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

The cost of successful antiviral therapy in hepatitis C patients: a comparison of IFN-free versus IFN-based regimens at an individual patient level in Australia

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Lee AS

2017-10-01

Full Text Available Allister Sebastian Lee,1 Mieke L van Driel,2 Darrell HG Crawford3,4 1Faculty of Medicine, 2Primary Care Clinical Unit, Faculty of Medicine, 3School of Clinical Medicine, Faculty of Medicine, University of Queensland, 4Gallipoli Medical Research Foundation, Greenslopes Private Hospital, Brisbane, Australia Background: Chronic hepatitis C remains a major global health burden with serious long-term consequences if left untreated. Recently the treatment standard of care has shifted to new interferon (IFN-free drug regimens, which have been shown to be safe and effective. The aim of our study was to assess and compare medical resource utilization and costs of successfully treating patients with IFN-based and IFN-free therapies in Australia. Methods: We performed a retrospective chart review of 30 HCV-infected patients successfully treated with IFN-based therapy between 2013 and 2015. We also generated a model for a virtual group of 100 genotype 1 (GT1 and 100 genotype 3 (GT3 patients treated with IFN-free therapy derived from national guidelines and clinical trial data. Results: In comparison to virtual patients receiving IFN-free therapy, our IFN-treated patients on average had distinctively more liver clinic visits and blood tests. However, mean total cost per patient was $19,164 and $85,300 (AUD more for GT1 and GT3 patients receiving IFN-free therapy, respectively. This difference was largely accounted for by higher antiviral drug costs. Of our 30 patients treated with IFN, total mean cost per patient during the study period was $33,595. Conclusion: Resource utilization is lower with IFN-free treatment, which reflects the reduced need for patient monitoring and improved side-effect profile of these new drugs. However, total costs are still largely dominated by antiviral drug costs, representing a huge burden on national budgets. Our insight into resource utilization and costs associated with both types of treatment can serve as a reference for

Cost analysis of inappropriate treatments for suspected dermatomycoses

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Emanuela Fiammenghi

2015-06-01

Full Text Available Superficial mycoses are estimated to affect more than 20-25% of the world’s population with a consistent increase over the years. Most patients referred to our clinic for suspected dermatomycoses have already been treated with pharmacotherapy, without a previous mycological examination and many show changes in the clinical manifestations. Indeed, some medications, such as steroids, antiviral, antibiotics and antihistamines are not able to erase a fungal infection, but also they can cause atypical clinical manifestations. The consequences of inappropriate treatment include delayed diagnosis, prolonged healing time, and additional costs. The aims of this study were (1 to evaluate the incidence of increased costs attributable to inappropriate therapy sustained by the National Health Service and patients and (2 to highlight the importance of mycological evaluation before starting treatment, in order to improve diagnostic accuracy. An observational retrospective and prospective study was performed from September 2013 to February 2014, in 765 patients referred to our center (University Hospital “ Federico II” in Naples, Italy, for suspected mycological infection. The following treatments (alone or in combination were defined as inappropriate: (1 cortisone in a patient with at least one positive site; (2 antifungals in (a patients with all negative sites or (b ineffective antifungal treatment (in terms of drug chosen, dose or duration in those with all positive sites; or (3 antibiotics; (4 antivirals or (5 antihistamines, in patients with ≥ 1 positive site. Five hundred and fifty patients were using medications before the assessment visit. The total amount of avoidable costs related to inappropriate previous treatments was € 121,417, representing 74% of the total treatment costs. 253/550 patients received drugs also after the visit. For these patients, the cost of treatment prescribed after mycological testing was € 42,952, with a decrease

Antiviral agents for infectious mononucleosis (glandular fever).

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

2016-12-08

outcome did not find any significant difference between treatment and control groups.There was a mean reduction in 'duration of lymphadenopathy' of nine days (95% CI -11.75 to -6.14, two studies, 61 participants) in favour of the treatment group.In terms of viral shedding, the overall effect from six studies was that viral shedding was suppressed while on antiviral treatment, but this effect was not sustained when treatment stopped.For all other outcomes there was no statistically significant difference between antiviral treatment and control groups. The effectiveness of antiviral agents (acyclovir, valomaciclovir and valacyclovir) in acute IM is uncertain. The quality of the evidence is very low. The majority of included studies were at unclear or high risk of bias and so questions remain about the effectiveness of this intervention. Although two of the 12 outcomes have results that favour treatment over control, the quality of the evidence of these results is very low and may not be clinically meaningful. Alongside the lack of evidence of effectiveness, decision makers need to consider the potential adverse events and possible associated costs, and antiviral resistance. Further research in this area is warranted.

Antiviral therapy in chronic hepatitis C (G1 in Russia: cost and effectiveness

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A. V. Rudakova

2015-01-01

Full Text Available Genotype 1 HCV treatment in Russia assume as bitherapy (pegylated interferon – PG plus ribavirin – RBV as three therapy based on HCV protease inhibitor such as telaprevir (TLV, boceprevir (BCV or simeprevir (SMV plus PG/RBV. Medical technologies characterize neither clinical effectiveness, safety profile nor cost-effectiveness so it’s crucial to assess different costs related antiviral regimens. Three therapy costs for naïve patients including TLV, BCV, SMV are higher bitherapy 2,6; 2,5; 3,1 times accordingly. Similar TLV and BCV effectiveness for naïve patients defines TLV or BCV as the preferable 1-st line regimen, depending on regional features of pricing. SMV and TLV efficacy is similar among naïve patients and ralapsers but SMV is affordable for partially responders and non-responders after previous bitherapy. SMV cost is 1,4 times higher vs TLV but SMV has improved tolerability, less drug-drug interactions and shorter course. Insufficient bitherapy effectiveness for G1 HCV (SVR 24 – 39%-55% is required repeated course of three therapy for half of patient population. The first line regimen based on innovation will improve clinical outcomes for more patients and provide cost saving vs previous bitherapy based on PG/RBV. 

The cost effectiveness of pandemic influenza interventions: a pandemic severity based analysis.

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George J Milne

Full Text Available BACKGROUND: The impact of a newly emerged influenza pandemic will depend on its transmissibility and severity. Understanding how these pandemic features impact on the effectiveness and cost effectiveness of alternative intervention strategies is important for pandemic planning. METHODS: A cost effectiveness analysis of a comprehensive range of social distancing and antiviral drug strategies intended to mitigate a future pandemic was conducted using a simulation model of a community of ∼30,000 in Australia. Six pandemic severity categories were defined based on case fatality ratio (CFR, using data from the 2009/2010 pandemic to relate hospitalisation rates to CFR. RESULTS: Intervention strategies combining school closure with antiviral treatment and prophylaxis are the most cost effective strategies in terms of cost per life year saved (LYS for all severity categories. The cost component in the cost per LYS ratio varies depending on pandemic severity: for a severe pandemic (CFR of 2.5% the cost is ∼$9 k per LYS; for a low severity pandemic (CFR of 0.1% this strategy costs ∼$58 k per LYS; for a pandemic with very low severity similar to the 2009 pandemic (CFR of 0.03% the cost is ∼$155 per LYS. With high severity pandemics (CFR >0.75% the most effective attack rate reduction strategies are also the most cost effective. During low severity pandemics costs are dominated by productivity losses due to illness and social distancing interventions, while for high severity pandemics costs are dominated by hospitalisation costs and productivity losses due to death. CONCLUSIONS: The most cost effective strategies for mitigating an influenza pandemic involve combining sustained social distancing with the use of antiviral agents. For low severity pandemics the most cost effective strategies involve antiviral treatment, prophylaxis and short durations of school closure; while these are cost effective they are less effective than other strategies in

The Cost Effectiveness of Pandemic Influenza Interventions: A Pandemic Severity Based Analysis

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Milne, George J.; Halder, Nilimesh; Kelso, Joel K.

2013-01-01

Background The impact of a newly emerged influenza pandemic will depend on its transmissibility and severity. Understanding how these pandemic features impact on the effectiveness and cost effectiveness of alternative intervention strategies is important for pandemic planning. Methods A cost effectiveness analysis of a comprehensive range of social distancing and antiviral drug strategies intended to mitigate a future pandemic was conducted using a simulation model of a community of ∼30,000 in Australia. Six pandemic severity categories were defined based on case fatality ratio (CFR), using data from the 2009/2010 pandemic to relate hospitalisation rates to CFR. Results Intervention strategies combining school closure with antiviral treatment and prophylaxis are the most cost effective strategies in terms of cost per life year saved (LYS) for all severity categories. The cost component in the cost per LYS ratio varies depending on pandemic severity: for a severe pandemic (CFR of 2.5%) the cost is ∼$9 k per LYS; for a low severity pandemic (CFR of 0.1%) this strategy costs ∼$58 k per LYS; for a pandemic with very low severity similar to the 2009 pandemic (CFR of 0.03%) the cost is ∼$155 per LYS. With high severity pandemics (CFR >0.75%) the most effective attack rate reduction strategies are also the most cost effective. During low severity pandemics costs are dominated by productivity losses due to illness and social distancing interventions, while for high severity pandemics costs are dominated by hospitalisation costs and productivity losses due to death. Conclusions The most cost effective strategies for mitigating an influenza pandemic involve combining sustained social distancing with the use of antiviral agents. For low severity pandemics the most cost effective strategies involve antiviral treatment, prophylaxis and short durations of school closure; while these are cost effective they are less effective than other strategies in reducing the

Cost-effectiveness of treating chronic hepatitis C virus with direct-acting antivirals in people who inject drugs in Australia.

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Scott, Nick; Iser, David M; Thompson, Alexander J; Doyle, Joseph S; Hellard, Margaret E

2016-04-01

Reducing the burden of hepatitis C virus (HCV) related liver disease will require treating people who inject drugs (PWID), the group at most risk of infection and transmission. We determine the cost-effectiveness of treating PWID with interferon-free direct-acting antiviral therapy in Australia. Using a deterministic model of HCV treatment and liver disease progression, including a fixed rate of re-infection, the expected healthcare costs and quality-adjusted life years (QALYs) of a cohort of newly HCV-infected PWID were calculated for: no treatment; treatment after initial infection ("early-treatment"); and treatment prior to developing compensated cirrhosis ("late-treatment"). Incremental cost-effectiveness ratios (ICERs) were used to compare scenarios. Late-treatment was cost-effective compared to no treatment, with a discounted average gain of 2.98 (95%confidence interval 2.88-5.22) QALYs per person for an additional cost of $15,132 ($11,246-18,922), giving an ICER of $5078 ($2847-5295) per QALY gained. Compared to late-treatment, early-treatment gained a further discounted average of 2.27 (0.58-4.80) QALYs per person for $38,794 ($34,789-41,367), giving an ICER of $17,090 ($2847-63,282), which was cost-effective in approximately 90% of Monte-Carlo uncertainty simulations. For every 100 newly HCV-infected PWID, there were an estimated 40 (39-56) eventual liver-related deaths without treatment, compared to 7 (6-11) and 8 (7-13) with early-treatment and late-treatment available respectively. Treating HCV-infected PWID with new therapies is cost-effective and could prevent a significant number of liver-related deaths. Although late-treatment was the most cost-effective option, the cost per QALY gained for early-treatment compared to late-treatment is likely to be below unofficial Australian willingness to pay thresholds. © 2015 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Exploiting Genetic Interference for Antiviral Therapy.

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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.

Studies on Antiviral and Immuno-Regulation Activity of Low Molecular Weight Fucoidan from Laminaria japonica

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Sun, Taohua; Zhang, Xinhui; Miao, Ying; Zhou, Yang; Shi, Jie; Yan, Meixing; Chen, Anjin

2018-06-01

The antiviral activity in vitro and in vivo and the effect of the immune system of two fucoidan fractions with low molecular weight and different sulfate content from Laminaria japonica (LMW fucoidans) were investigated in order to examine the possible mechanism. In vitro, I-type influenza virus, adenovirus and Parainfluenza virus I were used to infect Hep-2, Hela and MDCK cells, respectively. And 50% tissue culture infective dose was calculated to detect the antiviral activity of two LMW fucoidans. The results indicated that compared with the control group, 2 kinds of LMW fucoidans had remarkable antiviral activity in vitro in middle and high doses, while at low doses, the antiviral activity of 2 kinds of LMW fucoidans was not statistically different from that in the blank control group. And there was no statistically difference between two LMW fucoidans in antiviral activity. In vivo, LMW fucoidans could prolong the survival time of virus-infected mice, and could improve the lung index of virus-infected mice significantly, which have statistical differences with the control group significantly ( p 0.05). In this study, it was shown that both of two LMW fucoidans (LF1, LF2) could increase the thymus index, spleen index, phagocytic index, phagocytosis coefficient and half hemolysin value in middle and high doses, which suggested that LMW fucoidans could play an antiviral role by improving the quality of immune organs, improving immune cell phagocytosis and humoral immunity.

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

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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

High antiviral effects of hibiscus tea extract on the H5 subtypes of low and highly pathogenic avian influenza viruses.

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Baatartsogt, Tugsbaatar; Bui, Vuong N; Trinh, Dai Q; Yamaguchi, Emi; Gronsang, Dulyatad; Thampaisarn, Rapeewan; Ogawa, Haruko; Imai, Kunitoshi

2016-10-01

Viral neuraminidase inhibitors are widely used as synthetic anti-influenza drugs for the prevention and treatment of influenza. However, drug-resistant influenza A virus variants, including H5N1 highly pathogenic avian influenza viruses (HPAIVs), have been reported. Therefore, the discovery of novel and effective antiviral agents is warranted. We screened the antiviral effects of 11 herbal tea extracts (hibiscus, black tea, tencha, rosehip tea, burdock tea, green tea, jasmine tea, ginger tea, lavender tea, rose tea and oak tea) against the H5N1 HPAIV in vitro. Among the tested extracts, only the hibiscus extract and its fractionated extract (frHibis) highly and rapidly reduced the titers of all H5 HPAIVs and low pathogenic AIVs (LPAIVs) used in the pre-treatment tests of Madin-Darby canine kidney (MDCK) cells that were inoculated with a mixture of the virus and the extract. Immunogold electron microscopy showed that anti-H5 monoclonal antibodies could not bind to the deformed H5 virus particles pretreated with frHibis. In post-treatment tests of MDCK cells cultured in the presence of frHibis after infection with H5N1 HPAIV, the frHibis inhibited viral replication and the expression of viral antigens and genes. Among the plants tested, hibiscus showed the most prominent antiviral effects against both H5 HPAIV and LPAIV.

Cervical Precancer Treatment in Low- and Middle-Income Countries: A Technology Overview

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Mauricio Maza

2017-08-01

Full Text Available Cervical cancer is the fourth leading cause of cancer-related death in women worldwide, with 90% of cases occurring in low- and middle-income countries (LMICs. There has been a global effort to increase access to affordable screening in these settings; however, a corresponding increase in availability of effective and inexpensive treatment modalities for ablating or excising precancerous lesions is also needed to decrease mortality. This article reviews the current landscape of available and developing technologies for treatment of cervical precancer in LMICs. At present, the standard treatment of most precancerous lesions in LMICs is gas-based cryotherapy. This low-cost, effective technology is an expedient treatment in many areas; however, obtaining and transporting gas is often difficult, and unwieldy gas tanks are not conducive to mobile health campaigns. There are several promising ablative technologies in development that are gasless or require less gas than conventional cryotherapy. Although further evaluation of the efficacy and cost-effectiveness is needed, several of these technologies are safe and can now be implemented in LMICs. Nonsurgical therapies, such as therapeutic vaccines, antivirals, and topical applications, are also promising, but most remain in early-stage trials. The establishment of evidence-based standardized protocols for available treatments and the development and introduction of novel technologies are necessary steps in overcoming barriers to treatment in LMICs and decreasing the global burden of cervical cancer. Guidance from WHO on emerging treatment technologies is also needed.

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

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…

Hepatitis C Virus and Antiviral Drug Resistance.

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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.

Cost-effectiveness and budget impact of hepatitis C virus treatment with sofosbuvir and ledipasvir in the United States.

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Chhatwal, Jagpreet; Kanwal, Fasiha; Roberts, Mark S; Dunn, Michael A

2015-03-17

Sofosbuvir and ledipasvir, which have recently been approved for treatment of chronic hepatitis C virus (HCV) infection, are more efficacious and safer than the old standard of care (oSOC) but are substantially more expensive. Whether and in which patients their improved efficacy justifies their increased cost is unclear. To evaluate the cost-effectiveness and budget impact of sofosbuvir and ledipasvir. Microsimulation model of the natural history of HCV infection. Published literature. Treatment-naive and treatment-experienced HCV population defined on the basis of HCV genotype, age, and fibrosis distribution in the United States. Lifetime. Third-party payer. Simulation of sofosbuvir-ledipasvir compared with the oSOC (interferon-based therapies). Quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and 5-year spending on antiviral drugs. Sofosbuvir-based therapies added 0.56 QALY relative to the oSOC at an ICER of $55 400 per additional QALY. The ICERs ranged from $9700 to $284 300 per QALY depending on the patient's status with respect to treatment history, HCV genotype, and presence of cirrhosis. At a willingness-to-pay threshold of $100 000 per QALY, sofosbuvir-based therapies were cost-effective in 83% of treatment-naive and 81% of treatment-experienced patients. Compared with the oSOC, treating eligible HCV-infected persons in the United States with the new drugs would cost an additional $65 billion in the next 5 years, whereas the resulting cost offsets would be $16 billion. Results were sensitive to drug price, drug efficacy, and quality of life after successful treatment. Data on real-world effectiveness of new antivirals are lacking. Treatment of HCV is cost-effective in most patients, but additional resources and value-based patient prioritization are needed to manage patients with HCV. National Institutes of Health.

Smallpox Antiviral Drug

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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

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

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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.

Decision Making with Regard to Antiviral Intervention during an Influenza Pandemic

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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

Antiviral resistance and the control of pandemic influenza.

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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

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.

Operating cost guidelines for benchmarking DOE thermal treatment systems for low-level mixed waste

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Salmon, R.; Loghry, S.L.; Hermes, W.H.

1994-11-01

This report presents guidelines for estimating operating costs for use in benchmarking US Department of Energy (DOE) low-level mixed waste thermal treatment systems. The guidelines are based on operating cost experience at the DOE Toxic Substances Control Act (TSCA) mixed waste incinerator at the K-25 Site at Oak Ridge. In presenting these guidelines, it should be made clear at the outset that it is not the intention of this report to present operating cost estimates for new technologies, but only guidelines for estimating such costs

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

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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.

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...

Efficacy of Antiviral Drugs against Feline Immunodeficiency Virus

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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.

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.

Strategies for antiviral stockpiling for future influenza pandemics: a global epidemic-economic perspective.

Science.gov (United States)

Carrasco, Luis R; Lee, Vernon J; Chen, Mark I; Matchar, David B; Thompson, James P; Cook, Alex R

2011-09-07

Influenza pandemics present a global threat owing to their potential mortality and substantial economic impacts. Stockpiling antiviral drugs to manage a pandemic is an effective strategy to offset their negative impacts; however, little is known about the long-term optimal size of the stockpile under uncertainty and the characteristics of different countries. Using an epidemic-economic model we studied the effect on total mortality and costs of antiviral stockpile sizes for Brazil, China, Guatemala, India, Indonesia, New Zealand, Singapore, the UK, the USA and Zimbabwe. In the model, antivirals stockpiling considerably reduced mortality. There was greater potential avoidance of expected costs in the higher resourced countries (e.g. from $55 billion to $27 billion over a 30 year time horizon for the USA) and large avoidance of fatalities in those less resourced (e.g. from 11.4 to 2.3 million in Indonesia). Under perfect allocation, higher resourced countries should aim to store antiviral stockpiles able to cover at least 15 per cent of their population, rising to 25 per cent with 30 per cent misallocation, to minimize fatalities and economic costs. Stockpiling is estimated not to be cost-effective for two-thirds of the world's population under current antivirals pricing. Lower prices and international cooperation are necessary to make the life-saving potential of antivirals cost-effective in resource-limited countries.

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.

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

Science.gov (United States)

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.

New antivirals for the treatment of chronic hepatitis B.

Science.gov (United States)

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.

Low-cost in vitro fertilization: current insights

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Teoh PJ

2014-08-01

Full Text Available Pek Joo Teoh, Abha MaheshwariAberdeen Fertility Centre, Aberdeen Maternity Hospital, University of Aberdeen, Aberdeen, UKAbstract: Despite the development of in vitro fertilization (IVF more than 30 years ago, the cost of treatment remains high. Furthermore, over the years, more sophisticated technologies and expensive medications have been introduced, making IVF increasingly inaccessible despite the increasing need. Globally, the option to undergo IVF is only available to a privileged few. In recent years, there has been growing interest in exploring strategies to reduce the cost of IVF treatment, which would allow the service to be provided in low-resource settings. In this review, we explore the various ways in which the cost of this treatment can be reduced.Keywords: IVF, low-cost, accessible, developing world

Cost-benefit analysis of targeted hearing directed early testing for congenital cytomegalovirus infection.

Science.gov (United States)

Bergevin, Anna; Zick, Cathleen D; McVicar, Stephanie Browning; Park, Albert H

2015-12-01

In this study, we estimate an ex ante cost-benefit analysis of a Utah law directed at improving early cytomegalovirus (CMV) detection. We use a differential cost of treatment analysis for publicly insured CMV-infected infants detected by a statewide hearing-directed CMV screening program. Utah government administrative data and multi-hospital accounting data are used to estimate and compare costs and benefits for the Utah infant population. If antiviral treatment succeeds in mitigating hearing loss for one infant per year, the public savings will offset the public costs incurred by screening and treatment. If antiviral treatment is not successful, the program represents a net cost, but may still have non-monetary benefits such as accelerated achievement of diagnostic milestones. The CMV education and treatment program costs are modest and show potential for significant cost savings. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Costs of mixed low-level waste stabilization options

International Nuclear Information System (INIS)

Schwinkendorf, W.E.; Cooley, C.R.

1998-01-01

Selection of final waste forms to be used for disposal of DOE's mixed low-level waste (MLLW) depends on the waste form characteristics and total life cycle cost. In this paper the various cost factors associated with production and disposal of the final waste form are discussed and combined to develop life-cycle costs associated with several waste stabilization options. Cost factors used in this paper are based on a series of treatment system studies in which cost and mass balance analyses were performed for several mixed low-level waste treatment systems and various waste stabilization methods including vitrification, grout, phosphate bonded ceramic and polymer. Major cost elements include waste form production, final waste form volume, unit disposal cost, and system availability. Production of grout costs less than the production of a vitrified waste form if each treatment process has equal operating time (availability) each year; however, because of the lower volume of a high temperature slag, certification and handling costs and disposal costs of the final waste form are less. Both the total treatment cost and life cycle costs are higher for a system producing grout than for a system producing high temperature slag, assuming equal system availability. The treatment costs decrease with increasing availability regardless of the waste form produced. If the availability of a system producing grout is sufficiently greater than a system producing slag, then the cost of treatment for the grout system will be less than the cost for the slag system, and the life cycle cost (including disposal) may be less depending on the unit disposal cost. Treatment and disposal costs will determine the return on investment in improved system availability

Provider costs for prevention and treatment of cardiovascular and related conditions in low- and middle-income countries: a systematic review.

Science.gov (United States)

Brouwer, Elizabeth D; Watkins, David; Olson, Zachary; Goett, Jane; Nugent, Rachel; Levin, Carol

2015-11-26

The burden of cardiovascular disease (CVD) and CVD risk conditions is rapidly increasing in low- and middle-income countries, where health systems are generally ill-equipped to manage chronic disease. Policy makers need an understanding of the magnitude and drivers of the costs of cardiovascular disease related conditions to make decisions on how to allocate limited health resources. We undertook a systematic review of the published literature on provider-incurred costs of treatment for cardiovascular diseases and risk conditions in low- and middle-income countries. Total costs of treatment were inflated to 2012 US dollars for comparability across geographic settings and time periods. This systematic review identified 60 articles and 143 unit costs for the following conditions: ischemic heart disease, non-ischemic heart diseases, stroke, heart failure, hypertension, diabetes, and chronic kidney disease. Cost data were most readily available in middle-income countries, especially China, India, Brazil, and South Africa. The most common conditions with cost studies were acute ischemic heart disease, type 2 diabetes mellitus, stroke, and hypertension. Emerging economies are currently providing a base of cost evidence for NCD treatment that may prove useful to policy-makers in low-income countries. Initial steps to publicly finance disease interventions should take account of costs. The gaps and limitations in the current literature include a lack of standardized reporting as well as sparse evidence from low-income countries.

Cost-effective strategies for mitigating a future influenza pandemic with H1N1 2009 characteristics.

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Nilimesh Halder

Full Text Available BACKGROUND: We performed an analysis of the cost-effectiveness of pandemic intervention strategies using a detailed, individual-based simulation model of a community in Australia together with health outcome data of infected individuals gathered during 2009-2010. The aim was to examine the cost-effectiveness of a range of interventions to determine the most cost-effective strategies suitable for a future pandemic with H1N1 2009 characteristics. METHODOLOGY/PRINCIPAL FINDINGS: Using transmissibility, age-stratified attack rates and health outcomes determined from H1N1 2009 data, we determined that the most cost-effective strategies involved treatment and household prophylaxis using antiviral drugs combined with limited duration school closure, with costs ranging from $632 to $777 per case prevented. When school closure was used as a sole intervention we found the use of limited duration school closure to be significantly more cost-effective compared to continuous school closure, a result with applicability to countries with limited access to antiviral drugs. Other social distancing strategies, such as reduced workplace attendance, were found to be costly due to productivity losses. CONCLUSION: The mild severity (low hospitalisation and case fatality rates and low transmissibility of H1N1 2009 meant that health treatment costs were dominated by the higher productivity losses arising from workplace absence due to illness and childcare requirements following school closure. Further analysis for higher transmissibility but with the same, mild severity had no effect on the overall findings.

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

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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

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.

Hepatitis C Treatment Regimens Are Cost-Effective: But Compared With What?

Science.gov (United States)

Mattingly, T Joseph; Slejko, Julia F; Mullins, C Daniel

2017-11-01

Numerous economic models have been published evaluating treatment of chronic hepatitis C virus (HCV) infection, but none provide a comprehensive comparison among new antiviral agents. Evaluate the cost-effectiveness of all recommended therapies for treatment of genotypes 1 and 4 chronic HCV. Using data from clinical trials, observational analyses, and drug pricing databases, Markov decision models were developed for HCV genotypes 1 and 4 to compare all recommended drugs from the perspective of the third-party payer over a 5-, 10-, and 50-year time horizon. A probabilistic sensitivity analysis (PSA) was conducted by assigning distributions for clinical cure, age entering the model, costs for each health state, and quality-adjusted life years (QALYs) for each health state in a Monte Carlo simulation of 10 000 repetitions of the model. In the lifetime model for genotype 1, effects ranged from 18.08 to 18.40 QALYs and total costs ranged from $88 107 to $184 636. The lifetime model of genotype 4 treatments had a range of effects from 18.23 to 18.43 QALYs and total costs ranging from $87 063 to $127 637. Grazoprevir/elbasvir was the optimal strategy followed by velpatasvir/sofosbuvir as the second-best strategy in most simulations for both genotypes 1 and 4, with drug costs and efficacy of grazoprevir/elbasvir as the primary model drivers. Grazoprevir/elbasvir was cost-effective compared with all strategies for genotypes 1 and 4. Effects for all strategies were similar with cost of drug in the initial year driving the results.

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.

Research progress in antiviral therapy for chronic hepatitis C

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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.

Minimum target prices for production of direct-acting antivirals and associated diagnostics to combat hepatitis C virus.

Science.gov (United States)

van de Ven, Nikolien; Fortunak, Joe; Simmons, Bryony; Ford, Nathan; Cooke, Graham S; Khoo, Saye; Hill, Andrew

2015-04-01

Combinations of direct-acting antivirals (DAAs) can cure hepatitis C virus (HCV) in the majority of treatment-naïve patients. Mass treatment programs to cure HCV in developing countries are only feasible if the costs of treatment and laboratory diagnostics are very low. This analysis aimed to estimate minimum costs of DAA treatment and associated diagnostic monitoring. Clinical trials of HCV DAAs were reviewed to identify combinations with consistently high rates of sustained virological response across hepatitis C genotypes. For each DAA, molecular structures, doses, treatment duration, and components of retrosynthesis were used to estimate costs of large-scale, generic production. Manufacturing costs per gram of DAA were based upon treating at least 5 million patients per year and a 40% margin for formulation. Costs of diagnostic support were estimated based on published minimum prices of genotyping, HCV antigen tests plus full blood count/clinical chemistry tests. Predicted minimum costs for 12-week courses of combination DAAs with the most consistent efficacy results were: US$122 per person for sofosbuvir+daclatasvir; US$152 for sofosbuvir+ribavirin; US$192 for sofosbuvir+ledipasvir; and US$115 for MK-8742+MK-5172. Diagnostic testing costs were estimated at US$90 for genotyping US$34 for two HCV antigen tests and US$22 for two full blood count/clinical chemistry tests. Minimum costs of treatment and diagnostics to cure hepatitis C virus infection were estimated at US$171-360 per person without genotyping or US$261-450 per person with genotyping. These cost estimates assume that existing large-scale treatment programs can be established. © 2014 The Authors. Hepatology published by Wiley Periodicals, Inc., on behalf of the American Association for the Study of Liver Diseases.

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.

Cost-Effectiveness of Hepatitis C Treatment for People Who Inject Drugs and the Impact of the Type of Epidemic; Extrapolating from Amsterdam, the Netherlands

NARCIS (Netherlands)

van Santen, Daniëla K.; de Vos, Anneke S.; Matser, Amy; Willemse, Sophie B.; Lindenburg, Karen; Kretzschmar, Mirjam E. E.; Prins, Maria; de Wit, G. Ardine

2016-01-01

People who inject drugs (PWID) are disproportionally affected by the hepatitis C virus (HCV) infection. The efficacy of HCV treatment has significantly improved in recent years with the introduction of direct-acting antivirals (DAAs). However, DAAs are more costly than pegylated-interferon and

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 ...

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

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.

A prospective randomized study of the efficacy and cost-effectiveness of high and low dose regimens of I-131 treatment in hyperthyroidism.

Science.gov (United States)

Pusuwan, Pawana; Tuntawiroon, Malulee; Sritongkul, Nopamol; Chaudakshetrin, Pachee; Nopmaneejumruslers, Cherdchai; Komoltri, Chulalak; Thepamongkhol, Kullathorn; Khiewvan, Benjapa; Tuchinda, Pongpija; Sriussadaporn, Sutin

2011-03-01

To compare the efficacy and cost-effectiveness of high and low dose regimens of I-131 treatment in patients with hyperthyroidism. One hundred fifty patients with proven hyperthyroidism were randomly allocated into the high (74 patients) and low (76 patients) dose regimen of I-131 treatment. Four patients of the high dose group and one patient of the low dose group were excluded because of lost follow-up. A gland-specific dosage was calculated on the estimated weight of thyroid gland and 24-hour I-131 uptake. The high and low I-131 dose regimens were 150 microCi/gm and 100 microCi/gm, respectively. The first mean radioiodine activity administered to the high and low dose group was 10.2 and 8 mCi, respectively. Repeated treatment was given to 25 patients of the high dose group and 40 patients of the low dose group. Clinical outcome and calculated costs for outpatient attendances, and laboratory tests together with initial and subsequent treatments were evaluated for one year after I-131 treatment. Elimination of hyperthyroidism that resulted in either euthyroidism or hypothyroidism was classified as therapeutic success. The cost effectiveness was also compared. At 6 months after treatment, 45 (64.3%) patients receiving high dose and 59 (78.7%) patients receiving low dose were hyperthyroidism. Clinical outcome at one year showed persistence of hyperthyroidism in 21 (30%) patients of the high dose regimen and 36 (48%) patients of the low dose regimen. At one year post treatment, it was demonstrated that the high dose regimen could eliminate hyperthyroidism in a significantly shorter time than the low dose regimen, i.e., 259.6 days and 305.5 days, respectively, p = 0.008). For the persistent hyperthyroid patients, the average total cost of treatment in the low dose group was significantly higher than that of the high dose group, i.e., 13,422.78 baht and 10,942.79 baht, respectively; p = 0.050). A high dose regimen of radioactive iodine treatment is more effective than

Low-cost in vitro fertilization: current insights

Science.gov (United States)

Teoh, Pek Joo; Maheshwari, Abha

2014-01-01

Despite the development of in vitro fertilization (IVF) more than 30 years ago, the cost of treatment remains high. Furthermore, over the years, more sophisticated technologies and expensive medications have been introduced, making IVF increasingly inaccessible despite the increasing need. Globally, the option to undergo IVF is only available to a privileged few. In recent years, there has been growing interest in exploring strategies to reduce the cost of IVF treatment, which would allow the service to be provided in low-resource settings. In this review, we explore the various ways in which the cost of this treatment can be reduced. PMID:25187741

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

Science.gov (United States)

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.

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

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.

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.

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

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.

Topoisomerase 1 Inhibition Promotes Cyclic GMP-AMP Synthase-Dependent Antiviral Responses.

Science.gov (United States)

Pépin, Geneviève; Nejad, Charlotte; Ferrand, Jonathan; Thomas, Belinda J; Stunden, H James; Sanij, Elaine; Foo, Chwan-Hong; Stewart, Cameron R; Cain, Jason E; Bardin, Philip G; Williams, Bryan R G; Gantier, Michael P

2017-10-03

Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1) by low-dose camptothecin (CPT) can suppress transcriptional induction of antiviral and inflammatory genes and protect animals from excessive and damaging inflammatory responses. We describe the unexpected finding that minor DNA damage from topoisomerase 1 inhibition with low-dose CPT can trigger a strong antiviral immune response through cyclic GMP-AMP synthase (cGAS) detection of cytoplasmic DNA. This argues against CPT having only anti-inflammatory activity. Furthermore, expression of the simian virus 40 (SV40) large T antigen was paramount to the proinflammatory antiviral activity of CPT, as it potentiated cytoplasmic DNA leakage and subsequent cGAS recruitment in human and mouse cell lines. This work suggests that the capacity of Top1 inhibitors to blunt inflammatory responses can be counteracted by viral oncogenes and that this should be taken into account for their therapeutic development. IMPORTANCE Recent studies suggest that low-dose DNA-damaging compounds traditionally used in cancer therapy can have opposite effects on antiviral responses, either suppressing (with the example of CPT) or potentiating (with the example of doxorubicin) them. Our work demonstrates that the minor DNA damage promoted by low-dose CPT can also trigger strong antiviral responses, dependent on the presence of viral oncogenes. Taken together, these results call for caution in the therapeutic use of low-dose chemotherapy agents to modulate antiviral responses in humans. Copyright © 2017 Pépin et al.

Peg-interferon plus nucleotide analogue treatment versus no treatment in patients with chronic hepatitis B with a low viral load: a randomised controlled, open-label trial

NARCIS (Netherlands)

de Niet, Annikki; Jansen, Louis; Stelma, Femke; Willemse, Sophie B.; Kuiken, Sjoerd D.; Weijer, Sebastiaan; van Nieuwkerk, Carin M. J.; Zaaijer, Hans L.; Molenkamp, Richard; Takkenberg, R. Bart; Koot, Maarten; Verheij, Joanne; Beuers, Ulrich; Reesink, Hendrik W.

2017-01-01

Antiviral treatment is currently not recommended for patients with chronic hepatitis B with a low viral load. However, they might benefit from acquiring a functional cure (hepatitis B surface antigen [HBsAg] loss with or without formation of antibodies against hepatitis B surface antigen

Cost-effectiveness analysis of entecavir versus lamivudine in the first-line treatment of Australian patients with chronic hepatitis B.

Science.gov (United States)

Arnold, Elizabeth; Yuan, Yong; Iloeje, Uchenna; Cook, Greg

2008-01-01

Chronic hepatitis B (CHB) virus infection is a major global healthcare problem. The recent introduction of entecavir in Australia for the treatment of CHB patients in the naive treatment setting has triggered significant optimism with regards to improved clinical outcomes for CHB patients. To estimate, from an Australian healthcare perspective, the cost effectiveness of entecavir 0.5 mg/day versus lamivudine 100 mg/day in the treatment of CHB patients naive to nucleos(t)ide therapy. A cost-utility analysis to project the clinical and economic outcomes associated with CHB disease and treatment was conducted by developing two decision-tree models specific to hepatitis B e antigen-positive (HBeAg+ve) and HBeAg-ve CHB patient subsets. This analysis was constructed using the Australian payer perspective of direct costs and outcomes, with indirect medical costs and lost productivity not being included. The study population comprised a hypothetical cohort of 1000 antiviral treatment-naive CHB patients who received either entecavir 0.5 mg/day or lamivudine 100 mg/day at model entry. The population of patients used in this analysis was representative of those patients likely to receive initial antiviral therapy in clinical practice in Australia. The long-term cost effectiveness of entecavir compared with lamivudine in the first-line treatment of CHB patients was expressed as an incremental cost per life-year gained (LYG) or QALY gained. Results revealed that the availability of entecavir 0.5 mg/day as part of the Australian hepatologist's treatment armamentarium should result in significantly lower future rates of compensated cirrhosis (CC), decompensated cirrhosis (DC), and hepatocellular carcinoma (HCC) events (i.e. 54 fewer cases of CC, seven fewer cases of DC, and 20 fewer cases of HCC over the model's timeframe for HBeAg+ve CHB patients, and 69 fewer cases of CC, eight fewer cases of DC and 25 fewer cases of HCC over the model's timeframe for HBeAg-ve CHB patients

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

Science.gov (United States)

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.

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...

[Cost effectiveness in treatment of acute myeloid leukemia].

Science.gov (United States)

Nordmann, P; Schaffner, A; Dazzi, H

2000-12-23

Although the rise in health costs is a widely debated issue, in Switzerland it was until recently taken for granted that patients are given the best available treatment regardless of cost. An example of a disease requiring costly treatment is acute myelogenous leukaemia (AML). To relate cost to benefit we calculated expenditure per life years gained. To assess costs we determined the real cost of treatment up to total remission, followed by consolidation or withdrawal of treatment or death. For survival time exceeding the 2-year observation period we used data from recent literature. The average cost of treatment ranges up to 107,592 Swiss francs (CHF). In 1997 we treated 23 leukaemia patients at Zurich University Hospital and gained a total of 210 life years. This represents an average cost of CHF 11,741 per life year gained. Chief cost items were therapy and personnel costs for nursing staff, followed by hotel business and personnel costs for doctors and diagnosis. Our results for AML treatment are far removed from the $61,500 ranging up to $166,000 discussed in the literature as the "critical" QALY (quality adjusted life years) value. This is the first time the actual costs of AML therapy have been shown for a Swiss cohort. Despite high initial treatment costs and success only in a limited number of patients, the expenditure per QALY is surprisingly low and shows clearly the effectiveness of apparently costly acute medicine.

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

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.

High efficiency and low cost preparation of size controlled starch nanoparticles through ultrasonic treatment and precipitation.

Science.gov (United States)

Chang, Yanjiao; Yan, Xiaoxia; Wang, Qian; Ren, Lili; Tong, Jin; Zhou, Jiang

2017-07-15

The purpose of this work was to develop an approach to produce size controlled starch nanoparticles (SNPs), via precipitation with high efficiency and low cost. High concentration starch aqueous pastes (up to 5wt.%) were treated by ultrasound. Viscosity measurements and size exclusion chromatography characterization revealed that, after 30min ultrasonic treatment, viscosity of the starch pastes decreased two orders of magnitude and the weight average molecular weight of the starch decreased from 8.4×10 7 to 2.7×10 6 g/mol. Dynamic light scattering measurements and scanning electron microscopy observations showed that the SNPs prepared from the starch pastes with ultrasonic treatments were smaller (∼75nm) and more uniform. Moreover, SNPs could be obtained using less non-solvents. X-ray diffraction results indicated that effect of the ultrasonic treatment on crystalline structure of the SNPs was negligible. Ultrasound can be utilized to prepare smaller SNPs through nanoprecipitation with higher efficiency and lower cost. Copyright © 2017 Elsevier Ltd. All rights reserved.

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...

Potential market size and impact of hepatitis C treatment in low- and middle-income countries.

Science.gov (United States)

Woode, M E; Abu-Zaineh, M; Perriëns, J; Renaud, F; Wiktor, S; Moatti, J-P

2016-07-01

The introduction of direct-acting antiviral agents (DAAs) has made hepatitis C infection curable in the vast majority of cases and the elimination of the infection possible. Although initially too costly for large-scale use, recent reductions in DAA prices in some low- and middle-income countries (LaMICs) has improved the prospect of many people having access to these drugs/medications in the future. This article assesses the pricing and financing conditions under which the uptake of DAAs can increase to the point where the elimination of the disease in LaMICs is feasible. A Markov simulation model is used to study the dynamics of the infection with the introduction of treatment over a 10-year period. The impact on HCV-related mortality and HCV incidence is assessed under different financing scenarios assuming that the cost of the drugs is completely paid for out-of-pocket or reduced through either subsidy or drug price decreases. It is also assessed under different diagnostic and service delivery capacity scenarios separately for low-income (LIC), lower-middle-income (LMIC) and upper-middle-income countries (UMIC). Monte Carlo simulations are used for sensitivity analyses. At a price of US$ 1680 per 12-week treatment duration (based on negotiated Egyptian prices for an all oral two-DAA regimen), most of the people infected in LICs and LMICs would have limited access to treatment without subsidy or significant drug price decreases. However, people in UMICs would be able to access it even in the absence of a subsidy. For HCV treatment to have a significant impact on mortality and incidence, a significant scaling-up of diagnostic and service delivery capacity for HCV infection is needed. © 2016 The Authors. The Journal of Viral Hepatitis Published by John Wiley & Sons Ltd.

Prophylactic Antiviral Treatment in Recurrent Herpes Zoster: A Case Report

Directory of Open Access Journals (Sweden)

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.

Low cost methods of treatment of agricultural effluents in warm climates

Energy Technology Data Exchange (ETDEWEB)

Parker, C.D.

Treatment of effluents by anaerobic-aerobic lagoons, flood and spray irrigation and grass filtration is outlined and there are 4 examples of plants disposing respectively of waste from a domestic population with a cannery, vegetable and milk processing plants and a slaughterhouse; 2 wineries and a brandy distillery; a milk processing plant; and a potato processing plant. In the 3rd example high-strength dairy factory effluent (12,000 mg BOD/1) is fermented to methane and CO/sub 2/ with a daily yield of 59,000 cubic feet gas from 35,000 gal of waste; the outflow from fermenters and low strength waste (2500 mg BOD/1) is treated in a lagoon which removes greater than 90% BOD and passes to an oxidation ditch before irrigating pasture. A cost comparison of the various systems is included.

Biochar-based water treatment systems as a potential low-cost and sustainable technology for clean water provision.

Science.gov (United States)

Gwenzi, Willis; Chaukura, Nhamo; Noubactep, Chicgoua; Mukome, Fungai N D

2017-07-15

Approximately 600 million people lack access to safe drinking water, hence achieving Sustainable Development Goal 6 (Ensure availability and sustainable management of water and sanitation for all by 2030) calls for rapid translation of recent research into practical and frugal solutions within the remaining 13 years. Biochars, with excellent capacity to remove several contaminants from aqueous solutions, constitute an untapped technology for drinking water treatment. Biochar water treatment has several potential merits compared to existing low-cost methods (i.e., sand filtration, boiling, solar disinfection, chlorination): (1) biochar is a low-cost and renewable adsorbent made using readily available biomaterials and skills, making it appropriate for low-income communities; (2) existing methods predominantly remove pathogens, but biochars remove chemical, biological and physical contaminants; (3) biochars maintain organoleptic properties of water, while existing methods generate carcinogenic by-products (e.g., chlorination) and/or increase concentrations of chemical contaminants (e.g., boiling). Biochars have co-benefits including provision of clean energy for household heating and cooking, and soil application of spent biochar improves soil quality and crop yields. Integrating biochar into the water and sanitation system transforms linear material flows into looped material cycles, consistent with terra preta sanitation. Lack of design information on biochar water treatment, and environmental and public health risks constrain the biochar technology. Seven hypotheses for future research are highlighted under three themes: (1) design and optimization of biochar water treatment; (2) ecotoxicology and human health risks associated with contaminant transfer along the biochar-soil-food-human pathway, and (3) life cycle analyses of carbon and energy footprints of biochar water treatment systems. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents

Directory of Open Access Journals (Sweden)

Kamal SM

2014-06-01

Full Text Available Sanaa M Kamal1,21Department of Medicine, Division of Hepatology, Gastroenterology and Tropical Medicine, Ain Shams Faculty of Medicine, Cairo, Egypt, 2Department of Medicine, Salman Bin Abdul Aziz College of Medicine, Kingdom of Saudi ArabiaAbstract: Hepatitis C virus (HCV has emerged as a major viral pandemic over the past two decades, infecting 170 million individuals, which equates to approximately 3% of the world's population. The prevalence of HCV varies according to geographic region, being highest in developing countries such as Egypt. HCV has a high tendency to induce chronic progressive liver damage in the form of hepatic fibrosis, cirrhosis, or liver cancer. To date, there is no vaccine against HCV infection. Combination therapy comprising PEGylated interferon-alpha and ribavirin has been the standard of care for patients with chronic hepatitis C for more than a decade. However, many patients still do not respond to therapy or develop adverse events. Recently, direct antiviral agents such as protease inhibitors, polymerase inhibitors, or NS5A inhibitors have been used to augment PEGylated interferon and ribavirin, resulting in better efficacy, better tolerance, and a shorter treatment duration. However, most clinical trials have focused on assessing the efficacy and safety of direct antiviral agents in patients with genotype 1, and the response of other HCV genotypes has not been elucidated. Moreover, the prohibitive costs of such triple therapies will limit their use in patients in developing countries where most of the HCV infection exists. Understanding the host and viral factors associated with viral clearance is necessary for individualizing therapy to maximize sustained virologic response rates, prevent progression to liver disease, and increase the overall benefits of therapy with respect to its costs. Genome wide studies have shown significant associations between a set of polymorphisms in the region of the interleukin-28B (IL

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.

Cost-effectiveness of root caries preventive treatments.

Science.gov (United States)

Schwendicke, Falk; Göstemeyer, Gerd

2017-01-01

With a growing number of individuals retaining their teeth lifelong, often with periodontitis-induced root surface exposure, there is the need for cost-effective management strategies for root caries lesions. The present study aimed to assess the cost-effectiveness of root caries preventive treatments. Patients were simulated over 10 years using a Markov model. Four treatments were compared: No treatment, daily 225-800ppm fluoride rinses, chlorhexidine (CHX) varnish (2×/year), silver diamine fluoride (SDF) varnish (2×/year). Data from a systematic review were submitted to network meta-analysis for inferring relative efficacies of treatments. The health outcome was years of teeth being free of root caries. A mixed public-private payer perspective within 2016 German healthcare was taken, with costs being estimated from fee item catalogues or based on market prices. Populations with different numbers of teeth and tooth-level risks were modelled. Monte-Carlo microsimulations, univariate- and probabilistic sensitivity analyses were performed. In populations with 16 teeth at risk and low tooth-level risk for root caries, providing no preventive treatment was least costly, but also least effective (130 Euro, 144 years). SDF ranked next, being more costly (180 Euro), but also more effective (151 years). Payers willing to invest 8.30 Euro per root caries-free tooth-year found SDF most cost-effective. CHX varnish and fluoride rinse were not cost-effective. In populations with more teeth and high tooth-level risk, SDF was the most effective and least costly option. Root caries preventive treatments (like SDF) are effective and might even be cost-saving in high risk populations. Application of SDF can be recommended as a cost-saving treatment for prevention of root caries in patients with high risk of root caries. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ignoring the sacroiliac joint in chronic low back pain is costly

Directory of Open Access Journals (Sweden)

Polly DW

2016-01-01

Full Text Available David W Polly,1,2 Daniel Cher3 1Department of Orthopedic Surgery, 2Department of Neurosurgery, University of Minnesota, Minneapolis, MN, 3SI-BONE, Inc., San Jose, CA, USA Background: Increasing evidence supports minimally invasive sacroiliac joint (SIJ fusion as a safe and effective treatment for SIJ dysfunction. Failure to include the SIJ in the diagnostic evaluation of low back pain could result in unnecessary health care expenses. Design: Decision analytic cost model. Methods: A decision analytic model calculating 2-year direct health care costs in patients with chronic low back pain considering lumbar fusion surgery was used. Results: The strategy of including the SIJ in the preoperative diagnostic workup of chronic low back pain saves an expected US$3,100 per patient over 2 years. Cost savings were robust to reasonable ranges for costs and probabilities, such as the probability of diagnosis and the probability of successful surgical treatment. Conclusion: Including the SIJ as part of the diagnostic strategy in preoperative patients with chronic low back pain is likely to be cost saving in the short term. Keywords: chronic low back pain, lumbar fusion, sacroiliac joint pain, sacroiliac joint fusion, healthcare costs, decision modeling

Permeable treatment wall design and cost analysis

International Nuclear Information System (INIS)

Manz, C.; Quinn, K.

1997-01-01

A permeable treatment wall utilizing the funnel and gate technology has been chosen as the final remedial solution for one industrial site, and is being considered at other contaminated sites, such as a closed municipal landfill. Reactive iron gates will be utilized for treatment of chlorinated VOCs identified in the groundwater. Alternatives for the final remedial solution at each site were evaluated to achieve site closure in the most cost effective manner. This paper presents the remedial alternatives and cost analyses for each site. Several options are available at most sites for the design of a permeable treatment wall. Our analysis demonstrates that the major cost factor's for this technology are the design concept, length, thickness, location and construction methods for the reactive wall. Minimizing the amount of iron by placement in the most effective area and construction by the lowest cost method is critical to achieving a low cost alternative. These costs dictate the design of a permeable treatment wall, including selection of a variety of alternatives (e.g., a continuous wall versus a funnel and gate system, fully penetrating gates versus partially penetrating gates, etc.). Selection of the appropriate construction methods and materials for the site can reduce the overall cost of the wall

Topoisomerase 1 Inhibition Promotes Cyclic GMP-AMP Synthase-Dependent Antiviral Responses

OpenAIRE

Pépin, Geneviève; Nejad, Charlotte; Ferrand, Jonathan; Thomas, Belinda J.; Stunden, H. James; Sanij, Elaine; Foo, Chwan-Hong; Stewart, Cameron R.; Cain, Jason E.; Bardin, Philip G.; Williams, Bryan R. G.; Gantier, Michael P.

2017-01-01

ABSTRACT Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1) by low-dose camptothecin (CPT) can suppress transcriptional induction of antiviral and inflammatory genes and protect animals from excessive and damaging inflammatory responses. We describe the unexpected finding that minor DNA damage from topoisomerase 1 inhibition with low-dose CPT can trigger a strong antiviral immune response through c...

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.

Direct costs of first-generation protease inhibitors for the treatment of genotype 1 chronic hepatitis C viral infection.

Science.gov (United States)

Sethi, N; Tapper, E B; Vong, A; Sethi, S; Rourke, M; Afdhal, N H

2015-12-01

To evaluate the cost-effectiveness of Hepatitis C therapy, robust real-world data are needed to understand the costs and benefits of treatment alternatives. The objective of this study was to evaluate the true direct cost of treatment in an unselected sequential population of patients treated at a tertiary care centre for hepatitis C virus genotype 1. A total of 200 consecutive patients were treated with interferon, ribavirin and a first-generation direct-acting antiviral agent (DAA) between 2011 and 2013. A total of 41% had cirrhosis, 31% were prior relapsers, and 41% were prior partial or null responders. Costs used were wholesale acquisition cost prices for medications, average hospital costs per day for each diagnosis code based on US inpatient hospital charges. All costs were adjusted to 2013 dollars. Sustained virologic response (SVR) was achieved in 97 patients (48.5%). A total of 14% experienced relapse, 19% breakthrough or nonresponse, and 18.5% discontinued secondary to side effects. Twenty per cent of patients had at least one hospitalization attributable to a complication of therapy. Thirty-seven per cent of patients required erythropoietin-stimulating agents, 16% received filgastrim, and 15% needed a red blood cell transfusion. The mean overall cost of treatment was $83,851 per patient. The cost per SVR was $172,889; $266,670 for patients with cirrhosis. The costs per SVR after treatment with first-generation DAAs are dependent on the stage of disease and therapy side effects. These real-world costs significantly exceed those described in prior cost-effectiveness assessments and should be used instead for future studies. © 2015 John Wiley & Sons Ltd.

[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.

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.

Estimating costs of care for meningitis infections in low- and middle-income countries.

Science.gov (United States)

Portnoy, Allison; Jit, Mark; Lauer, Jeremy; Blommaert, Adriaan; Ozawa, Sachiko; Stack, Meghan; Murray, Jillian; Hutubessy, Raymond

2015-05-07

Meningitis infections are often associated with high mortality and risk of sequelae. The costs of treatment and care for meningitis are a great burden on health care systems, particularly in resource-limited settings. The objective of this study is to review data on the costs of care for meningitis in low- and middle-income countries, as well as to show how results could be extrapolated to countries without sound data. We conducted a systematic review of the literature from six databases to identify studies examining the cost of care in low- and middle-income countries for all age groups with suspected, probable, or confirmed meningitis. We extracted data on treatment costs and sequelae by infectious agent and/or pathogen, where possible. Using multiple regression analysis, a relationship between hospital costs and associated determinants was investigated in order to predict costs in countries with missing data. This relationship was used to predict treatment costs for all 144 low- and middle-income countries. The methodology of conducting a systematic review, extrapolating, and setting up a standard database can be used as a tool to inform cost-effectiveness analyses in situations where cost of care data are poor. Both acute and long-term costs of meningitis could be extrapolated to countries without reliable data. Although only bacterial causes of meningitis can be vaccine-preventable, a better understanding of the treatment costs for meningitis is crucial for low- and middle-income countries to assess the cost-effectiveness of proposed interventions in their country. This cost information will be important as inputs in future cost-effectiveness studies, particularly for vaccines. Copyright © 2014 Elsevier Ltd. All rights reserved.

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.

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

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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.

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

Science.gov (United States)

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.

Treatment Cost Analysis Tool (TCAT) for estimating costs of outpatient treatment services.

Science.gov (United States)

Flynn, Patrick M; Broome, Kirk M; Beaston-Blaakman, Aaron; Knight, Danica K; Horgan, Constance M; Shepard, Donald S

2009-02-01

A Microsoft Excel-based workbook designed for research analysts to use in a national study was retooled for treatment program directors and financial officers to allocate, analyze, and estimate outpatient treatment costs in the U.S. This instrument can also be used as a planning and management tool to optimize resources and forecast the impact of future changes in staffing, client flow, program design, and other resources. The Treatment Cost Analysis Tool (TCAT) automatically provides feedback and generates summaries and charts using comparative data from a national sample of non-methadone outpatient providers. TCAT is being used by program staff to capture and allocate both economic and accounting costs, and outpatient service costs are reported for a sample of 70 programs. Costs for an episode of treatment in regular, intensive, and mixed types of outpatient treatment were $882, $1310, and $1381 respectively (based on 20% trimmed means and 2006 dollars). An hour of counseling cost $64 in regular, $85 intensive, and $86 mixed. Group counseling hourly costs per client were $8, $11, and $10 respectively for regular, intensive, and mixed. Future directions include use of a web-based interview version, much like some of the commercially available tax preparation software tools, and extensions for use in other modalities of treatment.

The Cost-Effectiveness of Low-Cost Essential Antihypertensive Medicines for Hypertension Control in China: A Modelling Study.

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Dongfeng Gu

2015-08-01

Full Text Available Hypertension is China's leading cardiovascular disease risk factor. Improved hypertension control in China would result in result in enormous health gains in the world's largest population. A computer simulation model projected the cost-effectiveness of hypertension treatment in Chinese adults, assuming a range of essential medicines list drug costs.The Cardiovascular Disease Policy Model-China, a Markov-style computer simulation model, simulated hypertension screening, essential medicines program implementation, hypertension control program administration, drug treatment and monitoring costs, disease-related costs, and quality-adjusted life years (QALYs gained by preventing cardiovascular disease or lost because of drug side effects in untreated hypertensive adults aged 35-84 y over 2015-2025. Cost-effectiveness was assessed in cardiovascular disease patients (secondary prevention and for two blood pressure ranges in primary prevention (stage one, 140-159/90-99 mm Hg; stage two, ≥160/≥100 mm Hg. Treatment of isolated systolic hypertension and combined systolic and diastolic hypertension were modeled as a reduction in systolic blood pressure; treatment of isolated diastolic hypertension was modeled as a reduction in diastolic blood pressure. One-way and probabilistic sensitivity analyses explored ranges of antihypertensive drug effectiveness and costs, monitoring frequency, medication adherence, side effect severity, background hypertension prevalence, antihypertensive medication treatment, case fatality, incidence and prevalence, and cardiovascular disease treatment costs. Median antihypertensive costs from Shanghai and Yunnan province were entered into the model in order to estimate the effects of very low and high drug prices. Incremental cost-effectiveness ratios less than the per capita gross domestic product of China (11,900 international dollars [Int$] in 2015 were considered cost-effective. Treating hypertensive adults with prior

Waste Management Facilities cost information for low-level waste

Energy Technology Data Exchange (ETDEWEB)

Shropshire, D.; Sherick, M.; Biadgi, C.

1995-06-01

This report contains preconceptual designs and planning level life-cycle cost estimates for managing low-level waste. The report`s information on treatment, storage, and disposal modules can be integrated to develop total life-cycle costs for various waste management options. A procedure to guide the US Department of Energy and its contractor personnel in the use of cost estimation data is also summarized in this report.

Treatment of a simulated textile wastewater in a sequencing batch reactor (SBR) with addition of a low-cost adsorbent

International Nuclear Information System (INIS)

Santos, Sílvia C.R.; Boaventura, Rui A.R.

2015-01-01

Highlights: • Treating textile dyeing effluents by SBR coupled with waste sludge adsorption. • Metal hydroxide sludge: a good adsorbent for a direct textile dye. • Good adsorption capacities were found with the low-cost adsorbent. • Adsorbent performance considerably reduced by auxiliary products. • Color removal complies with discharge limits. - Abstract: Color removal from textile wastewaters, at a low-cost and consistent technology, is even today a challenge. Simultaneous biological treatment and adsorption is a known alternative to the treatment of wastewaters containing biodegradable and non-biodegradable contaminants. The present work aims at evaluating the treatability of a simulated textile wastewater by simultaneously combining biological treatment and adsorption in a SBR (sequencing batch reactor), but using a low-cost adsorbent, instead of a commercial one. The selected adsorbent was a metal hydroxide sludge (WS) from an electroplating industry. Direct Blue 85 dye (DB) was used in the preparation of the synthetic wastewater. Firstly, adsorption kinetics and equilibrium were studied, in respect to many factors (temperature, pH, WS dosage and presence of salts and dyeing auxiliary chemicals in the aqueous media). At 25 °C and pH 4, 7 and 10, maximum DB adsorption capacities in aqueous solution were 600, 339 and 98.7 mg/g, respectively. These values are quite considerable, compared to other reported in literature, but proved to be significantly reduced by the presence of dyeing auxiliary chemicals in the wastewater. The simulated textile wastewater treatment in SBR led to BOD 5 removals of 53–79%, but color removal was rather limited (10–18%). The performance was significantly enhanced by the addition of WS, with BOD 5 removals above 91% and average color removals of 60–69%

Treatment of a simulated textile wastewater in a sequencing batch reactor (SBR) with addition of a low-cost adsorbent

Energy Technology Data Exchange (ETDEWEB)

Santos, Sílvia C.R., E-mail: scrs@fe.up.pt; Boaventura, Rui A.R.

2015-06-30

Highlights: • Treating textile dyeing effluents by SBR coupled with waste sludge adsorption. • Metal hydroxide sludge: a good adsorbent for a direct textile dye. • Good adsorption capacities were found with the low-cost adsorbent. • Adsorbent performance considerably reduced by auxiliary products. • Color removal complies with discharge limits. - Abstract: Color removal from textile wastewaters, at a low-cost and consistent technology, is even today a challenge. Simultaneous biological treatment and adsorption is a known alternative to the treatment of wastewaters containing biodegradable and non-biodegradable contaminants. The present work aims at evaluating the treatability of a simulated textile wastewater by simultaneously combining biological treatment and adsorption in a SBR (sequencing batch reactor), but using a low-cost adsorbent, instead of a commercial one. The selected adsorbent was a metal hydroxide sludge (WS) from an electroplating industry. Direct Blue 85 dye (DB) was used in the preparation of the synthetic wastewater. Firstly, adsorption kinetics and equilibrium were studied, in respect to many factors (temperature, pH, WS dosage and presence of salts and dyeing auxiliary chemicals in the aqueous media). At 25 °C and pH 4, 7 and 10, maximum DB adsorption capacities in aqueous solution were 600, 339 and 98.7 mg/g, respectively. These values are quite considerable, compared to other reported in literature, but proved to be significantly reduced by the presence of dyeing auxiliary chemicals in the wastewater. The simulated textile wastewater treatment in SBR led to BOD{sub 5} removals of 53–79%, but color removal was rather limited (10–18%). The performance was significantly enhanced by the addition of WS, with BOD{sub 5} removals above 91% and average color removals of 60–69%.

The cost of treatment failure: resource use and costs incurred by hepatitis C virus genotype 1-infected patients who do or do not achieve sustained virological response to therapy.

Science.gov (United States)

Backx, M; Lewszuk, A; White, J R; Cole, J; Sreedharan, A; van Sanden, S; Diels, J; Lawson, A; Neal, K R; Wiselka, M J; Ito, T; Irving, W L

2014-03-01

Chronic hepatitis C virus (HCV) infection places a considerable economic burden on health services. Cost-effectiveness analyses of antiviral treatment for patients with chronic HCV infection are dependent on assumptions about cost reductions following sustained virological response (SVR) to therapy. This study quantified the medium-term difference in health resource usage and costs depending on treatment outcome. Retrospective chart review of patients with HCV genotype 1 infection who had received at least 2 months pegylated interferon and ribavirin therapy, with known treatment outcome was conducted. Disease status was categorized as chronic hepatitis, cirrhosis or decompensated liver disease. Health resource use was documented for each patient in each disease state. Unit costs were from the NHS 'Payment by Results' database and the British National Formulary. One hundred and ninety three patients (108 SVR, 85 non-SVR) with mean follow-up of 3.5 (SVR) and 4.9 (non-SVR) years were enrolled. No SVR patient progressed to a more severe liver disease state. Annual transition rates for non-SVR patients were 7.4% (chronic hepatitis to cirrhosis) and 4.9% (cirrhosis to decompensated liver disease). By extrapolation of modelled data over a 5-year post-treatment period, failure of patients with chronic hepatitis to achieve SVR was associated with a 13-fold increase (roughly £2300) in costs, whilst for patients who were retreated, the increase was 56-fold, equating to more than £10 000. Achievement of an SVR has significant effects on health service usage and costs. This work provides real-life data for future cost-effectiveness analyses related to the treatment for chronic HCV infection. © 2013 John Wiley & Sons Ltd.

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)

Hidden costs of antiretroviral treatment: the public health efficiency of drug packaging.

Science.gov (United States)

Andreu-Crespo, Àngels; Llibre, Josep M; Cardona-Peitx, Glòria; Sala-Piñol, Ferran; Clotet, Bonaventura; Bonafont-Pujol, Xavier

2015-01-01

While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals) - with a cost of 47,139.91 € - would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar), should minimize the treatment expenditures paid by national health budgets.

Ophthalmic antiviral chemotherapy : An overview

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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.

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

Development and Performance Evaluation of a Low Cost Waste ...

African Journals Online (AJOL)

The design, development and performance evaluation of a low cost waste-water treatment plant had been carried out. The aim was to harness the usefulness of waste-waters from residential, institutional and commercial sources. The facultative lagoon method of waste-water treatment was adopted. Biological analysis of ...

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.

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.

Low-cost electrochemical treatment of indium tin oxide anodes for high-efficiency organic light-emitting diodes

Energy Technology Data Exchange (ETDEWEB)

Hui Cheng, Chuan, E-mail: chengchuanhui@dlut.edu.cn; Shan Liang, Ze; Gang Wang, Li; Dong Gao, Guo; Zhou, Ting; Ming Bian, Ji; Min Luo, Ying [School of Physics and Optoelectronic Technology, Dalian University of Technology, Dalian 116024 (China); Tong Du, Guo, E-mail: dugt@dlut.edu.cn [School of Physics and Optoelectronic Technology, Dalian University of Technology, Dalian 116024 (China); State Key Laboratory on Integrated Optoelectronics, College of Electronic Science and Engineering, Jilin University, Changchun 130012 (China)

2014-01-27

We demonstrate a simple low-cost approach as an alternative to conventional O{sub 2} plasma treatment to modify the surface of indium tin oxide (ITO) anodes for use in organic light-emitting diodes. ITO is functionalized with F{sup −} ions by electrochemical treatment in dilute hydrofluoric acid. An electrode with a work function of 5.2 eV is achieved following fluorination. Using this electrode, a maximum external quantum efficiency of 26.0% (91 cd/A, 102 lm/W) is obtained, which is 12% higher than that of a device using the O{sub 2} plasma-treated ITO. Fluorination also increases the transparency in the near-infrared region.

Regional differences in treatment rates for patients with chronic hepatitis C infection: Systematic review and meta-analysis.

Directory of Open Access Journals (Sweden)

Philip Vutien

Full Text Available Treatment rates with interferon-based therapies for chronic hepatitis C have been low. Our aim was to perform a systematic review of available data to estimate the rates and barriers for antiviral therapy for chronic hepatitis C.We conducted a systematic review and meta-analysis searching MEDLINE, SCOPUS through March 2016 and abstracts from recent major liver meetings for primary literature with available hepatitis C treatment rates. Random-effects models were used to estimate effect sizes and meta-regression to test for potential sources of heterogeneity.We included 39 studies with 476,443 chronic hepatitis C patients. The overall treatment rate was 25.5% (CI: 21.1-30.5% and by region 34% for Europe, 28.3% for Asia/Pacific, and 18.7% for North America (p = 0.008. On multivariable meta-regression, practice setting (tertiary vs. population-based, p = 0.04, region (Europe vs. North America p = 0.004, and data source (clinical chart review vs. administrative database, p = 0.025 remained significant predictors of heterogeneity. The overall treatment eligibility rate was 52.5%, and 60% of these received therapy. Of the patients who refused treatment, 16.2% cited side effects, 13.8% cited cost as reasons for treatment refusal, and 30% lacked access to specialist care.Only one-quarter of chronic hepatitis C patients received antiviral therapy in the pre-direct acting antiviral era. Treatment rates should improve in the new interferon-free era but, cost, co-morbidities, and lack of specialist care will likely remain and need to be addressed. Linkage to care should even be of higher priority now that well-tolerated cure is available.

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...

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

Directory of Open Access Journals (Sweden)

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.

Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects.

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Jurgeit, Andreas; McDowell, Robert; Moese, Stefan; Meldrum, Eric; Schwendener, Reto; Greber, Urs F

2012-01-01

Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV) and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+)-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.

Niclosamide is a proton carrier and targets acidic endosomes with broad antiviral effects.

Directory of Open Access Journals (Sweden)

Andreas Jurgeit

Full Text Available Viruses use a limited set of host pathways for infection. These pathways represent bona fide antiviral targets with low likelihood of viral resistance. We identified the salicylanilide niclosamide as a broad range antiviral agent targeting acidified endosomes. Niclosamide is approved for human use against helminthic infections, and has anti-neoplastic and antiviral effects. Its mode of action is unknown. Here, we show that niclosamide, which is a weak lipophilic acid inhibited infection with pH-dependent human rhinoviruses (HRV and influenza virus. Structure-activity studies showed that antiviral efficacy and endolysosomal pH neutralization co-tracked, and acidification of the extracellular medium bypassed the virus entry block. Niclosamide did not affect the vacuolar H(+-ATPase, but neutralized coated vesicles or synthetic liposomes, indicating a proton carrier mode-of-action independent of any protein target. This report demonstrates that physico-chemical interference with host pathways has broad range antiviral effects, and provides a proof of concept for the development of host-directed antivirals.

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

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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.

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

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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.

Low-cost inertial measurement unit.

Energy Technology Data Exchange (ETDEWEB)

Deyle, Travis Jay

2005-03-01

Sandia National Laboratories performs many expensive tests using inertial measurement units (IMUs)--systems that use accelerometers, gyroscopes, and other sensors to measure flight dynamics in three dimensions. For the purpose of this report, the metrics used to evaluate an IMU are cost, size, performance, resolution, upgradeability and testing. The cost of a precision IMU is very high and can cost hundreds of thousands of dollars. Thus the goals and results of this project are as follows: (1) Examine the data flow in an IMU and determine a generic IMU design. (2) Discuss a high cost IMU implementation and its theoretically achievable results. (3) Discuss design modifications that would save money for suited applications. (4) Design and implement a low cost IMU and discuss its theoretically achievable results. (5) Test the low cost IMU and compare theoretical results with empirical results. (6) Construct a more streamlined printed circuit board design reducing noise, increasing capabilities, and constructing a self-contained unit. Using these results, we can compare a high cost IMU versus a low cost IMU using the metrics from above. Further, we can examine and suggest situations where a low cost IMU could be used instead of a high cost IMU for saving cost, size, or both.

Vaccination strategies for future influenza pandemics: a severity-based cost effectiveness analysis.

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Kelso, Joel K; Halder, Nilimesh; Milne, George J

2013-02-11

A critical issue in planning pandemic influenza mitigation strategies is the delay between the arrival of the pandemic in a community and the availability of an effective vaccine. The likely scenario, born out in the 2009 pandemic, is that a newly emerged influenza pandemic will have spread to most parts of the world before a vaccine matched to the pandemic strain is produced. For a severe pandemic, additional rapidly activated intervention measures will be required if high mortality rates are to be avoided. A simulation modelling study was conducted to examine the effectiveness and cost effectiveness of plausible combinations of social distancing, antiviral and vaccination interventions, assuming a delay of 6-months between arrival of an influenza pandemic and first availability of a vaccine. Three different pandemic scenarios were examined; mild, moderate and extreme, based on estimates of transmissibility and pathogenicity of the 2009, 1957 and 1918 influenza pandemics respectively. A range of different durations of social distancing were examined, and the sensitivity of the results to variation in the vaccination delay, ranging from 2 to 6 months, was analysed. Vaccination-only strategies were not cost effective for any pandemic scenario, saving few lives and incurring substantial vaccination costs. Vaccination coupled with long duration social distancing, antiviral treatment and antiviral prophylaxis was cost effective for moderate pandemics and extreme pandemics, where it saved lives while simultaneously reducing the total pandemic cost. Combined social distancing and antiviral interventions without vaccination were significantly less effective, since without vaccination a resurgence in case numbers occurred as soon as social distancing interventions were relaxed. When social distancing interventions were continued until at least the start of the vaccination campaign, attack rates and total costs were significantly lower, and increased rates of vaccination

Utilizing time-driven activity-based costing to understand the short- and long-term costs of treating localized, low-risk prostate cancer.

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Laviana, Aaron A; Ilg, Annette M; Veruttipong, Darlene; Tan, Hung-Jui; Burke, Michael A; Niedzwiecki, Douglas R; Kupelian, Patrick A; King, Chris R; Steinberg, Michael L; Kundavaram, Chandan R; Kamrava, Mitchell; Kaplan, Alan L; Moriarity, Andrew K; Hsu, William; Margolis, Daniel J A; Hu, Jim C; Saigal, Christopher S

2016-02-01

Given the costs of delivering care for men with prostate cancer remain poorly described, this article reports the results of time-driven activity-based costing (TDABC) for competing treatments of low-risk prostate cancer. Process maps were developed for each phase of care from the initial urologic visit through 12 years of follow-up for robotic-assisted laparoscopic prostatectomy (RALP), cryotherapy, high-dose rate (HDR) and low-dose rate (LDR) brachytherapy, intensity-modulated radiation therapy (IMRT), stereotactic body radiation therapy (SBRT), and active surveillance (AS). The last modality incorporated both traditional transrectal ultrasound (TRUS) biopsy and multiparametric-MRI/TRUS fusion biopsy. The costs of materials, equipment, personnel, and space were calculated per unit of time and based on the relative proportion of capacity used. TDABC for each treatment was defined as the sum of its resources. Substantial cost variation was observed at 5 years, with costs ranging from $7,298 for AS to $23,565 for IMRT, and they remained consistent through 12 years of follow-up. LDR brachytherapy ($8,978) was notably cheaper than HDR brachytherapy ($11,448), and SBRT ($11,665) was notably cheaper than IMRT, with the cost savings attributable to shorter procedure times and fewer visits required for treatment. Both equipment costs and an inpatient stay ($2,306) contributed to the high cost of RALP ($16,946). Cryotherapy ($11,215) was more costly than LDR brachytherapy, largely because of increased single-use equipment costs ($6,292 vs $1,921). AS reached cost equivalence with LDR brachytherapy after 7 years of follow-up. The use of TDABC is feasible for analyzing cancer services and provides insights into cost-reduction tactics in an era focused on emphasizing value. By detailing all steps from diagnosis and treatment through 12 years of follow-up for low-risk prostate cancer, this study has demonstrated significant cost variation between competing treatments. © 2015

Hidden costs of antiretroviral treatment: the public health efficiency of drug packaging

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Andreu-Crespo À

2015-08-01

Full Text Available Àngels Andreu-Crespo,1,* Josep M Llibre,2,3,* Glòria Cardona-Peitx,1 Ferran Sala-Piñol,1 Bonaventura Clotet,2,4 Xavier Bonafont-Pujol1 1Pharmacy Department, 2HIV Unit and “Lluita contra la SIDA” Foundation, University Hospital Germans Trias i Pujol, Badalona, 3Universitat Autònoma de Barcelona, 4Universitat de Vic-Universitat Central de Catalunya (UVIC-UCC, Vic, Barcelona, Spain *These authors contributed equally to the work Abstract: While the overall percentage of unused antiretroviral medicines returned to the hospital pharmacy is low, their cost is quite high. Adverse events, treatment failure, pharmacokinetic interactions, pregnancy, or treatment simplification are common reasons for unplanned treatment changes. Socially inefficient antiretroviral packages prevent the reuse of drugs returned to the hospital pharmacy. We defined antiretroviral package categories based on the excellence of drug packaging and analyzed the number of pills and costs of drugs returned during a period of 1 year in a hospital-based HIV unit attending to 2,413 treated individuals. A total of 6,090 pills (34% of all returned antiretrovirals – with a cost of 47,139.91€ – would be totally lost, mainly due to being packed up in the lowest efficiency packages. Newer treatments are packaged in low-excellence categories of packages, thus favoring the maintenance of these hidden costs in the near future. Therefore, costs of this low-efficiency drug packaging, where medication packages are started but not completed, in high-cost medications are substantial and should be properly addressed. Any improvement in the packaging by the manufacturer, and favoring the choice of drugs supplied through efficient packages (when efficacy, toxicity, and convenience are similar, should minimize the treatment expenditures paid by national health budgets. Keywords: antiretroviral treatment, cost efficacy, drug packaging, treatment change

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.

Activation of cGAS-dependent antiviral responses by DNA intercalating agents.

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Pépin, Geneviève; Nejad, Charlotte; Thomas, Belinda J; Ferrand, Jonathan; McArthur, Kate; Bardin, Philip G; Williams, Bryan R G; Gantier, Michael P

2017-01-09

Acridine dyes, including proflavine and acriflavine, were commonly used as antiseptics before the advent of penicillins in the mid-1940s. While their mode of action on pathogens was originally attributed to their DNA intercalating activity, work in the early 1970s suggested involvement of the host immune responses, characterized by induction of interferon (IFN)-like activities through an unknown mechanism. We demonstrate here that sub-toxic concentrations of a mixture of acriflavine and proflavine instigate a cyclic-GMP-AMP (cGAMP) synthase (cGAS)-dependent type-I IFN antiviral response. This pertains to the capacity of these compounds to induce low level DNA damage and cytoplasmic DNA leakage, resulting in cGAS-dependent cGAMP-like activity. Critically, acriflavine:proflavine pre-treatment of human primary bronchial epithelial cells significantly reduced rhinovirus infection. Collectively, our findings constitute the first evidence that non-toxic DNA binding agents have the capacity to act as indirect agonists of cGAS, to exert potent antiviral effects in mammalian cells. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

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.

Topoisomerase 1 Inhibition Promotes Cyclic GMP-AMP Synthase-Dependent Antiviral Responses

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Geneviève Pèépin

2017-10-01

Full Text Available Inflammatory responses, while essential for pathogen clearance, can also be deleterious to the host. Chemical inhibition of topoisomerase 1 (Top1 by low-dose camptothecin (CPT can suppress transcriptional induction of antiviral and inflammatory genes and protect animals from excessive and damaging inflammatory responses. We describe the unexpected finding that minor DNA damage from topoisomerase 1 inhibition with low-dose CPT can trigger a strong antiviral immune response through cyclic GMP-AMP synthase (cGAS detection of cytoplasmic DNA. This argues against CPT having only anti-inflammatory activity. Furthermore, expression of the simian virus 40 (SV40 large T antigen was paramount to the proinflammatory antiviral activity of CPT, as it potentiated cytoplasmic DNA leakage and subsequent cGAS recruitment in human and mouse cell lines. This work suggests that the capacity of Top1 inhibitors to blunt inflammatory responses can be counteracted by viral oncogenes and that this should be taken into account for their therapeutic development.

Cost-Effective Fuel Treatment Planning

Science.gov (United States)

Kreitler, J.; Thompson, M.; Vaillant, N.

2014-12-01

The cost of fighting large wildland fires in the western United States has grown dramatically over the past decade. This trend will likely continue with growth of the WUI into fire prone ecosystems, dangerous fuel conditions from decades of fire suppression, and a potentially increasing effect from prolonged drought and climate change. Fuel treatments are often considered the primary pre-fire mechanism to reduce the exposure of values at risk to wildland fire, and a growing suite of fire models and tools are employed to prioritize where treatments could mitigate wildland fire damages. Assessments using the likelihood and consequence of fire are critical because funds are insufficient to reduce risk on all lands needing treatment, therefore prioritization is required to maximize the effectiveness of fuel treatment budgets. Cost-effectiveness, doing the most good per dollar, would seem to be an important fuel treatment metric, yet studies or plans that prioritize fuel treatments using costs or cost-effectiveness measures are absent from the literature. Therefore, to explore the effect of using costs in fuel treatment planning we test four prioritization algorithms designed to reduce risk in a case study examining fuel treatments on the Sisters Ranger District of central Oregon. For benefits we model sediment retention and standing biomass, and measure the effectiveness of each algorithm by comparing the differences among treatment and no treat alternative scenarios. Our objective is to maximize the averted loss of net benefits subject to a representative fuel treatment budget. We model costs across the study landscape using the My Fuel Treatment Planner software, tree list data, local mill prices, and GIS-measured site characteristics. We use fire simulations to generate burn probabilities, and estimate fire intensity as conditional flame length at each pixel. Two prioritization algorithms target treatments based on cost-effectiveness and show improvements over those

Treatment of a simulated textile wastewater in a sequencing batch reactor (SBR) with addition of a low-cost adsorbent.

Science.gov (United States)

Santos, Sílvia C R; Boaventura, Rui A R

2015-06-30

Color removal from textile wastewaters, at a low-cost and consistent technology, is even today a challenge. Simultaneous biological treatment and adsorption is a known alternative to the treatment of wastewaters containing biodegradable and non-biodegradable contaminants. The present work aims at evaluating the treatability of a simulated textile wastewater by simultaneously combining biological treatment and adsorption in a SBR (sequencing batch reactor), but using a low-cost adsorbent, instead of a commercial one. The selected adsorbent was a metal hydroxide sludge (WS) from an electroplating industry. Direct Blue 85 dye (DB) was used in the preparation of the synthetic wastewater. Firstly, adsorption kinetics and equilibrium were studied, in respect to many factors (temperature, pH, WS dosage and presence of salts and dyeing auxiliary chemicals in the aqueous media). At 25 °C and pH 4, 7 and 10, maximum DB adsorption capacities in aqueous solution were 600, 339 and 98.7 mg/g, respectively. These values are quite considerable, compared to other reported in literature, but proved to be significantly reduced by the presence of dyeing auxiliary chemicals in the wastewater. The simulated textile wastewater treatment in SBR led to BOD5 removals of 53-79%, but color removal was rather limited (10-18%). The performance was significantly enhanced by the addition of WS, with BOD5 removals above 91% and average color removals of 60-69%. Copyright © 2015 Elsevier B.V. All rights reserved.

Hidden costs of low-cost screening mammography

International Nuclear Information System (INIS)

Cyrlak, D.

1987-01-01

Twenty-two hundred women in Orange County, California, took part in a low-cost mammography screening project sponsored by the American Cancer Society and the KCBS-TV. Patients were followed up by telephone and questioned about actual costs incurred as a result of screening mammography, including costs of repeated and follow-up mammograms, US examinations and surgical consultations. The total number of biopsies, cancers found, and the costs involved were investigated. The authors' results suggest that particularly in centers with a high positive call rate, the cost of screening mammograms accounts for only a small proportion of the medical costs

Cost-utility analysis of antiviral use under pandemic influenza using a novel approach - linking pharmacology, epidemiology and heath economics.

Science.gov (United States)

Wu, D B C; Chaiyakunapruk, N; Pratoomsoot, C; Lee, K K C; Chong, H Y; Nelson, R E; Smith, P F; Kirkpatrick, C M; Kamal, M A; Nieforth, K; Dall, G; Toovey, S; Kong, D C M; Kamauu, A; Rayner, C R

2018-03-01

Simulation models are used widely in pharmacology, epidemiology and health economics (HEs). However, there have been no attempts to incorporate models from these disciplines into a single integrated model. Accordingly, we explored this linkage to evaluate the epidemiological and economic impact of oseltamivir dose optimisation in supporting pandemic influenza planning in the USA. An HE decision analytic model was linked to a pharmacokinetic/pharmacodynamics (PK/PD) - dynamic transmission model simulating the impact of pandemic influenza with low virulence and low transmissibility and, high virulence and high transmissibility. The cost-utility analysis was from the payer and societal perspectives, comparing oseltamivir 75 and 150 mg twice daily (BID) to no treatment over a 1-year time horizon. Model parameters were derived from published studies. Outcomes were measured as cost per quality-adjusted life year (QALY) gained. Sensitivity analyses were performed to examine the integrated model's robustness. Under both pandemic scenarios, compared to no treatment, the use of oseltamivir 75 or 150 mg BID led to a significant reduction of influenza episodes and influenza-related deaths, translating to substantial savings of QALYs. Overall drug costs were offset by the reduction of both direct and indirect costs, making these two interventions cost-saving from both perspectives. The results were sensitive to the proportion of inpatient presentation at the emergency visit and patients' quality of life. Integrating PK/PD-EPI/HE models is achievable. Whilst further refinement of this novel linkage model to more closely mimic the reality is needed, the current study has generated useful insights to support influenza pandemic planning.

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.

Low cost UV-Ozone reactor mounted for treatment of electrode anodes used in P-OLEDs devices

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Emerson Roberto Santos

Full Text Available Abstract Low cost UV-Ozone reactor using a high pressure mercury vapor lamp of 80 watts without outer bulb showed good results for treatment of ITO films used as anode electrode in the assembly of P-OLED (polymer-organic light emitting diode devices. This study revealed 20 minutes as effective treatment time and it was verified also that the effect of UV-Ozone treatment loses its efficiency as the elapsed time increases. It was analyzed with measurements of contact angle using a droplet of PEDOT:PSS polymer. P-OLEDs devices were mounted with architecture: ITO/PEDOT:PSS/PVK/Alq3/Al. The PVK polymer was diluted in organic solvent of 1,2,4-trichlorobenzene with concentrations of: 5, 10, 20 and 30 mg/mL. Results revealed better performance of P-OLED devices for concentration of 5 mg/mL resulting in lower threshold voltage, elevation of electrical current and similar diode curve.

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.

Application of low-cost adsorbents for dye removal--a review.

Science.gov (United States)

Gupta, V K; Suhas

2009-06-01

Dyes are an important class of pollutants, and can even be identified by the human eye. Disposal of dyes in precious water resources must be avoided, however, and for that various treatment technologies are in use. Among various methods adsorption occupies a prominent place in dye removal. The growing demand for efficient and low-cost treatment methods and the importance of adsorption has given rise to low-cost alternative adsorbents (LCAs). This review highlights and provides an overview of these LCAs comprising natural, industrial as well as synthetic materials/wastes and their application for dyes removal. In addition, various other methods used for dye removal from water and wastewater are also complied in brief. From a comprehensive literature review, it was found that some LCAs, in addition to having wide availability, have fast kinetics and appreciable adsorption capacities too. Advantages and disadvantages of adsorbents, favourable conditions for particular adsorbate-adsorbent systems, and adsorption capacities of various low-cost adsorbents and commercial activated carbons as available in the literature are presented. Conclusions have been drawn from the literature reviewed, and suggestions for future research are proposed.

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.

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.

Cost-effectiveness of Early Treatment of Hepatitis C Virus Genotype 1 by Stage of Liver Fibrosis in a US Treatment-Naive Population

Science.gov (United States)

Chahal, Harinder S.; Marseille, Elliot A.; Tice, Jeffrey A.; Pearson, Steve D.; Ollendorf, Daniel A.; Fox, Rena K.; Kahn, James G.

2016-01-01

IMPORTANCE Novel treatments for hepatitis C virus (HCV) infection are highly efficacious but costly. Thus, many insurers cover therapy only in advanced fibrosis stages. The added health benefits and costs of early treatment are unknown. OBJECTIVE To assess the cost-effectiveness of (1) treating all patients with HCV vs only those with advanced fibrosis and (2) treating each stage of fibrosis. DESIGN, SETTING, AND PARTICIPANTS This study used a decision-analytic model for the treatment of HCV genotype 1. The model used a lifetime horizon and societal perspective and was representative of all US patients with HCV genotype 1 who had not received previous treatment. Comparisons in the model included antiviral treatment of all fibrosis stages (METAVIR [Meta-analysis of Histological Data in Virial Hepatitis] stages F0 [no fibrosis] to F4 [cirrhosis]) vs treatment of stages F3 (numerous septa without cirrhosis) and F4 only and by specific fibrosis stage. Data were collected from March 1 to September 1, 2014, and analyzed from September 1, 2014, to June 30, 2015. INTERVENTIONS Six HCV therapy options (particularly combined sofosbuvir and ledipasvir therapy) or no treatment. MAIN OUTCOMES AND MEASURES Cost and health outcomes were measured using total medical costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs), calculated as the difference in costs between strategies divided by the difference in QALYs. RESULTS We simulated 1000 individuals, but present the results normalized to a single HCV-infected person. In the base-case analysis, among patients receiving 8 or 12 weeks of sofosbuvir-ledipasvir treatment, treating all fibrosis stages compared with treating stages F3 and F4 adds 0.73 QALYs and $28 899, for an ICER of $39 475 per QALY gained. Treating at stage F2 (portal fibrosis with rare septa) costs $19 833 per QALY gained vs waiting until stage F3; treating at stage F1 (portal fibrosis without septa), $81 165 per QALY gained

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.

Low-cost high purity production

Science.gov (United States)

Kapur, V. K.

1978-01-01

Economical process produces high-purity silicon crystals suitable for use in solar cells. Reaction is strongly exothermic and can be initiated at relatively low temperature, making it potentially suitable for development into low-cost commercial process. Important advantages include exothermic character and comparatively low process temperatures. These could lead to significant savings in equipment and energy costs.

Modeling cost-effectiveness and health gains of a "universal" versus "prioritized" hepatitis C virus treatment policy in a real-life cohort.

Science.gov (United States)

Kondili, Loreta A; Romano, Federica; Rolli, Francesca Romana; Ruggeri, Matteo; Rosato, Stefano; Brunetto, Maurizia Rossana; Zignego, Anna Linda; Ciancio, Alessia; Di Leo, Alfredo; Raimondo, Giovanni; Ferrari, Carlo; Taliani, Gloria; Borgia, Guglielmo; Santantonio, Teresa Antonia; Blanc, Pierluigi; Gaeta, Giovanni Battista; Gasbarrini, Antonio; Chessa, Luchino; Erne, Elke Maria; Villa, Erica; Ieluzzi, Donatella; Russo, Francesco Paolo; Andreone, Pietro; Vinci, Maria; Coppola, Carmine; Chemello, Liliana; Madonia, Salvatore; Verucchi, Gabriella; Persico, Marcello; Zuin, Massimo; Puoti, Massimo; Alberti, Alfredo; Nardone, Gerardo; Massari, Marco; Montalto, Giuseppe; Foti, Giuseppe; Rumi, Maria Grazia; Quaranta, Maria Giovanna; Cicchetti, Americo; Craxì, Antonio; Vella, Stefano

2017-12-01

We evaluated the cost-effectiveness of two alternative direct-acting antiviral (DAA) treatment policies in a real-life cohort of hepatitis C virus-infected patients: policy 1, "universal," treat all patients, regardless of fibrosis stage; policy 2, treat only "prioritized" patients, delay treatment of the remaining patients until reaching stage F3. A liver disease progression Markov model, which used a lifetime horizon and health care system perspective, was applied to the PITER cohort (representative of Italian hepatitis C virus-infected patients in care). Specifically, 8,125 patients naive to DAA treatment, without clinical, sociodemographic, or insurance restrictions, were used to evaluate the policies' cost-effectiveness. The patients' age and fibrosis stage, assumed DAA treatment cost of €15,000/patient, and the Italian liver disease costs were used to evaluate quality-adjusted life-years (QALY) and incremental cost-effectiveness ratios (ICER) of policy 1 versus policy 2. To generalize the results, a European scenario analysis was performed, resampling the study population, using the mean European country-specific health states costs and mean treatment cost of €30,000. For the Italian base-case analysis, the cost-effective ICER obtained using policy 1 was €8,775/QALY. ICERs remained cost-effective in 94%-97% of the 10,000 probabilistic simulations. For the European treatment scenario the ICER obtained using policy 1 was €19,541.75/QALY. ICER was sensitive to variations in DAA costs, in the utility value of patients in fibrosis stages F0-F3 post-sustained virological response, and in the transition probabilities from F0 to F3. The ICERs decrease with decreasing DAA prices, becoming cost-saving for the base price (€15,000) discounts of at least 75% applied in patients with F0-F2 fibrosis. Extending hepatitis C virus treatment to patients in any fibrosis stage improves health outcomes and is cost-effective; cost-effectiveness significantly increases

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

Effects of Taxing Sugar-Sweetened Beverages on Caries and Treatment Costs.

Science.gov (United States)

Schwendicke, F; Thomson, W M; Broadbent, J M; Stolpe, M

2016-11-01

Caries increment is affected by sugar-sweetened beverage (SSB) consumption. Taxing SSBs could reduce sugar consumption and caries increment. The authors aimed to estimate the impact of a 20% SSB sales tax on caries increment and associated treatment costs (as well as the resulting tax revenue) in the context of Germany. A model-based approach was taken, estimating the effects for the German population aged 14 to 79 y over a 10-y period. Taxation was assumed to affect beverage-associated sugar consumption via empirical demand elasticities. Altered consumption affected caries increments and treatment costs, with cost estimates being calculated under the perspective of the statutory health insurance. National representative consumption and price data were used to estimate tax revenue. Microsimulations were performed to estimate health outcomes, costs, and revenue impact in different age, sex, and income groups. Implementing a 20% SSB sales tax reduced sugar consumption in nearly all male groups but in fewer female groups. The reduction was larger among younger than older individuals and among those with low income. Taxation reduced caries increment and treatment costs especially in younger (rather than older) individuals and those with low income. Over 10 y, mean (SD) net caries increments at the population level were 82.27 (1.15) million and 83.02 (1.08) million teeth at 20% and 0% SSB tax, respectively. These generated treatment costs of 2.64 (0.39) billion and 2.72 (0.35) billion euro, respectively. Additional tax revenue was 37.99 (3.41) billion euro over the 10 y. In conclusion and within the limitations of this study's perspective, database, and underlying assumptions, implementing a 20% sales tax on SSBs is likely to reduce caries increment, especially in young low-income males, thereby also reducing inequalities in the distribution of caries experience. Taxation would also reduce treatment costs. However, these reductions might be limited in the total

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.

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

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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.

Health benefits, costs, and cost-effectiveness of earlier eligibility for adult antiretroviral therapy and expanded treatment coverage

DEFF Research Database (Denmark)

Eaton, Jeffrey W; Menzies, Nicolas A; Stover, John

2014-01-01

therapy accordingly. We aimed to assess the potential health benefits, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy and expanded treatment coverage. METHODS: We used several independent mathematical models in four settings-South Africa (generalised...... epidemic, moderate antiretroviral therapy coverage), Zambia (generalised epidemic, high antiretroviral therapy coverage), India (concentrated epidemic, moderate antiretroviral therapy coverage), and Vietnam (concentrated epidemic, low antiretroviral therapy coverage)-to assess the potential health benefits......, costs, and cost-effectiveness of various eligibility criteria for adult antiretroviral therapy under scenarios of existing and expanded treatment coverage, with results projected over 20 years. Analyses assessed the extension of eligibility to include individuals with CD4 counts of 500 cells per μ...

Assessment of cost of innovation versus the value of health gains associated with treatment of chronic hepatitis C in the United States: The quality-adjusted cost of care.

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Younossi, Zobair M; Park, Haesuk; Dieterich, Douglas; Saab, Sammy; Ahmed, Aijaz; Gordon, Stuart C

2016-10-01

New direct-acting antiviral (DAA) therapy has dramatically increased cure rates for patients infected with hepatitis C virus (HCV), but has also substantially raised treatment costs. The aim of this analysis was to evaluate the therapeutic benefit and net costs (i.e. efficiency frontier) and the quality-adjusted cost of care associated with the evolution of treatment regimens for patients with HCV genotype 1 in the United States. A decision-analytic Markov model. Published literature and clinical trial data. Life Time. Third-party payer. This study compared four approved regimens in treatment-naïve genotype 1 chronic hepatitis C patients, including pegylated interferon and ribavirin (PR), first generation triple therapy (boceprevir + PR and telaprevir + PR), second generation triple therapy (sofosbuvir + PR and simeprevir + PR) and all-oral DAA regimens (ledipasvir/sofosbuvir and ombitasvir + paritaprevir/ritonavir + dasabuvir ± ribavirin). Quality-adjusted cost of care (QACC). QACC was defined as the increase in treatment cost minus the increase in the patient's quality-adjusted life years (QALYs) when valued at $50,000 per QALY. All-oral therapy improved the average sustained virologic response (SVR) rate to 96%, thereby offsetting the high drug acquisition cost of $85,714, which resulted in the highest benefit based on the efficiency frontier. Furthermore, while oral therapies increased HCV drug costs by $48,350, associated QALY gains decreased quality-adjusted cost of care by $14,120 compared to dual therapy. When the value of a QALY was varied from $100,000 to $300,000, the quality adjusted cost of care compared to dual therapy ranged from - $21,234 to - $107,861, - $89,007 to - $293,130, - $176,280 to - $500,599 for first generation triple, second generation triple, and all-oral therapies, respectively. Primary efficacy and safety measurements for drug regimens were sourced from clinical trials data rather than a real

Low-dosage epoetin in maintenance haemodialysis: costs and quality-of-life improvement.

Science.gov (United States)

Harris, D C

1994-01-01

Decisions about epoetin (recombinant human erythropoetin) dosage and target haematocrit in dialysis patients have been determined largely by the high acquisition cost of epoetin, but are made with incomplete knowledge about which target haematocrit gives the optimum clinical benefit. Haematopoietic response to epoetin may be determined by pharmacodynamic factors such as rate and frequency of administration, as well as by individual patient characteristics such as ethnicity. Resistance to epoetin may be due to iron or vitamin deficiency, natural or exogenous inhibitors of erythropoiesis and bone marrow fibrosis. The high acquisition cost of epoetin must be considered along with a number of other factors that can influence the true cost of epoetin treatment. Hidden costs of epoetin treatment include administration costs, changes in other treatments, extra laboratory tests and adverse events. Administration costs and extra laboratory surveillance add little to overall cost. Depletion of iron stores, hypertension, increased blood coagulability and reduced dialyser efficiency resulting from epoetin treatment may all add a small additional component to the true cost. Severe complications with significant cost implications are rare. Amongst the various components of true cost, only the acquisition cost can definitely be reduced by low dosage treatment. Balanced against the true and potential costs of epoetin are a number of benefits which can result in potential savings. The need for blood transfusion is all but abolished, avoiding the cost of transfusion and its complications. Sensitisation against histocompatibility antigens is reduced by avoiding transfusion, and so the waiting time for cadaveric transplantation may be reduced. Rates of hospitalisation for all causes, especially those associated with anaemia, may be reduced by epoetin treatment. By improving well-being, epoetin may allow patients to be transferred to minimal-care units or home where dialysis can be

Cost-effectiveness of benign Wirsung duct strictures treatment in chronic pancreatitis.

Science.gov (United States)

Łaski, Dariusz; Hać, Stanisław; Marek, Iwona; Kobiela, Jarosław; Kostro, Justyna; Adrych, Krystian; Śledziński, Zbigniew

2018-03-01

Chronic pancreatitis (CP) is an important problem for modern medicine, the healthcare system (Poland - NFZ) and the national insurance system (Poland - ZUS). The chronic nature of the disease, the lack of targeted treatment and the low mortality rate lead to an accumulation of patients who demand expensive treatment, both conservative and invasive. Rising costs in health care are forcing the need for a more cost-effective method of treatment. The primary aim of this study was to perform a retrospective calculation of costs in both surgical and endoscopic treatment, hospital stay, healthcare, and public insurance of patients suffering from chronic pancreatitis. Parallel quality of life analysis was performed. It was possible to develop a cost-effective therapeutic algorithm for patients with an uncomplicated stricture of Wirsung's duct within the Polish health care system. In Poland, the hospital costs of endoscopic treatment of patients with chronic pancreatitis were higher than those of the surgical treatment group despite both resulting in a similar life quality. From a cost-effectiveness perspective, it was shown that surgical intervention is a more cost-effective therapy than endotherapy. Furthermore, patients with benign stricture of the main pancreatic duct in chronic pancreatitis should not be treated with endotherapy for longer than 12 months.

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.

Hot forming and quenching pilot process development for low cost and low environmental impact manufacturing.

Science.gov (United States)

Hall, Roger W.; Foster, Alistair; Herrmann Praturlon, Anja

2017-09-01

The Hot Forming and in-tool Quenching (HFQ®) process is a proven technique to enable complex shaped stampings to be manufactured from high strength aluminium. Its widespread uptake for high volume production will be maximised if it is able to wholly amortise the additional investment cost of this process compared to conventional deep drawing techniques. This paper discusses the use of three techniques to guide some of the development decisions taken during upscaling of the HFQ® process. Modelling of Process timing, Cost and Life-cycle impact were found to be effective tools to identify where development budget could be focused in order to be able to manufacture low cost panels of different sizes from many different alloys in a sustainable way. The results confirm that raw material cost, panel trimming, and artificial ageing were some of the highest contributing factors to final component cost. Additionally, heat treatment and lubricant removal stages played a significant role in the overall life-cycle assessment of the final products. These findings confirmed development priorities as novel furnace design, fast artificial ageing and low-cost alloy development.

A cost-effectiveness analysis of "test" versus "treat" patients hospitalized with suspected influenza in Hong Kong.

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Joyce H S You

Full Text Available BACKGROUND: Seasonal and 2009 H1N1 influenza viruses may cause severe diseases and result in excess hospitalization and mortality in the older and younger adults, respectively. Early antiviral treatment may improve clinical outcomes. We examined potential outcomes and costs of test-guided versus empirical treatment in patients hospitalized for suspected influenza in Hong Kong. METHODS: We designed a decision tree to simulate potential outcomes of four management strategies in adults hospitalized for severe respiratory infection suspected of influenza: "immunofluorescence-assay" (IFA or "polymerase-chain-reaction" (PCR-guided oseltamivir treatment, "empirical treatment plus PCR" and "empirical treatment alone". Model inputs were derived from literature. The average prevalence (11% of influenza in 2010-2011 (58% being 2009 H1N1 among cases of respiratory infections was used in the base-case analysis. Primary outcome simulated was cost per quality-adjusted life-year (QALY expected (ICER from the Hong Kong healthcare providers' perspective. RESULTS: In base-case analysis, "empirical treatment alone" was shown to be the most cost-effective strategy and dominated the other three options. Sensitivity analyses showed that "PCR-guided treatment" would dominate "empirical treatment alone" when the daily cost of oseltamivir exceeded USD18, or when influenza prevalence was <2.5% and the predominant circulating viruses were not 2009 H1N1. Using USD50,000 as the threshold of willingness-to-pay, "empirical treatment alone" and "PCR-guided treatment" were cost-effective 97% and 3% of time, respectively, in 10,000 Monte-Carlo simulations. CONCLUSIONS: During influenza epidemics, empirical antiviral treatment appears to be a cost-effective strategy in managing patients hospitalized with severe respiratory infection suspected of influenza, from the perspective of healthcare providers in Hong Kong.

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.

The Antiviral Effect of Baicalin on Enterovirus 71 In Vitro

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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.

Low cost technologies for the industrial waste water treatment; Tecnologia de tratamiento de aguas residuales industriales de bajo coste

Energy Technology Data Exchange (ETDEWEB)

NONE

1995-12-31

Nowadays, the industrialism is gradually becoming more and more concerned on the way of reducing the disposal of pollutant waste. As well, he demands solutions for this problem but he usually guests a great disparity of technologies and costs. This article presents three low cost systems for purification of industrial waste water which are suitable for numerous applications.

Low-Cost Alternative External Rotation Shoulder Brace and Review of Treatment in Acute Shoulder Dislocations

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Lacy, Kyle

2015-01-01

Full Text Available Traumatic dislocations of the shoulder commonly present to emergency departments (EDs. Immediate closed reduction of both anterior and posterior glenohumeral dislocations is recommended and is frequently performed in the ED. Recurrence of dislocation is common, as anteroinferior labral tears (Bankart lesions are present in many anterior shoulder dislocations.14,15,18,23 Immobilization of the shoulder following closed reduction is therefore recommended; previous studies support the use of immobilization with the shoulder in a position of external rotation, for both anterior and posterior shoulder dislocations.7-11,19 In this study, we present a technique for assembling a low-cost external rotation shoulder brace using materials found in most hospitals: cotton roll, stockinette, and shoulder immobilizers. This brace is particularly suited for the uninsured patient, who lacks the financial resources to pay for a pre-fabricated brace out of pocket. We also performed a cost analysis for our low-cost external rotation shoulder brace, and a cost comparison with pre-fabricated brand name braces. At our institution, the total materials cost for our brace was $19.15. The cost of a pre-fabricated shoulder brace at our institution is $150 with markup, which is reimbursed on average at $50.40 according to our hospital billing data. The low-cost external rotation shoulder brace is therefore a more affordable option for the uninsured patient presenting with acute shoulder dislocation. [West J Emerg Med. 2015;16(1:114–120.

Use and costs of prescription medications and alternative treatments in patients with osteoarthritis and chronic low back pain in community-based settings.

Science.gov (United States)

Gore, Mugdha; Tai, Kei-Sing; Sadosky, Alesia; Leslie, Douglas; Stacey, Brett R

2012-09-01

To evaluate the use and direct medical costs of pharmacologic and alternative treatments for patients with osteoarthritis (OA) and chronic low back pain (CLBP). The LifeLink™ Health Plan Claims Database was used to identify patients ≥18 years old, diagnosed with OA (N = 112,951) or CLBP (N = 101,294). Of these patients, 64,085 with OA and 47,386 with CLBP received pain-related treatments during CY2008 and were selected for inclusion. For patients in both cohorts, pharmacologic and alternative treatments, and direct medical costs were examined during CY2008. Opioids were the most frequently prescribed medication (>70%) in both groups, followed by nonselective nonsteroidal anti-inflammatory drugs (>50%). Over 30% received antidepressants, >20% received benzodiazepines, and 15% in each group received sedative hypnotics. Use of alternative treatments was as follows: chiropractor, OA 11%, CLBP 34%; physical therapy, 20% in both groups; transcutaneous electrical nerve stimulations (TENS), OA 14%, CLBP 22%; acupuncture, hydrotherapy, massage therapy, and biofeedback, patients were, OA: $15,638 ($22,595); CLBP: $11,829 ($20,035). Pharmacologic therapies accounted for approximately 20% of these costs, whereas alternative treatments accounted for only 3% to 4% of the total costs. Patients with OA and CLBP used a variety of pain-related and adjunctive medications. Although, alternative treatments are widely recommended, we found limited use of several of these in clinical practice, potentially due to the source of our data (commercial claims). Further research is needed to ascertain the extent to which such therapies contribute to the total costs of OA and CLBP management. © 2012 The Authors. Pain Practice © 2012 World Institute of Pain.

Antiviral activity of maca (Lepidium meyenii) against human influenza virus.

Science.gov (United States)

Del Valle Mendoza, Juana; Pumarola, Tomàs; Gonzales, Libertad Alzamora; Del Valle, Luis J

2014-09-01

To investigate antiviral activity of maca to reduce viral load in Madin-Darby canine kidney (MDCK) cells infected with influenza type A and B viruses (Flu-A and Flu-B, respectively). Maca were extracted with methanol (1:2, v/v). The cell viability and toxicity of the extracts were evaluated on MDCK cells using method MTT assay. Antiviral activity of compounds against Flu-A and Flu-B viruses was assayed using a test for determining the inhibition of the cytopathic effect on cell culture and multiplex RT-PCR. The methanol extract of maca showed low cytotoxicity and inhibited influenza-induced cytopathic effect significantly, while viral load was reduced via inhibition of viral growth in MDCK infected cells. Maca contains potent inhibitors of Flu-A and Flu-B with a selectivity index [cytotoxic concentration 50%/IC50] of 157.4 and 110.5, respectively. In vitro assays demonstrated that maca has antiviral activity not only against Flu-A (like most antiviral agents) but also Flu-B viruses, providing remarkable therapeutic benefits. Copyright © 2014 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

Antiviral Activity of Natural Products Extracted from Marine Organisms

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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.

Cost-effectiveness analysis of apixaban compared to low-molecularweight heparins and vitamin k antagonists for treatment and secondary prevention of venous thromboembolism

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Isabel Elías

2016-05-01

Full Text Available Objective: Cost-effectiveness analysis of a 6-month treatment of apixaban (10 mg/12h, first 7 days; 5 mg/12h afterwards for the treatment of the first event of venous thromboembolism (VTE and prevention of recurrences, versus low-molecular-weight heparins/vitamin K antagonists treatment (LMWH/VKA. Material and methods: A lifetime Markov model with 13 health states was used for describing the course of the disease. Efficacy and safety data were obtained from AMPLIFY and AMPLIFY-EXT clinical trials; health outcomes were measured as life years gained (LYG and quality-adjusted life years (QALY. The chosen perspective of this analysis has been the Spanish National Health System (NHS. Drugs, management of VTE and complications costs were obtained from several Spanish data sources (€, 2014. A 3% discount rate was applied to health outcomes and costs. Univariate and probabilistic sensitivity analyses (SA were performed in order to assess the robustness of the results. Results: Apixaban was the most effective therapy with 7.182 LYG and 5.865 QALY, versus 7.160 LYG and 5.838 QALYs with LMWH/VKA. Furthermore, apixaban had a lower total cost (€13,374.70 vs €13,738.30. Probabilistic SA confirmed dominance of apixaban (led to better health outcomes with less associated costs in 89% of the simulations. Conclusions: Apixaban 5 mg/12h versus LMWH/VKA was an efficient therapeutic strategy for the treatment and prevention of recurrences of VTE from the NHS perspective.

Application of a Low Cost Ceramic Filter for Recycling Sand Filter Backwash Water

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Md Shafiquzzaman

2018-02-01

Full Text Available The aim of this study is to examine the application of a low cost ceramic filter for the treatment of sand filter backwash water (SFBW. The treatment process is comprised of pre-coagulation of SFBW with aluminum sulfate (Alum followed by continuous filtration usinga low cost ceramic filter at different trans-membrane pressures (TMPs. Jar test results showed that 20 mg/L of alum is the optimum dose for maximum removal of turbidity, Fe, and Mn from SFBW. The filter can be operated at a TMP between 0.6 and 3 kPa as well as a corresponding flux of 480–2000 L/m2/d without any flux declination. Significant removal, up to 99%, was observed forturbidity, iron (Fe, and manganese (Mn. The flux started to decline at 4.5 kPa TMP (corresponding flux 3280 L/m2/d, thus indicated fouling of the filter. The complete pore blocking model was found as the most appropriate model to explain the insight mechanism of flux decline. The optimum operating pressure and the permeate flux were found to be 3 kPa and 2000 L/m2/d, respectively. Treated SFBW by a low cost ceramic filter was found to be suitable to recycle back to the water treatment plant. The ceramic filtration process would be a low cost and efficient option to recycle the SFBW.

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)

La respuesta inmune antiviral

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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

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

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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.

Integrated thermal and nonthermal treatment technology and subsystem cost sensitivity analysis

International Nuclear Information System (INIS)

Harvego, L.A.; Schafer, J.J.

1997-02-01

The U.S. Department of Energy's (DOE) Environmental Management Office of Science and Technology (EM-50) authorized studies on alternative systems for treating contact-handled DOE mixed low-level radioactive waste (MLLW). The on-going Integrated Thermal Treatment Systems' (ITTS) and the Integrated Nonthermal Treatment Systems' (INTS) studies satisfy this request. EM-50 further authorized supporting studies including this technology and subsystem cost sensitivity analysis. This analysis identifies areas where technology development could have the greatest impact on total life cycle system costs. These areas are determined by evaluating the sensitivity of system life cycle costs relative to changes in life cycle component or phase costs, subsystem costs, contingency allowance, facility capacity, operating life, and disposal costs. For all treatment systems, the most cost sensitive life cycle phase is the operations and maintenance phase and the most cost sensitive subsystem is the receiving and inspection/preparation subsystem. These conclusions were unchanged when the sensitivity analysis was repeated on a present value basis. Opportunity exists for technology development to reduce waste receiving and inspection/preparation costs by effectively minimizing labor costs, the major cost driver, within the maintenance and operations phase of the life cycle

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.

Primary treatments for clinically localised prostate cancer: a comprehensive lifetime cost-utility analysis.

Science.gov (United States)

Cooperberg, Matthew R; Ramakrishna, Naren R; Duff, Steven B; Hughes, Kathleen E; Sadownik, Sara; Smith, Joseph A; Tewari, Ashutosh K

2013-03-01

WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Multiple treatment alternatives exist for localised prostate cancer, with few high-quality studies directly comparing their comparative effectiveness and costs. The present study is the most comprehensive cost-effectiveness analysis to date for localised prostate cancer, conducted with a lifetime horizon and accounting for survival, health-related quality-of-life, and cost impact of secondary treatments and other downstream events, as well as primary treatment choices. The analysis found minor differences, generally slightly favouring surgical methods, in quality-adjusted life years across treatment options. However, radiation therapy (RT) was consistently more expensive than surgery, and some alternatives, e.g. intensity-modulated RT for low-risk disease, were dominated - that is, both more expensive and less effective than competing alternatives. To characterise the costs and outcomes associated with radical prostatectomy (open, laparoscopic, or robot-assisted) and radiation therapy (RT: dose-escalated three-dimensional conformal RT, intensity-modulated RT, brachytherapy, or combination), using a comprehensive, lifetime decision analytical model. A Markov model was constructed to follow hypothetical men with low-, intermediate-, and high-risk prostate cancer over their lifetimes after primary treatment; probabilities of outcomes were based on an exhaustive literature search yielding 232 unique publications. In each Markov cycle, patients could have remission, recurrence, salvage treatment, metastasis, death from prostate cancer, and death from other causes. Utilities for each health state were determined, and disutilities were applied for complications and toxicities of treatment. Costs were determined from the USA payer perspective, with incorporation of patient costs in a sensitivity analysis. Differences across treatments in quality-adjusted life years across methods were modest, ranging from 10.3 to

Efficacy and Safety of Direct Acting Antivirals in Kidney Transplant Recipients with Chronic Hepatitis C Virus Infection

OpenAIRE

Lin, Ming V.; Sise, Meghan E.; Pavlakis, Martha; Amundsen, Beth M.; Chute, Donald; Rutherford, Anna E.; Chung, Raymond T.; Curry, Michael P.; Hanifi, Jasmine M.; Gabardi, Steve; Chandraker, Anil; Heher, Eliot C.; Elias, Nahel; Riella, Leonardo V.

2016-01-01

The prevalence of Hepatitis C Virus (HCV) infection is significantly higher in patients with end-stage renal disease compared to the general population and poses important clinical challenges in patients who undergo kidney transplantation. Historically, interferon-based treatment options have been limited by low rates of efficacy and significant side effects, including risk of precipitating rejection. Limited data exist on the use of all-oral, interferon-free direct-acting antiviral (DAA) the...

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

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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.

Cost effectiveness of medical devices to diagnose pre-eclampsia in low-resource settings

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Zoë M. McLaren

Full Text Available Background: Maternal mortality remains a major health challenge facing developing countries, with pre-eclampsia accounting for up to 17% of maternal deaths. Diagnosis requires skilled health providers and devices that are appropriate for low-resource settings. This study presents the first cost-effectiveness analysis of multiple medical devices used to diagnose pre-eclampsia in low- and middle-income countries (LMICs. Methods: Blood pressure and proteinuria measurement devices, identified from compendia for LMICs, were included. We developed a decision tree framework to assess the cost-effectiveness of each device using parameter values that reflect the general standard of care based on a survey of relevant literature and expert opinion. We examined the sensitivity of our results using one-way and second-order probabilistic multivariate analyses. Results: Because the disability-adjusted life years (DALYs averted for each device were very similar, the results were influenced by the per-use cost ranking. The most cost-effective device combination was a semi-automatic blood pressure measurement device and visually read urine strip test with the lowest combined per-use cost of $0.2004 and an incremental cost effectiveness ratio of $93.6 per DALY gained relative to a baseline with no access to diagnostic devices. When access to treatment is limited, it is more cost-effective to improve access to treatment than to increase testing rates or diagnostic device sensitivity. Conclusions: Our findings were not sensitive to changes in device sensitivity, however they were sensitive to changes in the testing rate and treatment rate. Furthermore, our results suggest that simple devices are more cost-effective than complex devices. The results underscore the desirability of two design features for LMICs: ease of use and accuracy without calibration. Our findings have important implications for policy makers, health economists, health care providers and

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

Waste Management Facilities cost information for mixed low-level waste. Revision 1

International Nuclear Information System (INIS)

Shropshire, D.; Sherick, M.; Biadgi, C.

1995-06-01

This report contains preconceptual designs and planning level life-cycle cost estimates for managing mixed low-level waste. The report's information on treatment, storage, and disposal modules can be integrated to develop total life-cycle costs for various waste management options. A procedure to guide the US Department of Energy and its contractor personnel in the use of cost estimation data is also summarized in this report

Antiviral Drug Research Proposal Activity

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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.

Low cost solar air heater

International Nuclear Information System (INIS)

Gill, R.S.; Singh, Sukhmeet; Singh, Parm Pal

2012-01-01

Highlights: ► Single glazed low cost solar air heater is more efficient during summer while double glazed is better in winter. ► For the same initial investment, low cost solar air heaters collect more energy than packed bed solar air heater. ► During off season low cost solar air heater can be stored inside as it is light in weight. - Abstract: Two low cost solar air heaters viz. single glazed and double glazed were designed, fabricated and tested. Thermocole, ultraviolet stabilised plastic sheet, etc. were used for fabrication to reduce the fabrication cost. These were tested simultaneously at no load and with load both in summer and winter seasons along with packed bed solar air heater using iron chips for absorption of radiation. The initial costs of single glazed and double glazed are 22.8% and 26.8% of the initial cost of packed bed solar air heater of the same aperture area. It was found that on a given day at no load, the maximum stagnation temperatures of single glazed and double glazed solar air heater were 43.5 °C and 62.5 °C respectively. The efficiencies of single glazed, double glazed and packed bed solar air heaters corresponding to flow rate of 0.02 m 3 /s-m 2 were 30.29%, 45.05% and 71.68% respectively in winter season. The collector efficiency factor, heat removal factor based on air outlet temperature and air inlet temperature for three solar air heaters were also determined.

New Approaches for Quantitating the Inhibition of HIV-1 Replication by Antiviral Drugs in vitro and in vivo

Science.gov (United States)

McMahon, Moira A.; Shen, Lin; Siliciano, Robert F.

2014-01-01

Purpose of review With highly active anti-retroviral therapy (HAART), HIV-1 infection has become a manageable lifelong disease. Developing optimal treatment regimens requires understanding how to best measure anti-HIV activity in vitro and how drug dose response curves generated in vitro correlate with in vivo efficacy. Recent findings Several recent studies have indicated that conventional multi-round infectivity assays are inferior to single cycle assays at both low and high levels of inhibition. Multi-round infectivity assays can fail to detect subtle but clinically significant anti-HIV activity. The discoveries of the anti-HIV activity of the hepatitis B drug entecavir and the herpes simplex drug acyclovir were facilitated by single round infectivity assays. Recent studies using a single round infectivity assay have shown that a previously neglected parameter, the dose response curve slope, is an extremely important determinant of antiviral activity. Some antiretroviral drugs have steep slopes that result in extraordinary levels of antiviral activity. The instantaneous inhibitory potential (IIP), the log reduction in infectivity in a single round assay at clinical drug concentrations, has been proposed as a novel index for comparing antiviral activity. Summary Among in vitro measures of antiviral activity, single round infection assays have the advantage of measure instantaneous inhibition by a drug. Re-evaluating the antiviral activity of approved HIV-1 drugs has shown that the slope parameter is an important factor in drug activity. Determining the IIP by using a single round infectivity assay may provide important insights that can predict the in vivo efficacy of anti-HIV-1 drugs. PMID:19841584

An RNA polymerase II-driven Ebola virus minigenome system as an advanced tool for antiviral drug screening.

Science.gov (United States)

Nelson, Emily V; Pacheco, Jennifer R; Hume, Adam J; Cressey, Tessa N; Deflubé, Laure R; Ruedas, John B; Connor, John H; Ebihara, Hideki; Mühlberger, Elke

2017-10-01

Ebola virus (EBOV) causes a severe disease in humans with the potential for significant international public health consequences. Currently, treatments are limited to experimental vaccines and therapeutics. Therefore, research into prophylaxis and antiviral strategies to combat EBOV infections is of utmost importance. The requirement for high containment laboratories to study EBOV infection is a limiting factor for conducting EBOV research. To overcome this issue, minigenome systems have been used as valuable tools to study EBOV replication and transcription mechanisms and to screen for antiviral compounds at biosafety level 2. The most commonly used EBOV minigenome system relies on the ectopic expression of the T7 RNA polymerase (T7), which can be limiting for certain cell types. We have established an improved EBOV minigenome system that utilizes endogenous RNA polymerase II (pol II) as a driver for the synthesis of minigenome RNA. We show here that this system is as efficient as the T7-based minigenome system, but works in a wider range of cell types, including biologically relevant cell types such as bat cells. Importantly, we were also able to adapt this system to a reliable and cost-effective 96-well format antiviral screening assay with a Z-factor of 0.74, indicative of a robust assay. Using this format, we identified JG40, an inhibitor of Hsp70, as an inhibitor of EBOV replication, highlighting the potential for this system as a tool for antiviral drug screening. In summary, this updated EBOV minigenome system provides a convenient and effective means of advancing the field of EBOV research. Copyright © 2017 Elsevier B.V. All rights reserved.

Cost-effectiveness of exercise therapy in the treatment of non-specific neck pain and low back pain : a systematic review with meta-analysis

NARCIS (Netherlands)

Miyamoto, Gisela Cristiane; Lin, Chung-Wei Christine; Cabral, Cristina Maria Nunes; van Dongen, Johanna M; van Tulder, Maurits W

2018-01-01

OBJECTIVE: To investigate the cost-effectiveness of exercise therapy in the treatment of patients with non-specific neck pain and low back pain. DESIGN: Systematic review of economic evaluations. DATA SOURCES: The search was performed in 5 clinical and 3 economic electronic databases. ELIGIBILITY

A systematic review of the cost and cost effectiveness of treatment for multidrug-resistant tuberculosis.

Science.gov (United States)

Fitzpatrick, Christopher; Floyd, Katherine

2012-01-01

chosen (the extent to which hospitalization or ambulatory care were relied upon) and (ii) the second-line drugs included in the treatment regimen. When extrapolated to other settings, the best estimate of the cost of treatment varied from US3401 to US195 078, depending on the region and model of care. The cost per DALY averted was lower than GDP per capita in all 14 WHO sub-regions considered, with better cost effectiveness for outpatient versus inpatient models of care. Treatment for MDR-TB can be cost effective in low- and middle-income countries. Evidence about the relative cost effectiveness of outpatient versus inpatient models of care is limited and more data are needed from Africa and Asia--especially India and China, which have the largest number of cases. Unless there is strong evidence that hospitalization is necessary to achieve high rates of adherence to treatment, patients with MDR-TB should be treated using mainly ambulatory care.

Low-cost low-enthalpy geothermal heat for freshwater production: Innovative applications using thermal desalination processes

KAUST Repository

Bundschuh, Jochen; Ghaffour, NorEddine; Mahmoudi, Hacè ne; Goosen, Mattheus F A; Mushtaq, Shahbaz; Hoinkis, Jan

2015-01-01

The study is dedicated to exploring different types of low-cost low-enthalpy geothermal and their potential integration with conventional thermal-based water desalination and treatment technologies to deliver energy efficient, environmentally friendly solutions for water desalination and treatment, addressing global water crises. Our in-depth investigation through reviews of various low-enthalpy geothermal and conventional thermal-based technologies suggest that the geothermal option is superior to the solar option if low-cost geothermal heat is available because it provides a constant heat source in contrast to solar. Importantly, the stable heat source further allows up-scaling (> 1000 m3/day), which is not currently possible with solar. Solar-geothermal hybrid constellations may also be suitable in areas where both sources are available. The review also discovers that the innovative Membrane distillation (MD) process is very promising as it can be used for many different water compositions, salinity and temperature ranges. Either the geothermal water itself can be desalinated/treated or the geothermal heat can be used to heat feed water from other sources using heat exchangers. However, there are only few economic analyses for large-scale MD units and these are based on theoretical models using often uncertain assumptions resulting in a large variety of results.

Low-cost low-enthalpy geothermal heat for freshwater production: Innovative applications using thermal desalination processes

KAUST Repository

Bundschuh, Jochen

2015-03-01

The study is dedicated to exploring different types of low-cost low-enthalpy geothermal and their potential integration with conventional thermal-based water desalination and treatment technologies to deliver energy efficient, environmentally friendly solutions for water desalination and treatment, addressing global water crises. Our in-depth investigation through reviews of various low-enthalpy geothermal and conventional thermal-based technologies suggest that the geothermal option is superior to the solar option if low-cost geothermal heat is available because it provides a constant heat source in contrast to solar. Importantly, the stable heat source further allows up-scaling (> 1000 m3/day), which is not currently possible with solar. Solar-geothermal hybrid constellations may also be suitable in areas where both sources are available. The review also discovers that the innovative Membrane distillation (MD) process is very promising as it can be used for many different water compositions, salinity and temperature ranges. Either the geothermal water itself can be desalinated/treated or the geothermal heat can be used to heat feed water from other sources using heat exchangers. However, there are only few economic analyses for large-scale MD units and these are based on theoretical models using often uncertain assumptions resulting in a large variety of results.

The costs and cost-effectiveness of an integrated sepsis treatment protocol.

Science.gov (United States)

Talmor, Daniel; Greenberg, Dan; Howell, Michael D; Lisbon, Alan; Novack, Victor; Shapiro, Nathan

2008-04-01

Sepsis is associated with high mortality and treatment costs. International guidelines recommend the implementation of integrated sepsis protocols; however, the true cost and cost-effectiveness of these are unknown. To assess the cost-effectiveness of an integrated sepsis protocol, as compared with conventional care. Prospective cohort study of consecutive patients presenting with septic shock and enrolled in the institution's integrated sepsis protocol. Clinical and economic outcomes were compared with a historical control cohort. Beth Israel Deaconess Medical Center. Overall, 79 patients presenting to the emergency department with septic shock in the treatment cohort and 51 patients in the control group. An integrated sepsis treatment protocol incorporating empirical antibiotics, early goal-directed therapy, intensive insulin therapy, lung-protective ventilation, and consideration for drotrecogin alfa and steroid therapy. In-hospital treatment costs were collected using the hospital's detailed accounting system. The cost-effectiveness analysis was performed from the perspective of the healthcare system using a lifetime horizon. The primary end point for the cost-effectiveness analysis was the incremental cost per quality-adjusted life year gained. Mortality in the treatment group was 20.3% vs. 29.4% in the control group (p = .23). Implementing an integrated sepsis protocol resulted in a mean increase in cost of approximately $8,800 per patient, largely driven by increased intensive care unit length of stay. Life expectancy and quality-adjusted life years were higher in the treatment group; 0.78 and 0.54, respectively. The protocol was associated with an incremental cost of $11,274 per life-year saved and a cost of $16,309 per quality-adjusted life year gained. In patients with septic shock, an integrated sepsis protocol, although not cost-saving, appears to be cost-effective and compares very favorably to other commonly delivered acute care interventions.

Waste Management Facilities cost information for mixed low-level waste. Revision 1

Energy Technology Data Exchange (ETDEWEB)

Shropshire, D.; Sherick, M.; Biadgi, C.

1995-06-01

This report contains preconceptual designs and planning level life-cycle cost estimates for managing mixed low-level waste. The report`s information on treatment, storage, and disposal modules can be integrated to develop total life-cycle costs for various waste management options. A procedure to guide the US Department of Energy and its contractor personnel in the use of cost estimation data is also summarized in this report.

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 ...

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

EVALUATION OF EFFECTIVENESS OF ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C, CAUSED BY HCV GENOTYPE 6

Directory of Open Access Journals (Sweden)

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.

A human genome-wide loss-of-function screen identifies effective chikungunya antiviral drugs.

Science.gov (United States)

Karlas, Alexander; Berre, Stefano; Couderc, Thérèse; Varjak, Margus; Braun, Peter; Meyer, Michael; Gangneux, Nicolas; Karo-Astover, Liis; Weege, Friderike; Raftery, Martin; Schönrich, Günther; Klemm, Uwe; Wurzlbauer, Anne; Bracher, Franz; Merits, Andres; Meyer, Thomas F; Lecuit, Marc

2016-05-12

Chikungunya virus (CHIKV) is a globally spreading alphavirus against which there is no commercially available vaccine or therapy. Here we use a genome-wide siRNA screen to identify 156 proviral and 41 antiviral host factors affecting CHIKV replication. We analyse the cellular pathways in which human proviral genes are involved and identify druggable targets. Twenty-one small-molecule inhibitors, some of which are FDA approved, targeting six proviral factors or pathways, have high antiviral activity in vitro, with low toxicity. Three identified inhibitors have prophylactic antiviral effects in mouse models of chikungunya infection. Two of them, the calmodulin inhibitor pimozide and the fatty acid synthesis inhibitor TOFA, have a therapeutic effect in vivo when combined. These results demonstrate the value of loss-of-function screening and pathway analysis for the rational identification of small molecules with therapeutic potential and pave the way for the development of new, host-directed, antiviral agents.

The Cost and Cost-Effectiveness of Scaling up Screening and Treatment of Syphilis in Pregnancy: A Model

Science.gov (United States)

Kahn, James G.; Jiwani, Aliya; Gomez, Gabriela B.; Hawkes, Sarah J.; Chesson, Harrell W.; Broutet, Nathalie; Kamb, Mary L.; Newman, Lori M.

2014-01-01

Background Syphilis in pregnancy imposes a significant global health and economic burden. More than half of cases result in serious adverse events, including infant mortality and infection. The annual global burden from mother-to-child transmission (MTCT) of syphilis is estimated at 3.6 million disability-adjusted life years (DALYs) and $309 million in medical costs. Syphilis screening and treatment is simple, effective, and affordable, yet, worldwide, most pregnant women do not receive these services. We assessed cost-effectiveness of scaling-up syphilis screening and treatment in existing antenatal care (ANC) programs in various programmatic, epidemiologic, and economic contexts. Methods and Findings We modeled the cost, health impact, and cost-effectiveness of expanded syphilis screening and treatment in ANC, compared to current services, for 1,000,000 pregnancies per year over four years. We defined eight generic country scenarios by systematically varying three factors: current maternal syphilis testing and treatment coverage, syphilis prevalence in pregnant women, and the cost of healthcare. We calculated program and net costs, DALYs averted, and net costs per DALY averted over four years in each scenario. Program costs are estimated at $4,142,287 – $8,235,796 per million pregnant women (2010 USD). Net costs, adjusted for averted medical care and current services, range from net savings of $12,261,250 to net costs of $1,736,807. The program averts an estimated 5,754 – 93,484 DALYs, yielding net savings in four scenarios, and a cost per DALY averted of $24 – $111 in the four scenarios with net costs. Results were robust in sensitivity analyses. Conclusions Eliminating MTCT of syphilis through expanded screening and treatment in ANC is likely to be highly cost-effective by WHO-defined thresholds in a wide range of settings. Countries with high prevalence, low current service coverage, and high healthcare cost would benefit most. Future analyses can be

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.

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. 

A cost-benefit analysis of a proposed overseas refugee latent tuberculosis infection screening and treatment program.

Science.gov (United States)

Wingate, La'Marcus T; Coleman, Margaret S; de la Motte Hurst, Christopher; Semple, Marie; Zhou, Weigong; Cetron, Martin S; Painter, John A

2015-12-01

This study explored the effect of screening and treatment of refugees for latent tuberculosis infection (LTBI) before entrance to the United States as a strategy for reducing active tuberculosis (TB). The purpose of this study was to estimate the costs and benefits of LTBI screening and treatment in United States bound refugees prior to arrival. Costs were included for foreign and domestic LTBI screening and treatment and the domestic treatment of active TB. A decision tree with multiple Markov nodes was developed to determine the total costs and number of active TB cases that occurred in refugee populations that tested 55, 35, and 20 % tuberculin skin test positive under two models: no overseas LTBI screening and overseas LTBI screening and treatment. For this analysis, refugees that tested 55, 35, and 20 % tuberculin skin test positive were divided into high, moderate, and low LTBI prevalence categories to denote their prevalence of LTBI relative to other refugee populations. For a hypothetical 1-year cohort of 100,000 refugees arriving in the United States from regions with high, moderate, and low LTBI prevalence, implementation of overseas screening would be expected to prevent 440, 220, and 57 active TB cases in the United States during the first 20 years after arrival. The cost savings associated with treatment of these averted cases would offset the cost of LTBI screening and treatment for refugees from countries with high (net cost-saving: $4.9 million) and moderate (net cost-saving: $1.6 million) LTBI prevalence. For low LTBI prevalence populations, LTBI screening and treatment exceed expected future TB treatment cost savings (net cost of $780,000). Implementing LTBI screening and treatment for United States bound refugees from countries with high or moderate LTBI prevalence would potentially save millions of dollars and contribute to United States TB elimination goals. These estimates are conservative since secondary transmission from tuberculosis cases

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.

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.

Low energy, low cost, efficient CO{sub 2} capture

Energy Technology Data Exchange (ETDEWEB)

Michael C. Trachtenberg; Lihong Bao; David A. Smith; Remy Dumortier [Carbozyme, Inc., Monmouth Junction, NJ (United States)

2006-07-01

This paper discusses the development and some characteristics of a new, enzyme-based, contained liquid membrane contactor to capture CO{sub 2}. The enzyme carbonic anhydrase catalyzes the removal of CO{sub 2} while the membrane contactor increases the surface area to allow the reduction of the size of the system. The modular system design is easily scaled to any required size reducing the investment costs. The system captures CO{sub 2} at a low energy and low cost promising to be a cost effective technology for CO{sub 2} capture. 5 refs., 7 figs.

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.

Cost Effective Recovery of Low-TDS Frac Flowback Water for Re-use

Energy Technology Data Exchange (ETDEWEB)

Claire Henderson; Harish Acharya; Hope Matis; Hareesh Kommepalli; Brian Moore; Hua Wang

2011-03-31

The project goal was to develop a cost-effective water recovery process to reduce the costs and envi-ronmental impact of shale gas production. This effort sought to develop both a flowback water pre-treatment process and a membrane-based partial demineralization process for the treatment of the low-Total Dissolved Solids (TDS) portion of the flowback water produced during hydrofracturing operations. The TDS cutoff for consideration in this project is < 35,000 {approx} 45,000 ppm, which is the typical limit for economic water recovery employing reverse osmosis (RO) type membrane desalination processes. The ultimate objective is the production of clean, reclaimed water suitable for re-use in hydrofracturing operations. The team successfully compiled data on flowback composition and other attributes across multiple shale plays, identified the likely applicability of membrane treatment processes in those shales, and expanded the proposed product portfolio to include four options suitable for various reuse or discharge applications. Pretreatment technologies were evaluated at the lab scale and down-selected based upon their efficacy in removing key contaminants. The chosen technologies were further validated by performing membrane fouling studies with treated flowback water to demonstrate the technical feasibility of flowback treatment with RO membranes. Process flow schemes were constructed for each of the four product options based on experimental performance data from actual flowback water treatment studies. For the products requiring membrane treatment, membrane system model-ing software was used to create designs for enhanced water recovery beyond the typical seawater desalination benchmark. System costs based upon vendor and internal cost information for all process flow schemes were generated and are below target and in line with customer expectations. Finally, to account for temporal and geographic variability in flowback characteristics as well as local

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.

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 ...

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)

Efficacy of a low-cost bubble CPAP system in treatment of respiratory distress in a neonatal ward in Malawi.

Directory of Open Access Journals (Sweden)

Kondwani Kawaza

Full Text Available Respiratory failure is a leading cause of neonatal mortality in the developing world. Bubble continuous positive airway pressure (bCPAP is a safe, effective intervention for infants with respiratory distress and is widely used in developed countries. Because of its high cost, bCPAP is not widely utilized in low-resource settings. We evaluated the performance of a new bCPAP system to treat severe respiratory distress in a low resource setting, comparing it to nasal oxygen therapy, the current standard of care.We conducted a non-randomized convenience sample study to test the efficacy of a low-cost bCPAP system treating newborns with severe respiratory distress in the neonatal ward of Queen Elizabeth Central Hospital, in Blantyre, Malawi. Neonates weighing >1,000 g and presenting with severe respiratory distress who fulfilled inclusion criteria received nasal bCPAP if a device was available; if not, they received standard care. Clinical assessments were made during treatment and outcomes compared for the two groups.87 neonates (62 bCPAP, 25 controls were recruited. Survival rate for neonates receiving bCPAP was 71.0% (44/62 compared with 44.0% (11/25 for controls. 65.5% (19/29 of very low birth weight neonates receiving bCPAP survived to discharge compared to 15.4% (1/13 of controls. 64.6% (31/48 of neonates with respiratory distress syndrome (RDS receiving bCPAP survived to discharge, compared to 23.5% (4/17 of controls. 61.5% (16/26 of neonates with sepsis receiving bCPAP survived to discharge, while none of the seven neonates with sepsis in the control group survived.Use of a low-cost bCPAP system to treat neonatal respiratory distress resulted in 27% absolute improvement in survival. The beneficial effect was greater for neonates with very low birth weight, RDS, or sepsis. Implementing appropriate bCPAP devices could reduce neonatal mortality in developing countries.

Efficacy of a low-cost bubble CPAP system in treatment of respiratory distress in a neonatal ward in Malawi.

Science.gov (United States)

Kawaza, Kondwani; Machen, Heather E; Brown, Jocelyn; Mwanza, Zondiwe; Iniguez, Suzanne; Gest, Al; Smith, E O'Brian; Oden, Maria; Richards-Kortum, Rebecca R; Molyneux, Elizabeth

2014-01-01

Respiratory failure is a leading cause of neonatal mortality in the developing world. Bubble continuous positive airway pressure (bCPAP) is a safe, effective intervention for infants with respiratory distress and is widely used in developed countries. Because of its high cost, bCPAP is not widely utilized in low-resource settings. We evaluated the performance of a new bCPAP system to treat severe respiratory distress in a low resource setting, comparing it to nasal oxygen therapy, the current standard of care. We conducted a non-randomized convenience sample study to test the efficacy of a low-cost bCPAP system treating newborns with severe respiratory distress in the neonatal ward of Queen Elizabeth Central Hospital, in Blantyre, Malawi. Neonates weighing >1,000 g and presenting with severe respiratory distress who fulfilled inclusion criteria received nasal bCPAP if a device was available; if not, they received standard care. Clinical assessments were made during treatment and outcomes compared for the two groups. 87 neonates (62 bCPAP, 25 controls) were recruited. Survival rate for neonates receiving bCPAP was 71.0% (44/62) compared with 44.0% (11/25) for controls. 65.5% (19/29) of very low birth weight neonates receiving bCPAP survived to discharge compared to 15.4% (1/13) of controls. 64.6% (31/48) of neonates with respiratory distress syndrome (RDS) receiving bCPAP survived to discharge, compared to 23.5% (4/17) of controls. 61.5% (16/26) of neonates with sepsis receiving bCPAP survived to discharge, while none of the seven neonates with sepsis in the control group survived. Use of a low-cost bCPAP system to treat neonatal respiratory distress resulted in 27% absolute improvement in survival. The beneficial effect was greater for neonates with very low birth weight, RDS, or sepsis. Implementing appropriate bCPAP devices could reduce neonatal mortality in developing countries.

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.

Antiviral Activity of Novel Quinoline Derivatives against Dengue Virus Serotype 2

Directory of Open Access Journals (Sweden)

Carolina de la Guardia

2018-03-01

Full Text Available Dengue virus causes dengue fever, a debilitating disease with an increasing incidence in many tropical and subtropical territories. So far, there are no effective antivirals licensed to treat this virus. Here we describe the synthesis and antiviral activity evaluation of two compounds based on the quinoline scaffold, which has shown potential for the development of molecules with various biological activities. Two of the tested compounds showed dose-dependent inhibition of dengue virus serotype 2 in the low and sub micromolar range. The compounds 1 and 2 were also able to impair the accumulation of the viral envelope glycoprotein in infected cells, while showing no sign of direct virucidal activity and acting possibly through a mechanism involving the early stages of the infection. The results are congruent with previously reported data showing the potential of quinoline derivatives as a promising scaffold for the development of new antivirals against this important virus.

Low-cost carriers fare competition effect

NARCIS (Netherlands)

Carmona Benitez, R.B.; Lodewijks, G.

2010-01-01

This paper examines the effects that low-cost carriers (LCC’s) produce when entering new routes operated only by full-service carriers (FSC’s) and routes operated by low-cost carriers in competition with full-service carriers. A mathematical model has been developed to determine what routes should

Low-Cost Spectral Sensor Development Description.

Energy Technology Data Exchange (ETDEWEB)

Armijo, Kenneth Miguel; Yellowhair, Julius

2014-11-01

Solar spectral data for all parts of the US is limited due in part to the high cost of commercial spectrometers. Solar spectral information is necessary for accurate photovoltaic (PV) performance forecasting, especially for large utility-scale PV installations. A low-cost solar spectral sensor would address the obstacles and needs. In this report, a novel low-cost, discrete- band sensor device, comprised of five narrow-band sensors, is described. The hardware is comprised of commercial-off-the-shelf components to keep the cost low. Data processing algorithms were developed and are being refined for robustness. PV module short-circuit current ( I sc ) prediction methods were developed based on interaction-terms regression methodology and spectrum reconstruction methodology for computing I sc . The results suggest the computed spectrum using the reconstruction method agreed well with the measured spectrum from the wide-band spectrometer (RMS error of 38.2 W/m 2 -nm). Further analysis of computed I sc found a close correspondence of 0.05 A RMS error. The goal is for ubiquitous adoption of the low-cost spectral sensor in solar PV and other applications such as weather forecasting.

Wastewater treatment using low cost activated carbons derived from agricultural byproducts-A case study

Energy Technology Data Exchange (ETDEWEB)

Mohan, Dinesh [Environmental Chemistry Division, Industrial Toxicology Research Centre, Post Box No. 80, Mahatma Gandhi Marg, Lucknow 226001, U.P. (India)], E-mail: dm_1967@hotmail.com; Singh, Kunwar P.; Singh, Vinod K. [Environmental Chemistry Division, Industrial Toxicology Research Centre, Post Box No. 80, Mahatma Gandhi Marg, Lucknow 226001, U.P. (India)

2008-04-15

A variety of low cost activated carbons were developed from agricultural waste materials viz., coconut shell, coconut shell fibers and rice husk. The low cost activated carbons were fully characterized and utilized for the remediation of various pollutants viz., chemical oxygen demand (COD), heavy metals, anions, etc., from industrial wastewater. Sorption studies were carried out at different temperatures and particle sizes to study the effect of temperatures and surface areas. The removal of chloride and fluoride increased with rise in temperature while COD and metal ions removal decreased with increase in temperature, thereby, indicating the processes to be endothermic and exothermic, respectively. The kinetics of COD adsorption was also carried out at different temperatures to establish the sorption mechanism and to determine various kinetic parameters. The COD removal was 47-72% by coconut shell fiber carbon (ATFAC), 50-74% by coconut shell carbon (ATSAC) and 45-73% by rice husk carbon (ATRHC). Furthermore, COD removal kinetics by rice husk carbon, coconut shell carbon and coconut fiber carbon at different temperatures was approximately represented by a first order rate law. Results of this fundamental study demonstrate the effectiveness and feasibility of low cost activated carbons. The parameters obtained in this study can be fully utilized to establish fixed bed reactors on large scale to treat the contaminated water.

Wastewater treatment using low cost activated carbons derived from agricultural byproducts-A case study

International Nuclear Information System (INIS)

Mohan, Dinesh; Singh, Kunwar P.; Singh, Vinod K.

2008-01-01

A variety of low cost activated carbons were developed from agricultural waste materials viz., coconut shell, coconut shell fibers and rice husk. The low cost activated carbons were fully characterized and utilized for the remediation of various pollutants viz., chemical oxygen demand (COD), heavy metals, anions, etc., from industrial wastewater. Sorption studies were carried out at different temperatures and particle sizes to study the effect of temperatures and surface areas. The removal of chloride and fluoride increased with rise in temperature while COD and metal ions removal decreased with increase in temperature, thereby, indicating the processes to be endothermic and exothermic, respectively. The kinetics of COD adsorption was also carried out at different temperatures to establish the sorption mechanism and to determine various kinetic parameters. The COD removal was 47-72% by coconut shell fiber carbon (ATFAC), 50-74% by coconut shell carbon (ATSAC) and 45-73% by rice husk carbon (ATRHC). Furthermore, COD removal kinetics by rice husk carbon, coconut shell carbon and coconut fiber carbon at different temperatures was approximately represented by a first order rate law. Results of this fundamental study demonstrate the effectiveness and feasibility of low cost activated carbons. The parameters obtained in this study can be fully utilized to establish fixed bed reactors on large scale to treat the contaminated water

Viral-specific T-cell transfer from HSCT donor for the treatment of viral infections or diseases after HSCT.

Science.gov (United States)

Qian, C; Wang, Y; Reppel, L; D'aveni, M; Campidelli, A; Decot, V; Bensoussan, D

2018-02-01

Allogeneic hematopoietic stem cell transplantation (HSCT) is a curative option for treatment of some malignant and non-malignant hematological diseases. However, post-HSCT patients are severely immunocompromised and susceptible to viral infections, which are a major cause of morbidity and mortality. Although antiviral agents are now available for most types of viral infections, they are not devoid of side effects and their efficacy is limited when there is no concomitant antiviral immune reconstitution. In recent decades, adoptive transfer of viral-specific T cells (VSTs) became an alternative treatment for viral infection after HSCT. However, two major issues are concerned in VST transfer: the risk of GVHD and antiviral efficacy. We report an exhaustive review of the published studies that focus on prophylactic and/or curative therapy by donor VST transfer for post-HSCT common viral infections. A low incidence of GVHD and a good antiviral efficacy was observed after adoptive transfer of VSTs from HSCT donor. Viral-specific T-cell transfer is a promising approach for a broad clinical application. Nevertheless, a randomized controlled study in a large cohort of patients comparing antiviral treatment alone to antiviral treatment combined with VSTs is still needed to demonstrate efficacy and safety.

Economic aspects of complicated osteoporosis: The cost of treatment in the first year after fracture

Directory of Open Access Journals (Sweden)

O. V. Dobrovolskaya

2016-01-01

Full Text Available Objective: to estimate the cost of treatment in patients with complicated osteoporosis (OP in the first year after fracture under the conditions of the Moscow municipal healthcare system.Patients and methods. The investigation enrolled 196 women (mean age, 65.8±9.1 years who had sustained fractures at five major osteoporotic sites (proximal hip (PH, distal forearm (DF, surgical humeral neck, vertebral column, and medial and/or lateral ankle. A unified questionnaire that included data on inpatient and outpatient treatment, patients' personal costs, and social benefits, as well as tariffs on services of the Moscow City Fund of Obligatory Health Insurance was used to estimate the cost of treatment for complicated OP during one year after fracture.Results. The direct cost of treatment for PH fracture amounted to 101,243 rubles and was significantly higher (p < 0.01 than that for fractures at other sites: DF (22,080 rubles; humeral neck (39,855 rubles, vertebral column (51,167 rubles, and ankle (43,345 rubles. The average cost of treatment in terms of indirect costs of treatment for complicated OP during a year was as high as 61,151 rubles. In the overall cost structure for the disease, hospital costs accounted for 44%; social benefits were 12% and the cost of antiosteoporotic drugs was only 7%, which was associated with the fact that the latter were rarely prescribed by primary healthcare physicians.Conclusion. Costs of treatment in patients with complicated OP in Moscow were estimated in relation to the site of low-energy fracture. The disease was shown to cause considerable economic losses regardless of the site of osteoporotic fracture; however, the cost of antiosteoporotic drugs has an insignificant share in the overall cost structure for treatment. At the same time, secondary prevention of OP requires that combination antiosteoporotic therapy should be performed in all patients who have sustained low-energy fracture.

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.

Antiviral activity of human lactoferrin: inhibition of alphavirus interaction with heparan sulfate

International Nuclear Information System (INIS)

Waarts, Barry-Lee; Aneke, Onwuchekwa J.C.; Smit, Jolanda M.; Kimata, Koji; Bittman, Robert; Meijer, Dirk K.F.; Wilschut, Jan

2005-01-01

Human lactoferrin is a component of the non-specific immune system with distinct antiviral properties. We used alphaviruses, adapted to interaction with heparan sulfate (HS), as a tool to investigate the mechanism of lactoferrin's antiviral activity. Lactoferrin inhibited infection of BHK-21 cells by HS-adapted, but not by non-adapted, Sindbis virus (SIN) or Semliki Forest virus (SFV). Lactoferrin also inhibited binding of radiolabeled HS-adapted viruses to BHK-21 cells or liposomes containing lipid-conjugated heparin as a receptor analog. On the other hand, low-pH-induced fusion of the viruses with liposomes, which occurs independently of virus-receptor interaction, was unaffected. Studies involving preincubation of virus or cells with lactoferrin suggested that the protein does not bind to the virus, but rather blocks HS-moieties on the cell surface. Charge-modified human serum albumin, with a net positive charge, had a similar antiviral effect against HS-adapted SIN and SFV, suggesting that the antiviral activity of lactoferrin is related to its positive charge. It is concluded that human lactoferrin inhibits viral infection by interfering with virus-receptor interaction rather than by affecting subsequent steps in the viral cell entry or replication processes

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.

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.

Impact of generic alendronate cost on the cost-effectiveness of osteoporosis screening and treatment.

Directory of Open Access Journals (Sweden)

Smita Nayak

Full Text Available Since alendronate became available in generic form in the Unites States in 2008, its price has been decreasing. The objective of this study was to investigate the impact of alendronate cost on the cost-effectiveness of osteoporosis screening and treatment in postmenopausal women.Microsimulation cost-effectiveness model of osteoporosis screening and treatment for U.S. women age 65 and older. We assumed screening initiation at age 65 with central dual-energy x-ray absorptiometry (DXA, and alendronate treatment for individuals with osteoporosis; with a comparator of "no screening" and treatment only after fracture occurrence. We evaluated annual alendronate costs of $20 through $800; outcome measures included fractures; nursing home admission; medication adverse events; death; costs; quality-adjusted life-years (QALYs; and incremental cost-effectiveness ratios (ICERs in 2010 U.S. dollars per QALY gained. A lifetime time horizon was used, and direct costs were included. Base-case and sensitivity analyses were performed.Base-case analysis results showed that at annual alendronate costs of $200 or less, osteoporosis screening followed by treatment was cost-saving, resulting in lower total costs than no screening as well as more QALYs (10.6 additional quality-adjusted life-days. When assuming alendronate costs of $400 through $800, screening and treatment resulted in greater lifetime costs than no screening but was highly cost-effective, with ICERs ranging from $714 per QALY gained through $13,902 per QALY gained. Probabilistic sensitivity analyses revealed that the cost-effectiveness of osteoporosis screening followed by alendronate treatment was robust to joint input parameter estimate variation at a willingness-to-pay threshold of $50,000/QALY at all alendronate costs evaluated.Osteoporosis screening followed by alendronate treatment is effective and highly cost-effective for postmenopausal women across a range of alendronate costs, and may be cost

Factors influencing the cost of prosthetic joint infection treatment.

Science.gov (United States)

Peel, T N; Cheng, A C; Lorenzo, Y P; Kong, D C M; Buising, K L; Choong, P F M

2013-11-01

Prosthetic joint infection (PJI) is associated with significant costs to the healthcare system. Current literature examines the cost of specific treatment modalities without assessing other cost drivers for PJI. To examine the overall cost of the treatment of PJI and to identify factors associated with management costs. The costs of treatment of prosthetic joint infections were examined in 139 patients across 10 hospitals over a 3-year period (January 2006 to December 2008). Cost calculations included hospitalization costs, surgical costs, hospital-in-the-home costs and antibiotic therapy costs. Negative binomial regression analysis was performed to model factors associated with total cost. The median cost of treating prosthetic joint infection per patient was Australian $34,800 (interquartile range: 20,305, 56,929). The following factors were associated with increased treatment costs: septic revision arthroplasty (67% increase in treatment cost; P = 0.02), hypotension at presentation (70% increase; P = 0.03), polymicrobial infections (41% increase; P = 0.009), surgical treatment with one-stage exchange (100% increase; P = 0.002) or resection arthroplasty (48% increase; P = 0.001) were independently associated with increased treatment costs. Culture-negative prosthetic joint infections were associated with decreased costs (29% decrease in treatment cost; P = 0.047). Treatment failure was associated with 156% increase in treatment costs. This study identifies clinically important factors influencing treatment costs that may be of relevance to policy-makers, particularly in the setting of hospital reimbursement and guiding future research into cost-effective preventive strategies. Copyright © 2013 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Comparison of low-cost and engineered materials for phosphorus removal from organic-rich surface water.

Science.gov (United States)

Boyer, Treavor H; Persaud, Amar; Banerjee, Poulomi; Palomino, Pedro

2011-10-15

Excess phosphorus (P) in lakes and rivers remains a major water quality problem on a global scale. As a result, new materials and innovative approaches to P remediation are required. Natural materials and waste byproduct materials from industrial processes have the potential to be effective materials for P removal from surface water. Advantages of natural and waste byproduct materials include their low-cost, abundant supply, and minimal preparation, especially compared with engineered materials, such as ion exchange resins and polymeric adsorbents. As a result, natural and waste byproduct materials are commonly referred to as low-cost materials. Despite the potential advantages of low-cost materials, there are critical gaps in knowledge that are preventing their effective use. In particular, there are limited data on the performance of low-cost materials in surface waters that have high concentrations of natural organic matter (NOM), and there are no systematic studies that track the changes in water chemistry following treatment with low-cost materials or compare their performance with engineered materials. Accordingly, the goal of this work was to evaluate and compare the effectiveness of low-cost and engineered materials for P removal from NOM-rich surface water. Seven low-cost materials and three engineered materials were evaluated using jar tests and mini-column experiments. The test water was a surface water that had a total P concentration of 132-250 μg P/L and a total organic carbon concentration of 15-32 mg C/L. Alum sludge, a byproduct of drinking water treatment, and a hybrid anion exchange resin loaded with nanosize iron oxide were the best performing materials in terms of selective P removal in the presence of NOM and minimum undesirable secondary changes to the water chemistry. Copyright © 2011 Elsevier Ltd. All rights reserved.

Identification of groups with poor cost-effectiveness of peginterferon plus ribavirin for naïve hepatitis C patients with a real-world cohort and database.

Science.gov (United States)

Tsai, Pei-Chien; Liu, Ta-Wei; Tsai, Yi-Shan; Ko, Yu-Min; Chen, Kuan-Yu; Lin, Ching-Chih; Huang, Ching-I; Liang, Po-Cheng; Lin, Yi-Hung; Hsieh, Ming-Yen; Hou, Nai-Jen; Huang, Chung-Feng; Yeh, Ming-Lun; Lin, Zu-Yau; Chen, Shinn-Cherng; Dai, Chia-Yen; Chuang, Wan-Long; Huang, Jee-Fu; Yu, Ming-Lung

2017-06-01

For decades, peginterferon and ribavirin (PegIFN/RBV) have been the standard-of-care for chronic hepatitis C virus (CHC) infection. However, the actual cost-effectiveness of this therapy remains unclear. We purposed to explore the real-world cost effectiveness for subgroups of treatment-naïve CHC patients with PegIFN/RBV therapy in a large real-world cohort using a whole population database. A total of 1809 treatment-naïve chronic hepatitis C virus (HCV) patients (829 HCV genotype 1 [G1] and 980 HCV G2) treated with PegIFN/RBV therapies were linked to the National Health Insurance Research Database, covering the entire population of Taiwan from 1998 to 2013 to collect the total medical-care expenses of outpatient (antiviral agents, nonantiviral agents, laboratory, and consultation costs) and inpatient (medication, logistic, laboratory, and intervention costs) visits. The costs per treatment and the cost per sustained virological response (SVR) achieved were calculated. The average medical-care cost was USD $4823 (±$2984) per treatment and $6105 (±$3778) per SVR achieved. With SVR rates of 68.6% and 87.8%, the cost/SVR was significantly higher in G1 than those in G2 patients, respectively ($8285 vs $4663, P incurred significantly higher costs per SVR than their counterparts. The cost/SVR was extremely high among patients without RVR and in patients without cEVR. We investigated the real-world cost effectiveness data for different subgroups of treatment-naïve HCV patients with PegIFN/RBV therapies, which could provide useful, informative evidence for making decisions regarding future therapeutic strategies comprising costly direct-acting antivirals.

Closing the mental health treatment gap in South Africa: a review of costs and cost-effectiveness

Science.gov (United States)

Jack, Helen; Wagner, Ryan G.; Petersen, Inge; Thom, Rita; Newton, Charles R.; Stein, Alan; Kahn, Kathleen; Tollman, Stephen; Hofman, Karen J.

2014-01-01

Background Nearly one in three South Africans will suffer from a mental disorder in his or her lifetime, a higher prevalence than many low- and middle-income countries. Understanding the economic costs and consequences of prevention and packages of care is essential, particularly as South Africa considers scaling-up mental health services and works towards universal health coverage. Economic evaluations can inform how priorities are set in system or spending changes. Objective To identify and review research from South Africa and sub-Saharan Africa on the direct and indirect costs of mental, neurological, and substance use (MNS) disorders and the cost-effectiveness of treatment interventions. Design Narrative overview methodology. Results and conclusions Reviewed studies indicate that integrating mental health care into existing health systems may be the most effective and cost-efficient approach to increase access to mental health services in South Africa. Integration would also direct treatment, prevention, and screening to people with HIV and other chronic health conditions who are at high risk for mental disorders. We identify four major knowledge gaps: 1) accurate and thorough assessment of the health burdens of MNS disorders, 2) design and assessment of interventions that integrate mental health screening and treatment into existing health systems, 3) information on the use and costs of traditional medicines, and 4) cost-effectiveness evaluation of a range of specific interventions or packages of interventions that are tailored to the national context. PMID:24848654

Closing the mental health treatment gap in South Africa: a review of costs and cost-effectiveness

Directory of Open Access Journals (Sweden)

Helen Jack

2013-05-01

Full Text Available Background: Nearly one in three South Africans will suffer from a mental disorder in his or her lifetime, a higher prevalence than many low- and middle-income countries. Understanding the economic costs and consequences of prevention and packages of care is essential, particularly as South Africa considers scaling-up mental health services and works towards universal health coverage. Economic evaluations can inform how priorities are set in system or spending changes. Objective: To identify and review research from South Africa and sub-Saharan Africa on the direct and indirect costs of mental, neurological, and substance use (MNS disorders and the cost-effectiveness of treatment interventions. Design: Narrative overview methodology. Results and conclusions: Reviewed studies indicate that integrating mental health care into existing health systems may be the most effective and cost-efficient approach to increase access to mental health services in South Africa. Integration would also direct treatment, prevention, and screening to people with HIV and other chronic health conditions who are at high risk for mental disorders. We identify four major knowledge gaps: 1 accurate and thorough assessment of the health burdens of MNS disorders, 2 design and assessment of interventions that integrate mental health screening and treatment into existing health systems, 3 information on the use and costs of traditional medicines, and 4 cost-effectiveness evaluation of a range of specific interventions or packages of interventions that are tailored to the national context.

Strategies to fight low-cost rivals.

Science.gov (United States)

Kumar, Nirmalya

2006-12-01

Companies find it challenging and yet strangely reassuring to take on opponents whose strategies, strengths, and weaknesses resemble their own. Their obsession with familiar rivals, however, has blinded them to threats from disruptive, low-cost competitors. Successful price warriors, such as the German retailer Aldi, are changing the nature of competition by employing several tactics: focusing on just one or a few consumer segments, delivering the basic product or providing one benefit better than rivals do, and backing low prices with superefficient operations. Ignoring cutprice rivals is a mistake because they eventually force companies to vacate entire market segments. Price wars are not the answer, either: Slashing prices usually lowers profits for incumbents without driving the low-cost entrants out of business. Companies take various approaches to competing against cut-price players. Some differentiate their products--a strategy that works only in certain circumstances. Others launch low-cost businesses of their own, as many airlines did in the 1990s--a so-called dual strategy that succeeds only if companies can generate synergies between the existing businesses and the new ventures, as the financial service providers HSBC and ING did. Without synergies, corporations are better off trying to transform themselves into low-cost players, a difficult feat that Ryanair accomplished in the 1990s, or into solution providers. There will always be room for both low-cost and value-added players. How much room each will have depends not only on the industry and customers' preferences, but also on the strategies traditional businesses deploy.

low-cost apparatus from locally available materials for teaching

African Journals Online (AJOL)

unesco

twofold: i) to design and produce appropriate low cost apparatus from locally .... How are the low-cost and manufactured apparatus compared in terms of cost and efficiency? ... BASIC TOOLS FOR THE LOW COST APPARATUS PRODUCTION.

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....

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.

ANTI-VIRAL ACTIVITY OF GLYCIRRHETINIC AND GLYCIRRHIZIC ACIDS

Directory of Open Access Journals (Sweden)

V. V. Zarubaev

2016-01-01

Full Text Available Influenza is a highly contagious human disease. In the course of use of antiviral drugs drug-resistant strains of the virus are formed, resulting in reduced efficiency of the chemotherapy. The review describes the biological activity of glycirrhetinic (GLA and glycirrhizic (GA acids in terms of their use as a therapeutic agent for viral infections. So, these compounds are against a broad spectrum of viruses, including herpes, corona-, alphaand flaviviruses, human immunodeficiency virus, vaccinia virus, poliovirus type I, vesicular stomatitis virus and influenza A virus. These data indicate that anti-viral effect of these compounds is due to several types of activity — direct antiviral effects, effects on cellular proand anti-viral and immunomodulating pathways, in particular by activation of innate immunity system. GA interferes with early steps of the viral reproductive cycle such as virus binding to its receptor, the absorption of the virus by endocytosis or virus decapsidation in the cytoplasm. This is due to the effect of GA-induced reduction of membrane fluidity. Thus, one mechanism for the antiviral activity of GA is that GA molecule increases the rigidity of cellular and viral membranes after incorporation in there. This results in increasing of energy threshold required for the formation of negative curvature at the fusion zones, as well as difficult lateral migration of the virus-receptor complexes. In addition, glycyrrhizin prevents interaction of viral nucleoprotein with cellular protein HMGB1, which is necessary for the viral life cycle. Glycyrrhizin also inhibits the induction of oxidative stress during influenza infection, exhibiting antioxidant properties, which leads to a reduction of virus-induced production of cytokines/chemokines, without affecting the replication of the virus. A wide spectrum of biological activity and effect on various aspects of the viral pathogenesis substantiate the effect of GA and GLA as a component

Palliative and low cost radiotherapy in developing countries

International Nuclear Information System (INIS)

Allen, Barry; Hussein, S.M.A.

2011-01-01

Full text: The International Agency for Research on Cancer predicts that cancer incidence in developing countries will increase dramatically in the first two decades of this millennium. Already some 80% of cancer patients in developing countries present with incurable disease. In many cases pain is a severe problem and palliation is needed to improve quality of life as well as extending survival. This paper will consider the physical and clinical aspects of palliative radiotherapy (PRT), choice of radiation modality, alternative approaches to imaging and therapy and cost-benefit considerations. The potential benefits of a dedicated palliative care centre include lower cost and therefore more centres, enabling more patients access to regional palliative care. Simple curative treatments could also be managed. Co60 radiotherapy has important advantages in developing countries, because of the higher initial cost of a linear accelerator, as well as the need for reliable power supply and the level of skill required by linac technicians and physicists. The beam characteristics of both Co60 units and low energy linacs are compared and both are found to be acceptable for palliation. The role of palliative and low cost radiotherapy in Bangladesh is reviewed. The concept of telemedicine is also discussed, using mobile phones and internet communication to allow rural clinics to receive support from specialists based in the cities, to send images for remote diagnosis and remote dose planning for radiotherapy.

Development of low-cost devices for image-guided photodynamic therapy treatment of oral cancer in global health settings

Science.gov (United States)

Liu, Hui; Rudd, Grant; Daly, Liam; Hempstead, Joshua; Liu, Yiran; Khan, Amjad P.; Mallidi, Srivalleesha; Thomas, Richard; Rizvi, Imran; Arnason, Stephen; Cuckov, Filip; Hasan, Tayyaba; Celli, Jonathan P.

2016-03-01

Photodynamic therapy (PDT) is a light-based modality that shows promise for adaptation and implementation as a cancer treatment technology in resource-limited settings. In this context PDT is particularly well suited for treatment of pre-cancer and early stage malignancy of the oral cavity, that present a major global health challenge, but for which light delivery can be achieved without major infrastructure requirements. In recent reports we demonstrated that a prototype low-cost batterypowered 635nm LED light source for ALA-PpIX PDT achieves tumoricidal efficacy in vitro and vivo, comparable to a commercial turn-key laser source. Here, building on these reports, we describe the further development of a prototype PDT device to enable intraoral light delivery, designed for ALA- PDT treatment of precancerous and cancerous lesions of the oral cavity. We evaluate light delivery via fiber bundles and customized 3D printed light applicators for flexible delivery to lesions of varying size and position within the oral cavity. We also briefly address performance requirements (output power, stability, and light delivery) and present validation of the device for ALA-PDT treatment in monolayer squamous carcinoma cell cultures.

Costs of day hospital and community residential chemical dependency treatment.

Science.gov (United States)

Kaskutas, Lee Ann; Zavala, Silvana K; Parthasarathy, Sujaya; Witbrodt, Jane

2008-03-01

Patient placement criteria developed by the American Society of Addiction Medicine (ASAM) have identified a need for low-intensity residential treatment as an alternative to day hospital for patients with higher levels of severity. A recent clinical trial found similar outcomes at social model residential treatment and clinically-oriented day hospital programs, but did not report on costs. This paper addresses whether the similar outcomes in the recent trial were delivered with comparable costs, overall and within gender and ethnicity stratum. This paper reports on clients not at environmental risk who participated in a randomized trial conducted in three metropolitan areas served by a large pre-paid health plan. Cost data were collected using the Drug Abuse Treatment Cost Analysis Program (DATCAP). Costs per episode were calculated by multiplying DATCAP-derived program-specific costs by each client's length of stay. Differences in length of stay, and in per-episode costs, were compared between residential and day hospital subjects. Lengths of stay at residential treatment were significantly longer than at day hospital, in the sample overall and in disaggregated analyses. This difference was especially marked among non-Whites. The average cost per week was USD 575 per week at day hospital, versus USD 370 per week at the residential programs. However, because of the longer stays in residential, per-episode costs were significantly higher in the sample overall and among non-Whites (and marginally higher for men). These cost results must be considered in light of the null findings comparing outcomes between subjects randomized to residential versus day hospital programs. The longer stays in the sample overall and for non-White clients at residential programs came at higher costs but did not lead to better rates of abstinence. The short stays in day hospital among non-Whites call into question the attractiveness of day hospital for minority clients. Outcomes and costs

Low Cost Benefit Suggestions.

Science.gov (United States)

Doyel, Hoyt W.; McMillan, John D.

1980-01-01

Outlines eight low-cost employee benefits and summarizes their relative advantages. The eight include a stock ownership program, a sick leave pool, flexible working hours, production incentives, and group purchase plans. (IRT)

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

Low Cost, Low Power, High Sensitivity Magnetometer

Science.gov (United States)

2008-12-01

which are used to measure the small magnetic signals from brain. Other types of vector magnetometers are fluxgate , coil based, and magnetoresistance...concentrator with the magnetometer currently used in Army multimodal sensor systems, the Brown fluxgate . One sees the MEMS fluxgate magnetometer is...Guedes, A.; et al., 2008: Hybrid - LOW COST, LOW POWER, HIGH SENSITIVITY MAGNETOMETER A.S. Edelstein*, James E. Burnette, Greg A. Fischer, M.G

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

Cost of New Technologies in Prostate Cancer Treatment: Systematic Review of Costs and Cost Effectiveness of Robotic-assisted Laparoscopic Prostatectomy, Intensity-modulated Radiotherapy, and Proton Beam Therapy.

Science.gov (United States)

Schroeck, Florian Rudolf; Jacobs, Bruce L; Bhayani, Sam B; Nguyen, Paul L; Penson, David; Hu, Jim

2017-11-01

Some of the high costs of robot-assisted radical prostatectomy (RARP), intensity-modulated radiotherapy (IMRT), and proton beam therapy may be offset by better outcomes or less resource use during the treatment episode. To systematically review the literature to identify the key economic trade-offs implicit in a particular treatment choice for prostate cancer. We systematically reviewed the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement and protocol. We searched Medline, Embase, and Web of Science for articles published between January 2001 and July 2016, which compared the treatment costs of RARP, IMRT, or proton beam therapy to the standard treatment. We identified 37, nine, and three studies, respectively. RARP is costlier than radical retropubic prostatectomy for hospitals and payers. However, RARP has the potential for a moderate cost advantage for payers and society over a longer time horizon when optimal cancer and quality-of-life outcomes are achieved. IMRT is more expensive from a payer's perspective compared with three-dimensional conformal radiotherapy, but also more cost effective when defined by an incremental cost effectiveness ratio new versus traditional technologies is costlier. However, given the low quality of evidence and the inconsistencies across studies, the precise difference in costs remains unclear. Attempts to estimate whether this increased cost is worth the expense are hampered by the uncertainty surrounding improvements in outcomes, such as cancer control and side effects of treatment. If the new technologies can consistently achieve better outcomes, then they may be cost effective. We review the cost and cost effectiveness of robot-assisted radical prostatectomy, intensity-modulated radiotherapy, and proton beam therapy in prostate cancer treatment. These technologies are costlier than their traditional counterparts. It remains unclear whether their use is associated

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.

Economics of social trade-off: Balancing wastewater treatment cost and ecosystem damage.

Science.gov (United States)

Jiang, Yu; Dinar, Ariel; Hellegers, Petra

2018-04-01

We have developed a social optimization model that integrates the financial and ecological costs associated with wastewater treatment and ecosystem damage. The social optimal abatement level of water pollution is determined by finding the trade-off between the cost of pollution control and its resulting ecosystem damage. The model is applied to data from the Lake Taihu region in China to demonstrate this trade-off. A wastewater treatment cost function is estimated with a sizable sample from China, and an ecological damage cost function is estimated following an ecosystem service valuation framework. Results show that the wastewater treatment cost function has economies of scale in facility capacity, and diseconomies in pollutant removal efficiency. Results also show that a low value of the ecosystem service will lead to serious ecological damage. One important policy implication is that the assimilative capacity of the lake should be enhanced by forbidding over extraction of water from the lake. It is also suggested that more work should be done to improve the accuracy of the economic valuation. Copyright © 2018 Elsevier Ltd. All rights reserved.

In vitro characterization of the antiviral activity of fucoidan from Cladosiphon okamuranus against Newcastle Disease Virus

Directory of Open Access Journals (Sweden)

Elizondo-Gonzalez Regina

2012-12-01

Full Text Available Abstract Background Newcastle Disease Virus (NDV causes a serious infectious disease in birds that results in severe losses in the worldwide poultry industry. Despite vaccination, NDV outbreaks have increased the necessity of alternative prevention and control measures. Several recent studies focused on antiviral compounds obtained from natural resources. Many extracts from marine organisms have been isolated and tested for pharmacological purposes, and their antiviral activity has been demonstrated in vitro and in vivo. Fucoidan is a sulfated polysaccharide present in the cell wall matrix of brown algae that has been demonstrated to inhibit certain enveloped viruses with low toxicity. This study evaluated the potential antiviral activity and the mechanism of action of fucoidan from Cladosiphon okamuranus against NDV in the Vero cell line. Methods The cytotoxicity of fucoidan was determined by the MTT assay. To study its antiviral activity, fusion and plaque-forming unit (PFU inhibition assays were conducted. The mechanism of action was determined by time of addition, fusion inhibition, and penetration assays. The NDV vaccine strain (La Sota was used in the fusion inhibition assays. PFU and Western blot experiments were performed using a wild-type lentogenic NDV strain. Results Fucoidan exhibited antiviral activity against NDV La Sota, with an obtained IS50 >2000. In time of addition studies, we observed viral inhibition in the early stages of infection (0–60 min post-infection. The inhibition of viral penetration experiments with a wild-type NDV strain supported this result, as these experiments demonstrated a 48% decrease in viral infection as well as reduced HN protein expression. Ribavirin, which was used as an antiviral control, exhibited lower antiviral activity than fucoidan and high toxicity at active doses. In the fusion assays, the number of syncytia was significantly reduced (70% inhibition when fucoidan was added before cleavage of

Interim report: Waste management facilities cost information for mixed low-level waste

International Nuclear Information System (INIS)

Feizollahi, F.; Shropshire, D.

1994-03-01

This report contains preconceptual designs and planning level life-cycle cost estimates for treating alpha and nonalpha mixed low-level radioactive waste. This report contains information on twenty-seven treatment, storage, and disposal modules that can be integrated to develop total life cycle costs for various waste management options. A procedure to guide the US Department of Energy and its contractor personnel in the use of estimating data is also summarized in this report

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.

Hepatitis C virus resistance to the new direct-acting antivirals.

Science.gov (United States)

Esposito, Isabella; Trinks, Julieta; Soriano, Vicente

2016-10-01

The treatment of hepatitis C virus (HCV) infection has dramatically improved in recent years with the widespread use of interferon-free combination regimens. Despite the high sustained virological response (SVR) rates (over 90%) obtained with direct-acting antivirals (DAAs), drug resistance has emerged as a potential challenge. The high replication rate of HCV and the low fidelity of its RNA polymerase result in a high degree of genetic variability in the HCV population, which ultimately explains the rapid selection of drug resistance associated variants (RAVs). Results from clinical trials and real-world experience have both provided important information on the rate and clinical significance of RAVs. They can be present in treatment-naive patients as natural polymorphisms although more frequently they are selected upon treatment failure. In patients engaged in high-risk behaviors, RAVs can be transmitted. Although DAA failures generally occur in less than 10% of treated chronic hepatitis C patients, selection of drug resistance is the rule in most cases. HCV re-treatment options are available, but first-line therapeutic strategies should be optimized to efficiently prevent DAA failure due to baseline HCV resistance. Considerable progress is being made and next-generation DAAs are coming with pangenotypic activity and higher resistance barrier.

Low-cost satellite mechanical design and construction

Science.gov (United States)

Boisjolie-Gair, Nathaniel; Straub, Jeremy

2017-05-01

This paper presents a discussion of techniques for low-cost design and construction of a CubeSat mechanical structure that can serve as a basis for academic programs and a starting point for government, military and commercial large-scale sensing networks, where the cost of each node must be minimized to facilitate system affordability and lower the cost and associated risk of losing any node. Spacecraft Design plays a large role in manufacturability. An intentionally simplified mechanical design is presented which reduces machining costs, as compared to more intricate designs that were considered. Several fabrication approaches are evaluated relative to the low-cost goal.

The cost of pressure ulcer prevention and treatment in hospitals and nursing homes in Flanders: A cost-of-illness study.

Science.gov (United States)

Demarré, Liesbet; Verhaeghe, Sofie; Annemans, Lieven; Van Hecke, Ann; Grypdonck, Maria; Beeckman, Dimitri

2015-07-01

The economic impact of pressure ulcer prevention and treatment is high. The results of cost-of-illness studies can assist the planning, allocation, and priority setting of healthcare expenditures to improve the implementation of preventive measures. Data on the cost of current practice of pressure ulcer prevention or treatment in Flanders, a region of Belgium, is lacking. To examine the cost of pressure ulcer prevention and treatment in an adult population in hospitals and nursing homes from the healthcare payer perspective. A cost-of-illness study was performed using a bottom-up approach. Hospitals and nursing homes in Flanders, a region of Belgium. Data were collected in a series of prospective multicentre cross-sectional studies between 2008 and 2013. Data collection included data on risk assessment, pressure ulcer prevalence, preventive measures, unit cost of materials for prevention and treatment, nursing time measurements for activities related to pressure ulcer prevention and treatment, and nursing wages. The cost of pressure ulcer prevention and treatment in hospitals and nursing homes was calculated as annual cost for Flanders, per patient, and per patient per day. The mean (SD) cost for pressure ulcer prevention was €7.88 (8.21) per hospitalised patient at risk per day and €2.15 (3.10) per nursing home resident at risk per day. The mean (SD) cost of pressure ulcer prevention for patients and residents identified as not at risk for pressure ulcer development was €1.44 (4.26) per day in hospitals and €0.50 (1.61) per day in nursing homes. The main cost driver was the cost of labour, responsible for 79-85% of the cost of prevention. The mean (SD) cost of local treatment per patient per day varied between €2.34 (1.14) and €77.36 (35.95) in hospitals, and between €2.42 (1.15) and €16.18 (4.93) in nursing homes. Related to methodological differences between studies, the cost of pressure ulcer prevention and treatment in hospitals and nursing

A microbial fuel cell–membrane bioreactor integrated system for cost-effective wastewater treatment

International Nuclear Information System (INIS)

Wang, Yong-Peng; Liu, Xian-Wei; Li, Wen-Wei; Li, Feng; Wang, Yun-Kun; Sheng, Guo-Ping; Zeng, Raymond J.; Yu, Han-Qing

2012-01-01

Highlights: ► An MFC–MBR integrated system for wastewater treatment and electricity generation. ► Stable electricity generation during 1000-h continuous operation. ► Low-cost electrode, separator and filter materials were adopted. -- Abstract: Microbial fuel cell (MFC) and membrane bioreactor (MBR) are both promising technologies for wastewater treatment, but both with limitations. In this study, a novel MFC–MBR integrated system, which combines the advantages of the individual systems, was proposed for simultaneous wastewater treatment and energy recovery. The system favored a better utilization of the oxygen in the aeration tank of MBR by the MFC biocathode, and enabled a high effluent quality. Continuous and stable electricity generation, with the average current of 1.9 ± 0.4 mA, was achieved over a long period of about 40 days. The maximum power density reached 6.0 W m −3 . Moreover, low-cost materials were used for the reactor construction. This integrated system shows great promise for practical wastewater treatment application.

Low Cost Integrated Navigation System for Unmanned Vessel

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Yang Changsong

2017-11-01

Full Text Available Large errors of low-cost MEMS inertial measurement unit (MIMU lead to huge navigation errors, even wrong navigation information. An integrated navigation system for unmanned vessel is proposed. It consists of a low-cost MIMU and Doppler velocity sonar (DVS. This paper presents an integrated navigation method, to improve the performance of navigation system. The integrated navigation system is tested using simulation and semi-physical simulation experiments, whose results show that attitude, velocity and position accuracy has improved awfully, giving exactly accurate navigation results. By means of the combination of low-cost MIMU and DVS, the proposed system is able to overcome fast drift problems of the low cost IMU.

Costs of treatment of adult patients with cystic fibrosis in Poland and internationally.

Science.gov (United States)

Kopciuch, Dorota; Zaprutko, Tomasz; Paczkowska, Anna; Nowakowska, Elżbieta

2017-07-01

Despite its low prevalence, cystic fibrosis (CF) may have a considerable impact on healthcare system expenditures in terms of direct healthcare costs and lost productivity. This study was aimed at calculation of costs associated with CF treatment in Poland, as well as at comparison of average costs of treatment of CF patients in selected countries, taking into account the purchasing power parity. Retrospective study. The researchers undertook a retrospective study of adult patients with CF taking into account the broadest social perspective possible. Medical and non-medical direct costs as well as indirect costs were calculated. CF costs estimated by researchers from other countries over the last 15 years were also compared. Total annual treatment cost per one CF patient in Poland was on average EUR 19,581.08. Costs of treatment of CF patients over the last 15 years varied between the countries and ranged from EUR 23,330.82 in Bulgaria to EUR 68,696.42 in the United States. CF is an international problem. The data in this study could be the baseline for integrated and harmonised approaches for periodical assessment of the future impact of new public policies and interventions for rare diseases at the national and international levels. Copyright © 2017 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

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.

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.

Surface treatment of low-cost beta titanium alloy to combat wear

International Nuclear Information System (INIS)

Redmore, E.; Li, X.; Dong, H.

2010-01-01

The development of an effective ceramic conversion treatment of TIMETAL LCB (Ti-6.8Mo-4.5Fe-1.5Al) has been investigated. Various characterisation methods were used to analyse samples in order to identify the best process conditions including SEM, EDX, XRD, GDS, micro-indentation and scratch testing. The results show that the tribological properties of the TIMETAL LCB alloy have been significantly enhanced by the new ceramic conversion treatment specifically developed for beta alloys. The improved friction and wear properties can be attributed to the low-friction TiO_2 surface layer supported by an oxygen diffusion hardened case up to a depth of ∼70μm. (author)

Cost-effectiveness of decompression according to Gill versus instrumented spondylodesis in the treatment of sciatica due to low grade spondylolytic spondylolisthesis: a prospective randomised controlled trial [NTR1300].

Science.gov (United States)

Arts, Mark P; Verstegen, Marco J T; Brand, Ronald; Koes, Bart W; van den Akker, M Elske; Peul, Wilco C

2008-09-28

Nerve root decompression with instrumented spondylodesis is the most frequently performed surgical procedure in the treatment of patients with symptomatic low-grade spondylolytic spondylolisthesis. Nerve root decompression without instrumented fusion, i.e. Gill's procedure, is an alternative and less invasive approach. A comparative cost-effectiveness study has not been performed yet. We present the design of a randomised controlled trial on cost-effectiveness of decompression according to Gill versus instrumented spondylodesis. All patients (age between 18 and 70 years) with sciatica or neurogenic claudication lasting more than 3 months due to spondylolytic spondylolisthesis grade I or II, are eligible for inclusion. Patients will be randomly allocated to nerve root decompression according to Gill, either unilateral or bilateral, or pedicle screw fixation with interbody fusion. The main primary outcome measure is the functional assessment of the patient measured with the Roland Disability Questionnaire for Sciatica at 12 weeks and 2 years. Other primary outcome measures are perceived recovery and intensity of leg pain and low back pain. The secondary outcome measures include, incidence of re-operations, complications, serum creatine phosphokinase, quality of life, medical consumption, costs, absenteeism, work perception, depression and anxiety, and treatment preference. The study is a randomised prospective multicenter trial in which two surgical techniques are compared in a parallel group design. Patients and research nurse will not be blinded during the follow-up period of 2 years. Currently, nerve root decompression with instrumented fusion is the golden standard in the surgical treatment of low-grade spondylolytic spondylolisthesis, although scientific proof justifying instrumented spondylodesis over simple decompression is lacking. This trial is designed to elucidate the controversy in best surgical treatment of symptomatic patients with low

Cost-effectiveness of decompression according to Gill versus instrumented spondylodesis in the treatment of sciatica due to low grade spondylolytic spondylolisthesis: A prospective randomised controlled trial [NTR1300

Directory of Open Access Journals (Sweden)

Brand Ronald

2008-09-01

Full Text Available Abstract Background Nerve root decompression with instrumented spondylodesis is the most frequently performed surgical procedure in the treatment of patients with symptomatic low-grade spondylolytic spondylolisthesis. Nerve root decompression without instrumented fusion, i.e. Gill's procedure, is an alternative and less invasive approach. A comparative cost-effectiveness study has not been performed yet. We present the design of a randomised controlled trial on cost-effectiveness of decompression according to Gill versus instrumented spondylodesis. Methods/design All patients (age between 18 and 70 years with sciatica or neurogenic claudication lasting more than 3 months due to spondylolytic spondylolisthesis grade I or II, are eligible for inclusion. Patients will be randomly allocated to nerve root decompression according to Gill, either unilateral or bilateral, or pedicle screw fixation with interbody fusion. The main primary outcome measure is the functional assessment of the patient measured with the Roland Disability Questionnaire for Sciatica at 12 weeks and 2 years. Other primary outcome measures are perceived recovery and intensity of leg pain and low back pain. The secondary outcome measures include, incidence of re-operations, complications, serum creatine phosphokinase, quality of life, medical consumption, costs, absenteeism, work perception, depression and anxiety, and treatment preference. The study is a randomised prospective multicenter trial in which two surgical techniques are compared in a parallel group design. Patients and research nurse will not be blinded during the follow-up period of 2 years. Discussion Currently, nerve root decompression with instrumented fusion is the golden standard in the surgical treatment of low-grade spondylolytic spondylolisthesis, although scientific proof justifying instrumented spondylodesis over simple decompression is lacking. This trial is designed to elucidate the controversy in best

BiliLED low cost neonatal phototherapy, from prototype to industry

Energy Technology Data Exchange (ETDEWEB)

Geido, Daniel; Failache, Horacio [Instituto de Fisica de la Facultad de Ingenieria - Universidad de la Republica, Montevideo (Uruguay); Simini, Franco [Nucleo de Ingenieria Biomedica de las Facultades de Medicina e Ingenieria (Uruguay); Hospital de ClInicas. Av Italia S/N. Piso 15 sala 2, 11600 Montevideo (Uruguay)

2007-11-15

BiliLED is a phototherapy instrument designed to reduce bilirrubin blood rates in new born babies with jaundice. The light source is centred at 470 nm with a bandwidth of 35 nm and includes a matrix of 196 (14x14) InGaN LEDs. The optical elements are designed to maximize the light intensity useful for treatment, with a small number of LEDs in a compact and low cost unit. The optic array is such that every LED illuminates all the treatment area, which ensures redundancy and, thus, a high reliability not to be found in single-lamp instruments. Thermal dissipation and cost of BiliLED are both an order-of-magnitude smaller than conventional therapy lamps. BiliLED adjusts coetaneous irradiation with a feedback loop to compensate the loss or aging of LEDs achieving a calibrated light source for over a decade of use. A clinical trial in 20 hyperbilirrubinaemia patients shows 16% bilirrubin degradation within 24 hours of treatment, higher than most lamp phototherapy instruments. The steps from prototype to commercial model are described.

BiliLED low cost neonatal phototherapy, from prototype to industry

Science.gov (United States)

Geido, Daniel; Failache, Horacio; Simini, Franco

2007-11-01

BiliLED is a phototherapy instrument designed to reduce bilirrubin blood rates in new born babies with jaundice. The light source is centred at 470 nm with a bandwidth of 35 nm and includes a matrix of 196 (14×14) InGaN LEDs. The optical elements are designed to maximize the light intensity useful for treatment, with a small number of LEDs in a compact and low cost unit. The optic array is such that every LED illuminates all the treatment area, which ensures redundancy and, thus, a high reliability not to be found in single-lamp instruments. Thermal dissipation and cost of BiliLED are both an order-of-magnitude smaller than conventional therapy lamps. BiliLED adjusts coetaneous irradiation with a feedback loop to compensate the loss or aging of LEDs achieving a calibrated light source for over a decade of use. A clinical trial in 20 hyperbilirrubinaemia patients shows 16% bilirrubin degradation within 24 hours of treatment, higher than most lamp phototherapy instruments. The steps from prototype to commercial model are described.

BiliLED low cost neonatal phototherapy, from prototype to industry

International Nuclear Information System (INIS)

Geido, Daniel; Failache, Horacio; Simini, Franco

2007-01-01

BiliLED is a phototherapy instrument designed to reduce bilirrubin blood rates in new born babies with jaundice. The light source is centred at 470 nm with a bandwidth of 35 nm and includes a matrix of 196 (14x14) InGaN LEDs. The optical elements are designed to maximize the light intensity useful for treatment, with a small number of LEDs in a compact and low cost unit. The optic array is such that every LED illuminates all the treatment area, which ensures redundancy and, thus, a high reliability not to be found in single-lamp instruments. Thermal dissipation and cost of BiliLED are both an order-of-magnitude smaller than conventional therapy lamps. BiliLED adjusts coetaneous irradiation with a feedback loop to compensate the loss or aging of LEDs achieving a calibrated light source for over a decade of use. A clinical trial in 20 hyperbilirrubinaemia patients shows 16% bilirrubin degradation within 24 hours of treatment, higher than most lamp phototherapy instruments. The steps from prototype to commercial model are described

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.

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

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

Light-activated nanotube–porphyrin conjugates as effective antiviral agents

International Nuclear Information System (INIS)

Banerjee, Indrani; Douaisi, Marc P; Mondal, Dhananjoy; Kane, Ravi S

2012-01-01

Porphyrins have been used for photodynamic therapy (PDT) against a wide range of targets like bacteria, viruses and tumor cells. In this work, we report porphyrin-conjugated multi-walled carbon nanotubes (NT-P) as potent antiviral agents. Specifically, we used Protoporphyrin IX (PPIX), which we attached to acid-functionalized multi-walled carbon nanotubes (MWNTs). We decided to use carbon nanotubes as scaffolds because of their ease of recovery from a solution through filtration. In the presence of visible light, NT-P was found to significantly reduce the ability of Influenza A virus to infect mammalian cells. NT-P may be used effectively against influenza viruses with little or no chance of them developing resistance to the treatment. Furthermore, NT-P can be easily recovered through filtration which offers a facile strategy to reuse the active porphyrin moiety to its fullest extent. Thus NT-P conjugates represent a new approach for preparing ex vivo reusable antiviral agents. (paper)

Mixed and low-level waste treatment facility project

International Nuclear Information System (INIS)

1992-04-01

The technology information provided in this report is only the first step toward the identification and selection of process systems that may be recommended for a proposed mixed and low-level waste treatment facility. More specific information on each technology will be required to conduct the system and equipment tradeoff studies that will follow these preengineering studies. For example, capacity, maintainability, reliability, cost, applicability to specific waste streams, and technology availability must be further defined. This report does not currently contain all needed information; however, all major technologies considered to be potentially applicable to the treatment of mixed and low-level waste are identified and described herein. Future reports will seek to improve the depth of information on technologies

Mixed and low-level waste treatment facility project

Energy Technology Data Exchange (ETDEWEB)

1992-04-01

The technology information provided in this report is only the first step toward the identification and selection of process systems that may be recommended for a proposed mixed and low-level waste treatment facility. More specific information on each technology will be required to conduct the system and equipment tradeoff studies that will follow these preengineering studies. For example, capacity, maintainability, reliability, cost, applicability to specific waste streams, and technology availability must be further defined. This report does not currently contain all needed information; however, all major technologies considered to be potentially applicable to the treatment of mixed and low-level waste are identified and described herein. Future reports will seek to improve the depth of information on technologies.

Cost-effective treatment for the couple with infertility.

Science.gov (United States)

Van Voorhis, B J; Syrop, C H

2000-12-01

Although the evaluation of cost-effective approaches to infertility treatment remains in its infancy, several important principles have emerged from the initial studies in this field. Currently, in treating couples with infertility without tubal disease or severe male-factor infertility, the most cost-effective approach is to start with IUI or superovulation-IUI treatments before resorting to IVF procedures. The woman's age and number of sperm present for insemination are significant factors influencing cost-effectiveness. The influence of certain diagnoses on the cost-effectiveness of infertility treatments requires further study. Even when accounting for the costs associated with multiple gestations and premature deliveries, the cost of IVF decreases within the range of other cost-effective medical procedures and decreases to less than the willingness to pay for these procedures. Indeed, for patients with severe tubal disease, IVF has been found to be more cost-effective than surgical repair. The cost-effectiveness of IVF will likely improve as success rates show continued improvements over the course of time. In addition, usefulness of embryo selection and practices to reduce the likelihood of high-order multiple pregnancies, without reductions in pregnancy rates, will significantly impact cost-effectiveness. The exclusion of infertility treatments from insurance plans is unfortunate and accentuates the importance of physicians understanding the economics of infertility treatment with costs that are often passed directly to the patient. The erroneous economic policies and judgments that have led to inequities in access to infertility health care should not be tolerated.

Antiviral Activity of Peanut (Arachis hypogaea L.) Skin Extract Against Human Influenza Viruses.

Science.gov (United States)

Makau, Juliann Nzembi; Watanabe, Ken; Mohammed, Magdy M D; Nishida, Noriyuki

2018-05-30

The high propensity of influenza viruses to develop resistance to antiviral drugs necessitates the continuing search for new therapeutics. Peanut skins, which are low-value byproducts of the peanut industry, are known to contain high levels of polyphenols. In this study, we investigated the antiviral activity of ethanol extracts of peanut skins against various influenza viruses using cell-based assays. Extracts with a higher polyphenol content exhibited higher antiviral activities, suggesting that the active components are the polyphenols. An extract prepared from roasted peanut skins effectively inhibited the replication of influenza virus A/WSN/33 with a half maximal inhibitory concentration of 1.3 μg/mL. Plaque assay results suggested that the extract inhibits the early replication stages of the influenza virus. It demonstrated activity against both influenza type A and type B viruses. Notably, the extract exhibited a potent activity against a clinical isolate of the 2009 H1N1 pandemic, which had reduced sensitivity to oseltamivir. Moreover, a combination of peanut skin extract with the anti-influenza drugs, oseltamivir and amantadine, synergistically increased their antiviral activity. These data demonstrate the potential application of peanut skin extract in the development of new therapeutic options for influenza management.

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.

Developing low-cost carbon-based sorbents for Hg capture from flue gas

Energy Technology Data Exchange (ETDEWEB)

Perry, R.; Lakatos, J.; Snape, C.E.; Sun, C. [University of Nottingham, Nottingham (United Kingdom). Nottingham Fuel and Energy Centre

2005-07-01

To help reduce the cost of Hg capture from flue gas a number of low-cost carbons are being investigated, including activated tyre char and PFA carbon, in conjunction with some of the pre-treatments that have been found to be effective for commercial actived carbons. Experimental conditions for screening the sorbents have been selected to determine breakthrough capacities rapidly. The unactivated carbons have low breakthrough capacities under the test conditions employed (around 0.1 mg g{sup -1}) but these improve upon steam activation (around 0.25 mg g{sup -1}) but are still lower than those of non-impregnated commercial activated carbons (around 0.4-0.7 mg g{sup -1}), due to their lower surface areas. Comparable improvements to the commercial carbons have been achieved for impregnation treatments, including sulfur and bromine. However, certain gasification chars do have much higher breakthrough capacities than commercial carbons used for flue gas injection. Manganese oxide impregnation with low concentration is particularly effective for the activated and unactivated carbons giving breakthrough capacities comparable to the commercial carbons. Pointers for further increasing breakthrough and equilibrium capacities for carbon-based sorbents are discussed. 7 refs., 1 fig., 3 tabs.

Low-cost glass ionomer cement as ART sealant in permanent molars: a randomized clinical trial

Directory of Open Access Journals (Sweden)

Daniela HESSE

2015-01-01

Full Text Available Clinical trials are normally performed with well-known brands of glass ionomer cement (GIC, but the cost of these materials is high for public healthcare in less-affluent communities. Given the need to research cheaper materials, it seems pertinent to investigate the retention rate of a low-cost GIC applied as atraumatic restorative treatment (ART sealants in two centers in Brazil. Four hundred and thirty-seven 6-to-8-year-old schoolchildren were selected in two cities in Brazil. The children were randomly divided into two groups, according to the tested GIC applied in the first permanent molars. The retention rate was evaluated after 3, 6 and 12 months. Kaplan-Meier survival analysis and the log-rank test were performed. The variables were tested for association with sealant longevity, using logistic regression analyses (α = 5%. The retention rate of sealants after 12 months was 19.1%. The high-cost GIC brand presented a 2-fold-more-likely-to-survive rate than the low-cost brand (p < 0.001. Significant difference was also found between the cities where the treatments were performed, in that Barueri presented a higher sealant survival rate than Recife (p < 0.001. The retention rate of a low-cost GIC sealant brand was markedly lower than that of a well-known GIC sealant brand.

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

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

A low-cost colorimeter.

Science.gov (United States)

Jones, N B; Riley, C; Sheya, M S; Hosseinmardi, M M

1984-01-01

A need for a colorimeter with low capital and maintenance costs has been suggested for countries with foreign exchange problems and no local medical instrumentation industry. This paper puts forward a design for such a device based on a domestic light-bulb, photographic filters and photovoltaic cells. The principle of the design is the use of a balancing technique involving twin light paths for test solution and reference solution and an electronic bridge circuit. It is shown that proper selection of the components will allow the cost objectives to be met and also provide acceptable linearity, precision, accuracy and repeatability.

Integrated process analysis of treatment systems for mixed low level waste

International Nuclear Information System (INIS)

Cooley, C.R.; Schwinkendorf, W.E.; Bechtold, T.E.

1997-10-01

Selection of technologies to be developed for treatment of DOE's mixed low level waste (MLLW) requires knowledge and understanding of the expected costs, schedules, risks, performance, and reliability of the total engineered systems that use these technologies. Thus, an integrated process analysis program was undertaken to identify the characteristics and needs of several thermal and nonthermal systems. For purposes of comparison, all systems were conceptually designed for a single facility processing the same amount of waste at the same rate. Thirty treatment systems were evaluated ranging from standard incineration to innovative thermal systems and innovative nonthermal chemical treatment. Treating 236 million pounds of waste in 20 years through a central treatment was found to be the least costly option with total life cycle cost ranging from $2.1 billion for a metal melting system to $3.9 billion for a nonthermal acid digestion system. Little cost difference exists among nonthermal systems or among thermal systems. Significant cost savings could be achieved by working towards maximum on line treatment time per year; vitrifying the final waste residue; decreasing front end characterization segregation and sizing requirements; using contaminated soil as the vitrifying agent; and delisting the final vitrified waste form from Resource Conservation and Recovery Act (RCRA) Land Disposal Restriction (LDR) requirements

The cost-utility of sodium oxybate as narcolepsy treatment

DEFF Research Database (Denmark)

Bolin, K; Berling, P; Wasling, P

2017-01-01

cost per additional QALY for the sodium oxybate treatment alternative compared with standard treatment was estimated above the informal Swedish willingness-to-pay threshold (SEK 500,000). The estimated cost per additional QALY obtained here is likely to overestimate the true cost-effectiveness ratio......AIMS AND OBJECTIVES: Based on class-I studies, sodium oxybate is regarded as a first-line treatment for both EDS and cataplexy. The cost-effectiveness of sodium oxybate is largely unknown, though. In this study, we estimate the cost-effectiveness of sodium oxybate as treatment for patients...... with narcolepsy as compared to standard treatment, by calculating incremental cost-effectiveness ratios (cost per quality-adjusted life year, QALY) for patients in a Swedish setting. MATERIALS AND METHODS: Calculations were performed using a Markov model with a 10-year time horizon. The study population consisted...

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

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.

Low Cost/Low Noise Variable Pitch Ducted Fan, Phase I

Data.gov (United States)

National Aeronautics and Space Administration — ACI proposes a design for a Propulsor (Low Cost/Low Noise Variable Pitch Ducted Fan) that has wide application in all sectors of Aviation. Propulsor hardware of this...

Alcoholism treatment and medical care costs from Project MATCH.

Science.gov (United States)

Holder, H D; Cisler, R A; Longabaugh, R; Stout, R L; Treno, A J; Zweben, A

2000-07-01

This paper examines the costs of medical care prior to and following initiation of alcoholism treatment as part of a study of patient matching to treatment modality. Longitudinal study with pre- and post-treatment initiation. The total medical care costs for inpatient and outpatient treatment for patients participating over a span of 3 years post-treatment. Three treatment sites at two of the nine Project MATCH locations (Milwaukee, WI and Providence, RI). Two hundred and seventy-nine patients. Patients were randomly assigned to one of three treatment modalities: a 12-session cognitive behavioral therapy (CBT), a four-session motivational enhancement therapy (MET) or a 12-session Twelve-Step facilitation (TSF) treatment over 12 weeks. Total medical care costs declined from pre- to post-treatment overall and for each modality. Matching effects independent of clinical prognosis showed that MET has potential for medical-care cost-savings. However, patients with poor prognostic characteristics (alcohol dependence, psychiatric severity and/or social network support for drinking) have better cost-savings potential with CBT and/or TSF. Matching variables have significant importance in increasing the potential for medical-care cost-reductions following alcoholism treatment.

NaVirCept - Nucleic Acid-Based Anti-Viral Project

International Nuclear Information System (INIS)

Stephen, E. R.; Wong, J.; Van Loon, D.

2007-01-01

Vaccines are generally considered to be the most effective countermeasures to bacterial and viral diseases, however, licensed vaccines against many disease agents are either not available or their efficacies have not been demonstrated. Vaccines are generally agent specific in terms of treatment spectrum and are subject to defeat through natural mutation or through directed efforts. With respect to viral therapeutics, one of the major limitations associated with antiviral drugs is acquired drug resistance caused by antigenic shift or drift. A number of next-generation prophylactic and/or therapeutic measures are on the horizon. Of these, nucleic acid-based drugs are showing great antiviral potential. These drugs elicit long-lasting, broad spectrum protective immune responses, especially to respiratory viral pathogens. The Nucleic Acid-Based Antiviral (NaVirCept) project provides the opportunity to demonstrate the effectiveness of novel medical countermeasures against military-significant endemic and other viral threat agents. This project expands existing DRDC drug delivery capability development, in the form of proprietary liposome intellectual property, by coupling it with leading-edge nucleic acid-based technology to deliver effective medical countermeasures that will protect deployed personnel and the warfighter against a spectrum of viral disease agents. The technology pathway will offer a means to combat emerging viral diseases or modified threat agents such as the bird flu or reconstructed Spanish flu without going down the laborious, time-consuming and expensive paths to develop countermeasures for each new and/or emerging viral disease organism.(author)

A Cost-Effectiveness Analysis of Seminatural Wetlands and Activated Sludge Wastewater-Treatment Systems

Science.gov (United States)

Mannino, Ilda; Franco, Daniel; Piccioni, Enrico; Favero, Laura; Mattiuzzo, Erika; Zanetto, Gabriele

2008-01-01

A cost-effectiveness analysis was performed to evaluate the competitiveness of seminatural Free Water Surface (FWS) wetlands compared to traditional wastewater-treatment plants. Six scenarios of the service costs of three FWS wetlands and three different wastewater-treatment plants based on active sludge processes were compared. The six scenarios were all equally effective in their wastewater-treatment capacity. The service costs were estimated using real accounting data from an experimental wetland and by means of a market survey. Some assumptions had to be made to perform the analysis. A reference wastewater situation was established to solve the problem of the different levels of dilution that characterize the inflow water of the different systems; the land purchase cost was excluded from the analysis, considering the use of public land as shared social services, and an equal life span for both seminatural and traditional wastewater-treatment plants was set. The results suggest that seminatural systems are competitive with traditional biotechnological systems, with an average service cost improvement of 2.1-fold to 8-fold, according to the specific solution and discount rate. The main improvement factor was the lower maintenance cost of the seminatural systems, due to the self-regulating, low artificial energy inputs and the absence of waste to be disposed. In this work, only the waste-treatment capacity of wetlands was considered as a parameter for the economic competitiveness analysis. Other goods/services and environmental benefits provided by FWS wetlands were not considered.

Utility of humanized BLT mice for analysis of dengue virus infection and antiviral drug testing.

Science.gov (United States)

Frias-Staheli, Natalia; Dorner, Marcus; Marukian, Svetlana; Billerbeck, Eva; Labitt, Rachael N; Rice, Charles M; Ploss, Alexander

2014-02-01

Dengue virus (DENV) is the cause of a potentially life-threatening disease that affects millions of people worldwide. The lack of a small animal model that mimics the symptoms of DENV infection in humans has slowed the understanding of viral pathogenesis and the development of therapies and vaccines. Here, we investigated the use of humanized "bone marrow liver thymus" (BLT) mice as a model for immunological studies and assayed their applicability for preclinical testing of antiviral compounds. Human immune system (HIS) BLT-NOD/SCID mice were inoculated intravenously with a low-passage, clinical isolate of DENV-2, and this resulted in sustained viremia and infection of leukocytes in lymphoid and nonlymphoid organs. In addition, DENV infection increased serum cytokine levels and elicited DENV-2-neutralizing human IgM antibodies. Following restimulation with DENV-infected dendritic cells, in vivo-primed T cells became activated and acquired effector function. An adenosine nucleoside inhibitor of DENV decreased the circulating viral RNA when administered simultaneously or 2 days postinfection, simulating a potential treatment protocol for DENV infection in humans. In summary, we demonstrate that BLT mice are susceptible to infection with clinical DENV isolates, mount virus-specific adaptive immune responses, and respond to antiviral drug treatment. Although additional refinements to the model are required, BLT mice are a suitable platform to study aspects of DENV infection and pathogenesis and for preclinical testing of drug and vaccine candidates. IMPORTANCE Infection with dengue virus remains a major medical problem. Progress in our understanding of the disease and development of therapeutics has been hampered by the scarcity of small animal models. Here, we show that humanized mice, i.e., animals engrafted with components of a human immune system, that were infected with a patient-derived dengue virus strain developed clinical symptoms of the disease and mounted

Low-Cost Servomotor Driver for PFM Control.

Science.gov (United States)

Aragon-Jurado, David; Morgado-Estevez, Arturo; Perez-Peña, Fernando

2017-12-31

Servomotors have already been around for some decades and they are extremely popular among roboticists due to their simple control technique, reliability and low-cost. They are usually controlled by using Pulse Width Modulation (PWM) and this paper aims to keep the idea of simplicity and low-cost, while introducing a new control technique: Pulse Frequency Modulation (PFM). The objective of this paper is to focus on our development of a low-cost servomotor controller which will allow the research community to use them with PFM. A low-cost commercial servomotor is used as the base system for the development: a small PCB that fits inside the case and allocates all the electronic components to control the motor has been designed to replace the original. The potentiometer is retained as the feedback sensor and a microcontroller is responsible for controlling the position of the motor. The paper compares the performance of a PWM and a PFM controlled servomotor. The comparison shows that the servomotor with our controller achieves a faster mechanism for switching targets and a lower latency. This controller can be used with neuromorphic systems to remove the conversion from events to PWM.

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.

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.

Low-level radioactive waste treatment systems in northern Europe

International Nuclear Information System (INIS)

Sjoeblom, R.

1987-08-01

In the United States, the use of low-level waste (LLW) treatment systems by low level waste generators can be expected to expand with increasing costs for disposal and continuing uncertainty over the availability of disposal space. This development increases the need for performance information and operational data and has prompted the US Department of Energy to commission several compilations of LLW systems experience. The present paper summarizes some of the know-how from Northern Europe where the incentive for LLW treatment and volume reduction is very high since deposition space has not been available for many years. 65 refs., 10 figs., 4 tabs

Low profile, low cost, new geometry integrated inductors

DEFF Research Database (Denmark)

Ouyang, Ziwei; Thomsen, Ole Cornelius; Andersen, Michael A. E.

2011-01-01

windings with well-defined thickness. Many advantages and disadvantages are described in depth. In this work, inverse coupling and direct coupling in the new geometry integrated inductors have been analyzed. Coupling characteristic caused by a special saturation behavior has been emphasis. And also...... variable inductors caused by the special saturation behavior may be utilized in some applications. The new integrated inductors make it possible to build low-profile, low-cost, flexibility DC/DC converters, and it can be extensively designed for the low-voltage and high-current required by the modern...

Cost and cost-effectiveness of tuberculosis treatment shortening: a model-based analysis.

Science.gov (United States)

Gomez, G B; Dowdy, D W; Bastos, M L; Zwerling, A; Sweeney, S; Foster, N; Trajman, A; Islam, M A; Kapiga, S; Sinanovic, E; Knight, G M; White, R G; Wells, W A; Cobelens, F G; Vassall, A

2016-12-01

Despite improvements in treatment success rates for tuberculosis (TB), current six-month regimen duration remains a challenge for many National TB Programmes, health systems, and patients. There is increasing investment in the development of shortened regimens with a number of candidates in phase 3 trials. We developed an individual-based decision analytic model to assess the cost-effectiveness of a hypothetical four-month regimen for first-line treatment of TB, assuming non-inferiority to current regimens of six-month duration. The model was populated using extensive, empirically-collected data to estimate the economic impact on both health systems and patients of regimen shortening for first-line TB treatment in South Africa, Brazil, Bangladesh, and Tanzania. We explicitly considered 'real world' constraints such as sub-optimal guideline adherence. From a societal perspective, a shortened regimen, priced at USD1 per day, could be a cost-saving option in South Africa, Brazil, and Tanzania, but would not be cost-effective in Bangladesh when compared to one gross domestic product (GDP) per capita. Incorporating 'real world' constraints reduces cost-effectiveness. Patient-incurred costs could be reduced in all settings. From a health service perspective, increased drug costs need to be balanced against decreased delivery costs. The new regimen would remain a cost-effective option, when compared to each countries' GDP per capita, even if new drugs cost up to USD7.5 and USD53.8 per day in South Africa and Brazil; this threshold was above USD1 in Tanzania and under USD1 in Bangladesh. Reducing the duration of first-line TB treatment has the potential for substantial economic gains from a patient perspective. The potential economic gains for health services may also be important, but will be context-specific and dependent on the appropriate pricing of any new regimen.

Solar disinfection: an approach for low-cost household water treatment technology in Southwestern Ethiopia.

Science.gov (United States)

Dessie, Awrajaw; Alemayehu, Esayas; Mekonen, Seblework; Legesse, Worku; Kloos, Helmut; Ambelu, Argaw

2014-01-10

Disinfection of contaminated water using solar radiation (SODIS) is known to inactivate bacteria. Its inactivation efficiency depends on local conditions where the disinfection is made. This study was aiming to test the efficiency of solar disinfection using different water parameters as low-cost household water treatment technology. Inactivation of microbes was tested using fecal coliform as test organism. The SODIS experiment was carried out at turbidity 2NTU, pH 7, and various water temperature (38.1°C, 41.8°C, 45.6°Cand 51.1°C) and solar intensities, using clear and black plastic bottles filled to different depths. The results show that the rate of microbial inactivation in relation to depth of water, turbidity, container type, intensity of light and color of container was statistically significant (p solar disinfection. By adjusting the parameters, complete and irreversible fecal coliform inactivation was achieved within an exposure time of less than four hours in the areas where the solar irradiance is about 3.99 kW/m2 and above. Our results indicate that application of SODIS could play a significant role in the provision of safe water in rural communities of developing countries where there is ample sunshine, specifically in sub-Saharan African countries.

The high cost of low-acuity ICU outliers.

Science.gov (United States)

Dahl, Deborah; Wojtal, Greg G; Breslow, Michael J; Holl, Randy; Huguez, Debra; Stone, David; Korpi, Gloria

2012-01-01

Direct variable costs were determined on each hospital day for all patients with an intensive care unit (ICU) stay in four Phoenix-area hospital ICUs. Average daily direct variable cost in the four ICUs ranged from $1,436 to $1,759 and represented 69.4 percent and 45.7 percent of total hospital stay cost for medical and surgical patients, respectively. Daily ICU cost and length of stay (LOS) were higher in patients with higher ICU admission acuity of illness as measured by the APACHE risk prediction methodology; 16.2 percent of patients had an ICU stay in excess of six days, and these LOS outliers accounted for 56.7 percent of total ICU cost. While higher-acuity patients were more likely to be ICU LOS outliers, 11.1 percent of low-risk patients were outliers. The low-risk group included 69.4 percent of the ICU population and accounted for 47 percent of all LOS outliers. Low-risk LOS outliers accounted for 25.3 percent of ICU cost and incurred fivefold higher hospital stay costs and mortality rates. These data suggest that severity of illness is an important determinant of daily resource consumption and LOS, regardless of whether the patient arrives in the ICU with high acuity or develops complications that increase acuity. The finding that a substantial number of long-stay patients come into the ICU with low acuity and deteriorate after ICU admission is not widely recognized and represents an important opportunity to improve patient outcomes and lower costs. ICUs should consider adding low-risk LOS data to their quality and financial performance reports.

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

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.

Key issues for low-cost FGD installations

Energy Technology Data Exchange (ETDEWEB)

DePriest, W.; Mazurek, J.M. [Sargent & Lundy LLC, Chicago, IL (United States)

1995-12-01

This paper will discuss various methods for installing low-cost FGD systems. The paper will include a discussion of various types of FGD systems available, both wet and dry, and will compare the relative cost of each type. Important design issues, such as use of spare equipment, materials of construction, etc. will be presented. An overview of various low-cost construction techniques (i.e., modularization) will be included. This paper will draw heavily from Sargent & Lundy`s database of past and current FGD projects together with information we gathered for several Electric Power Research Institute (EPRI) studies on the subject.

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.

Antiviral agents: structural basis of action and rational design.

Science.gov (United States)

Menéndez-Arias, Luis; Gago, Federico

2013-01-01

During the last 30 years, significant progress has been made in the development of novel antiviral drugs, mainly crystallizing in the establishment of potent antiretroviral therapies and the approval of drugs inhibiting hepatitis C virus replication. Although major targets of antiviral intervention involve intracellular processes required for the synthesis of viral proteins and nucleic acids, a number of inhibitors blocking virus assembly, budding, maturation, entry or uncoating act on virions or viral capsids. In this review, we focus on the drug discovery process while presenting the currently used methodologies to identify novel antiviral drugs by using a computer-based approach. We provide examples illustrating structure-based antiviral drug development, specifically neuraminidase inhibitors against influenza virus (e.g. oseltamivir and zanamivir) and human immunodeficiency virus type 1 protease inhibitors (i.e. the development of darunavir from early peptidomimetic compounds such as saquinavir). A number of drugs in preclinical development acting against picornaviruses, hepatitis B virus and human immunodeficiency virus and their mechanism of action are presented to show how viral capsids can be exploited as targets of antiviral therapy.

Potential Antiviral Agents from Marine Fungi: An Overview

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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.

Cost effectiveness of Tuberculosis Treatment from the Patients ...

African Journals Online (AJOL)

... Directly Observed Treatment Short course is more cost effective from the patients' point of view. DOTS needs to be re-focused out of the hospitals and clinics and made community based in view of the increasing TB caseload occasioned by HI V/AIDS. Key Words: Cost effectiveness, Tuberculosis treatment, personal cost, ...

Inkjet printing of antiviral PCL nanoparticles and anticancer cyclodextrin inclusion complexes on bioadhesive film for cervical administration.

Science.gov (United States)

Varan, Cem; Wickström, Henrika; Sandler, Niklas; Aktaş, Yeşim; Bilensoy, Erem

2017-10-15

Personalized medicine is an important treatment approach for diseases like cancer with high intrasubject variability. In this framework, printing is one of the most promising methods since it permits dose and geometry adjustment of the final product. With this study, a combination product consisting of anticancer (paclitaxel) and antiviral (cidofovir) drugs was manufactured by inkjet printing onto adhesive film for local treatment of cervical cancers as a result of HPV infection. Furthermore, solubility problem of paclitaxel was overcome by maintaining this poorly soluble drug in a cyclodextrin inclusion complex and release of cidofovir was controlled by encapsulation in polycaprolactone nanoparticles. In vitro characterization studies of printed film formulations were performed and cell culture studies showed that drug loaded film formulation was effective on human cervical adenocarcinoma cells. Our study suggests that inkjet printing technology can be utilized in the development of antiviral/anticancer combination dosage forms for mucosal application. The drug amount in the delivery system can be accurately controlled and modified. Moreover, prolonged drug release time can be obtained. Printing of anticancer and antiviral drugs on film seem to be a potential approach for HPV-related cervical cancer treatment and a good candidate for further studies. Copyright © 2017 Elsevier B.V. All rights reserved.

Efficacy and safety of direct-acting antivirals-based antiviral therapies for hepatitis C virus patients with stage 4-5 chronic kidney disease: a meta-analysis.

Science.gov (United States)

Li, Tao; Qu, Yundong; Guo, Ying; Wang, Yan; Wang, Lei

2017-07-01

The aim of this study was to assess the efficacy and safety of direct-acting antivirals (DAA)-based antiviral therapies for HCV patients with stage 4-5 chronic kidney disease. We conducted a systematic literature search in PubMed, EMBASE, Web of Science, and CENTRAL on the Cochrane Library without time and language limitations. The search strategy used was "(End stage renal disease OR chronic kidney failure OR severe renal impairment OR chronic kidney disease OR dialysis) AND (sofosbuvir OR simeprevir OR grazoprevir OR elbasvir OR ombitasvir OR paritaprevir OR ritonavir OR dasabuvir OR daclatasvir OR asuparevir OR direct-acting antiviral OR DAA)". Sustained virologic response at 12 weeks after the end of treatment (SVR12), adverse events (AEs) and/or serious adverse events (SAEs) with 95% confidence intervals (CI) were pooled. Eleven studies, comprising a total of 264 patients were included for our meta-analysis. The pooled SVR12 rate were 93.2% (95% CI 89.9%-95.9%, I 2 =0.0%), 89.4% (95% CI 82.0%-95.0%, I 2 =0.0%) and 94.7% (95% CI 91.0%-97.5%, I 2 =0.0%) in total population, patients with sofosbuvir-based therapies and patients with non-sofosbuvir-based therapies respectively. For HCV genotype 1 patients, the pooled SVR12 rate was 93.1% (95% CI 88.3%-96.7%, I 2 =20.0%). The pooled incidence of SAEs was 12.1% (95% CI 6.2%-19.7%, I 2 =55.0%). The pooled discontinuation rate because of AEs or SAEs in our meta-analysis was 2.2% (95% CI 0.8%-4.4%, I 2 =0.0%). DAA-based antiviral therapies are effective and well-tolerated for HCV patients with stage 4-5 chronic kidney disease. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Low cost design of microprocessor EDAC circuit

International Nuclear Information System (INIS)

Hao Li; Yu Lixin; Peng Heping; Zhuang Wei

2015-01-01

An optimization method of error detection and correction (EDAC) circuit design is proposed. The method involves selecting or constructing EDAC codes of low cost hardware, associated with operation scheduling implementation based on 2-input XOR gates structure, and two actions for reducing hardware cells, which can reduce the delay penalties and area costs of the EDAC circuit effectively. The 32-bit EDAC circuit hardware implementation is selected to make a prototype, based on the 180 nm process. The delay penalties and area costs of the EDAC circuit are evaluated. Results show that the time penalty and area cost of the EDAC circuitries are affected with different parity-check matrices and different hardware implementation for the EDAC codes with the same capability of correction and detection code. This method can be used as a guide for low-cost radiation-hardened microprocessor EDAC circuit design and for more advanced technologies. (paper)

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

Science.gov (United States)

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.

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

Science.gov (United States)

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.

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.

Antiviral activity of some Tunisian medicinal plants against Herpes simplex virus type 1.

Science.gov (United States)

Sassi, A Ben; Harzallah-Skhiri, F; Bourgougnon, N; Aouni, M

2008-01-10

Fifteen species of Tunisian traditional medicinal plants, belonging to 10 families, were selected for this study. They were Inula viscosa (L.) Ait and Reichardia tingitana (L.) Roth ssp. discolor (Pom.) Batt. (Asteraceae), Mesembryanthemum cristallinum L. and M. nodiflorum L. (Aizoaceae), Arthrocnemum indicum (Willd.) Moq., Atriplex inflata Muell., A. parvifolia Lowe var. ifiniensis (Caball) Maire, and Salicornia fruticosa L. (Chenopodiaceae), Cistus monspeliensis L. (Cistaceae), Juniperus phoenicea L. (Cupressaceae), Erica multiflora L. (Ericaceae), Frankenia pulverulenta L. (Frankeniaceae), Hypericum crispum L. (Hypericaceae), Plantago coronopus L. ssp. eu-coronopus Pilger var. vulgaris G.G. (Plantaginaceae) and Zygophyllum album L. (Zygophyllaceae). Fifty extracts prepared from those plants were screened in order to assay their antiviral activity against Herpes simplex virus type 1 (HSV-1), using neutral red incorporation. Extracts from eight plants among these 15 showed some degree of antiviral activity, while the methanolic extract of E. multiflora was highly active with EC(50) of 132.6 microg mL(-1). These results corroborate that medicinal plants from Tunisia can be a rich source of potential antiviral compounds.

Mixed and low-level waste treatment facility project. Volume 3, Waste treatment technologies (Draft)

Energy Technology Data Exchange (ETDEWEB)

1992-04-01

The technology information provided in this report is only the first step toward the identification and selection of process systems that may be recommended for a proposed mixed and low-level waste treatment facility. More specific information on each technology will be required to conduct the system and equipment tradeoff studies that will follow these preengineering studies. For example, capacity, maintainability, reliability, cost, applicability to specific waste streams, and technology availability must be further defined. This report does not currently contain all needed information; however, all major technologies considered to be potentially applicable to the treatment of mixed and low-level waste are identified and described herein. Future reports will seek to improve the depth of information on technologies.

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.

Treatment technology of low concentration uranium-bearing wastewater and its research progress

International Nuclear Information System (INIS)

Wei Guangzhi; Xu Lechang

2007-01-01

With growth of the discharged uranium-bearing wastewater capacity, a low cost and effective treatment technology is required to avoid transferring and diffusion of the radioactive nuclides. On the basis of analyses of the source and characteristics of the low-concentration uranium-bearing wastewater, the conventional treatment technologies, such as, flocculating settling, ion exchange, concentration, adsorption, and some innovatory technologies, such as, membrane, microorganism, phytoremediation and zero-valent iron technology are introduced. (authors)

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.

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

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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.

Costs and cost-effectiveness of different DOT strategies for the treatment of tuberculosis in Pakistan. Directly Observed Treatment.

Science.gov (United States)

Khan, M A; Walley, J D; Witter, S N; Imran, A; Safdar, N

2002-06-01

An economic study was conducted alongside a clinical trial at three sites in Pakistan to establish the costs and effectiveness of different strategies for implementing directly observed treatment (DOT) for tuberculosis. Patients were randomly allocated to one of three arms: DOTS with direct observation by health workers (at health centres or by community health workers); DOTS with direct observation by family members; and DOTS without direct observation. The clinical trial found no statistically significant difference in cure rate for the different arms. The economic study collected data on the full range of health service costs and patient costs of the different treatment arms. Data were also disaggregated by gender, rural and urban patients, by treatment site and by economic categories, to investigate the costs of the different strategies, their cost-effectiveness and the impact that they might have on patient compliance with treatment. The study found that direct observation by health centre-based health workers was the least cost-effective of the strategies tested (US dollars 310 per case cured). This is an interesting result, as this is the model recommended by the World Health Organization and International Union against Tuberculosis and Lung Disease. Attending health centres daily during the first 2 months generated high patient costs (direct and in terms of time lost), yet cure rates for this group fell below those of the non-observed group (58%, compared with 62%). One factor suggested by this study is that the high costs of attending may be deterring patients, and in particular, economically active patients who have most to lose from the time taken by direct observation. Without stronger evidence of benefits, it is hard to justify the costs to health services and patients that this type of direct observation imposes. The self-administered group came out as most cost-effective (164 dollars per case cured). The community health worker sub-group achieved the

Antiviral Activity of Favipiravir (T-705) against a Broad Range of Paramyxoviruses In Vitro and against Human Metapneumovirus in Hamsters.

Science.gov (United States)

Jochmans, D; van Nieuwkoop, S; Smits, S L; Neyts, J; Fouchier, R A M; van den Hoogen, B G

2016-08-01

The clinical impact of infections with respiratory viruses belonging to the family Paramyxoviridae argues for the development of antiviral therapies with broad-spectrum activity. Favipiravir (T-705) has demonstrated potent antiviral activity against multiple RNA virus families and is presently in clinical evaluation for the treatment of influenza. Here we demonstrate in vitro activity of T-705 against the paramyxoviruses human metapneumovirus (HMPV), respiratory syncytial virus, human parainfluenza virus, measles virus, Newcastle disease virus, and avian metapneumovirus. In addition, we demonstrate activity against HMPV in hamsters. T-705 treatment inhibited replication of all paramyxoviruses tested in vitro, with 90% effective concentration (EC90) values of 8 to 40 μM. Treatment of HMPV-challenged hamsters with T-705 at 200 mg/kg of body weight/day resulted in 100% protection from infection of the lungs. In all treated and challenged animals, viral RNA remained detectable in the respiratory tract. The observation that T-705 treatment had a significant effect on infectious viral titers, with a limited effect on viral genome titers, is in agreement with its proposed mode of action of viral mutagenesis. However, next-generation sequencing of viral genomes isolated from treated and challenged hamsters did not reveal (hyper)mutation. Polymerase activity assays revealed a specific effect of T-705 on the activity of the HMPV polymerase. With the reported antiviral activity of T-705 against a broad range of RNA virus families, this small molecule is a promising broad-range antiviral drug candidate for limiting the viral burden of paramyxoviruses and for evaluation for treatment of infections with (re)emerging viruses, such as the henipaviruses. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Cost of treatment for breast cancer in central Vietnam

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Nguyen Hoang Lan

2013-02-01

Full Text Available Background: In recent years, cases of breast cancer have been on the rise in Vietnam. To date, there has been no study on the financial burden of the disease. This study estimates the direct medical cost of a 5-year treatment course for women with primary breast cancer in central Vietnam. Methods: Retrospective patient-level data from medical records at the Hue Central Hospital between 2001 and 2006 were analyzed. Cost analysis was conducted from the health care payers’ perspective. Various direct medical cost categories were computed for a 5-year treatment course for patients with breast cancer. Costs, in US dollars, discounted at a 3% rate, were converted to 2010 after adjusting for inflation. For each cost category, the mean, standard deviation, median, and cost range were estimated. Median regression was used to investigate the relationship between costs and the stage, age at diagnosis, and the health insurance coverage of the patients. Results: The total direct medical cost for a 5-year treatment course for breast cancer in central Vietnam was estimated at $975 per patient (range: $11.7–$3,955. The initial treatment cost, particularly the cost of chemotherapy, was found to account for the greatest proportion of total costs (64.9%. Among the patient characteristics studied, stage at diagnosis was significantly associated with total treatment costs. Patients at later stages of breast cancer did not differ significantly in their total costs from those at earlier stages however, but their survival time was much shorter. The absence of health insurance was the main factor limiting service uptake. Conclusion: From the health care payers’ perspective, the Government subsidization of public hospital charges lowered the direct medical costs of a 5-year treatment course for primary breast cancer in central Vietnam. However, the long treatment course was significantly influenced by out-of-pocket payments for patients without health insurance.

The cost of nephroblastoma treatment in South Africa: A very cost ...

African Journals Online (AJOL)

2014-11-08

Nov 8, 2014 ... To determine the direct costs of treatment of nephroblastoma in South Africa (SA) and to propose a more cost-effective ... by the standard management of this disease in children may be ..... Study weaknesses and challenges.

Direct Acting Antivirals in Patients with Chronic Hepatitis C and Down Syndrome

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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.

Anti-viral therapy is associated with improved survival but is underutilised in patients with hepatitis B virus-related hepatocellular carcinoma: real-world east and west experience.

Science.gov (United States)

Chen, V L; Yeh, M-L; Le, A K; Jun, M; Saeed, W K; Yang, J D; Huang, C-F; Lee, H Y; Tsai, P-C; Lee, M-H; Giama, N; Kim, N G; Nguyen, P P; Dang, H; Ali, H A; Zhang, N; Huang, J-F; Dai, C-Y; Chuang, W-L; Roberts, L R; Jun, D W; Lim, Y-S; Yu, M-L; Nguyen, M H

2018-07-01

Hepatitis B virus (HBV) is the leading cause of hepatocellular carcinoma (HCC) worldwide. It remains incompletely understood in the real world how anti-viral therapy affects survival after HCC diagnosis. This was an international multicentre cohort study of 2518 HBV-related HCC cases diagnosed between 2000 and 2015. Cox proportional hazards models were utilised to estimate hazard ratios (HR) with 95% (CI) for anti-viral therapy and cirrhosis on patients' risk of death. Approximately, 48% of patients received anti-viral therapy at any time, but only 17% were on therapy at HCC diagnosis (38% at US centres, 11% at Asian centres). Anti-viral therapy would have been indicated for >60% of the patients not on anti-viral therapy based on American criteria. Patients with cirrhosis had lower 5-year survival (34% vs 46%; P < 0.001) while patients receiving anti-viral therapy had increased 5-year survival compared to untreated patients (42% vs 25% with cirrhosis and 58% vs 36% without cirrhosis; P < 0.001 for both). Similar findings were seen for other patient subgroups by cancer stages and cancer treatment types. Anti-viral therapy was associated with a decrease in risk of death, whether started before or after HCC diagnosis (adjusted HR 0.62 and 0.79, respectively; P < 0.001). Anti-viral therapy improved overall survival in patients with HBV-related HCC across cancer stages and treatment types but was underutilised at both US and Asia centres. Expanded use of anti-viral therapy in HBV-related HCC and better linkage-to-care for HBV patients are needed. © 2018 John Wiley & Sons Ltd.

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

Costs of topical treatment of pressure ulcer patients

Directory of Open Access Journals (Sweden)

Cynthia Carolina Duarte Andrade

2016-04-01

Full Text Available Abstract OBJECTIVE To evaluate the costs of a topical treatment of pressure ulcer (PU patients in a hospital unit for treatment of chronic patients in 2014. METHOD This is an activity-based costing study. This method encompasses the identification, measurement and pricing of physical and human resources consumed for dressings. RESULTS Procedure costs varied between BRL 16.41 and BRL 260.18. For PUs of the same category, of near areas and with the same type of barrier/adjuvant, the cost varied between 3.5% and 614.6%. For most dressings, the cost increased proportionally to the increase of the area and to the development of PU category. The primary barrier accounted for a high percentage of costs among all items required to the application of dressings (human and material resources. Dressings applied in sacral PUs had longer application times. CONCLUSION This study allowed us to understand the costs involved in the treatment of PUs, and it may support decision-makers and other cost-effectiveness studies.

Integrated constructed wetland systems: design, operation, and performance of low-cost decentralized wastewater treatment systems.

Science.gov (United States)

Behrends, L L; Bailey, E; Jansen, P; Houke, L; Smith, S

2007-01-01

Several different types of constructed wetland systems are being used as decentralized treatment systems including surface-flow, subsurface-flow, vertical-flow, and hybrid systems. Archetypical wetland systems have design strengths and weaknesses, and therefore it should be possible to design combined (integrated) systems to optimize a number of important treatment processes. This study provides comparative efficacy data for two integrated wetland treatment systems (IWTS) designed to enhance treatment of medium strength wastewater generated from a pilot-scale intensive fish farm. Results from the twenty eight months study included consistently high removal of COD (84% +) and ammonia nitrogen (93%) in both systems. Initially, phosphorus removal was also high (>90%) in both systems, but removal efficacy declined significantly over time. Nitrate removal was significantly better in the system that provided sequential aerobic and anoxic environments. Short hydraulic retention times coupled with sustained removal of COD and ammonia indicate that the ReCip components could be a least-cost wastewater treatment technology in the decentralized market sector.

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

Time-driven activity-based costing of low-dose-rate and high-dose-rate brachytherapy for low-risk prostate cancer.

Science.gov (United States)

Ilg, Annette M; Laviana, Aaron A; Kamrava, Mitchell; Veruttipong, Darlene; Steinberg, Michael; Park, Sang-June; Burke, Michael A; Niedzwiecki, Douglas; Kupelian, Patrick A; Saigal, Christopher

Cost estimates through traditional hospital accounting systems are often arbitrary and ambiguous. We used time-driven activity-based costing (TDABC) to determine the true cost of low-dose-rate (LDR) and high-dose-rate (HDR) brachytherapy for prostate cancer and demonstrate opportunities for cost containment at an academic referral center. We implemented TDABC for patients treated with I-125, preplanned LDR and computed tomography based HDR brachytherapy with two implants from initial consultation through 12-month followup. We constructed detailed process maps for provision of both HDR and LDR. Personnel, space, equipment, and material costs of each step were identified and used to derive capacity cost rates, defined as price per minute. Each capacity cost rate was then multiplied by the relevant process time and products were summed to determine total cost of care. The calculated cost to deliver HDR was greater than LDR by $2,668.86 ($9,538 vs. $6,869). The first and second HDR treatment day cost $3,999.67 and $3,955.67, whereas LDR was delivered on one treatment day and cost $3,887.55. The greatest overall cost driver for both LDR and HDR was personnel at 65.6% ($4,506.82) and 67.0% ($6,387.27) of the total cost. After personnel costs, disposable materials contributed the second most for LDR ($1,920.66, 28.0%) and for HDR ($2,295.94, 24.0%). With TDABC, the true costs to deliver LDR and HDR from the health system perspective were derived. Analysis by physicians and hospital administrators regarding the cost of care afforded redesign opportunities including delivering HDR as one implant. Our work underscores the need to assess clinical outcomes to understand the true difference in value between these modalities. Copyright © 2016 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Plant residues--a low cost, effective bioremediation treatment for petrogenic hydrocarbon-contaminated soil.

Science.gov (United States)

Shahsavari, Esmaeil; Adetutu, Eric M; Anderson, Peter A; Ball, Andrew S

2013-01-15

copy numbers. These results suggest that pea straw in particular represents a low cost, effective treatment to enhance the remediation of aliphatic hydrocarbons in contaminated soils. Copyright © 2012 Elsevier B.V. All rights reserved.

A Low-Cost Data Acquisition System for Automobile Dynamics Applications.

Science.gov (United States)

González, Alejandro; Olazagoitia, José Luis; Vinolas, Jordi

2018-01-27

This project addresses the need for the implementation of low-cost acquisition technology in the field of vehicle engineering: the design, development, manufacture, and verification of a low-cost Arduino-based data acquisition platform to be used in <80 Hz data acquisition in vehicle dynamics, using low-cost accelerometers. In addition to this, a comparative study is carried out of professional vibration acquisition technologies and low-cost systems, obtaining optimum results for low- and medium-frequency operations with an error of 2.19% on road tests. It is therefore concluded that these technologies are applicable to the automobile industry, thereby allowing the project costs to be reduced and thus facilitating access to this kind of research that requires limited resources.

Detection of the antiviral drug oseltamivir in aquatic environments.

Directory of Open Access Journals (Sweden)

Hanna Söderström

Full Text Available Oseltamivir (Tamiflu is the most important antiviral drug available and a cornerstone in the defence against a future influenza pandemic. Recent publications have shown that the active metabolite, oseltamivir carboxylate (OC, is not degraded in sewage treatment plants and is also persistent in aquatic environments. This implies that OC will be present in aquatic environments in areas where oseltamivir is prescribed to patients for therapeutic use. The country where oseltamivir is used most is Japan, where it is used to treat seasonal flu. We measured the levels of OC in water samples from the Yodo River system in the Kyoto and Osaka prefectures, Japan, taken before and during the flu-season 2007/8. No OC was detected before the flu-season but 2-58 ng L(-1 was detected in the samples taken during the flu season. This study shows, for the first time, that low levels of oseltamivir can be found in the aquatic environment. Therefore the natural reservoir of influenza virus, dabbling ducks, is exposed to oseltamivir, which could promote the evolution of viral resistance.

Patient medical costs for tuberculosis treatment and impact on adherence in China: a systematic review

Directory of Open Access Journals (Sweden)

Zhang Tuohong

2011-05-01

Full Text Available Abstract Background Charging for tuberculosis (TB treatment could reduce completion rates, particularly in the poor. We identified and synthesised studies that measure costs of TB treatment, estimates of adherence and the potential impact of charging on treatment completion in China. Methods Inclusion criteria were primary research studies, including surveys and studies using qualitative methods, conducted in mainland China. We searched MEDLINE, PUBMED, EMBASE, Science Direct, HEED, CNKI to June 2010; and web pages of relevant Chinese and international organisations. Cost estimates were extracted, transformed, and expressed in absolute values and as a percentage of household income. Results Low income patients, defined at household or district level, pay a total of US$ 149 to 724 (RMB 1241 to 5228 for medical costs for a treatment course; as a percentage of annual household income, estimates range from 42% to 119%. One national survey showed 73% of TB patients at the time of the survey had interrupted or suspended treatment, and estimates from 9 smaller more recent studies showed that the proportion of patients at the time of the survey who had run out of drugs or were not taking them ranged from 3 to 25%. Synthesis of surveys and qualitative research indicate that cost is the most cited reason for default. Conclusions Despite a policy of free drug treatment for TB in China, health services charge all income groups, and costs are high. Adherence measured in cross sectional surveys is often low, and the cumulative failure to adhere is likely to be much higher. These findings may be relevant to those concerned with the development and spread of multi-drug resistant TB. New strategies need to take this into account and ensure patient adherence.

Oral antiviral therapy for prevention of genital herpes outbreaks in immunocompetent and nonpregnant patients.

Science.gov (United States)

Le Cleach, Laurence; Trinquart, Ludovic; Do, Giao; Maruani, Annabel; Lebrun-Vignes, Benedicte; Ravaud, Philippe; Chosidow, Olivier

2014-08-03

Genital herpes is caused by herpes simplex virus 1 (HSV-1) or 2 (HSV-2). Some infected people experience outbreaks of genital herpes, typically, characterized by vesicular and erosive localized painful genital lesions. To compare the effectiveness and safety of three oral antiviral drugs (acyclovir, famciclovir and valacyclovir) prescribed to suppress genital herpes outbreaks in non-pregnant patients. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the search portal of the World Health Organization International Clinical Trials Registry Platform and pharmaceutical company databases up to February 2014. We also searched US Food and Drug Administration databases and proceedings of seven congresses to a maximum of 10 years. We contacted trial authors and pharmaceutical companies. We selected parallel-group and cross-over randomized controlled trials including patients with recurrent genital herpes caused by HSV, whatever the type (HSV-1, HSV-2, or undetermined), with at least four recurrences per year (trials concerning human immunodeficiency virus (HIV)-positive patients or pregnant women were not eligible) and comparing suppressive oral antiviral treatment with oral acyclovir, famciclovir, and valacyclovir versus placebo or another suppressive oral antiviral treatment. Two review authors independently selected eligible trials and extracted data. The Risk of bias tool was used to assess risk of bias. Treatment effect was measured by the risk ratio (RR) of having at least one genital herpes recurrence. Pooled RRs were derived by conventional pairwise meta-analyses. A network meta-analysis allowed for estimation of all possible two-by-two comparisons between antiviral drugs. A total of 26 trials (among which six had a cross-over design) were included. Among the 6950 randomly assigned participants, 54% (range 0 to 100%) were female, mean age was 35 years (range 26 to 45.1), and the mean number of recurrences per year was 11

High-Efficient Low-Cost Photovoltaics Recent Developments

CERN Document Server

Petrova-Koch, Vesselinka; Goetzberger, Adolf

2009-01-01

A bird's-eye view of the development and problems of recent photovoltaic cells and systems and prospects for Si feedstock is presented. High-efficient low-cost PV modules, making use of novel efficient solar cells (based on c-Si or III-V materials), and low cost solar concentrators are in the focus of this book. Recent developments of organic photovoltaics, which is expected to overcome its difficulties and to enter the market soon, are also included.

Delivery Unit Costs for Antiretroviral Treatment and Prevention of Mother-to-Child-Transmission of HIV

Science.gov (United States)

Galárraga, Omar; Wirtz, Veronika J.; Figueroa-Lara, Alejandro; Santa-Ana-Tellez, Yared; Coulibaly, Ibrahima; Viisainen, Kirsi; Medina-Lara, Antonieta; Korenromp, Eline L.

2013-01-01

Background As antiretroviral treatment (ART) for HIV/AIDS is scaled-up globally, information on per-person costs is critical to improve efficiency in service delivery and maximize coverage and health impact. Objective To review studies on delivery unit costs for adult and pediatric ART provision per-patient-year, and prevention of mother-to-child transmission (PMTCT) interventions per mother-infant pair screened or treated, in low- and middle-income countries. Methods Systematic review of English, French and Spanish publications from 2001 to 2009, reporting empirical costing that accounted for at least antiretroviral (ARV) medicines, laboratory testing and personnel. Expenditures were analyzed by country income level and cost component. All costs were standardized to 2009 US dollars. Results Analyses covered 29 eligible, comprehensive costing studies. In the base case, in low-income countries (LIC), median, ART cost per patient-year was $792 (mean: $839, range: $682-$1089); for lower-middle-income countries (LMIC), the median was $932 (mean: $1246, range: $156-$3904); and for upper-middle-income countries (UMIC) the median was $1454 (mean: $2783, range: $1230-$5667). ARV drugs were largest component of overall ART cost in all settings (62%, 50% and 47% in LIC, LMIC and UMIC respectively). Out of 26 ART studies, 14 report which drug regimes were used, and only one study explicitly reported second line treatment costs. The second cost driver was laboratory cost in LIC and LMIC (14% and 19.5%) whereas it was personnel costs in UMIC (26%). Two studies specified the types of laboratory tests costed, and three studies specifically included above-facility-level personnel costs. Three studies reported detailed PMTCT costs, and two studies reported on pediatric ART. Conclusions There is a paucity of data on the full ART and PMTCT delivery unit costs, in particular for low-and middle-income countries. Heterogeneity in activities costed and insufficient detail regarding

IRF-4 and c-Rel expression in antiviral-resistant adult T-cell leukemia/lymphoma

Science.gov (United States)

Ramos, Juan Carlos; Ruiz, Phillip; Ratner, Lee; Reis, Isildinha M.; Brites, Carlos; Pedroso, Celia; Byrne, Gerald E.; Toomey, Ngoc L.; Andela, Valentine; Harhaj, Edward W.; Lossos, Izidore S.

2007-01-01

Adult T-cell leukemia/lymphoma (ATLL) is a generally fatal malignancy. Most ATLL patients fare poorly with conventional chemotherapy; however, antiviral therapy with zidovudine (AZT) and interferon alpha (IFN-α) has produced long-term clinical remissions. We studied primary ATLL tumors and identified molecular features linked to sensitivity and resistance to antiviral therapy. Enhanced expression of the proto-oncogene c-Rel was noted in 9 of 27 tumors. Resistant tumors exhibited c-Rel (6 of 10; 60%) more often than did sensitive variants (1 of 9; 11%). This finding was independent of the disease form. Elevated expression of the putative c-Rel target, interferon regulatory factor-4 (IRF-4), was observed in 10 (91%) of 11 nonresponders and in all tested patients with c-Rel+ tumors and occurred in the absence of the HTLV-1 oncoprotein Tax. In contrast, tumors in complete responders did not express c-Rel or IRF-4. Gene rearrangement studies demonstrated the persistence of circulating T-cell clones in long-term survivors maintained on antiviral therapy. The expression of nuclear c-Rel and IRF-4 occurs in the absence of Tax in primary ATLL and is associated with antiviral resistance. These molecular features may help guide treatment. AZT and IFN-α is a suppressive rather than a curative regimen, and patients in clinical remission should remain on maintenance therapy indefinitely. PMID:17138822

Laser-based microstructuring of materials surfaces using low-cost microlens arrays

Science.gov (United States)

Nieto, Daniel; Vara, G.; Diez, J. A.; O`Connor, Gerard M.; Arines, Justo; Gómez-Reino, C.; Flores-Arias, M.

2012-03-01

Since frictional interactions in microscopically small components are becoming increasingly important for the development of new products for all modern technology, we present a laser-based technique for micro-patterning surfaces of materials using low-cost microlens arrays. The microlens used were fabricated on soda-lime glass using a laser direct-write technique, followed by a thermal treatment into an oven. By combining laser direct-write and the thermal treatment it was possible to obtain high quality elements using a low cost infrared laser widely implemented in industry which makes this technique attractive in comparison with other more expensive methods. The main advantage of using microlens arrays for micropatterning surfaces is the possibility of fabricating a large number of identical structures simultaneously, leading to a highly efficient process. In order to study the capabilities of the microlens fabricated for microstructuring materials, identical structures and arrays of holes were fabricated over a variety of materials, such us, stainless steel, polymer and ceramic. The minimum diameter of the individual microstructure generated at surface is 5 μm. Different nanosecond lasers operating at Infrared, Green and UV were used. The topography and morphology of the elements obtained were determined using a confocal microscope SENSOFAR 2300 Plμ.

Cost of Tuberculosis Diagnosis and Treatment in Patients with HIV: A Systematic Literature Review.

Science.gov (United States)

de Siqueira-Filha, Noemia Teixeira; Legood, Rosa; Cavalcanti, Aracele; Santos, Andreia Costa

2018-04-01

To summarize the costs of tuberculosis (TB) diagnosis and treatment in human immunodeficiency virus (HIV)-infected patients and to assess the methodological quality of these studies. We included cost, cost-effectiveness, and cost-utility studies that reported primary costing data, conducted worldwide and published between 1990 and August 2016. We retrieved articles in PubMed, Embase, EconLit, CINAHL plus, and LILACS databases. The quality assessment was performed using two guidelines-the Consolidated Health Economic Evaluation Reporting Standards and the Tool to Estimate Patient's Costs. TB diagnosis was reported as cost per positive result or per suspect case. TB treatment was reported as cost of TB drugs, TB/HIV hospitalization, and treatment. We analyzed the data per level of TB/HIV endemicity and perspective of analysis. We included 34 articles, with 24 addressing TB/HIV treatment and 10 addressing TB diagnosis. Most of the studies were carried out in high TB/HIV burden countries (82%). The cost of TB diagnosis per suspect case varied from $0.5 for sputum smear microscopy to $175 for intensified case finding. The cost of TB/HIV hospitalization was higher in low/medium TB/HIV burden countries than in high TB/HIV burden countries ($75,406 vs. $2,474). TB/HIV co-infection presented higher costs than TB from the provider perspective ($814 vs. $604 vs. $454). Items such as "choice of discount rate," "patient interview procedures," and "methods used for valuing indirect costs" did not achieve a good score in the quality assessment. Our findings point to the need of generation of more standardized methods for cost data collection to generate more robust estimates and thus, support decision-making process. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

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

Optical incremental rotary encoder in low-cost-design; Optischer inkrementaler Drehgeber in Low-Cost-Bauweise

Energy Technology Data Exchange (ETDEWEB)

Hopp, David; Pruss, Christof; Osten, Wolfgang [Stuttgart Univ. (Germany). Inst. fuer Technische Optik; Seybold, Jonathan; Mayer, Volker [Hans-Schickard-Gesellschaft, Stuttgart (DE). Inst. fuer Mikroaufbautechnik (IMAT); Kueck, Heinz [Hans-Schickard-Gesellschaft, Stuttgart (DE). Inst. fuer Mikroaufbautechnik (IMAT); Stuttgart Univ. (Germany). Inst. fuer Zeitmesstechnik, Fein- und Mikrotechnik

2010-07-01

We have developed a new concept for low-cost optical encoders to come up to meet the increasing demand for inexpensive rotary sensors. The principal idea is to use a micro patterned plastic disc with metal coating, as it is used for Compact Discs or DVDs. Such encoder discs can be manufactured by an efficient injection compression moulding process. With this well established technique it is possible to achieve highly precise micro patterns while running a cost effective process for high volume production. (orig.)

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.

Synthesis and antiviral activities of a novel class of thioflavone and flavonoid analogues

Directory of Open Access Journals (Sweden)

Dajun Zhang

2012-12-01

Full Text Available A novel class of thioflavone and flavonoid derivatives has been prepared and their antiviral activities against enterovirus 71 (EV71 and the coxsackievirus B3 (CVB3 and B6 (CVB6 were evaluated. Compounds 7d and 9b showed potent antiviral activities against EV71 with IC50 values of 8.27 and 5.48 μM, respectively. Compound 7f, which has been synthesized for the first time in this work, showed the highest level of inhibitory activity against both CVB3 and CVB6 with an IC50 value of 0.62 and 0.87 μM. Compounds 4b, 7a, 9c and 9e also showed strong inhibitory activities against both the CVB3 and CVB6 at low concentrations (IC50=1.42−7.15 μM, whereas compounds 4d, 7c, 7e and 7g showed strong activity against CVB6 (IC50=2.91–3.77 μM together with low levels of activity against CVB3. Compound 7d exhibited stronger inhibitory activity against CVB3 (IC50=6.44 μM than CVB6 (IC50>8.29 μM. The thioflavone derivatives 7a, 7c, 7d, 7e, 7f and 7g, represent a new class of lead compounds for the development of novel antiviral agents.

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.

Low-Cost Sorbents: A Literature Summary

National Research Council Canada - National Science Library

Bailey, Susan

1997-01-01

The capital and regeneration costs of activated carbon and ion exchange media suggest that better process economics may be achieved with disposable sorbents for the treatment of metals-contaminated...

Development of low-cost digital subtraction angiography system

International Nuclear Information System (INIS)

Ando, Yutaka; Kobayashi, Takeshi; Imai, Yutaka; Yagishita, Akira; Kunieda, Etsuo.

1983-01-01

We developed a simple and low-cost DSA system. This system consists of a conventional fluoroscopic equipment for the GI tract and a mini-computer (GAMMA-11) which are connected each other with a video-disc recorder. The uniqueness of our system are 1. low-cost, 2. low-radiation dose, 3. off-line processing, 4. flexibility of software. The analysis of the time-density curve and image processing will bring us a more usefull information than DSA alone. (author)

Cost-effectiveness analysis of treatments for premenstrual dysphoric disorder.

Science.gov (United States)

Rendas-Baum, Regina; Yang, Min; Gricar, Joseph; Wallenstein, Gene V

2010-01-01

Premenstrual syndrome (PMS) is reported to affect between 13% and 31% of women. Between 3% and 8% of women are reported to meet criteria for the more severe form of PMS, premenstrual dysphoric disorder (PMDD). Although PMDD has received increased attention in recent years, the cost effectiveness of treatments for PMDD remains unknown. To evaluate the cost effectiveness of the four medications with a US FDA-approved indication for PMDD: fluoxetine, sertraline, paroxetine and drospirenone plus ethinyl estradiol (DRSP/EE). A decision-analytic model was used to evaluate both direct costs (medication and physician visits) and clinical outcomes (treatment success, failure and discontinuation). Medication costs were based on average wholesale prices of branded products; physician visit costs were obtained from a claims database study of PMDD patients and the Agency for Healthcare Research and Quality. Clinical outcome probabilities were derived from published clinical trials in PMDD. The incremental cost-effectiveness ratio (ICER) was calculated using the difference in costs and percentage of successfully treated patients at 6 months. Deterministic and probabilistic sensitivity analyses were used to assess the impact of uncertainty in parameter estimates. Threshold values where a change in the cost-effective strategy occurred were identified using a net benefit framework. Starting therapy with DRSP/EE dominated both sertraline and paroxetine, but not fluoxetine. The estimated ICER of initiating treatment with fluoxetine relative to DRSP/EE was $US4385 per treatment success (year 2007 values). Cost-effectiveness acceptability curves revealed that for ceiling ratios>or=$US3450 per treatment success, fluoxetine had the highest probability (>or=0.37) of being the most cost-effective treatment, relative to the other options. The cost-effectiveness acceptability frontier further indicated that DRSP/EE remained the option with the highest expected net monetary benefit for

Correlation of radioactive waste treatment costs and the environmental impact of waste effluents in the nuclear fuel cycle for use in establishing ''as low as practicable'' guides: nuclear fuel reprocessing

International Nuclear Information System (INIS)

Finney, B.C.; Blanco, R.E.; Dahlman, R.C.; Kitts, F.G.; Witherspoon, J.P.

1975-05-01

A cost-benefit study was made to determine the cost and effectiveness of radioactive waste (radwaste) treatment systems for decreasing the release of radioactive materials from a model nuclear fuel reprocessing plant which processes light-water reactor (LWR) fuels, and to determine the radiological impact (dose commitment) of the released materials on the environment. The study is designed to assist in defining the term ''as low as practicable'' in relation to limiting the release of radioactive materials from nuclear facilities. The base case model plant is representative of current plant technology and has an annual capacity of 1500 metric tons of LWR fuel. Additional radwaste treatment systems are added to the base case plant in a series of case studies to decrease the amounts of radioactive materials released and to reduce the radiological dose commitment to the population in the surrounding area. The cost for the added waste treatment operations and the corresponding dose commitments are calculated for each case. In the final analysis, radiological dose is plotted vs the annual cost for treatment of the radwastes. The status of the radwaste treatment methods used in the case studies is discussed. Much of the technology used in the advanced cases is in an early stage of development and is not suitable for immediate use. The methodology used in estimating the costs and the radiological doses, detailed calculations, and tabulations is presented in Appendix A and ORNL-4992. (U.S.)

Therapies for treatment of osteoporosis in US women: cost-effectiveness and budget impact considerations.

Science.gov (United States)

Tosteson, Anna N A; Burge, Russel T; Marshall, Deborah A; Lindsay, Robert

2008-09-01

To evaluate the cost-effectiveness of osteoporosis treatments for women at high fracture risk and estimate the population-level impact of providing bisphosphonate therapy to all eligible high-risk US women. Fractures, healthcare costs, and quality-adjusted life-years (QALYs) were estimated over 10 years using a Markov model. No therapy, risedronate, alendronate, ibandronate, and teriperatide (PTH) were compared among 4 risk groups. Sensitivity analyses examined the robustness of model results for 65-year-old women with low bone density and previous vertebral fracture. Women treated with a bisphosphonate experienced fewer fractures and more QALYs compared with no therapy or PTH. Total costs were lowest for the untreated cohort, followed by risedronate, alendronate, ibandronate, and PTH in all risk groups except women aged 75 years with previous fracture. The incremental cost-effectiveness of risedronate compared with no therapy ranged from cost saving for the base case to $66,722 per QALY for women aged 65 years with no previous fracture. Ibandronate and PTH were dominated in all risk groups. (A dominated treatment has a higher cost and poorer outcome.) Treating all eligible women with a bisphosphonate would cost an estimated additional $5563 million (21% total increase) and would result in 390,049 fewer fractures (35% decrease). In the highest risk group, the additional cost of therapy was offset by other healthcare cost savings. Osteoporosis treatment of high-risk women is cost-effective, with bisphosphonates providing the most benefit at lowest cost. For highest risk women, costs are offset by savings from fracture prevention.

Cost-effectiveness of In-Home Cognitive Behavioral Therapy for low-income depressed mothers participating in early childhood prevention programs.

Science.gov (United States)

Ammerman, Robert T; Mallow, Peter J; Rizzo, John A; Putnam, Frank W; Van Ginkel, Judith B

2017-01-15

To determine the cost-effectiveness of In-Home Cognitive Behavioral Therapy (IH-CBT) for low-income mothers enrolled in a home visiting program. A cost-utility analysis was conducted using results from a clinical trial of IH-CBT and standard of care for depression derived from the literature. A probabilistic, patient-level Markov model was developed to determine Quality Adjusted Life Years (QALYs). Costs were determined using the Medical Expenditure Panel Survey. A three-year time horizon and payer perspective were used. Sensitivity analyses were employed to determine robustness of the model. IH-CBT was cost-effective relative to standard of care. IH-CBT was expected to be cost-effective at a three-year time horizon 99.5%, 99.7%, and 99.9% of the time for willingness-to-pay thresholds of US$25,000, US$50,000, and US$100,000, respectively. Patterns were upheld at one-year and five-year time horizons. Over the three-year time horizon, mothers receiving IH-CBT were expected to have 345.6 fewer days of depression relative to those receiving standard home visiting and treatment in the community. IH-CBT is a more cost-effective treatment for low-income, depressed mothers than current standards of practice. These findings add to the growing literature demonstrating the cost-effectiveness of CBT for depression, and expand it to cover new mothers. From a payer perspective, IH-CBT is a sound option for treatment of depressed, low-income mothers. Limitations include a restricted time horizon and estimating of standard of care costs. Copyright © 2016 Elsevier B.V. All rights reserved.

Nucleic acid-induced antiviral immunity in invertebrates: an evolutionary perspective.

Science.gov (United States)

Wang, Pei-Hui; Weng, Shao-Ping; He, Jian-Guo

2015-02-01

Nucleic acids derived from viral pathogens are typical pathogen associated molecular patterns (PAMPs). In mammals, the recognition of viral nucleic acids by pattern recognition receptors (PRRs), which include Toll-like receptors (TLRs) and retinoic acid-inducible gene (RIG)-I-like receptors (RLRs), induces the release of inflammatory cytokines and type I interferons (IFNs) through the activation of nuclear factor κB (NF-κB) and interferon regulatory factor (IRF) 3/7 pathways, triggering the host antiviral state. However, whether nucleic acids can induce similar antiviral immunity in invertebrates remains ambiguous. Several studies have reported that nucleic acid mimics, especially dsRNA mimic poly(I:C), can strongly induce non-specific antiviral immune responses in insects, shrimp, and oyster. This behavior shows multiple similarities to the hallmarks of mammalian IFN responses. In this review, we highlight the current understanding of nucleic acid-induced antiviral immunity in invertebrates. We also discuss the potential recognition and regulatory mechanisms that confer non-specific antiviral immunity on invertebrate hosts. Copyright © 2014 Elsevier Ltd. All rights reserved.

Organizing for low cost space operations - Status and plans

Science.gov (United States)

Lee, C.

1976-01-01

Design features of the Space Transportation System (vehicle reuse, low cost expendable components, simple payload interfaces, standard support systems) must be matched by economical operational methods to achieve low operating and payload costs. Users will be responsible for their own payloads and will be charged according to the services they require. Efficient use of manpower, simple documentation, simplified test, checkout, and flight planning are firm goals, together with flexibility for quick response to varying user needs. Status of the Shuttle hardware, plans for establishing low cost procedures, and the policy for user charges are discussed.

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

DMPD: Regulation of mitochondrial antiviral signaling pathways. [Dynamic Macrophage Pathway CSML Database

Lifescience Database Archive (English)

Full Text Available 18549796 Regulation of mitochondrial antiviral signaling pathways. Moore CB, Ting J...P. Immunity. 2008 Jun;28(6):735-9. (.png) (.svg) (.html) (.csml) Show Regulation of mitochondrial antiviral ...signaling pathways. PubmedID 18549796 Title Regulation of mitochondrial antiviral signaling pathways. Author

The Cost of Providing Comprehensive HIV Treatment in PEPFAR-Supported Programs

Science.gov (United States)

Menzies, Nicolas A; Berruti, Andres A; Berzon, Richard; Filler, Scott; Ferris, Robert; Ellerbrock, Tedd V; Blandford, John M

2011-01-01

PEPFAR, national governments, and other stakeholders are investing unprecedented resources to provide HIV treatment in developing countries. This study reports empirical data on costs and cost trends in a large sample of HIV treatment sites. In 2006–2007, we conducted cost analyses at 43 PEPFAR-supported outpatient clinics providing free comprehensive HIV treatment in Botswana, Ethiopia, Nigeria, Uganda, and Vietnam. We collected data on HIV treatment costs over consecutive 6-month periods from scale-up of dedicated HIV treatment services at each site. The study included all patients receiving HIV treatment and care at study sites (62,512 ART and 44,394 pre-ART patients). Outcomes were costs per-patient and total program costs, subdivided by major cost categories. Median annual economic costs were $202 (2009 USD) for pre-ART patients and $880 for ART patients. Excluding ARVs, per-patient ART costs were $298. Care for newly initiated ART patients cost 15–20% more than for established patients. Per-patient costs dropped rapidly as sites matured, with per-patient ART costs dropping 46.8% between first and second 6-month periods after the beginning of scale-up, and an additional 29.5% the following year. PEPFAR provided 79.4% of funding for service delivery, and national governments provided 15.2%. Treatment costs vary widely between sites, and high early costs drop rapidly as sites mature. Treatment costs vary between countries and respond to changes in ARV regimen costs and the package of services. While cost reductions may allow near-term program growth, programs need to weigh the trade-off between improving services for current patients and expanding coverage to new patients. PMID:21412127

Low-cost, low-weight CNG cylinder development. Final report

Energy Technology Data Exchange (ETDEWEB)

Richards, Mark E.; Melford, K.; Wong, J.; Gambone, L.

1999-09-01

This program was established to develop and commercialize new high-strength steel-lined, composite hoop-wrapped compressed natural gas (CNG) cylinders for vehicular applications. As much as 70% of the cost of natural gas vehicles can be related to on-board natural gas storage costs. The cost and weight targets for this program represent significant savings in each characteristic when compared to comparable containers available at the initiation of the program. The program objectives were to optimize specific weight and cost goals, yielding CNG cylinders with dimensions that should, allowing for minor modifications, satisfy several vehicle market segments. The optimization process encompassed material, design, and process improvement. In optimizing the CNG cylinder design, due consideration was given to safety aspects relative to national, international, and vehicle manufacturer cylinder standards and requirements. The report details the design and development effort, encompassing plant modifications, material selection, design issues, tooling development, prototype development, and prototype testing. Extenuating circumstances prevented the immediate commercialization of the cylinder designs, though significant progress was made towards improving the cost and performance of CNG cylinders. A new low-cost fiber was successfully employed while the weight target was met and the cost target was missed by less than seven percent.

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 ...

Low-cost uncooled VOx infrared camera development

Science.gov (United States)

Li, Chuan; Han, C. J.; Skidmore, George D.; Cook, Grady; Kubala, Kenny; Bates, Robert; Temple, Dorota; Lannon, John; Hilton, Allan; Glukh, Konstantin; Hardy, Busbee

2013-06-01

The DRS Tamarisk® 320 camera, introduced in 2011, is a low cost commercial camera based on the 17 µm pixel pitch 320×240 VOx microbolometer technology. A higher resolution 17 µm pixel pitch 640×480 Tamarisk®640 has also been developed and is now in production serving the commercial markets. Recently, under the DARPA sponsored Low Cost Thermal Imager-Manufacturing (LCTI-M) program and internal project, DRS is leading a team of industrial experts from FiveFocal, RTI International and MEMSCAP to develop a small form factor uncooled infrared camera for the military and commercial markets. The objective of the DARPA LCTI-M program is to develop a low SWaP camera (costs less than US $500 based on a 10,000 units per month production rate. To meet this challenge, DRS is developing several innovative technologies including a small pixel pitch 640×512 VOx uncooled detector, an advanced digital ROIC and low power miniature camera electronics. In addition, DRS and its partners are developing innovative manufacturing processes to reduce production cycle time and costs including wafer scale optic and vacuum packaging manufacturing and a 3-dimensional integrated camera assembly. This paper provides an overview of the DRS Tamarisk® project and LCTI-M related uncooled technology development activities. Highlights of recent progress and challenges will also be discussed. It should be noted that BAE Systems and Raytheon Vision Systems are also participants of the DARPA LCTI-M program.

Estimating average inpatient and outpatient costs and childhood pneumonia and diarrhoea treatment costs in an urban health centre in Zambia

Directory of Open Access Journals (Sweden)

Chola Lumbwe

2009-10-01

Full Text Available Abstract Background Millions of children die every year in developing countries, from preventable diseases such as pneumonia and diarrhoea, owing to low levels of investment in child health. Investment efforts are hampered by a general lack of adequate information that is necessary for priority setting in this sector. This paper measures the health system costs of providing inpatient and outpatient services, and also the costs associated with treating pneumonia and diarrhoea in under-five children at a health centre in Zambia. Methods Annual economic and financial cost data were collected in 2005-2006. Data were summarized in a Microsoft excel spreadsheet to obtain total department costs and average disease treatment costs. Results The total annual cost of operating the health centre was US$1,731,661 of which US$1 284 306 and US$447,355 were patient care and overhead departments costs, respectively. The average cost of providing out-patient services was US$3 per visit, while the cost of in-patient treatment was US$18 per bed day. The cost of providing dental services was highest at US$20 per visit, and the cost of VCT services was lowest, with US$1 per visit. The cost per out-patient visit for under-five pneumonia was US$48, while the cost per bed day was US$215. The cost per outpatient visit attributed to under-five diarrhoea was US$26, and the cost per bed day was US$78. Conclusion In the face of insufficient data, a cost analysis exercise is a difficult but feasible undertaking. The study findings are useful and applicable in similar settings, and can be used in cost effectiveness analyses of health interventions.

Comparison of porosity assessment techniques for low-cost ceramic membranes

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Maria-Magdalena Lorente-Ayza

2017-01-01

Full Text Available Several characterization methods were applied to low cost ceramic membranes developed for wastewater treatment in membrane bioreactors (MBRs and/or tertiary treatments. The membranes were prepared by four different procedures (uniaxial pressing and extrusion, both with and without starch addition to generate pores. The pore size of these symmetric ceramic membranes was measured by two different methods: bubble point and intrusion mercury porosimetry. A good agreement between both methods was achieved, confirming the validity of the bubble point method for the measurement of the mean pore size of membranes. Air and water permeations of these ceramic membranes were also studied. The relationship between the permeation of both fluids is consistent with the ratio of viscosities, according to the Hagen–Poiseuille equation.

Comparison of porosity assessment techniques for low-cost ceramic membranes

Energy Technology Data Exchange (ETDEWEB)

Lorente-Ayza, M.M.; Perez-Fernandez, O.; Alcala, R.; Sanchez, A.; Mestre, S.; Coronas, J.; Menendez, M.

2017-07-01

Several characterization methods were applied to low cost ceramic membranes developed for wastewater treatment in membrane bioreactors (MBRs) and/or tertiary treatments. The membranes were prepared by four different procedures (uniaxial pressing and extrusion, both with and without starch addition to generate pores). The pore size of these symmetric ceramic membranes was measured by two different methods: bubble point and intrusion mercury porosimetry. A good agreement between both methods was achieved, confirming the validity of the bubble point method for the measurement of the mean pore size of membranes. Air and water permeations of these ceramic membranes were also studied. The relationship between the permeation of both fluids is consistent with the ratio of viscosities, according to the Hagen–Poiseuille equation. (Author)

Prices paid for adult and paediatric antiretroviral treatment by low- and middle-income countries in 2012: high, low or just right?

Science.gov (United States)

Perriëns, Joseph H; Habiyambere, Vincent; Dongmo-Nguimfack, Boniface; Hirnschall, Gottfried

2014-01-01

A viable market for antiretroviral drugs in low- and middle-income countries is key to the continued scale-up of antiretroviral treatment. We describe the price paid by low- and middle-income countries for 10 first- and 7 second-line adult and paediatric treatment regimens from 2003 to 2012, and compare the price of their finished formulations with the price of their active pharmaceutical ingredients in 2005, 2007, 2010 and 2012. Between 2003 and 2012 the median price of adult first-line treatment regimens per treatment-year decreased from USD499 to USD122, and that of second-line regimens from USD2,934 to USD497. In 2005 adult formulations were sold for a price 170% higher than the cost of their active pharmaceutical ingredients. This margin had decreased to 28% in 2012. Between 2004 and 2013, the price of paediatric treatment per treatment-year decreased from USD585 to USD147 for first-line and from USD763 to USD288 for second-line treatment. In 2005, paediatric treatment regimens were sold at a price 231% higher than the cost of their active pharmaceutical ingredients. This margin remained high and was 195% in 2012. The prices paid for antiretroviral drugs by low- and middle-income countries decreased between 2003 and 2012. Although the margins on their sale decreased, there is likely still space for price reduction, especially for the more recent World Health Organization recommended adult first-line regimens and for paediatric treatment.

Risk-Cost Estimation of On-Site Wastewater Treatment System Failures Using Extreme Value Analysis.

Science.gov (United States)

Kohler, Laura E; Silverstein, JoAnn; Rajagopalan, Balaji

2017-05-01

  Owner resistance to increasing regulation of on-site wastewater treatment systems (OWTS), including obligatory inspections and upgrades, moratoriums and cease-and-desist orders in communities around the U.S. demonstrate the challenges associated with managing risks of inadequate performance of owner-operated wastewater treatment systems. As a result, determining appropriate and enforceable performance measures in an industry with little history of these requirements is challenging. To better support such measures, we develop a statistical method to predict lifetime failure risks, expressed as costs, in order to identify operational factors associated with costly repairs and replacement. A binomial logistic regression is used to fit data from public records of reported OWTS failures, in Boulder County, Colorado, which has 14 300 OWTS to determine the probability that an OWTS will be in a low- or high-risk category for lifetime repair and replacement costs. High-performing or low risk OWTS with repairs and replacements below the threshold of $9000 over a 40-year life are associated with more frequent inspections and upgrades following home additions. OWTS with a high risk of exceeding the repair cost threshold of $18 000 are further analyzed in a variation of extreme value analysis (EVA), Points Over Threshold (POT) where the distribution of risk-cost exceedance values are represented by a generalized Pareto distribution. The resulting threshold cost exceedance estimates for OWTS in the high-risk category over a 40-year expected life ranged from $18 000 to $44 000.

Discovery of dapivirine, a nonnucleoside HIV-1 reverse transcriptase inhibitor, as a broad-spectrum antiviral against both influenza A and B viruses.

Science.gov (United States)

Hu, Yanmei; Zhang, Jiantao; Musharrafieh, Rami Ghassan; Ma, Chunlong; Hau, Raymond; Wang, Jun

2017-09-01

The emergence of multidrug-resistant influenza viruses poses a persistent threat to public health. The current prophylaxis and therapeutic interventions for influenza virus infection have limited efficacy due to the continuous antigenic drift and antigenic shift of influenza viruses. As part of our ongoing effort to develop the next generation of influenza antivirals with broad-spectrum antiviral activity and a high genetic barrier to drug resistance, in this study we report the discovery of dapivirine, an FDA-approved HIV nonnucleoside reverse transcriptase inhibitor, as a broad-spectrum antiviral against multiple strains of influenza A and B viruses with low micromolar efficacy. Mechanistic studies revealed that dapivirine inhibits the nuclear entry of viral ribonucleoproteins at the early stage of viral replication. As a result, viral RNA and protein synthesis were inhibited. Furthermore, dapivirine has a high in vitro genetic barrier to drug resistance, and its antiviral activity is synergistic with oseltamivir carboxylate. In summary, the in vitro antiviral results of dapivirine suggest it is a promising candidate for the development of the next generation of dual influenza and HIV antivirals. Copyright © 2017 Elsevier B.V. All rights reserved.

An introduction to constructed wetlands (reed beds) sustainable low cost wastewater treatment plants

International Nuclear Information System (INIS)

Ahmad, M.I.

2005-01-01

The use of 'conventional' wastewater treatment technology (trickling filters and activated sludge) in developing countries has often been unsuccessful due to high cost, complex operating requirements and expensive maintenance procedures. Typical examples of such projects are wastewater plants in Islamabad and Karachi. Actually the conventional systems, such as trickling filters and activated sludge plants were developed to address the concerns about organic pollution of natural water bodies in western temperate climates, rather than the reduction of organic matter as well as pathogens which is often a priority in developing countries. Pakistan, being a developing country cannot and should not follow the western technology blindly but needs the use of a ppropriate technology . Appropriate technology is defined as a treatment system which meets the following criteria: Affordable: Total amount costs, including capital, operation, maintenance and depreciation are within the user's ability to pay. Operable: Operation of the system is possible with locally available labor and support. Reliable: Effluent quality requirements can be met consistently. Currently there are a limited number of appropriate technologies for small communities, which should be considered by a community and their designers. These include conventional and non-conventional systems such as stabilization ponds or lagoons, slow sand filters, land treatment systems, and wetlands (natural or constructed). The non-conventional systems often utilize 'ecological' treatment mechanism (such as aquatic systems or wetlands) and do not have the mechanical parts or energy requirements of conventional systems. Waste Stabilization Ponds are one such solution but sometimes are constrained by land availability, topography, and are not environment friendly. In such locations, natural or constructed wetlands (Reed Beds) could provide an alternative technology. It is what we call a LOW technology, rather than HI TECH

Antiviral Screening of Multiple Compounds against Ebola Virus.

Science.gov (United States)

Dowall, Stuart D; Bewley, Kevin; Watson, Robert J; Vasan, Seshadri S; Ghosh, Chandradhish; Konai, Mohini M; Gausdal, Gro; Lorens, James B; Long, Jason; Barclay, Wendy; Garcia-Dorival, Isabel; Hiscox, Julian; Bosworth, Andrew; Taylor, Irene; Easterbrook, Linda; Pitman, James; Summers, Sian; Chan-Pensley, Jenny; Funnell, Simon; Vipond, Julia; Charlton, Sue; Haldar, Jayanta; Hewson, Roger; Carroll, Miles W

2016-10-27

In light of the recent outbreak of Ebola virus (EBOV) disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine). A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna). The three most promising compounds (17-DMAG; BGB324; and NCK-8) were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.

Antiviral Screening of Multiple Compounds against Ebola Virus

Directory of Open Access Journals (Sweden)

Stuart D. Dowall

2016-10-01

Full Text Available In light of the recent outbreak of Ebola virus (EBOV disease in West Africa, there have been renewed efforts to search for effective antiviral countermeasures. A range of compounds currently available with broad antimicrobial activity have been tested for activity against EBOV. Using live EBOV, eighteen candidate compounds were screened for antiviral activity in vitro. The compounds were selected on a rational basis because their mechanisms of action suggested that they had the potential to disrupt EBOV entry, replication or exit from cells or because they had displayed some antiviral activity against EBOV in previous tests. Nine compounds caused no reduction in viral replication despite cells remaining healthy, so they were excluded from further analysis (zidovudine; didanosine; stavudine; abacavir sulphate; entecavir; JB1a; Aimspro; celgosivir; and castanospermine. A second screen of the remaining compounds and the feasibility of appropriateness for in vivo testing removed six further compounds (ouabain; omeprazole; esomeprazole; Gleevec; D-LANA-14; and Tasigna. The three most promising compounds (17-DMAG; BGB324; and NCK-8 were further screened for in vivo activity in the guinea pig model of EBOV disease. Two of the compounds, BGB324 and NCK-8, showed some effect against lethal infection in vivo at the concentrations tested, which warrants further investigation. Further, these data add to the body of knowledge on the antiviral activities of multiple compounds against EBOV and indicate that the scientific community should invest more effort into the development of novel and specific antiviral compounds to treat Ebola virus disease.

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.

Species-independent bioassay for sensitive quantification of antiviral type I interferons

Directory of Open Access Journals (Sweden)

Penski Nicola

2010-02-01

Full Text Available Abstract Background Studies of the host response to infection often require quantitative measurement of the antiviral type I interferons (IFN-α/β in biological samples. The amount of IFN is either determined via its ability to suppress a sensitive indicator virus, by an IFN-responding reporter cell line, or by ELISA. These assays however are either time-consuming and lack convenient readouts, or they are rather insensitive and restricted to IFN from a particular host species. Results An IFN-sensitive, Renilla luciferase-expressing Rift Valley fever virus (RVFV-Ren was generated using reverse genetics. Human, murine and avian cells were tested for their susceptibility to RVFV-Ren after treatment with species-specific IFNs. RVFV-Ren was able to infect cells of all three species, and IFN-mediated inhibition of viral reporter activity occurred in a dose-dependent manner. The sensitivity limit was found to be 1 U/ml IFN, and comparison with a standard curve allowed to determine the activity of an unknown sample. Conclusions RVFV-Ren replicates in cells of several species and is highly sensitive to pre-treatment with IFN. These properties allowed the development of a rapid, sensitive, and species-independent antiviral assay with a convenient luciferase-based readout.

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

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

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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.

The cost of assisted outpatient treatment: can it save states money?

Science.gov (United States)

Swanson, Jeffrey W; Van Dorn, Richard A; Swartz, Marvin S; Robbins, Pamela Clark; Steadman, Henry J; McGuire, Thomas G; Monahan, John

2013-12-01

The authors assessed a state's net costs for assisted outpatient treatment, a controversial court-ordered program of community-based mental health services designed to improve outcomes for persons with serious mental illness and a history of repeated hospitalizations attributable to nonadherence with outpatient treatment. A comprehensive cost analysis was conducted using 36 months of observational data for 634 assisted outpatient treatment participants and 255 voluntary recipients of intensive community-based treatment in New York City and in five counties elsewhere in New York State. Administrative, budgetary, and service claims data were used to calculate and summarize costs for program administration, legal and court services, mental health and other medical treatment, and criminal justice involvement. Adjusted effects of assisted outpatient treatment and voluntary intensive services on total service costs were examined using multivariate time-series regression analysis. In the New York City sample, net costs declined 43% in the first year after assisted outpatient treatment began and an additional 13% in the second year. In the five-county sample, costs declined 49% in the first year and an additional 27% in the second year. Psychotropic drug costs increased during the first year after initiation of assisted outpatient treatment, by 40% and 44% in the city and five-county samples, respectively. Regression analyses revealed significant declines in costs associated with both assisted outpatient treatment and voluntary participation in intensive services, although the cost declines associated with assisted outpatient treatment were about twice as large as those seen for voluntary services. Assisted outpatient treatment requires a substantial investment of state resources but can reduce overall service costs for persons with serious mental illness. For those who do not qualify for assisted outpatient treatment, voluntary participation in intensive community

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 combination with other anti-HCV agents. LDV has picomolar antiviral activity against genotype 1a and genotype 1b replicons with 50% effective concentration (EC50) values of 0.031 nM and 0.004 nM, respectively. LDV is also active against HCV genotypes 4a, 4d, 5a, and 6a with EC50 values of 0.11 to 1.1 nM. LDV has relatively less in vitro antiviral activity against genotypes 2a, 2b, 3a, and 6e, with EC50 values of 16 to 530 nM. In vitro resistance selection with LDV identified the single Y93H and Q30E resistance-associated variants (RAVs) in the NS5A gene; these RAVs were also observed in patients after a 3-day monotherapy treatment. In vitro antiviral combination studies indicate that LDV has additive to moderately synergistic antiviral activity when combined with other classes of HCV direct-acting antiviral (DAA) agents, including NS3/4A protease inhibitors and the nucleotide NS5B polymerase inhibitor SOF. Furthermore, LDV is active against known NS3 protease and NS5B polymerase inhibitor RAVs with EC50 values equivalent to those for the wild type. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Endovascular treatment of cerebral aneurysms - a cost analysis | Le ...

African Journals Online (AJOL)

The average cost for endovascular treatment per patient was R37 041. Surgical treatment was more expensive at R44 104, a difference of 16%. Conclusions. Despite the high cost of endovascular devices, appropriate use of this technology ultimately offers less expensive treatment than microsurgical clipping of aneurysms.

Modelling the cost effectiveness of antidepressant treatment in primary care.

Science.gov (United States)

Revicki, D A; Brown, R E; Palmer, W; Bakish, D; Rosser, W W; Anton, S F; Feeny, D

1995-12-01

The aim of this study was to estimate the cost effectiveness of nefazodone compared with imipramine or fluoxetine in treating women with major depressive disorder. Clinical decision analysis and a Markov state-transition model were used to estimate the lifetime health outcomes and medical costs of 3 antidepressant treatments. The model, which represents ideal primary care practice, compares treatment with nefazodone to treatment with either imipramine or fluoxetine. The economic analysis was based on the healthcare system of the Canadian province of Ontario, and considered only direct medical costs. Health outcomes were expressed as quality-adjusted life years (QALYs) and costs were in 1993 Canadian dollars ($Can; $Can1 = $US0.75, September 1995). Incremental cost-utility ratios were calculated comparing the relative lifetime discounted medical costs and QALYs associated with nefazodone with those of imipramine or fluoxetine. Data for constructing the model and estimating necessary parameters were derived from the medical literature, clinical trial data, and physician judgement. Data included information on: Ontario primary care physicians' clinical management of major depression; medical resource use and costs; probabilities of recurrence of depression; suicide rates; compliance rates; and health utilities. Estimates of utilities for depression-related hypothetical health states were obtained from patients with major depression (n = 70). Medical costs and QALYs were discounted to present value using a 5% rate. Sensitivity analyses tested the assumptions of the model by varying the discount rate, depression recurrence rates, compliance rates, and the duration of the model. The base case analysis found that nefazodone treatment costs $Can1447 less per patient than imipramine treatment (discounted lifetime medical costs were $Can50,664 vs $Can52,111) and increases the number of QALYs by 0.72 (13.90 vs 13.18). Nefazodone treatment costs $Can14 less than fluoxetine

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

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

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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.

SECONDARY WASTE MANAGEMENT STRATEGY FOR EARLY LOW ACTIVITY WASTE TREATMENT

Energy Technology Data Exchange (ETDEWEB)

TW, CRAWFORD

2008-07-17

This study evaluates parameters relevant to River Protection Project secondary waste streams generated during Early Low Activity Waste operations and recommends a strategy for secondary waste management that considers groundwater impact, cost, and programmatic risk. The recommended strategy for managing River Protection Project secondary waste is focused on improvements in the Effiuent Treatment Facility. Baseline plans to build a Solidification Treatment Unit adjacent to Effluent Treatment Facility should be enhanced to improve solid waste performance and mitigate corrosion of tanks and piping supporting the Effiuent Treatment Facility evaporator. This approach provides a life-cycle benefit to solid waste performance and reduction of groundwater contaminants.

Antiviral Activities of Several Oral Traditional Chinese Medicines against Influenza Viruses.

Science.gov (United States)

Ma, Lin-Lin; Ge, Miao; Wang, Hui-Qiang; Yin, Jin-Qiu; Jiang, Jian-Dong; Li, Yu-Huan

2015-01-01

Influenza is still a serious threat to human health with significant morbidity and mortality. The emergence of drug-resistant influenza viruses poses a great challenge to existing antiviral drugs. Traditional Chinese medicines (TCMs) may be an alternative to overcome the challenge. Here, 10 oral proprietary Chinese medicines were selected to evaluate their anti-influenza activities. These drugs exhibit potent inhibitory effects against influenza A H1N1, influenza A H3N2, and influenza B virus. Importantly, they demonstrate potent antiviral activities against drug-resistant strains. In the study of mechanisms, we found that Xiaoqinglong mixture could increase antiviral interferon production by activating p38 MAPK, JNK/SAPK pathway, and relative nuclear transcription factors. Lastly, our studies also indicate that some of these medicines show inhibitory activities against EV71 and CVB strains. In conclusion, the 10 traditional Chinese medicines, as kind of compound combination medicines, show broad-spectrum antiviral activities, possibly also including inhibitory activities against strains resistant to available antiviral drugs.

Assessment of radiotherapy photon beams: A practical and low cost methodology

International Nuclear Information System (INIS)

Reis, C.Q.M.; Nicolucci, P.

2017-01-01

Dosimetric properties of radiation beams used in radiotherapy are directly related to the energy spectrum produced by the treatment unit. Therefore, the development of methodologies to evaluate in a simple and accurate way the spectra of clinical beams can help establishing the quality control of the treatment. The purpose of this study is to present a practical and low cost methodology for determining primary spectra of radiotherapy photon beams from transmission measurements in attenuators of aluminum and using the method of the inverse Laplace transform. Monte Carlo simulation with PENELOPE code was used in order to evaluate and validate the reconstructed spectra by the calculation of dosimetric parameters that characterize the beam. Percentage depth dose values simulated with a 6 MV reconstructed spectrum shows maximum difference of 4.4% when compared to values measured at the corresponding clinical beam. For a 10 MV beam that difference was around 4.2%. Results obtained in this study confirm the adequacy of the proposed methodology for assessing primary photon beams produced by clinical accelerators. - Highlights: • Primary spectra of radiotherapy photon beams are determined from transmission measurements. • Monte Carlo calculations are used to evaluate the method of the inverse Laplace transform. • The proposed methodology is practical and of low cost for clinical purposes. • Results are in fair agreement with literature and clinical data.

The French centralized low level radwaste treatment centre named CENTRACO

International Nuclear Information System (INIS)

Barnes, C.; Sixou, Y.

1996-01-01

Socodei, a subsidiary company of EdF and Cogema is commissioned to design, finance, build and operate two low level radwaste treatment facilities: a contaminated scrap metal melting unit, and a solid and liquid waste incinerator. These units frame a low level radwaste treatment centre named Centraco, located near Marcoule in the south of France, and will receive in 1998 waste coming from dismantling, maintenance and operating works of French and foreign nuclear sites. The decision to create this centre is due to the low density and large variety of low level radwaste which take a volume out of proportion with their activity, specially in the surface storage centre. Up to now, all low level radwaste were sent and stored with no treatment optimization in surface storage centres. Socodei proposes in one single site, to optimize low level radwaste management and reduce the volume of ultimate waste to be stored: in a ratio of one to ten by casting ingots coming from melting contaminated scrap metals; in a ratio of one to twenty by encapsulating earth ashes and ashes resulting from incineration of solid and liquid waste. This is a centralized treatment centre and that's why Centraco is a new waste management system. Getting together all means in one place reduces costs, avoids mismanagement and risk increase, and allows consistency in safety, environmental impact, transport and personnel radioprotection. (author)

Clinical Experience of Complex Application of Antiviral Therapy, Natural and Preformed Physical Factors in Patients with Chronic Hepatitis C

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N.V. Dragomiretska

2013-02-01

Full Text Available The article deals with the results of complex application of antiviral therapy, low-mineralized hydrocarbonate-sulphate-chloride sodium mineral water, EHF- and vibroacoustic therapy of the patients with chronic viral hepatitis C. The developed complex liquidates adverse effects of the antiviral therapy (leukocytopenia, thrombocytopenia and flu-like syndromes, promotes the normalization of the functional tests of the liver and normalization of the majority of indicators of the immune status, stimulates the synthesis of the endogenous interferon α.

Thermo-mechanical treatment of low-cost alloy Ti-4.5Al-6.9Cr-2.3Mn and microstructure and mechanical characteristics

Science.gov (United States)

Chen, Guangyao; Kang, Juyun; Wang, Shusen; Wang, Shihua; Lu, Xionggang; Li, Chonghe

2018-04-01

In this study, the thermo-mechanical treatment process for low-cost Ti-4.5Al-6.9Cr-2.3Mn alloy were designed on the basis of assessment of Ti-Al-Cr-Mn thermodynamic system. The microstructure and mechanical properties of Ti-4.5Al-6.9Cr-2.3Mn forging and sheet were investigated by using the OM, SEM and universal tensile testing machine. The results show that both the forging and sheet were consisted of α + β phase, which is consistent with the expectation, and no element Cr and Mn existed in the grain boundaries of the sheet after quenching, and the C14 laves phase was not detected. The average ultimate tensile strength (σ b), 0.2% proof strength (σ 0.2) and elongation (EI) of alloy sheet after quenching can reach 1059 MPa, 1051 MPa and 24.6 Pct., respectively. Moreover, the average ultimate tensile strength of Ti-4.5Al-6.9Cr-2.3Mn forgings can reach 1599 MPa and the average elongation can reach 11.2 Pct., and a more excellent property of Ti-4.5Al-6.9Cr-2.3Mn forging is achieved than that of TC4 forging. It provides a theoretical support for further developing this low-cost alloy.

Cost minimization analysis of high-dose-rate versus low-dose-rate brachytherapy in endometrial cancer

International Nuclear Information System (INIS)

Pinilla, James

1998-01-01

Purpose: Endometrial cancer is a common, usually curable malignancy whose treatment frequently involves low-dose-rate (LDR) or high-dose-rate (HDR) brachytherapy. These treatments involve substantial resource commitments and this is increasingly important. This paper presents a cost minimization analysis of HDR versus LDR brachytherapy in the treatment of endometrial cancer. Methods and Materials: The perspective of the analysis is that of the payor, in this case the Ministry of Health. One course of LDR treatment is compared to two courses of HDR treatment. The two alternatives are considered to be comparable with respect to local control, survival, and toxicities. Labor, overhead, and capital costs are accounted for and carefully measured. A 5% inflation rate is used where applicable. A univariate sensitivity analysis is performed. Results: The HDR regime is 22% less expensive compared to the LDR regime. This is $991.66 per patient or, based on the current workload of this department (30 patients per year) over the useful lifetime of the after loader, $297,498 over 10 years in 1997 dollars. Conclusion: HDR brachytherapy minimizes costs in the treatment of endometrial cancer relative to LDR brachytherapy. These results may be used by other centers to make rational decisions regarding brachytherapy equipment replacement or acquisition

Antiviral effects of Curcuma longa L. against dengue virus in vitro and in vivo

Science.gov (United States)

Ichsyani, M.; Ridhanya, A.; Risanti, M.; Desti, H.; Ceria, R.; Putri, D. H.; Sudiro, T. M.; Dewi, B. E.

2017-12-01

Dengue is the most common infective disease caused by dengue virus (DENV) and endemic diseases in tropical and subtropical areas. Until now, there is no specific antiviral for dengue infection. It is known that viral load is related to disease severity. Curcuma longa L. (turmeric) with curcumin as major active compound has been identified for its antiviral effect. This study to determine antiviral effect of C. longa extract on DENV-2 in vitro and in vivo along with its toxicity in liver and kidney of ddY mice. Antiviral activity (IC50) and toxicity (CC50) in vitro was examined on Huh7it-1 cells by focus assay and a MTT assay, respectively. To determine the selectivity index (SI), we used CC50 and IC50 value. The safe doses obtained were used for toxicity tests of liver and kidney with histopathological and biochemical observations. The C. longa extracts was given orally with dose of 0.147 mg/mL for each mice at 2 hours after injected with DENV-2 infected Huh7it-1 cells. Serum was collected from intraorbital at 6 hours and 24 hours after infection and focus assay was used to determine viral load. In this study, the acquired value of IC50 was 17,91 μg/mL whereas the value of CC50 was 85,4 μg/mL. The value of SI of C. longa was 4.8. In vivo, we found that C. longa remarkable reduced of viral load after 24 hour. Histopathological examination showed no specific abnormalities in liver and kidney. There was no significant increase in levels of SGPT, SGOT, urea, and creatinine. From this study it can be concluded that C. longa could potentially be used as antiviral against DENV with low cytotoxicity and effective inhibition.

Cost effectiveness of recombinant factor VIIa for treatment of intracerebral hemorrhage

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Eckman Mark H

2008-05-01

Full Text Available Abstract Background Phase I/II placebo-controlled clinical trials of recombinant Factor VIIa (rFVIIa suggested that administration of rFVIIa within 4 hours after onset of intracerebral hemorrhage (ICH is safe, limits ICH growth, and improves outcomes. We sought to determine the cost-effectiveness of rFVIIa for acute ICH treatment, using published Phase II data. We hypothesized that rFVIIa would have a low marginal cost-effectiveness ratio (mCER given the poor neurologic outcomes after ICH with conventional management. Methods We performed an incremental cost-effectiveness analysis from the societal perspective, considering conventional management vs. 80 ug/kg rFVIIa treatment for acute ICH cases meeting Phase II inclusion criteria. The time frame for the analysis was 1. 25 years: data from the Phase II trial was used for 90 day outcomes and rFVIIa complications – arterial thromboembolic events (ATE. We assumed no substantial cost differences in care between the two strategies except: 1 cost of rFVIIa (for an 80 mcg/kg dose in an 80 kg patient, assumed cost of $6,408; 2 cost of ATE side effects from rFVIIa (which also decrease quality of life and increase the chance of death; and 3 differential monetary costs of outcomes and their impact on quality of life, including disposition (home vs. nursing home, and outpatient vs. inpatient rehabilitation. Sensitivity analyses were performed to explore uncertainty in parameter estimates, impact of rFVIIa cost, direct cost of neurologic outcomes, probability of ATE, and outcomes after ATE. Results In the "base case", treating ICH with rFVIIa dominates the usual care strategy by being more effective and less costly. rFVIIa maintained a mCER Conclusion Based on data from preliminary trials, treating selected ICH patients with rFVIIa results in lower cost and improved clinical outcomes. This potential cost-effectiveness must be considered in light of the Phase III trial results.

Liver-related death among HIV/hepatitis C virus-co-infected individuals

DEFF Research Database (Denmark)

Grint, Daniel; Peters, Lars; Rockstroh, Juergen K

2015-01-01

BACKGROUND: Potent, less toxic, directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection promise to improve HCV cure rates among HIV/HCV-co-infected individuals. However, the costs of treatment will necessitate prioritization of those at greatest risk of liver-related ......BACKGROUND: Potent, less toxic, directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection promise to improve HCV cure rates among HIV/HCV-co-infected individuals. However, the costs of treatment will necessitate prioritization of those at greatest risk of liver.......7-2.9), but substantial in those with F2/F3 and F4 fibrosis (sHR 10.3%, 95% CI 7.6-13.5; and sHR 14.0%, 95% CI 10.3-18.3, respectively). CONCLUSION: Treatment with DAAs should be prioritized for those with at least F2 fibrosis. Early initiation of cART with the aim of avoiding low CD4 cell counts should be considered...

Efficacy of Low-Cost PC-Based Aviation Training Devices

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Savern l Reweti

2017-03-01

Full Text Available Aim/Purpose: The aim of this study was to explore whether a full cost flight training device (FTD was significantly better for simulator training than a low cost PC-Based Aviation Training Device (PCATD. Background: A quasi-transfer study was undertaken to ascertain whether a Civil Aviation Authority certified Flight Training Device (FTD was more effective at improving pilot proficiency in the performance of a standard VFR traffic pattern (Overhead Rejoin Procedure than a customised low cost PCATD. Methodology: In this quasi-transfer study, a high fidelity FTD rather than an aircraft was used to test both training and transfer tasks. Ninety-three pilots were recruited to participate in the study. Contribution: The use of PCATDs is now well established for pilot training, especially for Instrument Flight Rules (IFR skills training. However, little substantive research has been undertaken to examine their efficacy for VFR training. Findings: There was no evidence of a pre-test/post-test difference in VFR task perfor-mance between participants trained on the PCATD and the FTD, when post tested on the FTD. The use of both PCATD and FTD demonstrated signifi-cant improvements in VFR task performance compared to a control group that received no PCATD or FTD training. Recommendations for Practitioners\t: We discuss the possibility that low cost PCATDs may be a viable alternative for flight schools wishing to use a flight simulator but not able to afford a FTD. Recommendation for Researchers: We discuss the introduction of improved low cost technologies that allow PCATDs to be used more effectively for training in VFR procedures. The development and testing of new technologies requires more research. Impact on Society: Flight training schools operate in a difficult economic environment with continued increases in the cost of aircraft maintenance, compliance costs, and aviation fuel. The increased utilisation of low cost PCATD’s especially for VFR

Free fatty acids induce ER stress and block antiviral activity of interferon alpha against hepatitis C virus in cell culture

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Gunduz Feyza

2012-08-01

Full Text Available Abstract Background Hepatic steatosis is recognized as a major risk factor for liver disease progression and impaired response to interferon based therapy in chronic hepatitis C (CHC patients. The mechanism of response to interferon-alpha (IFN-α therapy under the condition of hepatic steatosis is unexplored. We investigated the effect of hepatocellular steatosis on hepatitis C virus (HCV replication and IFN-α antiviral response in a cell culture model. Methods Sub-genomic replicon (S3-GFP and HCV infected Huh-7.5 cells were cultured with a mixture of saturated (palmitate and unsaturated (oleate long-chain free fatty acids (FFA. Intracytoplasmic fat accumulation in these cells was visualized by Nile red staining and electron microscopy then quantified by microfluorometry. The effect of FFA treatment on HCV replication and IFN-α antiviral response was measured by flow cytometric analysis, Renilla luciferase activity, and real-time RT-PCR. Results FFA treatment induced dose dependent hepatocellular steatosis and lipid droplet accumulation in the HCV replicon cells was confirmed by Nile red staining, microfluorometry, and by electron microscopy. Intracellular fat accumulation supports replication more in the persistently HCV infected culture than in the sub-genomic replicon (S3-GFP cell line. FFA treatment also partially blocked IFN-α response and viral clearance by reducing the phosphorylation of Stat1 and Stat2 dependent IFN-β promoter activation. We show that FFA treatment induces endoplasmic reticulum (ER stress response and down regulates the IFNAR1 chain of the type I IFN receptor leading to defective Jak-Stat signaling and impaired antiviral response. Conclusion These results suggest that intracellular fat accumulation in HCV cell culture induces ER stress, defective Jak-Stat signaling, and attenuates the antiviral response, thus providing an explanation to the clinical observation regarding how hepatocellular steatosis influences IFN

In vitro antiviral activities of Caesalpinia pulcherrima and its related flavonoids.

Science.gov (United States)

Chiang, L C; Chiang, W; Liu, M C; Lin, C C

2003-08-01

The aim of this study was to search for new antiviral agents from Chinese herbal medicine. Pure flavonoids and aqueous extracts of Caesalpinia pulcherrima Swartz were used in experiments to test their influence on a series of viruses, namely herpesviruses (HSV-1, HSV-2) and adenoviruses (ADV-3, ADV-8, ADV-11). The EC50 was defined as the concentration required to achieve 50% protection against virus-induced cytopathic effects, and the selectivity index (SI) was determined as the ratio of CC50 (concentration of 50% cellular cytotoxicity) to EC50. Results showed that aqueous extracts of C. pulcherrima and its related quercetin possessed a broad-spectrum antiviral activity. Among them, the strongest activities against ADV-8 were fruit and seed (EC50 = 41.2 mg/l, SI = 83.2), stem and leaf (EC50 = 61.8 mg/l, SI = 52.1) and flower (EC50 = 177.9 mg/l, SI = 15.5), whereas quercetin possessed the strongest anti-ADV-3 activity (EC50 = 24.3 mg/l, SI = 20.4). In conclusion, some compounds of C. pulcherrima which possess antiviral activities may be derived from the flavonoid of quercetin. The mode of action of quercetin against HSV-1 and ADV-3 was found to be at the early stage of multiplication and with SI values greater than 20, suggesting the potential use of this compound for treatment of the infection caused by these two viruses.

How much does an antiinflammatory treatment cost?

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S. Adami

2011-06-01

Full Text Available NSAIDs are among the most popular drugs in the world for their efficacy in controlling pain and acute and chronic inflammation. The efficacy of these therapies is hampered by their safety profile, in particular regarding the gastroenteric tract. The NSAIDs’ side effects may heavily influence the health of the single patient and the economy of the health systems. The pharmacoeconomic evaluation of antinflammatory treatment usually considers, in addition to the drug purchase prize, also the shadow costs. This cost is mainly due to the management and prevention of gastropathy. Coxibs, even if more expensive, may become cost-effective for their better gastronteric safety. As a matter of fact, coxib treatment can be considered equivalent to a treatment with NSAID plus PPI. However, the first requirement of these drugs, that should control pain, must be the efficacy and not only safety. In this case the NNT (Number Needed to Treat is a good marker of efficacy. To calculate the real cost we must pay to reach the target (pain resolution in one patient, we can multiply NNT for the prize of a specific drug. The total cost will depend on drug prize (the cheaper, the better and on the efficacy expressed by NNT (the lower, the better. In a recent meta-analysis, the NNT of several antinflammatory drugs has been calculated. When the treatment cost was adjusted for its efficacy (NNT, the difference in favour of NSAIDs became so little to disappear because of the higher safety of coxibs (especially of etoricoxiband the possibility to reach antinflammatory and analgesic doses that are difficult to obtain with NSAIDs. Moreover, if also the cost of gastroprotection is considered, the economic impact of NSAIDs can be much higher. In conclusion the pharmacoeconomic analysis of an antinflammatory therapy cannot be based only on safety issues but also on efficacy evaluation that is the main effect we ask to these drugs.

Analysis of the Production Cost for Various Grades of Biomass Thermal Treatment