproprietary name (INN since July 2012. All participants were proposed to write down their preferred antihypertensive agents for initial mono- or combined therapy of mild to moderate HT with moderate cardiovascular risk and absence of compelling indications.Results. Angiotensin converting enzyme inhibitors (ACEI remained the leading class of antihypertensive agents, though their popularity slightly but significantly declined from 44.4% in 2011-12 to 37.2% in 2013-14 (р<0.05. Angiotensin receptor blockers partially displaced the leaders and increased their popularity from 11.3% in 2011-12 to 18.0% in 2013-14 (р<0.01. ACEI/diuretic combination remained on the 3rd position (16.4% and 15.3% respectively. Beta-blockers and diuretics as monotherapy shared 4th and 5th places in this rating. Calcium channel blockers popularity among Moscow prescribers remained unchanged and poor – 2.1%. The most popular medicine by trade name was Noliprel, perindopril/indapamide fixed combination, – 14.0% and 13.7% of respondents in 2011-12 and 2013-14, respectively. The share of medicine products recommended by INN went up from 11.9% to 22.8% among top-10 popular medications (р<0.01.Conclusion. Blockers of renin-angiotensin-aldosterone system remain the leading drugs for the initial treatment of uncomplicated mild to moderate HT without compelling indications

  17. In vitro inhibition of canine distemper virus by flavonoids and phenolic acids: implications of structural differences for antiviral design.

    Science.gov (United States)

    Carvalho, O V; Botelho, C V; Ferreira, C G T; Ferreira, H C C; Santos, M R; Diaz, M A N; Oliveira, T T; Soares-Martins, J A P; Almeida, M R; Silva, A

    2013-10-01

    Infection caused by canine distemper virus (CDV) is a highly contagious disease with high incidence and lethality in the canine population. Antiviral activity of flavonoids quercetin, morin, rutin and hesperidin, and phenolic cinnamic, trans-cinnamic and ferulic acids were evaluated in vitro against the CDV using the time of addition assay to determine which step of the viral replicative cycle was affected. All flavonoids displayed great viral inhibition when they were added at the times 0 (adsorption) and 1h (penetration) of the viral replicative cycle. Both quercetin and hesperidin presented antiviral activity at the time 2h (intracellular). In the other hand, cinnamic acid showed antiviral activity at the times 0 and 2h while trans-cinnamic acid showed antiviral effect at the times -1h (pre-treatment) and 0 h. Ferulic acid inhibited CDV replicative cycle at the times 0 and 1h. Our study revealed promising candidates to be considered in the treatment of CDV. Structural differences among compounds and correlation to their antiviral activity were also explored. Our analysis suggest that these compounds could be useful in order to design new antiviral drugs against CDV as well as other viruses of great meaning in veterinary medicine. Copyright © 2013 Elsevier Ltd. All rights reserved.

  18. Do personality traits predict outcome of psychodynamically oriented psychosomatic inpatient treatment beyond initial symptoms?

    Science.gov (United States)

    Steinert, Christiane; Klein, Susanne; Leweke, Frank; Leichsenring, Falk

    2015-03-01

    Whether personality characteristics have an impact on treatment outcome is an important question in psychotherapy research. One of the most common approaches for the description of personality is the five-factor model of personality. Only few studies investigated whether patient personality as measured with the NEO-Five-Factor Inventory (NEO-FFI, Costa & McCrae [1992b]. Revised NEO-PI-R and NEO-FFI. Professional manual. Odessa, FL: Psychological Assessment Recources) predicts outcome. Results were inconsistent. Studies reporting personality to be predictive of outcome did not control for baseline symptoms, while studies controlling initial symptoms could not support these findings. We hypothesized that after taking into account baseline symptoms, the NEO-FFI would not predict outcome and tested this in a large sample of inpatients at a psychosomatic clinic. Naturalistic, non-controlled study using patients' data for multiple regression analysis to identify predictors of outcome. Data of 254 inpatients suffering primarily from depressive, anxiety, stress, and somatoform disorders were analysed. Personality was assessed at the beginning of therapy. For psychotherapy outcome, changes in anxiety and depression (Hospital Anxiety and Depression Scale; HADS), overall psychopathology (Symptom Checklist-90-R Global Severity Index [GSI]), and interpersonal problems (Inventory of Interpersonal Problems; IIP) were measured. The treatment resulted in significant decreases on all outcome measures corresponding to moderate to large effect sizes (HADS: d = 1.03; GSI: d = 0.90; IIP: d = 0.38). Consistent with our hypothesis, none of the personality domains predicted outcome when baseline symptoms were controlled for. Personality assessment at baseline does not seem to have an added value in the prediction of inpatient psychotherapy outcome beyond initial symptoms. Clinical implications Personality dimensions overlap with symptomatic distress. Rather than serve as predictors of

  19. Initial experience of percutaneous treatment of mitral regurgitation with MitraClip® therapy in Spain.

    Science.gov (United States)

    Carrasco-Chinchilla, Fernando; Arzamendi, Dabit; Romero, Miguel; Gimeno de Carlos, Federico; Alonso-Briales, Juan Horacio; Li, Chi-Hion; Mesa, Maria Dolores; Arnold, Roman; Serrador Frutos, Ana María; Pan, Manuel; Roig, Eulalia; Rodríguez-Bailón, Isabel; de la Fuente Galán, Luis; Hernández, José María; Serra, Antonio; Suárez de Lezo, José

    2014-12-01

    Symptomatic mitral regurgitation has an unfavorable prognosis unless treated by surgery. However, the European registry of valvular heart disease reports that 49% of patients with this condition do not undergo surgery. Percutaneous treatment of mitral regurgitation with MitraClip® has been proved a safe, efficient adjunct to medical treatment in patients with this profile. The objective of the present study is to describe initial experience of MitraClip® therapy in Spain. Retrospective observational study including all patients treated between November 2011 and July 2013 at the 4 Spanish hospitals recording the highest numbers of implantations. A total of 62 patients (77.4% men) were treated, mainly for restrictive functional mitral regurgitation (85.4%) of grade III (37%) or grade IV (63%), mean (standard deviation) ejection fraction 36% (14%), and New York Heart Association functional class III (37%) or IV (63%). Device implantation was successful in 98% of the patients. At 1 year, 81.2% had mitral regurgitation ≤ 2 and 90.9% were in New York Heart Association functional class ≤ II. One periprocedural death occurred (sepsis at 20 days post-implantation) and another 3 patients died during follow-up (mean, 9.1 months). Two patients needed a second implantation due to partial dehiscence of the first device and 2 others underwent heart transplantation. In Spain, MitraClip® therapy has principally been aimed at patients with functional mitral regurgitation, significant systolic ventricular dysfunction, and high surgical risk. It is considered a safe alternative treatment, which can reduce mitral regurgitation and improve functional capacity. Copyright © 2014 Sociedad Española de Cardiología. Published by Elsevier Espana. All rights reserved.

  20. [Evaluation of initial results of treatment of lead poisoning with EDTA].

    Science.gov (United States)

    Petkova, V; Adjarov, D; Pavlova, S; Naydenova, E; Kerimova, M; Kuneva, T

    1994-01-01

    treatment no association was observed between ALA-D and PP variations in erythrocytes and improvement in clinical symptoms; measurement of these indices therefore seems to be of little use in assessing the efficacy of the treatment. In spite of its limited diagnostic sensitivity during intoxication, measurement of ALA in urine could be useful to assess the efficacy of chelating therapy in subjects in whom the values are initially altered.

  1. Preemptive antiviral therapy with entecavir can reduce acute deterioration of hepatic function following transarterial chemoembolization

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    Sun Hong Yoo

    2016-12-01

    Full Text Available Background/Aims Hepatic damage during transarterial chemoembolization (TACE is a critical complication in patients with hepatitis B virus (HBV-related hepatocellular carcinoma (HCC. Apart from its role in preventing HBV reactivation, there is some evidence for the benefits of preemptive antiviral therapy in TACE. This study evaluated the effect of preemptive antiviral therapy on acute hepatic deterioration following TACE. Methods This retrospective observational study included a prospectively collected cohort of 108 patients with HBV-related HCC who underwent TACE between January 2007 and January 2013. Acute hepatic deterioration following TACE was evaluated. Treatment-related hepatic decompensation was defined as newly developed encephalopathy, ascites, variceal bleeding, elevation of the bilirubin level, prolongation of prothrombin time, or elevation of the Child-Pugh score by ≥2 within 2 weeks following TACE. Univariate and multivariate analyses were conducted to identify factors influencing treatment-related decompensation. Preemptive antiviral therapy involves directing prophylaxis only toward high-risk chronic hepatitis B patients in an attempt to prevent the progression of liver disease. We regarded at least 6 months as a significant duration of preemptive antiviral treatment before diagnosis of HCC. Results Of the 108 patients, 30 (27.8% patients received preemptive antiviral therapy. Treatment-related decompensation was observed in 25 (23.1% patients during the follow-up period. Treatment-related decompensation following TACE was observed more frequently in the nonpreemptive group than in the preemptive group (29.5% vs. 6.7%, P=0.008. In the multivariate analysis, higher serum total bilirubin (Hazard ratio [HR] =3.425, P=0.013, hypoalbuminemia (HR=3.990, P=0.015, and absence of antiviral therapy (HR=7.597, P=0.006 were significantly associated with treatment-related hepatic decompensation. Conclusions Our findings suggest that

  2. Progress and challenges in implementing HIV care and treatment policies in Latin America following the treatment 2.0 initiative.

    Science.gov (United States)

    Perez, Freddy; Gomez, Bertha; Ravasi, Giovanni; Ghidinelli, Massimo

    2015-12-19

    The Pan American Health Organization provides technical cooperation to countries in Latin America and the Caribbean for the scale-up of HIV care and treatment based on the Treatment 2.0 initiative. Fourteen Joint Review Missions (JRMs) were conducted between March 2012 and October 2014. Evaluating the degree of implementation of the recommendations of the JRMs and their impact on health policies, would help countries identify their gaps and areas for priority interventions. A descriptive analysis of the JRM recommendations was conducted for eight countries. An in-depth cross-sectional retrospective analysis of the degree of implementation of these recommendations in Ecuador, Venezuela, Bolivia, and El Salvador was performed through a standardized self-administered questionnaire applied to key informants. A comparative quantitative analysis on the optimization of antiretroviral regimens 'before/after' JRMs was conducted in three of the latter four countries, using data reported in 2013 and 2014. The priority areas with most recommendations were the optimization of antiretroviral treatment (ART) regimens (n = 57), the rational and efficient use of resources (n = 27) and the provision of point-of-care diagnostics and monitoring tools (n = 26), followed by community mobilization (n = 23), strategic information (n = 17) and the adaptation of delivery services (n = 15). The in-depth analysis in four countries showed that the two priority areas where most progress was observed were the rational and efficient use of resources (62%) and the optimization of ART regimens (60%). Adaptation of delivery services, community mobilization and strategic information were rated at 52% and the provision of point-of-care diagnostics and monitoring tools 38%. The quantitative analysis on optimization evidenced a 36% reduction in the number of first-line and second-line ART regimens, a 5.4% increase in the proportion of patients on WHO-recommended first-line regimens, a 19.4% increase in

  3. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals.

    Science.gov (United States)

    Ahmed, Asma; Felmlee, Daniel J

    2015-12-18

    There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR) rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

  4. Mechanisms of Hepatitis C Viral Resistance to Direct Acting Antivirals

    Directory of Open Access Journals (Sweden)

    Asma Ahmed

    2015-12-01

    Full Text Available There has been a remarkable transformation in the treatment of chronic hepatitis C in recent years with the development of direct acting antiviral agents targeting virus encoded proteins important for viral replication including NS3/4A, NS5A and NS5B. These agents have shown high sustained viral response (SVR rates of more than 90% in phase 2 and phase 3 clinical trials; however, this is slightly lower in real-life cohorts. Hepatitis C virus resistant variants are seen in most patients who do not achieve SVR due to selection and outgrowth of resistant hepatitis C virus variants within a given host. These resistance associated mutations depend on the class of direct-acting antiviral drugs used and also vary between hepatitis C virus genotypes and subtypes. The understanding of these mutations has a clear clinical implication in terms of choice and combination of drugs used. In this review, we describe mechanism of action of currently available drugs and summarize clinically relevant resistance data.

  5. Broad-spectrum antiviral properties of andrographolide.

    Science.gov (United States)

    Gupta, Swati; Mishra, K P; Ganju, Lilly

    2017-03-01

    Andrographolide, a diterpenoid, is known for its anti-inflammatory effects. It can be isolated from various plants of the genus Andrographis, commonly known as 'creat'. This purified compound has been tested for its anti-inflammatory effects in various stressful conditions, such as ischemia, pyrogenesis, arthritis, hepatic or neural toxicity, carcinoma, and oxidative stress, Apart from its anti-inflammatory effects, andrographolide also exhibits immunomodulatory effects by effectively enhancing cytotoxic T cells, natural killer (NK) cells, phagocytosis, and antibody-dependent cell-mediated cytotoxicity (ADCC). All these properties of andrographolide form the foundation for the use of this miraculous compound to restrain virus replication and virus-induced pathogenesis. The present article covers antiviral properties of andrographolide in variety of viral infections, with the hope of developing of a new highly potent antiviral drug with multiple effects.

  6. Study of the effect of antiviral therapy on homocysteinemia in hepatitis C virus- infected patients

    Directory of Open Access Journals (Sweden)

    Mustafa Mubin

    2012-08-01

    Full Text Available Abstract Background Hepatitis C virus (HCV infection is one of the leading causes of chronic liver disease (CLD. About 80% of those exposed to the virus develop a chronic infection. Hyperhomocysteinemia, which is an independent risk factor for atherosclerotic vascular disease and thromboembolism, may develop in HCV-infected patients although altered alanine amino transferase (ALT enzyme levels are generally associated with damage to liver cells. The gold standard therapy for chronic hepatitis C patients is pegylated interferon combined with an anti-viral drug (ribavirin. The current study aimed to investigate the effect of antiviral therapy on plasma homocysteine (Hcy levels in HCV patients in addition to other parameters. Methods 532 HCV-infected patients and 70 healthy controls were recruited for the study. All patients were subjected to laboratory investigations including HCV-RNA levels, complete blood cell counts, serum levels of homocysteine, ALT, alkaline phosphatase (ALP, lipid profile and liver ultrasonographic examination. The outcome of treatment with pegylated interferon α plus ribavirin treatment and sustained virologic response (SVR was determined 6–9 months post-therapy. Results Hyperhomocysteinemia was found in 91.35% of HCV-infected patients. The difference in plasma Hcy concentrations reached statistical significance between the patient and control groups. ALT, cholesterol and triglycerides (TGs levels were found higher than normal in the patients group. After receiving a combined therapy for 24 weeks, 43.66% patients showed an SVR (responders; 30.98% patients were non-responders while 25.35% patients initially responded to therapy but again retrieved positive status of HCV infection six months post-therapy (relapse-cirrhotic patients. The mean levels of plasma Hcy, ALT and ALP were significantly reduced in responders within 10 weeks of therapy when compared with non-responders and relapse-cirrhotic patients. Conclusion

  7. Optimal antiviral switching to minimize resistance risk in HIV therapy.

    Directory of Open Access Journals (Sweden)

    Rutao Luo

    Full Text Available The development of resistant strains of HIV is the most significant barrier to effective long-term treatment of HIV infection. The most common causes of resistance development are patient noncompliance and pre-existence of resistant strains. In this paper, methods of antiviral regimen switching are developed that minimize the risk of pre-existing resistant virus emerging during therapy switches necessitated by virological failure. Two distinct cases are considered; a single previous virological failure and multiple virological failures. These methods use optimal control approaches on experimentally verified mathematical models of HIV strain competition and statistical models of resistance risk. It is shown that, theoretically, order-of-magnitude reduction in risk can be achieved, and multiple previous virological failures enable greater success of these methods in reducing the risk of subsequent treatment failures.

  8. Initial treatment dropout in patients with substance use disorders attending a tertiary care de-addiction centre in north India

    Directory of Open Access Journals (Sweden)

    Debasish Basu

    2017-01-01

    Interpretation & conclusions: This study identified some socio-demographic and clinical variables which might predict treatment attrition in substance use disorders. Clinician's awareness towards these factors and tailor-made intervention might improve initial treatment retention. Future research could be directed to find the validity of this assumption.

  9. Direct-acting antiviral therapy decreases hepatocellular carcinoma recurrence rate in cirrhotic patients with chronic hepatitis C.

    Science.gov (United States)

    Virlogeux, Victor; Pradat, Pierre; Hartig-Lavie, Kerstin; Bailly, François; Maynard, Marianne; Ouziel, Guillaume; Poinsot, Domitille; Lebossé, Fanny; Ecochard, Marie; Radenne, Sylvie; Benmakhlouf, Samir; Koffi, Joseph; Lack, Philippe; Scholtes, Caroline; Uhres, Anne-Claire; Ducerf, Christian; Mabrut, Jean-Yves; Rode, Agnès; Levrero, Massimo; Combet, Christophe; Merle, Philippe; Zoulim, Fabien

    2017-08-01

    Arrival of direct-acting antiviral agents against hepatitis C virus with high-sustained virological response rates and very few side effects has drastically changed the management of hepatitis C virus infection. The impact of direct-acting antiviral exposure on hepatocellular carcinoma recurrence after a first remission in patients with advanced fibrosis remains to be clarified. 68 consecutive hepatitis C virus patients with a first hepatocellular carcinoma diagnosis and under remission, subsequently treated or not with a direct-acting antiviral combination, were included. Clinical, biological and virological data were collected at first hepatocellular carcinoma diagnosis, at remission and during the surveillance period. All patients were cirrhotic. Median age was 62 years and 76% of patients were male. Twenty-three patients (34%) were treated with direct-acting antivirals and 96% of them achieved sustained virological response. Median time between hepatocellular carcinoma remission and direct-acting antivirals initiation was 7.2 months (IQR: 3.6-13.5; range: 0.3-71.4) and median time between direct-acting antivirals start and hepatocellular carcinoma recurrence was 13.0 months (IQR: 9.2-19.6; range: 3.0-24.7). Recurrence rate was 1.7/100 person-months among treated patients vs 4.2/100 person-months among untreated patients (P=.008). In multivariate survival analysis, the hazard ratio for hepatocellular carcinoma recurrence after direct-acting antivirals exposure was 0.24 (95% confidence interval: 0.10-0.55; PHepatocellular carcinoma recurrence rate was significantly lower among patients treated with direct-acting antivirals compared with untreated patients. Given the potential impact of our observation, large-scale prospective cohort studies are needed to confirm these results. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. Smoking Habits of Patients Undergoing Treatment for Intermittent Claudication in the Vascular Quality Initiative.

    Science.gov (United States)

    Gabel, Joshua; Jabo, Brice; Patel, Sheela; Kiang, Sharon; Bianchi, Christian; Chiriano, Jason; Teruya, Theodore; Abou-Zamzam, Ahmed M

    2017-10-01

    Society for Vascular Surgery practice guidelines for the medical treatment of intermittent claudication give a GRADE 1A recommendation for smoking cessation. Active smoking is therefore expected to be low in patients suffering from intermittent claudication selected for vascular surgical intervention. The aim of this study is to evaluate the prevalence of smoking in patients undergoing intervention for intermittent claudication at the national level and to determine the relationship between smoking status and intervention. The Vascular Quality Initiative (VQI) registries for infra-inguinal bypass, supra-inguinal bypass, and peripheral vascular intervention (PVI) were queried to identify patients who underwent invasive treatment for intermittent claudication. Patient factors, procedure type (bypass versus PVI), and level of disease (supra-inguinal versus infra-inguinal) were evaluated for associations with smoking status (active smoking or nonsmoking) by univariate and covariate analysis. Between 2010 and 2015, 101,055 procedures were entered in the 3 registries, with 40,269 (40%) performed for intermittent claudication. Complete data for analysis were present in 37,632 cases. At the time of intervention, 44% of patients were active smokers, with wide variation by regional quality group (16-53%). In covariate analysis, active smoking at treatment was associated with age smoking status. During follow-up, 36% of patients had quit smoking. Predictors of smoking cessation included age ≥70 years (RR 1.45), ABI ≥0.9 (RR 1.12), and bypass procedures (RR 1.22). At the time of treatment, 44% of patients undergoing intervention for intermittent claudication in the VQI were active smokers and there was a wide regional variation. Prevalence of active smoking was greater in the presence of younger age, fewer comorbidities, lower ABI, and supra-inguinal disease. Type of procedure performed, and in turn level of invasiveness required, did not appear to be influenced by smoking

  11. Coxsackievirus cloverleaf RNA containing a 5' triphosphate triggers an antiviral response via RIG-I activation.

    Directory of Open Access Journals (Sweden)

    Qian Feng

    Full Text Available Upon viral infections, pattern recognition receptors (PRRs recognize pathogen-associated molecular patterns (PAMPs and stimulate an antiviral state associated with the production of type I interferons (IFNs and inflammatory markers. Type I IFNs play crucial roles in innate antiviral responses by inducing expression of interferon-stimulated genes and by activating components of the adaptive immune system. Although pegylated IFNs have been used to treat hepatitis B and C virus infections for decades, they exert substantial side effects that limit their use. Current efforts are directed toward the use of PRR agonists as an alternative approach to elicit host antiviral responses in a manner similar to that achieved in a natural infection. RIG-I is a cytosolic PRR that recognizes 5' triphosphate (5'ppp-containing RNA ligands. Due to its ubiquitous expression profile, induction of the RIG-I pathway provides a promising platform for the development of novel antiviral agents and vaccine adjuvants. In this study, we investigated whether structured RNA elements in the genome of coxsackievirus B3 (CVB3, a picornavirus that is recognized by MDA5 during infection, could activate RIG-I when supplied with 5'ppp. We show here that a 5'ppp-containing cloverleaf (CL RNA structure is a potent RIG-I inducer that elicits an extensive antiviral response that includes induction of classical interferon-stimulated genes, as well as type III IFNs and proinflammatory cytokines and chemokines. In addition, we show that prophylactic treatment with CVB3 CL provides protection against various viral infections including dengue virus, vesicular stomatitis virus and enterovirus 71, demonstrating the antiviral efficacy of this RNA ligand.

  12. Salvage treatment for local or local-regional recurrence after initial breast conservation treatment with radiation for ductal carcinoma in situ

    NARCIS (Netherlands)

    Solin, Lawrence J.; Fourquet, Alain; Vicini, Frank A.; Taylor, Marie; Haffty, Bruce; Strom, Eric A.; Wai, Elaine; Pierce, Lori J.; Marks, Lawrence B.; Bartelink, Harry; Campana, Francois; McNeese, Marsha D.; Jhingran, Anuja; Olivotto, Ivo A.; Bijker, Nina; Hwang, Wei-Ting

    2005-01-01

    The present study evaluated the outcome of salvage treatment for women with local or local-regional recurrence after initial breast conservation treatment with radiation for mammographically detected ductal carcinoma in situ (DCIS; intraductal carcinoma) of the breast. The study cohort consisted of

  13. Identification and Analysis of Antiviral Compounds Against Poliovirus.

    Science.gov (United States)

    Leyssen, Pieter; Franco, David; Tijsma, Aloys; Lacroix, Céline; De Palma, Armando; Neyts, Johan

    2016-01-01

    The Global Polio Eradication Initiative, launched in 1988, had as its goal the eradication of polio worldwide by the year 2000 through large-scale vaccinations campaigns with the live attenuated oral PV vaccine (OPV) (Griffiths et al., Biologicals 34:73-74, 2006). Despite substantial progress, polio remains endemic in several countries and new imported cases are reported on a regular basis ( http://www.polioeradication.org/casecount.asp ).It was recognized by the poliovirus research community that developing antivirals against poliovirus would be invaluable in the post-OPV era. Here, we describe three methods essential for the identification of selective inhibitors of poliovirus replication and for determining their mode of action by time-of-drug-addition studies as well as by the isolation of compound-resistant poliovirus variants.

  14. Initiation of glucose-lowering treatment decreases international normalized ratio levels among users of vitamin K antagonists

    DEFF Research Database (Denmark)

    Stage, Tore Bjerregaard; Pottegård, Anton; Henriksen, Daniel Pilsgaard

    2016-01-01

    -lowering treatment affects international normalized ratio (INR) and dose requirements of the anticoagulant VKAs warfarin and phenprocoumon. PATIENTS/METHODS: We performed a self-controlled retrospective register-based study. A total of 118 patients initiating glucose-lowering treatment while being treated......-lowering treatment reduces the anticoagulant effect of VKA to an extent that is likely to be clinically relevant. This finding needs confirmation and mechanistic explanation. This article is protected by copyright. All rights reserved....

  15. Influence of initial thermomechanical treatment on high temperature properties of laves phase strengthened ferritic steels

    International Nuclear Information System (INIS)

    Talik, Michal

    2016-01-01

    The aim of this work was to design 17 wt%Cr Laves phase strengthened HiperFer (High performance Ferrite) steels and evaluate their properties. This class of steel is supposed to be used in Advanced Ultra Super Critical power plants. Such cycles exhibit higher efficiency and are environmentally friendly, but improved materials with high resistance to reside/steam oxidation and sufficient creep strength are required. The work focused on the characterization of creep properties of 17Cr2.5W0.5Nb0.25Si heat resistant steel. Small batches of steels with nominal compositions of 17Cr3W0.5Nb0.25Si and 17Cr3W0.9Nb0.25Si were used to analyze the influence of chemical composition on the precipitation behaviour in comparison to 17Cr2.5W0.5Nb0.25Si steel. Creep strength of HiperFer steels is ensured by ne dispersion of thermodynamically stable Laves phase particles, while maintaining high corrosion resistance by a relatively high chromium content. Design of HiperFer steels was accomplished by thermodynamic modeling (Thermocalc) with the main tasks of elimination of the unwelcome brittle (Fe,Cr)-σ phase and maximization of the content of the strengthening C14 Fe_2Nb type Laves phase particles. Long term annealing experiments of all HiperFer steels were performed at 650 C in order to evaluate the role of chemical composition and initial thermo-mechanical treatment state on precipitation behaviour. Laves phase particles formed quickly after few hours and the size of precipitates did not change significantly within 1,000 hours. The observed development of Laves phase particles was compared with thermodynamical calculations (TC-Prisma). The creep properties of 17Cr2.5W0.5Nb0.25Si steel in different initial thermo-mechanical treatment states were tested at 650 C. The influence of different cold rolling procedures, and heat treatments was investigated. Increased cold rolling deformation had a positive effect resulting not only from work hardening, but from the acceleration of Laves

  16. Initial Evaluation of a Titration Appliance for Temporary Treatment of Obstructive Sleep Apnea.

    Science.gov (United States)

    Levendowski, Daniel J; Morgan, Todd; Westbrook, Philip

    2012-01-01

    Custom oral appliances that adjustably advance the mandible provide superior outcomes when treating patients with moderate or severe sleep apnea. Custom appliances, however, are expensive, must be fitted by a dentist, and the likelihood of successful outcomes are difficult to predict. An inexpensive trial appliance, if proven efficacious, might be used to predict custom appliance outcomes or to provide temporary therapeutic benefit. The aim of this initial study was to assess the treatment efficacy of a novel titration oral appliance with that of an optimized custom appliance. Seventeen patients, treated with a custom oral appliance for at least one year, successfully completed a three-night home sleep test. The baseline obstructive sleep apnea severity was established on Night 1 with seven patients exhibiting severe, six moderate and four mild apnea/hypopnea indexes. Patients were randomly assigned to wear their custom appliance or the titration appliance on Nights 2 and 3. Significant reductions in the mean overall and supine apnea indexes (p titration and custom appliances. The proportion of patients who exhibited at least a 50% reduction in the overall apnea index and supine apnea/hypopnea were similar for the titration and custom appliance (~60%). The custom appliance reduced the overall apnea/hypopnea index by 50% in a greater proportion of the patients compared to the titration appliance (77% vs. 53%). The titration appliance significantly reduced the degree of hypoxic exposure across sleep disordered breathing events overall (p titration appliance, but preferred the titration appliance to no therapy. The titration appliance may be useful in assessing oral appliance treatment efficacy. When set to 70% of maximum protrusion, the titration appliance may provide immediate, temporary therapeutic benefit.

  17. Initial primary endovascular treatment in the management of ruptured intracranial aneurysms: a prospective consecutive series

    International Nuclear Information System (INIS)

    Mejdoubi, Mehdi; Cognard, Christophe; Gigaud, Michel; Tremoulet, Michel; Albucher, Jean-Francois

    2006-01-01

    From January 1998 to December 2002, endovascular treatment (EVT) was used as first intention in all patients with ruptured aneurysms. The objective of this study was to analyze the results of this therapeutic strategy. Among 401 patients admitted with a subarachnoid hemorrhage (SAH), 73 (18%) had a nonaneurysmal perimesencephalic SAH, 28 were not explored by angiography due to very poor clinical status, and 28 with aneurysmal SAH were not treated due to poor clinical status. Thus, of the 300 patients with a proven aneurysmal SAH, 272 (83%) were treated. EVT was attempted in 230 patients and was successful in 222 (82%), and clipping was performed in 50 (18%). Finally, EVT was successful in 234 aneurysms (96.7%) in 222 patients out of 242 aneurysms in 230 patients (some of the patients were treated for more than one aneurysm in the same procedure). EVT-related morbidity occurred in ten patients (4.5%) and mortality in eight (3.6%). Rate of dependency or death (modified Rankin scale 3-5) was 24.5% at 26 months. Initially, complete aneurysm occlusion was obtained in 81%, a dog ear in 3.4%, a neck remnant in 8% and incomplete occlusion in 8.1% of the patients. At follow-up (mean 26 months), the occlusion rate remained stable at 75%. This consecutive prospective series shows that EVT can be performed routinely as first-intention treatment in most aneurysmal SAH. Using this therapeutic strategy, EVT was performed in 82% of patients with long-term clinical results similar to those of the ISAT study. (orig.)

  18. Early initiation of antiretroviral treatment: Challenges in the Middle East and North Africa.

    Science.gov (United States)

    Sardashti, Sara; Samaei, Mehrnoosh; Firouzeh, Mona Mohammadi; Mirshahvalad, Seyed Ali; Pahlaviani, Fatemeh Golsoorat; SeyedAlinaghi, SeyedAhmad

    2015-05-12

    New World Health Organization guidelines recommend the initiation of antiretroviral treatment (ART) for asymptomatic patients with CD4+ T-cell counts of ≤ 500 cells/mm(3). Substantial reduction of human immunodeficiency virus (HIV) transmission is addressed as a major public health outcome of this new approach. Middle East and North Africa (MENA), known as the area of controversies in terms of availability of comprehensive data, has shown concentrated epidemics among most of it's at risk population groups. Serious challenges impede the applicability of new guidelines in the MENA Region. Insufficient resources restrict ART coverage to less than 14%, while only one fourth of the countries had reportable data on patients' CD4 counts at the time of diagnosis. Clinical guidelines need to be significantly modified to reach practical utility, and surveillance systems have not yet been developed in many countries of MENA. Based on available evidence in several countries people who inject drugs and men who have sex with men are increasingly vulnerable to HIV and viral hepatitis, while their sexual partners - either female sex workers or women in monogamous relationships with high-risk men - are potential bridging populations that are not appropriately addressed by regional programs. Research to monitor the response to ART among the mentioned groups are seriously lacking, while drug resistant HIV strains and limited information on adherence patterns to treatment regimens require urgent recognition by health policymakers. Commitment to defined goals in the fight against HIV, development of innovative methods to improve registration and reporting systems, monitoring and evaluation of current programs followed by cost-effective modifications are proposed as effective steps to be acknowledged by National AIDS Programs of the countries of MENA Region.

  19. Initial conservative treatment for grade 3 Ta-1 superficial bladder cancer

    International Nuclear Information System (INIS)

    Fujimoto, Kiyohide; Chihara, Yoshitomo; Kondo, Hideaki; Hirao, Yoshihiko

    2006-01-01

    We retrospectively investigated the therapeutic outcomes of our series of 7 Ta and 62 T1 bladder cancers with grade 3 (G3) malignancy in 61 men and 8 women having a mean age of 66.2 years. Following transurethral resection of bladder tumor (TURBT), 35 and 6 patients received intravesical instillations of bacillus Calmette-Guerin (BCG) and anthracycline-derivants, respectively, whereas 15 received no adjuvant therapy. Five and 2 patients received systemic and local chemotherapy with irradiation, respectively, and six underwent radical cystectomy for invasive potential. The 5-year non-recurrence, progression-free, and overall (cancer-specific) survival rates were 66, 82%, and 76 (88)%, respectively, after a median follow-up of 52 months. The 5-year non-recurrence rates were 24% in non-adjuvant, 85% in BCG, 0% in anthracycline-derivants, 65% in systemic and local chemoradiation therapy, and 68% in cystectomy. The 5-year progression-free and overall (cancer-specific) survival rates of the patients treated with BCG instillation were 91% and 94 (100)%. There were no significant differences in the 5-year non-recurrence and progression-free rates between 12 patients with carcinoma in situ (CIS) and 23 patients without CIS. Complete TUR of all visible tumors and a reliable histopathological diagnosis of appropriate specimens bearing the muscle layer are mandatory for assessment of recurrence. G3 Ta-1 bladder cancers and CIS showed a high risk of recurrence, and required aggressive treatment. Since BCG therapy following TURBT significantly reduced the risk of recurrence and progression, adjuvant BCG therapy is considered to be the most promising initial conservative treatment for G3 Ta-1 bladder cancers. (author)

  20. Quality assurance in the treatment of colorectal cancer: the EURECCA initiative.

    Science.gov (United States)

    Breugom, A J; Boelens, P G; van den Broek, C B M; Cervantes, A; Van Cutsem, E; Schmoll, H J; Valentini, V; van de Velde, C J H

    2014-08-01

    Colorectal cancer is one of the most common cancers in Europe. Over the past few decades, important advances have been made in screening, staging and treatment of colorectal cancer. However, considerable variation between and within European countries remains, which implies that further improvements are possible. The most important remaining question now is: when are we, health care professionals, delivering the best available care to patients with colon or rectal cancer? Currently, quality assurance is a major issue in colorectal cancer care and quality assurance awareness is developing in almost all disciplines involved in the treatment of colorectal cancer patients. Quality assurance has shown to be effective in clinical trials. For example, standardisation and quality control were introduced in the Dutch TME trial and led to marked improvements of local control and survival in rectal cancer patients. Besides, audit structures can also be very effective in monitoring cancer management and national audits showed to further improve outcome in colorectal cancer patients. To reduce the differences between European countries, an international, multidisciplinary, outcome-based quality improvement programme, European Registration of Cancer Care (EURECCA), has been initiated. In the near future, the EURECCA dataset will perform research on subgroups as elderly patients or patients with comorbidities, which are often excluded from trials. For optimal colorectal cancer care, quality assurance in guideline formation and in multidisciplinary team management is also of great importance. The aim of this review was to create greater awareness and to give an overview of quality assurance in the management of colorectal cancer. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  1. A small effect of adding antiviral agents in treating patients with severe Bell palsy.

    Science.gov (United States)

    van der Veen, Erwin L; Rovers, Maroeska M; de Ru, J Alexander; van der Heijden, Geert J

    2012-03-01

    In this evidence-based case report, the authors studied the following clinical question: What is the effect of adding antiviral agents to corticosteroids in the treatment of patients with severe or complete Bell palsy? The search yielded 250 original research articles. The 6 randomized trials of these that could be used all reported low-quality data for answering the clinical question; apart from apparent flaws, they did not primarily include patients with severe or complete Bell palsy. Complete functional facial nerve recovery was seen in 75% of the patients receiving prednisolone only and in 83% with additional antiviral treatment. The pooled risk difference of 7% (95% confidence interval, -1% to 15%) results in a number needed to treat of 14 (ie, slightly favors adding an antiviral agent). The authors conclude that although a strong recommendation for adding antiviral agents to corticosteroids to further improve the recovery of patients with severe Bell palsy is precluded by the lack of robust evidence, it should be discussed with the patient.

  2. Tannic acid modified silver nanoparticles show antiviral activity in herpes simplex virus type 2 infection.

    Directory of Open Access Journals (Sweden)

    Piotr Orlowski

    Full Text Available The interaction between silver nanoparticles and herpesviruses is attracting great interest due to their antiviral activity and possibility to use as microbicides for oral and anogenital herpes. In this work, we demonstrate that tannic acid modified silver nanoparticles sized 13 nm, 33 nm and 46 nm are capable of reducing HSV-2 infectivity both in vitro and in vivo. The antiviral activity of tannic acid modified silver nanoparticles was size-related, required direct interaction and blocked virus attachment, penetration and further spread. All tested tannic acid modified silver nanoparticles reduced both infection and inflammatory reaction in the mouse model of HSV-2 infection when used at infection or for a post-infection treatment. Smaller-sized nanoparticles induced production of cytokines and chemokines important for anti-viral response. The corresponding control buffers with tannic acid showed inferior antiviral effects in vitro and were ineffective in blocking in vivo infection. Our results show that tannic acid modified silver nanoparticles are good candidates for microbicides used in treatment of herpesvirus infections.

  3. Danish recommendations on treatment of ankylosing spondylitis and spondyloarthritis based on multinational project initiative

    DEFF Research Database (Denmark)

    Pedersen, Susanne Juhl; Madsen, Ole Rintek; Erlendsson, J.

    2008-01-01

    INTRODUCTION: The multinational initiative "3e Initiative in Rheumatology - Multi-national Recommendations for the Management of Ankylosing Spondylitis 2006-7" served the primary purpose of providing specific recommendations for the management of ankylosing spondylitis and spondyloarthritis...

  4. Automatic treatment plan re-optimization for adaptive radiotherapy guided with the initial plan DVHs

    International Nuclear Information System (INIS)

    Li, Nan; Zarepisheh, Masoud; Uribe-Sanchez, Andres; Moore, Kevin; Tian, Zhen; Zhen, Xin; Graves, Yan Jiang; Gautier, Quentin; Mell, Loren; Jia, Xun; Jiang, Steve; Zhou, Linghong

    2013-01-01

    Adaptive radiation therapy (ART) can reduce normal tissue toxicity and/or improve tumor control through treatment adaptations based on the current patient anatomy. Developing an efficient and effective re-planning algorithm is an important step toward the clinical realization of ART. For the re-planning process, manual trial-and-error approach to fine-tune planning parameters is time-consuming and is usually considered unpractical, especially for online ART. It is desirable to automate this step to yield a plan of acceptable quality with minimal interventions. In ART, prior information in the original plan is available, such as dose–volume histogram (DVH), which can be employed to facilitate the automatic re-planning process. The goal of this work is to develop an automatic re-planning algorithm to generate a plan with similar, or possibly better, DVH curves compared with the clinically delivered original plan. Specifically, our algorithm iterates the following two loops. An inner loop is the traditional fluence map optimization, in which we optimize a quadratic objective function penalizing the deviation of the dose received by each voxel from its prescribed or threshold dose with a set of fixed voxel weighting factors. In outer loop, the voxel weighting factors in the objective function are adjusted according to the deviation of the current DVH curves from those in the original plan. The process is repeated until the DVH curves are acceptable or maximum iteration step is reached. The whole algorithm is implemented on GPU for high efficiency. The feasibility of our algorithm has been demonstrated with three head-and-neck cancer IMRT cases, each having an initial planning CT scan and another treatment CT scan acquired in the middle of treatment course. Compared with the DVH curves in the original plan, the DVH curves in the resulting plan using our algorithm with 30 iterations are better for almost all structures. The re-optimization process takes about 30

  5. Pilot scale test of a produced water-treatment system for initial removal of organic compounds

    Energy Technology Data Exchange (ETDEWEB)

    Sullivan, Enid J [Los Alamos National Laboratory; Kwon, Soondong [UT-AUSTIN; Katz, Lynn [UT-AUSTIN; Kinney, Kerry [UT-AUSTIN

    2008-01-01

    A pilot-scale test to remove polar and non-polar organics from produced water was performed at a disposal facility in Farmington NM. We used surfactant-modified zeolite (SMZ) adsorbent beds and a membrane bioreactor (MBR) in combination to reduce the organic carbon content of produced water prior to reverse osmosis (RO). Reduction of total influent organic carbon (TOC) to 5 mg/L or less is desirable for efficient RO system operation. Most water disposed at the facility is from coal-bed gas production, with oil production waters intermixed. Up to 20 gal/d of produced water was cycled through two SMZ adsorbent units to remove volatile organic compounds (BTEX, acetone) and semivolatile organic compounds (e.g., napthalene). Output water from the SMZ units was sent to the MBR for removal of the organic acid component of TOC. Removal of inorganic (Mn and Fe oxide) particulates by the SMZ system was observed. The SMZ columns removed up to 40% of the influent TOC (600 mg/L). BTEX concentrations were reduced from the initial input of 70 mg/L to 5 mg/L by the SMZ and to an average of 2 mg/L after the MBR. Removal rates of acetate (input 120-170 mg/L) and TOC (input up to 45 mg/L) were up to 100% and 92%, respectively. The water pH rose from 8.5 to 8.8 following organic acid removal in the MBR; this relatively high pH was likely responsible for observed scaling of the MBR internal membrane. Additional laboratory studies showed the scaling can be reduced by metered addition of acid to reduce the pH. Significantly, organic removal in the MBR was accomplished with a very low biomass concentration of 1 g/L throughout the field trial. An earlier engineering evaluation shows produced water treatment by the SMZ/MBR/RO system would cost from $0.13 to $0.20 per bbl at up to 40 gpm. Current estimated disposal costs for produced water are $1.75 to $4.91 per bbl when transportation costs are included, with even higher rates in some regions. Our results suggest that treatment by an SMZ

  6. Metronidazole combined with nystatin (vagitories) in the prevention of bacterial vaginosis after initial treatment with oral metronidazole.

    Science.gov (United States)

    Pulkkinen, P; Saranen, M; Kaaja, R

    1993-01-01

    In a double-blind trial comprising 66 patients we assessed the effect of metronidazole-nystatin vagitories on the prevention of bacterial vaginosis (BV) in women using IUD as a contraceptive method after an initial oral single dose of 2.0 g metronidazole and 7 days of intravaginal metronidazole-nystatin or placebo treatment. The prophylactic treatment consisted of metronidazole-nystatin or placebo vagitories applied at bedtime for 3 days after menstruation over 6 consecutive menstrual periods. The patients were randomized in two study groups: a treatment group of 32 patients (group A) and a placebo group of 34 patients (group B). The overall objective cure rate after the initial treatment was 97% in group A and 91% in group B. After 6 months of follow-up, the overall cumulative objective cure rate in group A was 100%, and 76% in group B. The single-dose oral treatment was well tolerated and no notable side effects were recorded.

  7. Molecular Mechanisms of Foot-and-Mouth Disease Virus Targeting the Host Antiviral Response.

    Science.gov (United States)

    Rodríguez Pulido, Miguel; Sáiz, Margarita

    2017-01-01

    Foot-and-mouth disease virus (FMDV) is the causative agent of an acute vesicular disease affecting pigs, cattle and other domestic, and wild animals worldwide. The aim of the host interferon (IFN) response is to limit viral replication and spread. Detection of the viral genome and products by specialized cellular sensors initiates a signaling cascade that leads to a rapid antiviral response involving the secretion of type I- and type III-IFNs and other antiviral cytokines with antiproliferative and immunomodulatory functions. During co-evolution with their hosts, viruses have acquired strategies to actively counteract host antiviral responses and the balance between innate response and viral antagonism may determine the outcome of disease and pathogenesis. FMDV proteases Lpro and 3C have been found to antagonize the host IFN response by a repertoire of mechanisms. Moreover, the putative role of other viral proteins in IFN antagonism is being recently unveiled, uncovering sophisticated immune evasion strategies different to those reported to date for other members of the Picornaviridae family. Here, we review the interplay between antiviral responses induced by FMDV infection and viral countermeasures to block them. Research on strategies used by viruses to modulate immunity will provide insights into the function of host pathways involved in defense against pathogens and will also lead to development of new therapeutic strategies to fight virus infections.

  8. Systemic corticosteroids and early administration of antiviral agents for pneumonia with acute wheezing due to influenza A(H1N1pdm09 in Japan.

    Directory of Open Access Journals (Sweden)

    Koichiro Kudo

    Full Text Available BACKGROUND: Pneumonia patients with wheezing due to influenza A(H1N1pdm09 were frequently treated with systemic corticosteroids in Japan although systemic corticosteroid for critically ill patients with pneumonia caused by influenza A(H1N1pdm09 has been controversial. Applicability of systemic corticosteroid treatment needs to be evaluated. METHODS/PRINCIPAL FINDINGS: We retrospectively reviewed 89 subjects who were diagnosed with influenza A(H1N1pdm09 and admitted to a national hospital, Tokyo during the pandemic period. The median age of subjects (45 males was 8 years (range, 0-71. All subjects were treated with antiviral agents and the median time from symptom onset to initiation of antiviral agents was 2 days (range, 0-7. Subjects were classified into four groups: upper respiratory tract infection, wheezing illness, pneumonia with wheezing, and pneumonia without wheezing. The characteristics of each group was evaluated. A history of asthma was found more frequently in the wheezing illness (55.6% and pneumonia with wheezing (43.3% groups than in the other two groups (p = 0.017. Corticosteroid treatment was assessed among subjects with pneumonia. Oxygen saturation was lower in subjects receiving corticosteroids (steroid group than in subjects not receiving corticosteroids (no-steroid group (p<0.001. The steroid group required greater oxygen supply than the no-steroid group (p<0.001. No significant difference was found by the Kaplan-Meier method between the steroid and the no-steroid groups in hours to fever alleviation from the initiation of antiviral agents and hospitalization days. In logistic regression analysis, wheezing, pneumonia and oxygen saturation were independent factors associated with using systemic corticosteroids. CONCLUSION: Patients with wheezing and a history of asthma were frequently found in the study subjects. Systemic corticosteroids together with early administration of antiviral agents to pneumonia with wheezing and

  9. Smoking behavior and motivation to quit among chronic pain patients initiating multidisciplinary pain treatment: a prospective study.

    Science.gov (United States)

    Unrod, Marina; Gironda, Ronald J; Clark, Michael E; White, Kristi E; Simmons, Vani N; Sutton, Steven K; Brandon, Thomas H

    2014-08-01

    The primary aim of this study was to assess smoking characteristics and cessation motivation prior to and after initiation of multidisciplinary chronic pain treatment. A secondary aim was to identify predictors of cessation motivation among smokers initiating treatment for chronic pain. We used a prospective, nonrandomized, repeated measures design. The study was conducted in a multidisciplinary specialty pain treatment program at a veterans hospital. Smokers (N = 90) referred to a multidisciplinary pain program for the treatment of chronic pain. Patients completed questionnaires assessing pain-related and smoking-related factors prior to (baseline) and 8 weeks post (follow-up) specialty pain treatment initiation. Primary outcome measures were the Contemplation Ladder and the Stages of Change (SOC) algorithm. At baseline, patients reported moderate levels of cessation motivation, and 69% were in the contemplation stage or higher on the SOC. Motivation to quit smoking was higher at follow-up compared with baseline on both continuous, t(89) = 2.11, P motivation (e.g., pain intensity) were subsumed by more general predictors (e.g., nicotine dependence). Patients in this sample were more motivated to quit smoking a few weeks after, as compared with before initiating specialty pain treatment. Future research into pain-specific predictors of cessation motivation is warranted to inform the development of interventions that address pain patients' unique needs. Wiley Periodicals, Inc.

  10. Cost and consequences of noncompliance with osteoporosis treatment among women initiating therapy.

    Science.gov (United States)

    Modi, Ankita; Siris, Ethel S; Tang, Jackson; Sen, Shuvayu

    2015-04-01

    The objective was to evaluate compliance with osteoporosis (OP) treatments and determine the fracture and healthcare burden associated with noncompliance. This retrospective analysis of a US claims database identified women initiating an OP medication from 1 January 2002 to 30 June 2009. Patients were ≥55 years and had ≥1 pharmacy claim for a bisphosphonate or non-bisphosphonate (raloxifene, calcitonin, teriparatide); the index date was the first pharmacy claim. There were three study periods: baseline (12 months pre-index); compliance period (0-12 months post-index); and follow-up period (12-24 months post-index). Medication possession ratio (MPR) was calculated during the compliance period to differentiate two cohorts: compliant (MPR ≥ 80%) and noncompliant (MPR costs), all adjusted for patient demographic and clinical characteristics. Overall, 685,505 women initiating OP therapy were identified and 57,913 (8.4%) met the inclusion criteria: only 23,430 (40.5%) were compliant and 34,483 (59.5%) were noncompliant. Mean age was 64 years. Noncompliance was associated with a 20% higher risk of any fracture (odds ratio: 1.20, 95% CI = 1.07-1.35), a higher incidence rate ratio (IRR) for inpatient utilization (IRR: 1.26, 95% CI = 1.19-1.34) and a lower rate of outpatient utilization (IRR: 0.97, 95% CI = 0.95-0.98). Noncompliant patients had 13% higher medical costs (cost ratio: 1.13, 95% CI = 1.06-1.21) than compliant patients. Inclusion in this study required 36 months of continuous healthcare coverage. Thus, the results are primarily applicable to a stable, managed care population and may not be generalizable to other populations. Noncompliance with OP therapy was associated with a higher risk of fracture, higher all-cause medical costs and a higher frequency of inpatient service utilization. Additional research is needed to identify barriers to compliance with OP therapy.

  11. Antiretroviral treatment initiation does not differentially alter neurocognitive functioning over time in youth with behaviorally acquired HIV.

    Science.gov (United States)

    Nichols, Sharon L; Bethel, James; Kapogiannis, Bill G; Li, Tiandong; Woods, Steven P; Patton, E Doyle; Ren, Weijia; Thornton, Sarah E; Major-Wilson, Hanna O; Puga, Ana M; Sleasman, John W; Rudy, Bret J; Wilson, Craig M; Garvie, Patricia A

    2016-04-01

    Although youth living with behaviorally acquired HIV (YLWH) are at risk for cognitive impairments, the relationship of impairments to HIV and potential to improve with antiretroviral therapy (ART) are unclear. This prospective observational study was designed to examine the impact of initiation and timing of ART on neurocognitive functioning in YLWH in the Adolescent Medicine Trials Network for HIV/AIDS Interventions. Treatment naïve YLWH age 18-24 completed baseline and four additional assessments of attention/working memory, complex executive, and motor functioning over 3 years. Group 1 co-enrolled in an early ART initiation study and initiated ART at enrollment CD4 >350 (n = 56); group 2 had CD4 >350 and were not initiating ART (n = 66); group 3 initiated ART with CD4 treatment guidelines at the time. Treatment was de-intensified to boosted protease inhibitor monotherapy at 48 weeks for those in group 1 with suppressed viral load. Covariates included demographic, behavioral, and medical history variables. Analyses used hierarchical linear modeling. All groups showed improved performance with peak at 96 weeks in all three functional domains. Trajectories of change were not significantly associated with treatment, timing of treatment initiation, or ART de-intensification. Demographic variables and comorbidities were associated with baseline functioning but did not directly interact with change over time. In conclusion, YLWH showed improvement in neurocognitive functioning over time that may be related to practice effects and nonspecific impact of study participation. Neither improvement nor decline in functioning was associated with timing of ART initiation or therapy de-intensification.

  12. Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses

    Directory of Open Access Journals (Sweden)

    Danielle Blondel

    2015-07-01

    Full Text Available Interferon (IFN treatment induces the expression of hundreds of IFN-stimulated genes (ISGs. However, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models. IFNs inhibit rhabdovirus replication at different stages via the induction of a variety of ISGs. This review will discuss how individual ISG products confer resistance to rhabdoviruses by blocking viral entry, degrading single stranded viral RNA, inhibiting viral translation or preventing release of virions from the cell. Furthermore, this review will highlight how these viruses counteract the host IFN system.

  13. Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses.

    Science.gov (United States)

    Blondel, Danielle; Maarifi, Ghizlane; Nisole, Sébastien; Chelbi-Alix, Mounira K

    2015-07-07

    Interferon (IFN) treatment induces the expression of hundreds of IFN-stimulated genes (ISGs). However, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models. IFNs inhibit rhabdovirus replication at different stages via the induction of a variety of ISGs. This review will discuss how individual ISG products confer resistance to rhabdoviruses by blocking viral entry, degrading single stranded viral RNA, inhibiting viral translation or preventing release of virions from the cell. Furthermore, this review will highlight how these viruses counteract the host IFN system.

  14. Resistance to Rhabdoviridae Infection and Subversion of Antiviral Responses

    Science.gov (United States)

    Blondel, Danielle; Maarifi, Ghizlane; Nisole, Sébastien; Chelbi-Alix, Mounira K.

    2015-01-01

    Interferon (IFN) treatment induces the expression of hundreds of IFN-stimulated genes (ISGs). However, only a selection of their products have been demonstrated to be responsible for the inhibition of rhabdovirus replication in cultured cells; and only a few have been shown to play a role in mediating the antiviral response in vivo using gene knockout mouse models. IFNs inhibit rhabdovirus  replication at different stages via the induction of a variety of ISGs. This review will discuss how individual ISG products confer resistance to rhabdoviruses by blocking viral entry, degrading single stranded viral RNA, inhibiting viral translation or preventing release of virions from the cell. Furthermore, this review will highlight how these viruses counteract the host IFN system. PMID:26198243

  15. Towards antiviral therapies for treating dengue virus infections.

    Science.gov (United States)

    Kaptein, Suzanne Jf; Neyts, Johan

    2016-10-01

    Dengue virus is an emerging human pathogen that poses a huge public health burden by infecting annually about 390 million individuals of which a quarter report with clinical manifestations. Although progress has been made in understanding dengue pathogenesis, a licensed vaccine or antiviral therapy against this virus is still lacking. Treatment of patients is confined to symptomatic alleviation and supportive care. The development of dengue therapeutics thus remains of utmost importance. This review focuses on the few molecules that were evaluated in dengue virus-infected patients: balapiravir, chloroquine, lovastatin, prednisolone and celgosivir. The lessons learned from these clinical trials can be very helpful for the design of future trials for the next generation of dengue virus inhibitors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. The development of a gender identity psychosocial clinic: treatment issues, logistical considerations, interdisciplinary cooperation, and future initiatives.

    Science.gov (United States)

    Leibowitz, Scott F; Spack, Norman P

    2011-10-01

    Few interdisciplinary treatment programs that tend to the needs of youth with gender nonconforming behaviors, expressions, and identities exist in academic medical centers with formal residency training programs. Despite this, the literature provides evidence that these youth have higher rates of poor psychosocial adjustment and suicide attempts. This article explores the logistical considerations involved in developing a specialized interdisciplinary service to these gender minority youth in accordance with the existing treatment guidelines.Demographic data will be presented and treatment issues will be explored. The impact that a specialized interdisciplinary treatment program has on clinical expansion, research development, education and training, and community outreach initiatives is discussed.

  17. Antiviral potential of a diterpenoid compound sugiol from Metasequoia glyptostroboides.

    Science.gov (United States)

    Bajpai, Vivek K; Kim, Na-Hyung; Kim, Kangmin; Kang, Sun Chul

    2016-05-01

    This research reports first time antiviral activity of sugiol, a diterpenoid isolated from Metasequoia glyptostroboides in terms of its ability to inhibit in vitro growth of H1N1 influenza virus. Antiviral potential of sugiol was evaluated through hcytopathogenic reduction assay using Madin-Darby canine kidney (MDCK) cell line. Sugiol (500 μg/ml) was found to exhibit considerable anti-cytopathic effect on MDCK cell line confirming its antiviral efficacy against H1N1 influenza virus. These findings strongly reinforce the suggestion that sugiol could be a candidate of choice in combinational regimen with potential antiviral efficacy.

  18. Filtering data from the collaborative initial glaucoma treatment study for improved identification of glaucoma progression.

    Science.gov (United States)

    Schell, Greggory J; Lavieri, Mariel S; Stein, Joshua D; Musch, David C

    2013-12-21

    Open-angle glaucoma (OAG) is a prevalent, degenerate ocular disease which can lead to blindness without proper clinical management. The tests used to assess disease progression are susceptible to process and measurement noise. The aim of this study was to develop a methodology which accounts for the inherent noise in the data and improve significant disease progression identification. Longitudinal observations from the Collaborative Initial Glaucoma Treatment Study (CIGTS) were used to parameterize and validate a Kalman filter model and logistic regression function. The Kalman filter estimates the true value of biomarkers associated with OAG and forecasts future values of these variables. We develop two logistic regression models via generalized estimating equations (GEE) for calculating the probability of experiencing significant OAG progression: one model based on the raw measurements from CIGTS and another model based on the Kalman filter estimates of the CIGTS data. Receiver operating characteristic (ROC) curves and associated area under the ROC curve (AUC) estimates are calculated using cross-fold validation. The logistic regression model developed using Kalman filter estimates as data input achieves higher sensitivity and specificity than the model developed using raw measurements. The mean AUC for the Kalman filter-based model is 0.961 while the mean AUC for the raw measurements model is 0.889. Hence, using the probability function generated via Kalman filter estimates and GEE for logistic regression, we are able to more accurately classify patients and instances as experiencing significant OAG progression. A Kalman filter approach for estimating the true value of OAG biomarkers resulted in data input which improved the accuracy of a logistic regression classification model compared to a model using raw measurements as input. This methodology accounts for process and measurement noise to enable improved discrimination between progression and nonprogression

  19. Initial experience with xenograft bioconduit for the treatment of complex prosthetic valve endocarditis.

    Science.gov (United States)

    Roubelakis, Apostolos; Karangelis, Dimos; Sadeque, Syed; Yanagawa, Bobby; Modi, Amit; Barlow, Clifford W; Livesey, Steven A; Ohri, Sunil K

    2017-07-01

    The treatment of complex prosthetic valve endocarditis (PVE) with aortic root abscess remains a surgical challenge. Several studies support the use of biological tissues to minimize the risk of recurrent infection. We present our initial surgical experience with the use of an aortic xenograft conduit for aortic valve and root replacement. Between October 2013 and August 2015, 15 xenograft bioconduits were implanted for complex PVE with abscess (13.3% female). In 6 patients, concomitant procedures were performed: coronary bypass (n=1), mitral valve replacement (n=5) and tricuspid annuloplasty (n=1). The mean age at operation was 60.3±15.5 years. The mean Logistic European system for cardiac operating risk evaluation (EuroSCORE) was 46.6±23.6. The median follow-up time was 607±328 days (range: 172-1074 days). There were two in-hospital deaths (14.3% mortality), two strokes (14.3%) and seven patients required permanent pacemaker insertion for conduction abnormalities (46.7%). The mean length of hospital stay was 26 days. At pre-discharge echocardiography, the conduit mean gradient was 9.3±3.3mmHg and there was either none (n=6), trace (n=6) or mild aortic insufficiency (n=1). There was no incidence of mid-term death, prosthesis-related complications or recurrent endocarditis. Xenograft bioconduits may be safe and effective for aortic valve and root replacement for complex PVE with aortic root abscess. Although excess early mortality reflects the complexity of the patient population, there was good valve hemodynamics, with no incidence of recurrent endocarditis or prosthesis failure in the mid-term. Our data support the continued use and evaluation of this biological prosthesis in this high-risk patient cohort.

  20. Atividade antiviral de Musa acuminata Colla, Musaceae

    Directory of Open Access Journals (Sweden)

    Fernanda Otaviano Martins

    Full Text Available O presente trabalho avalia a atividade antiviral de extratos e frações de Musa acuminata Colla, Musaceae, coletada em duas regiões do Estado do Rio de Janeiro (Petrópolis e Santo Antônio de Pádua. As inflorescências de M. acuminata apresentaram excelente atividade para os dois vírus avaliados: herpesvírus simples humano tipo 1 e herpesvírus simples humano tipo 2, ambos resistentes ao Aciclovir. Os resultados indicam que os extratos de M. acuminata testados podem constituir alvo potencial para uso em terapias antivirais.

  1. Mapping the Barriers and Facilitators of HCV Treatment Initiation in Methadone Maintenance Therapy Patients: Implications for Intervention Development.

    Science.gov (United States)

    Bass, Sarah Bauerle; Jessop, Amy; Maurer, Laurie; Gashat, Muhamed; Al Hajji, Mohammed; Gutierrez, Mercedes

    2018-01-01

    An estimated 70-90% of current methadone users have Hepatitis C (HCV). Current treatments have few side effects and can cure infection in 8-12 weeks, but less than 10% of methadone patients initiate treatment. Engaging this group in treatment is an important strategy to lower both morbidity and mortality from liver disease and eliminate a significant reservoir of HCV in communities. To understand how to address this treatment gap we used commercial marketing techniques called perceptual mapping and vector message modeling to analyze survey data from 100 HCV+ methadone patients from four centers in Philadelphia. Results were used to understand barriers and facilitators to treatment initiation and to devise targeted message strategies to adapt to a mobile health communication intervention. Results indicate that focusing on how treatment can make one feel "in charge", positive interactions with healthcare providers, the positive attributes of the new vs. old HCV treatments, and providing strategies to address tangible barriers to getting treatment, would be important to address in a communication intervention. These marketing methods allow for focusing on specific variables to "move" the group toward a treatment decision, making them an innovative technique to use in developing highly targeted health communication messages.

  2. Influence of psychiatric diagnosis on treatment uptake and interferon side effects in patients with hepatitis C.

    Science.gov (United States)

    Wu, Jing Yuan J; Shadbolt, Bruce; Teoh, Narci; Blunn, Anne; To, Caroline; Rodriguez-Morales, Ilys; Chitturi, Shivakumar; Kaye, Graham; Rodrigo, Kalyana; Farrell, Geoff

    2014-06-01

    Pegylated-interferon-α/ribavirin (PEG-IFN/RBV) treatment can cure hepatitis C virus (HCV) infection but has frequent neuropsychiatric side-effects. Patients with pre-existing psychiatric illness may not be offered therapy. We established prevalence of self-reported psychiatric comorbidity among HCV-infected patients in a hospital-liver clinic, and determined the impact of such diagnoses on uptake and tolerance to PEG-IFN/RBV. All HCV cases referred for assessment in Australian Capital Territory/surrounding regions April 2004-March 2012 were entered into a clinical database. We conducted univariate and multivariate analyses of variables correlating with uptake of antiviral therapy and frequency of treatment-related side-effects. Of 773 referred patients, 235 (30%) described pre-existing psychiatric illness. Among these, 26% received antiviral therapy, compared with 30% of 538 without psychiatric comorbidity. History of depression (usually validated by liaison psychiatry) was associated with higher incidence of treatment-related neuropsychiatric side-effects (odds ratio 2.79 [1.35-5.70], P schizophrenia: three (11%) received antiviral therapy, compared with 30% admitting depression and 20% with bipolar affective disorder (all assessed by psychiatrist). In most schizophrenia cases, the reason for not offering antiviral treatment was psychological illness, yet none of five treated (these three plus two others in a psychiatric rehabilitation facility) experienced worsening psychiatric symptoms. A history of depression is common with hepatitis C but does not affect initiation of antiviral treatment, despite substantially increased risk of psychiatric side-effects. In contrast, pre-existing schizophrenia appears to influence treatment decisions, despite little evidence that PEG-IFN/RBV exacerbates the psychiatric condition, and well-supervised antiviral therapy can have good outcomes.

  3. Limiting the access to direct-acting antivirals against HCV: an ethical dilemma.

    Science.gov (United States)

    Gentile, Ivan; Maraolo, Alberto E; Niola, Massimo; Graziano, Vincenzo; Borgia, Guglielmo; Paternoster, Mariano

    2016-11-01

    Hepatitis C virus (HCV) infection affects about 200 million people worldwide and represents a leading cause of liver-related mortality. Eradication of HCV infection, achieved mainly through direct-acting antivirals (DAA), results in a decrease of mortality and an improvement of quality of life. These drugs have a maximal efficacy and an optimal tolerability. However, their high cost precludes a universal access even in wealthy countries. Areas covered: This article deals with the policies adopted for the use of the new anti-HCV drugs, especially in Europe and most of all in Italy, supposedly the developed country with the highest HCV prevalence. The literature search was performed using Pubmed and Web of Science. Moreover, national regulatory institutional websites were consulted. Expert commentary: The current policy of limitation to the access of the DAA presents a series of ethical issues that makes it non-applicable. A 'treat-all' strategy should resolve all ethical dilemmas, by virtue of the wide benefits of anti-HCV treatment not only for the advanced stage of infection, but also for the initial stages. A reduction in price of the drugs is the actual condition to achieve such a change.

  4. Evasion of the Interferon-Mediated Antiviral Response by Filoviruses

    Directory of Open Access Journals (Sweden)

    Washington B. Cárdenas

    2010-01-01

    Full Text Available The members of the filoviruses are recognized as some of the most lethal viruses affecting human and non-human primates. The only two genera of the Filoviridae family, Marburg virus (MARV and Ebola virus (EBOV, comprise the main etiologic agents of severe hemorrhagic fever outbreaks in central Africa, with case fatality rates ranging from 25 to 90%. Fatal outcomes have been associated with a late and dysregulated immune response to infection, very likely due to the virus targeting key host immune cells, such as macrophages and dendritic cells (DCs that are necessary to mediate effective innate and adaptive immune responses. Despite major progress in the development of vaccine candidates for filovirus infections, a licensed vaccine or therapy for human use is still not available. During the last ten years, important progress has been made in understanding the molecular mechanisms of filovirus pathogenesis. Several lines of evidence implicate the impairment of the host interferon (IFN antiviral innate immune response by MARV or EBOV as an important determinant of virulence. In vitro and in vivo experimental infections with recombinant Zaire Ebola virus (ZEBOV, the best characterized filovirus, demonstrated that the viral protein VP35 plays a key role in inhibiting the production of IFN-α/β. Further, the action of VP35 is synergized by the inhibition of cellular responses to IFN-α/β by the minor matrix viral protein VP24. The dual action of these viral proteins may contribute to an efficient initial virus replication and dissemination in the host. Noticeably, the analogous function of these viral proteins in MARV has not been reported. Because the IFN response is a major component of the innate immune response to virus infection, this chapter reviews recent findings on the molecular mechanisms of IFN-mediated antiviral evasion by filovirus infection.

  5. A molecular arms race between host innate antiviral response and emerging human coronaviruses.

    Science.gov (United States)

    Wong, Lok-Yin Roy; Lui, Pak-Yin; Jin, Dong-Yan

    2016-02-01

    Coronaviruses have been closely related with mankind for thousands of years. Community-acquired human coronaviruses have long been recognized to cause common cold. However, zoonotic coronaviruses are now becoming more a global concern with the discovery of highly pathogenic severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS) coronaviruses causing severe respiratory diseases. Infections by these emerging human coronaviruses are characterized by less robust interferon production. Treatment of patients with recombinant interferon regimen promises beneficial outcomes, suggesting that compromised interferon expression might contribute at least partially to the severity of disease. The mechanisms by which coronaviruses evade host innate antiviral response are under intense investigations. This review focuses on the fierce arms race between host innate antiviral immunity and emerging human coronaviruses. Particularly, the host pathogen recognition receptors and the signal transduction pathways to mount an effective antiviral response against SARS and MERS coronavirus infection are discussed. On the other hand, the counter-measures evolved by SARS and MERS coronaviruses to circumvent host defense are also dissected. With a better understanding of the dynamic interaction between host and coronaviruses, it is hoped that insights on the pathogenesis of newly-identified highly pathogenic human coronaviruses and new strategies in antiviral development can be derived.

  6. Real-world effectiveness, adherence and persistence among patients with type 2 diabetes mellitus initiating dulaglutide treatment.

    Science.gov (United States)

    Mody, Reema; Grabner, Michael; Yu, Maria; Turner, Ralph; Kwan, Anita Y M; York, Whitney; Fernández Landó, Laura

    2018-06-01

    To assess glycemic effectiveness, adherence and persistence within 6 months of treatment initiation with dulaglutide, a once weekly GLP-1 receptor agonist, in a US real-world setting. This retrospective claims analysis included adults (≥18 years) with T2DM from the HealthCore Integrated Research Database, who had HbA1c laboratory results around initiation and within 6 months after initiation. Glycemic control was assessed by change in HbA1c from pre-initiation to post-initiation. Patients were considered adherent if their proportion of days covered (PDC) was ≥0.80; persistence was measured as days of continuous therapy from initiation to 6 months after initiation with no gaps >45 days between fills. Of the 308 analyzed patients, the majority (n = 188; 61%) were adherent to dulaglutide (mean PDC 0.76; SD 0.26), with 115 patients (37%) discontinuing treatment. Mean persistence was 152 days/5 months. Mean HbA1c decreased from 8.49% (SD 1.70, median 8.20%) at baseline to 7.59% (SD 1.51, median 7.30%) at follow-up, corresponding to a mean HbA1c change of -0.90% (95% confidence interval [CI] -1.08 to -0.73; p < .01; median -0.70%). Patients who were adherent to or persistent with dulaglutide experienced larger reductions (-1.14% and -1.12% respectively), as did those without prior GLP-1 RA use (-1.03%). The proportion of patients with HbA1c <7% increased from 18% to 40%. Dulaglutide was associated with a significant decrease in HbA1c levels 6 months after treatment initiation. Patients who adhered to or persisted with dulaglutide therapy, or were naïve to GLP-1 RA use, experienced greater decreases in HbA1c levels.

  7. The Impact of a Line Probe Assay Based Diagnostic Algorithm on Time to Treatment Initiation and Treatment Outcomes for Multidrug Resistant TB Patients in Arkhangelsk Region, Russia.

    Science.gov (United States)

    Eliseev, Platon; Balantcev, Grigory; Nikishova, Elena; Gaida, Anastasia; Bogdanova, Elena; Enarson, Donald; Ornstein, Tara; Detjen, Anne; Dacombe, Russell; Gospodarevskaya, Elena; Phillips, Patrick P J; Mann, Gillian; Squire, Stephen Bertel; Mariandyshev, Andrei

    2016-01-01

    In the Arkhangelsk region of Northern Russia, multidrug-resistant (MDR) tuberculosis (TB) rates in new cases are amongst the highest in the world. In 2014, MDR-TB rates reached 31.7% among new cases and 56.9% among retreatment cases. The development of new diagnostic tools allows for faster detection of both TB and MDR-TB and should lead to reduced transmission by earlier initiation of anti-TB therapy. The PROVE-IT (Policy Relevant Outcomes from Validating Evidence on Impact) Russia study aimed to assess the impact of the implementation of line probe assay (LPA) as part of an LPA-based diagnostic algorithm for patients with presumptive MDR-TB focusing on time to treatment initiation with time from first-care seeking visit to the initiation of MDR-TB treatment rather than diagnostic accuracy as the primary outcome, and to assess treatment outcomes. We hypothesized that the implementation of LPA would result in faster time to treatment initiation and better treatment outcomes. A culture-based diagnostic algorithm used prior to LPA implementation was compared to an LPA-based algorithm that replaced BacTAlert and Löwenstein Jensen (LJ) for drug sensitivity testing. A total of 295 MDR-TB patients were included in the study, 163 diagnosed with the culture-based algorithm, 132 with the LPA-based algorithm. Among smear positive patients, the implementation of the LPA-based algorithm was associated with a median decrease in time to MDR-TB treatment initiation of 50 and 66 days compared to the culture-based algorithm (BacTAlert and LJ respectively, ptime to MDR-TB treatment initiation of 78 days when compared to the culture-based algorithm (LJ, ptime to MDR diagnosis and earlier treatment initiation as well as better treatment outcomes for patients with MDR-TB. These findings also highlight the need for further improvements within the health system to reduce both patient and diagnostic delays to truly optimize the impact of new, rapid diagnostics.

  8. Barriers to initiating tuberculosis treatment in sub-Saharan Africa: a systematic review focused on children and youth.

    Science.gov (United States)

    Sullivan, Brittney J; Esmaili, B Emily; Cunningham, Coleen K

    2017-01-01

    Tuberculosis (TB) is the deadliest infectious disease globally, with 10.4 million people infected and more than 1.8 million deaths in 2015. TB is a preventable, treatable, and curable disease, yet there are numerous barriers to initiating treatment. These barriers to treatment are exacerbated in low-resource settings and may be compounded by factors related to childhood. Timely initiation of tuberculosis (TB) treatment is critical to reducing disease transmission and improving patient outcomes. The aim of this paper is to describe patient- and system-level barriers to TB treatment initiation specifically for children and youth in sub-Saharan Africa through systematic review of the literature. This review was conducted in October 2015 in accordance with preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Six databases were searched to identify studies where primary or secondary objectives were related to barriers to TB treatment initiation and which included children or youth 0-24 years of age. A total of 1490 manuscripts met screening criteria; 152 met criteria for full-text review and 47 for analysis. Patient-level barriers included limited knowledge, attitudes and beliefs regarding TB, and economic burdens. System-level barriers included centralization of services, health system delays, and geographical access to healthcare. Of the 47 studies included, 7 evaluated cost, 19 health-seeking behaviors, and 29 health system infrastructure. Only 4 studies primarily assessed pediatric cohorts yet all 47 studies were inclusive of children. Recognizing and removing barriers to treatment initiation for pediatric TB in sub-Saharan Africa are critical. Both patient- and system-level barriers must be better researched in order to improve patient outcomes.

  9. Parents report on stimulant-treated children in the Netherlands : Initiation of treatment and follow-up care

    NARCIS (Netherlands)

    Faber, Adrianne; Kalverdijk, Luuk J.; de Jong-van den Berg, Lolkje T. W.; Hugtenburg, Jacqueline G.; Minderaa, Ruud B.; Tobi, Hilde

    Objectives: The aim of this study was to describe current practices around initiation and follow-up care of stimulant treatment among stimulant-treated children in a nationwide survey among parents. Methods: A total of 115 pharmacies detected current stimulant users <16 years old in their pharmacy

  10. Predicting Post-Treatment-Initiation Alcohol Use among Patients with Severe Mental Illness and Alcohol Use Disorders

    Science.gov (United States)

    Bradizza, Clara M.; Maisto, Stephen A.; Vincent, Paula C.; Stasiewicz, Paul R.; Connors, Gerard J.; Mercer, Nicole D.

    2009-01-01

    Few investigators studying alcohol abuse among individuals with a severe mental illness (SMI) have examined predictors of posttreatment alcohol outcomes. In the present study, a multivariate approach based on a theoretical model was used to study the relationship between psychosocial factors and post-treatment-initiation alcohol use. Predictors of…

  11. Initiation of Addiction Treatment and Access to Services: Young Adults' Accounts of Their Help-Seeking Experiences.

    Science.gov (United States)

    Wagner, Vincent; Bertrand, Karine; Flores-Aranda, Jorge; Acier, Didier; Brunelle, Natacha; Landry, Michel; Brochu, Serge

    2017-09-01

    Substance addiction in young adults is particularly problematic. Yet, much remain at stake in understanding the specifics of this population's access to services. The objective of this study is to explore young adults' initiation of substance misuse treatment. Our study sample was composed of 35 individuals aged 18 to 30 with problematic psychoactive substance use who have been identified in criminal courts, hospital emergency departments, and Health and Social Services Centers in Québec (Canada). A thematic analysis was performed on the 62 semi-structured interviews conducted with participants. Three components emerged. First, personal elements-expectations, individual motivations, perceptions of use, and capacity to control it-influence initiation of substance misuse treatment. Second, family and peers have noticeable influences. Finally, system characteristics and prior care experiences also shape the process. Consideration should be given to tailor interventions that can reach young adults and encourage them to initiate appropriate care.

  12. The long-term prognosis for live birth in couples initiating fertility treatments

    DEFF Research Database (Denmark)

    Malchau, S. S.; Henningsen, A. A.; Loft, A.

    2017-01-01

    -26% in women ≥40 years, overall, 14% of couples conceived naturally and one-third of couples starting treatments with intrauterine insemination delivered from that treatment. WHAT IS KNOWN ALREADY: Few studies report success rates in fertility treatments across a couple's complete fertility treatment history......STUDY QUESTION: What are the long-term chances of having a child for couples starting fertility treatments and how many conceive with ART, IUI and without treatment? SUMMARY ANSWER: Total 5-year live birthrates were strongly influenced by female age and ranged from 80% in women under 35...... years (N = 3553), 35-39 years (N = 1156) and ≥40 years (N = 451), a total of 64%, 49% and 16% had a live birth due to treatment, respectively. Additionally, in women aged years, 35-39 years and ≥40 years, 16%, 11% and 10% delivered after natural conception, yielding total 5-year birthrates of 80...

  13. Autophagy is involved in anti-viral activity of pentagalloylglucose (PGG) against Herpes simplex virus type 1 infection in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Pei, Ying, E-mail: peiying-19802@163.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Chen, Zhen-Ping, E-mail: 530670663@qq.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Ju, Huai-Qiang, E-mail: 344464448@qq.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Komatsu, Masaaki, E-mail: komatsu-ms@igakuken.or.jp [Laboratory of Frontier Science, Tokyo Metropolitan Institute of Medical Science, Bunkyo-ku, Tokyo 113-8613 (Japan); Ji, Yu-hua, E-mail: tjyh@jnu.edu.cn [Institute of Tissue Transplantation and Immunology, College of Life Science and Technology, Jinan University, Guangzhou 510632 (China); Liu, Ge, E-mail: lggege_15@hotmail.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Guo, Chao-wan, E-mail: chaovan_kwok@hotmail.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan); Zhang, Ying-Jun, E-mail: zhangyj@mail.kib.ac.cn [Kunming Institute of Botany, the Chinese Academy of Sciences, Yunnan, Kunming 650204 (China); Yang, Chong-Ren, E-mail: cryang@mail.kib.ac.cn [Kunming Institute of Botany, the Chinese Academy of Sciences, Yunnan, Kunming 650204 (China); Wang, Yi-Fei, E-mail: twang-yf@163.com [Biomedicine Research and Development Center of Jinan University, Guangzhou, Guangdong 510632 (China); Kitazato, Kaio, E-mail: kkholi@msn.com [Division of Molecular Pharmacology of Infectious agents, Department of Molecular Microbiology and Immunology, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki 852-8521 (Japan)

    2011-02-11

    Research highlights: {yields} We showed PGG has anti-viral activity against Herpes simplex virus type 1 (HSV-1) and can induce autophgy. {yields} Autophagy may be a novel and important mechanism mediating PGG anti-viral activities. {yields} Inhibition of mTOR pathway is an important mechanism of induction of autophagy by PGG. -- Abstract: Pentagalloylglucose (PGG) is a natural polyphenolic compound with broad-spectrum anti-viral activity, however, the mechanisms underlying anti-viral activity remain undefined. In this study, we investigated the effects of PGG on anti-viral activity against Herpes simplex virus type 1 (HSV-1) associated with autophagy. We found that the PGG anti-HSV-1 activity was impaired significantly in MEF-atg7{sup -/-} cells (autophagy-defective cells) derived from an atg7{sup -/-} knockout mouse. Transmission electron microscopy revealed that PGG-induced autophagosomes engulfed HSV-1 virions. The mTOR signaling pathway, an essential pathway for the regulation of autophagy, was found to be suppressed following PGG treatment. Data presented in this report demonstrated for the first time that autophagy induced following PGG treatment contributed to its anti-HSV activity in vitro.

  14. Autophagy is involved in anti-viral activity of pentagalloylglucose (PGG) against Herpes simplex virus type 1 infection in vitro

    International Nuclear Information System (INIS)

    Pei, Ying; Chen, Zhen-Ping; Ju, Huai-Qiang; Komatsu, Masaaki; Ji, Yu-hua; Liu, Ge; Guo, Chao-wan; Zhang, Ying-Jun; Yang, Chong-Ren; Wang, Yi-Fei; Kitazato, Kaio

    2011-01-01

    Research highlights: → We showed PGG has anti-viral activity against Herpes simplex virus type 1 (HSV-1) and can induce autophgy. → Autophagy may be a novel and important mechanism mediating PGG anti-viral activities. → Inhibition of mTOR pathway is an important mechanism of induction of autophagy by PGG. -- Abstract: Pentagalloylglucose (PGG) is a natural polyphenolic compound with broad-spectrum anti-viral activity, however, the mechanisms underlying anti-viral activity remain undefined. In this study, we investigated the effects of PGG on anti-viral activity against Herpes simplex virus type 1 (HSV-1) associated with autophagy. We found that the PGG anti-HSV-1 activity was impaired significantly in MEF-atg7 -/- cells (autophagy-defective cells) derived from an atg7 -/- knockout mouse. Transmission electron microscopy revealed that PGG-induced autophagosomes engulfed HSV-1 virions. The mTOR signaling pathway, an essential pathway for the regulation of autophagy, was found to be suppressed following PGG treatment. Data presented in this report demonstrated for the first time that autophagy induced following PGG treatment contributed to its anti-HSV activity in vitro.

  15. Clinical features and effect of antiviral therapy on anti-liver/kidney microsomal antibody type 1 positive chronic hepatitis C.

    Science.gov (United States)

    Ferri, Silvia; Muratori, Luigi; Quarneti, Chiara; Muratori, Paolo; Menichella, Rita; Pappas, Georgios; Granito, Alessandro; Ballardini, Giorgio; Bianchi, Francesco B; Lenzi, Marco

    2009-06-01

    Anti-liver/kidney microsomal antibody type 1 (anti-LKM1), a serological marker of type 2 autoimmune hepatitis, is also detected in a small proportion of patients with hepatitis C. This study aimed to evaluate clinical features and effect of antiviral therapy in patients with hepatitis C who are anti-LKM1 positive. Sixty consecutive anti-LKM1 positive and 120 age and sex-matched anti-LKM1 negative chronic hepatitis C patients were assessed at diagnosis and during follow-up. Of these, 26 anti-LKM1 positive and 72 anti-LKM1 negative received antiviral therapy. Anti-LKM1 was detected by indirect immunofluorescence and immunoblot. Number of HCV-infected hepatocytes and intrahepatic CD8+ lymphocytes was determined by immunohistochemistry. At diagnosis anti-LKM1 positive patients had higher IgG levels and more intrahepatic CD8+ lymphocytes (p 0.022 and 0.046, respectively). Viral genotypes distribution and response to therapy were identical. Hepatic flares during antiviral treatment only occurred in a minority of patients in concomitance with anti-LKM1 positivity. Immune system activation is more pronounced in anti-LKM1 positive patients with hepatitis C, possibly representing the expression of autoimmune mechanisms of liver damage. Antiviral treatment is as beneficial in these patients as in anti-LKM1 negative patients, and the rare necroinflammatory flares are effectively controlled by corticosteroids, allowing subsequent resumption of antiviral therapy.

  16. Potential of small-molecule fungal metabolites in antiviral chemotherapy.

    Science.gov (United States)

    Roy, Biswajit G

    2017-08-01

    Various viral diseases, such as acquired immunodeficiency syndrome, influenza, and hepatitis, have emerged as leading causes of human death worldwide. Scientific endeavor since invention of DNA-dependent RNA polymerase of pox virus in 1967 resulted in better understanding of virus replication and development of various novel therapeutic strategies. Despite considerable advancement in every facet of drug discovery process, development of commercially viable, safe, and effective drugs for these viruses still remains a big challenge. Decades of intense research yielded a handful of natural and synthetic therapeutic options. But emergence of new viruses and drug-resistant viral strains had made new drug development process a never-ending battle. Small-molecule fungal metabolites due to their vast diversity, stereochemical complexity, and preapproved biocompatibility always remain an attractive source for new drug discovery. Though, exploration of therapeutic importance of fungal metabolites has started early with discovery of penicillin, recent prediction asserted that only a small percentage (5-10%) of fungal species have been identified and much less have been scientifically investigated. Therefore, exploration of new fungal metabolites, their bioassay, and subsequent mechanistic study bears huge importance in new drug discovery endeavors. Though no fungal metabolites so far approved for antiviral treatment, many of these exhibited high potential against various viral diseases. This review comprehensively discussed about antiviral activities of fungal metabolites of diverse origin against some important viral diseases. This also highlighted the mechanistic details of inhibition of viral replication along with structure-activity relationship of some common and important classes of fungal metabolites.

  17. More Chemotherapy May Help after Initial Treatment for Childhood Leukemia Fails

    Science.gov (United States)

    A study suggests that at least some children diagnosed with acute lymphoblastic leukemia who respond poorly to initial chemotherapy may do better if they receive additional chemotherapy rather than a stem cell transplant.

  18. Initial treatment of severe malaria in children is inadequate – a study ...

    African Journals Online (AJOL)

    -medicated at home. Initial consultations are at primary local health facilities where less effective drugs are prescribed at inadequate dosages. Recommended ACTs were also often prescribed at inadequate dosages. Education in the use of ...

  19. Plants as sources of antiviral agents | Abonyi | African Journal of ...

    African Journals Online (AJOL)

    Antivirals are substances other than a virus or virus containing vaccine or specific antibody which can produce either a protective or therapeutic effect to the clear detectable advantage of the virus infected host. The search for antiviral agents began in earnest in the 1950s but this was directed mainly by chance, with little or ...

  20. Anti-viral effect of herbal medicine Korean traditional Cynanchum ...

    African Journals Online (AJOL)

    Background: Pestiviruses in general, and Bovine Viral Diarrhea (BVD) in particular, present several potential targets for directed antiviral therapy. Material and Methods: The antiviral effect of Cynanchum paniculatum (Bge.) Kitag (Dog strangling vine: DS) extract on the bovine viral diarrhea (BVD) virus was tested. First ...

  1. Antiviral activity and mechanism of action of arbidol against Hantaan ...

    African Journals Online (AJOL)

    Keywords: Hantavirus, Arbidol, Toll-like receptors, inducible nitric oxide synthase, Antiviral activity, ... hantavirus infection. Arbidol is a broad-spectrum antiviral compound that has been shown to have inhibitory effect on influenza virus [4,5], respiratory syncytial virus [6], ..... species in hantavirus cardiopulmonary syndrome.

  2. Antibiotic treatment at delivery shapes the initial oral microbiome in neonates

    OpenAIRE

    Gomez-Arango, Luisa F.; Barrett, Helen L.; McIntyre, H. David.; Callaway, Leonie K.; Morrison, Mark; Dekker Nitert, Marloes

    2017-01-01

    Oral microorganisms are important determinants of health and disease. The source of the initial neonatal microbiome and the factors dictating initial human oral microbiota development are unknown. This study aimed to investigate this in placental, oral and gut microbiome profiles from 36 overweight or obese mother-baby dyads as determined by 16S rRNA sequencing. Expression of five antibiotic resistance genes of the ?-lactamase class was analysed in the infant oral microbiota samples by QPCR. ...

  3. Durations and Delays in Care Seeking, Diagnosis and Treatment Initiation in Uncomplicated Pulmonary Tuberculosis Patients in Mumbai, India.

    Directory of Open Access Journals (Sweden)

    Nerges Mistry

    Full Text Available Timely diagnosis and treatment initiation are critical to reduce the chain of transmission of Tuberculosis (TB in places like Mumbai, where almost 60% of the inhabitants reside in overcrowded slums. This study documents the pathway from the onset of symptoms suggestive of TB to initiation of TB treatment and examines factors responsible for delay among uncomplicated pulmonary TB patients in Mumbai.A population-based retrospective survey was conducted in the slums of 15 high TB burden administrative wards to identify 153 self-reported TB patients. Subsequently in-depth interviews of 76 consenting patients that fit the inclusion criteria were undertaken using an open-ended interview schedule. Mean total, first care seeking, diagnosis and treatment initiation duration and delays were computed for new and retreatment patients. Patients showing defined delays were divided into outliers and non-outliers for all three delays using the median values.The mean duration for the total pathway was 65 days with 29% of patients being outliers. Importantly the mean duration of first care seeking was similar in new (24 days and retreatment patients (25 days. Diagnostic duration contributed to 55% of the total pathway largely in new patients. Treatment initiation was noted to be the least among the three durations with mean duration in retreatment patients twice that of new patients. Significantly more female patients experienced diagnostic delay. Major shift of patients from the private to public sector and non-allopaths to allopaths was observed, particularly for treatment initiation.Achieving positive behavioural changes in providers (especially non-allopaths and patients needs to be considered in TB control strategies. Specific attention is required in counselling of TB patients so that timely care seeking is effected at the time of relapse. Prioritizing improvement of environmental health in vulnerable locations and provision of point of care diagnostics

  4. Durations and Delays in Care Seeking, Diagnosis and Treatment Initiation in Uncomplicated Pulmonary Tuberculosis Patients in Mumbai, India.

    Science.gov (United States)

    Mistry, Nerges; Rangan, Sheela; Dholakia, Yatin; Lobo, Eunice; Shah, Shimoni; Patil, Akshaya

    2016-01-01

    Timely diagnosis and treatment initiation are critical to reduce the chain of transmission of Tuberculosis (TB) in places like Mumbai, where almost 60% of the inhabitants reside in overcrowded slums. This study documents the pathway from the onset of symptoms suggestive of TB to initiation of TB treatment and examines factors responsible for delay among uncomplicated pulmonary TB patients in Mumbai. A population-based retrospective survey was conducted in the slums of 15 high TB burden administrative wards to identify 153 self-reported TB patients. Subsequently in-depth interviews of 76 consenting patients that fit the inclusion criteria were undertaken using an open-ended interview schedule. Mean total, first care seeking, diagnosis and treatment initiation duration and delays were computed for new and retreatment patients. Patients showing defined delays were divided into outliers and non-outliers for all three delays using the median values. The mean duration for the total pathway was 65 days with 29% of patients being outliers. Importantly the mean duration of first care seeking was similar in new (24 days) and retreatment patients (25 days). Diagnostic duration contributed to 55% of the total pathway largely in new patients. Treatment initiation was noted to be the least among the three durations with mean duration in retreatment patients twice that of new patients. Significantly more female patients experienced diagnostic delay. Major shift of patients from the private to public sector and non-allopaths to allopaths was observed, particularly for treatment initiation. Achieving positive behavioural changes in providers (especially non-allopaths) and patients needs to be considered in TB control strategies. Specific attention is required in counselling of TB patients so that timely care seeking is effected at the time of relapse. Prioritizing improvement of environmental health in vulnerable locations and provision of point of care diagnostics would be

  5. Effect of antiviral prophylaxis on influenza outbreaks om aged care facilities in three local health districts in New South Wales, Australia, 2014

    Directory of Open Access Journals (Sweden)

    Tony Merritt

    2016-02-01

    Full Text Available Background: There was a record number (n = 111 of influenza outbreaks in aged care facilities in New South Wales, Australia during 2014. To determine the impact of antiviral prophylaxis recommendations in practice, influenza outbreak data were compared for facilities in which antiviral prophylaxis and treatment were recommended and for those in which antivirals were recommended for treatment only. Methods: Routinely collected outbreak data were extracted from the Notifiable Conditions Information Management System for two Local Health Districts where antiviral prophylaxis was routinely recommended and one Local Health District where antivirals were recommended for treatment but not routinely for prophylaxis. Data collected on residents included counts of influenza-like illness, confirmed influenza, hospitalizations and related deaths. Dates of onset, notification, influenza confirmation and antiviral recommendations were also collected for analysis. The Mann–Whitney U test was used to assess the significance of differences between group medians for key parameters. Results: A total of 41 outbreaks (12 in the prophylaxis group and 29 in the treatment-only group were included in the analysis. There was no significant difference in overall outbreak duration; outbreak duration after notification; or attack, hospitalization or case fatality rates between the two groups. The prophylaxis group had significantly higher cases with influenza-like illness (P = 0.03 and cases recommended antiviral treatment per facility (P = 0.01. Discussion: This study found no significant difference in key outbreak parameters between the two groups. However, further high quality evidence is needed to guide the use of antivirals in responding to influenza outbreaks in aged care facilities.

  6. Analysis of correlation between initial alveolar bone density and apical root resorption after 12 months of orthodontic treatment without extraction

    Directory of Open Access Journals (Sweden)

    Paula Cabrini Scheibel

    2014-10-01

    Full Text Available OBJECTIVE: The aim of the present study was to investigate the correlation between initial alveolar bone density of upper central incisors (ABD-UI and external apical root resorption (EARR after 12 months of orthodontic movement in cases without extraction. METHODS: A total of 47 orthodontic patients 11 years old or older were submitted to periapical radiography of upper incisors prior to treatment (T1 and after 12 months of treatment (T2. ABD-UI and EARR were measured by means of densitometry. RESULTS: No statistically significant correlation was found between initial ABD-UI and EARR at T2 (r = 0.149; p = 0.157. CONCLUSION: Based on the present findings, alveolar density assessed through periapical radiography is not predictive of root resorption after 12 months of orthodontic treatment in cases without extraction.

  7. Analysis of correlation between initial alveolar bone density and apical root resorption after 12 months of orthodontic treatment without extraction

    Science.gov (United States)

    Scheibel, Paula Cabrini; Ramos, Adilson Luiz; Iwaki, Lilian Cristina Vessoni; Micheletti, Kelly Regina

    2014-01-01

    OBJECTIVE: The aim of the present study was to investigate the correlation between initial alveolar bone density of upper central incisors (ABD-UI) and external apical root resorption (EARR) after 12 months of orthodontic movement in cases without extraction. METHODS: A total of 47 orthodontic patients 11 years old or older were submitted to periapical radiography of upper incisors prior to treatment (T1) and after 12 months of treatment (T2). ABD-UI and EARR were measured by means of densitometry. RESULTS: No statistically significant correlation was found between initial ABD-UI and EARR at T2 (r = 0.149; p = 0.157). CONCLUSION: Based on the present findings, alveolar density assessed through periapical radiography is not predictive of root resorption after 12 months of orthodontic treatment in cases without extraction. PMID:25715722

  8. Baseline MELD score predicts hepatic decompensation during antiviral therapy in patients with chronic hepatitis C and advanced cirrhosis.

    Directory of Open Access Journals (Sweden)

    Georg Dultz

    Full Text Available In patients with advanced liver cirrhosis due to chronic hepatitis C virus (HCV infection antiviral therapy with peginterferon and ribavirin is feasible in selected cases only due to potentially life-threatening side effects. However, predictive factors associated with hepatic decompensation during antiviral therapy are poorly defined.In a retrospective cohort study, 68 patients with HCV-associated liver cirrhosis (mean MELD score 9.18 ± 2.72 were treated with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (onset of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks after initiation of antiviral therapy. To monitor long term sequelae of end stage liver disease an extended follow up for HCC development, transplantation and death was applied (240 weeks, ± SD 136 weeks.Eighteen patients (26.5% achieved a sustained virologic response. During the observational period a hepatic decompensation was observed in 36.8%. Patients with hepatic decompensation had higher MELD scores (10.84 vs. 8.23, p14, respectively. Baseline MELD score was significantly associated with the risk for transplantation/death (p<0.001.Our data suggest that the baseline MELD score predicts the risk of hepatic decompensation during antiviral therapy and thus contributes to decision making when antiviral therapy is discussed in HCV patients with advanced liver cirrhosis.

  9. Physiotherapy in hip and knee osteoarthritis: development of a practice guideline concerning initial assessment, treatment and evaluation.

    Science.gov (United States)

    Peter, W F; Jansen, M J; Hurkmans, E J; Bloo, H; Dekker, J; Dilling, R G; Hilberdink, W; Kersten-Smit, C; de Rooij, M; Veenhof, C; Vermeulen, H M; de Vos, R J; Schoones, J W; Vliet Vlieland, T P

    2011-01-01

    An update of a Dutch physiotherapy practice guideline in Hip and Knee Osteoarthritis (HKOA) was made, based on current evidence and best practice. A guideline steering committee, comprising 10 expert physiotherapists, selected topics concerning the guideline chapters: initial assessment, treatment and evaluation. With respect to treatment a systematic literature search was performed using various databases, and the evidence was graded (1-4). For the initial assessment and evaluation mainly review papers and textbooks were used. Based on evidence and expert opinion, recommendations were formulated. A first draft of the guideline was reviewed by 17 experts from different professional backgrounds. A second draft was field-tested by 45 physiotherapists. In total 11 topics were selected. For the initial assessment, three recommendations were formulated, pertaining to history taking, red flags, and formulating treatment goals. Concerning treatment, 7 recommendations were formulated; (supervised) exercise therapy, education and self management interventions, a combination of exercise and manual therapy, postoperative exercise therapy and taping of the patella were recommended. Balneotherapy and hydrotherapy in HKOA, and thermotherapy, TENS, and Continuous Passive Motion in knee OA were neither recommended nor discouraged. Massage therapy, ultrasound, electrotherapy, electromagnetic field, Low Level Laser Therapy, preoperative physiotherapy and education could not be recommended. For the evaluation of treatment goals the following measurement instruments were recommended: Lequesne index, Western Ontario and McMaster Universities osteoarthritis index, Hip disability and Osteoarthritis Outcome Score and Knee injury and Osteoarthritis Outcome Score, 6-minute walktest, Timed Up and Go test, Patient Specific Complaint list, Visual Analoge Scale for pain, Intermittent and Constant OsteoArthritis Pain Questionnaire, goniometry, Medical Research Council for strength, handheld

  10. Histophilus somni Stimulates Expression of Antiviral Proteins and Inhibits BRSV Replication in Bovine Respiratory Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    C Lin

    Full Text Available Our previous studies showed that bovine respiratory syncytial virus (BRSV followed by Histophilus somni causes more severe bovine respiratory disease and a more permeable alveolar barrier in vitro than either agent alone. However, microarray analysis revealed the treatment of bovine alveolar type 2 (BAT2 epithelial cells with H. somni concentrated culture supernatant (CCS stimulated up-regulation of four antiviral protein genes as compared with BRSV infection or dual treatment. This suggested that inhibition of viral infection, rather than synergy, may occur if the bacterial infection occurred before the viral infection. Viperin (or radical S-adenosyl methionine domain containing 2--RSAD2 and ISG15 (IFN-stimulated gene 15--ubiquitin-like modifier were most up-regulated. CCS dose and time course for up-regulation of viperin protein levels were determined in treated bovine turbinate (BT upper respiratory cells and BAT2 lower respiratory cells by Western blotting. Treatment of BAT2 cells with H. somni culture supernatant before BRSV infection dramatically reduced viral replication as determined by qRT PCR, supporting the hypothesis that the bacterial infection may inhibit viral infection. Studies of the role of the two known H. somni cytotoxins showed that viperin protein expression was induced by endotoxin (lipooligosaccharide but not by IbpA, which mediates alveolar permeability and H. somni invasion. A naturally occurring IbpA negative asymptomatic carrier strain of H. somni (129Pt does not cause BAT2 cell retraction or permeability of alveolar cell monolayers, so lacks virulence in vitro. To investigate initial steps of pathogenesis, we showed that strain 129Pt attached to BT cells and induced a strong viperin response in vitro. Thus colonization of the bovine upper respiratory tract with an asymptomatic carrier strain lacking virulence may decrease viral infection and the subsequent enhancement of bacterial respiratory infection in vivo.

  11. Increased Persistence of Initial Treatment for HIV Infection With Modern Antiretroviral Therapy.

    Science.gov (United States)

    Davy-Mendez, Thibaut; Eron, Joseph J; Zakharova, Oksana; Wohl, David A; Napravnik, Sonia

    2017-10-01

    Initiating antiretroviral therapy (ART) early improves clinical outcomes and prevents transmission. Guidelines for first-line therapy have changed with the availability of newer ART agents. In this study, we compared persistence and virologic responses with initial ART according to the class of anchor agent used. An observational clinical cohort study in the Southeastern United States. All HIV-infected patients participating in the UNC Center for AIDS Research Clinical Cohort (UCHCC) and initiating ART between 1996 and 2014 were included. Separate time-to-event analyses with regimen discontinuation and virologic failure as outcomes were used, including Kaplan-Meier survival curves and adjusted Cox proportional hazards models. One thousand six hundred twenty-four patients were included (median age of 37 years at baseline, 28% women, 60% African American, and 28% white). Eleven percent initiated integrase strand transfer inhibitor (INSTI), 33% non-nucleoside reverse transcriptase inhibitor (NNRTI), 20% boosted protease inhibitor, 27% other, and 9% NRTI only regimens. Compared with NNRTI-containing regimens, INSTI-containing regimens had an adjusted hazard ratio of 0.49 (95% confidence interval, 0.35 to 0.69) for discontinuation and 0.70 (95% confidence interval, 0.46 to 1.06) for virologic failure. All other regimen types were associated with increased rates of discontinuation and failure compared with NNRTI. Initiating ART with an INSTI-containing regimen was associated with lower rates of regimen discontinuation and virologic failure.

  12. Sequential Treatment Initiation with Timothy Grass and Ragweed Sublingual Immunotherapy Tablets Followed by Simultaneous Treatment Is Well Tolerated.

    Science.gov (United States)

    Maloney, Jennifer; Berman, Gary; Gagnon, Remi; Bernstein, David I; Nelson, Harold S; Kleine-Tebbe, Jörg; Kaur, Amarjot; Li, Qing; Nolte, Hendrik

    2016-01-01

    Dual treatment with grass and ragweed sublingual immunotherapy (SLIT) tablets has not been studied. To characterize the safety and tolerability of dual grass and ragweed SLIT-tablet administration. This open-label, multicenter trial (NCT02256553) enrolled North American adults (N = 102) allergic to grass and ragweed. The trial had 3 periods, each of 2 weeks duration. In period 1, subjects received once-daily timothy grass SLIT tablet (2800 bioequivalent allergen unit; Merck, Inc, Kenilworth, NJ/ALK, Hørsholm, Denmark). In period 2, subjects received a short ragweed SLIT tablet (12 Ambrosia artemisiifolia 1-U; Merck/ALK) every morning and a grass SLIT tablet every evening. In period 3, subjects received once-daily grass and ragweed SLIT tablets within 5 minutes (simultaneous intake). The primary end point was the proportion of subjects with 1 or more local swelling events in each period. Secondary end points were the proportion of subjects with 1 or more local adverse events (AEs), that discontinued the treatment because of AEs, and subjects with 1 or more local AEs requiring treatment. No severe swellings, systemic allergic reactions, asthma attacks, or reactions requiring epinephrine were reported. Most (99%) AEs were graded mild to moderate. The proportions of subjects with 1 or more local swelling events were 14%, 22%, and 15% for periods 1, 2, and 3, respectively. For periods 1, 2, and 3, the proportions of subjects with 1 or more local AEs were 71%, 69%, and 56%, respectively; the proportions discontinuing the treatment because of treatment-related AEs were 5%, 1%, and 2%, and the proportions with 1 or more local AEs requiring treatment were 4%, 4%, and 1%. In this trial, a 4-week sequential SLIT-tablet dosing schedule followed by simultaneous intake of timothy grass and ragweed tablets was well tolerated. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Initial Effects of Reproduction Cutting Treatments on Residual Hard Mast Production in the Ouachita Mountains

    Science.gov (United States)

    Roger W. Perry; Ronald E. Thill

    2003-01-01

    We compared indices of total hard mast production (oak and hickory combined) in 20, second-growth, pine-hardwood stands under five treatments to determine the effects of different reproduction treatments on mast production in the Ouachita Mountains. We evaluated mast production in mature unharvested controls and stands under four reproduction cutting methods (single-...

  14. Factors affecting the purpose suppressive antiviral therapy for patients with recurrent genital herpes

    Directory of Open Access Journals (Sweden)

    I. S. Коlova

    2017-01-01

    Full Text Available Objective: To study the factors that influence the destination of suppressive antiviral therapy in patients with recurrent genital herpes doctors of different specialties.Material and Methods: The study was conducted based on an anonymous survey of professionals providing medical care to patients with genital herpes. The survey involved 67 experts – 44 dermatologist, 13 obstetricians and 10 urologists working in Skin and Venereal Diseases, Women’s consuitation post and Saint Petersburg clinics.Results: Most respondents indicated that among patients with genital herpes, seeking an appointment, dominated by patients with relapsing nature of the disease. Suppressive antiviral therapy is recommended 68,7% of specialists, including dermatologists 61,3%, 84,6% of obstetricians and gynecologists, and 80% of urologists. The main indications for its experts consider high frequency of relapses, the patient’s tendency to promiscuity, the desire of the patient with fewer relapses, and the emotional response of the patient for the presence of the disease. Do not prescribe suppressive therapy for recurrent genital herpes 31,4% of the doctors surveyed. Among the reasons for which are not appointed by the type of treatment, the patient is dominated by the rejection of this type of treatment, the lack of experience of the destination suppressive therapy, as well as the uncertainty of specialists in its effectiveness.Conclusion: Suppressive antiviral therapy is recommended 68,7% of specialists. Do not prescribe this type of treatment for recurrent genital herpes 31,4% of the doctors surveyed. The proportion of professionals who refuse the appointment of suppressive antiviral therapy, the highest among dermatologists (38,7% compared with 15,4% among obstetricians and 20% of urologists. The most frequent grounds for refusal from this type of treatment is the lack of confidence in its effectiveness. 

  15. HIV-1 accessory proteins VPR and Vif modulate antiviral response by targeting IRF-3 for degradation

    International Nuclear Information System (INIS)

    Okumura, Atsushi; Alce, Tim; Lubyova, Barbora; Ezelle, Heather; Strebel, Klaus; Pitha, Paula M.

    2008-01-01

    The activation of IRF-3 during the early stages of viral infection is critical for the initiation of the antiviral response; however the activation of IRF-3 in HIV-1 infected cells has not yet been characterized. We demonstrate that the early steps of HIV-1 infection do not lead to the activation and nuclear translocation of IRF-3; instead, the relative levels of IRF-3 protein are decreased due to the ubiquitin-associated proteosome degradation. Addressing the molecular mechanism of this effect we show that the degradation is independent of HIV-1 replication and that virion-associated accessory proteins Vif and Vpr can independently degrade IRF-3. The null mutation of these two genes reduced the capacity of the HIV-1 virus to down modulate IRF-3 levels. The degradation was associated with Vif- and Vpr-mediated ubiquitination of IRF-3 and was independent of the activation of IRF-3. N-terminal lysine residues were shown to play a critical role in the Vif- and Vpr-mediated degradation of IRF-3. These data implicate Vif and Vpr in the disruption of the initial antiviral response and point to the need of HIV-1 to circumvent the antiviral response during the very early phase of replication

  16. "Transcend": initial outcomes from a posttraumatic stress disorder/substance abuse treatment program.

    Science.gov (United States)

    Donovan, B; Padin-Rivera, E; Kowaliw, S

    2001-10-01

    This paper describes the development of a comprehensive treatment program for combat veterans diagnosed with posttraumatic stress disorder (PTSD) and substance abuse (SA). Outcome data are presented on 46 male patients who completed treatment between 1996 and 1998. The treatment approach, defined by a detailed manual, integrates elements of cognitive-behavioral skills training, constructivist theory approaches, SA relapse prevention strategies, and peer social support into a group-focused program. The Clinician-Administered PTSD Scale (CAPS) and the Addiction Severity Index (ASI) were used to assess treatment effectiveness at discharge and 6- and 12-month follow-up. Significant symptom changes revealed on CAPS and ASI scores at discharge and follow-up are analyzed. Discussion focuses on hypotheses regarding treatment effectiveness, study limitations, and suggestions for further research.

  17. Antiviral potential of medicinal plants against HIV, HSV, influenza, hepatitis, and coxsackievirus: A systematic review.

    Science.gov (United States)

    Akram, Muhammad; Tahir, Imtiaz Mahmood; Shah, Syed Muhammad Ali; Mahmood, Zahed; Altaf, Awais; Ahmad, Khalil; Munir, Naveed; Daniyal, Muhammad; Nasir, Suhaila; Mehboob, Huma

    2018-05-01

    Viral infections are being managed therapeutically through available antiviral regimens with unsatisfactory clinical outcomes. The refractory viral infections resistant to available antiviral drugs are alarming threats and a serious health concern. For viral hepatitis, the interferon and vaccine therapies solely are not ultimate solutions due to recurrence of hepatitis C virus. Owing to the growing incidences of viral infections and especially of resistant viral strains, the available therapeutic modalities need to be improved, complemented with the discovery of novel antiviral agents to combat refractory viral infections. It is widely accepted that medicinal plant heritage is nature gifted, precious, and fueled with the valuable resources for treatment of metabolic and infectious disorders. The aims of this review are to assemble the facts and to conclude the therapeutic potential of medicinal plants in the eradication and management of various viral diseases such as influenza, human immunodeficiency virus (HIV), herpes simplex virus (HSV), hepatitis, and coxsackievirus infections, which have been proven in diverse clinical studies. The articles, published in the English language since 1982 to 2017, were included from Web of Science, Cochrane Library, AMED, CISCOM, EMBASE, MEDLINE, Scopus, and PubMed by using relevant keywords including plants possessing antiviral activity, the antiviral effects of plants, and plants used in viral disorders. The scientific literature mainly focusing on plant extracts and herbal products with therapeutic efficacies against experimental models of influenza, HIV, HSV, hepatitis, and coxsackievirus were included in the study. Pure compounds possessing antiviral activity were excluded, and plants possessing activity against viruses other than viruses in inclusion criteria were excluded. Hundreds of plant extracts with antiviral effect were recognized. However, the data from only 36 families investigated through in vitro and in vivo

  18. Pokeweed Antiviral Protein: Its Cytotoxicity Mechanism and Applications in Plant Disease Resistance

    Directory of Open Access Journals (Sweden)

    Rong Di

    2015-03-01

    Full Text Available Pokeweed antiviral protein (PAP is a 29 kDa type I ribosome inactivating protein (RIP found in pokeweed plants. Pokeweed produces different forms of PAP. This review focuses on the spring form of PAP isolated from Phytolacca americana leaves. PAP exerts its cytotoxicity by removing a specific adenine from the α-sarcin/ricin loop of the large ribosomal RNA. Besides depurination of the rRNA, PAP has additional activities that contribute to its cytotoxicity. The mechanism of PAP cytotoxicity is summarized based on evidence from the analysis of transgenic plants and the yeast model system. PAP was initially found to be anti-viral when it was co-inoculated with plant viruses onto plants. Transgenic plants expressing PAP and non-toxic PAP mutants have displayed broad-spectrum resistance to both viral and fungal infection. The mechanism of PAP-induced disease resistance in transgenic plants is summarized.

  19. Bugs Are Not to Be Silenced: Small RNA Pathways and Antiviral Responses in Insects.

    Science.gov (United States)

    Mongelli, Vanesa; Saleh, Maria-Carla

    2016-09-29

    Like every other organism on Earth, insects are infected with viruses, and they rely on RNA interference (RNAi) mechanisms to circumvent viral infections. A remarkable characteristic of RNAi is that it is both broadly acting, because it is triggered by double-stranded RNA molecules derived from virtually any virus, and extremely specific, because it targets only the particular viral sequence that initiated the process. Reviews covering the different facets of the RNAi antiviral immune response in insects have been published elsewhere. In this review, we build a framework to guide future investigation. We focus on the remaining questions and avenues of research that need to be addressed to move the field forward, including issues such as the activity of viral suppressors of RNAi, comparative genomics, the development of detailed maps of the subcellular localization of viral replication complexes with the RNAi machinery, and the regulation of the antiviral RNAi response.

  20. Renal outcomes of agalsidase beta treatment for Fabry disease: role of proteinuria and timing of treatment initiation

    NARCIS (Netherlands)

    Warnock, David G.; Ortiz, Alberto; Mauer, Michael; Linthorst, Gabor E.; Oliveira, João P.; Serra, Andreas L.; Maródi, László; Mignani, Renzo; Vujkovac, Bojan; Beitner-Johnson, Dana; Lemay, Roberta; Cole, J. Alexander; Svarstad, Einar; Waldek, Stephen; Germain, Dominique P.; Wanner, Christoph

    2012-01-01

    Background. The purpose of this study was to identify determinants of renal disease progression in adults with Fabry disease during treatment with agalsidase beta. Methods. Renal function was evaluated in 151 men and 62 women from the Fabry Registry who received agalsidase beta at an average dose of

  1. Delays before Diagnosis and Initiation of Treatment in Patients Presenting to Mental Health Services with Bipolar Disorder.

    Science.gov (United States)

    Patel, Rashmi; Shetty, Hitesh; Jackson, Richard; Broadbent, Matthew; Stewart, Robert; Boydell, Jane; McGuire, Philip; Taylor, Matthew

    2015-01-01

    Bipolar disorder is a significant cause of morbidity and mortality. Although existing treatments are effective, there is often a substantial delay before diagnosis and treatment initiation. We sought to investigate factors associated with the delay before diagnosis of bipolar disorder and the onset of treatment in secondary mental healthcare. Retrospective cohort study using anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust (SLaM) Biomedical Research Centre (BRC) Case Register on 1364 adults diagnosed with bipolar disorder between 2007 and 2012. The following predictor variables were analysed in a multivariable Cox regression analysis: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder. The outcomes were time to recorded diagnosis from first presentation to specialist mental health services (the diagnostic delay), and time to the start of appropriate therapy (treatment delay). The median diagnostic delay was 62 days (interquartile range: 17-243) and median treatment delay was 31 days (4-122). Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18-3.06) and treatment delay (4.40, 3.63-5.62). Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33-0.41) and substance misuse disorders (0.44, 0.31-0.61). Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay. Some individuals experience a significant delay in diagnosis and treatment of bipolar disorder after initiation of specialist mental healthcare, particularly those who have prior diagnoses of alcohol and substance misuse disorders. These findings highlight a need for further study on strategies to better identify underlying symptoms and offer appropriate treatment sooner

  2. Delays before Diagnosis and Initiation of Treatment in Patients Presenting to Mental Health Services with Bipolar Disorder.

    Directory of Open Access Journals (Sweden)

    Rashmi Patel

    Full Text Available Bipolar disorder is a significant cause of morbidity and mortality. Although existing treatments are effective, there is often a substantial delay before diagnosis and treatment initiation. We sought to investigate factors associated with the delay before diagnosis of bipolar disorder and the onset of treatment in secondary mental healthcare.Retrospective cohort study using anonymised electronic mental health record data from the South London and Maudsley NHS Foundation Trust (SLaM Biomedical Research Centre (BRC Case Register on 1364 adults diagnosed with bipolar disorder between 2007 and 2012. The following predictor variables were analysed in a multivariable Cox regression analysis: age, gender, ethnicity, compulsory admission to hospital under the UK Mental Health Act, marital status and other diagnoses prior to bipolar disorder. The outcomes were time to recorded diagnosis from first presentation to specialist mental health services (the diagnostic delay, and time to the start of appropriate therapy (treatment delay.The median diagnostic delay was 62 days (interquartile range: 17-243 and median treatment delay was 31 days (4-122. Compulsory hospital admission was associated with a significant reduction in both diagnostic delay (hazard ratio 2.58, 95% CI 2.18-3.06 and treatment delay (4.40, 3.63-5.62. Prior diagnoses of other psychiatric disorders were associated with increased diagnostic delay, particularly alcohol (0.48, 0.33-0.41 and substance misuse disorders (0.44, 0.31-0.61. Prior diagnosis of schizophrenia and psychotic depression were associated with reduced treatment delay.Some individuals experience a significant delay in diagnosis and treatment of bipolar disorder after initiation of specialist mental healthcare, particularly those who have prior diagnoses of alcohol and substance misuse disorders. These findings highlight a need for further study on strategies to better identify underlying symptoms and offer appropriate treatment

  3. The initial experience of electronic brachytherapy for the treatment of non-melanoma skin cancer

    Directory of Open Access Journals (Sweden)

    Bhatnagar Ajay

    2010-09-01

    Full Text Available Abstract Background Millions of people are diagnosed with non-melanoma skin cancers (NMSC worldwide each year. While surgical approaches are the standard treatment, some patients are appropriate candidates for radiation therapy for NMSC. High dose rate (HDR brachytherapy using surface applicators has shown efficacy in the treatment of NMSC and shortens the radiation treatment schedule by using a condensed hypofractionated approach. An electronic brachytherapy (EBT system permits treatment of NMSC without the use of a radioactive isotope. Methods Data were collected retrospectively from patients treated from July 2009 through March 2010. Pre-treatment biopsy was performed to confirm a malignant cutaneous diagnosis. A CT scan was performed to assess lesion depth for treatment planning, and an appropriate size of surface applicator was selected to provide an acceptable margin. An HDR EBT system delivered a dose of 40.0 Gy in eight fractions twice weekly with 48 hours between fractions, prescribed to a depth of 3-7 mm. Treatment feasibility, acute safety, efficacy outcomes, and cosmetic results were assessed. Results Thirty-seven patients (mean age 72.5 years with 44 cutaneous malignancies were treated. Of 44 lesions treated, 39 (89% were T1, 1 (2% Tis, 1 (2% T2, and 3 (7% lesions were recurrent. Lesion locations included the nose for 16 lesions (36.4%, ear 5 (11%, scalp 5 (11%, face 14 (32%, and an extremity for 4 (9%. Median follow-up was 4.1 months. No severe toxicities occurred. Cosmesis ratings were good to excellent for 100% of the lesions at follow-up. Conclusions The early outcomes of EBT for the treatment of NMSC appear to show acceptable acute safety and favorable cosmetic outcomes. Using a hypofractionated approach, EBT provides a convenient treatment schedule.

  4. Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection

    Directory of Open Access Journals (Sweden)

    Pécheur Eve-Isabelle

    2006-07-01

    Full Text Available Abstract Arbidol (ARB is an antiviral compound that was originally proven effective for treatment of influenza and several other respiratory viral infections. The broad spectrum of ARB anti-viral activity led us to evaluate its effect on hepatitis C virus (HCV infection and replication in cell culture. Long-term ARB treatment of Huh7 cells chronically replicating a genomic length genotype 1b replicon resulted in sustained reduction of viral RNA and protein expression, and eventually cured HCV infected cells. Pre-treatment of human hepatoma Huh7.5.1 cells with 15 μM ARB for 24 to 48 hours inhibited acute infection with JFH-1 virus by up to 1000-fold. The inhibitory effect of ARB on HCV was not due to generalized cytotoxicity, nor to augmentation of IFN antiviral signaling pathways, but involved impaired virus-mediated membrane fusion. ARB's affinity for membranes may inhibit several aspects of the HCV lifecycle that are membrane-dependent.

  5. 78 FR 62506 - TRICARE; Coverage of Care Related to Non-Covered Initial Surgery or Treatment

    Science.gov (United States)

    2013-10-22

    ... Duty member. Additionally, with respect to care that is related to a non-covered initial surgery or... interest; namely, protecting former active duty members who have received private sector care pursuant to a... incorporated by reference for the benefits provided in the civilian health care sector to active duty family...

  6. Epimedium koreanum Nakai Water Extract Exhibits Antiviral Activity against Porcine Epidermic Diarrhea Virus In Vitro and In Vivo

    Directory of Open Access Journals (Sweden)

    Won-Kyung Cho

    2012-01-01

    Full Text Available Porcine epidemic diarrhea virus (PEDV causes diarrhea of pigs age-independently and death of young piglets, resulting in economic loss of porcine industry. We have screened 333 natural oriental herbal medicines to search for new antiviral candidates against PEDV. We found that two herbal extracts, KIOM 198 and KIOM 124, contain significant anti-PED viral effect. KIOM 198 and KIOM 124 were identified as Epimedium koreanum Nakai and Lonicera japonica Thunberg, respectively. The further plaque and CPE inhibition assay in vitro showed that KIOM 198 has much stronger antiviral activity than KIOM 124. Additionally, KIOM 198 exhibited a similar extent of antiviral effect against other subtypes of Corona virus such as sm98 and TGE viruses. Cytotoxicity results showed that KIOM 198 is nontoxic on the cells and suggest that it can be delivered safely for therapy. Furthermore, when we orally administered KIOM 198 to piglets and then infected them with PEDV, the piglets did not show any disease symptoms like diarrhea and biopsy results showed clean intestine, whereas control pigs without KIOM 198 treatment exhibited PED-related severe symptoms. These results imply that KIOM 198 contains strong antiviral activity and has a potential to be developed as an antiviral phytomedicine to treat PEDV-related diseases in pigs.

  7. Initial indication of treatment in 60 patients with sleep obstructive ventilatory disturbance.

    Science.gov (United States)

    de Tarso Moura Borges, Paulo; Paschoal, Jorge Rizzato

    2005-01-01

    The author present a retrospective descriptive study of 60 patients with sleep obstructive ventilatory disturbance who have taken medical advice at the Centro Campinas de Otorrinolaringologia e Cirurgia de Cabeça e Pescoço during a period of three years. All the patients have been examined after standardized protocol and decisions related to the treatment have been taken after systematic multidisciplinary discussion. clinical retrospective. The patients were distributed into two groups according to the proposal of surgical and non-surgical treatment. After so, they were studied according to the model of treatment proposed and the main propaedeutic findings: respiratory disturbance index (RDI), body mass index (BMI), cephalometric analysis and Müller maneuver. The main features were compared--isolated or in association--with the model of treatment proposed. Amongst several conclusions obtained, the most important were: surgical and non-surgical treatment were indicated almost in the same proportion for of snoring; surgical treatments were most indicated for snoring and Apnoea-Hipopnoea Syndrome, despite of its modality; RDI, BMI and cephalometric analysis and Müller maneuver had no influence at any therapeutic modality; the therapeutic decision was taken after standardized protocol and systematic multidisciplinary discussion, where each case was discussed individually.

  8. Cognitive rehabilitation therapy after acquired brain injury in Argentina: psychosocial outcomes in connection with the time elapsed before treatment initiation.

    Science.gov (United States)

    Saux, Gastón; Demey, Ignacio; Rojas, Galeno; Feldberg, Carolina

    2014-01-01

    To examine the effect of cognitive rehabilitation therapy (CRT) on psychosocial outcomes in Argentinean patients with acquired brain injury (ABI), in connection with the time elapsed between injury and treatment initiation. Self-reported data from patients in a naturalistic setting was collected before and after CRT. An outpatient sample of 75 Spanish-speaking patients with cognitive disturbances secondary to ABI (49 male/26 female, age: 50.2 ± 20.1 years; education 14.3 ± 3.2 years) completed a set of scales on their daily living activities, memory self-perception, quality-of-life and mood. Single and multi-group analyses were conducted, considering pre- and post- responses and the time elapsed between injury and treatment initiation. The influence of socio-demographic moderators was controlled during comparisons. Results suggest an improvement in several psychosocial indicators after treatment. Additionally, correlations and group comparisons showed greater improvement in subjective memory and quality-of-life self-reports in patients who began treatment earlier than those who began treatment after a longer time period. Overall, results suggest that CRT is associated with positive results in different areas of the psychosocial domain and that post-injury time can mediate this effect.

  9. Clinical value of MSCTA in the interventional treatment of the initial origin stenotic segment of the internal carotid artery

    International Nuclear Information System (INIS)

    Qi Yueyong; Zou Liguang; Chen Lin; Sun Qingrong; Shuai Jie; Zhou Zheng; Huang Lan

    2007-01-01

    Objective: To assess the clinical value of MSCTA in the interventional treatment of the initial origin stenotic segment of internal carotid artery. Methods: Forty two patients with stenosis of initial origin stenotic segment of internal carotid artery underwent interventional treatment and MSCTA were analyzed retrospectively. Results: Forty two patients were diagnosed correctly through MSCTA. The percentages of stenotic area were measured from the multiplanar reconstruction (MPR)images of MSCTA, including mild stenosis( 70%)in 30, obstruction in 4 (>100%)and normal in 18. Plaques and endoscopic views of stenosis were delineated on MSCTA and CTVE. Conclusion: MSCTA is an accurate method for the assessment of the stenosis and plaques of the stenotic origin segment of internal carotid artery. MSCTA can be used as a convenient follow-up modality for instent restenosis. (authors)

  10. Initial performance of corn in response to treatment of seeds with humic acids isolated from bokashi

    Directory of Open Access Journals (Sweden)

    Marihus Altoé Baldotto

    2016-02-01

    Full Text Available ABSTRACT The humified organic matter presents bioactivity similar to the auxinic effect. As bokashi is produced by a special process of humification, information is needed about the bioactive potential of its humic acids. The objective of this work was studying the initial performance of corn-indicator plants in response to the application of different concentrations of humic acids isolated from bokashi. The corn seeds were treated for 16 hours with solutions containing 0, 10, 20, 30, 40 and 80 mmol L-1 of C in the form of humic acids. Then, the seeds were planted in pots of 1 dm3 containing corrected and fertilized soil, in greenhouse. Growth characteristics of shoot and root systems were evaluated. The results showed that the humic acids extracted from bokashi had positive effects on the initial performance of corn.

  11. SPINAL CORD STIMULATION IN TREATMENT OF THE NEUROPATHIC PAIN SYNDROMES: INITIAL EXPERIENCE

    Directory of Open Access Journals (Sweden)

    D. A. Rzaev

    2010-01-01

    Full Text Available In the article initial experience of spinal cord stimulation for chronic pain syndromes is described. The trial was done for 62 patients, in 52 cases trial was successful and subcutaneous pulse generator were implanated. Maximal follow-up is 26 months. The level of pain evaluates at VAS. Permanent pain-relieve results were achieved in 46 patients (74,2%. These results correspond to literature data.

  12. Coformulated bictegravir, Emtricitabine (F), tenofovir alafenamide (TAF) after initial treatment with bictegravir or dolutegravir plus F/TAF.

    Science.gov (United States)

    Sax, Paul E; Dejesus, Edwin; Crofoot, Gordon; Ward, Douglas; Benson, Paul; Dretler, Robin; Mills, Anthony; Brinson, Cynthia; Wei, Xuelian; Collins, Sean E; Cheng, Andrew

    2018-05-22

    : A phase 2, randomized, active-controlled study of initial antiretroviral therapy with bictegravir or dolutegravir in combination with emtricitabine and tenofovir alafenamide showed excellent efficacy. After 60 weeks of blinded treatment, participants switched to a single tablet regimen of bictegravir, emtricitabine and tenofovir alafenamide. Switching maintained viral suppression in all participants who chose to remain on the study through at least 12 weeks in the open-label phase, was safe and well tolerated.

  13. 3D angiography in the evaluation of intracranial aneurysms before and after treatment. Initial experience

    International Nuclear Information System (INIS)

    Lauriola, Walter; Nardella, Michele; Strizzi, Vincenzo; Florio, Francesco; Cali, Alessandro; D'Angelo, Vincenzo

    2005-01-01

    Purpose: The aim of the study is to evaluate the advantages of 3D angiography as compared to 2D angiography in assessing intracranial aneurysms before and after treatment and, in particular, in selecting and planning the correct treatment. Materials and methods: Thirty intracranial aneurysms were retrospectively reviewed before and after treatment. The study population consisted of 12 men and 18 women (age range: 35-77 years; mean age: 58 years). Eighteen aneurysms were treated surgically, 10 endovascularly and 2 with combined treatment. The 2D and 3D finding before and after the treatment were compared , and the pre-treatment angiographic images were compared with surgical findings. The following parameters were assessed and compared: aneurysmal sac and neck size, vascular involvement and evaluation of post-treatment residual mass. Results: On the 2D DSA images, visualisation of the sac and neck was optimal in 45% and 15% of cases, adequate in 10% and 35% of cases and inadequate in 5% and 50% of cases, respectively. On the 3D DSA images, visualisation of the sac and neck was optimal in 100% of cases. Three-dimensional DSA was able to detect 8 aneurysms with vessel involvement in all cases (100%). Of these, four (50%) went undetected on 2D DSA; in two cases, two-dimensional DSA erroneously detected the presence of vascular involvement (false positive). Three-dimensional angiography proved superior to 2D angiography in the evaluation of the residual aneurysms treated with clipping. Finally, 3D DSA was able to reduce the number of the radiographic projections, the quantity of contrast medium, the time and associated risks necessary for a precise evaluation of the aneurysm. Conclusions: In our first experience, 3D DSA proved useful in reducing the risks and diagnostic time as well as in selecting and planning the treatment. Moreover, it improved the operating conditions of both surgical and endovascular treatment. Technological advances in this field will enable the

  14. Antireflux Metal Stent for Initial Treatment of Malignant Distal Biliary Obstruction

    Directory of Open Access Journals (Sweden)

    Shinichi Morita

    2018-01-01

    Full Text Available Objectives. To compare the use of an antireflux metal stent (ARMS with that of a conventional covered self-expandable metal stent (c-CSEMS for initial stenting of malignant distal biliary obstruction (MDBO. Materials and Methods. We retrospectively investigated 59 consecutive patients with unresectable MDBO undergoing initial endoscopic biliary drainage. ARMS was used in 32 patients and c-CSEMS in 27. Technical success, functional success, complications, causes of recurrent biliary obstruction (RBO, time to RBO (TRBO, and reintervention were compared between the groups. Results. Stent placement was technically successful in all patients. There were no significant intergroup differences in functional success (ARMS [96.9%] versus c-CSEMS [96.2%], complications (6.2 versus 7.4%, and RBO (48.4 versus 42.3%. Food impaction was significantly less frequent for ARMS than for c-CSEMS (P=0.037, but TRBO did not differ significantly between the groups (log-rank test, P=0.967. The median TRBO was 180.0 [interquartile range (IQR, 114.0–349.0] days for ARMS and 137.0 [IQR, 87.0–442.0] days for c-CSEMS. In both groups, reintervention for RBO was successfully completed in all patients thus treated. Conclusion. ARMS offers no advantage for initial stent placement, but food impaction is significantly prevented by the antireflux valve.

  15. Critical challenges and emerging opportunities in hepatitis C virus research in an era of potent antiviral therapy

    DEFF Research Database (Denmark)

    Bartenschlager, Ralf; Baumert, Thomas F.; Bukh, Jens

    2018-01-01

    The development and clinical implementation of direct-acting antivirals (DAAs) has revolutionized the treatment of chronic hepatitis C. Infection with any hepatitis C virus (HCV) genotype can now be eliminated in more than 95% of patients with short courses of all-oral, well-tolerated drugs, even...

  16. Parents report on stimulant-treated children in the Netherlands: initiation of treatment and follow-up care.

    Science.gov (United States)

    Faber, Adrianne; Kalverdijk, Luuk J; de Jong-van den Berg, Lolkje T W; Hugtenburg, Jacqueline G; Minderaa, Ruud B; Tobi, Hilde

    2006-08-01

    The aim of this study was to describe current practices around initiation and follow-up care of stimulant treatment among stimulant-treated children in a nationwide survey among parents. A total of 115 pharmacies detected current stimulant users parents a questionnaire regarding their child's stimulant treatment. Parents returned 924 of 1,307 questionnaires (71%). The median age of the stimulant users was 10 years and 85% were boys. In all, 91% were diagnosed with attention-deficit/hyperactivity disorder (ADHD). In 77% of the cases, the child or parents received other therapies besides stimulants-21% received psychotropic co-medication, with melatonin (11%) and antipsychotics (7%) being mentioned most frequently. Stimulant use was primarily initiated by child psychiatrists (51%) and pediatricians (32%), but most children received repeat prescriptions from general practitioners (61%). Of these 924 children, 19% did not receive any follow-up care, and transfer of prescribing responsibility increased the risk of not receiving follow-up care. The 732 children (79%) who were monitored visited a physician approximately twice a year. During follow-up visits, pediatricians performed physical check ups significantly more often. Stimulant treatment in The Netherlands is initiated mainly by specialists such as child psychiatrists and pediatricians. In the current study, follow-up care for stimulant-treated children in The Netherlands appeared to be poor, suggesting an urgent need for improvement.

  17. Striatal Reward Activity and Antipsychotic-Associated Weight Change in Patients With Schizophrenia Undergoing Initial Treatment

    DEFF Research Database (Denmark)

    Nielsen, Mette Ødegaard; Rostrup, Egill; Wulff, Sanne

    2016-01-01

    -nine antipsychotic-naive inpatients and outpatients with schizophrenia were included in a multimodal longitudinal cohort study from December 16, 2008, to December 11, 2013. Fifty-eight patients underwent functional magnetic resonance imaging (fMRI) while performing a monetary reward task. After 6 weeks of treatment...... with amisulpride, a relatively selective dopamine D2 antagonist, 39 patients underwent a second fMRI scan and measurement of change in body weight. Final follow-up was completed on January 14, 2014, and data were analyzed from October 25, 2014, to June 15, 2015 and August 31 to September 19, 2015. Exposures: Six...... weeks of individually dosed amisulpride treatment. Main Outcomes and Measures: Reward-anticipation activity in the striatum before and after treatment and weight change. Results: Of the 69 patients who consented to the study, 39 underwent the follow-up fMRI and weight measurement (age range, 18-45 years...

  18. Real-world treatment patterns and opioid use in chronic low back pain patients initiating duloxetine versus standard of care

    Directory of Open Access Journals (Sweden)

    Andrews JS

    2013-11-01

    Full Text Available Jeffrey Scott Andrews,1 Ning Wu,2 Shih-Yin Chen,2 Xia Yu,2 Xiaomei Peng,1 Diego Novick1 1Global Health Outcomes, Eli Lilly and Company, Indianapolis, IN, USA; 2Evidera, Lexington, MA, USA Abstract: To describe the use of pain medications in patients with chronic low back pain (CLBP after initiating duloxetine or standard of care (SOC [muscle relaxants, gabapentin, pregabalin, venlafaxine, and tricyclic antidepressants] for pain management, pharmacy and medical claims from Surveillance Data, Inc (SDI Health were analyzed. Adult patients with CLBP who initiated duloxetine or SOC between November 2010 and April 2011 were identified. Treatment initiation was defined as no pill coverage for duloxetine or SOC in the previous 90 days. Included patients had no opioid use in the 90 days before initiation. Propensity score matching was used to select patients with similar baseline demographic and clinical characteristics for duloxetine and SOC cohorts. Compliance with index medication was assessed via medication possession ratio (MPR and proportion of days covered (PDC for 6 months after initiation. The proportion of patients receiving opioids and days on opioids after index date were assessed, and regression models were estimated to compare opioid use between cohorts. A total of 766 patients initiated duloxetine and 6,206 patients initiated SOC. After matching, 743 patients were selected for the duloxetine (mean age 57 years; female 74% and SOC (mean age 57 years; female 75% cohorts, respectively. Of the duloxetine cohort, 92% started on or below recommended daily dose (≤60 mg. The duloxetine cohort had significantly higher MPR (0.78 versus [vs] 0.60 and PDC (0.50 vs 0.31, were less likely to use opioids (45% vs 61%, and had fewer days on opioids (median 0 vs 7 days than the SOC cohort (all P < 0.001. After adjusting for demographic and clinical characteristics, the duloxetine cohort initiated opioids later than the SOC cohort (hazard ratio 0.77, 95

  19. Initial diagnosis and treatment in first-episode psychosis: can an operationalized diagnostic classification system enhance treating clinicians' diagnosis and the treatment chosen?

    LENUS (Irish Health Repository)

    Coentre, Ricardo

    2011-05-01

    Diagnosis during the initial stages of first-episode psychosis is particularly challenging but crucial in deciding on treatment. This is compounded by important differences in the two major classification systems, International Classification of Diseases, 10th revision (ICD-10) and Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). We aimed to compare the concordance between an operationalized diagnosis using Operational Criteria Checklist (OPCRIT) and treating clinician-generated diagnosis in first episode psychosis diagnosis and its correlation with treatment prescribed.

  20. Evaluation of photodynamic treatment efficiency on glioblastoma cells received from malignant lesions: initial studies

    Science.gov (United States)

    Borisova, Ekaterina; Kyurkchiev, Dobroslav; Tumangelova-Yuzeir, Kalina; Angelov, Ivan; Genova-Hristova, Tsanislava; Semyachkina-Glushkovskaya, Oxana; Minkin, Krassimir

    2018-04-01

    Photodynamic therapy is well-established and extensively used method in treatment of different cancer types. This research reveals its potential in the treatment of cultivated human glioblastoma cells with adherent morphology. As the blood-brain barrier (BBB) permeability of the drugs is a significant problem that could not be solved easily for large biomolecules, we search for an appropriate low-molecular weight photosensitizer that could be applied for photodynamic treatment of glioblastoma cells. We used delta-aminolevulinic acid (5-ALA), which could pass BBB and plays the role of precursor of a protoporphyrin IX (PpIX) - photosensitizer, that is accumulated selectively in the tumour cells and could be a proper tool in PDT of glioblastoma. However, differences from patient to patient and between the cell activities could also lead to different effectiveness of the PDT treatment of the tumour areas. Therefore in our study we investigated not only the effect of using different fluence rates and light doses, but aims to establish more efficient values for further clinical applications for each sub-type of the GBM lesions. For the needs of PDT application an illumination device was developed in Laboratory of Biophotonics, BAS based on light-emitting diode (LED) matrix light sources for therapeutic application emitting at 635 nm. The device is optimized for PDT in combination with aminolevulinic acid/protoporphyrin IX applied as a photosensitizer drug. By the means of FACSCalibur flow cytometer (Becton Dickinson, USA) and Cell Quest Software was made evaluation of PDT effect on used human glioblastoma cells. Treatment of glioblastoma tumours continues to be a very serious issue and there is growing need in development of new concepts, methods and cancer-fighting strategies. PDT may contribute in accomplishing better results in cancer treatment and can be applied as well in combination with other techniques.

  1. Initial treatment of complete rotator cuff tear and transition to surgical treatment: systematic review of the evidence

    Science.gov (United States)

    Abdul-Wahab, Taiceer A.; Betancourt, Jean P.; Hassan, Fadi; Thani, Saeed Al.; Choueiri, Hened; Jain, Nitin B.; Malanga, Gerard A.; Murrell, William D.; Prasad, Anil; Verborgt, Olivier

    2016-01-01

    Summary Background rotator cuff tear affects many people. Natural history, and evidence for non-operative treatment remains limited. Our objective is to assess evidence available for the efficacy and morbidity of commonly used systemic medications, physiotherapy, and injections alongside evaluating any negative long-term effects. Methods a systematic search was performed of PubMed, Cochrane, EMBASE and CINAHL dates (1 January 1960 – 1 December 2014), search terms: ‘rotator cuff tear’, ‘natural history’, ‘atraumatic’, ‘injection’, ‘physiotherapy’ or ‘physical therapy’, ‘injection’, ‘corticosteroid’, ‘PRP‘, ‘MSC’, risk of conservative treatment’, and ‘surgical indication’. Results eleven studies were included. The mean Coleman Methodology Score modified for conservative therapy is 69.21 (range 88–44) (SD 12.31). This included 2 RCTs, 7 prospective, and 2 retrospective studies. Evidence suggests it is safe to monitor symptomatic rotator cuff tears, as tear size and symptoms are not correlated with pain, function, and/or ultimate outcome. Conclusions complete rotator cuff tears may be effectively treated with injections, exercise in the short and intermediate terms respectively. Negative effect of corticosteroids on rotator cuff tissue has not been demonstrated. Timing to end conservative treatment is unknown, but likely indicated when a patient demonstrates increased weakness and loss of function not recoverable by physiotherapy. PMID:27331030

  2. An antiviral protein from Bougainvillea spectabilis roots; purification and characterisation.

    Science.gov (United States)

    Balasaraswathi, R; Sadasivam, S; Ward, M; Walker, J M

    1998-04-01

    An antiviral protein active against mechanical transmission of tomato spotted wilt virus was identified in the root tissues of Bougainvillea spectabilis Willd. Bougainvillea Antiviral Protein I (BAP I) was purified to apparent homogeneity from the roots of Bougainvillea by ammonium sulphate precipitation, CM- and DEAE-Sepharose chromatography and reverse phase HPLC. BAP I is a highly basic protein (pI value > 8.6) with an Mr of 28,000. The N-terminal sequence of BAP I showed homology with other plant antiviral proteins. Preliminary tests suggest that purified BAP I is capable of interfering with in vitro protein synthesis.

  3. Controversies in Neurology: why monoamine oxidase B inhibitors could be a good choice for the initial treatment of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Reichmann Heinz

    2011-09-01

    Full Text Available Abstract Background Early initiation of pharmacotherapy in Parkinson's disease (PD is nowadays widely advocated by experts since the delay of treatment has shown to be associated with a significant deterioration of health related quality of life in affected patients. Due to marked advances in PD treatment during the last decades, physicians are nowadays fortunately equipped with a variety of substances that can effectively ameliorate emerging motor symptoms of the disease, among them levodopa, dopamine agonists and monoamine oxidase type B (MAO-B inhibitors. Despite numerous drug intervention trials in early PD, there is however still ongoing controversy among neurologists which substance to use for the initial treatment of the disease. Discussion In multiple studies, MAO-B inhibitors, such as selegiline and rasagiline, have shown to provide mild symptomatic effects, delay the need for levodopa, and to reduce the incidence of motor fluctuations. Although their symptomatic efficacy is inferior compared to dopamine agonists and levodopa, MAO-B inhibitors undoubtedly have fewer side effects and are easy to administer. In contrary to their competitors, MAO-B inhibitors may furthermore offer a chance for disease modification, which so far remains a major unmet need in the management of PD and eventually makes them ideal candidates for the early treatment of the disease. Summary MAO-B inhibitors may constitute a preferable therapeutic option for early PD, mainly due to their favourable safety profile and their putative neuroprotective capabilities. Since the symptomatic effects of MAO-B inhibitors are comparatively mild, dopamine agonists and levodopa should however be considered for initial treatment in those PD patients, in whom robust and immediate symptomatic relief needs to be prioritized.

  4. Controversies in neurology: why monoamine oxidase B inhibitors could be a good choice for the initial treatment of Parkinson's disease.

    Science.gov (United States)

    Löhle, Matthias; Reichmann, Heinz

    2011-09-22

    Early initiation of pharmacotherapy in Parkinson's disease (PD) is nowadays widely advocated by experts since the delay of treatment has shown to be associated with a significant deterioration of health related quality of life in affected patients. Due to marked advances in PD treatment during the last decades, physicians are nowadays fortunately equipped with a variety of substances that can effectively ameliorate emerging motor symptoms of the disease, among them levodopa, dopamine agonists and monoamine oxidase type B (MAO-B) inhibitors. Despite numerous drug intervention trials in early PD, there is however still ongoing controversy among neurologists which substance to use for the initial treatment of the disease. In multiple studies, MAO-B inhibitors, such as selegiline and rasagiline, have shown to provide mild symptomatic effects, delay the need for levodopa, and to reduce the incidence of motor fluctuations. Although their symptomatic efficacy is inferior compared to dopamine agonists and levodopa, MAO-B inhibitors undoubtedly have fewer side effects and are easy to administer. In contrary to their competitors, MAO-B inhibitors may furthermore offer a chance for disease modification, which so far remains a major unmet need in the management of PD and eventually makes them ideal candidates for the early treatment of the disease. MAO-B inhibitors may constitute a preferable therapeutic option for early PD, mainly due to their favourable safety profile and their putative neuroprotective capabilities. Since the symptomatic effects of MAO-B inhibitors are comparatively mild, dopamine agonists and levodopa should however be considered for initial treatment in those PD patients, in whom robust and immediate symptomatic relief needs to be prioritized.

  5. Readiness to adopt a performance measurement system for substance abuse treatment: Findings from the Service Quality Measures initiative

    Directory of Open Access Journals (Sweden)

    B Myers

    2017-02-01

    Full Text Available Background. A performance measurement system – the Service Quality Measures (SQM initiative – has been developed to monitor the quality of South Africa (SA’s substance abuse treatment services. Identifying factors associated with readiness to adopt this system may inform strategies to facilitate its robust implementation. Objective. To examine factors associated with readiness to adopt a performance measurement system among SA substance abuse treatment providers. Methods. We surveyed 81 treatment providers from 13 treatment sites in the Western Cape, SA. The survey examined awareness, resources, organisational climate, leadership support and readiness to adopt the SQM system. Regression analysis was used to identify factors associated with readiness to adopt this system. Results. Readiness to adopt the SQM initiative was high (M=5.64, standard deviation 1.63. In bivariate analyses, caseload size (F=3.73 (degrees of freedom (df=3.70, p=0.015, awareness (r=0.78, p<0.0001, leadership support (r=0.70, p<0.0001, resources (r=0.65, p<0.0001, openness to change (r=0.372, p=0.001, and external pressure to change were associated with readiness to adopt the SQM. In multivariate analyses, only awareness of the SQM initiative (B=0.34, standard error (SE 0.08, t=4.4, p<0.0001 and leadership support (B=0.45, SE 0.11, t=4.0, p<0.0001 were significantly associated with readiness to adopt this system. Conclusion. While treatment providers report high levels of readiness to adopt the SQM system, findings show that the likelihood of adoption can be further increased through improved provider awareness and enhanced leadership support for this health innovation.

  6. Readiness to adopt a performance measurement system for substance abuse treatment: Findings from the Service Quality Measures initiative.

    Science.gov (United States)

    Myers, B; Petersen Williams, P; Johnson, K; Govender, R; Manderscheid, R; Koch, J R

    2017-01-30

    A performance measurement system - the Service Quality Measures (SQM) initiative - has been developed to monitor the quality of South Africa (SA)'s substance abuse treatment services. Identifying factors associated with readiness to adopt this system may inform strategies to facilitate its robust implementation. To examine factors associated with readiness to adopt a performance measurement system among SA substance abuse treatment providers. We surveyed 81 treatment providers from 13 treatment sites in the Western Cape, SA. The survey examined awareness, resources, organisational climate, leadership support and readiness to adopt the SQM system. Regression analysis was used to identify factors associated with readiness to adopt this system. Readiness to adopt the SQM initiative was high (M=5.64, standard deviation 1.63). In bivariate analyses, caseload size (F=3.73 (degrees of freedom (df)=3.70), p=0.015), awareness (r=0.78, p<0.0001), leadership support (r=0.70, p<0.0001), resources (r=0.65, p<0.0001), openness to change (r=0.372, p=0.001), and external pressure to change were associated with readiness to adopt the SQM. In multivariate analyses, only awareness of the SQM initiative (B=0.34, standard error (SE) 0.08, t=4.4, p<0.0001) and leadership support (B=0.45, SE 0.11, t=4.0, p<0.0001) were significantly associated with readiness to adopt this system. While treatment providers report high levels of readiness to adopt the SQM system, findings show that the likelihood of adoption can be further increased through improved provider awareness and enhanced leadership support for this health innovation.

  7. Guidelines for screening, prophylaxis and critical information prior to initiating anti-TNF-alpha treatment

    DEFF Research Database (Denmark)

    Nordgaard-Lassen, Inge; Dahlerup, Jens Frederik; Belard, Erika

    2012-01-01

    a history of previous malignancies (cases of malignant disease within 5 years of anti-TNF-alpha treatment should be carefully considered). The physical examination should include lung/heart auscultation and lymph node examination, and the paraclinical investigations should include chest X...

  8. National Registries of Systemic Treatment for Psoriasis and the European 'Psonet' Initiative

    NARCIS (Netherlands)

    Lecluse, L. L. A.; Naldi, L.; Stern, R. S.; Spuls, P. I.

    2009-01-01

    About 11 million people suffer from psoriasis in Europe. This chronic condition may have a dramatic impact on quality of life. About 20% of patients may need systemic treatment to effectively control their disease activity. The introduction of biological agents greatly increased the options of

  9. High-Dose Radioiodine Outpatient Treatment: An Initial Experience in Thailand

    International Nuclear Information System (INIS)

    Nantajit, Danupon; Saengsuda, Sureerat; NaNakorn, Pattama; Saengsuda, Yuthana

    2015-01-01

    The aim of this study was to determine whether high-dose radioactive iodine (Na 131 I) outpatient treatment of patients with thyroid carcinoma is a pragmatically safe approach, particularly for the safety of caregivers. A total of 79 patients completed the radiation-safety questionnaires prior to receiving high-dose radioactive iodine treatment. The questionnaire studied the subjects’ willingness to be treated as outpatients, along with the radiation safety status of their caregivers and family members. In patients, who were selected to be treated as outpatients, both internal and external radiation exposures of their primary caregivers were measured, using thyroid uptake system and electronic dosimeter, respectively. Overall, 62 out of 79 patients were willing to be treated as outpatients; however, only 44 cases were eligible for the treatment. The primary reason was that the patients did not use exclusive, separated bathrooms. The caregivers of 10 subjects, treated as outpatients, received an average radiation dose of 138.1 microsievert (mSv), which was almost entirely from external exposure; the internal radiation exposures were mostly at negligible values. Therefore, radiation exposure to caregivers was significantly below the public exposure limit (1 mSv) and the recommended limit for caregivers (5 mSv). A safe 131 I outpatient treatment in patients with thyroid carcinoma could be achieved by selective screening and providing instructions for patients and their caregivers

  10. In vitro and in vivo antiviral activity of scopadulcic acid B from Scoparia dulcis, Scrophulariaceae, against herpes simplex virus type 1.

    Science.gov (United States)

    Hayashi, K; Niwayama, S; Hayashi, T; Nago, R; Ochiai, H; Morita, N

    1988-09-01

    The antiviral activity of five diterpenoids isolated from Scoparia dulcis L., Scrophulariaceae, was examined in vitro against herpes simplex virus type 1. Among these compounds, only scopadulcic acid B was found to inhibit the viral replication with the in vitro therapeutic index of 16.7. The action of scopadulcic acid B was not due to a direct virucidal effect or inhibition of virus attachment to host cells. Single-cycle replication experiments indicated that the compound interfered with considerably early events of virus growth. The influence of scopadulcic acid B on the course of the primary corneal herpes simplex virus infection was investigated by means of a hamster test model. When the treatment was initiated immediately after virus inoculation, scopadulcic acid B, when applied orally or intraperitoneally, effectively prolonged both the appearance of herpetic lesions and the survival time at the dose of 100 and 200 mg/kg per day.

  11. The human cathelicidin LL-37 has antiviral activity against respiratory syncytial virus.

    Directory of Open Access Journals (Sweden)

    Silke M Currie

    Full Text Available Respiratory syncytial virus is a leading cause of lower respiratory tract illness among infants, the elderly and immunocompromised individuals. Currently, there is no effective vaccine or disease modifying treatment available and novel interventions are urgently required. Cathelicidins are cationic host defence peptides expressed in the inflamed lung, with key roles in innate host defence against infection. We demonstrate that the human cathelicidin LL-37 has effective antiviral activity against RSV in vitro, retained by a truncated central peptide fragment. LL-37 prevented virus-induced cell death in epithelial cultures, significantly inhibited the production of new infectious particles and diminished the spread of infection, with antiviral effects directed both against the viral particles and the epithelial cells. LL-37 may represent an important targetable component of innate host defence against RSV infection. Prophylactic modulation of LL-37 expression and/or use of synthetic analogues post-infection may represent future novel strategies against RSV infection.

  12. Direct Acting Antivirals in Patients with Chronic Hepatitis C and Down Syndrome

    Directory of Open Access Journals (Sweden)

    Eric R. Yoo

    2016-01-01

    Full Text Available Patients with Down syndrome who received blood transfusions, likely in conjunction with cardiothoracic surgery for congenital heart disease and prior to the implementation of blood-donor screening for hepatitis C virus infection, face a substantial risk of acquiring the infection. In the past, interferon-based therapy for chronic hepatitis C infection in patients with Down syndrome was noted to have lower efficacy and potentially higher risk of adverse effects. Recently, the treatment for chronic hepatitis C has been revolutionized with the introduction of interferon-free direct acting antivirals with favorable safety, tolerability, and efficacy profile. Based on our experiences, the newly approved sofosbuvir-based direct acting antiviral therapy is well tolerated and highly efficacious in this subpopulation of hepatitis C virus infected patients with Down syndrome.

  13. Longitudinal Liver Stiffness Assessment in Patients with Chronic Hepatitis C Undergoing Antiviral Therapy

    Science.gov (United States)

    Martinez, Stella M.; Foucher, Juliette; Combis, Jean-Marc; Métivier, Sophie; Brunetto, Maurizia; Capron, Dominique; Bourlière, Marc; Bronowicki, Jean-Pierre; Dao, Thong; Maynard-Muet, Marianne; Lucidarme, Damien; Merrouche, Wassil; Forns, Xavier; de Lédinghen, Victor

    2012-01-01

    Background/Aims Liver stiffness (LS) measurement by means of transient elastography (TE) is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC). Methods TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. Results 323 treated (62.7%) and 192 untreated patients (37.3%) were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001). The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥9.5 and ≥7.1 kPa vs lower values, respectively). Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change −16%, −10% and −2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR). In multivariate analysis, high baseline LS (P<0.0001) and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. Conclusions LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS) and suggests an improvement in liver damage. PMID:23082200

  14. Longitudinal liver stiffness assessment in patients with chronic hepatitis C undergoing antiviral therapy.

    Directory of Open Access Journals (Sweden)

    Stella M Martinez

    Full Text Available BACKGROUND/AIMS: Liver stiffness (LS measurement by means of transient elastography (TE is accurate to predict fibrosis stage. The effect of antiviral treatment and virologic response on LS was assessed and compared with untreated patients with chronic hepatitis C (CHC. METHODS: TE was performed at baseline, and at weeks 24, 48, and 72 in 515 patients with CHC. RESULTS: 323 treated (62.7% and 192 untreated patients (37.3% were assessed. LS experienced a significant decline in treated patients and remained stable in untreated patients at the end of study (P<0.0001. The decline was significant for patients with baseline LS ≥ 7.1 kPa (P<0.0001 and P 0.03, for LS ≥ 9.5 and ≥ 7.1 kPa vs lower values, respectively. Sustained virological responders and relapsers had a significant LS improvement whereas a trend was observed in nonresponders (mean percent change -16%, -10% and -2%, for SVR, RR and NR, respectively, P 0.03 for SVR vs NR. In multivariate analysis, high baseline LS (P<0.0001 and ALT levels, antiviral therapy and non-1 genotype were independent predictors of LS improvement. CONCLUSIONS: LS decreases during and after antiviral treatment in patients with CHC. The decrease is significant in sustained responders and relapsers (particularly in those with high baseline LS and suggests an improvement in liver damage.

  15. EVALUATION OF EFFECTIVENESS OF ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C, CAUSED BY HCV GENOTYPE 6

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    D. A. Lioznov

    2017-01-01

    Full Text Available Objectives: Evaluating the effectiveness of 2 therapeutic schemes for chronic hepatitis C (genotype 6 which combined sofosbuvir and ribavirin, one of them also included pegylated interferon. Materials and methods: The study included 110 patients with chronic hepatitis C (genotype 6, who have undergone antiviral therapy (HTP in Hepatology Clinic inHo Chi Minh City,Vietnamfrom November 2015 to July 2016. 24 patients were treated by Pegylated interferon alfa-2a, ribavirin and sofosbuvir for 12 weeks, 86 patients – by sofosbuvir and ribavirin for 24 weeks. Non-interferon regimen was administered primarily to patients with contraindications to the use of interferon. To monitor the effectiveness of antiviral therapy, quantification of HCV RNA in serum was performed by PCR prior to treatment, at 4th, 12th or 24th week (depending on the observation group from the starting of treatment and at 12th, 24th week after completion of treatment. Results: All patients, who were treated with pegylated interferon, ribavirin and sofosbuvir, completed the full course of treatment and 100% of them are registered with sustained virological response at 12th and 24th week after the end of antiviral therapy (SVR-12 and SVR-24, respectively. In the group of patients, who treated with ribavirin and sofosbuvir, 97,7% of patients completed full course of treatment (SVR-12 was registered in 93% of patients, and SVR-24 – in 91,9% of patients. Of 75 patients without a history of HCC, SVR24 was registered in 74 people (98,7%, of 11 patients with HCC – in 5 patients (45,5%. SVR-24 was registered in 98% of patients with cirrhosis (F4 without HCC. Conclusion: The results can serve as a justification for the use of these schemes of antiviral therapy for special groups of patients and/or conditions when it is impossible to follow the latest recommendations, which will help to expand the access of patients to effective antiviral therapy for chronic hepatitis C.

  16. Considerations for initial dosing of botulinum toxin in treatment of adductor spasmodic dysphonia.

    Science.gov (United States)

    Rosow, David E; Parikh, Punam; Vivero, Richard J; Casiano, Roy R; Lundy, Donna S

    2013-06-01

    To assess the effect on voice improvement and duration of breathiness based on initial dose of onabotulinum toxin A (BTX-A) in the management of adductor spasmodic dysphonia (SD) and to compare voice outcomes for initial bilaterally injected doses of 1.25 units (group A) vs 2.5 units (group B) of BTX-A. Case series with chart review of patients with adductor SD treated at a tertiary care facility from 1990 to 2011. Academic subspecialty laryngology practice. Demographic data (age and sex), voice rating, duration of voice improvement, and breathiness were evaluated and compared between groups A and B using the Student t test and χ(2) analysis. Of 478 patients identified, 305 (223 in group A, 82 in group B) patients met inclusion criteria. The average age was 56.2 years in group A and 57.4 years in group B (P = .5). The female to male ratio was 2.91 for group A vs 3.56 for group B (P = .61). Good voice outcomes (grade 3 or 4) were reported by 91% of group A patients vs 94% of group B (P = .75). The average duration of voice improvement was 99.7 days for group A and 108.3 days for group B (P = .54). The average duration of breathiness was 10.88 days for group A vs 15.42 days for group B (P = .02). Patients injected with 1.25 units bilaterally had a statistically significant shorter duration of breathiness without a statistically significant difference in clinical effectiveness or voice outcome. It is therefore recommended that a relatively low initial BTX-A dose be used with subsequent titration to achieve improved voice outcomes.

  17. Current antiviral drugs and their analysis in biological materials - Part II: Antivirals against hepatitis and HIV viruses.

    Science.gov (United States)

    Nováková, Lucie; Pavlík, Jakub; Chrenková, Lucia; Martinec, Ondřej; Červený, Lukáš

    2018-01-05

    This review is a Part II of the series aiming to provide comprehensive overview of currently used antiviral drugs and to show modern approaches to their analysis. While in the Part I antivirals against herpes viruses and antivirals against respiratory viruses were addressed, this part concerns antivirals against hepatitis viruses (B and C) and human immunodeficiency virus (HIV). Many novel antivirals against hepatitis C virus (HCV) and HIV have been introduced into the clinical practice over the last decade. The recent broadening portfolio of these groups of antivirals is reflected in increasing number of developed analytical methods required to meet the needs of clinical terrain. Part II summarizes the mechanisms of action of antivirals against hepatitis B virus (HBV), HCV, and HIV, their use in clinical practice, and analytical methods for individual classes. It also provides expert opinion on state of art in the field of bioanalysis of these drugs. Analytical methods reflect novelty of these chemical structures and use by far the most current approaches, such as simple and high-throughput sample preparation and fast separation, often by means of UHPLC-MS/MS. Proper method validation based on requirements of bioanalytical guidelines is an inherent part of the developed methods. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Initiating Childhood Cancer Treatment in Rural Rwanda: A Partnership-Based Approach.

    Science.gov (United States)

    Stulac, Sara; Mark Munyaneza, Richard B; Chai, Jeanne; Bigirimana, Jean Bosco; Nyishime, Merab; Tapela, Neo; Chaffee, Sara; Lehmann, Leslie; Shulman, Lawrence N

    2016-05-01

    More than 85% of pediatric cancer cases and 95% of deaths occur in resource-poor countries that use less than 5% of the world's health resources. In the developed world, approximately 81% of children with cancer can be cured. Models applicable in the most resource-poor settings are needed to address global inequities in pediatric cancer treatment. Between 2006 and 2011, a cohort of children received cancer therapy using a new approach in rural Rwanda. Children were managed by a team of a Rwandan generalist doctor, Rwandan nurse case manager, Rwanda-based US-trained pediatrician, and US-based pediatric oncologist. Biopsies and staging studies were obtained in-country. Pathologic diagnoses were made at US or European laboratories. Rwanda-based clinicians and the pediatric oncologist jointly generated treatment plans by telephone and email. Treatment was provided to 24 patients. Diagnoses included lymphomas (n = 10), sarcomas (n = 9), leukemias (n = 2), and other malignancies (n = 3). Standard chemotherapy regimens included CHOP, ABVD, VA, COP/COMP, and actino-VAC. Thirteen patients were in remission at the completion of data collection. Two succumbed to treatment complications and nine had progressive disease. There were no patients who abandoned treatment. The mean overall survival was 31 months and mean disease-free survival was 18 months. These data suggest that chemotherapy can be administered with curative intent to a subset of cancer patients in this setting. This approach provides a platform for pediatric cancer care models, relying on local physicians collaborating with remote specialist consultants to deliver subspecialty care in resource-poor settings. © 2016 Wiley Periodicals, Inc.

  19. Treatment Modalities and Antimicrobial Stewardship Initiatives in the Management of Intra-Abdominal Infections

    Directory of Open Access Journals (Sweden)

    Charles Hoffmann

    2016-02-01

    Full Text Available Antimicrobial stewardship programs (ASPs focus on improving the utilization of broad spectrum antibiotics to decrease the incidence of multidrug-resistant Gram positive and Gram negative pathogens. Hospital admission for both medical and surgical intra-abdominal infections (IAIs commonly results in the empiric use of broad spectrum antibiotics such as fluoroquinolones, beta-lactam beta-lactamase inhibitors, and carbapenems that can select for resistant organisms. This review will discuss the management of uncomplicated and complicated IAIs as well as highlight stewardship initiatives focusing on the proper use of broad spectrum antibiotics.

  20. Validation of the INNO-LiPA HBV DR Assay (Version 2) in Monitoring Hepatitis B Virus-Infected Patients Receiving Nucleoside Analog Treatment

    NARCIS (Netherlands)

    Niesters, H. G. M.; Zoulim, F.; Pichoud, C.; Buti, M.; Shapiro, F.; D'Heuvaert, N.; Celis, L.; Doutreloigne, J.; Sablon, E.

    Hepatitis B virus (HBV) antiviral drug resistance mutations prevent successful outcome of treatment and lead to worsening of liver disease. Detection of its emergence permits opportune treatment with alternative drugs. Unfortunately, the use of newly approved antivirals, including adefovir

  1. Fondaparinux in the initial and long-term treatment of venous thromboembolism.

    Science.gov (United States)

    Pesavento, Raffaele; Amitrano, Maria; Trujillo-Santos, Javier; Di Micco, Pierpaolo; Mangiacapra, Sara; López-Jiménez, Luciano; Falgá, Conxita; García-Bragado, Fernando; Piovella, Chiara; Prandoni, Paolo; Monreal, Manuel

    2015-02-01

    Even in the absence of evidence on its long-term efficacy and safety, a number of patients with venous thromboembolism (VTE) receive long-term therapy with fondaparinux alone in everyday practice. We used the Registro Informatizado de Enfermedad Tromboembólica (RIETE) registry to compare the rate of VTE recurrences and major bleeding at 10 and 90 days in patients with and without cancer. For long-term therapy, fondaparinux was compared with vitamin K antagonists (VKA) in patients without cancer and with low-molecular-weight heparin (LMWH) in those with cancer. Of 47,378 patients recruited, 46,513 were initially treated with heparin, 865 with fondaparinux. Then, 263 patients (78 with cancer) were treated for at least 3 months with fondaparinux. After propensity-score matching, there were no differences between patients receiving initial therapy with heparin or fondaparinux. Among patients with cancer, there were no differences between fondaparinux and LMWH. Among patients without cancer, the long-term use of fondaparinux was associated with an increased risk of major bleeding (3.24 % vs. 0.95 %, p<0.05). An unexpected high rate of major bleeding was observed in non-cancer patients treated with long-term fondaparinux. Our small sample does not allow to derive relevant conclusions on the use of fondaparinux in cancer patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Dealing with initial chemotherapy doses: a new basis for treatment optimization in limited small-cell lung cancer

    International Nuclear Information System (INIS)

    Le Chevalier, T.; Le Cesne, A.; Arriagada, R.

    1995-01-01

    Treatment of patients with small-cell lung cancer (SCLC) remains disappointing despite high initial complete response rates. The dramatic initial chemosensitivity of tumor cells is frustrated by the early emergence of chemoresistant clonogenic cells, regardless of front line treatments. Although the dose relationship is fairly well established regarding the response rate, its effect on survival is inconclusive. From 1980 to 1988, 202 patients with limited SCLC were included in four consecutive protocols using an alternating schedule of thoracic radiotherapy and chemotherapy. Despite an increase of chemotherapy and/or total radiation doses, no significant difference was observed between the four protocols in terms of response rate, disease free and overall survival. However, a retrospective analysis performed on a total of 131 consecutive patients led us to propose the hypothesis that a moderate increase in the initial dose, ie first course, of cisplatin and cyclophosphamide could improve overall survival. From 1988 to 1991, 105 patients were subsequently included in a large randomized trial raising this question. The treatment difference only concerned the initial doses of cisplatin (80 vs 100 mg/m 2 ) and cyclophosphamide (900 vs 1200 mg/m 2 ). The trial was closed after inclusion of 105 patients, 32 months after the start of the study because at that time overall survival was significantly better in the higher-dose group (p = 0.001). The emergence of this debatable concept opens new directions in the therapeutic strategy of SCLC and the contribution of hematopoietic growth factors may be a great interest in the management of this disease. (authors). 27 refs., 1 tab

  3. Cervical mature teratoma 17 years after initial treatment of testicular teratocarcinoma: report of a late relapse

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    Alavion Mina

    2007-01-01

    Full Text Available Abstract Background Late relapses of testicular germ cell tumor are uncommon. We report a case of cervical mature teratoma appeared 17 years after treatment of testicular teratocarcinoma. Case presentation A 20- year- old patient underwent left sided orchiectomy followed by systemic therapy and retroperitoneal residual mass resection in 1989. He remained in complete remission for 200 months. In 2005 a huge left supraclavicular neck mass with extension to anterior mediastinum appeared. Radical surgical resection of the mass was performed and pathologic examination revealed mature teratoma. Conclusion This is one of the longest long-term reported intervals of a mature teratoma after treatment of a testicular nonseminoma germ cell tumor. This case emphasizes the necessity for follow up of testicular cancer throughout the patient's life.

  4. Separation methods for acyclovir and related antiviral compounds.

    Science.gov (United States)

    Loregian, A; Gatti, R; Palù, G; De Palo, E F

    2001-11-25

    Acyclovir (ACV) is an antiviral drug, which selectively inhibits replication of members of the herpes group of DNA viruses with low cell toxicity. Valaciclovir (VACV), a prodrug of ACV is usually preferred in the oral treatment of viral infections, mainly herpes simplex virus (HSV). Also other analogues such as ganciclovir and penciclovir are discussed here. The former acts against cytomegalovirus (CMV) in general and the latter against CMV retinitis. The action mechanism of these antiviral drugs is presented briefly here, mainly via phosphorylation and inhibition of the viral DNA polymerase. The therapeutic use and the pharmacokinetics are also outlined. The measurement of the concentration of acyclovir and related compounds in biological samples poses a particularly significant challenge because these drugs tend to be structurally similar to endogenous substances. The analysis requires the use of highly selective analytical techniques and chromatography methods are a first choice to determine drug content in pharmaceuticals and to measure them in body fluids. Chromatography can be considered the procedure of choice for the bio-analysis of this class of antiviral compounds, as this methodology is characterised by good specificity and accuracy and it is particularly useful when metabolites need to be monitored. Among chromatographic techniques, the reversed-phase (RP) HPLC is widely used for the analysis. C18 Silica columns from 7.5 to 30 cm in length are used, the separation is carried out mainly at room temperature and less than 10 min is sufficient for the analysis at 1.0-1.5 ml/min of flow-rate. The separation methods require an isocratic system, and various authors have proposed a variety of mobile phases. The detection requires absorbance or fluorescence measurements carried out at 250-254 nm and at lambdaex=260-285 nm, lambdaem=375-380 nm, respectively. The detection limit is about 0.3-10 ng/ml but the most important aspect is related to the sample treatment

  5. Yield Responses of Black Spruce to Forest Vegetation Management Treatments: Initial Responses and Rotational Projections

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    Peter F. Newton

    2012-01-01

    Full Text Available The objectives of this study were to (1 quantitatively summarize the early yield responses of black spruce (Picea mariana (Mill. B.S.P. to forest vegetation management (FVM treatments through a meta-analytical review of the scientific literature, and (2 given (1, estimate the rotational consequences of these responses through model simulation. Based on a fixed-effects meta-analytic approach using 44 treated-control yield pairs derived from 12 experiments situated throughout the Great Lakes—St. Lawrence and Canadian Boreal Forest Regions, the resultant mean effect size (response ratio and associated 95% confidence interval for basal diameter, total height, stem volume, and survival responses, were respectively: 54.7% (95% confidence limits (lower/upper: 34.8/77.6, 27.3% (15.7/40.0, 198.7% (70.3/423.5, and 2.9% (−5.5/11.8. The results also indicated that early and repeated treatments will yield the largest gains in terms of mean tree size and survival. Rotational simulations indicated that FVM treatments resulted in gains in stand-level operability (e.g., reductions of 9 and 5 yr for plantations established on poor-medium and good-excellent site qualities, resp.. The challenge of maintaining coniferous forest cover on recently disturbed sites, attaining statutory-defined free-to-grow status, and ensuring long-term productivity, suggest that FVM will continue to be an essential silvicultural treatment option when managing black spruce plantations.

  6. Initial Clinical Experience Performing Patient Treatment Verification With an Electronic Portal Imaging Device Transit Dosimeter

    Energy Technology Data Exchange (ETDEWEB)

    Berry, Sean L., E-mail: BerryS@MSKCC.org [Department of Applied Physics and Applied Mathematics, Columbia University, New York, New York (United States); Department of Medical Physics, Memorial Sloan-Kettering Cancer Center, New York, New York (United States); Polvorosa, Cynthia; Cheng, Simon; Deutsch, Israel; Chao, K. S. Clifford; Wuu, Cheng-Shie [Department of Radiation Oncology, Columbia University, New York, New York (United States)

    2014-01-01

    Purpose: To prospectively evaluate a 2-dimensional transit dosimetry algorithm's performance on a patient population and to analyze the issues that would arise in a widespread clinical adoption of transit electronic portal imaging device (EPID) dosimetry. Methods and Materials: Eleven patients were enrolled on the protocol; 9 completed and were analyzed. Pretreatment intensity modulated radiation therapy (IMRT) patient-specific quality assurance was performed using a stringent local 3%, 3-mm γ criterion to verify that the planned fluence had been appropriately transferred to and delivered by the linear accelerator. Transit dosimetric EPID images were then acquired during treatment and compared offline with predicted transit images using a global 5%, 3-mm γ criterion. Results: There were 288 transit images analyzed. The overall γ pass rate was 89.1% ± 9.8% (average ± 1 SD). For the subset of images for which the linear accelerator couch did not interfere with the measurement, the γ pass rate was 95.7% ± 2.4%. A case study is presented in which the transit dosimetry algorithm was able to identify that a lung patient's bilateral pleural effusion had resolved in the time between the planning CT scan and the treatment. Conclusions: The EPID transit dosimetry algorithm under consideration, previously described and verified in a phantom study, is feasible for use in treatment delivery verification for real patients. Two-dimensional EPID transit dosimetry can play an important role in indicating when a treatment delivery is inconsistent with the original plan.

  7. Antiviral activity of gliotoxin, gentian violet and brilliant green against Nipah and Hendra virus in vitro

    Directory of Open Access Journals (Sweden)

    Meyer Adam G

    2009-11-01

    Full Text Available Abstract Background Using a recently described monolayer assay amenable to high throughput screening format for the identification of potential Nipah virus and Hendra virus antivirals, we have partially screened a low molecular weight compound library (>8,000 compounds directly against live virus infection and identified twenty eight promising lead molecules. Initial single blind screens were conducted with 10 μM compound in triplicate with a minimum efficacy of 90% required for lead selection. Lead compounds were then further characterised to determine the median efficacy (IC50, cytotoxicity (CC50 and the in vitro therapeutic index in live virus and pseudotype assay formats. Results While a number of leads were identified, the current work describes three commercially available compounds: brilliant green, gentian violet and gliotoxin, identified as having potent antiviral activity against Nipah and Hendra virus. Similar efficacy was observed against pseudotyped Nipah and Hendra virus, vesicular stomatitis virus and human parainfluenza virus type 3 while only gliotoxin inhibited an influenza A virus suggesting a non-specific, broad spectrum activity for this compound. Conclusion All three of these compounds have been used previously for various aspects of anti-bacterial and anti-fungal therapy and the current results suggest that while unsuitable for internal administration, they may be amenable to topical antiviral applications, or as disinfectants and provide excellent positive controls for future studies.

  8. Antiprotozoan and Antiviral Activities of Non-Cytotoxic Truncated and Variant Analogues of Mussel Defensin

    Directory of Open Access Journals (Sweden)

    Philippe Roch

    2004-01-01

    Full Text Available We previously reported the crucial role displayed by loop 3 of defensin isolated from the Mediterranean mussel, Mytilus galloprovincialis, in antibacterial and antifungal activities. We now investigated antiprotozoan and antiviral activities of some previously reported fragments B, D, E, P and Q. Two fragments (D and P efficiently killed Trypanosoma brucei (ID50 4–12 μM and Leishmania major (ID50 12–45 μM in a time/dose-dependent manner. Killing of T. brucei started as early as 1 h after initiation of contact with fragment D and reached 55% mortality after 6 h. Killing was temperature dependent and a temperature of 4°C efficiently impaired the ability to kill T. brucei. Fragments bound to the entire external epithelium of T. brucei. Prevention of HIV-1 infestation was obtained only with fragments P and Q at 20 μM. Even if fragment P was active on both targets, the specificity of fragments D and Q suggest that antiprotozoan and antiviral activities are mediated by different mechanisms. Truncated sequences of mussel defensin, including amino acid replacement to maintain 3D structure and increased positive net charge, also possess antiprotozoan and antiviral capabilities. New alternative and/or complementary antibiotics can be derived from the vast reservoir of natural antimicrobial peptides (AMPs contained in marine invertebrates.

  9. Systems-Biology Approaches to Discover Anti-Viral Effectors of the Human Innate Immune Response

    Directory of Open Access Journals (Sweden)

    Andreas F.R. Sommer

    2011-07-01

    Full Text Available Virus infections elicit an immediate innate response involving antiviral factors. The activities of some of these factors are, in turn, blocked by viral countermeasures. The ensuing battle between the host and the viruses is crucial for determining whether the virus establishes a foothold and/or induces adaptive immune responses. A comprehensive systems-level understanding of the repertoire of anti-viral effectors in the context of these immediate virus-host responses would provide significant advantages in devising novel strategies to interfere with the initial establishment of infections. Recent efforts to identify cellular factors in a comprehensive and unbiased manner, using genome-wide siRNA screens and other systems biology “omics” methodologies, have revealed several potential anti-viral effectors for viruses like Human immunodeficiency virus type 1 (HIV-1, Hepatitis C virus (HCV, West Nile virus (WNV, and influenza virus. This review describes the discovery of novel viral restriction factors and discusses how the integration of different methods in systems biology can be used to more comprehensively identify the intimate interactions of viruses and the cellular innate resistance.

  10. Antiviral activity against human immunodeficiency virus-1 in vitro by myristoylated-peptide from Heliothis virescens

    International Nuclear Information System (INIS)

    Ourth, Donald D.

    2004-01-01

    An insect antiviral compound was purified from Heliothis virescens larval hemolymph by gel-filtration high pressure liquid chromatography (HPLC) and C-18 reverse-phase HPLC and its structure was determined by mass spectrometry. The antiviral compound is an N-myristoylated-peptide containing six amino acids with calculated molecular weight of 916 Da. The N-terminus contains the fatty acid myristoyl, and the C-terminus contains histidine with two methyl groups giving the histidine a permanent positive charge. The remainder of the compound is essentially non-polar. The structure of the compound corresponds with the 'myristate plus basic' motif expressed by certain viral proteins in their binding to the cytoplasmic side of the plasma membrane to initiate viral assembly and budding from a host cell. The insect antiviral compound may inhibit viral assembly and/or budding of viruses from host cells that could include the human immunodeficiency virus-1 (HIV-1) and herpes simplex virus-1 that use this motif for exit from a host cell. Using the formazan assay, the myristoylated-peptide was effective against HIV-1, with a nine times increase in the viability and protection in vitro of treated CEM-SS cells when compared with infected but untreated control cells

  11. A heritable antiviral RNAi response limits Orsay virus infection in Caenorhabditis elegans N2.

    Directory of Open Access Journals (Sweden)

    Mark G Sterken

    Full Text Available Orsay virus (OrV is the first virus known to be able to complete a full infection cycle in the model nematode species Caenorhabditis elegans. OrV is transmitted horizontally and its infection is limited by antiviral RNA interference (RNAi. However, we have no insight into the kinetics of OrV replication in C. elegans. We developed an assay that infects worms in liquid, allowing precise monitoring of the infection. The assay revealed a dual role for the RNAi response in limiting Orsay virus infection in C. elegans. Firstly, it limits the progression of the initial infection at the step of recognition of dsRNA. Secondly, it provides an inherited protection against infection in the offspring. This establishes the heritable RNAi response as anti-viral mechanism during OrV infections in C. elegans. Our results further illustrate that the inheritance of the anti-viral response is important in controlling the infection in the canonical wild type Bristol N2. The OrV replication kinetics were established throughout the worm life-cycle, setting a standard for further quantitative assays with the OrV-C. elegans infection model.

  12. Enterprise stent for the treatment of symptomatic intracranial atherosclerotic stenosis: an initial experience of 44 patients.

    Science.gov (United States)

    Feng, Zhengzhe; Duan, Guoli; Zhang, Ping; Chen, Lei; Xu, Yi; Hong, Bo; Zhao, Wenyuan; Liu, Jianmin; Huang, Qinghai

    2015-10-08

    Wingspan stenting for the treatment of complex intracranial atherosclerotic stenosis (ICAS), i.e., that involving tortuous vascular pathways, long (>15 mm) lesions or arterial bifurcations, has a relatively high risk of complications. This retrospective study assessed the safety and efficacy of undersized balloon angioplasty followed by deployment of the more flexible Enterprise stent for the treatment of complex symptomatic ICAS. Forty-four patients on combined antiplatelet therapy and intensive risk factor management and a symptomatic 70-99% stenosis of a major intracranial artery in complex settings that was treated with balloon angioplasty and Enterprise stent deployment between July 2009 and August 2013 were enrolled. Primary outcome was occurrence of ischemic or hemorrhagic stroke or death within 30 days after intervention. Secondary outcomes included procedural success (defined as achievement of 50% in-stent restenosis after mean 22 months follow-up. In this retrospective, single-center experience, undersized balloon angioplasty followed by Enterprise stent deployment appears technically feasible with a relatively low rate of complications for the treatment of complex symptomatic ICAS. Prospective, multicenter, randomized controlled trials against optimal medical management are warranted.

  13. An initial report of cyberknife radiosurgery treatment in early stage lung cancer

    International Nuclear Information System (INIS)

    Yuan Zhiyong; Song Yongchun; Li Fengtong; Dong Yang; Wang Jingsheng; Wang Jun; Wang Changli; Wang Ping

    2008-01-01

    Objective: To study the efficacy and toxicity of the cyberknife in the treatment of medically inoperable patients with early stage lung cancer. Methods: From September 2006 to July 2007,17 patients with clinical stage I a-I b lung cancer were treated with cyberknife at Tianjin Cancer Hospital. Of the 11 patients receiving CT guided biopsy, 3 were squamous cell cancer and 8 were adenocarcinoma. Six patients refused intrusive operation and were diagnosed by PET-CT scan. All patients were medically inoperable evaluated by a thoracic surgeon. The PTV=GTV + 3-5 mm, and the median volume of PTV was 36 cm 3 (6-82 cm 3 ). The median total prescription dose was 50 Gy(45-60 Gy) at 3-5 fractions. Results: The median follow-up time was 7 months(3-11 months). All the patients finished the treatment and were alive by the last follow-up. Slight fatigue was the most common complain. Evaluated by CT scan, 13 were complete response and 4 were partial response. No recurrence, progression or distant metastasis occurred. There were 3 patients with grade I granulocytopenia, 3 grade I pneumonitis and 1 grade II pneumonitis. Conclusions: The cyberknife radiosurgery treatment in early stage lung cancer shows a high rate of local control and minimal toxicity. Long time follow-up is necessary to evaluate the survival data and late toxicity. (authors)

  14. Intervening factors for the initiation of treatment of patients with stomach and colorectal cancer

    Directory of Open Access Journals (Sweden)

    Thaína Dalla Valle

    Full Text Available ABSTRACT Objective: to identify the time between symptoms, the request for care and the beginning of treatment in patients with stomach and colorectal cancer as well as the factors that interfere in these processes. Method: correlational descriptive study, including 101 patients diagnosed with stomach or colorectal cancer, treated in a hospital specialized in oncology. Results: the 101 patients investigated there was predominance of males, mean age of 61.7 years. The search for medical care occurred within 30 days after the onset of symptoms, in most cases. The mean total time between the onset of symptoms and the beginning of treatment ranged from 15 to 16 months, and the mean time between the search for medical care and the diagnosis was 4.78 months. The family history of cancer (p=0.008 and the implementation of preventive follow-up (p<0.001 were associated with shorter periods between the search for care and the beginning of treatment. Nausea, vomiting, hematochezia, weight loss and pain were associated with faster demand for care. Conclusion: the longer interval between the search for medical care and the diagnosis was possibly due to the non-association between the presented symptoms and the disease.

  15. Initial evaluation, diagnosis, and treatment of anorexia nervosa and bulimia nervosa.

    Science.gov (United States)

    Harrington, Brian C; Jimerson, Michelle; Haxton, Christina; Jimerson, David C

    2015-01-01

    Eating disorders are life-threatening conditions that are challenging to address; however, the primary care setting provides an important opportunity for critical medical and psychosocial intervention. The recently published Diagnostic and Statistical Manual of Mental Disorders, 5th ed., includes updated diagnostic criteria for anorexia nervosa (e.g., elimination of amenorrhea as a diagnostic criterion) and for bulimia nervosa (e.g., criterion for frequency of binge episodes decreased to an average of once per week). In addition to the role of environmental triggers and societal expectations of body size and shape, research has suggested that genes and discrete biochemical signals contribute to the development of eating disorders. Anorexia nervosa and bulimia nervosa occur most often in adolescent females and are often accompanied by depression and other comorbid psychiatric disorders. For low-weight patients with anorexia nervosa, virtually all physiologic systems are affected, ranging from hypotension and osteopenia to life-threatening arrhythmias, often requiring emergent assessment and hospitalization for metabolic stabilization. In patients with frequent purging or laxative abuse, the presence of electrolyte abnormalities requires prompt intervention. Family-based treatment is helpful for adolescents with anorexia nervosa, whereas short-term psychotherapy, such as cognitive behavior therapy, is effective for most patients with bulimia nervosa. The use of psychotropic medications is limited for anorexia nervosa, whereas treatment studies have shown a benefit of antidepressant medications for patients with bulimia nervosa. Treatment is most effective when it includes a multidisciplinary, teambased approach.

  16. Newly Diagnosed Meniere's Disease: Clinical Course With Initiation of Noninvasive Treatment Including an Accounting of Vestibular Migraine.

    Science.gov (United States)

    Sbeih, Firas; Christov, Florian; Gluth, Michael B

    2018-05-01

    To describe the course of Meniere's disease with noninvasive treatment during the first few years after initial diagnosis. A retrospective review of consecutive patients with newly diagnosed definite Meniere's disease between 2013 and 2016 and a minimum follow-up of 1 year. Patients received a written plan for low sodium, water therapy, and treatment with a diuretic and/or betahistine. Subjects were screened and treated for vestibular migraine as needed. Vertigo control and hearing status at most recent follow-up were assessed. Forty-four subjects had an average follow up of 24.3 months. Thirty-four percent had Meniere's disease and vestibular migraine, and 84% had unilateral Meniere's disease. Seventy-five percent had vertigo well controlled at most recent follow-up, with only noninvasive treatments. Age, gender, body mass index, presence of vestibular migraine, bilateral disease, and duration of follow-up did not predict noninvasive treatment failure. Worse hearing threshold at 250 Hz and lower pure tone average (PTA) at the time of diagnosis did predict failure. Fifty-two percent of ears had improved PTA at most recent visit, 20% had no change, and 28% were worse Conclusions: Encountering excellent vertigo control and stable hearing after a new diagnosis of Meniere's disease is possible with noninvasive treatments. Worse hearing status at diagnosis predicted treatment failure.

  17. Treatment of the loss of ultimate heat sink initiating events in the IRSN level 1 PSA

    International Nuclear Information System (INIS)

    Dupuy, Patricia; Georgescu, Gabriel; Corenwinder, Francois

    2014-01-01

    The total loss of the ultimate heat sink is an initiating event which, even it is mainly of external origin, has been considered in the frame of internal events Level 1 PSA by IRSN. The on-going actions on the development of external hazards PSA and the recent incident of loss of the heat sink induced by the ingress of vegetable matter that occurred in France in 2009 have pointed out the need to improve the modeling of the loss of the heat sink initiating event and sequences to better take into account the fact that this loss may be induced by external hazards and thus affect all the site units. The paper presents the historical steps of the modeling of the total loss of the heat sink, the safety stakes of this modeling, the main assumptions used by IRSN in the associated PSA for the 900 MWe reactors and the results obtained. The total loss of the heat sink was not initially addressed in the safety demonstration of French NPPs. On the basis of the insights of the first probabilistic assessments performed in the 80's, the risks associated to this 'multiple failure situation' turned out to be very significant and design and organisational improvements were implemented on the plants. Reviews of the characterization of external hazards and of their consequences on the installations and French operating feedback have revealed that extreme hazards may induce a total loss of the heat sink. Moreover, the accident that occurred at Fukushima in 2011 has pointed out the risk of such a loss of long duration at all site units in case of extreme hazards. In this context, it seems relevant to further improve the modelling of the total loss of the heat sink by considering the external hazards that may cause this loss. In a first step, IRSN has improved the assumptions and data used in the loss of the heat sink PSA model, in particular by considering that such a loss may affect all the site units. The next challenge will be the deeper analysis of the impact of external hazards on

  18. Antiviral effect of compounds derived from the seeds of Mammea americana and Tabernaemontana cymosa on Dengue and Chikungunya virus infections.

    Science.gov (United States)

    Gómez-Calderón, Cecilia; Mesa-Castro, Carol; Robledo, Sara; Gómez, Sergio; Bolivar-Avila, Santiago; Diaz-Castillo, Fredyc; Martínez-Gutierrez, Marlen

    2017-01-18

    The transmission of Dengue virus (DENV) and Chikungunya virus (CHIKV) has increased worldwide, due in part to the lack of a specific antiviral treatment. For this reason, the search for compounds with antiviral potential, either as licensed drugs or in natural products, is a research priority. The objective of this study was to identify some of the compounds that are present in Mammea americana (M. americana) and Tabernaemontana cymosa (T. cymosa) plants and, subsequently, to evaluate their cytotoxicity in VERO cells and their potential antiviral effects on DENV and CHIKV infections in those same cells. Dry ethanolic extracts of M. americana and T. cymosa seeds were subjected to open column chromatographic fractionation, leading to the identification of four compounds: two coumarins, derived from M. americana; and lupeol acetate and voacangine derived from T. cymosa.. The cytotoxicity of each compound was subsequently assessed by the MTT method (at concentrations from 400 to 6.25 μg/mL). Pre- and post-treatment antiviral assays were performed at non-toxic concentrations; the resulting DENV inhibition was evaluated by Real-Time PCR, and the CHIKV inhibition was tested by the plating method. The results were analyzed by means of statistical analysis. The compounds showed low toxicity at concentrations ≤ 200 μg/mL. The compounds coumarin A and coumarin B, which are derived from the M. americana plant, significantly inhibited infection with both viruses during the implementation of the two experimental strategies employed here (post-treatment with inhibition percentages greater than 50%, p treatment with percentages of inhibition greater than 40%, p treatment strategy (at inhibition percentages greater than 70%, p treating Dengue and Chikungunya fever. Additionally, lupeol acetate and voacangine efficiently inhibit infection with DENV, also turning them into promising antivirals for Dengue fever.

  19. Amphipathic DNA polymers exhibit antiviral activity against systemic Murine Cytomegalovirus infection

    Directory of Open Access Journals (Sweden)

    Juteau Jean-Marc

    2009-12-01

    Full Text Available Abstract Background Phosphorothioated oligonucleotides (PS-ONs have a sequence-independent, broad spectrum antiviral activity as amphipathic polymers (APs and exhibit potent in vitro antiviral activity against a broad spectrum of herpesviruses: HSV-1, HSV-2, HCMV, VZV, EBV, and HHV-6A/B, and in vivo activity in a murine microbiocide model of genital HSV-2 infection. The activity of these agents against animal cytomegalovirus (CMV infections in vitro and in vivo was therefore investigated. Results In vitro, a 40 mer degenerate AP (REP 9 inhibited both murine CMV (MCMV and guinea pig CMV (GPCMV with an IC50 of 0.045 μM and 0.16 μM, respectively, and a 40 mer poly C AP (REP 9C inhibited MCMV with an IC50 of 0.05 μM. Addition of REP 9 to plaque assays during the first two hours of infection inhibited 78% of plaque formation whereas addition of REP 9 after 10 hours of infection did not significantly reduce the number of plaques, indicating that REP 9 antiviral activity against MCMV occurs at early times after infection. In a murine model of CMV infection, systemic treatment for 5 days significantly reduced virus replication in the spleens and livers of infected mice compared to saline-treated control mice. REP 9 and REP 9C were administered intraperitoneally for 5 consecutive days at 10 mg/kg, starting 2 days prior to MCMV infection. Splenomegaly was observed in infected mice treated with REP 9 but not in control mice or in REP 9 treated, uninfected mice, consistent with mild CpG-like activity. When REP 9C (which lacks CpG motifs was compared to REP 9, it exhibited comparable antiviral activity as REP 9 but was not associated with splenomegaly. This suggests that the direct antiviral activity of APs is the predominant therapeutic mechanism in vivo. Moreover, REP 9C, which is acid stable, was effective when administered orally in combination with known permeation enhancers. Conclusion These studies indicate that APs exhibit potent, well tolerated

  20. Review of proton pump inhibitors for the initial treatment of heartburn: is there a dose ceiling effect?

    Science.gov (United States)

    Kushner, Pamela R; Peura, David A

    2011-05-01

    Proton pump inhibitors (PPIs) are widely used in clinical practice. However, concerns have been expressed about their long-term use, particularly with regard to bone health, Clostridium difficile infections, and drug interactions with platelet aggregation inhibitors. There has been limited guidance for clinicians concerning appropriate dose selection of PPIs for the initial treatment of heartburn. This review explored whether published clinical trials provide evidence of a ceiling above which higher PPI doses do not provide additional clinical benefit over the lowest approved dose. All articles of randomized, controlled clinical trials in nonerosive gastroesophageal reflux disease (GERD) in which the effects of two or more doses of the same PPI on symptomatic relief of heartburn were quantified as a study endpoint were identified and analyzed through PubMed searches up to the end of September 2010. The majority of trials evaluated provided no evidence that higher PPI doses were superior to the lowest approved dose for the initial treatment of heartburn. There were no clinically relevant findings with respect to dose dependence and safety outcomes in these studies. Efficacy outcomes from the trials suggest there may be a dose ceiling effect and highlight the need for further research on the use of the lowest effective PPI doses as an appropriate strategy in the initial treatment of uncomplicated heartburn. Observational studies and some meta-analyses have suggested that long-term PPI pharmacotherapy might be associated with safety concerns, which necessitate the periodic evaluation of therapeutic benefit in terms of symptom resolution and regimen tolerability. However, evidence to date suggests that use of the lowest effective dose for the indication is not associated with significant adverse events, particularly in the short term. Clinical practice suggests that patients requiring long-term treatment should be maintained on the lowest dose necessary to control

  1. A Quest for Initiating Cells of Head and Neck Cancer and Their Treatment

    International Nuclear Information System (INIS)

    Chen, Chao; Köberle, Beate; Kaufmann, Andreas M.; Albers, Andreas E.

    2010-01-01

    The biology of head and neck squamous cell carcinomas (HNSCC) and other cancers have been related to cancer stem-like cells (CSC). Specific markers, which vary considerably depending on tumor type or tissue of origin, characterize CSC. CSC are cancer initiating, sustaining and mostly quiescent. Compared to bulk tumors, CSC are less sensitive to chemo- and radiotherapy and may have low immunogenicity. Therapeutic targeting of CSC may improve clinical outcome. HNSCC has two main etiologies: human papillomavirus, a virus infecting epithelial stem cells, and tobacco and alcohol abuse. Here, current knowledge of HNSCC-CSC biology is reviewed and parallels to CSC of other origin are drawn where necessary for a comprehensive picture

  2. Potential Antiviral Agents from Marine Fungi: An Overview

    Directory of Open Access Journals (Sweden)

    Soheil Zorofchian Moghadamtousi

    2015-07-01

    Full Text Available Biodiversity of the marine world is only partially subjected to detailed scientific scrutiny in comparison to terrestrial life. Life in the marine world depends heavily on marine fungi scavenging the oceans of lifeless plants and animals and entering them into the nutrient cycle by. Approximately 150 to 200 new compounds, including alkaloids, sesquiterpenes, polyketides, and aromatic compounds, are identified from marine fungi annually. In recent years, numerous investigations demonstrated the tremendous potential of marine fungi as a promising source to develop new antivirals against different important viruses, including herpes simplex viruses, the human immunodeficiency virus, and the influenza virus. Various genera of marine fungi such as Aspergillus, Penicillium, Cladosporium, and Fusarium were subjected to compound isolation and antiviral studies, which led to an illustration of the strong antiviral activity of a variety of marine fungi-derived compounds. The present review strives to summarize all available knowledge on active compounds isolated from marine fungi with antiviral activity.

  3. Antiviral evaluation of an Hsp90 inhibitor, gedunin, against dengue ...

    African Journals Online (AJOL)

    Further, in silico molecular docking data revealed strong interaction of gedunin with the ATP/ADP ... Keywords: Dengue virus replication, Hsp90, Gedunin, Antiviral, Molecular docking ..... Conformational dynamics of the molecular chaperone.

  4. Antiviral activities of streptomycetes against tobacco mosaic virus ...

    African Journals Online (AJOL)

    Mahera Shinwari

    2012-01-26

    Jan 26, 2012 ... Key words: Antiviral activity, tobacco mosaic virus, actinomycetes, Streptomyces, Datura metel ... have received less attention than those caused by fungal .... leaves were divided in to three partitions each containing triplicates.

  5. Development of Small-Molecule Antivirals for Ebola

    Czech Academy of Sciences Publication Activity Database

    Janeba, Zlatko

    2015-01-01

    Roč. 35, č. 6 (2015), s. 1175-1194 ISSN 0198-6325 Institutional support: RVO:61388963 Keywords : antiviral * filovirus * Ebola virus * Marburg virus * hemorrhagic fever Subject RIV: CC - Organic Chemistry Impact factor: 9.135, year: 2015

  6. Cost-effectiveness analysis of treatment strategies for initial Clostridium difficile infection.

    Science.gov (United States)

    Varier, R U; Biltaji, E; Smith, K J; Roberts, M S; Jensen, M K; LaFleur, J; Nelson, R E

    2014-12-01

    Clostridium difficile infection (CDI) is costly. Current guidelines recommend metronidazole as first-line therapy and vancomycin as an alternative. Recurrence is common. Faecal microbiota transplantation (FMT) is an effective therapy for recurrent CDI (RCDI). This study explores the cost-effectiveness of FMT, vancomycin and metronidazole for initial CDI. We constructed a decision-analytic computer simulation using inputs from published literature to compare FMT with a 10-14-day course of oral metronidazole or vancomycin for initial CDI. Parameters included cure rates (baseline value (range)) for metronidazole (80% (65-85%)), vancomycin (90% (88-92%)) and FMT(91% (83-100%)). Direct costs of metronidazole, vancomycin and FMT, adjusted to 2011 dollars, were $57 ($43-72), $1347 ($1195-1499) and $1086 ($815-1358), respectively. Our effectiveness measure was quality-adjusted life years (QALYs). One-way and probabilistic sensitivity analyses were conducted from the third-party payer perspective. Analysis using baseline values showed that FMT($1669, 0.242 QALYs) dominated (i.e. was less costly and more effective) vancomycin ($1890, 0.241 QALYs). FMT was more costly and more effective than metronidazole ($1167, 0.238 QALYs), yielding an incremental cost-effectiveness ratio (ICER) of $124 964/QALY. One-way sensitivity analyses showed that metronidazole dominated both strategies if its probability of cure were >90%; FMT dominated if it cost costly. FMT and vancomycin are more effective. However, FMT is less likely to be economically favourable, and vancomycin is unlikely to be favourable as first-line therapy when compared with FMT. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

  7. Trabeculectomy or Transscleral Cyclophotocoagulation as Initial Treatment of Secondary Childhood Glaucoma in Northern Tanzania.

    Science.gov (United States)

    Fieß, Achim; Shah, Peter; Sii, Freda; Godfrey, Furahini; Abbott, Joe; Bowman, Richard; Bauer, Jacqueline; Dithmar, Stefan; Philippin, Heiko

    2017-07-01

    The purpose is to describe the outcome of trabeculectomy with transscleral cyclophotocoagulation (TSCPC) as an initial intervention for secondary childhood glaucoma in Northern Tanzania. A retrospective, consecutive case series was analyzed of all children with secondary childhood glaucoma who underwent initial trabeculectomy or TSCPC between 2000 and 2013 at a referral eye unit in Northern Tanzania. Retrospective data were collected on causes of glaucoma, intraocular pressure (IOP), visual acuity, complications, and subsequent interventions. Outcomes were evaluated using Kaplan-Meier survival analysis and compared with Cox regression analysis. The main outcome measure was failure (IOP>21 mm Hg). Thirty-six eyes of 27 children (male, 21; median age, 9 y; range, 0.3 to 15 y) with secondary childhood glaucoma underwent trabeculectomy (19 eyes, 53%) or TSCPC (17 eyes, 47%). Causes included ocular trauma (13, 36%), previous cataract surgery (12, 33%), congenital aniridia (5, 14%), Sturge-Weber syndrome (2, 6%), steroid-induced glaucoma (2, 6%), uveitis (1, 3%), and unspecified leucoma (1, 3%). After 12 months, success was achieved in 48% after trabeculectomy and 18% after TSCPC, with visual acuity remaining unchanged in 11 of 14 (79%) and 4 of 5 eyes (80%), respectively. One third of the children did not return for follow-up after 1 year. Distance to the hospital (>100 km) was a significant risk factor for trabeculectomy failure (P=0.031). A high proportion of secondary childhood glaucoma in Northern Tanzania was caused by trauma and previous cataract surgery. Trabeculectomy was associated with better IOP control but also a higher complication rate. The ability to maintain visual function was comparable after both interventions. Failure was associated with a journey to the eye hospital (>100 km) possibly leading to late presentation with advanced disease and erratic follow-up.

  8. Initial assessment and treatment of refugees in the Mediterranean Sea (a secondary data analysis concerning the initial assessment and treatment of 2656 refugees rescued from distress at sea in support of the EUNAVFOR MED relief mission of the EU).

    Science.gov (United States)

    Kulla, M; Josse, F; Stierholz, M; Hossfeld, B; Lampl, L; Helm, M

    2016-05-20

    As a part of the European Union Naval Force - Mediterranean Operation Sophia (EUNAVFOR Med), the Federal Republic of Germany is contributing to avoid further loss of lives at sea by supplying two naval vessels. In the study presented here we analyse the medical requirements of such rescue missions, as well as the potential benefits of various additional monitoring devices in identifying sick/injured refugees within the primary onboard medical assessment process. Retrospective analysis of the data collected between May - September 2015 from a German Naval Force frigate. Initial data collection focused on the primary medical assessment and treatment process of refugees rescued from distress at sea. Descriptive statistics, uni- and multivariate analysis were performed. The study has received a positive vote from the Ethics Commission of the University of Ulm, Germany (request no. 284/15) and has been registered in the German Register of Clinical Studies (no. DRKS00009535). A total of 2656 refugees had been rescued. 16.9 % of them were classified as "medical treatment required" within the initial onboard medical assessment process. In addition to the clinical assessment by an emergency physician, pulse rate (PR), core body temperature (CBT) and oxygen saturation (SpO2) were evaluated. Sick/injured refugees displayed a statistically significant higher PR (114/min vs. 107/min; p refugee boats. A cut-off value of clinical importance could not be found. Predominant diagnoses have been dermatological diseases (55.4), followed by internal diseases (27.7) and trauma (12.1 %). None of the refugees classified as "healthy" within the primary medical assessment process changed to "medical treatment required" during further observation. The initial medical assessment by an emergency physician has proved successful. PR, CBT and SpO2 didn't have any clinical impact to improve the identification of sick/injured refugees within the primary onboard assessment process.

  9. A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats

    Energy Technology Data Exchange (ETDEWEB)

    Li, Xiaoguang [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Department of Medical Microbiology, Harbin Medical University, Harbin 150086 (China); Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 (Japan); Qian, Hua [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811 (Japan); Miyamoto, Fusako [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Naito, Takeshi [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Kawaji, Kumi [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Kajiwara, Kazumi [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); JST Innovation Plaza Kyoto, Japan Science and Technology Agency, Nishigyo-ku, Kyoto 615-8245 (Japan); Hattori, Toshio [Tohoku University Graduate School of Medicine, Department of Internal Medicine/Division of Emerging Infectious Diseases, Sendai 980-8575 (Japan); Matsuoka, Masao [Laboratory of Virus Control, Institute for Virus Research, Kyoto University, 53 Kawaramachi, Shogoin, Sakyo-ku, Kyoto 606-8507 (Japan); Watanabe, Kentaro; Oishi, Shinya; Fujii, Nobutaka [Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501 (Japan); and others

    2012-07-27

    Highlights: Black-Right-Pointing-Pointer We established a novel, simple and rapid in vivo system for evaluation of anti-HIV-1 drugs with rats. Black-Right-Pointing-Pointer The system may be applicable for other antiviral drugs, and/or useful for initial screening in vivo. Black-Right-Pointing-Pointer In this system, TRI-1144 displayed the most potent anti-HIV-1 activity in vivo. -- Abstract: The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1{sub IIIB} and HIV-1{sub BaL} as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1{sub IIIB} activity, whereas fusion inhibitors showed both anti-HIV-1{sub IIIB} and anti-HIV-1{sub BaL} activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, 'phenotypic drug evaluation', may be applicable for the evaluation of various antiviral drugs in vivo.

  10. A simple, rapid, and sensitive system for the evaluation of anti-viral drugs in rats

    International Nuclear Information System (INIS)

    Li, Xiaoguang; Qian, Hua; Miyamoto, Fusako; Naito, Takeshi; Kawaji, Kumi; Kajiwara, Kazumi; Hattori, Toshio; Matsuoka, Masao; Watanabe, Kentaro; Oishi, Shinya; Fujii, Nobutaka

    2012-01-01

    Highlights: ► We established a novel, simple and rapid in vivo system for evaluation of anti-HIV-1 drugs with rats. ► The system may be applicable for other antiviral drugs, and/or useful for initial screening in vivo. ► In this system, TRI-1144 displayed the most potent anti-HIV-1 activity in vivo. -- Abstract: The lack of small animal models for the evaluation of anti-human immunodeficiency virus type 1 (HIV-1) agents hampers drug development. Here, we describe the establishment of a simple and rapid evaluation system in a rat model without animal infection facilities. After intraperitoneal administration of test drugs to rats, antiviral activity in the sera was examined by the MAGI assay. Recently developed inhibitors for HIV-1 entry, two CXCR4 antagonists, TF14016 and FC131, and four fusion inhibitors, T-20, T-20EK, SC29EK, and TRI-1144, were evaluated using HIV-1 IIIB and HIV-1 BaL as representative CXCR4- and CCR5-tropic HIV-1 strains, respectively. CXCR4 antagonists were shown to only possess anti-HIV-1 IIIB activity, whereas fusion inhibitors showed both anti-HIV-1 IIIB and anti-HIV-1 BaL activities in rat sera. These results indicate that test drugs were successfully processed into the rat sera and could be detected by the MAGI assay. In this system, TRI-1144 showed the most potent and sustained antiviral activity. Sera from animals not administered drugs showed substantial anti-HIV-1 activity, indicating that relatively high dose or activity of the test drugs might be needed. In conclusion, the novel rat system established here, “phenotypic drug evaluation”, may be applicable for the evaluation of various antiviral drugs in vivo.

  11. Veterans in substance abuse treatment program self-initiate box gardening as a stress reducing therapeutic modality.

    Science.gov (United States)

    Lehmann, Lauren P; Detweiler, Jonna G; Detweiler, Mark B

    2018-02-01

    To assess the experiences of a veteran initiated horticultural therapy garden during their 28-day inpatient Substance Abuse Residential Rehabilitation Treatment Program (SARRTP). Retrospective study. Veterans Affairs Medical Center (VAMC), Salem, Virginia, USA INTERVENTIONS: Group interviews with veterans from the last SARRTP classes and individual interviews with VAMC greenhouse staff in summer of 2016. Time spent in garden, frequency of garden visits, types of passive and active garden activities, words describing the veterans' emotional reactions to utilizing the garden. In 3 summer months of 2016, 50 percent of the 56 veterans interviewed visited and interacted with the gardens during their free time. Frequency of visits generally varied from 3 times weekly to 1-2 times a day. Amount of time in the garden varied from 10min to 2h. The veterans engaged in active and/or passive gardening activities during their garden visits. The veterans reported feeling "calm", "serene", and "refreshed" during garden visitation and after leaving the garden. Although data was secured only at the end of the 2016 growing season, interviews of the inpatient veterans revealed that they used their own initiative and resources to continue the horticulture therapy program for 2 successive growing years after the original pilot project ended in 2014. These non-interventionist, therapeutic garden projects suggest the role of autonomy and patient initiative in recovery programs for veterans attending VAMC treatment programs and they also suggest the value of horticulture therapy as a meaningful evidence- based therapeutic modality for veterans. Published by Elsevier Ltd.

  12. Initial North American experience with botulinum toxin type A for treatment of anismus.

    Science.gov (United States)

    Joo, J S; Agachan, F; Wolff, B; Nogueras, J J; Wexner, S D

    1996-10-01

    Botulinum toxin type A (BTX-A), produced by Clostridium botulinum, is a potent neurotoxin. The purpose of this study was to evaluate the efficacy of BTX-A for treatment of anismus. All patients treated with BTX-A for anismus were evaluated. Eligibility criteria included a history of chronic assisted evacuation (laxatives, enemas, or suppositories), demonstration of anismus by cinedefecogram and electromyography, and failure of a minimum of three sessions of supervised biofeedback therapy (BF). Contingent on body mass, 6 to 15 units of BTX-A was injected bilaterally under electromyography guidance into the external sphincter or the puborectalis muscle. Treatment was repeated as necessary for a maximum of three sessions during a three-month period. Success was considered as discontinuation of evacuatory assistance and was evaluated between one and three months and again at up to one year. Between July 1994 and May 1995, four patients ranging from 29 to 82 years in age (2 females, 2 males) had anismus that failed to respond to between 3 and 15 biofeedback sessions. All patients improved between one and three months after BTX-A injection, and two had sustained improvement for a range of three months to one year. There was no morbidity or mortality associated with BTX-A injection. BTX-A is extremely successful for temporary treatment of anismus that is refractory to BF management. However, because the mechanism of action is short, longer term results are only 50 percent successful. Hopefully, modifications in the strain of BTX-A and dose administered will allow longer periods of success or a repeat trial of BF. Nonetheless, this preliminary report is very encouraging in offering a method of managing this recalcitrant condition.

  13. Mushrooms as a source of substances with antiviral activity

    Directory of Open Access Journals (Sweden)

    Martyna Kandefer-Szerszeń

    2014-08-01

    Full Text Available Water extracts the fructifications of 56 species of fungi were examined as a source of antiviral substances with activity against VS and vaccinia viruses. Extracts from 16 fungal species exhibited the antiviral activity. Water extracts from Boletus edulis active against vaccinia virus and extract from Armillariella mellea active against VS virus are particularly worth nothing. Both of them in applied concentrations were not toxic in chick embryo fibroblasts tissue culture.

  14. Antiviral Roles of Abscisic Acid in Plants

    Directory of Open Access Journals (Sweden)

    Mazen Alazem

    2017-10-01

    Full Text Available Abscisic acid (ABA is a key hormone involved in tuning responses to several abiotic stresses and also has remarkable impacts on plant defense against various pathogens. The roles of ABA in plant defense against bacteria and fungi are multifaceted, inducing or reducing defense responses depending on its time of action. However, ABA induces different resistance mechanisms to viruses regardless of the induction time. Recent studies have linked ABA to the antiviral silencing pathway, which interferes with virus accumulation, and the micro RNA (miRNA pathway through which ABA affects the maturation and stability of miRNAs. ABA also induces callose deposition at plasmodesmata, a mechanism that limits viral cell-to-cell movement. Bamboo mosaic virus (BaMV is a member of the potexvirus group and is one of the most studied viruses in terms of the effects of ABA on its accumulation and resistance. In this review, we summarize how ABA interferes with the accumulation and movement of BaMV and other viruses. We also highlight aspects of ABA that may have an effect on other types of resistance and that require further investigation.

  15. Viral respiratory diseases: vaccines and antivirals.

    Science.gov (United States)

    Lennette, E H

    1981-01-01

    Acute respiratory diseases, most of which are generally attributed to viruses, account for about 6% of all deaths and for about 60% of the deaths associated with all respiratory disease. The huge cost attributable to viral respiratory infections as a result of absenteeism and the disruption of business and the burden of medical care makes control of these diseases an important objective. The viruses that infect the respiratory tract fall taxonomically into five viral families. Although immunoprophylaxis would appear to be the logical approach, the development of suitable vaccines has been confronted with numerous obstacles, including antigenic drift and shift in the influenzaviruses, the large number of antigenically distinct immunotypes among rhinoviruses, the occurrence after immunization of rare cases of a severe form of the disease following subsequent natural infection with respiratory syncytial virus, and the risk of oncogenicity of adenoviruses for man. Considerable expenditure on the development of new antiviral drugs has so far resulted in only three compounds that are at present officially approved and licensed for use in the USA. Efforts to improve the tools available for control should continue and imaginative and inventive approaches are called for. However, creativity and ingenuity must operate within the constraints imposed by economic, political, ethical, and legal considerations.

  16. [Barriers to ART initiation in HIV infected subjects and with treatment indication in Spain. Why don't they start their treatment? Bridgap Study].

    Science.gov (United States)

    Viciana-Fernández, Pompeyo; Falcó, Vicenç; Castaño, Manuel; de los Santos-Gil, Ignacio; Olalla-Sierra, Julián; Hernando, Asunción; Deig, Elisabet; Clotet, Bonaventura; Knobel, Hernando; Podzamczer, Daniel; Pedrol, Pere Domingo

    2015-01-01

    In Spain, HIV treatment guidelines are well known and generally followed. However, in some patients there are no plans to initiate ART despite having treatment indications. The current barriers to ART initiation are presented. A cross-sectional survey including every HIV infected patient in care in 19 hospitals across Spain in 2012, with ≥1 indication to start ART according to 2011 national treatment guidelines, who had not been scheduled for ART initiation. Reasons for deferring treatment were categorized as follows (non-exclusive categories): a) The physician thinks the indication is not absolute and prefers to defer it; b) The patient does not want to start it; c) The physician thinks ART must be started, but there is some limitation to starting it, and d) The patient has undetectable viral load in absence of ART. A total of 256 patients, out of 784 originally planned, were included. The large majority (84%) were male, median age 39 years, 57% MSM, 24% heterosexuals, and 16% IDUs. Median time since HIV diagnosis was 3 years, median CD4 count, 501 cells/mm3, median viral load 4.4 log copies/ml. Main ART indications were: CD4 count ART indication were on it. The most frequent barriers among those who did not receive it were physician-related, suggesting that the relevance of the conditions that indicate ART may need reinforcing. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  17. Osteogenic Treatment Initiating a Tissue-Engineered Cartilage Template Hypertrophic Transition.

    Science.gov (United States)

    Fu, J Y; Lim, S Y; He, P F; Fan, C J; Wang, D A

    2016-10-01

    Hypertrophic chondrocytes play a critical role in endochondral bone formation as well as the progress of osteoarthritis (OA). An in vitro cartilage hypertrophy model can be used as a platform to study complex molecular mechanisms involved in these processes and screen new drugs for OA. To develop an in vitro cartilage hypertrophy model, we treated a tissue-engineered cartilage template, living hyaline cartilaginous graft (LhCG), with osteogenic medium for hypertrophic induction. In addition, endothelial progenitor cells (EPCs) were seeded onto LhCG constructs to mimic vascular invasion. The results showed that osteogenic treatment significantly inhibited the synthesis of endostatin in LhCG constructs and enhanced expression of hypertrophic marker-collagen type X (Col X) and osteogenic markers, as well as calcium deposition in vitro. Upon subcutaneous implantation, osteogenic medium-treated LhCG constructs all stained positive for Col X and showed significant calcium deposition and blood vessel invasion. Col X staining and calcium deposition were most obvious in osteogenic medium-treated only group, while there was no difference between EPC-seeded and non-seeded group. These results demonstrated that osteogenic treatment was of the primary factor to induce hypertrophic transition of LhCG constructs and this model may contribute to the establishment of an in vitro cartilage hypertrophy model.

  18. Treatment of initial parenchymal central nervous system involvement in systemic aggressive B-cell lymphoma.

    Science.gov (United States)

    Nijland, Marcel; Jansen, Anne; Doorduijn, Jeanette K; Enting, Roelien H; Bromberg, Jacoline E C; Kluin-Nelemans, Hanneke C

    2017-09-01

    Central nervous system (CNS) involvement in systemic B-cell non-Hodgkin lymphoma (B-NHL) at diagnosis (sysCNS) is rare. We investigated the outcome of 21 patients with sysCNS, most commonly diffuse large B-cell lymphoma, treated with high dose methotrexate (HD-MTX) and R-CHOP. The median number of cycles of HD-MTX and R-CHOP was 4 (range 1-8) and 6 (range 0-8), respectively. Consolidative whole brain radiotherapy (WBRT) was given to 33% (7/21) patients. With a median follow-up of 44 months the 3-year progression free survival (PFS) and overall survival (OS) were 45% (95%CI 34-56%) and 49% (95%CI 38-60%), respectively. Over 90% of patients had an unfavorable international prognostic index score, reflected by treatment-related mortality of 19% (4/21) and relapse-related mortality of 28% (6/21). The outcome of these patients was, however, unexpectedly good when compared to secondary CNS relapses. Prospective studies are needed to define the optimal treatment for patients with sysCNS, but its rarity might be challenging.

  19. Treatment of intracranial stenoses using the Neuroform stent system: initial experience in five cases

    International Nuclear Information System (INIS)

    Haehnel, Stefan; Hartmann, Marius; Ringleb, Peter

    2006-01-01

    We assessed the technical feasibility of balloon-assisted angioplasty with consecutive stenting using a flexible, self-expanding neurovascular stent for the treatment of intracranial arteriosclerotic vascular stenoses. Five consecutive patients with symptomatic drug-resistant stenoses of the intracranial internal carotid artery (ICA) or the main stem of the middle cerebral artery (MCA) were treated by balloon-assisted angioplasty with consecutive stenting using the Neuroform stent system. Balloon dilatation of the stenoses and consecutive stent placement with complete coverage of the stenoses was feasible in all patients. One patient suffered acute thrombosis distally to the stented vessel segment which was successfully treated by fibrinolysis, and one patient suffered acute subarachnoid and parenchymal hemorrhage probably due to vessel perforation. In the other three patients, no complications occurred during or immediately after angioplasty. All patients were free of further ischemic events up to the 6-month follow-up. Our findings demonstrate that the Neuroform stent system can used successfully for the treatment of intracranial stenoses of the ICA and the main stem of the MCA. Although immediate angiographic results are promising, long-term angiographic and clinical follow-up is essential to demonstrate long-term outcome. (orig.)

  20. Treatment of Complete and Partial Obstruction of the Nasolacrimal System with Polyurethane Stents: Initial Experience

    International Nuclear Information System (INIS)

    Pulido-Duque, Juan M.; Reyes, Ricardo; Carreira, Jose M.; Vega, Francisco; Gorriz, Elias; Pardo, M. Dolores; Perez, Francisco; Maynar, Manuel

    1998-01-01

    Purpose: To present our experience in the treatment of nasolacrimal occlusion by means of polyurethane stents. Methods: Forty polyurethane stents were placed under fluoroscopic guidance in 35 consecutive patients with epiphora due to total or partial obstruction of the nasolacrimal system. The set designed by Song was used in all patients. The procedure was performed by introducing a guidewire through the superior punctum into the canaliculus and advancing it across the obstruction into the inferior meatus of the nasal cavity. After pulling out the guidewire, the stent was advanced in retrograde fashion and released into the sac and the nasolacrimal duct.Results: The technical success rate was 100%. The average time for the procedure was 25 min (range 10-60 min). Immediate complications were: mild pain (n= 5), severe pain (n= 1), minimal epistaxis (n= 7), and moderate epistaxis (n= 1). No major complications occurred. The last clinical control revealed complete resolution of epiphora in 35 eyes and partial resolution in four; one patient did not improve. Conclusion: This technique for treatment of obstruction of the nasolacrimal system is simple and safe, and may obviate the use of more invasive procedures

  1. Readability of Spanish language online information for the initial treatment of burns.

    Science.gov (United States)

    Votta, Kaitlyn; Metivier, Meghan; Romo, Stephanie; Garrigan, Hannah; Drexler, Alana; Nodoushani, Ariana; Sheridan, Robert

    2018-06-01

    This study's aim is to identify the most popular online resources for burn treatment information available in the Spanish language, and to evaluate the readability of this information. The phrase "tratamiento de quemaduras" (burn treatment) was entered into search engines Google and Bing on 9/15/2014 and 9/13/2017. The top 12 Spanish web results on each site were identified and analyzed using Readability Studio Professional Edition v2012.1. The software generated a "mean grade reading level" for each article, or the grade of students that could be expected to understand the article's language. 21 distinct articles were identified at T1 and 17 at T2, with seven overlapping between T1 and T2. The average grade reading level of all the websites ranged from 7.8 to 13.8 at T1 (approximately 8th grade to sophomore year of college) and 7.8 to 12.2 at T2. No websites were within 1 standard deviation of the American Medical Association recommended 6th grade reading level. With readability showing little improvement during the past three years, providers should be aware of the complexity of online literature, and the potential complications this presents to patients. Additionally, burn centers should prioritize generating more accessible information for the Spanish speaking public. Copyright © 2017 Elsevier Ltd and ISBI. All rights reserved.

  2. Nitrosourea-based chemotherapy for low grade gliomas failing initial treatment with temozolomide.

    Science.gov (United States)

    Kaloshi, Gentian; Sierra del Rio, Monica; Ducray, François; Psimaras, Dimitri; Idbaih, Ahmed; Laigle-Donadey, Florence; Taillibert, Sophie; Houillier, Caroline; Dehais, Caroline; Omuro, Antonio; Sanson, Marc; Delattre, Jean-Yves; Hoang-Xuan, Khe

    2010-12-01

    There is a growing evidence of using Temozolomide as upfront therapy for progressive low grade gliomas. No data exist on the efficacy of nitrosoureas as an alternative to radiotherapy in those patients who progress after Temozolomide. We retrospectively reviewed 30 patients with median age of 46 years. Twenty-one patients had pure oligodendrogliomas. Thirteen patients had a non-enhancing tumor at progression after Temozolomide. The chromosomes 1p/19q were co-deleted in 5 cases and retained in 10 cases. Response rate was 10% (3 minor responses achieved in non-enhancing tumors). Tolerance was acceptable (17% grade III and IV myelosupression). Median PFS was 6.5 months. Median OS from start of salvage treatment was 23.4 months. Tumors without contrast enhancement demonstrated a better prognosis than those with contrast enhancement both in term of PFS (P = 0.0003) and OS (P = 0.0006). Chromosomes 1p/19q codeletion was not predictive for objective response to salvage treatment but correlated with a better PFS (P = 0.02). In conclusion, salvage NU chemotherapy provide disappointing results in TMZ-pretreated low grade gliomas (LGG), which should be treated in priority by conventional radiotherapy especially in LGG that display contrast enhancement at progression.

  3. Evaluation of smoking cessation treatment initiated during hospitalization in patients with heart disease or respiratory disease

    Directory of Open Access Journals (Sweden)

    Thaís Garcia

    Full Text Available ABSTRACT Objective: To evaluate the effectiveness of a smoking cessation program, delivered by trained health care professionals, in patients hospitalized for acute respiratory disease (RD or heart disease (HD. Methods: Of a total of 393 patients evaluated, we included 227 (146 and 81 active smokers hospitalized for HD and RD, respectively. All participants received smoking cessation treatment during hospitalization and were followed in a cognitive-behavioral smoking cessation program for six months after hospital discharge. Results: There were significant differences between the HD group and the RD group regarding participation in the cognitive-behavioral program after hospital discharge (13.0% vs. 35.8%; p = 0.003; smoking cessation at the end of follow-up (29% vs. 31%; p < 0.001; and the use of nicotine replacement therapy (3.4% vs. 33.3%; p < 0.001. No differences were found between the HD group and the RD group regarding the use of bupropion (11.0% vs. 12.3%; p = 0.92. Varenicline was used by only 0.7% of the patients in the HD group. Conclusions: In our sample, smoking cessation rates at six months after hospital discharge were higher among the patients with RD than among those with HD, as were treatment adherence rates. The implementation of smoking cessation programs for hospitalized patients with different diseases, delivered by the health care teams that treat these patients, is necessary for greater effectiveness in smoking cessation.

  4. Inhibition of replicon initiation and DNA elongation in Chinese hamster ovary cells by treatment at 45.5 degrees C

    International Nuclear Information System (INIS)

    Wong, R.S.; Dewey, W.C.

    1982-01-01

    Heat treatment of Chinese hamster ovary cells at 45.5 degrees C for 15 minutes resulted in the inhibition of both the replicon initiation and the DNA elongation processes. Analysis of the DNA made after treatment showed that for up to 30 minutes after hyperthermia, there was a significant increase (45-80% above control level) in the amount of labeled DNA less than or equal to 40S in size and having a distinct peak of 20S. Therefore, elongation of 20S molecules into larger molecules was inhibited or slowed down. These small molecules did not accumulate when recovery times were longer than 30 minutes. The DNA made after 120 and 240 minutes postheat incubation was larger than control size and indicated that, although replicon initiation was still inhibited, elongation between replicons into 120S molecules could take place. However, their subsequent elongation into parental-size molecules was inhibited. The same delay in DNA elongation seen in cells examined immediately after treatment was still observed in cells heated and allowed to recover for 30 minutes. Also, after 30 minutes of recovery, heated cells still had more newly synthesized DNA in the single-stranded fraction than did control cells, which indicates that DNA elongation within a replicon is delayed for at least 30 minutes after heating. Furthermore, at 4 hours after heating, the inhibition of elongation of clusters of replicons into parental molecules prevailed

  5. In Vitro Antiviral Activity and Resistance Profile Characterization of the Hepatitis C Virus NS5A Inhibitor Ledipasvir.

    Science.gov (United States)

    Cheng, Guofeng; Tian, Yang; Doehle, Brian; Peng, Betty; Corsa, Amoreena; Lee, Yu-Jen; Gong, Ruoyu; Yu, Mei; Han, Bin; Xu, Simin; Dvory-Sobol, Hadas; Perron, Michel; Xu, Yili; Mo, Hongmei; Pagratis, Nikos; Link, John O; Delaney, William

    2016-01-11

    Ledipasvir (LDV; GS-5885), a component of Harvoni (a fixed-dose combination of LDV with sofosbuvir [SOF]), is approved to treat chronic hepatitis C virus (HCV) infection. Here, we report key preclinical antiviral properties of LDV, including in vitro potency, in vitro resistance profile, and activity in combina