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Sample records for baseline anti-malarial treatment

  1. Molecular markers of anti-malarial drug resistance in Lahj Governorate, Yemen: baseline data and implications

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    Chance Michael L

    2011-08-01

    Full Text Available Abstract Background This is an investigation of anti-malarial molecular markers coupled with a therapeutic efficacy test of chloroquine (CQ against falciparum malaria in an area of unstable malaria in Lahj Governorate, Yemen. The study was aimed at assessment of therapeutic response to CQ and elucidation of baseline information on molecular markers for Plasmodium falciparum resistance against CQ and sulphadoxine/pyrimethamine (SP. Methods Between 2002 and 2003 the field test was conducted according to the standard WHO protocol to evaluate the therapeutic efficacy of CQ in 124 patients with falciparum malaria in an endemic area in Lahj Governorate in Yemen. Blood samples collected during this study were analysed for P. falciparum chloroquine resistance transporter gene (pfcrt-76 polymorphisms, mutation pfcrt-S163R and the antifolate resistance-associated mutations dihydrofolate reductase (dhfr-C59R and dihydropteroate synthase (dhps-K540E. Direct DNA sequencing of the pfcrt gene from three representative field samples was carried out after DNA amplification of the 13 exons of the pfcrt gene. Results Treatment failure was detected in 61% of the 122 cases that completed the 14-day follow-up. The prevalence of mutant pfcrt T76 was 98% in 112 amplified pre-treatment samples. The presence of pfcrt T76 was poorly predictive of in vivo CQ resistance (PPV = 61.8%, 95% CI = 52.7-70.9. The prevalence of dhfr Arg-59 mutation in 99 amplified samples was 5%, while the dhps Glu-540 was not detected in any of 119 amplified samples. Sequencing the pfcrt gene confirmed that Yemeni CQ resistant P. falciparum carry the old world (Asian and African CQ resistant haplotype CVIETSESI at positions 72,73,74,75,76,220,271, 326 and 371. Conclusion This is the first study to report baseline information on the characteristics and implications of anti-malarial drug resistance markers in Yemen. It is also the first report of the haplotype associated with CQR P. falciparum

  2. Molecular markers of anti-malarial drug resistance in Lahj Governorate, Yemen: baseline data and implications.

    Science.gov (United States)

    Mubjer, Reem A; Adeel, Ahmed A; Chance, Michael L; Hassan, Amir A

    2011-08-21

    This is an investigation of anti-malarial molecular markers coupled with a therapeutic efficacy test of chloroquine (CQ) against falciparum malaria in an area of unstable malaria in Lahj Governorate, Yemen. The study was aimed at assessment of therapeutic response to CQ and elucidation of baseline information on molecular markers for Plasmodium falciparum resistance against CQ and sulphadoxine/pyrimethamine (SP). Between 2002 and 2003 the field test was conducted according to the standard WHO protocol to evaluate the therapeutic efficacy of CQ in 124 patients with falciparum malaria in an endemic area in Lahj Governorate in Yemen. Blood samples collected during this study were analysed for P. falciparum chloroquine resistance transporter gene (pfcrt)-76 polymorphisms, mutation pfcrt-S163R and the antifolate resistance-associated mutations dihydrofolate reductase (dhfr)-C59R and dihydropteroate synthase (dhps)-K540E. Direct DNA sequencing of the pfcrt gene from three representative field samples was carried out after DNA amplification of the 13 exons of the pfcrt gene. Treatment failure was detected in 61% of the 122 cases that completed the 14-day follow-up. The prevalence of mutant pfcrt T76 was 98% in 112 amplified pre-treatment samples. The presence of pfcrt T76 was poorly predictive of in vivo CQ resistance (PPV = 61.8%, 95% CI = 52.7-70.9). The prevalence of dhfr Arg-59 mutation in 99 amplified samples was 5%, while the dhps Glu-540 was not detected in any of 119 amplified samples. Sequencing the pfcrt gene confirmed that Yemeni CQ resistant P. falciparum carry the old world (Asian and African) CQ resistant haplotype CVIETSESI at positions 72,73,74,75,76,220,271, 326 and 371. This is the first study to report baseline information on the characteristics and implications of anti-malarial drug resistance markers in Yemen. It is also the first report of the haplotype associated with CQR P. falciparum parasites from Yemen. Mutant pfcrtT76 is highly prevalent but it

  3. Compliance with a three-day course of artesunate-mefloquine combination and baseline anti-malarial treatment in an area of Thailand with highly multidrug resistant falciparum malaria

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    Na-Bangchang Kesara

    2010-02-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is presently recommended by the World Health Organization as first-line treatment for uncomplicated Plasmodium falciparum malaria in several countries, as a mean of prolonging the effectiveness of first-line malaria treatment regimens. A three-day course of artesunate-mefloquine (4 mg/kg body weight once daily for three consecutive days, plus 15 and 10 mg/kg body weight mefloquine on the first and second days has been adopted by Malaria Control Programme of Thailand as first-line treatment for uncomplicated falciparum malaria all over the country since 2008. The gametocytocydal anti-malarial drug primaquine is administered at the dose of 30 mg (0.6 mg/kg on the last day. The aim of the present study was to assess patient compliance of this combination regimen when applied to field condition. Methods A total of 240 patients (196 males and 44 females who were attending the malaria clinics in Mae-Sot, Tak Province and presenting with symptomatic acute uncomplicated falciparum malaria, with no reappearance of Plasmodium vivax parasitaemia during follow-up were included into the study. The first dose of the treatment was given to the patients under direct supervision. All patients were given the medication for self-treatment at home and were requested to come back for follow-up on day 3 of the initial treatment. Baseline (day 0 and day 3 whole blood mefloquine and plasma primaquine concentrations were determined by high performance liquid chromatography. Results Two patients had recrudescence on days 28 and 35. The Kaplan-Meier estimate of the 42-day efficacy rate of this combination regimen was 99.2% (238/240. Based on whole blood mefloquine and plasma primaquine concentrations on day 3 of the initial treatment, compliance with mefloquine and primaquine in this three-day artesunate-mefloquine combination regimen were 96.3% (207/215, and 98.5% (197/200, respectively. Baseline mefloquine

  4. Anti-malarial treatment outcomes in Ethiopia: a systematic review and meta-analysis.

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    Gebreyohannes, Eyob Alemayehu; Bhagavathula, Akshaya Srikanth; Seid, Mohammed Assen; Tegegn, Henok Getachew

    2017-07-03

    Ethiopia is among countries with a high malaria burden. There are several studies that assessed the efficacy of anti-malarial agents in the country and this systematic review and meta-analysis was performed to obtain stronger evidence on treatment outcomes of malaria from the existing literature in Ethiopia. A systematic literature search using the preferred reporting items for systematic review and meta-analysis (PRISMA) statement was conducted on studies from Pubmed, Google Scholar, and ScienceDirect databases to identify published and unpublished literature. Comprehensive meta-analysis software was used to perform all meta-analyses. The Cochrane Q and the I 2 were used to evaluate heterogeneity of studies. Random effects model was used to combine studies showing heterogeneity of Cochrane Q p  50. Twenty-one studies were included in the final analysis with a total number of 3123 study participants. Treatment outcomes were assessed clinically and parasitologically using World Health Organization guidelines. Adequate clinical and parasitological response was used to assess treatment success at the 28th day. Overall, a significant high treatment success of 92.9% (95% CI 89.1-96.6), p Ethiopia, but associated with high rates of adverse drug reactions (ADRs). However, these ADRs were not serious enough to discontinue anti-malarial treatment. The results of this study suggest that the current anti-malarial medications are effective and safe; however, greater priority should be placed on the discovery of new anti-malarial drugs to achieve successful outcomes as resistance seems inevitable since cases of anti-malarial drug resistance have been reported from other areas of the world.

  5. Saleability of anti-malarials in private drug shops in Muheza, Tanzania: a baseline study in an era of assumed artemisinin combination therapy (ACT

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    Ringsted Frank M

    2011-08-01

    Full Text Available Abstract Background Artemether-lumefantrine (ALu replaced sulphadoxine-pymimethamine (SP as the official first-line anti-malarial in Tanzania in November 2006. So far, artemisinin combination therapy (ACT is contra-indicated during pregnancy by the national malaria treatment guidelines, and pregnant women depend on SP for Intermittent Preventive Treatment (IPTp during pregnancy. SP is still being dispensed by private drug stores, but it is unknown to which extent. If significant, it may undermine its official use for IPTp through induction of resistance. The main study objective was to perform a baseline study of the private market for anti-malarials in Muheza town, an area with widespread anti-malarial drug resistance, prior to the implementation of a provider training and accreditation programme that will allow accredited drug shops to sell subsidized ALu. Methods All drug shops selling prescription-only anti-malarials, in Muheza town, Tanga Region voluntarily participated from July to December 2009. Qualitative in-depth interviews were conducted with owners or shopkeepers on saleability of anti-malarials, and structured questionnaires provided quantitative data on drugs sales volume. Results All surveyed drug shops illicitly sold SP and quinine (QN, and legally amodiaquine (AQ. Calculated monthly sale was 4,041 doses, in a town with a population of 15,000 people. Local brands of SP accounted for 74% of sales volume, compared to AQ (13%, QN (11% and ACT (2%. Conclusions In community practice, the saleability of ACT was negligible. SP was best-selling, and use was not reserved for IPTp, as stipulated in the national anti-malarial policy. It is a major reason for concern that such drug-pressure in the community equals de facto intermittent presumptive treatment. In an area where SP drug resistance remains high, unregulated SP dispensing to people other than pregnant women runs the risk of eventually jeopardizing the effectiveness of the IPTp

  6. Gel versus capillary electrophoresis genotyping for categorizing treatment outcomes in two anti-malarial trials in Uganda

    OpenAIRE

    Hubbard Alan E; Dorsey Grant; Gupta Vinay; Rosenthal Philip J; Greenhouse Bryan

    2010-01-01

    Abstract Background Molecular genotyping is performed in anti-malarial trials to determine whether recurrent parasitaemia after therapy represents a recrudescence (treatment failure) or new infection. The use of capillary instead of agarose gel electrophoresis for genotyping offers technical advantages, but it is unclear whether capillary electrophoresis will result in improved classification of anti-malarial treatment outcomes. Methods Samples were genotyped using both gel and capillary elec...

  7. Clinical manifestations of new versus recrudescent malaria infections following anti-malarial drug treatment

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    Shaukat Ayesha M

    2012-06-01

    Full Text Available Abstract Background Distinguishing new from recrudescent infections in post-treatment episodes of malaria is standard in anti-malarial drug efficacy trials. New infections are not considered malaria treatment failures and as a result, the prevention of subsequent episodes of malaria infection is not reported as a study outcome. However, in moderate and high transmission settings, new infections are common and the ability of a short-acting medication to cure an initial infection may be outweighed by its inability to prevent the next imminent infection. The clinical benefit of preventing new infections has never been compared to that of curing the initial infection. Methods Children enrolled in a sulphadoxine-pyrimethamine efficacy study in Blantyre, Malawi from 1998–2004 were prospectively evaluated. Six neutral microsatellites were used to classify new and recrudescent infections in children aged less than 10 years with recurrent malaria infections. Children from the study who did not experience recurrent parasitaemia comprised the baseline group. The odds of fever and anaemia, the rate of haemoglobin recovery and time to recurrence were compared among the groups. Results Fever and anemia were more common among children with parasitaemia compared to those who remained infection-free throughout the study period. When comparing recrudescent vs. new infections, the incidence of fever was not statistically different. However, children with recrudescent infections had a less robust haematological recovery and also experienced recurrence sooner than those whose infection was classified as new. Conclusions The results of this study confirm the paramount importance of providing curative treatment for all malaria infections. Although new and recrudescent infections caused febrile illnesses at a similar rate, recurrence due to recrudescent infection did have a worsened haemological outcome than recurrence due to new infections. Local decision

  8. Co-treatment with the anti-malarial drugs mefloquine and primaquine highly sensitizes drug-resistant cancer cells by increasing P-gp inhibition.

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    Kim, Ju-Hwa; Choi, Ae-Ran; Kim, Yong Kee; Yoon, Sungpil

    2013-11-22

    The purpose of this study was to identify conditions that will increase the sensitivity of resistant cancer cells to anti-mitotic drugs. Currently, atovaquine (ATO), chloroquine (CHL), primaquine (PRI), mefloquine (MEF), artesunate (ART), and doxycycline (DOY) are the most commonly used anti-malarial drugs. Herein, we tested whether anti-malarial drugs can sensitize drug-resistant KBV20C cancer cells. None of the six tested anti-malarial drugs was found to better sensitize the drug-resistant cells compared to the sensitive KB cells. With an exception of DOY, all other anti-malarial drugs tested could sensitize both KB and KBV20C cells to a similar extent, suggesting that anti-malarial drugs could be used for sensitive as well as resistant cancer cells. Furthermore, we examined the effects of anti-malarial drugs in combination with an antimitotic drug, vinblastine (VIN) on the sensitisation of resistant KBV20C cells. Using viability assay, microscopic observation, assessment of cleaved PARP, and Hoechst staining, we identified that two anti-malarial drugs, PRI and MEF, highly sensitized KBV20C-resistant cells to VIN treatment. Moreover, PRI- or MEF-induced sensitisation was not observed in VIN-treated sensitive KB parent cells, suggesting that the observed effect is specific to resistant cancer cells. We demonstrated that the PRI and MEF sensitisation mechanism mainly depends on the inhibition of p-glycoprotein (P-gp). Our findings may contribute to the development of anti-malarial drug-based combination therapies for patients resistant to anti-mitotic drugs. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. Gel versus capillary electrophoresis genotyping for categorizing treatment outcomes in two anti-malarial trials in Uganda

    Science.gov (United States)

    2010-01-01

    Background Molecular genotyping is performed in anti-malarial trials to determine whether recurrent parasitaemia after therapy represents a recrudescence (treatment failure) or new infection. The use of capillary instead of agarose gel electrophoresis for genotyping offers technical advantages, but it is unclear whether capillary electrophoresis will result in improved classification of anti-malarial treatment outcomes. Methods Samples were genotyped using both gel and capillary electrophoresis from randomized trials of artemether-lumefantrine (AL) vs. dihydroartemisinin-piperaquine (DP) performed in two areas of Uganda: Kanungu, where transmission is moderate, and Apac, where transmission is very high. Both gel and capillary methods evaluated polymorphic regions of the merozoite surface protein 1 and 2 and glutamine rich protein genes. Results Capillary electrophoresis detected more alleles and provided higher discriminatory power than agarose gel electrophoresis at both study sites. There was only moderate agreement between classification of outcomes with the two methods in Kanungu (kappa = 0.66) and poor agreement in Apac (kappa = 0.24). Overall efficacy results were similar when using gel vs. capillary methods in Kanungu (42-day risk of treatment failure for AL: 6.9% vs. 5.5%, p = 0.4; DP 2.4% vs. 2.9%, p = 0.5). However, the measured risk of recrudescence was significantly higher when using gel vs. capillary electrophoresis in Apac (risk of treatment failure for AL: 17.0% vs. 10.7%, p = 0.02; DP: 8.5% vs. 3.4%, p = 0.03). Risk differences between AL and DP were not significantly different whether gel or capillary methods were used. Conclusions Genotyping with gel electrophoresis overestimates the risk of recrudescence in anti-malarial trials performed in areas of high transmission intensity. Capillary electrophoresis provides more accurate outcomes for such trials and should be performed when possible. In areas of moderate transmission, gel electrophoresis

  10. Gel versus capillary electrophoresis genotyping for categorizing treatment outcomes in two anti-malarial trials in Uganda.

    Science.gov (United States)

    Gupta, Vinay; Dorsey, Grant; Hubbard, Alan E; Rosenthal, Philip J; Greenhouse, Bryan

    2010-01-15

    Molecular genotyping is performed in anti-malarial trials to determine whether recurrent parasitaemia after therapy represents a recrudescence (treatment failure) or new infection. The use of capillary instead of agarose gel electrophoresis for genotyping offers technical advantages, but it is unclear whether capillary electrophoresis will result in improved classification of anti-malarial treatment outcomes. Samples were genotyped using both gel and capillary electrophoresis from randomized trials of artemether-lumefantrine (AL) vs. dihydroartemisinin-piperaquine (DP) performed in two areas of Uganda: Kanungu, where transmission is moderate, and Apac, where transmission is very high. Both gel and capillary methods evaluated polymorphic regions of the merozoite surface protein 1 and 2 and glutamine rich protein genes. Capillary electrophoresis detected more alleles and provided higher discriminatory power than agarose gel electrophoresis at both study sites. There was only moderate agreement between classification of outcomes with the two methods in Kanungu (kappa = 0.66) and poor agreement in Apac (kappa = 0.24). Overall efficacy results were similar when using gel vs. capillary methods in Kanungu (42-day risk of treatment failure for AL: 6.9% vs. 5.5%, p = 0.4; DP 2.4% vs. 2.9%, p = 0.5). However, the measured risk of recrudescence was significantly higher when using gel vs. capillary electrophoresis in Apac (risk of treatment failure for AL: 17.0% vs. 10.7%, p = 0.02; DP: 8.5% vs. 3.4%, p = 0.03). Risk differences between AL and DP were not significantly different whether gel or capillary methods were used. Genotyping with gel electrophoresis overestimates the risk of recrudescence in anti-malarial trials performed in areas of high transmission intensity. Capillary electrophoresis provides more accurate outcomes for such trials and should be performed when possible. In areas of moderate transmission, gel electrophoresis appears adequate to estimate comparative

  11. Gel versus capillary electrophoresis genotyping for categorizing treatment outcomes in two anti-malarial trials in Uganda

    Directory of Open Access Journals (Sweden)

    Hubbard Alan E

    2010-01-01

    Full Text Available Abstract Background Molecular genotyping is performed in anti-malarial trials to determine whether recurrent parasitaemia after therapy represents a recrudescence (treatment failure or new infection. The use of capillary instead of agarose gel electrophoresis for genotyping offers technical advantages, but it is unclear whether capillary electrophoresis will result in improved classification of anti-malarial treatment outcomes. Methods Samples were genotyped using both gel and capillary electrophoresis from randomized trials of artemether-lumefantrine (AL vs. dihydroartemisinin-piperaquine (DP performed in two areas of Uganda: Kanungu, where transmission is moderate, and Apac, where transmission is very high. Both gel and capillary methods evaluated polymorphic regions of the merozoite surface protein 1 and 2 and glutamine rich protein genes. Results Capillary electrophoresis detected more alleles and provided higher discriminatory power than agarose gel electrophoresis at both study sites. There was only moderate agreement between classification of outcomes with the two methods in Kanungu (kappa = 0.66 and poor agreement in Apac (kappa = 0.24. Overall efficacy results were similar when using gel vs. capillary methods in Kanungu (42-day risk of treatment failure for AL: 6.9% vs. 5.5%, p = 0.4; DP 2.4% vs. 2.9%, p = 0.5. However, the measured risk of recrudescence was significantly higher when using gel vs. capillary electrophoresis in Apac (risk of treatment failure for AL: 17.0% vs. 10.7%, p = 0.02; DP: 8.5% vs. 3.4%, p = 0.03. Risk differences between AL and DP were not significantly different whether gel or capillary methods were used. Conclusions Genotyping with gel electrophoresis overestimates the risk of recrudescence in anti-malarial trials performed in areas of high transmission intensity. Capillary electrophoresis provides more accurate outcomes for such trials and should be performed when possible. In areas of moderate transmission

  12. Quinine, an old anti-malarial drug in a modern world: role in the treatment of malaria.

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    Achan, Jane; Talisuna, Ambrose O; Erhart, Annette; Yeka, Adoke; Tibenderana, James K; Baliraine, Frederick N; Rosenthal, Philip J; D'Alessandro, Umberto

    2011-05-24

    Quinine remains an important anti-malarial drug almost 400 years after its effectiveness was first documented. However, its continued use is challenged by its poor tolerability, poor compliance with complex dosing regimens, and the availability of more efficacious anti-malarial drugs. This article reviews the historical role of quinine, considers its current usage and provides insight into its appropriate future use in the treatment of malaria. In light of recent research findings intravenous artesunate should be the first-line drug for severe malaria, with quinine as an alternative. The role of rectal quinine as pre-referral treatment for severe malaria has not been fully explored, but it remains a promising intervention. In pregnancy, quinine continues to play a critical role in the management of malaria, especially in the first trimester, and it will remain a mainstay of treatment until safer alternatives become available. For uncomplicated malaria, artemisinin-based combination therapy (ACT) offers a better option than quinine though the difficulty of maintaining a steady supply of ACT in resource-limited settings renders the rapid withdrawal of quinine for uncomplicated malaria cases risky. The best approach would be to identify solutions to ACT stock-outs, maintain quinine in case of ACT stock-outs, and evaluate strategies for improving quinine treatment outcomes by combining it with antibiotics. In HIV and TB infected populations, concerns about potential interactions between quinine and antiretroviral and anti-tuberculosis drugs exist, and these will need further research and pharmacovigilance.

  13. Saleability of anti-malarials in private drug shops in Muheza, Tanzania

    DEFF Research Database (Denmark)

    Ringsted, Frank M; Massawe, Isolide S; Lemnge, Martha M

    2011-01-01

    prescription-only anti-malarials, in Muheza town, Tanga Region voluntarily participated from July to December 2009. Qualitative in-depth interviews were conducted with owners or shopkeepers on saleability of anti-malarials, and structured questionnaires provided quantitative data on drugs sales volume. Results...... women depend on SP for Intermittent Preventive Treatment (IPTp) during pregnancy. SP is still being dispensed by private drug stores, but it is unknown to which extent. If significant, it may undermine its official use for IPTp through induction of resistance. The main study objective was to perform...... a baseline study of the private market for anti-malarials in Muheza town, an area with widespread anti-malarial drug resistance, prior to the implementation of a provider training and accreditation programme that will allow accredited drug shops to sell subsidized ALu. Methods: All drug shops selling...

  14. The effect of intermittent preventive treatment on anti-malarial drug resistance spread in areas with population movement.

    Science.gov (United States)

    Teboh-Ewungkem, Miranda I; Mohammed-Awel, Jemal; Baliraine, Frederick N; Duke-Sylvester, Scott M

    2014-11-15

    The use of intermittent preventive treatment in pregnant women (IPTp), children (IPTc) and infant (IPTi) is an increasingly popular preventive strategy aimed at reducing malaria risk in these vulnerable groups. Studies to understand how this preventive intervention can affect the spread of anti-malarial drug resistance are important especially when there is human movement between neighbouring low and high transmission areas. Because the same drug is sometimes utilized for IPTi and for symptomatic malaria treatment, distinguishing their individual roles on accelerating the spread of drug resistant malaria, with or without human movement, may be difficult to isolate experimentally or by analysing data. A theoretical framework, as presented here, is thus relevant as the role of IPTi on accelerating the spread of drug resistance can be isolated in individual populations and when the populations are interconnected and interact. A previously published model is expanded to include human movement between neighbouring high and low transmission areas, with focus placed on the malaria parasites. Parasite fitness functions, determined by how many humans the parasites can infect, are used to investigate how fast resistance can spread within the neighbouring communities linked by movement, when the populations are at endemic equilibrium. Model simulations indicate that population movement results in resistance spreading fastest in high transmission areas, and the more complete the anti-malarial resistance the faster the resistant parasite will tend to spread through a population. Moreover, the demography of infection in low transmission areas tends to change to reflect the demography of high transmission areas. Additionally, when regions are strongly connected the rate of spread of partially resistant parasites (R1) relative to drug sensitive parasites (RS), and fully resistant parasites (R2) relative to partially resistant parasites (R1) tend to behave the same in both

  15. Multiple treatment comparisons in a series of anti-malarial trials with an ordinal primary outcome and repeated treatment evaluations

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    Youdom Solange

    2012-05-01

    Full Text Available Abstract Background Artemisinin-based combination therapies (ACT are widely used in African countries, including Cameroon. Between 2005 and 2007, five randomized studies comparing different treatment arms among artesunate-amodiaquine and other ACT were conducted in Cameroonian children aged two to 60 months who had uncomplicated Plasmodium falciparum malaria. In these studies, the categorical criterion proposed by the World Health Organization (WHO to assess the relative effectiveness of anti-malarial drugs was repeatedly evaluated on Days 14, 21 and 28 after treatment initiation. The aim of the present study was to compare the effects of different treatments on this repeated ordinal outcome, hence using the fully available information. Methods The quantitative synthesis was based on individual patient data. Due to the incomplete block design concerning treatment arms between different trials, a mixed treatment comparison (MTC meta-analysis approach was adopted. The repeated ordinal outcome was modelled through a latent variable, as a proportional odds mixed model with trial, period and treatment arms as covariates. The model was further complexified to account for the variance heterogeneity, and the individual log-residual variance was modelled as a linear mixed model, as well. The effects of individual covariates at inclusion, such as parasitaemia, fever, gender and weight, were also tested. Model parameters were estimated using a Bayesian approach via the WinBUGS software. After selecting the best model using Deviance Information Criterion (DIC, mixed treatment comparisons were based on the estimated treatment effects. Results Modeling the residual variance improved the model ability to adjust the data. The results showed that, compared to artesunate-amodiaquine (ASAQ, dihydroartemisinin-piperaquine (DHPP was significantly more efficacious. Artesunate-chlorproguanil-dapsone (ASCD was less efficacious than artesunate

  16. Access to artemisinin-based anti-malarial treatment and its related factors in rural Tanzania.

    Science.gov (United States)

    Khatib, Rashid A; Selemani, Majige; Mrisho, Gumi A; Masanja, Irene M; Amuri, Mbaraka; Njozi, Mustafa H; Kajungu, Dan; Kuepfer, Irene; Abdulla, Salim M; de Savigny, Don

    2013-05-07

    Artemisinin-based combination treatment (ACT) has been widely adopted as one of the main malaria control strategies. However, its promise to save thousands of lives in sub-Saharan Africa depends on how effective the use of ACT is within the routine health system. The INESS platform evaluated effective coverage of ACT in several African countries. Timely access within 24 hours to an authorized ACT outlet is one of the determinants of effective coverage and was assessed for artemether-lumefantrine (Alu), in two district health systems in rural Tanzania. From October 2009 to June 2011 we conducted continuous rolling household surveys in the Kilombero-Ulanga and the Rufiji Health and Demographic Surveillance Sites (HDSS). Surveys were linked to the routine HDSS update rounds. Members of randomly pre-selected households that had experienced a fever episode in the previous two weeks were eligible for a structured interview. Data on individual treatment seeking, access to treatment, timing, source of treatment and household costs per episode were collected. Data are presented on timely access from a total of 2,112 interviews in relation to demographics, seasonality, and socio economic status. In Kilombero-Ulanga, 41.8% (CI: 36.6-45.1) and in Rufiji 36.8% (33.7-40.1) of fever cases had access to an authorized ACT provider within 24 hours of fever onset. In neither of the HDSS site was age, sex, socio-economic status or seasonality of malaria found to be significantly correlated with timely access. Timely access to authorized ACT providers is below 50% despite interventions intended to improve access such as social marketing and accreditation of private dispensing outlets. To improve prompt diagnosis and treatment, access remains a major bottle neck and new more innovative interventions are needed to raise effective coverage of malaria treatment in Tanzania.

  17. Anti-malarial Drug Design by Targeting Apicoplasts: New Perspectives

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    Avinaba Mukherjee

    2016-03-01

    Full Text Available Objectives: Malaria has been a major global health problem in recent times with increasing mortality. Current treatment methods include parasiticidal drugs and vaccinations. However, resistance among malarial parasites to the existing drugs has emerged as a significant area of concern in anti-malarial drug design. Researchers are now desperately looking for new targets to develop anti-malarials drug which is more target specific. Malarial parasites harbor a plastid-like organelle known as the ‘apicoplast’, which is thought to provide an exciting new outlook for the development of drugs to be used against the parasite. This review elaborates on the current state of development of novel compounds targeted againstemerging malaria parasites. Methods: The apicoplast, originates by an endosymbiotic process, contains a range of metabolic pathways and housekeeping processes that differ from the host body and thereby presents ideal strategies for anti-malarial drug therapy. Drugs are designed by targeting the unique mechanism of the apicoplasts genetic machinery. Several anabolic and catabolic processes, like fatty acid, isopenetyl diphosphate and heme synthess in this organelle, have also been targeted by drugs. Results: Apicoplasts offer exciting opportunities for the development of malarial treatment specific drugs have been found to act by disrupting this organelle’s function, which wouldimpede the survival of the parasite. Conclusion: Recent advanced drugs, their modes of action, and their advantages in the treatment of malaria by using apicoplasts as a target are discussed in this review which thought to be very useful in desigining anti-malarial drugs. Targetting the genetic machinery of apicoplast shows a great advantange regarding anti-malarial drug design. Critical knowledge of these new drugs would give a healthier understanding for deciphering the mechanism of action of anti-malarial drugs when targeting apicoplasts to overcome drug

  18. Combination treatment of glioblastoma multiforme cell lines with the anti-malarial artesunate and the epidermal growth factor receptor tyrosine kinase inhibitor OSI-774.

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    Efferth, Thomas; Ramirez, Tzutzuy; Gebhart, Erich; Halatsch, Marc-Eric

    2004-05-01

    New drugs and combination modalities for otherwise non-responsive brain tumors are urgently required. The anti-malarial artesunate (ART) and the EGFR tyrosine kinase inhibitor OSI-774 reveal profound cytotoxic activity. The effectiveness of a combination treatment and the underlying molecular determinants of cellular response are unknown. In the present investigation, we studied ART and OSI-774 in glioblastoma multiforme (GBM) cell lines. Supra-additive inhibition of cell growth was observed in U-87MG.DeltaEGFR cells transduced with a deletion-mutant constitutively active EGFR gene, while additive effects were present in cells transduced with wild-type EGFR (U-87MG.WT-2N), kinase-deficient EGFR (U-87MG.DK-2N), mock vector controls (U-87MG.LUX), or non-transduced parental U-87MG cells. Among nine other non-transduced GBM cell lines, supra-additive effects were found in two cell lines (G-210GM, G-599GM), while ART and OSI-774 acted in an additive manner in the other seven cell lines (G-211GM, G-750GM, G-1163GM, G-1187GM, G-1265GM, G-1301GM, and G-1408GM). Sub-additive or antagonistic effects were not observed. Genomic gains and losses of genetic material in the non-transduced cell lines as assessed by comparative genomic hybridization were correlated with the IC(50) values for ART and OSI-774 and subsequently subjected to hierarchical cluster analysis and cluster image mapping. A genomic profile of imbalances was detected that predicted cellular response to ART and OSI-774. The genes located at the genomic imbalances of interest may serve as candidate resistance genes of GBM cells towards ART and OSI-774. In conclusion, the combination treatment of ART and OSI-774 resulted in an increased growth inhibition of GBM cell lines as compared to each drug alone.

  19. Artemisinin anti-malarial drugs in China

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    Zongru Guo

    2016-03-01

    Full Text Available Discovered by Youyou Tu, one of the 2015 Nobel Prize winners in Physiology or Medicine, together with many other Chinese scientists, artemisinin, artemether and artesunate, as well as other artemisinins, have brought the global anti-malarial treatment to a new era, saving millions of lives all around the world for the past 40 years. The discoveries of artemisinins were carried out beginning from the 1970s, a special period in China, by hundreds of scientists all together under the “whole nation” system. This article focusing on medicinal chemistry research, briefly introduced the discovery and invention course of the scientists according to the published papers, and highlighted their academic contribution and achievements.

  20. Atovaquone and quinine anti-malarials inhibit ATP binding cassette transporter activity

    NARCIS (Netherlands)

    Rijpma, S.R.; Heuvel, J.J.; Velden, M. van der; Sauerwein, R.W.; Russel, F.G.; Koenderink, J.B.

    2014-01-01

    BACKGROUND: Therapeutic blood plasma concentrations of anti-malarial drugs are essential for successful treatment. Pharmacokinetics of pharmaceutical compounds are dependent of adsorption, distribution, metabolism, and excretion. ATP binding cassette (ABC) transport proteins are particularly

  1. Evidence on anti-malarial and diagnostic markets in Cambodia to guide malaria elimination strategies and policies.

    Science.gov (United States)

    Phok, Sochea; Lek, Dysoley

    2017-04-25

    Understanding Cambodia's anti-malarial and diagnostic landscape in 2015 is critical for informing and monitoring strategies and policies as Cambodia moves forward with national efforts to eliminate malaria. The aim of this paper is to present timely and key findings on the public and private sector anti-malarial and diagnostic landscape in Cambodia. This evidence can serve as a baseline benchmark for guiding implementation of national strategies as well as other regional initiatives to address malaria elimination activities. From August 17th to October 1st, 2015, a cross sectional, nationally-representative malaria outlet survey was conducted in Cambodia. A census of all public and private outlets with potential to distribute malaria testing and/or treatment was conducted among 180 communes. An audit was completed for all anti-malarials, malaria rapid diagnostic tests (RDT) and microscopy. A total of 26,664 outlets were screened, and 1303 outlets were eligible and interviewed. Among all screened outlets in the public sector, 75.9% of public health facilities and 67.7% of community health workers stocked both malaria diagnostic testing and a first-line artemisinin-based combination therapy (ACT). Among anti-malarial-stocking private sector outlets, 64.7% had malaria blood testing available, and 70.9% were stocking a first-line ACT. Market share data illustrate that most of the anti-malarials were sold or distributed through the private sector (58.4%), including itinerant drug vendors (23.4%). First-line ACT accounted for the majority of the market share across the public and private sectors (90.3%). Among private sector outlets stocking any anti-malarial, the proportion of outlets with a first-line ACT or RDT was higher among outlets that had reportedly received one or more forms of 'support' (e.g. reportedly received training in the previous year on malaria diagnosis [RDT and/or microscopy] and/or the national treatment guidelines for malaria) compared to outlets

  2. Does anti-malarial drug knowledge predict anti-malarial dispensing practice in drug outlets? A survey of medicine retailers in western Kenya

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    Rusk Andria

    2012-08-01

    Full Text Available Abstract Background Malaria is a major cause of morbidity and mortality in Kenya, where it is the fifth leading cause of death in both children and adults. Effectively managing malaria is dependent upon appropriate treatment. In Kenya, between 17 to 83 percent of febrile individuals first seek treatment for febrile illness over the counter from medicine retailers. Understanding medicine retailer knowledge and behaviour in treating suspected malaria and dispensing anti-malarials is crucial. Methods To investigate medicine retailer knowledge about anti-malarials and their dispensing practices, a survey was conducted of all retail drug outlets that sell anti-malarial medications and serve residents of the Webuye Health and Demographic Surveillance Site in the Bungoma East District of western Kenya. Results Most of the medicine retailers surveyed (65% were able to identify artemether-lumefantrine (AL as the Kenyan Ministry of Health recommended first-line anti-malarial therapy for uncomplicated malaria. Retailers who correctly identified this treatment were also more likely to recommend AL to adult and paediatric customers. However, the proportion of medicine retailers who recommend the correct treatment is disappointingly low. Only 48% would recommend AL to adults, and 37% would recommend it to children. It was discovered that customer demand has an influence on retailer behaviour. Retailer training and education were found to be correlated with anti-malarial drug knowledge, which in turn is correlated with dispensing practices. Medicine retailer behaviour, including patient referral practice and dispensing practices, are also correlated with knowledge of the first-line anti-malarial medication. The Kenya Ministry of Health guidelines were found to influence retailer drug stocking and dispensing behaviours. Conclusion Most medicine retailers could identify the recommended first-line treatment for uncomplicated malaria, but the percentage that could

  3. Case management of malaria fever in Cambodia: results from national anti-malarial outlet and household surveys.

    Science.gov (United States)

    Littrell, Megan; Gatakaa, Hellen; Phok, Sochea; Allen, Henrietta; Yeung, Shunmay; Chuor, Char Meng; Dysoley, Lek; Socheat, Duong; Spiers, Angus; White, Chris; Shewchuk, Tanya; Chavasse, Desmond; O'Connell, Kathryn A

    2011-10-31

    Continued progress towards global reduction in morbidity and mortality due to malaria requires scale-up of effective case management with artemisinin-combination therapy (ACT). The first case of artemisinin resistance in Plasmodium falciparum was documented in western Cambodia. Spread of artemisinin resistance would threaten recent gains in global malaria control. As such, the anti-malarial market and malaria case management practices in Cambodia have global significance. Nationally-representative household and outlet surveys were conducted in 2009 among areas in Cambodia with malaria risk. An anti-malarial audit was conducted among all public and private outlets with the potential to sell anti-malarials. Indicators on availability, price and relative volumes sold/distributed were calculated across types of anti-malarials and outlets. The household survey collected information about management of recent "malaria fevers." Case management in the public versus private sector, and anti-malarial treatment based on malaria diagnostic testing were examined. Most public outlets (85%) and nearly half of private pharmacies, clinics and drug stores stock ACT. Oral artemisinin monotherapy was found in pharmacies/clinics (9%), drug stores (14%), mobile providers (4%) and grocery stores (2%). Among total anti-malarial volumes sold/distributed nationally, 6% are artemisinin monotherapies and 72% are ACT. Only 45% of people with recent "malaria fever" reportedly receive a diagnostic test, and the most common treatment acquired is a drug cocktail containing no identifiable anti-malarial. A self-reported positive diagnostic test, particularly when received in the public sector, improves likelihood of receiving anti-malarial treatment. Nonetheless, anti-malarial treatment of reportedly positive cases is low among people who seek treatment exclusively in the public (61%) and private (42%) sectors. While data on the anti-malarial market shows favourable progress towards replacing

  4. Case management of malaria fever in Cambodia: results from national anti-malarial outlet and household surveys

    Directory of Open Access Journals (Sweden)

    Littrell Megan

    2011-10-01

    Full Text Available Abstract Background Continued progress towards global reduction in morbidity and mortality due to malaria requires scale-up of effective case management with artemisinin-combination therapy (ACT. The first case of artemisinin resistance in Plasmodium falciparum was documented in western Cambodia. Spread of artemisinin resistance would threaten recent gains in global malaria control. As such, the anti-malarial market and malaria case management practices in Cambodia have global significance. Methods Nationally-representative household and outlet surveys were conducted in 2009 among areas in Cambodia with malaria risk. An anti-malarial audit was conducted among all public and private outlets with the potential to sell anti-malarials. Indicators on availability, price and relative volumes sold/distributed were calculated across types of anti-malarials and outlets. The household survey collected information about management of recent "malaria fevers." Case management in the public versus private sector, and anti-malarial treatment based on malaria diagnostic testing were examined. Results Most public outlets (85% and nearly half of private pharmacies, clinics and drug stores stock ACT. Oral artemisinin monotherapy was found in pharmacies/clinics (9%, drug stores (14%, mobile providers (4% and grocery stores (2%. Among total anti-malarial volumes sold/distributed nationally, 6% are artemisinin monotherapies and 72% are ACT. Only 45% of people with recent "malaria fever" reportedly receive a diagnostic test, and the most common treatment acquired is a drug cocktail containing no identifiable anti-malarial. A self-reported positive diagnostic test, particularly when received in the public sector, improves likelihood of receiving anti-malarial treatment. Nonetheless, anti-malarial treatment of reportedly positive cases is low among people who seek treatment exclusively in the public (61% and private (42% sectors. Conclusions While data on the anti-malarial

  5. Access to artesunate-amodiaquine, quinine and other anti-malarials: policy and markets in Burundi

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    Dismas Baza

    2011-02-01

    Full Text Available Abstract Background Malaria is the leading cause of morbidity and mortality in post-conflict Burundi. To counter the increasing challenge of anti-malarial drug resistance and improve highly effective treatment Burundi adopted artesunate-amodiaquine (AS-AQ as first-line treatment for uncomplicated Plasmodium falciparum malaria and oral quinine as second-line treatment in its national treatment policy in 2003. Uptake of this policy in the public, private and non-governmental (NGO retail market sectors of Burundi is relatively unknown. This study was conducted to evaluate access to national policy recommended anti-malarials. Methods Adapting a standardized methodology developed by Health Action International/World Health Organization (HAI/WHO, a cross-sectional survey of 70 (24 public, 36 private, and 10 NGO medicine outlets was conducted in three regions of Burundi, representing different levels of transmission of malaria. The availability on day of the survey, the median prices, and affordability (in terms of number of days' wages to purchase treatment of AS-AQ, quinine and other anti-malarials were calculated. Results Anti-malarials were stocked in all outlets surveyed. AS-AQ was available in 87.5%, 33.3%, and 90% of public, private, and NGO retail outlets, respectively. Quinine was the most common anti-malarial found in all outlet types. Non-policy recommended anti-malarials were mainly found in the private outlets (38.9% compared to public (4.2% and NGO (0% outlets. The median price of a course of AS-AQ was US$0.16 (200 Burundi Francs, FBu for the public and NGO markets, and 3.5-fold higher in the private sector (US$0.56 or 700 FBu. Quinine tablets were similarly priced in the public (US$1.53 or 1,892.50 FBu, private and NGO sectors (both US$1.61 or 2,000 FBu. Non-policy anti-malarials were priced 50-fold higher than the price of AS-AQ in the public sector. A course of AS-AQ was affordable at 0.4 of a day's wage in the public and NGO sectors

  6. In vitro and in vivo assessment of the anti-malarial activity of Caesalpinia pluviosa

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    Eberlin Marcos N

    2011-05-01

    Full Text Available Abstract Background To overcome the problem of increasing drug resistance, traditional medicines are an important source for potential new anti-malarials. Caesalpinia pluviosa, commonly named "sibipiruna", originates from Brazil and possess multiple therapeutic properties, including anti-malarial activity. Methods Crude extract (CE was obtained from stem bark by purification using different solvents, resulting in seven fractions. An MTT assay was performed to evaluate cytotoxicity in MCF-7 cells. The CE and its fractions were tested in vitro against chloroquine-sensitive (3D7 and -resistant (S20 strains of Plasmodium falciparum and in vivo in Plasmodium chabaudi-infected mice. In vitro interaction with artesunate and the active C. pluviosa fractions was assessed, and mass spectrometry analyses were conducted. Results At non-toxic concentrations, the 100% ethanolic (F4 and 50% methanolic (F5 fractions possessed significant anti-malarial activity against both 3D7 and S20 strains. Drug interaction assays with artesunate showed a synergistic interaction with the F4. Four days of treatment with this fraction significantly inhibited parasitaemia in mice in a dose-dependent manner. Mass spectrometry analyses revealed the presence of an ion corresponding to m/z 303.0450, suggesting the presence of quercetin. However, a second set of analyses, with a quercetin standard, showed distinct ions of m/z 137 and 153. Conclusions The findings show that the F4 fraction of C. pluviosa exhibits anti-malarial activity in vitro at non-toxic concentrations, which was potentiated in the presence of artesunate. Moreover, this anti-malarial activity was also sustained in vivo after treatment of infected mice. Finally, mass spectrometry analyses suggest that a new compound, most likely an isomer of quercetin, is responsible for the anti-malarial activity of the F4.

  7. The ACTwatch project: methods to describe anti-malarial markets in seven countries.

    Science.gov (United States)

    Shewchuk, Tanya; O'Connell, Kathryn A; Goodman, Catherine; Hanson, Kara; Chapman, Steven; Chavasse, Desmond

    2011-10-31

    Policy makers, governments and donors are faced with an information gap when considering ways to improve access to artemisinin-based combination therapy (ACT) and malaria diagnostics including rapid diagnostic tests (RDTs). To help address some of these gaps, a five-year multi-country research project called ACTwatch was launched. The project is designed to provide a comprehensive picture of the anti-malarial market to inform national and international anti-malarial drug policy decision-making. The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012.ACTwatch measures which anti-malarials are available, where they are available and at what price and who they are used by. These indicators are measured over time and across countries through three study components: outlet surveys, supply chain studies and household surveys. Nationally representative outlet surveys examine the market share of different anti-malarials passing through public facilities and private retail outlets. Supply chain research provides a picture of the supply chain serving drug outlets, and measures mark-ups at each supply chain level. On the demand side, nationally representative household surveys capture treatment seeking patterns and use of anti-malarial drugs, as well as respondent knowledge of anti-malarials. The research project provides findings on both the demand and supply side determinants of anti-malarial access. There are four key features of ACTwatch. First is the overlap of the three study components where nationally representative data are collected over similar periods, using a common sampling approach. A second feature is the number and diversity of countries that are studied which allows for cross-country comparisons. Another distinguishing feature is its ability to measure trends over time. Finally, the project aims to disseminate findings widely for decision

  8. The ACTwatch project: methods to describe anti-malarial markets in seven countries

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    Chapman Steven

    2011-10-01

    Full Text Available Abstract Background Policy makers, governments and donors are faced with an information gap when considering ways to improve access to artemisinin-based combination therapy (ACT and malaria diagnostics including rapid diagnostic tests (RDTs. To help address some of these gaps, a five-year multi-country research project called ACTwatch was launched. The project is designed to provide a comprehensive picture of the anti-malarial market to inform national and international anti-malarial drug policy decision-making. Methods The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012. ACTwatch measures which anti-malarials are available, where they are available and at what price and who they are used by. These indicators are measured over time and across countries through three study components: outlet surveys, supply chain studies and household surveys. Nationally representative outlet surveys examine the market share of different anti-malarials passing through public facilities and private retail outlets. Supply chain research provides a picture of the supply chain serving drug outlets, and measures mark-ups at each supply chain level. On the demand side, nationally representative household surveys capture treatment seeking patterns and use of anti-malarial drugs, as well as respondent knowledge of anti-malarials. Discussion The research project provides findings on both the demand and supply side determinants of anti-malarial access. There are four key features of ACTwatch. First is the overlap of the three study components where nationally representative data are collected over similar periods, using a common sampling approach. A second feature is the number and diversity of countries that are studied which allows for cross-country comparisons. Another distinguishing feature is its ability to measure trends over time. Finally, the

  9. The ACTwatch project: methods to describe anti-malarial markets in seven countries

    Science.gov (United States)

    2011-01-01

    Background Policy makers, governments and donors are faced with an information gap when considering ways to improve access to artemisinin-based combination therapy (ACT) and malaria diagnostics including rapid diagnostic tests (RDTs). To help address some of these gaps, a five-year multi-country research project called ACTwatch was launched. The project is designed to provide a comprehensive picture of the anti-malarial market to inform national and international anti-malarial drug policy decision-making. Methods The project is being conducted in seven malaria-endemic countries: Benin, Cambodia, the Democratic Republic of Congo, Madagascar, Nigeria, Uganda and Zambia from 2008 to 2012. ACTwatch measures which anti-malarials are available, where they are available and at what price and who they are used by. These indicators are measured over time and across countries through three study components: outlet surveys, supply chain studies and household surveys. Nationally representative outlet surveys examine the market share of different anti-malarials passing through public facilities and private retail outlets. Supply chain research provides a picture of the supply chain serving drug outlets, and measures mark-ups at each supply chain level. On the demand side, nationally representative household surveys capture treatment seeking patterns and use of anti-malarial drugs, as well as respondent knowledge of anti-malarials. Discussion The research project provides findings on both the demand and supply side determinants of anti-malarial access. There are four key features of ACTwatch. First is the overlap of the three study components where nationally representative data are collected over similar periods, using a common sampling approach. A second feature is the number and diversity of countries that are studied which allows for cross-country comparisons. Another distinguishing feature is its ability to measure trends over time. Finally, the project aims to disseminate

  10. Epidemiological models for the spread of anti-malarial resistance

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    Antia R

    2003-02-01

    Full Text Available Abstract Background The spread of drug resistance is making malaria control increasingly difficult. Mathematical models for the transmission dynamics of drug sensitive and resistant strains can be a useful tool to help to understand the factors that influence the spread of drug resistance, and they can therefore help in the design of rational strategies for the control of drug resistance. Methods We present an epidemiological framework to investigate the spread of anti-malarial resistance. Several mathematical models, based on the familiar Macdonald-Ross model of malaria transmission, enable us to examine the processes and parameters that are critical in determining the spread of resistance. Results In our simplest model, resistance does not spread if the fraction of infected individuals treated is less than a threshold value; if drug treatment exceeds this threshold, resistance will eventually become fixed in the population. The threshold value is determined only by the rates of infection and the infectious periods of resistant and sensitive parasites in untreated and treated hosts, whereas the intensity of transmission has no influence on the threshold value. In more complex models, where hosts can be infected by multiple parasite strains or where treatment varies spatially, resistance is generally not fixed, but rather some level of sensitivity is often maintained in the population. Conclusions The models developed in this paper are a first step in understanding the epidemiology of anti-malarial resistance and evaluating strategies to reduce the spread of resistance. However, specific recommendations for the management of resistance need to wait until we have more data on the critical parameters underlying the spread of resistance: drug use, spatial variability of treatment and parasite migration among areas, and perhaps most importantly, cost of resistance.

  11. Mass anti-malarial administration in western Cambodia: a qualitative study of factors affecting coverage.

    Science.gov (United States)

    Pell, Christopher; Tripura, Rupam; Nguon, Chea; Cheah, Phaikyeong; Davoeung, Chan; Heng, Chhouen; Dara, Lim; Sareth, Ma; Dondorp, Arjen; von Seidlein, Lorenz; Peto, Thomas J

    2017-05-19

    Mass anti-malarial administration has been proposed as a key component of the Plasmodium falciparum malaria elimination strategy in the Greater Mekong sub-Region. Its effectiveness depends on high levels of coverage in the target population. This article explores the factors that influenced mass anti-malarial administration coverage within a clinical trial in Battambang Province, western Cambodia. Qualitative data were collected through semi-structured interviews and focus group discussions with villagers, in-depth interviews with study staff, trial drop-outs and refusers, and observations in the communities. Interviews were audio-recorded, transcribed and translated from Khmer to English for qualitative content analysis using QSR NVivo. Malaria was an important health concern and villagers reported a demand for malaria treatment. This was in spite of a fall in incidence over the previous decade and a lack of familiarity with asymptomatic malaria. Participants generally understood the overall study aim and were familiar with study activities. Comprehension of the study rationale was however limited. After the first mass anti-malarial administration, seasonal health complaints that participants attributed to the anti-malarial as "side effects" contributed to a decrease of coverage in round two. Staff therefore adapted the community engagement approach, bringing to prominence local leaders in village meetings. This contributed to a subsequent increase in coverage. Future mass anti-malarial administration must consider seasonal disease patterns and the importance of local leaders taking prominent roles in community engagement. Further research is needed to investigate coverage in scenarios that more closely resemble implementation i.e. without participation incentives, blood sampling and free healthcare.

  12. Increased pfmdr1 gene copy number and the decline in pfcrt and pfmdr1 resistance alleles in Ghanaian Plasmodium falciparum isolates after the change of anti-malarial drug treatment policy.

    Science.gov (United States)

    Duah, Nancy O; Matrevi, Sena A; de Souza, Dziedzom K; Binnah, Daniel D; Tamakloe, Mary M; Opoku, Vera S; Onwona, Christiana O; Narh, Charles A; Quashie, Neils B; Abuaku, Benjamin; Duplessis, Christopher; Kronmann, Karl C; Koram, Kwadwo A

    2013-10-30

    With the introduction of artemisinin-based combination therapy (ACT) in 2005, monitoring of anti-malarial drug efficacy, which includes the use of molecular tools to detect known genetic markers of parasite resistance, is important for first-hand information on the changes in parasite susceptibility to drugs in Ghana. This study investigated the Plasmodium falciparum multidrug resistance gene (pfmdr1) copy number, mutations and the chloroquine resistance transporter gene (pfcrt) mutations in Ghanaian isolates collected in seven years to detect the trends in prevalence of mutations. Archived filter paper blood blots collected from children aged below five years with uncomplicated malaria in 2003-2010 at sentinel sites were used. Using quantitative real-time polymerase chain reaction (qRT-PCR), 756 samples were assessed for pfmdr1 gene copy number. PCR and restriction fragment length polymorphism (RFLP) were used to detect alleles of pfmdr1 86 in 1,102 samples, pfmdr1 184, 1034, 1042 and 1246 in 832 samples and pfcrt 76 in 1,063 samples. Merozoite surface protein 2 (msp2) genotyping was done to select monoclonal infections for copy number analysis. The percentage of isolates with increased pfmdr1 copy number were 4, 27, 9, and 18% for 2003-04, 2005-06, 2007-08 and 2010, respectively. Significant increasing trends for prevalence of pfmdr1 N86 (×(2) = 96.31, p resistance has been reported. The decreasing trend in the prevalence of chloroquine resistance markers after change of treatment policy presents the possibility for future introduction of chloroquine as prophylaxis for malaria risk groups such as children and pregnant women in Ghana.

  13. The counterfeit anti-malarial is a crime against humanity: a systematic review of the scientific evidence

    Science.gov (United States)

    2014-01-01

    Background The counterfeiting of anti-malarials represents a form of attack on global public health in which fake and substandard anti-malarials serve as de facto weapons of mass destruction, particularly in resource-constrained endemic settings, where malaria causes nearly 660,000 preventable deaths and threatens millions of lives annually. It has been estimated that fake anti-malarials contribute to nearly 450,000 preventable deaths every year. This crime against humanity is often underestimated or ignored. This study attempts to describe and characterize the direct and indirect effects of counterfeit anti-malarials on public health, clinical care and socio-economic conditions. Methods A search was performed using key databases, WHO documents, and English language search engines. Of 262 potential articles that were identified using a fixed set of criteria, a convenience sample of 105 appropriate articles was selected for this review. Results Artemisinin-based combination therapy (ACT) is an important tool in the fight against malaria, but a sizable number of patients are unable to afford to this first-line treatment. Consequently, patients tend to procure cheaper anti-malarials, which may be fake or substandard. Forensic palynology reveals that counterfeits originate in Asia. Fragile drug regulations, ineffective law-enforcement agencies and corruption further burden ailing healthcare facilities. Substandard/fake anti-malarials can cause (a) economic sabotage; (b) therapeutic failure; (c) increased risk of the emergence and spread of resistant strains of Plasmodium falciparum and Plasmodium vivax; (d) an undermining of trust/confidence in healthcare stakeholders/systems; and, (e) serious side effects or death. Conclusion Combating counterfeit anti-malarials is a complex task due to limited resources and poor techniques for the detection and identification of fake anti-malarials. This situation calls for sustainable, global, scientific research and policy change

  14. The counterfeit anti-malarial is a crime against humanity: a systematic review of the scientific evidence.

    Science.gov (United States)

    Karunamoorthi, Kaliyaperumal

    2014-06-02

    The counterfeiting of anti-malarials represents a form of attack on global public health in which fake and substandard anti-malarials serve as de facto weapons of mass destruction, particularly in resource-constrained endemic settings, where malaria causes nearly 660,000 preventable deaths and threatens millions of lives annually. It has been estimated that fake anti-malarials contribute to nearly 450,000 preventable deaths every year. This crime against humanity is often underestimated or ignored. This study attempts to describe and characterize the direct and indirect effects of counterfeit anti-malarials on public health, clinical care and socio-economic conditions. A search was performed using key databases, WHO documents, and English language search engines. Of 262 potential articles that were identified using a fixed set of criteria, a convenience sample of 105 appropriate articles was selected for this review. Artemisinin-based combination therapy (ACT) is an important tool in the fight against malaria, but a sizable number of patients are unable to afford to this first-line treatment. Consequently, patients tend to procure cheaper anti-malarials, which may be fake or substandard. Forensic palynology reveals that counterfeits originate in Asia. Fragile drug regulations, ineffective law-enforcement agencies and corruption further burden ailing healthcare facilities. Substandard/fake anti-malarials can cause (a) economic sabotage; (b) therapeutic failure; (c) increased risk of the emergence and spread of resistant strains of Plasmodium falciparum and Plasmodium vivax; (d) an undermining of trust/confidence in healthcare stakeholders/systems; and, (e) serious side effects or death. Combating counterfeit anti-malarials is a complex task due to limited resources and poor techniques for the detection and identification of fake anti-malarials. This situation calls for sustainable, global, scientific research and policy change. Further, responsible stakeholders in

  15. Impact of introducing subsidized combination treatment with artemether-lumefantrine on sales of anti-malarial monotherapies: a survey of private sector pharmacies in Huambo, Angola.

    Science.gov (United States)

    Lussiana, Cristina; Floridia, Marco; Martinho do Rosário, Joana; Fortes, Filomeno; Allan, Richard

    2016-12-01

    Artemisinin-based combination therapies (ACTs) against malaria are subsidized in many African countries, but the impact of subsidy programs in reducing the sales of concomitantly available antimalarial monotherapies is poorly defined. Data from The MENTOR initiative, that introduced subsidized artemether-lumefantrine (sAL) in the private sector of Huambo province, Angola, were used. The main response variable was represented by sales of sAL and of monotherapies, measured as number of treatment courses. Sales in private pharmacies of sAL and four antimalarial monotherapies between 2009 and 2013 were organized in four time-periods, and analyzed using generalized linear models for repeated measures. A secondary analysis evaluated changes in relative market share. We analyzed data from 34 pharmacies at four time points, taken from a larger survey that involved 165 pharmacies between June 2009 and March 2013. The sAL, following its introduction, became the dominant antimalarial treatment in the private sector, usually exceeding the total sales of all antimalarial monotherapies combined (1480/2800 total treatment courses, 52.8% of all sales in March 2013). Sales of monotherapies decreased significantly, but did not stop, representing 36.7% (1028/2800) of sales at the end of the survey. Subsidized ACTs can attain rapidly a high relative market share. Their introduction reduced, but did not eliminate the demand for less effective monotherapies, that might favor parasite resistance. © The Author 2016. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  16. Active case detection, treatment of falciparum malaria with combined chloroquine and sulphadoxine/pyrimethamine and vivax malaria with chloroquine and molecular markers of anti-malarial resistance in the Republic of Vanuatu

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    Rogers William O

    2010-04-01

    Full Text Available Abstract Background Chloroquine-resistant Plasmodium falciparum was first described in the Republic of Vanuatu in the early 1980s. In 1991, the Vanuatu Ministry of Health instituted new treatment guidelines for uncomplicated P. falciparum infection consisting of chloroquine/sulphadoxine-pyrimethamine combination therapy. Chloroquine remains the recommended treatment for Plasmodium vivax. Methods In 2005, cross-sectional blood surveys at 45 sites on Malo Island were conducted and 4,060 adults and children screened for malaria. Of those screened, 203 volunteer study subjects without malaria at the time of screening were followed for 13 weeks to observe peak seasonal incidence of infection. Another 54 subjects with malaria were followed over a 28-day period to determine efficacy of anti-malarial therapy; chloroquine alone for P. vivax and chloroquine/sulphadoxine-pyrimethamine for P. falciparum infections. Results The overall prevalence of parasitaemia by mass blood screening was 6%, equally divided between P. falciparum and P. vivax. Twenty percent and 23% of participants with patent P. vivax and P. falciparum parasitaemia, respectively, were febrile at the time of screening. In the incidence study cohort, after 2,303 person-weeks of follow-up, the incidence density of malaria was 1.3 cases per person-year with P. vivax predominating. Among individuals participating in the clinical trial, the 28-day chloroquine P. vivax cure rate was 100%. The 28-day chloroquine/sulphadoxine-pyrimethamine P. falciparum cure rate was 97%. The single treatment failure, confirmed by merozoite surface protein-2 genotyping, was classified as a day 28 late parasitological treatment failure. All P. falciparum isolates carried the Thr-76 pfcrt mutant allele and the double Asn-108 + Arg-59 dhfr mutant alleles. Dhps mutant alleles were not detected in the study sample. Conclusion Peak seasonal malaria prevalence on Malo Island reached hypoendemic levels during the study

  17. Therapeutic efficacy of artesunate in the treatment of uncomplicated Plasmodium falciparum malaria and anti-malarial, drug-resistance marker polymorphisms in populations near the China-Myanmar border

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    Huang Fang

    2012-08-01

    Full Text Available Abstract Background The aim of this study was to evaluate the clinical outcome after seven-day artesunate monotherapy for uncomplicated Plasmodium falciparum malaria in Yingjiang County along the China-Myanmar border and investigate genetic polymorphisms in the P. falciparum chloroquine-resistance transporter (pfcrt, multidrug resistance 1 (pfmdr1, dihydrofolate reductase (pfdhfr, dihydropteroate synthase (pfdhps and ATPase (pfatp6 genes. Methods Patients ≥ one year of age with fever (axillary temperature ≥37.5°C or history of fever and P. falciparum mono-infection were included. Patients received anti-malarial treatment with artesunate (total dose of 16 mg/kg over seven days by directly observed therapy. After a 28-day follow-up, treatment efficacy and effectiveness were assessed based on clinical and parasitological outcomes. Treatment failure was defined as recrudescence of the original parasite and distinguished with new infection confirmed by PCR. Analysis of gene mutation and amplification were performed by nested polymerase chain reaction. Results Sixty-five patients were enrolled; 10 withdrew from the study, and six were lost to follow-up. All but two patients demonstrated adequate clinical and parasitological response; 12 had detectable parasitaemia on day 3. These two patients were confirmed to be new infection by PCR. The efficacy of artesunate was 95.9%. The pfcrt mutation in codon 76 was found in all isolates (100%, and mutations in codons 71 and 72 were found in 4.8% of parasite isolates. No mutation of pfmdr1 (codons 86 or 1246 was found. Among all samples, 5.1% were wild type for pfdhfr, whereas the other samples had mutations in four codons (51, 59, 108 and 164, and mutations in pfdhps (codons 436, 437, 540 and 581 were found in all isolates. No samples had mutations in pfatp6 codons 623 or 769, but two new mutations (N683K and R756K were found in 4.6% and 9.2% of parasite isolates, respectively. Conclusion Plasmodium

  18. A “reverse pharmacology” approach for developing an anti-malarial phytomedicine

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    Diakite Chiaka

    2011-03-01

    Full Text Available Abstract A “reverse pharmacology” approach to developing an anti-malarial phytomedicine was designed and implemented in Mali, resulting in a new standardized herbal anti-malarial after six years of research. The first step was to select a remedy for development, through a retrospective treatment-outcome study. The second step was a dose-escalating clinical trial that showed a dose-response phenomenon and helped select the safest and most efficacious dose. The third step was a randomized controlled trial to compare the phytomedicine to the standard first-line treatment. The last step was to identify active compounds which can be used as markers for standardization and quality control. This example of “reverse pharmacology” shows that a standardized phytomedicine can be developed faster and more cheaply than conventional drugs. Even if both approaches are not fully comparable, their efficiency in terms of public health and their complementarity should be thoroughly considered.

  19. Factors determining anti-malarial drug use in a peri-urban population from malaria holoendemic region of western kenya

    Directory of Open Access Journals (Sweden)

    Abong'o Benard

    2010-10-01

    Full Text Available Abstract Background Interventions to reverse trends in malaria-related morbidity and mortality in Kenya focus on preventive strategies and drug efficacy. However, the pattern of use of anti-malarials in malaria-endemic populations, such as in western Kenya, is still poorly understood. It is critical to understand the patterns of anti-malarial drug use to ascertain that the currently applied new combination therapy to malaria treatment, will achieve sustained cure rates and protection against parasite resistance. Therefore, this cross-sectional study was designed to determine the patterns of use of anti-malarial drugs in households (n = 397 in peri-urban location of Manyatta-B sub-location in Kisumu in western Kenya. Methods Household factors, associated with the pattern of anti-malarials use, were evaluated. Using clusters, questionnaire was administered to a particular household member who had the most recent malaria episode (within Results Stratification of the type of anti-malarial drugs taken revealed that 37.0% used sulphadoxine/pyrimethamine (SP, 32.0% artemisinin-based combined therapy (ACT, 11.1% anti-pyretics, 7.3% chloroquine (CQ, 7.1% quinine, 2.5% amodiaquine (AQ, while 3.0% used others which were perceived as anti-malarials (cough syrups and antibiotics. In a regression model, it was demonstrated that age (P = 0.050, household size (P = 0.047, household head (P = 0.049, household source of income (P = 0.015, monthly income (P = 0.020, duration of use (P = 0.029, dosage of drugs taken (P = 0.036, and source of drugs (P = 0.005 significantly influenced anti-malarial drug use. Overall, 38.8% of respondents used drugs as recommended by the Ministry of Health. Conclusion This study demonstrates that consumers require access to correct and comprehensible information associated with use of drugs, including self-prescription. There is potential need by the Kenyan government to improve malaria care and decrease malaria-related morbidity and

  20. Plasmodium falciparum neutral aminopeptidases: new targets for anti-malarials.

    Science.gov (United States)

    Skinner-Adams, Tina S; Stack, Colin M; Trenholme, Katharine R; Brown, Chris L; Grembecka, Jolanta; Lowther, Jonathan; Mucha, Artur; Drag, Marcin; Kafarski, Pawel; McGowan, Sheena; Whisstock, James C; Gardiner, Donald L; Dalton, John P

    2010-01-01

    The neutral aminopeptidases M1 alanyl aminopeptidase (PfM1AAP) and M17 leucine aminopeptidase (PfM17LAP) of the human malaria parasite Plasmodium falciparum are targets for the development of novel anti-malarial drugs. Although the functions of these enzymes remain unknown, they are believed to act in the terminal stages of haemoglobin degradation, generating amino acids essential for parasite growth and development. Inhibitors of both enzymes are lethal to P. falciparum in culture and kill the murine malaria P. chabaudi in vivo. Recent biochemical, structural and functional studies provide the substrate specificity and mechanistic binding data needed to guide the development of more potent anti-malarial drugs. Together with biological studies, these data form the rationale for choosing PfM1AAP and PfM17LAP as targets for anti-malarial development. Copyright 2009 Elsevier Ltd. All rights reserved.

  1. Atovaquone and quinine anti-malarials inhibit ATP binding cassette transporter activity.

    Science.gov (United States)

    Rijpma, Sanna R; van den Heuvel, Jeroen J M W; van der Velden, Maarten; Sauerwein, Robert W; Russel, Frans G M; Koenderink, Jan B

    2014-09-13

    Therapeutic blood plasma concentrations of anti-malarial drugs are essential for successful treatment. Pharmacokinetics of pharmaceutical compounds are dependent of adsorption, distribution, metabolism, and excretion. ATP binding cassette (ABC) transport proteins are particularly involved in drug deposition, as they are located at membranes of many uptake and excretory organs and at protective barriers, where they export endogenous and xenobiotic compounds, including pharmaceuticals. In this study, a panel of well-established anti-malarial drugs which may affect drug plasma concentrations was tested for interactions with human ABC transport proteins. The interaction of chloroquine, quinine, artemisinin, mefloquine, lumefantrine, atovaquone, dihydroartemisinin and proguanil, with transport activity of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), bile salt export pump (BSEP) and multidrug resistance-associated proteins (MRP) 1-4 were analysed. The effect of the anti-malarials on the ATP-dependent uptake of radio-labelled substrates was measured in membrane vesicles isolated from HEK293 cells overexpressing the ABC transport proteins. A strong and previously undescribed inhibition of BCRP-mediated transport by atovaquone with a 50% inhibitory concentration (IC50) of 0.23 μM (95% CI 0.17-0.29 μM) and inhibition of P-gp-mediated transport by quinine with an IC50 of 6.8 μM (95% CI 5.9-7.8 μM) was observed. Furthermore, chloroquine and mefloquine were found to significantly inhibit P-gp-mediated transport. BCRP transport activity was significantly inhibited by all anti-malarials tested, whereas BSEP-mediated transport was not inhibited by any of the compounds. Both MRP1- and MRP3-mediated transport were significantly inhibited by mefloquine. Atovaquone and quinine significantly inhibit BCRP- and P-gp- mediated transport at concentrations within the clinically relevant prophylactic and therapeutic range. Co-administration of these established anti-malarials

  2. Quality of anti-malarials collected in the private and informal sectors in Guyana and Suriname.

    Science.gov (United States)

    Evans, Lawrence; Coignez, Veerle; Barojas, Adrian; Bempong, Daniel; Bradby, Sanford; Dijiba, Yanga; James, Makeida; Bretas, Gustavo; Adhin, Malti; Ceron, Nicolas; Hinds-Semple, Alison; Chibwe, Kennedy; Lukulay, Patrick; Pribluda, Victor

    2012-06-15

    Despite a significant reduction in the number of malaria cases in Guyana and Suriname, this disease remains a major problem in the interior of both countries, especially in areas with gold mining and logging operations, where malaria is endemic. National malaria control programmes in these countries provide treatment to patients with medicines that are procured and distributed through regulated processes in the public sector. However, availability to medicines in licensed facilities (private sector) and unlicensed facilities (informal sector) is common, posing the risk of access to and use of non-recommended treatments and/or poor quality products. To assess the quality of circulating anti-malarial medicines, samples were purchased in the private and informal sectors of Guyana and Suriname in 2009. The sampling sites were selected based on epidemiological data and/or distance from health facilities. Samples were analysed for identity, content, dissolution or disintegration, impurities, and uniformity of dosage units or weight variation according to manufacturer, pharmacopeial, or other validated method. Quality issues were observed in 45 of 77 (58%) anti-malarial medicines sampled in Guyana of which 30 failed visual & physical inspection and 18 failed quality control tests. The proportion of monotherapy and ACT medicines failing quality control tests was 43% (13/30) and 11% (5/47) respectively. A higher proportion of medicines sampled from the private sector 34% (11/32) failed quality control tests versus 16% (7/45) in the informal sector. In Suriname, 58 medicines were sampled, of which 50 (86%) were Artecom®, the fixed-dose combination of piperaquine-dihydroartemisinin-trimethoprim co-blistered with a primaquine phosphate tablet. All Artecom samples were found to lack a label claim for primaquine, thus failing visual and physical inspection. The findings of the studies in both countries point to significant problems with the quality of anti-malarial medicines

  3. Quality of anti-malarials collected in the private and informal sectors in Guyana and Suriname

    Directory of Open Access Journals (Sweden)

    Evans Lawrence

    2012-06-01

    Full Text Available Abstract Background Despite a significant reduction in the number of malaria cases in Guyana and Suriname, this disease remains a major problem in the interior of both countries, especially in areas with gold mining and logging operations, where malaria is endemic. National malaria control programmes in these countries provide treatment to patients with medicines that are procured and distributed through regulated processes in the public sector. However, availability to medicines in licensed facilities (private sector and unlicensed facilities (informal sector is common, posing the risk of access to and use of non-recommended treatments and/or poor quality products. Methods To assess the quality of circulating anti-malarial medicines, samples were purchased in the private and informal sectors of Guyana and Suriname in 2009. The sampling sites were selected based on epidemiological data and/or distance from health facilities. Samples were analysed for identity, content, dissolution or disintegration, impurities, and uniformity of dosage units or weight variation according to manufacturer, pharmacopeial, or other validated method. Results Quality issues were observed in 45 of 77 (58% anti-malarial medicines sampled in Guyana of which 30 failed visual & physical inspection and 18 failed quality control tests. The proportion of monotherapy and ACT medicines failing quality control tests was 43% (13/30 and 11% (5/47 respectively. A higher proportion of medicines sampled from the private sector 34% (11/32 failed quality control tests versus 16% (7/45 in the informal sector. In Suriname, 58 medicines were sampled, of which 50 (86% were Artecom®, the fixed-dose combination of piperaquine-dihydroartemisinin-trimethoprim co-blistered with a primaquine phosphate tablet. All Artecom samples were found to lack a label claim for primaquine, thus failing visual and physical inspection. Conclusions The findings of the studies in both countries point to

  4. Molecular Farming in Artemisia annua, a sustainable approach to improve anti-malarial drug production

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    Giuseppe ePulice

    2016-03-01

    Full Text Available Malaria is a parasite infection affecting millions of people worldwide. Even though progresses in prevention and treatment have been developed, 198 million cases of malaria occurred in 2013, resulting in 584000 estimated deaths. 90% of all malaria deaths occurred in Africa, mostly among children under the age of five. This article aims to review malaria’s history, epidemiology and current treatments, with a particular focus on the potential of molecular farming that use metabolic engineering in plants as effective anti-malarial solution. Malaria indeed represents an example of how a health problem on one hand, may eventually influence the proper development of a country due to the burden of the disease, and on the other hand, constitutes an opportunity for lucrative business of diverse stakeholders. In contrast, plant biofarming is here proposed as a sustainable alternative for the production not only of natural herbal repellents used for malaria prevention but also for the production of sustainable anti-malarial drugs like artemisinin used for primary parasite infection treatments.Artemisinin, a sesquiterpene lactone, is a natural anti-malarial compound that can be found in Artemisia annua plant. However, the low concentration of artemisinin in plant makes this molecule relatively expensive and difficult to meet the worldwide demand of Artemisinin Combination Therapies, especially for economically disadvantaged people in developing countries. The biosynthetic pathway of artemisinin, a process that only takes place in glandular secretory trichomes of A. annua, is relatively well elucidated, and significant efforts using plant genetic engineering have been made to increase the production of this compound. These include studies on diverse transcription factors, which all have been shown to regulate artemisinin genetic pathway and other biological processes. Therefore, genetic manipulation of these genes may be used as a cost-effective potential

  5. In vivo validation of anti-malarial activity of crude extracts of Terminalia macroptera, a Malian medicinal plant

    OpenAIRE

    Haidara, Mahamane; Haddad, Mohamed; Denou, Adama; Marti, Guillaume; Bourgeade-Delmas, Sandra; Sanogo, Rokia; Bourdy, Geneviève; Aubouy, Agnès

    2018-01-01

    Background Plasmodium falciparum malaria is still one of the most deadly pathology worldwide. Efficient treatment is jeopardized by parasite resistance to artemisinin and its derivatives, and by poor access to treatment in endemic regions. Anti-malarial traditional remedies still offer new tracks for identifying promising antiplasmodial molecules, and a way to ensure that all people have access to care. The present study aims to validate the traditional use of Terminalia macroptera, a Malian ...

  6. In vivo validation of anti-malarial activity of crude extracts of Terminalia macroptera, a Malian medicinal plant

    OpenAIRE

    Haidara, M.; Haddad, Mohamed; Denou, A.; Marti, G.; Bourgeade-Delmas, Sandra; Sanogo, R.; Bourdy, Geneviève; Aubouy, Agnès

    2018-01-01

    Background: Plasmodium falciparum malaria is still one of the most deadly pathology worldwide. Efficient treatment is jeopardized by parasite resistance to artemisinin and its derivatives, and by poor access to treatment in endemic regions. Anti-malarial traditional remedies still offer new tracks for identifying promising antiplasmodial molecules, and a way to ensure that all people have access to care. The present study aims to validate the traditional use of Terminalia macroptera, a Malian...

  7. Systematic review on traditional medicinal plants used for the treatment of malaria in Ethiopia: trends and perspectives.

    Science.gov (United States)

    Alebie, Getachew; Urga, Befikadu; Worku, Amha

    2017-08-01

    Ethiopia is endowed with abundant medicinal plant resources and traditional medicinal practices. However, available research evidence on indigenous anti-malarial plants is highly fragmented in the country. The present systematic review attempted to explore, synthesize and compile ethno-medicinal research evidence on anti-malarial medicinal plants in Ethiopia. A systematic web search analysis and review was conducted on research literature pertaining to medicinal plants used for traditional malaria treatment in Ethiopia. Data were collected from a total of 82 Ethiopian studies meeting specific inclusion criteria including published research articles and unpublished thesis reports. SPSS Version 16 was used to summarize relevant ethno-botanical/medicinal information using descriptive statistics, frequency, percentage, tables, and bar graphs. A total of 200 different plant species (from 71 families) used for traditional malaria treatment were identified in different parts of Ethiopia. Distribution and usage pattern of anti-malarial plants showed substantial variability across different geographic settings. A higher diversity of anti-malarial plants was reported from western and southwestern parts of the country. Analysis of ethno-medicinal recipes indicated that mainly fresh leaves were used for preparation of remedies. Decoction, concoction and eating/chewing were found to be the most frequently employed herbal remedy preparation methods. Notably, anti-malarial herbal remedies were administered by oral route. Information on potential side effects of anti-malarial herbal preparations was patchy. However, some anti-malarial plants were reported to have potentially serious side effects using different local antidotes and some specific contra-indications. The study highlighted a rich diversity of indigenous anti-malarial medicinal plants with equally divergent herbal remedy preparation and use pattern in Ethiopia. Baseline information gaps were observed in key geographic

  8. Reduction of anti-malarial consumption after rapid diagnostic tests implementation in Dar es Salaam: a before-after and cluster randomized controlled study

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    Swai Ndeniria

    2011-04-01

    Full Text Available Abstract Background Presumptive treatment of all febrile patients with anti-malarials leads to massive over-treatment. The aim was to assess the effect of implementing malaria rapid diagnostic tests (mRDTs on prescription of anti-malarials in urban Tanzania. Methods The design was a prospective collection of routine statistics from ledger books and cross-sectional surveys before and after intervention in randomly selected health facilities (HF in Dar es Salaam, Tanzania. The participants were all clinicians and their patients in the above health facilities. The intervention consisted of training and introduction of mRDTs in all three hospitals and in six HF. Three HF without mRDTs were selected as matched controls. The use of routine mRDT and treatment upon result was advised for all patients complaining of fever, including children under five years of age. The main outcome measures were: (1 anti-malarial consumption recorded from routine statistics in ledger books of all HF before and after intervention; (2 anti-malarial prescription recorded during observed consultations in cross-sectional surveys conducted in all HF before and 18 months after mRDT implementation. Results Based on routine statistics, the amount of artemether-lumefantrine blisters used post-intervention was reduced by 68% (95%CI 57-80 in intervention and 32% (9-54 in control HF. For quinine vials, the reduction was 63% (54-72 in intervention and an increase of 2.49 times (1.62-3.35 in control HF. Before-and-after cross-sectional surveys showed a similar decrease from 75% to 20% in the proportion of patients receiving anti-malarial treatment (Risk ratio 0.23, 95%CI 0.20-0.26. The cluster randomized analysis showed a considerable difference of anti-malarial prescription between intervention HF (22% and control HF (60% (Risk ratio 0.30, 95%CI 0.14-0.70. Adherence to test result was excellent since only 7% of negative patients received an anti-malarial. However, antibiotic

  9. Substandard anti-malarial drugs in Burkina Faso

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    Sie Ali

    2008-05-01

    Full Text Available Abstract Background There is concern about an increasing infiltration of markets by substandard and fake medications against life-threatening diseases in developing countries. This is particularly worrying with regard to the increasing resistance development of Plasmodium falciparum against affordable anti-malarial medications, which has led to a change to more expensive drugs in most endemic countries. Methods A representative sample of modern anti-malarial medications from licensed (public and private pharmacies, community health workers and illicit (market and street vendors, shops sources has been collected in the Nouna Health District in north-western Burkina Faso in 2006. All drugs were tested for their quality with the standard procedures of the German Pharma Health Fund-Minilab. Detected low standard drugs were re-tested with European Pharmacopoeia 2.9.1 standards for disintegration and ultraviolet-visible spectroscopy at the laboratory of the Heidelberg University for confirmation. Results Overall, 86 anti-malarial drug samples were collected, of which 77 samples have been included in the final analysis. The sample consisted of 39/77 (50% chloroquine, 10/77 (13% pyrimethamine-sulphadoxine, 9/77 (12% quinine, 6/77 (8% amodiaquine, 9/77 (12% artesunate, and 4/77 (5% artemether-lumefantrine. 32/77 (42% drug samples were found to be of poor quality, of which 28 samples failed the visual inspection, nine samples had substandard concentrations of the active ingredient, four samples showed poor disintegration, and one sample contained non of the stated active ingredient. The licensed and the illicit market contributed 5/47 (10.6% and 27/30 (90.0% samples of substandard drugs respectively. Conclusion These findings provide further evidence for the wide-spread existence of substandard anti-malarial medications in Africa and call for strengthening of the regulatory and quality control capacity of affected countries, particularly in view of the

  10. Modulating effects of plasma containing anti-malarial antibodies on in vitro anti-malarial drug susceptibility in Plasmodium falciparum

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    Udomsangpetch Rachanee

    2010-11-01

    Full Text Available Abstract Background The efficacy of anti-malarial drugs is determined by the level of parasite susceptibility, anti-malarial drug bioavailability and pharmacokinetics, and host factors including immunity. Host immunity improves the in vivo therapeutic efficacy of anti-malarial drugs, but the mechanism and magnitude of this effect has not been characterized. This study characterized the effects of 'immune' plasma to Plasmodium falciparumon the in vitro susceptibility of P. falciparum to anti-malarial drugs. Methods Titres of antibodies against blood stage antigens (mainly the ring-infected erythrocyte surface antigen [RESA] were measured in plasma samples obtained from Thai patients with acute falciparum malaria. 'Immune' plasma was selected and its effects on in vitro parasite growth and multiplication of the Thai P. falciparum laboratory strain TM267 were assessed by light microscopy. The in vitro susceptibility to quinine and artesunate was then determined in the presence and absence of 'immune' plasma using the 3H-hypoxanthine uptake inhibition method. Drug susceptibility was expressed as the concentrations causing 50% and 90% inhibition (IC50 and IC90, of 3H-hypoxanthine uptake. Results Incubation with 'immune' plasma reduced parasite maturation and decreased parasite multiplication in a dose dependent manner. 3H-hypoxanthine incorporation after incubation with 'immune' plasma was decreased significantly compared to controls (median [range]; 181.5 [0 to 3,269] cpm versus 1,222.5 [388 to 5,932] cpm (p= 0.001. As a result 'immune' plasma reduced apparent susceptibility to quinine substantially; median (range IC50 6.4 (0.5 to 23.8 ng/ml versus 221.5 (174.4 to 250.4 ng/ml (p = 0.02, and also had a borderline effect on artesunate susceptibility; IC50 0.2 (0.02 to 0.3 ng/ml versus 0.8 (0.2 to 2.3 ng/ml (p = 0.08. Effects were greatest at low concentrations, changing the shape of the concentration-effect relationship. IC90 values were not

  11. Fake anti-malarials: start with the facts.

    Science.gov (United States)

    Kaur, Harparkash; Clarke, Siȃn; Lalani, Mirza; Phanouvong, Souly; Guérin, Philippe; McLoughlin, Andrew; Wilson, Benjamin K; Deats, Michael; Plançon, Aline; Hopkins, Heidi; Miranda, Debora; Schellenberg, David

    2016-02-13

    This meeting report presents the key findings and discussion points of a 1-day meeting entitled 'Fake anti-malarials: start with the facts' held on 28th May 2015, in Geneva, Switzerland, to disseminate the findings of the artemisinin combination therapy consortium's drug quality programme. The teams purchased over 10,000 samples, using representative sampling approaches, from six malaria endemic countries: Equatorial Guinea (Bioko Island), Cambodia, Ghana, Nigeria, Rwanda and Tanzania. Laboratory analyses of these samples showed that falsified anti-malarials (substandard artemisinin-based combinations were present in all six countries and, artemisinin-based monotherapy tablets are still available in some places despite the fact that the WHO has urged regulatory authorities in malaria-endemic countries to take measures to halt the production and marketing of these oral monotherapies since 2007. This report summarizes the presentations that reviewed the public health impact of falsified and substandard drugs, sampling strategies, techniques for drug quality analysis, approaches to strengthen health systems capacity for the surveillance of drug quality, and the ensuing discussion points from the dissemination meeting.

  12. Making the most of clinical data: reviewing the role of pharmacokinetic-pharmacodynamic models of anti-malarial drugs.

    Science.gov (United States)

    Simpson, Julie A; Zaloumis, Sophie; DeLivera, Alysha M; Price, Ric N; McCaw, James M

    2014-09-01

    Mechanistic within-host models integrating blood anti-malarial drug concentrations with the parasite-time profile provide a valuable decision tool for determining dosing regimens for anti-malarial treatments, as well as a formative component of population-level drug resistance models. We reviewed published anti-malarial pharmacokinetic-pharmacodynamic models to identify the challenges for these complex models where parameter estimation from clinical field data is limited. The inclusion of key pharmacodynamic processes in the mechanistic structure adopted varies considerably. These include the life cycle of the parasite within the red blood cell, the action of the anti-malarial on a specific stage of the life cycle, and the reduction in parasite growth associated with immunity. With regard to estimation of the pharmacodynamic parameters, the majority of studies simply compared descriptive summaries of the simulated outputs to published observations of host and parasite responses from clinical studies. Few studies formally estimated the pharmacodynamic parameters within a rigorous statistical framework using observed individual patient data. We recommend three steps in the development and evaluation of these models. Firstly, exploration through simulation to assess how the different parameters influence the parasite dynamics. Secondly, application of a simulation-estimation approach to determine whether the model parameters can be estimated with reasonable precision based on sampling designs that mimic clinical efficacy studies. Thirdly, fitting the mechanistic model to the clinical data within a Bayesian framework. We propose that authors present the model both schematically and in equation form and give a detailed description of each parameter, including a biological interpretation of the parameter estimates.

  13. Novel in vivo active anti-malarials based on a hydroxy-ethyl-amine scaffold.

    Science.gov (United States)

    Ciana, Claire-Lise; Siegrist, Romain; Aissaoui, Hamed; Marx, Léo; Racine, Sophie; Meyer, Solange; Binkert, Christoph; de Kanter, Ruben; Fischli, Christoph; Wittlin, Sergio; Boss, Christoph

    2013-02-01

    A novel series of anti-malarials, based on a hydroxy-ethyl-amine scaffold, initially identified as peptidomimetic protease inhibitors is described. Combination of the hydroxy-ethyl-amine anti-malarial phramacophore with the known Mannich base pharmacophore of amodiaquine (57) resulted in promising in vivo active novel derivatives. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Mechanochemical Synthesis, In vivo Anti-malarial and Safety Evaluation of Amodiaquine-zinc Complex

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    Arise Rotimi Olusanya

    2017-09-01

    Full Text Available So far, some prospective metal-based anti-malarial drugs have been developed. The mechanochemical synthesis and characterization of Zn (II complex with amodiaquine and its anti-malarial efficacy on Plasmodium berghei-infected mice and safety evaluation were described in this study.

  15. malaria and anti-malarial drugs utilisation among adults in a rural

    African Journals Online (AJOL)

    Vihar

    Magreth Komanya (Bsc Nursing). AMREF. ABSTRACT. Objective: To study malaria and examine determinants of anti-malarial drugs utilization among ..... anti-malarials for prophylaxis and chemotherapy or may be provided with prescription forms to buy drugs. Moreover the general understanding that pregnant women are ...

  16. Methods for implementing a medicine outlet survey: lessons from the anti-malarial market

    Science.gov (United States)

    2013-01-01

    Background In recent years an increasing number of public investments and policy changes have been made to improve the availability, affordability and quality of medicines available to consumers in developing countries, including anti-malarials. It is important to monitor the extent to which these interventions are successful in achieving their aims using quantitative data on the supply side of the market. There are a number of challenges related to studying supply, including outlet sampling, gaining provider cooperation and collecting accurate data on medicines. This paper provides guidance on key steps to address these issues when conducting a medicine outlet survey in a developing country context. While the basic principles of good survey design and implementation are important for all surveys, there are a set of specific issues that should be considered when conducting a medicine outlet survey. Methods This paper draws on the authors’ experience of designing and implementing outlet surveys, including the lessons learnt from ACTwatch outlet surveys on anti-malarial retail supply, and other key studies in the field. Key lessons and points of debate are distilled around the following areas: selecting a sample of outlets; techniques for collecting and analysing data on medicine availability, price and sales volumes; and methods for ensuring high quality data in general. Results and conclusions The authors first consider the inclusion criteria for outlets, contrasting comprehensive versus more focused approaches. Methods for developing a reliable sampling frame of outlets are then presented, including use of existing lists, key informants and an outlet census. Specific issues in the collection of data on medicine prices and sales volumes are discussed; and approaches for generating comparable price and sales volume data across products using the adult equivalent treatment dose (AETD) are explored. The paper concludes with advice on practical considerations

  17. Got ACTs? Availability, price, market share and provider knowledge of anti-malarial medicines in public and private sector outlets in six malaria-endemic countries.

    Science.gov (United States)

    O'Connell, Kathryn A; Gatakaa, Hellen; Poyer, Stephen; Njogu, Julius; Evance, Illah; Munroe, Erik; Solomon, Tsione; Goodman, Catherine; Hanson, Kara; Zinsou, Cyprien; Akulayi, Louis; Raharinjatovo, Jacky; Arogundade, Ekundayo; Buyungo, Peter; Mpasela, Felton; Adjibabi, Chérifatou Bello; Agbango, Jean Angbalu; Ramarosandratana, Benjamin Fanomezana; Coker, Babajide; Rubahika, Denis; Hamainza, Busiku; Chapman, Steven; Shewchuk, Tanya; Chavasse, Desmond

    2011-10-31

    Artemisinin-based combination therapy (ACT) is the first-line malaria treatment throughout most of the malaria-endemic world. Data on ACT availability, price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality-assured ACT supply. This paper presents supply side data from ACTwatch outlet surveys in Benin, the Democratic Republic of Congo (DRC), Madagascar, Nigeria, Uganda and Zambia. Between March 2009 and June 2010, nationally representative surveys of outlets providing anti-malarials to consumers were conducted. A census of all outlets with the potential to provide anti-malarials was conducted in clusters sampled randomly. 28,263 outlets were censused, 51,158 anti-malarials were audited, and 9,118 providers interviewed. The proportion of public health facilities with at least one first-line quality-assured ACT in stock ranged between 43% and 85%. Among private sector outlets stocking at least one anti-malarial, non-artemisinin therapies, such as chloroquine and sulphadoxine-pyrimethamine, were widely available (> 95% of outlets) as compared to first-line quality-assured ACT (price of first-line quality-assured ACT ($0.14 [IQR: $0.10, $0.57]) was significantly lower than the most popular treatment (chloroquine, $0.36 [IQR: $0.36, $0.36]). Quality-assured ACT accounted for less than 25% of total anti-malarial volumes; private-sector quality-assured ACT volumes represented less than 6% of the total market share. Most anti-malarials were distributed through the private sector, but often comprised non-artemisinin therapies, and in the DRC and Nigeria, oral artemisinin monotherapies. Provider knowledge of the first-line treatment was significantly lower in the private sector than in the public/not-for-profit sector. These standardized, nationally representative results demonstrate the typically low availability, low market share and high prices of ACT, in the private sector where most anti-malarials

  18. Got ACTs? Availability, price, market share and provider knowledge of anti-malarial medicines in public and private sector outlets in six malaria-endemic countries

    Directory of Open Access Journals (Sweden)

    O'Connell Kathryn A

    2011-10-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT is the first-line malaria treatment throughout most of the malaria-endemic world. Data on ACT availability, price and market share are needed to provide a firm evidence base from which to assess the current situation concerning quality-assured ACT supply. This paper presents supply side data from ACTwatch outlet surveys in Benin, the Democratic Republic of Congo (DRC, Madagascar, Nigeria, Uganda and Zambia. Methods Between March 2009 and June 2010, nationally representative surveys of outlets providing anti-malarials to consumers were conducted. A census of all outlets with the potential to provide anti-malarials was conducted in clusters sampled randomly. Results 28,263 outlets were censused, 51,158 anti-malarials were audited, and 9,118 providers interviewed. The proportion of public health facilities with at least one first-line quality-assured ACT in stock ranged between 43% and 85%. Among private sector outlets stocking at least one anti-malarial, non-artemisinin therapies, such as chloroquine and sulphadoxine-pyrimethamine, were widely available (> 95% of outlets as compared to first-line quality-assured ACT ( Conclusions These standardized, nationally representative results demonstrate the typically low availability, low market share and high prices of ACT, in the private sector where most anti-malarials are accessed, with some exceptions. The results confirm that there is substantial room to improve availability and affordability of ACT treatment in the surveyed countries. The data will also be useful for monitoring the impact of interventions such as the Affordable Medicines Facility for malaria.

  19. Post-marketing surveillance of anti-malarial medicines used in Malawi

    OpenAIRE

    Chikowe, Ibrahim; Osei-Safo, Dorcas; Harrison, Jerry JEK; Konadu, Daniel Y; Addae-Mensah, Ivan

    2015-01-01

    Background The growing concern over the extent of anti-malarial medicine resistance in sub-Saharan Africa, driven largely by administration of sub-therapeutic doses derived from falsified and substandard medicines necessitates regular monitoring of the quality of these medicines to avert any potential public health disaster. This study aimed at determining the active pharmaceutical ingredient (API) content of anti-malarial medicines available in Malawi with respect to the manufacturers? label...

  20. A qualitative assessment of the challenges of WHO prequalification for anti-malarial drugs in China.

    Science.gov (United States)

    Huang, Yangmu; Pan, Ke; Peng, Danlu; Stergachis, Andy

    2018-04-03

    While China is a major manufacturer of artemisinin and its derivatives, it lags as a global leader in terms of the total export value of anti-malarial drugs as finished pharmaceutical products ready for marketing and use by patients. This may be due to the limited number of World Health Organization (WHO) prequalified anti-malarial drugs from China. Understanding the reasons for the slow progress of WHO prequalification (PQ) in China can help improve the current situation and may lead to greater efforts in malaria eradication by Chinese manufacturers. In-depth interviews were conducted in China between November 2014 and December 2016. A total of 26 key informants from central government agencies, pharmaceutical companies, universities, and research institutes were interviewed, all of which had current or previous experience overseeing or implementing anti-malarial research and development in China. Chinese anti-malarial drugs that lack WHO PQ are mainly exported for use in the African private market. High upfront costs with unpredictable benefits, as well as limited information and limited technical support on WHO PQ, were reported as the main barriers to obtain WHO PQ for anti-malarial drugs by respondents from Chinese pharmaceutical companies. Potential incentives identified by respondents included tax relief, human resource training and consultation, as well as other incentives related to drug approval, such as China's Fast Track Channel. Government support, as well as innovative incentives and collaboration mechanisms are needed for further adoption of WHO PQ for anti-malarial drugs in China.

  1. Assessing the utility of an anti-malarial pharmacokinetic-pharmacodynamic model for aiding drug clinical development

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    Zaloumis Sophie

    2012-08-01

    Full Text Available Abstract Background Mechanistic within-host models relating blood anti-malarial drug concentrations with the parasite-time profile help in assessing dosing schedules and partner drugs for new anti-malarial treatments. A comprehensive simulation study to assess the utility of a stage-specific pharmacokinetic-pharmacodynamic (PK-PD model for predicting within-host parasite response was performed. Methods Three anti-malarial combination therapies were selected: artesunate-mefloquine, dihydroartemisinin-piperaquine, and artemether-lumefantrine. The PK-PD model included parameters to represent the concentration-time profiles of both drugs, the initial parasite burden and distribution across the parasite life cycle, and the parasite multiplication factor due to asexual reproduction. The model also included the maximal killing rate of each drug, and the blood drug concentration associated with half of that killing effect (in vivo EC50, derived from the in vitro IC50, the extent of binding to 0.5% Albumax present in the in vitro testing media, and the drugs plasma protein binding and whole blood to plasma partitioning ratio. All stochastic simulations were performed using a Latin-Hypercube-Sampling approach. Results The simulations demonstrated that the proportion of patients cured was highly sensitive to the in vivo EC50 and the maximal killing rate of the partner drug co-administered with the artemisinin derivative. The in vivo EC50 values that corresponded to on average 95% of patients cured were much higher than the adjusted values derived from the in vitro IC50. The proportion clinically cured was not strongly influenced by changes in the parameters defining the age distribution of the initial parasite burden (mean age of 4 to 16 hours and the parasite multiplication factor every life cycle (ranging from 8 to 12 fold/cycle. The median parasite clearance times, however, lengthened as the standard deviation of the initial parasite burden increased (i

  2. Spread of anti-malarial drug resistance: Mathematical model with implications for ACT drug policies

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    Dondorp Arjen M

    2008-11-01

    Full Text Available Abstract Background Most malaria-endemic countries are implementing a change in anti-malarial drug policy to artemisinin-based combination therapy (ACT. The impact of different drug choices and implementation strategies is uncertain. Data from many epidemiological studies in different levels of malaria endemicity and in areas with the highest prevalence of drug resistance like borders of Thailand are certainly valuable. Formulating an appropriate dynamic data-driven model is a powerful predictive tool for exploring the impact of these strategies quantitatively. Methods A comprehensive model was constructed incorporating important epidemiological and biological factors of human, mosquito, parasite and treatment. The iterative process of developing the model, identifying data needed, and parameterization has been taken to strongly link the model to the empirical evidence. The model provides quantitative measures of outcomes, such as malaria prevalence/incidence and treatment failure, and illustrates the spread of resistance in low and high transmission settings. The model was used to evaluate different anti-malarial policy options focusing on ACT deployment. Results The model predicts robustly that in low transmission settings drug resistance spreads faster than in high transmission settings, and treatment failure is the main force driving the spread of drug resistance. In low transmission settings, ACT slows the spread of drug resistance to a partner drug, especially at high coverage rates. This effect decreases exponentially with increasing delay in deploying the ACT and decreasing rates of coverage. In the high transmission settings, however, drug resistance is driven by the proportion of the human population with a residual drug level, which gives resistant parasites some survival advantage. The spread of drug resistance could be slowed down by controlling presumptive drug use and avoiding the use of combination therapies containing drugs with

  3. Molecular characterization of Plasmodium falciparum uracil-DNA glycosylase and its potential as a new anti-malarial drug target

    OpenAIRE

    Suksangpleng, Thidarat; Leartsakulpanich, Ubolsree; Moonsom, Saengduen; Siribal, Saranya; Boonyuen, Usa; Wright, George E; Chavalitshewinkoon-Petmitr, Porntip

    2014-01-01

    Background Based on resistance of currently used anti-malarials, a new anti-malarial drug target against Plasmodium falciparum is urgently needed. Damaged DNA cannot be transcribed without prior DNA repair; therefore, uracil-DNA glycosylase, playing an important role in base excision repair, may act as a candidate for a new anti-malarial drug target. Methods Initially, the native PfUDG from parasite crude extract was partially purified using two columns, and the glycosylase activity was monit...

  4. An ethnobotanical study of anti-malarial plants among indigenous people on the upper Negro River in the Brazilian Amazon.

    Science.gov (United States)

    Frausin, Gina; Hidalgo, Ari de Freitas; Lima, Renata Braga Souza; Kinupp, Valdely Ferreira; Ming, Lin Chau; Pohlit, Adrian Martin; Milliken, William

    2015-11-04

    In this article we present the plants used for the treatment of malaria and associated symptoms in Santa Isabel do Rio Negro in the Brazilian Amazon. The region has important biological and cultural diversities including more than twenty indigenous ethnic groups and a strong history in traditional medicine. The aims of this study are to survey information in the Baniwa, Baré, Desana, Piratapuia, Tariana, Tukano, Tuyuca and Yanomami ethnic communities and among caboclos (mixed-ethnicity) on (a) plant species used for the treatment of malaria and associated symptoms, (b) dosage forms and (c) distribution of these anti-malarial plants in the Amazon. Information was obtained through classical ethnobotanical and ethnopharmacological methods from interviews with 146 informants in Santa Isabel municipality on the upper Negro River, Brazil. Fifty-five mainly native neotropical plant species from 34 families were in use. The detailed uses of these plants were documented. The result was 187 records (64.5%) of plants for the specific treatment of malaria, 51 records (17.6%) of plants used in the treatment of liver problems and 29 records (10.0%) of plants used in the control of fevers associated with malaria. Other uses described were blood fortification ('dar sangue'), headache and prophylaxis. Most of the therapeutic preparations were decoctions and infusions based on stem bark, root bark and leaves. These were administered by mouth. In some cases, remedies were prepared with up to three different plant species. Also, plants were used together with other ingredients such as insects, mammals, gunpowder and milk. This is the first study on the anti-malarial plants from this region of the Amazon. Aspidosperma spp. and Ampelozizyphus amazonicus Ducke were the most cited species in the communities surveyed. These species have experimental proof supporting their anti-malarial efficacy. The dosage of the therapeutic preparations depends on the kind of plant, quantity of plant

  5. The influence of nevirapine and efavirenz-based anti-retroviral therapy on the pharmacokinetics of lumefantrine and anti-malarial dose recommendation in HIV-malaria co-treatment.

    Science.gov (United States)

    Maganda, Betty A; Ngaimisi, Eliford; Kamuhabwa, Appolinary A R; Aklillu, Eleni; Minzi, Omary M S

    2015-04-25

    daily for five days using the current dose could improve lumefantrine exposure and consequently malaria treatment outcomes. Co-treatment of AL with EFV-based ART but not NVP-based ART significantly reduces lumefantrine bioavailability and consequently total exposure. To ensure adequate lumefantrine exposure and malaria treatment success in HIV-malaria co-infected patients on EFV-based ART, an extension of the duration of AL treatment to five days using the current dose is proposed.

  6. A simple and inexpensive haemozoin-based colorimetric method to evaluate anti-malarial drug activity.

    Science.gov (United States)

    Men, Tran Thanh; Huy, Nguyen Tien; Trang, Dai Thi Xuan; Shuaibu, Mohammed Nasir; Hirayama, Kenji; Kamei, Kaeko

    2012-08-09

    The spread of drug resistance in malaria parasites and the limited number of effective drugs for treatment indicates the need for new anti-malarial compounds. Current assays evaluating drugs against Plasmodium falciparum require expensive materials and equipment, thus limiting the search for new drugs, particularly in developing countries. This study describes an inexpensive procedure that is based on the advantage of a positive correlation between the haemozoin level of infected erythrocytes and parasite load. The relationship between parasitaemia and the haemozoin level of infected erythrocytes was investigated after converting haemozoin into monomeric haem. The 50% inhibitory concentration (IC50) values of chloroquine, quinine, artemisinin, quinidine and clotrimazole against P. falciparum K1 and 9A strains were determined using the novel assay method. The haemozoin of parasites was extracted and converted into monomeric haem, allowing the use of a colorimeter to efficiently and rapidly measure the growth of the parasites. There was a strong and direct linear relationship between the absorbance of haem converted from haemozoin and the percentage of the parasite (R2 = 0.9929). Furthermore, the IC50 values of drugs were within the range of the values previously reported. The haemozoin-based colorimetric assay can be considered as an alternative, simple, robust, inexpensive and convenient method, making it applicable in developing countries.

  7. Accuracy of a Plasmodium falciparum specific histidine-rich protein 2 rapid diagnostic test in the context of the presence of non-malaria fevers, prior anti-malarial use and seasonal malaria transmission

    NARCIS (Netherlands)

    Kiemde, Francois; Bonko, Massa Dit Achille; Tahita, Marc Christian; Lompo, Palpouguini; Rouamba, Toussaint; Tinto, Halidou; Boele van Hensbroek, Michael; Mens, Petra F.; Schallig, Henk D. F. H.

    2017-01-01

    It remains challenging to distinguish malaria from other fever causing infections, as a positive rapid diagnostic test does not always signify a true active malaria infection. This study was designed to determine the influence of other causes of fever, prior anti-malarial treatment, and a possible

  8. Mass anti-malarial administration in western Cambodia: a qualitative study of factors affecting coverage

    NARCIS (Netherlands)

    Pell, Christopher; Tripura, Rupam; Nguon, Chea; Cheah, Phaikyeong; Davoeung, Chan; Heng, Chhouen; Dara, Lim; Sareth, Ma; Dondorp, Arjen; von Seidlein, Lorenz; Peto, Thomas J.

    2017-01-01

    Mass anti-malarial administration has been proposed as a key component of the Plasmodium falciparum malaria elimination strategy in the Greater Mekong sub-Region. Its effectiveness depends on high levels of coverage in the target population. This article explores the factors that influenced mass

  9. Assessing anti-malarial drug effects ex vivo using the haemozoin detection assay

    NARCIS (Netherlands)

    Rebelo, Maria; Tempera, Carolina; Fernandes, José F.; Grobusch, Martin P.; Hänscheid, Thomas

    2015-01-01

    In vitro sensitivity assays are crucial to detect and monitor drug resistance. Plasmodium falciparum has developed resistance to almost all anti-malarial drugs. Although different in vitro drug assays are available, some of their inherent characteristics limit their application, especially in the

  10. In vivo validation of anti-malarial activity of crude extracts of Terminalia macroptera, a Malian medicinal plant.

    Science.gov (United States)

    Haidara, Mahamane; Haddad, Mohamed; Denou, Adama; Marti, Guillaume; Bourgeade-Delmas, Sandra; Sanogo, Rokia; Bourdy, Geneviève; Aubouy, Agnès

    2018-02-05

    Plasmodium falciparum malaria is still one of the most deadly pathology worldwide. Efficient treatment is jeopardized by parasite resistance to artemisinin and its derivatives, and by poor access to treatment in endemic regions. Anti-malarial traditional remedies still offer new tracks for identifying promising antiplasmodial molecules, and a way to ensure that all people have access to care. The present study aims to validate the traditional use of Terminalia macroptera, a Malian plant used in traditional medicine. Terminalia macroptera was collected in Mali. Leaves (TML) and roots ethanolic extracts (TMR) were prepared and tested at 2000 mg/kg for in vivo acute toxicity in Albino Swiss mice. Antiplasmodial activity of the extracts was assessed against a chloroquine resistant strain P. falciparum (FcB1) in vitro. In vivo, anti-malarial efficacy was assessed by a 4-day suppressive test at 100 mg/kg in two malaria murine models of uncomplicated malaria (Plasmodium chabaudi chabaudi infection) and cerebral malaria (Plasmodium berghei strain ANKA infection). Constituents of TMR were characterized by ultra-high-performance liquid chromatography coupled to high resolution mass spectrometry. Top ranked compounds were putatively identified using plant databases and in silico fragmentation pattern. Lethal dose of TML and TMR were greater than 2000 mg/kg in Albino Swiss mice. According to the OECD's Globally Harmonized System of Classification, both extracts are non-toxic orally. Antiplasmodial activity of T. macroptera extracts was confirmed in vitro against P. falciparum FcB1 strain with IC50 values of 1.2 and 1.6 µg/mL for TML and TMR, respectively. In vivo, oral administration of TML and TMR induced significant reduction of parasitaemia (37.2 and 46.4% respectively) in P. chabaudi chabaudi infected mice at the 7th day of infection compared to untreated mice. In the cerebral malaria experimental model, mice treated with TMR and TML presented respectively 50 and 66

  11. Accessibility, availability and affordability of anti-malarials in a rural district in Kenya after implementation of a national subsidy scheme

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    Simiyu Chrispinus

    2011-10-01

    Full Text Available Abstract Background Poor access to prompt and effective treatment for malaria contributes to high mortality and severe morbidity. In Kenya, it is estimated that only 12% of children receive anti-malarials for their fever within 24 hours. The first point of care for many fevers is a local medicine retailer, such as a pharmacy or chemist. The role of the medicine retailer as an important distribution point for malaria medicines has been recognized and several different strategies have been used to improve the services that these retailers provide. Despite these efforts, many mothers still purchase ineffective drugs because they are less expensive than effective artemisinin combination therapy (ACT. One strategy that is being piloted in several countries is an international subsidy targeted at anti-malarials supplied through the retail sector. The goal of this strategy is to make ACT as affordable as ineffective alternatives. The programme, called the Affordable Medicines Facility - malaria was rolled out in Kenya in August 2010. Methods In December 2010, the affordability and accessibility of malaria medicines in a rural district in Kenya were evaluated using a complete census of all public and private facilities, chemists, pharmacists, and other malaria medicine retailers within the Webuye Demographic Surveillance Area. Availability, types, and prices of anti-malarials were assessed. There are 13 public or mission facilities and 97 medicine retailers (registered and unregistered. Results The average distance from a home to the nearest public health facility is 2 km, but the average distance to the nearest medicine retailer is half that. Quinine is the most frequently stocked anti-malarial (61% of retailers. More medicine retailers stocked sulphadoxine-pyramethamine (SP; 57% than ACT (44%. Eleven percent of retailers stocked AMFm subsidized artemether-lumefantrine (AL. No retailers had chloroquine in stock and only five were selling artemisinin

  12. Major reduction in anti-malarial drug consumption in Senegal after nation-wide introduction of malaria rapid diagnostic tests.

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    Sylla Thiam

    Full Text Available BACKGROUND: While WHO recently recommended universal parasitological confirmation of suspected malaria prior to treatment, debate has continued as to whether wide-scale use of rapid diagnostic tests (RDTs can achieve this goal. Adherence of health service personnel to RDT results has been poor in some settings, with little impact on anti-malarial drug consumption. The Senegal national malaria control programme introduced universal parasite-based diagnosis using malaria RDTs from late 2007 in all public health facilities. This paper assesses the impact of this programme on anti-malarial drug consumption and disease reporting. METHODS AND FINDINGS: Nationally-collated programme data from 2007 to 2009 including malaria diagnostic outcomes, prescription of artemisinin-based combination therapy (ACT and consumption of RDTs in public health facilities, were reviewed and compared. Against a marked seasonal variation in all-cause out-patient visits, non-malarial fever and confirmed malaria, parasite-based diagnosis increased nationally from 3.9% of reported malaria-like febrile illness to 86.0% over a 3 year period. The prescription of ACT dropped throughout this period from 72.9% of malaria-like febrile illness to 31.5%, reaching close equivalence to confirmed malaria (29.9% of 584,873 suspect fever cases. An estimated 516,576 courses of inappropriate ACT prescription were averted. CONCLUSIONS: The data indicate high adherence of anti-malarial prescribing practice to RDT results after an initial run-in period. The large reduction in ACT consumption enabled by the move from symptom-based to parasite-based diagnosis demonstrates that effective roll-out and use of malaria RDTs is achievable on a national scale through well planned and structured implementation. While more detailed information on management of parasite-negative cases is required at point of care level to assess overall cost-benefits to the health sector, considerable cost-savings were

  13. Major Reduction in Anti-Malarial Drug Consumption in Senegal after Nation-Wide Introduction of Malaria Rapid Diagnostic Tests

    Science.gov (United States)

    Thiam, Sylla; Thior, Moussa; Faye, Babacar; Ndiop, Médoune; Diouf, Mamadou Lamine; Diouf, Mame Birame; Diallo, Ibrahima; Fall, Fatou Ba; Ndiaye, Jean Louis; Albertini, Audrey; Lee, Evan; Jorgensen, Pernille; Gaye, Oumar; Bell, David

    2011-01-01

    Background While WHO recently recommended universal parasitological confirmation of suspected malaria prior to treatment, debate has continued as to whether wide-scale use of rapid diagnostic tests (RDTs) can achieve this goal. Adherence of health service personnel to RDT results has been poor in some settings, with little impact on anti-malarial drug consumption. The Senegal national malaria control programme introduced universal parasite-based diagnosis using malaria RDTs from late 2007 in all public health facilities. This paper assesses the impact of this programme on anti-malarial drug consumption and disease reporting. Methods and Findings Nationally-collated programme data from 2007 to 2009 including malaria diagnostic outcomes, prescription of artemisinin-based combination therapy (ACT) and consumption of RDTs in public health facilities, were reviewed and compared. Against a marked seasonal variation in all-cause out-patient visits, non-malarial fever and confirmed malaria, parasite-based diagnosis increased nationally from 3.9% of reported malaria-like febrile illness to 86.0% over a 3 year period. The prescription of ACT dropped throughout this period from 72.9% of malaria-like febrile illness to 31.5%, reaching close equivalence to confirmed malaria (29.9% of 584873 suspect fever cases). An estimated 516576 courses of inappropriate ACT prescription were averted. Conclusions The data indicate high adherence of anti-malarial prescribing practice to RDT results after an initial run-in period. The large reduction in ACT consumption enabled by the move from symptom-based to parasite-based diagnosis demonstrates that effective roll-out and use of malaria RDTs is achievable on a national scale through well planned and structured implementation. While more detailed information on management of parasite-negative cases is required at point of care level to assess overall cost-benefits to the health sector, considerable cost-savings were achieved in ACT

  14. Major reduction in anti-malarial drug consumption in Senegal after nation-wide introduction of malaria rapid diagnostic tests.

    Science.gov (United States)

    Thiam, Sylla; Thior, Moussa; Faye, Babacar; Ndiop, Médoune; Diouf, Mamadou Lamine; Diouf, Mame Birame; Diallo, Ibrahima; Fall, Fatou Ba; Ndiaye, Jean Louis; Albertini, Audrey; Lee, Evan; Jorgensen, Pernille; Gaye, Oumar; Bell, David

    2011-04-06

    While WHO recently recommended universal parasitological confirmation of suspected malaria prior to treatment, debate has continued as to whether wide-scale use of rapid diagnostic tests (RDTs) can achieve this goal. Adherence of health service personnel to RDT results has been poor in some settings, with little impact on anti-malarial drug consumption. The Senegal national malaria control programme introduced universal parasite-based diagnosis using malaria RDTs from late 2007 in all public health facilities. This paper assesses the impact of this programme on anti-malarial drug consumption and disease reporting. Nationally-collated programme data from 2007 to 2009 including malaria diagnostic outcomes, prescription of artemisinin-based combination therapy (ACT) and consumption of RDTs in public health facilities, were reviewed and compared. Against a marked seasonal variation in all-cause out-patient visits, non-malarial fever and confirmed malaria, parasite-based diagnosis increased nationally from 3.9% of reported malaria-like febrile illness to 86.0% over a 3 year period. The prescription of ACT dropped throughout this period from 72.9% of malaria-like febrile illness to 31.5%, reaching close equivalence to confirmed malaria (29.9% of 584,873 suspect fever cases). An estimated 516,576 courses of inappropriate ACT prescription were averted. The data indicate high adherence of anti-malarial prescribing practice to RDT results after an initial run-in period. The large reduction in ACT consumption enabled by the move from symptom-based to parasite-based diagnosis demonstrates that effective roll-out and use of malaria RDTs is achievable on a national scale through well planned and structured implementation. While more detailed information on management of parasite-negative cases is required at point of care level to assess overall cost-benefits to the health sector, considerable cost-savings were achieved in ACT procurement. Programmes need to be allowed

  15. Quality of anti-malarial drugs provided by public and private healthcare providers in south-east Nigeria

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    Uzochukwu Benjamin

    2009-02-01

    Full Text Available Abstract Background There is little existing knowledge about actual quality of drugs provided by different providers in Nigeria and in many sub-Saharan African countries. Such information is important for improving malaria treatment that will help in the development and implementation of actions designed to improve the quality of treatment. The objective of the study was to determine the quality of drugs used for the treatment of malaria in a broad spectrum of public and private healthcare providers. Methods The study was undertaken in six towns (three urban and three rural in Anambra state, south-east Nigeria. Anti-malarials (225 samples, which included artesunate, dihydroartemisinin, sulphadoxine-pyrimethamine (SP, quinine, and chloroquine, were either purchased or collected from randomly selected providers. The quality of these drugs was assessed by laboratory analysis of the dissolution profile using published pharmacopoeial monograms and measuring the amount of active ingredient using high performance liquid chromatography (HPLC. Findings It was found that 60 (37% of the anti-malarials tested did not meet the United States Pharmacopoeia (USP specifications for the amount of active ingredients, with the suspect drugs either lacking the active ingredients or containing suboptimal quantities of the active ingredients. Quinine (46% and SP formulations (39% were among drugs that did not satisfy the tolerance limits published in USP monograms. A total of 78% of the suspect drugs were from private facilities, mostly low-level providers, such as patent medicine dealers (vendors. Conclusion This study found that there was a high prevalence of poor quality drugs. The findings provide areas for public intervention to improve the quality of malaria treatment services. There should be enforced checks and regulation of drug supply management as well as stiffer penalties for people stocking substandard and counterfeit drugs.

  16. Frequency of glucose-6-phosphate dehydrogenase deficiency in malaria patients from six African countries enrolled in two randomized anti-malarial clinical trials

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    Duparc Stephan

    2011-08-01

    Full Text Available Abstract Background Glucose-6-phosphate dehydrogenase (G6PD deficiency is common in populations living in malaria endemic areas. G6PD genotype and phenotype were determined for malaria patients enrolled in the chlorproguanil-dapsone-artesunate (CDA phase III clinical trial programme. Methods Study participants, aged > 1 year, with microscopically confirmed uncomplicated Plasmodium falciparum malaria, and haemoglobin ≥ 70 g/L or haematocrit ≥ 25%, were recruited into two clinical trials conducted in six African countries (Burkina Faso, Ghana, Kenya, Nigeria, Tanzania, Mali. G6PD genotype of the three most common African forms, G6PD*B, G6PD*A (A376G, and G6PD*A- (G202A, A542T, G680T and T968C, were determined and used for frequency estimation. G6PD phenotype was assessed qualitatively using the NADPH fluorescence test. Exploratory analyses investigated the effect of G6PD status on baseline haemoglobin concentration, temperature, asexual parasitaemia and anti-malarial efficacy after treatment with CDA 2/2.5/4 mg/kg or chlorproguanil-dapsone 2/2.5 mg/kg (both given once daily for three days or six-dose artemether-lumefantrine. Results Of 2264 malaria patients enrolled, 2045 had G6PD genotype available and comprised the primary analysis population (1018 males, 1027 females. G6PD deficiency prevalence was 9.0% (184/2045; 7.2% [N = 147] male hemizygous plus 1.8% [N = 37] female homozygous, 13.3% (273/2045 of patients were heterozygous females, 77.7% (1588/2045 were G6PD normal. All deficient G6PD*A- genotypes were A376G/G202A. G6PD phenotype was available for 64.5% (1319/2045 of patients: 10.2% (134/1319 were G6PD deficient, 9.6% (127/1319 intermediate, and 80.2% (1058/1319 normal. Phenotype test specificity in detecting hemizygous males was 70.7% (70/99 and 48.0% (12/25 for homozygous females. Logistic regression found no significant effect of G6PD genotype on adjusted mean baseline haemoglobin (p = 0.154, adjusted mean baseline temperature (p = 0

  17. Post-marketing surveillance of anti-malarial medicines used in Malawi.

    Science.gov (United States)

    Chikowe, Ibrahim; Osei-Safo, Dorcas; Harrison, Jerry J E K; Konadu, Daniel Y; Addae-Mensah, Ivan

    2015-03-25

    The growing concern over the extent of anti-malarial medicine resistance in sub-Saharan Africa, driven largely by administration of sub-therapeutic doses derived from falsified and substandard medicines necessitates regular monitoring of the quality of these medicines to avert any potential public health disaster. This study aimed at determining the active pharmaceutical ingredient (API) content of anti-malarial medicines available in Malawi with respect to the manufacturers' label claim and pharmacopoeia specifications. Samples of anti-malarial medicines (112) collected from both licensed and unlicensed markets throughout Malawi were subjected to visual inspection of dosage form and packaging, and registration verification with the regulatory body. Basic (colourimetric) tests were employed to establish the presence and identity of the requisite APIs. Semi-quantitative thin layer chromatography (SQ-TLC) was employed as a quick assay for the verification of identity and estimation of the API content while HPLC assays were used to quantify the APIs. The results were compared with pharmacopoeia specifications and manufacturers' label claims. For combination therapies, a sample was considered to have failed if one or more of its component APIs did not meet pharmacopoeia specifications. There was 86.6% registration status and 100% compliance with visual inspection and basic tests confirming the presence of requisite APIs. The identification test was confirmed by the SQ-TLC assay. API quantification by HPLC assay however, showed that 88.4% (99/112) of the samples failed the quality tests due to the presence of either insufficient or excessive API. The results suggest the existence of substandard anti-malarial medicines in Malawi. The presence of both excessive and insufficient artemisinin-based and non-artemisinin-based API, clearly points to poor adherence to GMP and improper handling during storage or distribution. The country relies heavily on imported anti-malarial

  18. CPP-ZFN: A potential DNA-targeting anti-malarial drug

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    Nain Vikrant

    2010-09-01

    . Implications of the hypothesis Targeting of the Plasmodium genome using ZFN has great potential for the development of anti-malarial drugs. It allows the development of a single drug against all malarial infections, including multidrug-resistant strains. Availability of multiple ZFN target sites in a single gene will provide alternative drug target sites to combat the development of resistance in the future.

  19. In vitro and in vivo anti-malarial activity of Boerhavia elegans and Solanum surattense

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    Khodakarim Nastaran

    2010-05-01

    Full Text Available Abstract Background There is an urgent need to identify new anti-malarial drug targets for both prophylaxis and chemotherapy, due to the increasing problem of drug resistance to malaria parasites. In the present study, the aim was to discover novel, effective plant-based extracts for the activity against malaria. Methods Ten plants found in Iran were selected by ethnobotanical survey of medicinal plants. The crude ethanolic extracts were tested for in vitro anti-plasmodial activity against two strains of Plasmodium falciparum: K1 (chloroquine-resistant strain and CY27 (chloroquine-sensitive strain, using the parasite lactate dehydrogenase (pLDH assay. The anti-plasmodial activity of the extracts was also assessed in the 4-day suppressive anti-malarial assay in mice inoculated with Plasmodium berghei (ANKA strain. Crude ethanolic extracts showed good anti-plasmodial activity were further fractionated by partitioning in water and dichloromethane. Results Of 10 plant species assayed, three species: Boerhavia elegans (Choisy, Solanum surattense (Burm.f. and Prosopis juliflora (Sw. showed promising anti-plasmodial activity in vitro (IC50 ≤ 50 μg/ml and in vivo with no toxicity. The dichloromethane fraction of three extracts revealed stronger anti-plasmodial activity than the total extracts. Conclusion Anti-plasmodial activities of extracts of B. elegans and S. surattense are reported for the first time.

  20. Availability and quality of anti-malarials among private sector outlets in Myanmar in 2012: results from a large, community-based, cross-sectional survey before a large-scale intervention.

    Science.gov (United States)

    Khin, Hnin Su Su; Chen, Ingrid; White, Chris; Sudhinaraset, May; McFarland, Willi; Littrell, Megan; Montagu, Dominic; Aung, Tin

    2015-07-14

    Global malaria control efforts are threatened by the spread and emergence of artemisinin-resistant Plasmodium falciparum parasites. In 2012, the widespread sale of partial courses of artemisinin-based monotherapy was suspected to take place in the highly accessed, weakly regulated private sector in Myanmar, posing potentially major threats to drug resistance. This study investigated the presence of artemisinin-based monotherapies in the Myanmar private sector, particularly as partial courses of therapy, to inform the targeting of future interventions to stop artemisinin resistance. A large cross-sectional survey comprised of a screening questionnaire was conducted across 26 townships in Myanmar between March and May, 2012. For outlets that stocked anti-malarials at the time of survey, a stock audit was conducted, and for outlets that stocked anti-malarials within 3 months of the survey, a provider survey was conducted. A total of 3,658 outlets were screened, 83% were retailers (pharmacies, itinerant drug vendors and general retailers) and 17% were healthcare providers (private facilities and health workers). Of the 3,658 outlets screened, 1,359 outlets (32%) stocked at least one anti-malarial at the time of study. Oral artemisinin-based monotherapy comprised of 33% of self-reported anti-malarials dispensing volumes found. The vast majority of artemisinin-based monotherapy was sold by retailers, where 63% confirmed that they sold partial courses of therapy by cutting blister packets. Very few retailers (5%) had malaria rapid diagnostic tests available, and quality-assured artemisinin-based combination therapy was virtually nonexistent among retailers. Informal private pharmacies, itinerant drug vendors and general retailers should be targeted for interventions to improve malaria treatment practices in Myanmar, particularly those that threaten the emergence and spread of artemisinin resistance.

  1. Natural products as starting points for future anti-malarial therapies: going back to our roots?

    Science.gov (United States)

    2011-01-01

    Background The discovery and development of new anti-malarials are at a crossroads. Fixed dose artemisinin combination therapy is now being used to treat a hundred million children each year, with a cost as low as 30 cents per child, with cure rates of over 95%. However, as with all anti-infective strategies, this triumph brings with it the seeds of its own downfall, the emergence of resistance. It takes ten years to develop a new medicine. New classes of medicines to combat malaria, as a result of infection by Plasmodium falciparum and Plasmodium vivax are urgently needed. Results Natural product scaffolds have been the basis of the majority of current anti-malarial medicines. Molecules such as quinine, lapachol and artemisinin were originally isolated from herbal medicinal products. After improvement with medicinal chemistry and formulation technologies, and combination with other active ingredients, they now make up the current armamentarium of medicines. In recent years advances in screening technologies have allowed testing of millions of compounds from pharmaceutical diversity for anti-malarial activity in cellular assays. These initiatives have resulted in thousands of new sub-micromolar active compounds – starting points for new drug discovery programmes. Against this backdrop, the paucity of potent natural products identified has been disappointing. Now is a good time to reflect on the current approach to screening herbal medicinal products and suggest revisions. Nearly sixty years ago, the Chinese doctor Chen Guofu, suggested natural products should be approached by dao-xing-ni-shi or ‘acting in the reversed order’, starting with observational clinical studies. Natural products based on herbal remedies are in use in the community, and have the potential unique advantage that clinical observational data exist, or can be generated. The first step should be the confirmation and definition of the clinical activity of herbal medicinal products already

  2. Natural products as starting points for future anti-malarial therapies: going back to our roots?

    Directory of Open Access Journals (Sweden)

    Wells Timothy NC

    2011-03-01

    Full Text Available Abstract Background The discovery and development of new anti-malarials are at a crossroads. Fixed dose artemisinin combination therapy is now being used to treat a hundred million children each year, with a cost as low as 30 cents per child, with cure rates of over 95%. However, as with all anti-infective strategies, this triumph brings with it the seeds of its own downfall, the emergence of resistance. It takes ten years to develop a new medicine. New classes of medicines to combat malaria, as a result of infection by Plasmodium falciparum and Plasmodium vivax are urgently needed. Results Natural product scaffolds have been the basis of the majority of current anti-malarial medicines. Molecules such as quinine, lapachol and artemisinin were originally isolated from herbal medicinal products. After improvement with medicinal chemistry and formulation technologies, and combination with other active ingredients, they now make up the current armamentarium of medicines. In recent years advances in screening technologies have allowed testing of millions of compounds from pharmaceutical diversity for anti-malarial activity in cellular assays. These initiatives have resulted in thousands of new sub-micromolar active compounds – starting points for new drug discovery programmes. Against this backdrop, the paucity of potent natural products identified has been disappointing. Now is a good time to reflect on the current approach to screening herbal medicinal products and suggest revisions. Nearly sixty years ago, the Chinese doctor Chen Guofu, suggested natural products should be approached by dao-xing-ni-shi or ‘acting in the reversed order’, starting with observational clinical studies. Natural products based on herbal remedies are in use in the community, and have the potential unique advantage that clinical observational data exist, or can be generated. The first step should be the confirmation and definition of the clinical activity of herbal

  3. Effects of anti-malarial drugs on the electrocardiographic QT interval modelled in the isolated perfused guinea pig heart system

    Directory of Open Access Journals (Sweden)

    Kotaki Hajime

    2010-11-01

    Full Text Available Abstract Background Concern over the potential cardiotoxicity of anti-malarial drugs inducing a prolonged electrocardiographic QT interval has resulted in the almost complete withdrawal from the market of one anti-malarial drug - halofantrine. The effects on the QT interval of four anti-malarial drugs were examined, using the guinea pig heart. Methods The guinea pig heart was isolated, mounted on a Langendorff apparatus, and was then perfused with pyruvate-added Klebs-Henseleit solutions containing graded concentrations of the four agents such as quinidine (0.15 - 1.2 μM, quinine (0.3 - 2.4 μM, halofantrine (0.1 - 2.0 μM and mefloquine (0.1 - 2.0 μM. The heart rate-corrected QaTc intervals were measured to evaluate drug-induced QT prolongation effects. Results Quinidine, quinine, and halofantrine prolonged the QaTc interval in a dose-dependent manner, whereas no such effect was found with mefloquine. The EC50 values for the QaTc prolongation effects, the concentration that gives a half-maximum effect, were quinidine Conclusions In this study, an isolated, perfused guinea pig heart system was constructed to assess the cardiotoxic potential of anti-malarial drugs. This isolated perfused guinea pig heart system could be used to test newly developed anti-malarial drugs for their inherent QT lengthening potential. More information is required on the potential variation in unbound drug concentrations in humans, and their role in cardiotoxicity.

  4. Communicating the AMFm message: exploring the effect of communication and training interventions on private for-profit provider awareness and knowledge related to a multi-country anti-malarial subsidy intervention

    Science.gov (United States)

    2014-01-01

    Background The Affordable Medicines Facility - malaria (AMFm), implemented at national scale in eight African countries or territories, subsidized quality-assured artemisinin combination therapy (ACT) and included communication campaigns to support implementation and promote appropriate anti-malarial use. This paper reports private for-profit provider awareness of key features of the AMFm programme, and changes in provider knowledge of appropriate malaria treatment. Methods This study had a non-experimental design based on nationally representative surveys of outlets stocking anti-malarials before (2009/10) and after (2011) the AMFm roll-out. Results Based on data from over 19,500 outlets, results show that in four of eight settings, where communication campaigns were implemented for 5–9 months, 76%-94% awareness of the AMFm ‘green leaf’ logo, 57%-74% awareness of the ACT subsidy programme, and 52%-80% awareness of the correct recommended retail price (RRP) of subsidized ACT were recorded. However, in the remaining four settings where communication campaigns were implemented for three months or less, levels were substantially lower. In six of eight settings, increases of at least 10 percentage points in private for-profit providers’ knowledge of the correct first-line treatment for uncomplicated malaria were seen; and in three of these the levels of knowledge achieved at endline were over 80%. Conclusions The results support the interpretation that, in addition to the availability of subsidized ACT, the intensity of communication campaigns may have contributed to the reported levels of AMFm-related awareness and knowledge among private for-profit providers. Future subsidy programmes for anti-malarials or other treatments should similarly include communication activities. PMID:24495691

  5. SMS for Life: a pilot project to improve anti-malarial drug supply management in rural Tanzania using standard technology

    Science.gov (United States)

    2010-01-01

    Background Maintaining adequate supplies of anti-malarial medicines at the health facility level in rural sub-Saharan Africa is a major barrier to effective management of the disease. Lack of visibility of anti-malarial stock levels at the health facility level is an important contributor to this problem. Methods A 21-week pilot study, 'SMS for Life', was undertaken during 2009-2010 in three districts of rural Tanzania, involving 129 health facilities. Undertaken through a collaborative partnership of public and private institutions, SMS for Life used mobile telephones, SMS messages and electronic mapping technology to facilitate provision of comprehensive and accurate stock counts from all health facilities to each district management team on a weekly basis. The system covered stocks of the four different dosage packs of artemether-lumefantrine (AL) and quinine injectable. Results Stock count data was provided in 95% of cases, on average. A high response rate (≥ 93%) was maintained throughout the pilot. The error rate for composition of SMS responses averaged 7.5% throughout the study; almost all errors were corrected and messages re-sent. Data accuracy, based on surveillance visits to health facilities, was 94%. District stock reports were accessed on average once a day. The proportion of health facilities with no stock of one or more anti-malarial medicine (i.e. any of the four dosages of AL or quinine injectable) fell from 78% at week 1 to 26% at week 21. In Lindi Rural district, stock-outs were eliminated by week 8 with virtually no stock-outs thereafter. During the study, AL stocks increased by 64% and quinine stock increased 36% across the three districts. Conclusions The SMS for Life pilot provided visibility of anti-malarial stock levels to support more efficient stock management using simple and widely available SMS technology, via a public-private partnership model that worked highly effectively. The SMS for Life system has the potential to alleviate

  6. The anti-malarial drug Mefloquine disrupts central autonomic and respiratory control in the working heart brainstem preparation of the rat

    Directory of Open Access Journals (Sweden)

    Lall Varinder K

    2012-12-01

    Full Text Available Abstract Background Mefloquine is an anti-malarial drug that can have neurological side effects. This study examines how mefloquine (MF influences central nervous control of autonomic and respiratory systems using the arterially perfused working heart brainstem preparation (WHBP of the rat. Recordings of nerve activity were made from the thoracic sympathetic chain and phrenic nerve, while heart rate (HR and perfusion pressure were also monitored in the arterially perfused, decerebrate, rat WHBP. MF was added to the perfusate at 1 μM to examine its effects on baseline parameters as well as baroreceptor and chemoreceptor reflexes. Results MF caused a significant, atropine resistant, bradycardia and increased phrenic nerve discharge frequency. Chemoreceptor mediated sympathoexcitation (elicited by addition of 0.1 ml of 0.03% sodium cyanide to the aortic cannula was significantly attenuated by the application of MF to the perfusate. Furthermore MF significantly decreased rate of return to resting HR following chemoreceptor induced bradycardia. An increase in respiratory frequency and attenuated respiratory-related sympathetic nerve discharge during chemoreceptor stimulation was also elicited with MF compared to control. However, MF did not significantly alter baroreceptor reflex sensitivity. Conclusions These studies indicate that in the WHBP, MF causes profound alterations in autonomic and respiratory control. The possibility that these effects may be mediated through actions on connexin 36 containing gap junctions in central neurones controlling sympathetic nervous outflow is discussed.

  7. A new double-antibody sandwich ELISA targeting Plasmodium falciparum aldolase to evaluate anti-malarial drug sensitivity

    Directory of Open Access Journals (Sweden)

    Brun Reto

    2009-10-01

    Full Text Available Abstract Background The standard in vitro test to assess anti-malarial activity of chemical compounds is the [3H]hypoxanthine incorporation assay. It is a radioactivity-based method to measure DNA replication of Plasmodium in red blood cells. The method is highly reproducible, however, the handling of radioactive material is costly, hazardous and requires the availability of appropriate technology and trained staff. Several other ways to evaluate in vitro anti-malarial activity do exist, all with their own assets and limitations. Methods The newly developed double-antibody sandwich ELISA described here is based on the properties of a non-overlapping pair of monoclonal antibodies directed against Plasmodium falciparum aldolase. This glycolytic enzyme possesses some unique nucleotide sequences compared to the human isoenzymes and has been highly conserved through evolution. Out of twenty possibilities, the most sensitive antibody pair was selected and used to quantitatively detect parasite aldolase in infected blood lysates. Results A total of 34 compounds with anti-malarial activity were tested side-by-side by ELISA and the [3H]hypoxanthine incorporation assay. The novel ELISA provided IC50s closely paralleling those from the radioactivity-based assay (R = 0.99, p Conclusion The newly developed ELISA presents several advantages over the comparative method, the [3H]hypoxanthine incorporation assay. The assay is highly reproducible, less hazardous (involves no radioactivity and requires little and cheap technical equipment. Relatively unskilled personnel can conduct this user-friendly assay. All this makes it attractive to be employed in resource-poor laboratories.

  8. Anti-malarial drug safety information obtained through routine monitoring in a rural district of South-Western Senegal

    Directory of Open Access Journals (Sweden)

    Brasseur Philippe

    2012-12-01

    Full Text Available Abstract Background Knowing the safety profile of anti-malarial treatments in routine use is essential; millions of patients receive now artemisinin combination therapy (ACT annually, but the return on information through current systems is as yet inadequate. Cohort event monitoring (CEM is a WHO (World Health Organization-recommended practice; testing its performance and feasibility in routine practice in malaria-endemic is important. Methods A nine-year CEM-based study of the safety of artesunate-amodiaquine (ASAQ at five peripheral health facilities in a rural district of South-western Senegal. Staff (nurses, health workers were trained to collect actively and systematically information on the patient, treatment and events on a purposely designed questionnaire. The occurrence and severity of events was collected before, during and after treatment up to 28 days in order to generate information on all adverse events (AEs as well as treatment-emerging signs/symptoms (TESS. Laboratory tests (haematology, liver and renal was planned for at least 10% of cases. Results During 2001–2009, 3,708 parasitologically-confirmed malaria cases (mean age = 16.0 ± 12.7 years were enrolled (26% and 52% of all and parasitologically-confirmed ASAQ treatments, respectively. Treatment was supervised in 96% of cases. Products changed over time: 49% were a loose combination of individually-packaged products (available 2001–03, 42% co-blistered products (2004–09 and 9% a fixed-dose co-formulation (2006–09; dosing was age-based for 42%, weight-based for 58%. AS and AQ were correctly dosed in 97% and 82% of cases with the loose and 93% and 86% with the fixed combination, but only 50% and 42% with the co-blistered product. Thirty-three per cent (33% of patients had at least one sign/symptom pre-treatment, 12% had at least one AE and 9% a TESS (total events 3,914, 1,144 and 693, respectively. AEs overestimated TESS by 1.2-2 fold (average 1.7. Changes in

  9. Site-specific integration and expression of an anti-malarial gene in transgenic Anopheles gambiae significantly reduces Plasmodium infections.

    Directory of Open Access Journals (Sweden)

    Janet M Meredith

    2011-01-01

    Full Text Available Diseases transmitted by mosquitoes have a devastating impact on global health and this is worsening due to difficulties with existing control measures and climate change. Genetically modified mosquitoes that are refractory to disease transmission are seen as having great potential in the delivery of novel control strategies. Historically the genetic modification of insects has relied upon transposable elements which have many limitations despite their successful use. To circumvent these limitations the Streptomyces phage phiC31 integrase system has been successfully adapted for site-specific transgene integration in insects. Here, we present the first site-specific transformation of Anopheles gambiae, the principal vector of human malaria. Mosquitoes were initially engineered to incorporate the phiC31 targeting site at a defined genomic location. A second phase of genetic modification then achieved site-specific integration of Vida3, a synthetic anti-malarial gene. Expression of Vida3, specifically in the midgut of bloodfed females, offered consistent and significant protection against Plasmodium yoelii nigeriensis, reducing average parasite intensity by 85%. Similar protection was observed against Plasmodium falciparum in some experiments, although protection was inconsistent. In the fight against malaria, it is imperative to establish a broad repertoire of both anti-malarial effector genes and tissue-specific promoters for their expression, enabling those offering maximum effect with minimum fitness cost to be identified. In the future, this technology will allow effective comparisons and informed choices to be made, potentially leading to complete transmission blockade.

  10. Development and optimization of a novel 384-well anti-malarial imaging assay validated for high-throughput screening.

    Science.gov (United States)

    Duffy, Sandra; Avery, Vicky M

    2012-01-01

    With the increasing occurrence of drug resistance in the malaria parasite, Plasmodium falciparum, there is a great need for new and novel anti-malarial drugs. We have developed a 384-well, high-throughput imaging assay for the detection of new anti-malarial compounds, which was initially validated by screening a marine natural product library, and subsequently used to screen more than 3 million data points from a variety of compound sources. Founded on another fluorescence-based P. falciparum growth inhibition assay, the DNA-intercalating dye 4',6-diamidino-2-phenylindole, was used to monitor changes in parasite number. Fluorescent images were acquired on the PerkinElmer Opera High Throughput confocal imaging system and analyzed with a spot detection algorithm using the Acapella data processing software. Further optimization of this assay sought to increase throughput, assay stability, and compatibility with our high-throughput screening equipment platforms. The assay typically yielded Z'-factor values of 0.5-0.6, with signal-to-noise ratios of 12.

  11. Docking Based 3D-QSAR Study of Tricyclic Guanidine Analogues of Batzelladine K as anti-malarial agents

    Science.gov (United States)

    Ahmed, Nafees; Anwar, Sirajudheen; Thet Htar, Thet

    2017-06-01

    The Plasmodium falciparum Lactate Dehydrogenase enzyme (PfLDH) catalyzes inter-conversion of pyruvate to lactate during glycolysis producing the energy required for parasitic growth. The PfLDH has been studied as a potential molecular target for development of anti-malarial agents. In an attempt to find the potent inhibitor of PfLDH, we have used Discovery studio to perform molecular docking in the active binding pocket of PfLDH by CDOCKER, followed by three-dimensional quantitative structure-activity relationship (3D-QSAR) studies of tricyclic guanidine batzelladine compounds, which were previously synthesized in our laboratory. Docking studies showed that there is a very strong correlation between in silico and in vitro results. Based on docking results, a highly predictive 3D-QSAR model was developed with q2 of 0.516. The model has predicted r2 of 0.91 showing that predicted IC50 values are in good agreement with experimental IC50 values. The results obtained from this study revealed the developed model can be used to design new anti-malarial compounds based on tricyclic guanidine derivatives and to predict activities of new inhibitors.

  12. Hazard Baseline Downgrade Effluent Treatment Facility

    International Nuclear Information System (INIS)

    Blanchard, A.

    1998-01-01

    This Hazard Baseline Downgrade reviews the Effluent Treatment Facility, in accordance with Department of Energy Order 5480.23, WSRC11Q Facility Safety Document Manual, DOE-STD-1027-92, and DOE-EM-STD-5502-94. It provides a baseline grouping based on the chemical and radiological hazards associated with the facility. The Determination of the baseline grouping for ETF will aid in establishing the appropriate set of standards for the facility

  13. Ex vivo susceptibility of Plasmodium falciparum isolates from Dakar, Senegal, to seven standard anti-malarial drugs

    Directory of Open Access Journals (Sweden)

    Pradines Bruno

    2011-10-01

    Full Text Available Abstract Background As a result of widespread chloroquine and sulphadoxine-pyrimethamine resistance, artemisinin-based combination therapy (ACT (which includes artemether-lumefantrine and artesunate-amodiaquine has been recommended as a first-line anti-malarial regimen in Senegal since 2006. Since then, there have been very few reports on the ex vivo susceptibility of Plasmodium falciparum to anti-malarial drugs. To examine whether parasite susceptibility has been affected by the widespread use of ACT, the ex vivo susceptibility of local isolates was assessed at the military hospital of Dakar. Methods The ex vivo susceptibility of 93 P. falciparum isolates from Dakar was successfully determined using the Plasmodium lactate dehydrogenase (pLDH ELISA for the following drugs: chloroquine (CQ, quinine (QN, mefloquine (MQ, monodesethylamodiaquine (MDAQ, lumefantrine (LMF, dihydroartemisinin (DHA and doxycycline (DOX. Results After transformation of the isolate IC50 in ratio of IC50 according to the susceptibility of the 3D7 reference strain (isolate IC50/3D7 IC50, the prevalence of the in vitro resistant isolates with reduced susceptibility was 50% for MQ, 22% for CQ, 12% for DOX, 6% for both QN and MDAQ and 1% for the drugs LMF and DHA. The highest significant positive correlations were shown between responses to CQ and MDAQ (r = 0.569; P r = 0.511; P r = 0.428; P = 0.0001, LMF and MQ (r = 0.413; P = 0.0002, QN and DHA (r = 0.402; P = 0.0003 and QN and MQ (r = 0.421; P = 0.0001. Conclusions The introduction of ACT in 2002 has not induced a decrease in P. falciparum susceptibility to the drugs DHA, MDAQ and LMF, which are common ACT components. However, the prevalence of P. falciparum isolates with reduced susceptibility has increased for both MQ and DOX. Taken together, these data suggest that intensive surveillance of the P. falciparum in vitro susceptibility to anti-malarial drugs in Senegal is required.

  14. "Every drug goes to treat its own disease…" - a qualitative study of perceptions and experiences of taking anti-retrovirals concomitantly with anti-malarials among those affected by HIV and malaria in Tanzania

    DEFF Research Database (Denmark)

    Mangesho, Peter E; Reynolds, Joanna; Lemnge, Martha

    2014-01-01

    and supporting the clinical management and treatment for co-infected individuals. METHODS: A qualitative study was conducted in Tanzania alongside a clinical trial of concomitant treatment for HIV and malaria co-infection. Focus group discussions were held with people receiving treatment for HIV and/or malaria...... to their compromised immune status but saw the disease as unavoidable. For those enrolled in the clinical controlled study, taking anti-malarials together with ARVs was largely seen as unproblematic, with health workers' advice and endorsement of concomitant drug taking influential in reported adherence. However......, perceptions of drug strength appeared to compel some people not enrolled in the clinical study to take the drugs at separate times to avoid anticipated harm to the body. CONCLUSIONS: Management of HIV and malaria concurrently often requires individuals to cross the domains of different disease programmes...

  15. Anti-malarial prescribing practices in Sudan eight years after introduction of artemisinin-based combination therapies and implications for development of drug resistance.

    Science.gov (United States)

    Elmannan, Abeer Abuzeid Atta; Elmardi, Khalid Abdelmutalab; Idris, Yassir Ali; Spector, Jonathan M; Ali, Nahid Abdelgadir; Malik, Elfatih Mohamed

    2015-03-26

    The World Health Organization (WHO) recommends artemisinin-based combination therapies (ACTs) as first-line treatment for uncomplicated malaria. Sudan revised its malaria treatment policy accordingly in 2004. However, eight years after ACTs were introduced in Sudan the patterns of ACT prescribing practices among health care providers remain unclear. We systematically analyzed use of ACTs in a large number of primary health facilities and we discuss the public health implications of our findings. This cross-sectional study was based on WHO's guidance for investigating drug use in health facilities. Data were collected from 40 randomly selected primary health centers in five localities in Gezira State, Sudan. The primary outcome of the study was the proportion of patients who were adequately managed according to Sudan's recommended malaria treatment guidelines. Twelve drug-use indicators were used to assess key ACT prescribing practices. One thousand and two hundred patients diagnosed with uncomplicated malaria were recruited into the study. ACT was prescribed for 88.6%patients and artemether injections were (incorrectly) prescribed in 9.5% of cases. Only 40.9% of patients in the study were correctly diagnosed and 26.9% were adequately managed according to the nationally recommended treatment guidelines. Incorrect prescribing activities included failure to use generic medicine names (88.2%), incorrect dosage (27.7%), and unexplained antibiotic co-prescription (24.2%). Dispensing practices were also poor, with labeling practices inadequate (97.1%) and insufficient information given to patients about their prescribed treatment (50.5%). Irrational malaria treatment practices are common in Sudan. This has important public health implications since failure to adhere to nationally recommended guidelines could play a role in the future development of drug resistance. As such, identifying ways to improve the anti-malarial prescribing practices of heath workers in Sudan may

  16. Malavefes: A computational voice-enabled malaria fuzzy informatics software for correct dosage prescription of anti-malarial drugs

    Directory of Open Access Journals (Sweden)

    Olugbenga O. Oluwagbemi

    2018-04-01

    Full Text Available Malaria is one of the infectious diseases consistently inherent in many Sub-Sahara African countries. Among the issues of concern are the consequences of wrong diagnosis and dosage administration of anti-malarial drugs on sick patients; these have resulted into various degrees of complications ranging from severe headaches, stomach and body discomfort, blurred vision, dizziness, hallucinations, and in extreme cases, death. Many expert systems have been developed to support different infectious disease diagnoses, but not sure of any yet, that have been specifically designed as a voice-based application to diagnose and translate malaria patients’ symptomatic data for pre-laboratory screening and correct prescription of proper dosage of the appropriate medication. We developed Malavefes, (a malaria voice-enabled computational fuzzy expert system for correct dosage prescription of anti-malarial drugs using Visual Basic.NET., and Java programming languages. Data collation for this research was conducted by survey from existing literature and interview from public health experts. The database for this malaria drug informatics system was implemented using Microsoft Access. The Root Sum Square (RSS was implemented as the inference engine of Malavefes to make inferences from rules, while Centre of Gravity (CoG was implemented as the defuzzification engine. The drug recommendation module was voice-enabled. Additional anti-malaria drug expiration validation software was developed using Java programming language. We conducted a user-evaluation of the performance and user-experience of the Malavefes software. Keywords: Informatics, Bioinformatics, Fuzzy, Anti-malaria, Voice computing, Dosage prescription

  17. The potential of anti-malarial compounds derived from African medicinal plants, part I: a pharmacological evaluation of alkaloids and terpenoids.

    Science.gov (United States)

    Amoa Onguéné, Pascal; Ntie-Kang, Fidele; Lifongo, Lydia Likowo; Ndom, Jean Claude; Sippl, Wolfgang; Mbaze, Luc Meva'a

    2013-12-13

    Traditional medicine caters for about 80% of the health care needs of many rural populations around the world, especially in developing countries. In addition, plant-derived compounds have played key roles in drug discovery. Malaria is currently a public health concern in many countries in the world due to factors such as chemotherapy faced by resistance, poor hygienic conditions, poorly managed vector control programmes and no approved vaccines. In this review, an attempt has been made to assess the value of African medicinal plants for drug discovery by discussing the anti-malarial virtue of the derived phytochemicals that have been tested by in vitro and in vivo assays. This survey was focused on pure compounds derived from African flora which have exhibited anti-malarial properties with activities ranging from "very active" to "weakly active". However, only the compounds which showed anti-malarial activities from "very active" to "moderately active" are discussed in this review. The activity of 278 compounds, mainly alkaloids, terpenoids, flavonoids, coumarines, phenolics, polyacetylenes, xanthones, quinones, steroids, and lignans have been discussed. The first part of this review series covers the activity of 171 compounds belonging to the alkaloid and terpenoid classes. Data available in the literature indicated that African flora hold an enormous potential for the development of phytomedicines for malaria.

  18. Several Human Cyclin-Dependent Kinase Inhibitors, Structurally Related to Roscovitine, As New Anti-Malarial Agents

    Directory of Open Access Journals (Sweden)

    Sandrine Houzé

    2014-09-01

    Full Text Available In Africa, malaria kills one child each minute. It is also responsible for about one million deaths worldwide each year. Plasmodium falciparum, is the protozoan responsible for the most lethal form of the disease, with resistance developing against the available anti-malarial drugs. Among newly proposed anti-malaria targets, are the P. falciparum cyclin-dependent kinases (PfCDKs. There are involved in different stages of the protozoan growth and development but share high sequence homology with human cyclin-dependent kinases (CDKs. We previously reported the synthesis of CDKs inhibitors that are structurally-related to (R-roscovitine, a 2,6,9-trisubstituted purine, and they showed activity against neuronal diseases and cancers. In this report, we describe the synthesis and the characterization of new CDK inhibitors, active in reducing the in vitro growth of P. falciparum (3D7 and 7G8 strains. Six compounds are more potent inhibitors than roscovitine, and three exhibited IC50 values close to 1 µM for both 3D7 and 7G8 strains. Although, such molecules do inhibit P. falciparum growth, they require further studies to improve their selectivity for PfCDKs.

  19. Community perceptions of targeted anti-malarial mass drug administrations in two provinces in Vietnam: a quantitative survey.

    Science.gov (United States)

    Nguyen, Thuy-Nhien; Thu, Pham N Huong; Hung, Ngo Trong; Son, Do Hung; Tien, Nguyen Thanh; Van Dung, Nguyen; Quang, Huynh Hong; Seidlein, Lorenz von; Cheah, Phaik Yeong; Dondorp, Arjen M; Day, Nicholas P J; White, Nicholas J; Hien, Tran Tinh

    2017-01-06

    As part of a targeted malaria elimination project, mass drug administrations (MDAs) were conducted in Vietnam. The impact of MDAs on malaria transmission depends largely on the efficacy of the anti-malarial drug regimen, the malaria epidemiology in the site and the population coverage. To explore why some people participate in MDAs and others do not, a quantitative survey of the villagers' perceptions was undertaken in Vietnam. In 2013/2014 MDAs were conducted in a village in Binh Phuoc province and a village in Ninh Thuan province. Within three months of the drug administration, 59 respondents in a village in Binh Phuoc and 79 respondents in a village in Ninh Thuan were randomly selected and interviewed. Comprehension of the purpose of the intervention was of paramount importance for participation in the intervention. Respondents aware that the intervention aims to protect against malaria were significantly more likely to participate than respondents who were unaware of the MDA's purpose. Secondly, how and by whom villagers were informed was critical for participation. There was a strong association between sensitization by an informant such as a member of the local health team with participation in the intervention. The study suggests several approaches to increase participation in mass drug administration campaigns. Training trustworthy informants to sensitize the study population is critical to maximize village participation in this setting. To achieve high coverage the entire community must understand and agree with the intervention.

  20. Genotyping of Plasmodium falciparum using antigenic polymorphic markers and to study anti-malarial drug resistance markers in malaria endemic areas of Bangladesh

    Directory of Open Access Journals (Sweden)

    Akter Jasmin

    2012-11-01

    Full Text Available Abstract Background In the past many regions of Bangladesh were hyperendemic for malaria. Malaria control in the 1960s to 1970s eliminated malaria from the plains but in the Chittagong Hill Tracts remained a difficult to control reservoir. The Chittagong Hill Tracts have areas with between 1 and 10% annual malaria rates, predominately 90-95% Plasmodium falciparum. In Southeast Asia, multiplicity of infection for hypo-endemic regions has been approximately 1.5. Few studies on the genetic diversity of P. falciparum have been performed in Bangladesh. Anderson et al. performed a study in Khagrachari, northern Chittagong Hill Tracts in 2002 on 203 patients and found that parasites had a multiplicity of infection of 1.3 by MSP-1, MSP-2 and GLURP genotyping. A total of 94% of the isolates had the K76T Pfcrt chloroquine resistant genotype, and 70% showed the N86Y Pfmdr1 genotype. Antifolate drug resistant genotypes were high with 99% and 73% of parasites having two or more mutations at the dhfr or dhps loci. Methods Nested and real-time polymerase chain reaction (PCR methods were used to genotype P. falciparum using antigenic polymorphic markers and to study anti-malarial drug resistance markers in malaria endemic areas of Bangladesh. Results The analysis of polymorphic and drug resistant genotype on 33 paired recrudescent infections after drug treatment in the period 2004 to 2008 in the Chittagong Hill Tracts, which is just prior to countrywide provision of artemisinin combination therapy. Overall the multiplicity of infection for MSP-1 was 2.7 with a slightly smaller parasite diversity post-treatment. The 13 monoclonal infections by both GLURP and MSP-1 were evenly divided between pre- and post-treatment. The MSP-1 MAD block was most frequent in 66 of the samples. The prevalence of the K76T PfCRT chloroquine resistant allele was approximately 82% of the samples, while the resistant Pfmdr1 N86Y was present in 33% of the samples. Interestingly, the post-treatment

  1. Effects of anti-malarial alkaloids on the sperm properties and blood ...

    African Journals Online (AJOL)

    Venous blood and masturbation specimens of semen were obtained from the subjects before treatment, immediately post-treatment and by the 65th day from commencement of treatment. Blood levels of follicle stimulating hormones, leutinizing hormone and testosterone were determined by Enzyme Linked Imuno Assay.

  2. Factors related to compliance to anti-malarial drug combination: example of amodiaquine/sulphadoxine-pyrimethamine among children in rural Senegal

    Directory of Open Access Journals (Sweden)

    Sow Diarietou

    2009-06-01

    Full Text Available Abstract Background The introduction of new anti-malarial treatment that is effective, but more expensive, raises questions about whether the high level of effectiveness observed in clinical trials can be found in a context of family use. The objective of this study was to determine the factors related to adherence, when using the amodiaquine/sulphadoxine-pyrimethamine (AQ/SP association, a transitory strategy before ACT implementation in Senegal. Methods The study was conducted in five rural dispensaries. Children, between two and 10 years of age, who presented mild malaria were recruited at the time of the consultation and were prescribed AQ/SP. The child's primary caretaker was questioned at home on D3 about treatment compliance and factors that could have influenced his or her adherence to treatment. A logistic regression model was used for the analyses. Results The study sample included 289 children. The adherence rate was 64.7%. Two risks factors for non-adherence were identified: the children's age (8–10 years (ORa = 3.07 [1.49–6.29]; p = 0.004; and the profession of the head of household (retailer/employee versus farmer (ORa = 2.71 [1.34–5.48]; p = 0.006. Previously seeking care (ORa = 0.28 [0.105–0.736], p=0.001] satisfaction with received information (ORa = 0.45 [0.24–0.84]; p = 0.013, and the quality of history taking (ORa = 0.38 [0.21–0.69]; p = 0.001 were significantly associated with good compliance. Conclusion The results of the study show the importance of information and communication between caregivers and health center staff. The experience gained from this therapeutic transition emphasizes the importance of information given to the patients at the time of the consultation and drug delivery in order to improve drug use and thus prevent the emergence of rapid drug resistance.

  3. Longitudinal in vitro surveillance of Plasmodium falciparum sensitivity to common anti-malarials in Thailand between 1994 and 2010

    Directory of Open Access Journals (Sweden)

    Parker Daniel

    2012-08-01

    Full Text Available Abstract Background Drug and multidrug-resistant Plasmodium falciparum malaria has existed in Thailand for several decades. Furthermore, Thailand serves as a sentinel for drug-resistant malaria within the Greater Mekong sub-region. However, the drug resistance situation is highly dynamic, changing quickly over time. Here parasite in vitro drug sensitivity is reported for artemisinin derivatives, mefloquine, chloroquine and quinine, across Thailand. Methods Blood was drawn from patients infected with P. falciparum in seven sentinel provinces along Thai international borders with Cambodia, Myanmar, Laos, and Malaysia. In vitro parasite sensitivity was tested using the World Health Organization’s microtest (mark III (between 1994 and 2002 and the histidine-rich protein-2 (HRP2-based enzyme-linked immunosorbent assay (in 2010. Following World Health Organization protocol, at least 30 isolates were collected for each province and year represented in this study. Where possible, t-tests were used to test for significant differences. Results There appears to be little variation across study sites with regard to parasite sensitivity to chloroquine. Quinine resistance appears to have been rising prior to 1997, but has subsequently decreased. Mefloquine sensitivity appears high across the provinces, especially along the north-western border with Myanmar and the eastern border with Cambodia. Finally, the data suggest that parasite sensitivity to artemisinin and its derivatives is significantly higher in provinces along the north-western border with Myanmar. Conclusions Parasite sensitivity to anti-malarials in Thailand is highly variable over time and largely mirrors official drug use policy. The findings with regard to reduced sensitivity to artemisinin derivatives are supported by recent reports of reduced parasite clearance associated with artemisinin. This trend is alarming since artemisinin is considered the last defence against malaria. Continued

  4. In vivo anti-malarial potentials of some plants extracts on ICR-mice ...

    African Journals Online (AJOL)

    Five medicinal plants, Acacia nilotica (Fabaceae), Citrus aurantifolia (Rutaceae), Mangifera indica (Anacardiaceae) Carica papaya (Caricaceae), and Psidium guajava (Myrtaceae) used for the treatment of malaria/ fever by the Hausa people of Kano-Nigeria were selected based on their traditional claims. These were ...

  5. Reverse pharmacology for developing an anti-malarial phytomedicine. The example of Argemone mexicana

    Directory of Open Access Journals (Sweden)

    Claudia Simoes-Pires

    2014-12-01

    Reverse pharmacology, also called bedside-to-bench, is a research approach based on the traditional knowledge and relates to reversing the classical laboratory to clinic pathway to a clinic to laboratory practice. It is a trans-disciplinary approach focused on traditional knowledge, experimental observations and clinical experiences. This paper is an overview of the reverse pharmacology approach applied to the decoction of Argemone mexicana, used as an antimalarial traditional medicine in Mali. A. mexicana appeared as the most effective traditional medicine for the treatment of uncomplicated falciparum malaria in Mali, and the clinical efficacy of the decoction was comparable to artesunate–amodiaquine as previously published. Four stages of the reverse pharmacology process will be described here with a special emphasis on the results for stage 4. Briefly, allocryptopine, protopine and berberine were isolated through bioguided fractionation, and had their identity confirmed by spectroscopic analysis. The three alkaloids showed antiparasitic activity in vitro, of which allocryptopine and protopine were selective towards Plasmodium falciparum. Furthermore, the amount of the three active alkaloids in the decoction was determined by quantitative NMR, and preliminary in vivo assays were conducted. On the basis of these results, the reverse pharmacology approach is discussed and further pharmacokinetic studies appear to be necessary in order to determine whether these alkaloids can be considered as phytochemical markers for quality control and standardization of an improved traditional medicine made with this plant.

  6. What happened to anti-malarial markets after the Affordable Medicines Facility-malaria pilot? Trends in ACT availability, price and market share from five African countries under continuation of the private sector co-payment mechanism.

    Science.gov (United States)

    Tougher, Sarah; Hanson, Kara; Goodman, Catherine

    2017-04-25

    The private sector supplies anti-malarial treatment for large proportions of patients in sub-Saharan Africa. Following the large-scale piloting of the Affordable Medicines Facility-malaria (AMFm) from 2010 to 2011, a private sector co-payment mechanism (CPM) provided continuation of private sector subsidies for quality-assured artemisinin combination therapies (QAACT). This article analyses for the first time the extent to which improvements in private sector QAACT supply and distribution observed during the AMFm were maintained or intensified during continuation of the CPM through 2015 in Kenya, Madagascar, Nigeria, Tanzania and Uganda using repeat cross-sectional outlet survey data. QAACT market share in all five countries increased during the AMFm period (p co-payment mechanism for QAACT implemented at national scale for 5 years was associated with positive and sustained improvements in QAACT availability, price and market share in Nigeria, Tanzania and Uganda, with more mixed results in Kenya, and few improvements in Madagascar. The subsidy mechanism as implemented over time across countries was not sufficient on its own to achieve optimal QAACT uptake. Supporting interventions to address continued availability and distribution of non-artemisinin therapies, and to create demand for QAACT among providers and consumers need to be effectively implemented to realize the full potential of this subsidy mechanism. Furthermore, there is need for comprehensive market assessments to identify contemporary market barriers to high coverage with both confirmatory testing and appropriate treatment.

  7. Quality assessment of some selected brands of anti malarial drugs used in Ghana: A case study of Agona West Municipality

    International Nuclear Information System (INIS)

    Asare, Aquisman Ebenezer

    2016-07-01

    The availability of numerous brands of artesunate in our drug market today places clinicians and pharmacists in a difficult situation of choice of a suitable brand or the possibility of alternative use. Fake artesunate could compromise the hope that ACT (artemisinin combination therapy) offers for malaria control in Africa. In this study, quality of some selected brands of anti - malarial drugs used in the communities of Agona west Municipality, Ghana was determined. Blister or packs of anti – malarial tablets were randomly sampled. The Protocols of the International Pharmacopeia and Global Pharma Health Fund Minilab were used to assess the quality of anti – malarial tablets per blister pack manufactured by Bliss Gvs Pharma Ltd. India, Letap Pharmaceutical Company Ltd. Ghana and Guilin Pharmaceutical Company Ltd. China and sold in chemical sales outlets at the farming communities of Agona West Municipality, Ghana. The identification test was used to confirm the presence of active ingredients in the tablets. A confirmatory test for the active ingredient was achieved with artesunate (ICRS 1302) reference standards and Gsunate reference standard (ICRS4061). The friability test was used to confirm the hardness of the tablets to determine the drug ability to withstand abrasion in packaging, handling and shipping. The disintegration test was used to confirm the time required for the tablets to disintegrate into particles. Titrimetric analysis confirmed the amount of artesunate found in tablets.The results of the study are as follows for Artesunate by GPCL, LPL and Gsunate by BGPL; the identification test confirmed the presence of the active ingredient in all the brands. Based on the International Pharmacopoeia acceptable range of 1 to 15 min for genuine artesunate per tablet, 93.75 % of field selected artesunate blister pack tablets manufactured by GPCL passed the disintegration test and 6.25% failed. Also 85.57% of the sampled artesunate blister pack manufactured by

  8. Effect of anti-malarial interventions on trends of malaria cases, hospital admissions and deaths, 2005-2015, Ghana.

    Science.gov (United States)

    Aregawi, Maru; Malm, Keziah L; Wahjib, Mohammed; Kofi, Osae; Allotey, Naa-Korkor; Yaw, Peprah Nana; Abba-Baffoe, Wilmot; Segbaya, Sylvester; Owusu-Antwi, Felicia; Kharchi, Abderahmane T; Williams, Ryan O; Saalfeld, Mark; Workneh, Nibretie; Shargie, Estifanos Biru; Noor, Abdisalan M; Bart-Plange, Constance

    2017-04-26

    indicators were observed in the three epidemiological strata (coastal, forest, savannah). All-cause admissions increased significantly in patients covered by the National Health Insurance Scheme (NHIS) compared to the non-insured. The non-malaria cases and non-malaria deaths increased or remained unchanged during the same period. All-cause mortality for children under 5 years old in household surveys, similar to those observed in the hospitals, declined by 43% between 2008 and 2014. The data provide compelling evidence of impact following LLIN mass campaigns targeting all ages since 2011, while maintaining other anti-malarial interventions. Malaria cases and deaths decreased by over 50 and 65%, respectively. The declines were stronger in children under five. Test positivity rate in all ages decreased by >40%. The decrease in malaria deaths was against a backdrop of increased admissions owing to free access to hospitalization through the NHIS. The study demonstrated that retrospective health facility-based data minimize reporting biases to assess effect of interventions. Malaria control in Ghana is dependent on sustained coverage of effective interventions and strengthened surveillance is vital to monitor progress of these investments.

  9. Anti-malarial effect of 1-(N-acetyl-6-aminohexyl-3-hydroxy-2-methylpyridin-4-one and green tea extract on erythrocyte-stage Plasmodium berghei in mice

    Directory of Open Access Journals (Sweden)

    Phitsinee Thipubon

    2015-11-01

    Conclusions: CM1 would be effective per se and synergize with PYR in inhibiting growth of murine malaria parasites, possibly by limiting iron supply from plasma transferrin and host PRBC cytoplasm, and chelating catalytic iron cstitutive in parasites’ mitochondrial cytochromes and cytoplasmic ribonucleotide reductase. CM1 would be a promising adjuvant to enhance PYR anti-malarial activity and minimize the drug resistance.

  10. Global Nuclear Energy Partnership Waste Treatment Baseline

    Energy Technology Data Exchange (ETDEWEB)

    Gombert, Dirk; Ebert, William; Marra, James; Jubin, Robert; Vienna, John [Idaho National laboratory, 2525 Fremont Ave., Idaho Falls, ID 83402 (United States)

    2008-07-01

    The Global Nuclear Energy Partnership (GNEP) program is designed to demonstrate that a proliferation-resistant and sustainable integrated nuclear fuel cycle can be commercialized and used internationally. Alternative stabilization concepts for byproducts and waste streams generated by fuel recycling processes were evaluated and a baseline set of waste forms was recommended for the safe disposition of waste streams. Specific waste forms are recommended based on the demonstrated or expected commercial practicability and technical maturity of the processes needed to make the waste forms, and expected performance of the waste form materials when disposed. Significant issues remain in developing technologies to process some of the wastes into the recommended waste forms, and a detailed analysis of technology readiness may lead to the choice of a different waste form than what is recommended herein. Evolving regulations could also affect the selection of waste forms. (authors)

  11. Global Nuclear Energy Partnership Waste Treatment Baseline

    International Nuclear Information System (INIS)

    Gombert, Dirk; Ebert, William; Marra, James; Jubin, Robert; Vienna, John

    2008-01-01

    The Global Nuclear Energy Partnership (GNEP) program is designed to demonstrate that a proliferation-resistant and sustainable integrated nuclear fuel cycle can be commercialized and used internationally. Alternative stabilization concepts for byproducts and waste streams generated by fuel recycling processes were evaluated and a baseline set of waste forms was recommended for the safe disposition of waste streams. Specific waste forms are recommended based on the demonstrated or expected commercial practicability and technical maturity of the processes needed to make the waste forms, and expected performance of the waste form materials when disposed. Significant issues remain in developing technologies to process some of the wastes into the recommended waste forms, and a detailed analysis of technology readiness may lead to the choice of a different waste form than what is recommended herein. Evolving regulations could also affect the selection of waste forms. (authors)

  12. Global Nuclear Energy Partnership Waste Treatment Baseline

    Energy Technology Data Exchange (ETDEWEB)

    Dirk Gombert; William Ebert; James Marra; Robert Jubin; John Vienna

    2008-05-01

    The Global Nuclear Energy Partnership program (GNEP) is designed to demonstrate a proliferation-resistant and sustainable integrated nuclear fuel cycle that can be commercialized and used internationally. Alternative stabilization concepts for byproducts and waste streams generated by fuel recycling processes were evaluated and a baseline of waste forms was recommended for the safe disposition of waste streams. Waste forms are recommended based on the demonstrated or expected commercial practicability and technical maturity of the processes needed to make the waste forms, and performance of the waste form materials when disposed. Significant issues remain in developing technologies to process some of the wastes into the recommended waste forms, and a detailed analysis of technology readiness and availability may lead to the choice of a different waste form than what is recommended herein. Evolving regulations could also affect the selection of waste forms.

  13. Estimating the Impact of Means-tested Subsidies under Treatment Externalities with Application to Anti-Malarial Bednets

    DEFF Research Database (Denmark)

    Bhattacharya, Debopam; Dupas, Pascaline; Kanaya, Shin

    purchase price, causing free-riding and sub-optimal private procurement, such products may be subsidized in developing countries through means-testing. Owing to associated spillover effects, cost-benefit analysis of such subsidies requires modelling behavioral responses of both the subsidized household...... resulting from a specific targeting rule, depending on the resulting aggregate incidence of subsidy. Applying our method to the Kenyan data, we find that (i) individual ITN use rises with neighborhood subsidy-rates, (ii) under means-testing, predicted ITN use is a convex increasing function of the subsidy...

  14. Finding parasites and finding challenges: improved diagnostic access and trends in reported malaria and anti-malarial drug use in Livingstone district, Zambia

    Directory of Open Access Journals (Sweden)

    Masaninga Freddie

    2012-10-01

    Full Text Available Abstract Background Understanding the impact of malaria rapid diagnostic test (RDT use on management of acute febrile disease at a community level, and on the consumption of anti-malarial medicines, is critical to the planning and success of scale-up to universal parasite-based diagnosis by health systems in malaria-endemic countries. Methods A retrospective study of district-wide community-level RDT introduction was conducted in Livingstone District, Zambia, to assess the impact of this programmed on malaria reporting, incidence of mortality and on district anti-malarial consumption. Results Reported malaria declined from 12,186 cases in the quarter prior to RDT introduction in 2007 to an average of 12.25 confirmed and 294 unconfirmed malaria cases per quarter over the year to September 2009. Reported malaria-like fever also declined, with only 4,381 RDTs being consumed per quarter over the same year. Reported malaria mortality declined to zero in the year to September 2009, and all-cause mortality declined. Consumption of artemisinin-based combination therapy (ACT dropped dramatically, but remained above reported malaria, declining from 12,550 courses dispensed by the district office in the quarter prior to RDT implementation to an average of 822 per quarter over the last year. Quinine consumption in health centres also declined, with the district office ceasing to supply due to low usage, but requests for sulphadoxine-pyrimethamine (SP rose to well above previous levels, suggesting substitution of ACT with this drug in RDT-negative cases. Conclusions RDT introduction led to a large decline in reported malaria cases and in ACT consumption in Livingstone district. Reported malaria mortality declined to zero, indicating safety of the new diagnostic regime, although adherence and/or use of RDTs was still incomplete. However, a deficiency is apparent in management of non-malarial fever, with inappropriate use of a low-cost single dose drug, SP

  15. Exposure to anti-malarial drugs and monitoring of adverse drug reactions using toll-free mobile phone calls in private retail sector in Sagamu, Nigeria: implications for pharmacovigilance

    Directory of Open Access Journals (Sweden)

    Ogunwande Isiaka A

    2011-08-01

    Full Text Available Abstract Background Adverse drug reactions (ADRs contribute to ill-health or life-threatening outcomes of therapy during management of infectious diseases. The exposure to anti-malarial and use of mobile phone technology to report ADRs following drug exposures were investigated in Sagamu - a peri-urban community in Southwest Nigeria. Methods Purchase of medicines was actively monitored for 28 days in three Community Pharmacies (CP and four Patent and Proprietary Medicine Stores (PPMS in the community. Information on experience of ADRs was obtained by telephone from 100 volunteers who purchased anti-malarials during the 28-day period. Results and Discussion A total of 12,093 purchases were recorded during the period. Antibiotics, analgesics, vitamins and anti-malarials were the most frequently purchased medicines. A total of 1,500 complete courses of anti-malarials were purchased (12.4% of total purchases; of this number, purchases of sulphadoxine-pyrimethamine (SP and chloroquine (CQ were highest (39.3 and 25.2% respectiuvely. Other anti-malarials purchased were artesunate monotherapy (AS - 16.1%, artemether-lumefantrine (AL 10.0%, amodiaquine (AQ - 6.6%, quinine (QNN - 1.9%, halofantrine (HF - 0.2% and proguanil (PR - 0.2%. CQ was the cheapest (USD 0.3 and halofantrine the most expensive (USD 7.7. AL was 15.6 times ($4.68 more expensive than CQ. The response to mobile phone monitoring of ADRs was 57% in the first 24 hours (day 1 after purchase and decreased to 33% by day 4. Participants in this monitoring exercise were mostly with low level of education (54%. Conclusion The findings from this study indicate that ineffective anti-malaria medicines including monotherapies remain widely available and are frequently purchased in the study area. Cost may be a factor in the continued use of ineffective monotherapies. Availability of a toll-free telephone line may facilitate pharmacovigilance and follow up of response to medicines in a resource

  16. Hepatitis C treatment response kinetics and impact of baseline predictors

    DEFF Research Database (Denmark)

    Lindh, M; Arnholm, B; Eilard, A

    2011-01-01

    Summary. The optimal duration of treatment for hepatitis C virus (HCV) infections is highly variable but critical for achieving cure (sustained virological response, SVR). We prospectively investigated the impact of age, fibrosis, baseline viraemia and genotype on the early viral kinetics and tre...

  17. Development of ELISA-based methods to measure the anti-malarial drug chloroquine in plasma and in pharmaceutical formulations

    DEFF Research Database (Denmark)

    Khalil, Insaf F; Alifrangis, Michael; Recke, Camilla

    2011-01-01

    In Central and South America and Eastern and Southern Africa, Plasmodium vivax infections accounts for 71-81% and 5% of malaria cases, respectively. In these areas, chloroquine (CQ) remains the treatment of choice for P. vivax malaria. In addition, CQ has recently proven to be an effective HIV-1 ...... resistance. The aim of this study was to develop an inexpensive, simple antibody-based ELISA to measure CQ concentrations in tablets and in plasma....

  18. Target-similarity search using Plasmodium falciparum proteome identifies approved drugs with anti-malarial activity and their possible targets.

    Directory of Open Access Journals (Sweden)

    Reagan M Mogire

    Full Text Available Malaria causes about half a million deaths annually, with Plasmodium falciparum being responsible for 90% of all the cases. Recent reports on artemisinin resistance in Southeast Asia warrant urgent discovery of novel drugs for the treatment of malaria. However, most bioactive compounds fail to progress to treatments due to safety concerns. Drug repositioning offers an alternative strategy where drugs that have already been approved as safe for other diseases could be used to treat malaria. This study screened approved drugs for antimalarial activity using an in silico chemogenomics approach prior to in vitro verification. All the P. falciparum proteins sequences available in NCBI RefSeq were mined and used to perform a similarity search against DrugBank, TTD and STITCH databases to identify similar putative drug targets. Druggability indices of the potential P. falciparum drug targets were obtained from TDR targets database. Functional amino acid residues of the drug targets were determined using ConSurf server which was used to fine tune the similarity search. This study predicted 133 approved drugs that could target 34 P. falciparum proteins. A literature search done at PubMed and Google Scholar showed 105 out of the 133 drugs to have been previously tested against malaria, with most showing activity. For further validation, drug susceptibility assays using SYBR Green I method were done on a representative group of 10 predicted drugs, eight of which did show activity against P. falciparum 3D7 clone. Seven had IC50 values ranging from 1 μM to 50 μM. This study also suggests drug-target association and hence possible mechanisms of action of drugs that did show antiplasmodial activity. The study results validate the use of proteome-wide target similarity approach in identifying approved drugs with activity against P. falciparum and could be adapted for other pathogens.

  19. SENYAWA AKTIF ANTIKANKER PAYUDARA DAN ANTIMALARIA DARI TUMBUHAN DADAP AYAM (ERHYTHRINA VALERIEGATA SECARA IN VITRO (Anti Breast-cancer and anti-malarial Active Compounds of Erithrina Variegata by in Vitro Test

    Directory of Open Access Journals (Sweden)

    Tati Herlina

    2012-03-01

    Full Text Available ABSTRAK Tumbuhan Erythrina variegata (Leguminosae secara tradisional dikenal oleh masyarakat Indonesia sebagai obat antikanker dan antimalaria. Bagian tumbuhan ini yang biasa digunakan sebagai bahan pengobatan adalah daun dan kulit batang, tapi kandungan senyawa kimia aktif biologisnya belum banyak dilaporkan. Tujuan penelitian ini adalah untuk mengungkapkan senyawa aktif antikanker dan antimalaria secara in vitro yang terdapat di dalam daun dan kulit batang E. variegata. Penelitian dilakukan dengan cara ekstraksi metanol dan fraksionasi dari daun dan kulit batang E. variegata yang dipandu dengan uji antikanker secara in vitro terhadap sel kanker payudara T47D menggunakan metode Sulforodamin B (SRB dan uji antimalaria secara in vitro terhadap Plasmodium falciparum 3D7 (sensitif klorokuin dan K1 (resisten klorokuin menggunakan metode laktatdehidrogenase (LDH. Selanjutnya dilakukan pemisahan fraksi etil asetat daun dan kulit batang E. variegata yang dipantau dengan uji antikanker dan antimalaria secara in vitro menggunakan kombinasi kolom kromatografi diperoleh tiga senyawa aktif (1, 2, dan 3. Struktur kimia senyawa aktif (1, 2, dan 3 ditetapkan berdasarkan data-data spektroskopi dan diidentifikasikan sebagai turunan triterpenoid pentasiklik glikosida(1; flavonoid, eristagallin A (2; dan steroid, (22E-5α,8α-epidioksiergosta-6,22-dien-3β-ol (3. Senyawa (1 menunjukkan aktivitas antimalaria secara in vitro terhadap P. falciparum strain 3D7 (sensitif klorokuin dengan IC50 1,8 µg/mL dan terhadap strain K1 (resisten klorokuin dengan IC50 3,3 µg/mL. Senyawa (2 dan (3 menunjukkan aktivitas antikanker secara in vitro terhadap sel kanker payurada T47D dengan IC50 masing-masing 3,0 dan 3,2 µg/mL. Tumbuhan E. variegata mempunyai potensi sebagai bahan dasar obat herbal antikanker payudara dan antimalaria. ABSTRACT Erythrina variegata (Leguminosae plant used traditionaly as plant of  anti-cancer and anti-malarial in Indonesia. The leaves and stem bark of

  20. Revisiting the relationship between baseline risk and risk under treatment

    Directory of Open Access Journals (Sweden)

    Nony Patrice

    2009-02-01

    Full Text Available Abstract Background In medical practice, it is generally accepted that the 'effect model' describing the relationship between baseline risk and risk under treatment is linear, i.e. 'relative risk' is constant. Absolute benefit is then proportional to a patient's baseline risk and the treatment is most effective among high-risk patients. Alternatively, the 'effect model' becomes curvilinear when 'odds ratio' is considered to be constant. However these two models are based on purely empirical considerations, and there is still no theoretical approach to support either the linear or the non-linear relation. Presentation of the hypothesis From logistic and sigmoidal Emax (Hill models, we derived a phenomenological model which includes the possibility of integrating both beneficial and harmful effects. Instead of a linear relation, our model suggests that the relationship is curvilinear i.e. the moderate-risk patients gain most from the treatment in opposition to those with low or high risk. Testing the hypothesis Two approaches can be proposed to investigate in practice such a model. The retrospective one is to perform a meta-analysis of clinical trials with subgroups of patients including a great range of baseline risks. The prospective one is to perform a large clinical trial in which patients are recruited according to several prestratified diverse and high risk groups. Implications of the hypothesis For the quantification of the treatment effect and considering such a model, the discrepancy between odds ratio and relative risk may be related not only to the level of risk under control conditions, but also to the characteristics of the dose-effect relation and the amount of dose administered. In the proposed approach, OR may be considered as constant in the whole range of Rc, and depending only on the intrinsic characteristics of the treatment. Therefore, OR should be preferred rather than RR to summarize information on treatment efficacy.

  1. Development of ELISA-based methods to measure the anti-malarial drug chloroquine in plasma and in pharmaceutical formulations

    Directory of Open Access Journals (Sweden)

    Ronn Anita

    2011-08-01

    Full Text Available Abstract Background In Central and South America and Eastern and Southern Africa, Plasmodium vivax infections accounts for 71-81% and 5% of malaria cases, respectively. In these areas, chloroquine (CQ remains the treatment of choice for P. vivax malaria. In addition, CQ has recently proven to be an effective HIV-1 therapeutic agent. There is a dire need to continue monitoring quality of CQ as there is a major influx of substandard and fake formulations into malaria-endemic countries. The use of fake/substandard drugs will result in sub-therapeutic levels endangering the patient and possibly select for parasite resistance. The aim of this study was to develop an inexpensive, simple antibody-based ELISA to measure CQ concentrations in tablets and in plasma. Methods A monoclonal antibody (MAb that reacts with the N-side chain of the CQ molecule was prepared by use of a CQ analogue. A specific and reliable ELISA for detection of CQ was developed. The developed assay was validated by measuring CQ in tablets sold in Denmark, India and Sudan. Furthermore, kinetics of CQ concentrations in plasma of four volunteers, who ingested two tablets of Malarex® containing, 250 mg CQ base, were measured before drug intake, three hours later and thereafter at days 1, 3, 7, 14, 21 and 28. The same plasma samples were simultaneously measured by high performance liquid chromatography (HPLC. Results The ELISA proved an easy-to-handle and very sensitive tool for the detection of CQ with a lower limit of detection at 3.9 ng/ml. ELISA levels of CQ in plasma showed high agreement with the levels obtained by HPLC (r = 0.98. The specificity in the negative control group was 100%. Conclusion The developed ELISA can be used for quality screening of CQ in pharmaceutical formulations and for drug monitoring in malaria and in other infectious diseases, such as HIV, where CQ proved to be an effective therapeutic agent. The methodology has been exploited to develop monoclonal

  2. Trends in malaria cases, hospital admissions and deaths following scale-up of anti-malarial interventions, 2000-2010, Rwanda.

    Science.gov (United States)

    Karema, Corine; Aregawi, Maru W; Rukundo, Alphonse; Kabayiza, Alain; Mulindahabi, Monique; Fall, Ibrahima S; Gausi, Khoti; Williams, Ryan O; Lynch, Michael; Cibulskis, Richard; Fidele, Ngabo; Nyemazi, Jean-Pierre; Ngamije, Daniel; Umulisa, Irenee; Newman, Robert; Binagwaho, Agnes

    2012-07-23

    unchanged. Rainfall and temperature remained favourable for malaria transmission. The annual all-cause mortality in children under-five in household surveys declined from 152 per 1,000 live births during 2001-2005, to 76 per 1,000 live births in 2006-2010 (55% decline). The five-year cumulative number of all-cause deaths in hospital declined 28% (8,051 to 5,801) during the same period. A greater than 50% decline in confirmed malaria cases, admissions and deaths at district hospitals in Rwanda since 2005 followed a marked increase in ITN coverage and use of ACT. The decline occurred among both children under-five and in those five years and above, while hospital utilization increased and suitable conditions for malaria transmission persisted. Declines in malaria indicators in children under 5 years were more striking than in the older age groups. The resurgence in cases associated with decreased ITN coverage in 2009 highlights the need for sustained high levels of anti-malarial interventions in Rwanda and other malaria endemic countries.

  3. Autonomous and controlled motivation for eating disorders treatment: baseline predictors and relationship to treatment outcome.

    Science.gov (United States)

    Carter, Jacqueline C; Kelly, Allison C

    2015-03-01

    This study aimed to identify baseline predictors of autonomous and controlled motivation for treatment (ACMT) in a transdiagnostic eating disorder sample, and to examine whether ACMT at baseline predicted change in eating disorder psychopathology during treatment. Participants were 97 individuals who met DSM-IV-TR criteria for an eating disorder and were admitted to a specialized intensive treatment programme. Self-report measures of eating disorder psychopathology, ACMT, and various psychosocial variables were completed at the start of treatment. A subset of these measures was completed again after 3, 6, 9, and 12 weeks of treatment. Multiple regression analyses showed that baseline autonomous motivation was higher among patients who reported more self-compassion and more received social support, whereas the only baseline predictor of controlled motivation was shame. Multilevel modelling revealed that higher baseline autonomous motivation predicted faster decreases in global eating disorder psychopathology, whereas the level of controlled motivation at baseline did not. The current findings suggest that developing interventions designed to foster autonomous motivation specifically and employing autonomy supportive strategies may be important to improving eating disorders treatment outcome. The findings of this study suggest that developing motivational interventions that focus specifically on enhancing autonomous motivation for change may be important for promoting eating disorder recovery. Our results lend support for the use of autonomy supportive strategies to strengthen personally meaningful reasons to achieve freely chosen change goals in order to enhance treatment for eating disorders. One study limitation is that there were no follow-up assessments beyond the 12-week study and we therefore do not know whether the relationships that we observed persisted after treatment. Another limitation is that this was a correlational study and it is therefore important

  4. Antibodies to malaria vaccine candidates are associated with chloroquine or sulphadoxine/pyrimethamine treatment efficacy in children in an endemic area of Burkina Faso

    DEFF Research Database (Denmark)

    Diarra, Amidou; Nebie, Issa; Tiono, Alfred

    2012-01-01

    ABSTRACT: BACKGROUND: Patient immune status is thought to affect the efficacy of anti-malarial chemotherapy. This is a subject of some importance, since evidence of immunity-related interactions may influence our use of chemotherapy in populations with drug resistance, as well as assessment...... of the value of suboptimal vaccines. The study aim was to investigate relationship between antibodies and anti-malarial drug treatment outcomes. METHODS: Some 248 children aged 0.5 and 15 years were recruited prior to the high malaria transmission season. Venous blood (5 ml) was obtained from each child...

  5. The Impact of School Based Anti-Malarial Treatment on Adolescents' Cognition: Evidence from a Cluster-Randomized Intervention in Kenya

    Science.gov (United States)

    Gee, Kevin A.

    2010-01-01

    Children's health is an important factor that influences their success in education--poor health, especially when induced by disease, has been linked to poorer cognitive performance, particularly among children across the developing world (Behrman, 1996; UNESCO, 2008; Jukes et al., 2008). One health concern, particularly for sub-Saharan Africa,…

  6. Diagnosis and treatment based on quantitative PCR after controlled human malaria infection

    NARCIS (Netherlands)

    Walk, J.; Schats, R.; Langenberg, M.C.; Reuling, I.J.; Teelen, K.; Roestenberg, M.; Hermsen, C.C.; Visser, L.G.; Sauerwein, R.W.

    2016-01-01

    BACKGROUND: Controlled human malaria infection (CHMI) has become well-established in the evaluation of drugs and vaccines. Anti-malarial treatment is usually initiated when thick blood smears are positive by microscopy. This study explores the effects of using the more sensitive qPCR as the primary

  7. Combined effect of rifampicin-induced P-glycoprotein expression and lipopolysaccharide-induced intestinal sepsis on the effective permeability and pharmacokinetics of an anti-malarial candidate CDRI 97/78 in rats.

    Science.gov (United States)

    Singh, Yeshwant; Hidau, Mahendra Kumar; Krishna, Jampala; Singh, Shio Kumar

    2015-01-01

    1. The study aimed to investigate the influences on the pharmacokinetics (PK) of an anti-malarial drug 97/78 in rats pretreated with orally administered rifampicin and bacterial endotoxin lipopolysaccharide (LPS). 2. In-situ intestinal absorption studies were conducted on rats pretreated with rifampicin and LPS or both to estimate effective permeability (Peff) of 97/78. In-vivo studies were then conducted to explore 97/78 PK profile under these conditions. In-situ studies revealed that Peff value decreased to 64% (2.7 ± 0.6) × 10(-4 )cm/s in rats pretreated with rifampicin. This decrease was further enhanced very significantly to 4.5% (0.19 ± 0.03) × 10(-4 )cm/s in rats pretreated both with rifampicin and LPS (p97/78 in rifampicin-pretreated rats. This decrease was further augmented to 12-fold upon rifampicin and LPS pretreatment. 3. Orally administered rifampicin decreased the concentration of 97/78 in circulation. This decrease was further enhanced significantly to a very low level by LPS-induced intestinal sepsis.

  8. Network meta-analysis of disconnected networks: How dangerous are random baseline treatment effects?

    Science.gov (United States)

    Béliveau, Audrey; Goring, Sarah; Platt, Robert W; Gustafson, Paul

    2017-12-01

    In network meta-analysis, the use of fixed baseline treatment effects (a priori independent) in a contrast-based approach is regularly preferred to the use of random baseline treatment effects (a priori dependent). That is because, often, there is not a need to model baseline treatment effects, which carry the risk of model misspecification. However, in disconnected networks, fixed baseline treatment effects do not work (unless extra assumptions are made), as there is not enough information in the data to update the prior distribution on the contrasts between disconnected treatments. In this paper, we investigate to what extent the use of random baseline treatment effects is dangerous in disconnected networks. We take 2 publicly available datasets of connected networks and disconnect them in multiple ways. We then compare the results of treatment comparisons obtained from a Bayesian contrast-based analysis of each disconnected network using random normally distributed and exchangeable baseline treatment effects to those obtained from a Bayesian contrast-based analysis of their initial connected network using fixed baseline treatment effects. For the 2 datasets considered, we found that the use of random baseline treatment effects in disconnected networks was appropriate. Because those datasets were not cherry-picked, there should be other disconnected networks that would benefit from being analyzed using random baseline treatment effects. However, there is also a risk for the normality and exchangeability assumption to be inappropriate in other datasets even though we have not observed this situation in our case study. We provide code, so other datasets can be investigated. Copyright © 2017 John Wiley & Sons, Ltd.

  9. The malaria testing and treatment landscape in the southern Lao People's Democratic Republic (PDR).

    Science.gov (United States)

    Phanalasy, Saysana

    2017-04-25

    In the context of national and regional goals to eliminate malaria by 2030, the Center for Malaria Parasitology and Entomology in the Lao PDR is implementing strategies to ensure all malaria cases are detected and appropriately treated with first-line artemisinin combination therapy, artemether-lumefantrine (AL). Timely and relevant evidence to inform policies and strategies is needed to ensure the most effective and efficient use of resources, and to accelerate progress towards elimination goals. A 2015 outlet survey conducted in five provinces of the southern Lao PDR was the first of its kind to study the total market for malaria treatments and diagnostics. The sub-national outlet survey was designed to describe the market and to assess public and private sector readiness and performance for malaria case management. Additionally, key indicators were estimated among private outlets within districts with and without a Public Private Mix (PPM) programme. Over half of anti-malarial stockists were public sector (65.1%). In the private sector, pharmacies most commonly stocked anti-malarials, although anti-malarials were also found in private health facilities, drug stores, general retailers, and itinerant drug vendors. Nearly all anti-malarial stocking public health facilities had AL (99.5%) and 90.8% had confirmatory testing. Fewer than half of anti-malarial stocking private outlets stocked AL (40.8%) and malaria testing (43.5%). Chloroquine has not been a first-line treatment for Plasmodium falciparum malaria since 2005 and Plasmodium vivax since 2011 yet private sector availability was 77.6% and chloroquine accounted for 62.2% of the total anti-malarial market share. AL and confirmatory testing availability were higher in private outlets in PPM (68.1, 72.6%) versus non-PPM districts (2.5, 12.1%). Chloroquine was available in 63.6% of PPM and 96.7% of non-PPM-district outlets, and was the most commonly distributed anti-malarial among private outlets in both PPM (61

  10. effect of sorghum seed treatment in burkina faso varies with baseline

    African Journals Online (AJOL)

    ACSS

    or indirectly provide protection against pathogens propagating to high levels in fields showing low baseline yield, low baseline emergence and a strong effect of seed treatments. From the literature of other crops (soybean, sweet corn) a few reports exist of an interaction between trial location and the effect of antifungal seed.

  11. Antibodies to malaria vaccine candidates are associated with chloroquine or sulphadoxine/pyrimethamine treatment efficacy in children in an endemic area of Burkina Faso

    Directory of Open Access Journals (Sweden)

    Diarra Amidou

    2012-03-01

    Full Text Available Abstract Background Patient immune status is thought to affect the efficacy of anti-malarial chemotherapy. This is a subject of some importance, since evidence of immunity-related interactions may influence our use of chemotherapy in populations with drug resistance, as well as assessment of the value of suboptimal vaccines. The study aim was to investigate relationship between antibodies and anti-malarial drug treatment outcomes. Methods Some 248 children aged 0.5 and 15 years were recruited prior to the high malaria transmission season. Venous blood (5 ml was obtained from each child to measure antibody levels to selected malaria antigens, using ELISA. Blood smears were also performed to assess drug efficacy and malaria infection prevalence. Children were actively followed up to record clinical malaria cases. Results IgG levels to MSP3 were always higher in the successfully treated group than in the group with treatment failure. The same observation was made for GLURP but the reverse observation was noticed for MSP1-19. Cytophilic and non-cytophilic antibodies were significantly associated with protection against all three antigens, except for IgG4 to MSP1-19 and GLURP. Conclusion Acquired anti-malarial antibodies may play an important role in the efficacy of anti-malarial drugs in younger children more susceptible to the disease.

  12. Analysis of genetic mutations associated with anti-malarial drug resistance in Plasmodium falciparum from the Democratic Republic of East Timor

    Science.gov (United States)

    de Almeida, Afonso; Arez, Ana Paula; Cravo, Pedro VL; do Rosário, Virgílio E

    2009-01-01

    Background In response to chloroquine (CQ) resistance, the policy for the first-line treatment of uncomplicated malaria in the Democratic Republic of East Timor (DRET) was changed in early 2000. The combination of sulphadoxine-pyrimethamine (SP) was then introduced for the treatment of uncomplicated falciparum malaria. Methods Blood samples were collected in two different periods (2003–2004 and 2004–2005) from individuals attending hospitals or clinics in six districts of the DRET and checked for Plasmodium falciparum infection. 112 PCR-positive samples were inspected for genetic polymorphisms in the pfcrt, pfmdr1, pfdhfr and pfdhps genes. Different alleles were interrogated for potential associations that could be indicative of non-random linkage. Results Overall prevalence of mutations associated with resistance to CQ and SP was extremely high. The mutant form of Pfcrt (76T) was found to be fixed even after five years of alleged CQ removal. There was a significant increase in the prevalence of the pfdhps 437G mutation (X2 = 31.1; p = 0.001) from the first to second survey periods. A non-random association was observed between pfdhfr51/pfdhps437 (p = 0.001) and pfdhfr 59/pfdhps 437 (p = 0.013) alleles. Conclusion Persistence of CQ-resistant mutants even after supposed drug withdrawal suggests one or all of the following: local P. falciparum may still be inadvertently exposed to the drug, that mutant parasites are being "imported" into the country, and/or reduced genetic diversity and low parasite transmission help maintain mutant haplotypes. The association between pfdhfr51/pfdhps437 and pfdhfr 59/pfdhps 437 alleles indicates that these are undergoing concomitant positive selection in the DRET. PMID:19358729

  13. Analysis of an ordinal outcome in a multicentric randomized controlled trial: application to a 3- arm anti- malarial drug trial in Cameroon

    Directory of Open Access Journals (Sweden)

    Gwét Henri

    2010-06-01

    Full Text Available Abstract Background Malaria remains a burden in Sub-Saharan Countries. The strategy proposed by the World Health Organization (WHO is to systematically compare the therapeutic efficacy of antimalarial drugs using as primary outcome for efficacy, a four-category ordered criterion. The objective of the present work was to analyze the treatment effects on this primary outcome taking into account both a center-effect and individual covariates. A three-arm, three-centre trial of Amodiaquine (AQ, sulfadoxine-pyrimethamine (SP and their combination (AQ + SP, conducted by OCEAC-IRD in 2003, in 538 children with uncomplicated Plasmodium falciparum malaria, is used as an illustration. Methods Analyses were based on ordinal regression methods, assuming an underlying continuous latent variable, using either the proportional odds (PO or the proportional hazards (PH models. Different algorithms, corresponding to both frequentist- and bayesian-approaches, were implemented using the freely available softwares R and Winbugs, respectively. The performances of the different methods were evaluated on a simulated data set, and then they were applied on the trial data set. Results Good coverage probability and type-1 error for the treatment effect were achieved. When the methods were applied on the trial data set, results highlighted a significance decrease of SP efficacy when compared to AQ (PO, odds ratio [OR] 0.14, 95% confidence interval [CI] 0.04-0.57; hazard ratio [HR] 0.605, 95% CI 0.42-0.82, and an equal effectiveness between AQ + SP and AQ (PO, odds ratio [OR] 1.70, 95% confidence interval [CI] 0.25-11.44; hazard ratio [HR] 1.40, 95% CI 0.88-2.18. The body temperature was significantly related to the responses. The patient weights were marginally associated to the clinical response. Conclusion The proposed analyses, based on usual statistical packages, appeared adapted to take into account the full information contained in the four categorical outcome in

  14. Evaluation of chloroquine as a potent anti-malarial drug: issues of public health policy and healthcare delivery in post-war Liberia.

    Science.gov (United States)

    Massaquoi, Moses B F; Kennedy, Stephen B

    2003-02-01

    Chloroquine-resistant plasmodium falciparum malaria is a serious public health threat that is spreading rapidly across Sub-Saharan Africa. It affects over three quarters (80%) of malarial endemic countries. Of the estimated 300-500 million cases of malaria reported annually, the vast majority of malarial-related morbidities occur among young children in Africa, especially those concentrated in the remote rural areas with inadequate access to appropriate health care services. In Liberia, in vivo studies conducted between 1993 and 2000 observed varying degrees of plasmodium falciparum malaria infections that were resistant to chloroquine, including sulfadiazine-pyrimethamine. As the country emerges from a prolonged civil war, the health care delivery system may not be adequately prepared to implement an effective nation-wide malarial control strategy. As a result, the management of uncomplicated malaria in Liberia poses a significant public health challenge for the government-financed health care delivery system. Therefore, based on extensive literature review, we report the failure of chloroquine as an effective first-line drug for the treatment of uncomplicated plasmodium falciparum malaria in Liberia and recommend that national health efforts be directed at identifying alternative drug(s) to replace it.

  15. Improvements in access to malaria treatment in Tanzania following community, retail sector and health facility interventions -- a user perspective

    Directory of Open Access Journals (Sweden)

    Obrist Brigit

    2010-06-01

    Full Text Available Abstract Background The ACCESS programme aims at understanding and improving access to prompt and effective malaria treatment. Between 2004 and 2008 the programme implemented a social marketing campaign for improved treatment-seeking. To improve access to treatment in the private retail sector a new class of outlets known as accredited drug dispensing outlets (ADDO was created in Tanzania in 2006. Tanzania changed its first-line treatment for malaria from sulphadoxine-pyrimethamine (SP to artemether-lumefantrine (ALu in 2007 and subsidized ALu was made available in both health facilities and ADDOs. The effect of these interventions on understanding and treatment of malaria was studied in rural Tanzania. The data also enabled an investigation of the determinants of access to treatment. Methods Three treatment-seeking surveys were conducted in 2004, 2006 and 2008 in the rural areas of the Ifakara demographic surveillance system (DSS and in Ifakara town. Each survey included approximately 150 people who had suffered a fever case in the previous 14 days. Results Treatment-seeking and awareness of malaria was already high at baseline, but various improvements were seen between 2004 and 2008, namely: better understanding causes of malaria (from 62% to 84%; an increase in health facility attendance as first treatment option for patients older than five years (27% to 52%; higher treatment coverage with anti-malarials (86% to 96% and more timely use of anti-malarials (80% to 93-97% treatments taken within 24 hrs. Unfortunately, the change of treatment policy led to a low availability of ALu in the private sector and, therefore, to a drop in the proportion of patients taking a recommended malaria treatment (85% to 53%. The availability of outlets (health facilities or drug shops is the most important determinant of whether patients receive prompt and effective treatment, whereas affordability and accessibility contribute to a lesser extent. Conclusions An

  16. Poisoning by anti-malarial drugs

    African Journals Online (AJOL)

    and tinnitus, a david@tibbutt.co.uk. 1 Chloroquine is a 4-aminoquinolone and comes as a number of salts mainly the phosphate and sulphate. Vasodilatation. •. (flushing sensation more obvious in a pale skin). This may be exacerbated by the vasodilatation caused by the malaria itself and so cause postural (orthostatic) ...

  17. Plasmodium falciparum proteome changes in response to doxycycline treatment.

    Science.gov (United States)

    Briolant, Sébastien; Almeras, Lionel; Belghazi, Maya; Boucomont-Chapeaublanc, Elodie; Wurtz, Nathalie; Fontaine, Albin; Granjeaud, Samuel; Fusaï, Thierry; Rogier, Christophe; Pradines, Bruno

    2010-05-25

    The emergence of Plasmodium falciparum resistance to most anti-malarial compounds has highlighted the urgency to develop new drugs and to clarify the mechanisms of anti-malarial drugs currently used. Among them, doxycycline is used alone for malaria chemoprophylaxis or in combination with quinine or artemisinin derivatives for malaria treatment. The molecular mechanisms of doxycycline action in P. falciparum have not yet been clearly defined, particularly at the protein level. A proteomic approach was used to analyse protein expression changes in the schizont stage of the malarial parasite P. falciparum following doxycycline treatment. A comparison of protein expression between treated and untreated protein samples was performed using two complementary proteomic approaches: two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and isobaric tagging reagents for relative and absolute quantification (iTRAQ). After doxycycline treatment, 32 and 40 P. falciparum proteins were found to have significantly deregulated expression levels by 2D-DIGE and iTRAQ methods, respectively. Although some of these proteins have been already described as being deregulated by other drug treatments, numerous changes in protein levels seem to be specific to doxycycline treatment, which could perturb apicoplast metabolism. Quantitative reverse transcription polymerase chain reaction (RT-PCR) was performed to confirm this hypothesis. In this study, a specific response to doxycycline treatment was distinguished and seems to involve mitochondrion and apicoplast organelles. These data provide a starting point for the elucidation of drug targets and the discovery of mechanisms of resistance to anti-malarial compounds.

  18. One session treatment for pediatric blood-injection-injury phobia: A controlled multiple baseline trial.

    Science.gov (United States)

    Oar, Ella L; Farrell, Lara J; Waters, Allison M; Conlon, Elizabeth G; Ollendick, Thomas H

    2015-10-01

    The present study evaluated the effectiveness of a modified One Session Treatment (OST), which included an e-therapy homework maintenance program over 4 weeks for Blood-Injection-Injury (BII) phobia in children and adolescents. Using a single case, non-concurrent multiple-baseline design, 24 children and adolescents (8-18 years; 7 males, 17 females) with a primary diagnosis of BII phobia were randomly assigned to a one, two or three week baseline prior to receiving OST. Primary outcome measures included diagnostic severity, diagnostic status, and child and parent fear ratings. Secondary outcome measures included avoidance during behavioural avoidance tasks (BAT), global functioning and self and parent reported anxiety, fear and depression. Efficacy was assessed at post-treatment, 1-month, and 3-month follow-up. BII symptoms and diagnostic severity remained relatively stable during the baseline periods and then significantly improved following implementation of the intervention. Treatment response was supported by changes across multiple measures, including child, parent and independent clinician ratings. At post-treatment 8 of the 24 (33.33%) children were BII diagnosis free. Treatment gains improved at follow-ups with 14 (58.33%) children diagnosis free at 1-month follow-up and 15 (62.5%) diagnosis free at 3-month follow-up. Preliminary findings support the effectiveness of a modified OST approach for BII phobic youth with treatment outcomes improving over follow-up intervals. Copyright © 2015 Elsevier Ltd. All rights reserved.

  19. Baseline carcinoembryonic antigen (CEA) serum levels predict bevacizumab-based treatment response in metastatic colorectal cancer

    Science.gov (United States)

    Prager, Gerald W; Braemswig, Kira H; Martel, Alexandra; Unseld, Matthias; Heinze, Georg; Brodowicz, Thomas; Scheithauer, Werner; Kornek, Gabriela; Zielinski, Christoph C

    2014-01-01

    Carcinoembryonic antigen (CEA) affects tumorigenesis by enhancing tumor cell survival and by inducing tumor angiogenesis. This study aimed to evaluate baseline CEA serum levels to predict bevacizumab-based therapy effect and survival in patients with metastatic colorectal cancer (mCRC). Two hundred and ninety eight mCRC patients receiving chemotherapy plus either bevacizumab or cetuximab were analyzed in a retrospective study. Disease control (DC), progression-free survival (PFS), and overall survival were assessed and related to pretreatment CEA serum levels. Patients with baseline CEA serum levels below the statistical median of 26.8 ng/mL (group I) were compared with patients with higher CEA levels (group II). The cetuximab-based treatment cohort was analyzed for specificity assessment of CEA to predict the anti-vascular endothelial growth factor effect in mCRC. Baseline CEA serum levels inversely correlated with therapeutic response in patients receiving bevacizumab-based treatment (disease control rate, 84% vs 60%), inversely correlated with median PFS leading to a median PFS benefit of 2.1 months for patients in group I when compared with group II, as well as inversely correlated with median overall survival (37.5 months vs 21.4 months). In an independent cohort of 129 patients treated with cetuximab-based therapy, no association of therapeutic response or PFS with CEA serum levels was found. As expected, baseline CEA levels were prognostic for mCRC. These data give first evidence that baseline serum CEA levels might constitute an important predictor for the efficacy of first-line bevacizumab-based therapy in patients with mCRC. Previously, we found that CEA induces angiogenesis independent of VEGF. The data presented here now give first evidence that baseline serum CEA levels in patients might constitute an important predictor for the efficacy of first-line bevacizumab-based therapy for metastatic colorectal cancer. PMID:24850362

  20. The malaria testing and treatment landscape in mainland Tanzania, 2016.

    Science.gov (United States)

    Michael, Daniel; Mkunde, Sigsbert Patila

    2017-04-24

    Understanding the key characteristics of malaria testing and treatment is essential to the control of a disease that continues to pose a major risk of morbidity and mortality in mainland Tanzania, with evidence of a resurgence of the disease in recent years. The introduction of artemisinin combination therapy (ACT) as the first-line treatment for malaria, alongside policies to promote rational case management following testing, highlights the need for evidence of anti-malarial and testing markets in the country. The results of the most recent mainland Tanzania ACTwatch outlet survey are presented here, including data on the availability, market share and price of anti-malarials and malaria diagnosis in 2016. A nationally-representative malaria outlet survey was conducted between 18th May and 2nd July, 2016. A census of public and private outlets with potential to distribute malaria testing and/or treatment was conducted among a representative sample of administrative units. An audit was completed for all anti-malarials, malaria rapid (RDT) diagnostic tests and microscopy. A total of 5867 outlets were included in the nationally representative survey, across both public and private sectors. In the public sector, availability of malaria testing was 92.3% and quality-assured (QA) ACT was 89.1% among all screened outlets. Sulfadoxine-pyrimethamine (SP) was stocked by 51.8% of the public sector and injectable artesunate was found in 71.4% of all screened public health facilities. Among anti-malarial private-sector stockists, availability of testing was 15.7, and 65.1% had QA ACT available. The public sector accounted for 83.4% of the total market share for malaria diagnostics. The private sector accounted for 63.9% of the total anti-malarial market, and anti-malarials were most commonly distributed through accredited drug dispensing outlets (ADDOs) (39.0%), duka la dawa baridi (DLDBs) (13.3%) and pharmacies (6.7%). QA ACT comprised 33.1% of the national market share (12

  1. Baseline Predictors of Treatment Outcomes in Children With Multidrug-Resistant Tuberculosis: A Retrospective Cohort Study.

    Science.gov (United States)

    Chiang, Silvia S; Starke, Jeffrey R; Miller, Ann C; Cruz, Andrea T; Del Castillo, Hernán; Valdivia, William José; Tunque, Gabriela; García, Fanny; Contreras, Carmen; Lecca, Leonid; Alarcón, Valentina A; Becerra, Mercedes C

    2016-10-15

    Globally, >30 000 children fall sick with multidrug-resistant (MDR) tuberculosis every year. Without robust pediatric data, clinical management follows international guidelines that are based on studies in adults and expert opinion. We aimed to identify baseline predictors of death, treatment failure, and loss to follow-up among children with MDR tuberculosis disease treated with regimens tailored to their drug susceptibility test (DST) result or to the DST result of a source case. This retrospective cohort study included all children ≤15 years old with confirmed and probable MDR tuberculosis disease who began tailored regimens in Lima, Peru, between 2005 and 2009. Using logistic regression, we examined associations between baseline patient and treatment characteristics and (1) death or treatment failure and (2) loss to follow-up. Two hundred eleven of 232 (90.9%) children had known treatment outcomes, of whom 163 (77.2%) achieved cure or probable cure, 29 (13.7%) were lost to follow-up, 10 (4.7%) experienced treatment failure, and 9 (4.3%) died. Independent baseline predictors of death or treatment failure were the presence of severe disease (adjusted odds ratio [aOR], 4.96; 95% confidence interval [CI], 1.61-15.26) and z score ≤-1 (aOR, 3.39; 95% CI, 1.20-9.54). We did not identify any independent predictors of loss to follow-up. High cure rates can be achieved in children with MDR tuberculosis using tailored regimens containing second-line drugs. However, children faced significantly higher risk of death or treatment failure if they had severe disease or were underweight. These findings highlight the need for early interventions that can improve treatment outcomes for children with MDR tuberculosis. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  2. Baseline ALT levels as a marker of glycemic response to treatment with GLP-1 receptor agonists.

    Science.gov (United States)

    Gimeno-Orna, Jose A; Verdes-Sanz, Guayente; Borau-Maorad, Laura; Campos-Fernández, Julia; Lardiés-Sánchez, Beatriz; Monreal-Villanueva, Marta

    2016-04-01

    This study aimed to assess if ALT levels, as a marker of non-alcoholic fatty liver disease, may predict HbA1c response to treatment with GLP-1 receptor agonists (GLP-1 RAs). A retrospective, longitudinal, analytical study was conducted including patients with type 2 diabetes mellitus continuously treated with GLP-1 agonists (85% with liraglutide) for one year. Patients were divided into two groups according to baseline ALT levels, with 24 U/L (the median of the distribution) as the cut-off point. The dependent variable was HbA1c change (one-year follow-up minus baseline). The predictive value of ALT levels above 24 U/L and ALT change was analyzed using multivariate linear regression adjusted to age, gender, diabetes duration, type and dose of GLP-1 RA, baseline HbA1c, baseline body mass index (BMI), and change in BMI. A total of 117 patients (48% females) aged 58.6 (SD 9.6) years were enrolled into the study. Treatment was associated with a change in ALT of -4.3 U/L (p=0.041) and a change in HbA1c of -1.1% (pALT (-9.25 vs 0.46 U/L; p=0.002) were significantly higher in patients with ALT levels above the median. In the multivariate analysis, both ALT>24 U/L (b=-0.74; 95%CI: -1.31 to -0.18; p=0.011) and ALT change (b=0.028; 95%CI: 0.010 to 0.046; p=0.003), were significant response predictors. Elevated baseline transaminase values and decreased transaminase levels during follow-up are associated to a favorable glycemic response to GLP-1 RAs. Copyright © 2016 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

  3. Does baseline hematocrit influence the assays of on-treatment platelet reactivity to clopidogrel?

    Science.gov (United States)

    Pendyala, Lakshmana K; Loh, Joshua P; Lhermusier, Thibault; Minha, Sa'ar; Magalhaes, Marco A; Torguson, Rebecca; Chen, Fang; Satler, Lowell F; Pichard, Augusto D; Waksman, Ron

    2014-10-01

    High on-treatment platelet reactivity (HTPR) has been shown to be associated with adverse cardiac events in patients undergoing percutaneous coronary intervention, but the effect of baseline hematologic parameters upon platelet reactivity remains controversial. The present study aims to evaluate the impact of hematocrit on 2 different assay methods used to assess on-treatment platelet reactivity to clopidogrel. We tested clopidogrel on-treatment platelet reactivity in 466 consecutive patients using VerifyNow P2Y12 (VN) and light transmission aggregometry (LTA) with adenosine diphosphate (ADP) 5 and 20 μM assays 6 to 24 hours after percutaneous coronary intervention. Patients were categorized into 4 groups according to baseline hematocrit. One-year major adverse cardiac events, including death, nonfatal myocardial infarction, and definite stent thrombosis, were collected. Lower hematocrit was associated with higher P2Y12 reaction unit (PRU) and a higher rate of HTPR (P hematocrit was independently associated with PRU ≥208 (odds ratio [OR] 0.92, 95% CI 0.86-0.97, P = .005) but had no correlation with LTA ADP 5 μM ≥46% (OR 1.0, 95% CI 0.95-1.06, P = .88) or LTA ADP 20 μM ≥59% (OR 1.03, 95% CI 0.97-1.09, P = .39). In a logistic regression model, the addition of VN assay results, hematocrit, and interaction between the hematocrit and assay results had shown a significant influence on the area under curve for prediction of 1-year major adverse cardiac events compared with baseline clinical variables only for PRU (0.63 vs 0.76, P = .006) but not with LTA (0.64 vs 0.74, P = .13). Baseline hematocrit has a differential influence on results of the ex vivo platelet functional assays. Lower baseline hematocrit was independently associated with HTPR by VN but not LTA. This may affect the interpretation of platelet function testing in patients with significant anemia. Copyright © 2014 Mosby, Inc. All rights reserved.

  4. Economic evaluation of artesunate and three quinine regimens in the treatment of severe malaria in children at the Ebolowa Regional Hospital-Cameroon: a cost analysis.

    Science.gov (United States)

    Maka, Daniel Ethe; Chiabi, Andreas; Obadeyi, Bolaji; Mah, Evelyn; Nguefack, Séraphin; Nana, Pamela; Mbacham, Wilfred; Mbonda, Elie

    2016-12-07

    Severe malaria is a leading cause of morbidity and mortality in under-fives in sub-Saharan Africa. Recently quinine has been replaced by artesunate as the first-line drug in the treatment of severe malaria in Cameroon. Artesunate has been shown to be cost-effective in African children, but whether these findings are transferable to Cameroonian children remains to be explored. To conduct a cost-analysis of four different regimens used in the treatment from the perspective of the healthcare payer. An economic evaluation alongside a randomized comparative study was conducted in children aged 3 months to 15 years, admitted at the Ebolowa Regional Hospital with severe malaria due to Plasmodium falciparum. Patients were randomized to receive one of the four treatment alternatives. Group 1 (ARTES) received parenteral artesunate at 2.4 mg/kg at H 0 , H 12 , H 24 and then once daily; Group 2 (QLD) received a loading dose of quinine base at 16.6 mg/kg followed 8 h later by an 8-hourly maintenance dose of 8.3 mg/kg quinine base; Group 3 (QNLD3) received 8.3 mg/kg quinine base every 8 h, and Group 4 (QNLD2) received 12.5 mg/kg quinine base every 12 h. The main outcome measure for effectiveness of treatment was the parasite reduction rate. Based on a healthcare perspective, an evaluation of direct medical costs was done, including costs of anti-malarials, nursing care materials, adjuvant treatment, laboratory investigations, hospitalisation and professional fees. Guided by a cost minimalization approach, the relative costs of these treatment alternatives was compared and reported. Overall cost was higher for ARTES group at $65.14 (95% CI $57.68-72.60) than for quinine groups ($52.49-$62.40), but the difference was not statistically significant. Cost of the anti-malarial drug was significantly higher for artesunate-treated patients than for quinine-treated patients, whereas cost of hospitalization was significantly lower for artesunate-treated patients than for quinine

  5. Characteristics of Treatment Seeking Finnish Pathological Gamblers: Baseline Data from a Treatment Study

    Science.gov (United States)

    Lahti, Tuuli; Halme, Jukka; Pankakoski, Maiju; Sinclair, David; Alho, Hannu

    2013-01-01

    This article describes the socio-demographic characteristics and gambling behavior of 39 pathological gamblers who participated in our treatment study in 2009. The inclusion criteria of the study were: score of five or more on both the South Oaks Gambling Screen (SOGS) and a pathological gambling screen based on the Diagnostic and Statistical…

  6. Visual field progression in the Collaborative Initial Glaucoma Treatment Study the impact of treatment and other baseline factors.

    Science.gov (United States)

    Musch, David C; Gillespie, Brenda W; Lichter, Paul R; Niziol, Leslie M; Janz, Nancy K

    2009-02-01

    To evaluate factors associated with visual field (VF) progression, using all available follow-up through 9 years after treatment initiation, in the Collaborative Initial Glaucoma Treatment Study (CIGTS). Longitudinal follow-up of participants enrolled in a randomized clinical trial. Six hundred seven newly diagnosed glaucoma patients. In a randomized clinical trial, 607 subjects with newly diagnosed open-angle glaucoma initially were treated with either medication or trabeculectomy. After treatment initiation and early follow-up, subjects were evaluated clinically at 6-month intervals. Study participants in both arms of the CIGTS were treated aggressively in an effort to reduce intraocular pressure (IOP) to a level at or below a predetermined, eye-specific target pressure. Visual field progression was analyzed using repeated measures models. Visual field progression, measured by Humphrey 24-2 full-threshold testing and assessed by the change in the mean deviation (MD), and an indicator of substantial worsening of the VF (MD decrease of > or =3 dB from baseline), assessed at each follow-up visit. Follow-up indicated minimal change from baseline in each initial treatment group's average MD. However, at the 8-year follow-up examination, substantial worsening (> or =3 dB) of MD from baseline was found in 21.3% and 25.5% of the initial surgery and initial medicine groups, respectively. The effect of initial treatment on subsequent VF loss was modified by time (Ppresentation, but detrimental for patients with diabetes, are noteworthy and warrant independent confirmation. The author(s) have no proprietary or commercial interest in any materials discussed in this article.

  7. Malaria diagnostic testing and treatment practices in three different Plasmodium falciparum transmission settings in Tanzania: before and after a government policy change

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    Bousema Teun

    2011-04-01

    Full Text Available Abstract Background Patterns of decreasing malaria transmission intensity make presumptive treatment of malaria an unjustifiable approach in many African settings. The controlled use of anti-malarials after laboratory confirmed diagnosis is preferable in low endemic areas. Diagnosis may be facilitated by malaria rapid diagnostic tests (RDTs. In this study, the impact of a government policy change, comprising the provision of RDTs and advice to restrict anti-malarial treatment to RDT-positive individuals, was assessed by describing diagnostic behaviour and treatment decision-making in febrile outpatients Methods Prospective data from Biharamulo and Rubya Designated District Hospital (DDH were collected before and after policy change, in Sumve DDH no new policy was implemented. Diagnosis of malaria was confirmed by RDT; transmission intensity was evaluated by a serological marker of malaria exposure in hospital attendees. Results Prior to policy change, there was no evident association between the actual level of transmission intensity and drug-prescribing behaviour. After policy change, there was a substantial decrease in anti-malarial prescription and an increase in prescription of antibiotics. The proportion of parasite-negative individuals who received anti-malarials decreased from 89.1% (244/274 to 38.7% (46/119 in Biharamulo and from 76.9% (190/247 to 10.0% (48/479 in Rubya after policy change. Conclusion This study shows that an official policy change, where RDTs were provided and healthcare providers were advised to adhere to RDT results in prescribing drugs can be followed by more rational drug-prescribing behaviour. The current findings are promising for improving treatment policy in Tanzanian hospitals.

  8. Baseline results of the first malaria indicator survey in Iran at the health facility level

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    Taghizadeh-Asl Rahim

    2011-10-01

    Full Text Available Abstract Background Malaria continues to be a global public health challenge, particularly in developing countries. Delivery of prompt and effective diagnosis and treatment of malaria cases, detection of malaria epidemics within one week of onset and control them in less than a month, regular disease monitoring and operational classification of malaria are among the major responsibilities of the national malaria programme. The study was conducted to determine these indicators at the different level of primary health care facilities in malaria-affected provinces of Iran Methods In this survey, data was collected from 223 health facilities including health centres, malaria posts, health houses and hospitals as well as the profile of all 5, 836 recorded malaria cases in these facilities during the year preceding the survey. Descriptive statistics (i.e. frequencies, percentages were used to summarize the results and Chi square test was used to analyse data. Results All but one percent of uncomplicated cases took appropriate and correctly-dosed of anti-malarial drugs in accordance to the national treatment guideline. A larger proportion of patients [85.8%; 95% CI: 84.8 - 86.8] were also given complete treatment including anti-relapse course, in line with national guidelines. About one third [35.0%; 95% CI: 33.6 - 36.4] of uncomplicated malaria cases were treated more than 48 hours after first symptoms onset. Correspondingly, half of severe malaria cases took recommended anti-malarial drugs for severe or complicated disease more than 48 hours of onset of first symptoms. The latter cases had given regular anti-malarial drugs promptly. The majority of malaria epidemics [97%; 95% CI: 90.6 - 100] in study areas were detected within one week of onset, but only half of epidemics were controlled within four weeks of detection. Just half of target districts had at least one health facility/emergency site with adequate supply and equipment stocks. Nevertheless

  9. Malaria case management in Papua New Guinea prior to the introduction of a revised treatment protocol.

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    Pulford, Justin; Mueller, Ivo; Siba, Peter M; Hetzel, Manuel W

    2012-05-07

    This study aimed to document malaria case management practices in Papua New Guinea prior to the introduction of a revised national malaria treatment protocol. The revised protocol stipulates routine testing of malaria infection by rapid diagnostic test or microscopy, anti-malarial prescription to test positive cases only, and the introduction of a new artemisinin-based first-line anti-malarial. Findings presented in this paper primarily focus on diagnostic, prescription and treatment counselling practices. In a national cross-sectional survey of 79 randomly selected health facilities, data were collected via non-participant observation of the clinical case management of patients presenting with fever or a recent history of fever. Data were recorded on a structured clinical observation instrument. Overall, 15% of observed fever patients (n=468) were tested for malaria infection by rapid diagnostic test and a further 3.6% were tested via microscopy. An anti-malarial prescription was made in 96.4% (451/468) of cases, including 100% (17/17) of test positive cases and 82% (41/50) of test negative cases. In all, 79.8% of anti-malarial prescriptions conformed to the treatment protocol current at the time of data collection. The purpose of the prescribed medication was explained to patients in 63.4% of cases, dosage/regimen instructions were provided in 75.7% of cases and the possibility of adverse effects and what they might look like were discussed in only 1.1% of cases. The revised national malaria treatment protocol will require a substantial change in current clinical practice if it is to be correctly implemented and adhered to. Areas that will require the most change include the shift from presumptive to RDT/microscopy confirmed diagnosis, prescribing (or rather non-prescribing) of anti-malarials to patients who test negative for malaria infection, and the provision of thorough treatment counselling. A comprehensive clinician support programme, possibly inclusive of

  10. Can treatment of malaria be restricted to parasitologically confirmed malaria? A school-based study in Benin in children with and without fever

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    Ouendo Edgard

    2010-04-01

    Full Text Available Abstract Background Applying the switch from presumptive treatment of malaria to new policies of anti-malarial prescriptions restricted to parasitologically-confirmed cases is a still unsolved challenge. Pragmatic studies can provide data on consequences of such a switch. In order to assess whether restricting anti-malarials to rapid diagnostic test (RDT-confirmed cases in children of between five and 15 years of age is consistent with an adequate management of fevers, a school-based study was performed in Allada, Benin. Methods Children in the index group (with fever and a negative RDT and the matched control group (without fever and a negative RDT were not prescribed anti-malarials and actively followed-up during 14 days. Blood smears were collected at each assessment. Self-medication with chloroquine and quinine was assessed with blood spots. Malaria attacks during the follow-up were defined by persistent or recurrent fever concomitant to a positive malaria test. Results 484 children were followed-up (242 in each group. At day 3, fever had disappeared in 94% of children from the index group. The incidence of malaria was similar (five cases in the index group and seven cases in the control group between groups. Self-medication with chloroquine and quinine in this cohort was uncommon. Conclusions Applying a policy of restricting anti-malarials to RDT-confirmed cases is consistent with an adequate management of fevers in this population. Further studies on the management of fever in younger children are of upmost importance.

  11. Anti-bacterial activity of intermittent preventive treatment of malaria in pregnancy: comparative in vitro study of sulphadoxine-pyrimethamine, mefloquine, and azithromycin

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    Mombo-Ngoma Ghyslain

    2010-10-01

    Full Text Available Abstract Background Intermittent preventive treatment of malaria with sulphadoxine-pyrimethamine (SP is recommended for the prevention of malaria in pregnancy in sub-Saharan Africa. Increasing drug resistance necessitates the urgent evaluation of alternative drugs. Currently, the most promising candidates in clinical development are mefloquine and azithromycin. Besides the anti-malarial activity, SP is also a potent antibiotic and incurs significant anti-microbial activity when given as IPTp - though systematic clinical evaluation of this action is still lacking. Methods In this study, the intrinsic anti-bacterial activity of mefloquine and azithromycin was assessed in comparison to sulphadoxine-pyrimethamine against bacterial pathogens with clinical importance in pregnancy in a standard microdilution assay. Results SP was highly active against Staphylococcus aureus and Streptococcus pneumoniae. All tested Gram-positive bacteria, except Enterococcus faecalis, were sensitive to azithromycin. Additionally, azithromycin was active against Neisseria gonorrhoeae. Mefloquine showed good activity against pneumococci but lower in vitro action against all other tested pathogens. Conclusion These data indicate important differences in the spectrum of anti-bacterial activity for the evaluated anti-malarial drugs. Given the large scale use of IPTp in Africa, the need for prospective clinical trials evaluating the impact of antibiotic activity of anti-malarials on maternal and foetal health and on the risk of promoting specific drug resistance of bacterial pathogens is discussed.

  12. Improvements in access to malaria treatment in Tanzania after switch to artemisinin combination therapy and the introduction of accredited drug dispensing outlets - a provider perspective

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    Dillip Angel

    2010-06-01

    Full Text Available Abstract Background To improve access to treatment in the private retail sector a new class of outlets known as accredited drug dispensing outlets (ADDO was created in Tanzania. Tanzania changed its first-line treatment for malaria from sulphadoxine-pyrimethamine (SP to artemether-lumefantrine (ALu in 2007. Subsidized ALu was made available in both health facilities and ADDOs. The effect of these interventions on access to malaria treatment was studied in rural Tanzania. Methods The study was carried out in the villages of Kilombero and Ulanga Demographic Surveillance System (DSS and in Ifakara town. Data collection consisted of: 1 yearly censuses of shops selling drugs; 2 collection of monthly data on availability of anti-malarials in public health facilities; and 3 retail audits to measure anti-malarial sales volumes in all public, mission and private outlets. The data were complemented with DSS population data. Results Between 2004 and 2008 access to malaria treatment greatly improved and the number of anti-malarial treatment doses dispensed increased by 78%. Particular improvements were observed in the availability (from 0.24 shops per 1,000 people in 2004 to 0.39 in 2008 and accessibility (from 71% of households within 5 km of a shop in 2004 to 87% in 2008 of drug shops. Despite no improvements in affordability this resulted in an increase of the market share from 49% of anti-malarial sales 2005 to 59% in 2008. The change of treatment policy from SP to ALu led to severe stock-outs of SP in health facilities in the months leading up to the introduction of ALu (only 40% months in stock, but these were compensated by the wide availability of SP in shops. After the introduction of ALu stock levels of the drug were relatively high in public health facilities (over 80% months in stock, but the drug could only be found in 30% of drug shops and in no general shops. This resulted in a low overall utilization of the drug (19% of all anti-malarial

  13. Epidemiological and Clinical Baseline Characteristics as Predictive Biomarkers of Response to Anti-VEGF Treatment in Patients with Neovascular AMD

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    Miltiadis K. Tsilimbaris

    2016-01-01

    Full Text Available Purpose. To review the current literature investigating patient response to antivascular endothelial growth factor-A (VEGF therapy in the treatment of neovascular age-related macular degeneration (nAMD and to identify baseline characteristics that might predict response. Method. A literature search of the PubMed database was performed, using the keywords: AMD, anti-VEGF, biomarker, optical coherence tomography, treatment outcome, and predictor. The search was limited to articles published from 2006 to date. Exclusion criteria included phase 1 trials, case reports, studies focusing on indications other than nAMD, and oncology. Results. A total of 1467 articles were identified, of which 845 were excluded. Of the 622 remaining references, 47 met all the search criteria and were included in this review. Conclusion. Several baseline characteristics correlated with anti-VEGF treatment response, including best-corrected visual acuity, age, lesion size, and retinal thickness. The majority of factors were associated with disease duration, suggesting that longer disease duration before treatment results in worse treatment outcomes. This highlights the need for early treatment for patients with nAMD to gain optimal treatment outcomes. Many of the identified baseline characteristics are interconnected and cannot be evaluated in isolation; therefore multivariate analyses will be required to determine any specific relationship with treatment response.

  14. The influence of baseline marijuana use on treatment of cocaine dependence: application of an informative-priors Bayesian approach.

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    Charles eGreen

    2012-10-01

    Full Text Available Background: Marijuana use is prevalent among patients with cocaine dependence and often non-exclusionary in clinical trials of potential cocaine medications. The dual-focus of this study was to (1 examine the moderating effect of baseline marijuana use on response to treatment with levodopa/carbidopa for cocaine dependence; and (2 apply an informative-priors, Bayesian approach for estimating the probability of a subgroup-by-treatment interaction effect.Method: A secondary data analysis of two previously published, double-blind, randomized controlled trials provided samples for the historical dataset (Study 1: N = 64 complete observations and current dataset (Study 2: N = 113 complete observations. Negative binomial regression evaluated Treatment Effectiveness Scores (TES as a function of medication condition (levodopa/carbidopa, placebo, baseline marijuana use (days in past 30, and their interaction. Results: Bayesian analysis indicated that there was a 96% chance that baseline marijuana use predicts differential response to treatment with levodopa/carbidopa. Simple effects indicated that among participants receiving levodopa/carbidopa the probability that baseline marijuana confers harm in terms of reducing TES was 0.981; whereas the probability that marijuana confers harm within the placebo condition was 0.163. For every additional day of marijuana use reported at baseline, participants in the levodopa/carbidopa condition demonstrated a 5.4% decrease in TES; while participants in the placebo condition demonstrated a 4.9% increase in TES.Conclusion: The potential moderating effect of marijuana on cocaine treatment response should be considered in future trial designs. Applying Bayesian subgroup analysis proved informative in characterizing this patient-treatment interaction effect.

  15. Baseline psychophysiological and cortisol reactivity as a predictor of PTSD treatment outcome in virtual reality exposure therapy.

    Science.gov (United States)

    Norrholm, Seth Davin; Jovanovic, Tanja; Gerardi, Maryrose; Breazeale, Kathryn G; Price, Matthew; Davis, Michael; Duncan, Erica; Ressler, Kerry J; Bradley, Bekh; Rizzo, Albert; Tuerk, Peter W; Rothbaum, Barbara O

    2016-07-01

    Baseline cue-dependent physiological reactivity may serve as an objective measure of posttraumatic stress disorder (PTSD) symptoms. Additionally, prior animal model and psychological studies would suggest that subjects with greatest symptoms at baseline may have the greatest violation of expectancy to danger when undergoing exposure based psychotherapy; thus treatment approaches which enhanced the learning under these conditions would be optimal for those with maximal baseline cue-dependent reactivity. However methods to study this hypothesis objectively are lacking. Virtual reality (VR) methodologies have been successfully employed as an enhanced form of imaginal prolonged exposure therapy for the treatment of PTSD. Our goal was to examine the predictive nature of initial psychophysiological (e.g., startle, skin conductance, heart rate) and stress hormone responses (e.g., cortisol) during presentation of VR-based combat-related stimuli on PTSD treatment outcome. Combat veterans with PTSD underwent 6 weeks of VR exposure therapy combined with either d-cycloserine (DCS), alprazolam (ALP), or placebo (PBO). In the DCS group, startle response to VR scenes prior to initiation of treatment accounted for 76% of the variance in CAPS change scores, p < 0.001, in that higher responses predicted greater changes in symptom severity over time. Additionally, baseline cortisol reactivity was inversely associated with treatment response in the ALP group, p = 0.04. We propose that baseline cue-activated physiological measures will be sensitive to predicting patients' level of response to exposure therapy, in particular in the presence of enhancement (e.g., DCS). Published by Elsevier Ltd.

  16. Plasmodium falciparum proteome changes in response to doxycycline treatment

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    Fusaï Thierry

    2010-05-01

    Full Text Available Abstract Background The emergence of Plasmodium falciparum resistance to most anti-malarial compounds has highlighted the urgency to develop new drugs and to clarify the mechanisms of anti-malarial drugs currently used. Among them, doxycycline is used alone for malaria chemoprophylaxis or in combination with quinine or artemisinin derivatives for malaria treatment. The molecular mechanisms of doxycycline action in P. falciparum have not yet been clearly defined, particularly at the protein level. Methods A proteomic approach was used to analyse protein expression changes in the schizont stage of the malarial parasite P. falciparum following doxycycline treatment. A comparison of protein expression between treated and untreated protein samples was performed using two complementary proteomic approaches: two-dimensional fluorescence difference gel electrophoresis (2D-DIGE and isobaric tagging reagents for relative and absolute quantification (iTRAQ. Results After doxycycline treatment, 32 and 40 P. falciparum proteins were found to have significantly deregulated expression levels by 2D-DIGE and iTRAQ methods, respectively. Although some of these proteins have been already described as being deregulated by other drug treatments, numerous changes in protein levels seem to be specific to doxycycline treatment, which could perturb apicoplast metabolism. Quantitative reverse transcription polymerase chain reaction (RT-PCR was performed to confirm this hypothesis. Conclusions In this study, a specific response to doxycycline treatment was distinguished and seems to involve mitochondrion and apicoplast organelles. These data provide a starting point for the elucidation of drug targets and the discovery of mechanisms of resistance to anti-malarial compounds.

  17. Rorschach Inkblot Method data at baseline and after 2 years treatment of consecutively admitted patients with first-episode schizophrenia

    DEFF Research Database (Denmark)

    Rosenbaum, Bent; Andersen, Palle Bent; Knudsen, Per Bjerregaard

    2012-01-01

    Background: The Rorschach Inkblot Method is regarded as an important clinical instrument for detailed diagnostic description of the integrative capacities of individuals in psychotic states and as an instrument for measuring progression in the course of treatment. Aims: To describe relevant...... Rorschach variables at baseline in a group of consecutively admitted patients with first-episode schizophrenia. Furthermore, to describe the changes in these variables from baseline to year 2 for the group of patients given psychiatric standard treatment, and to compare these changes with changes in other...... outcome measures [Positive and Negative Syndrome Scale (PANSS), Global Assessment of Functioning (GAF), Strauss-Carpenter and socio-demographic variables]. Methods: In a prospective study, 34 patients consecutively admitted to treatment for a first episode of schizophrenia were tested using Exner...

  18. Antiviral treatment of Bell's palsy based on baseline severity: a systematic review and meta-analysis.

    Science.gov (United States)

    Turgeon, Ricky D; Wilby, Kyle J; Ensom, Mary H H

    2015-06-01

    We conducted a systematic review with meta-analysis to evaluate the efficacy of antiviral agents on complete recovery of Bell's palsy. We searched CENTRAL, Embase, MEDLINE, International Pharmaceutical Abstracts, and sources of unpublished literature to November 1, 2014. Primary and secondary outcomes were complete and satisfactory recovery, respectively. To evaluate statistical heterogeneity, we performed subgroup analysis of baseline severity of Bell's palsy and between-study sensitivity analyses based on risk of allocation and detection bias. The 10 included randomized controlled trials (2419 patients; 807 with severe Bell's palsy at onset) had variable risk of bias, with 9 trials having a high risk of bias in at least 1 domain. Complete recovery was not statistically significantly greater with antiviral use versus no antiviral use in the random-effects meta-analysis of 6 trials (relative risk, 1.06; 95% confidence interval, 0.97-1.16; I(2) = 65%). Conversely, random-effects meta-analysis of 9 trials showed a statistically significant difference in satisfactory recovery (relative risk, 1.10; 95% confidence interval, 1.02-1.18; I(2) = 63%). Response to antiviral agents did not differ visually or statistically between patients with severe symptoms at baseline and those with milder disease (test for interaction, P = .11). Sensitivity analyses did not show a clear effect of bias on outcomes. Antiviral agents are not efficacious in increasing the proportion of patients with Bell's palsy who achieved complete recovery, regardless of baseline symptom severity. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. The effect of support on Internet-delivered treatment for insomnia: Does baseline depression severity matter?

    NARCIS (Netherlands)

    Lancee, J.; Sorbi, M.J.; Eisma, M.C.; van Straten, A.; van den Bout, J.

    2014-01-01

    Internet-delivered cognitive-behavioral treatment is effective for insomnia. However, little is known about the beneficial effects of support. Recently we demonstrated that motivational support moderately improved the effects of Internet-delivered treatment for insomnia. In the present study, we

  20. Treatment-seeking patterns for malaria in pharmacies in five sub-Saharan African countries.

    Science.gov (United States)

    Ladner, Joël; Davis, Ben; Audureau, Etienne; Saba, Joseph

    2017-08-29

    Artemisinin-based combination therapy (ACT) is recommended as the first-line anti-malarial treatment strategy in sub-Saharan African countries. WHO policy recommends parasitological confirmation by microscopy or rapid diagnostic test (RDT) in all cases of suspected malaria prior to treatment. Gaps remain in understanding the factors that influence patient treatment-seeking behaviour and anti-malarial drug purchase decisions in the private sector. The objective of this study was to identify patient treatment-seeking behaviour in Ghana, Kenya, Nigeria, Tanzania, and Uganda. Face-to-face patient interviews were conducted at a total of 208 randomly selected retail outlets in five countries. At each outlet, exit interviews were conducted with five patients who indicated they had come seeking anti-malarial treatment. The questionnaire was anonymous and standardized in the five countries and collected data on different factors, including socio-demographic characteristics, history of illness, diagnostic practices (i.e. microscopy or RDT), prescription practices and treatment purchase. The price paid for the treatment was also collected from the outlet vendor. A total of 994 patients were included from the five countries. Location of malaria diagnosis was significantly different in the five countries. A total of 484 blood diagnostic tests were performed, (72.3% with microscopy and 27.7% with RDT). ACTs were purchased by 72.5% of patients who had undergone blood testing and 86.5% of patients without a blood test, regardless of whether the test result was positive or negative (p retail outlets and the role they play in providing anti-malaria drugs may support the design of effective malaria interventions.

  1. HIV prevention in care and treatment settings: baseline risk behaviors among HIV patients in Kenya, Namibia, and Tanzania.

    Directory of Open Access Journals (Sweden)

    Daniel P Kidder

    Full Text Available HIV care and treatment settings provide an opportunity to reach people living with HIV/AIDS (PLHIV with prevention messages and services. Population-based surveys in sub-Saharan Africa have identified HIV risk behaviors among PLHIV, yet data are limited regarding HIV risk behaviors of PLHIV in clinical care. This paper describes the baseline sociodemographic, HIV transmission risk behaviors, and clinical data of a study evaluating an HIV prevention intervention package for HIV care and treatment clinics in Africa. The study was a longitudinal group-randomized trial in 9 intervention clinics and 9 comparison clinics in Kenya, Namibia, and Tanzania (N = 3538. Baseline participants were mostly female, married, had less than a primary education, and were relatively recently diagnosed with HIV. Fifty-two percent of participants had a partner of negative or unknown status, 24% were not using condoms consistently, and 11% reported STI symptoms in the last 6 months. There were differences in demographic and HIV transmission risk variables by country, indicating the need to consider local context in designing studies and using caution when generalizing findings across African countries. Baseline data from this study indicate that participants were often engaging in HIV transmission risk behaviors, which supports the need for prevention with PLHIV (PwP.ClinicalTrials.gov NCT01256463.

  2. HIV Prevention in Care and Treatment Settings: Baseline Risk Behaviors among HIV Patients in Kenya, Namibia, and Tanzania

    Science.gov (United States)

    Kidder, Daniel P.; Bachanas, Pam; Medley, Amy; Pals, Sherri; Nuwagaba-Biribonwoha, Harriet; Ackers, Marta; Howard, Andrea; DeLuca, Nick; Mbatia, Redempta; Sheriff, Muhsin; Arthur, Gilly; Katuta, Frieda; Cherutich, Peter; Somi, Geoffrey

    2013-01-01

    HIV care and treatment settings provide an opportunity to reach people living with HIV/AIDS (PLHIV) with prevention messages and services. Population-based surveys in sub-Saharan Africa have identified HIV risk behaviors among PLHIV, yet data are limited regarding HIV risk behaviors of PLHIV in clinical care. This paper describes the baseline sociodemographic, HIV transmission risk behaviors, and clinical data of a study evaluating an HIV prevention intervention package for HIV care and treatment clinics in Africa. The study was a longitudinal group-randomized trial in 9 intervention clinics and 9 comparison clinics in Kenya, Namibia, and Tanzania (N = 3538). Baseline participants were mostly female, married, had less than a primary education, and were relatively recently diagnosed with HIV. Fifty-two percent of participants had a partner of negative or unknown status, 24% were not using condoms consistently, and 11% reported STI symptoms in the last 6 months. There were differences in demographic and HIV transmission risk variables by country, indicating the need to consider local context in designing studies and using caution when generalizing findings across African countries. Baseline data from this study indicate that participants were often engaging in HIV transmission risk behaviors, which supports the need for prevention with PLHIV (PwP). Trial Registration ClinicalTrials.gov NCT01256463 PMID:23459196

  3. Baseline autoantibody profile in rheumatoid arthritis is associated with early treatment response but not long-term outcomes.

    Science.gov (United States)

    de Moel, Emma C; Derksen, Veerle F A M; Stoeken, Gerrie; Trouw, Leendert A; Bang, Holger; Goekoop, Robbert J; Speyer, Irene; Huizinga, Tom W J; Allaart, Cornelia F; Toes, René E M; van der Woude, Diane

    2018-02-26

    The autoantibody profile of seropositive rheumatoid arthritis (RA) is very diverse and consists of various isotypes and antibodies to multiple post-translational modifications. It is yet unknown whether this varying breadth of the autoantibody profile is associated with treatment outcomes. Therefore, we investigated whether the composition of the autoantibody profile in RA, as a marker of the underlying immunopathology, influences initial and long-term treatment outcomes. In serum from 399 seropositive patients with RA in the IMPROVED study, drawn at baseline and at the moment of drug tapering, we measured IgG, IgM, and IgA isotypes for anti-cyclic citrullinated peptide-2 and anti-carbamylated protein antibodies, IgM and IgA rheumatoid factor, and reactivity against four citrullinated and two acetylated peptides (anti-modified protein antibodies (AMPAs)). We investigated the effect of the breadth of the autoantibody profile on (1) change in disease activity score (DAS)44 between 0 and 4 months, (2) initial drug-free remission (DFR, drug-free DAS44 profile at baseline had a significantly better early treatment response: ΔDAS 0-4 months of 1-2, 3-4, and 5-6 vs 7-8 isotypes, -1.5 (p profile achieved less initial DFR. For long-term sustained DFR there was no longer an association with the breadth of the autoantibody response. When assessing autoantibodies at the moment of tapering, similar trends were observed. A broad baseline autoantibody profile is associated with a better early treatment response. The breadth of the baseline autoantibody profile, reflecting a break in tolerance against several different autoantigens and extensive isotype switching, may indicate a more active humoral autoimmunity, which could make the underlying disease processes initially more suppressible by medication. The lack of association with long-term sustained DFR suggests that the relevance of the baseline autoantibody profile diminishes over time. ISRCTN11916566 . Registered on 7

  4. Baseline Characteristics of Patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) Trial

    Science.gov (United States)

    Shah, Sanjiv J.; Heitner, John F.; Sweitzer, Nancy K.; Anand, Inder S.; Kim, Hae-Young; Harty, Brian; Boineau, Robin; Clausell, Nadine; Desai, Akshay S.; Diaz, Rafael; Fleg, Jerome L.; Gordeev, Ivan; Lewis, Eldrin F.; Markov, Valetin; O’Meara, Eileen; Kobulia, Bondo; Shaburishvili, Tamaz; Solomon, Scott D.; Pitt, Bertram; Pfeffer, Marc A.; Li, Rebecca

    2013-01-01

    Background Treatment of Preserved Cardiac Function with an Aldosterone Antagonist (TOPCAT) is an ongoing randomized controlled trial of spironolactone versus placebo for heart failure with preserved ejection fraction (HFpEF). We sought to describe the baseline clinical characteristics of subjects enrolled in TOPCAT relative to other contemporary observational studies and randomized clinical trials of HFpEF. Methods and Results Between August 2006 and January 2012, 3445 patients with symptomatic HFpEF from 270 sites in 6 countries were enrolled in TOPCAT. At the baseline study visit, all subjects provided a detailed medical history and underwent physical examination, electrocardiography, quality of life, and laboratory assessment. Key parameters were compared to other large, contemporary HFpEF studies. The mean age was 68.6±9.6 years with a slight female predominance (52%); mean body mass index was 32 kg/m2; and comorbidities were common. History of hypertension (91% prevalence in TOPCAT) exceeded all other major HFpEF clinical trials. However, baseline blood pressure was well controlled (129/76 mmHg; systolic blood pressure 7-16 mmHg lower than other similar trials). Other common comorbidities included coronary artery disease (57%), atrial fibrillation (35%), chronic kidney disease (38%) and diabetes (32%). Self-reported activity levels were low, quality of life scores were comparable to those reported for patients with end-stage renal disease, and the prevalence of moderate or greater depression was 27%. Conclusions TOPCAT subjects share many common characteristics with contemporary HFpEF cohorts. Low activity level, significantly decreased quality of life, and depression were common at baseline in TOPCAT, underscoring the continued unmet need for evidence-based treatment strategies in HFpEF. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302. PMID:23258572

  5. Baseline characteristics of patients in the treatment of preserved cardiac function heart failure with an aldosterone antagonist trial.

    Science.gov (United States)

    Shah, Sanjiv J; Heitner, John F; Sweitzer, Nancy K; Anand, Inder S; Kim, Hae-Young; Harty, Brian; Boineau, Robin; Clausell, Nadine; Desai, Akshay S; Diaz, Rafael; Fleg, Jerome L; Gordeev, Ivan; Lewis, Eldrin F; Markov, Valetin; O'Meara, Eileen; Kobulia, Bondo; Shaburishvili, Tamaz; Solomon, Scott D; Pitt, Bertram; Pfeffer, Marc A; Li, Rebecca

    2013-03-01

    Treatment of Preserved Cardiac Function with an Aldosterone Antagonist (TOPCAT) is an ongoing randomized controlled trial of spironolactone versus placebo for heart failure with preserved ejection fraction (HFpEF). We sought to describe the baseline clinical characteristics of subjects enrolled in TOPCAT relative to other contemporary observational studies and randomized clinical trials of HFpEF. Between August 2006 and January 2012, 3445 patients with symptomatic HFpEF from 270 sites in 6 countries were enrolled in TOPCAT. At the baseline study visit, all subjects provided a detailed medical history and underwent physical examination, electrocardiography, quality of life, and laboratory assessment. Key parameters were compared with other large, contemporary HFpEF studies. The mean age was 68.6±9.6 years with a slight female predominance (52%); mean body mass index was 32 kg/m2; and comorbidities were common. History of hypertension (91% prevalence in TOPCAT) exceeded all other major HFpEF clinical trials. However, baseline blood pressure was well controlled (129/76 mm Hg; systolic blood pressure 7-16 mm Hg lower than other similar trials). Other common comorbidities included coronary artery disease (57%), atrial fibrillation (35%), chronic kidney disease (38%) and diabetes mellitus (32%). Self-reported activity levels were low, quality of life scores were comparable with those reported for patients with end-stage renal disease, and the prevalence of moderate or greater depression was 27%. TOPCAT subjects share many common characteristics with contemporary HFpEF cohorts. Low activity level, significantly decreased quality of life, and depression were common at baseline in TOPCAT, underscoring the continued unmet need for evidence-based treatment strategies in HFpEF. URL: http://www.clinicaltrials.gov. UNIQUE IDENTIFIER: NCT00094302.

  6. Dyadic discord at baseline is associated with lack of remission in the acute treatment of chronic depression.

    Science.gov (United States)

    Denton, W H; Carmody, T J; Rush, A J; Thase, M E; Trivedi, M H; Arnow, B A; Klein, D N; Keller, M B

    2010-03-01

    Dyadic discord, while common in depression, has not been specifically evaluated as an outcome predictor in chronic major depressive disorder. This study investigated pretreatment dyadic discord as a predictor of non-remission and its relationship to depressive symptom change during acute treatment for chronic depression. Out-patients with chronic depression were randomized to 12 weeks of treatment with nefazodone, the Cognitive Behavioral Analysis System of Psychotherapy or their combination. Measures included the Marital Adjustment Scale (MAS) and the Inventory of Depressive Symptomatology - Self Report (IDS-SR30). Of 681 original patients, 316 were partnered and 171 of these completed a baseline and exit MAS, and at least one post-baseline IDS-SR30. MAS scores were analysed as continuous and categorical variables ('dyadic discord' v. 'no dyadic discord' defined as an MAS score >2.36. Remission was defined as an IDS-SR30 of 14 at exit (equivalent to a 17-item Hamilton Rating Scale for Depression of 7). Patients with dyadic discord at baseline had lower remission rates (34.1%) than those without dyadic discord (61.2%) (all three treatment groups) (chi2=12.6, df=1, p=0.0004). MAS scores improved significantly with each of the treatments, although the change was reduced by controlling for improvement in depression. Depression remission at exit was associated with less dyadic discord at exit than non-remission for all three groups [for total sample, 1.8 v. 2.4, t(169)=7.3, p<0.0001]. Dyadic discord in chronically depressed patients is predictive of a lower likelihood of remission of depression. Couple therapy for those with dyadic discord may increase remission rates.

  7. Baseline study of methane emission from anaerobic ponds of palm oil mill effluent treatment.

    Science.gov (United States)

    Yacob, Shahrakbah; Ali Hassan, Mohd; Shirai, Yoshihito; Wakisaka, Minato; Subash, Sunderaj

    2006-07-31

    The world currently obtains its energy from the fossil fuels such as oil, natural gas and coal. However, the international crisis in the Middle East, rapid depletion of fossil fuel reserves as well as climate change have driven the world towards renewable energy sources which are abundant, untapped and environmentally friendly. Malaysia has abundant biomass resources generated from the agricultural industry particularly the large commodity, palm oil. This paper will focus on palm oil mill effluent (POME) as the source of renewable energy from the generation of methane and establish the current methane emission from the anaerobic treatment facility. The emission was measured from two anaerobic ponds in Felda Serting Palm Oil Mill for 52 weeks. The results showed that the methane content was between 35.0% and 70.0% and biogas flow rate ranged between 0.5 and 2.4 L/min/m(2). Total methane emission per anaerobic pond was 1043.1 kg/day. The total methane emission calculated from the two equations derived from relationships between methane emission and total carbon removal and POME discharged were comparable with field measurement. This study also revealed that anaerobic pond system is more efficient than open digesting tank system for POME treatment. Two main factors affecting the methane emission were mill activities and oil palm seasonal cropping.

  8. Impact of medical treatment on lung diffusion capacity in elderly patients with heart failure. Baseline characteristics and 1-year follow up after medical treatment

    DEFF Research Database (Denmark)

    Petersen, Claus Leth; Kjaer, Andreas

    2005-01-01

    treatment (baseline) and after 1 year of treatment with diuretics and ACE-inhibitors/angiotensin-II receptor antagonists. Age- and gender-matched healthy volunteers were included as control group. RESULTS: (mean+/-S.E.M.): K(CO) at baseline was 0.95+/-0.06 and 1.25+/-0.04 mmol/min x kPa/l in HF patients......AIM: The aim of this investigation was (1) to study the effect of untreated chronic heart failure (CHF) on alveolar membrane diffusion capacity (transfer coefficient, K(CO)) in elderly patients and (2) to study the impact of the standard regime of medical treatment with diuretics and ACE......-inhibitor/angiotensin-II receptor antagonists on K(CO) in these patients. METHODS: Non-medicated patients (except for diuretics) with symptoms of heart failure (NYHA II-III) and echocardiographically estimated left ventricular ejection fraction (LVEF)

  9. Baseline study of methane emission from open digesting tanks of palm oil mill effluent treatment.

    Science.gov (United States)

    Yacob, Shahrakbah; Hassan, Mohd Ali; Shirai, Yoshihito; Wakisaka, Minato; Subash, Sunderaj

    2005-06-01

    Anthropogenic release of greenhouse gases, especially CO2 and CH4 has been recognized as one of the main causes of global warming. Several measures under the Kyoto Protocol 1997 have been drawn up to reduce the greenhouse gases emission. One of the measures is Clean Development Mechanisms (CDM) that was created to enable developed countries to cooperate with developing countries in emission reduction activities. In Malaysia, palm oil industry particularly from palm oil mill effluent (POME) anaerobic treatment has been identified as an important source of CH4. However, there is no study to quantify the actual CH4 emission from the commercial scale wastewater treatment facility. Hence, this paper shall address the CH4 emission from the open digesting tanks in Felda Serting Hilir Palm Oil Mill. CH4 emission pattern was recorded for 52 weeks from 3600 m3 open digesting tanks. The findings indicated that the CH4 content was between 13.5% and 49.0% which was lower than the value of 65% reported earlier. The biogas flow rate ranged between 0.8l min(-1)m(-2) and 9.8l min(-1)m(-2). Total CH4 emission per open digesting tank was 518.9 kgday(-1). Relationships between CH4 emission and total carbon removal and POME discharged were also discussed. Fluctuation of biogas production was observed throughout the studies as a result of seasonal oil palm cropping, mill activities, variation of POME quality and quantity discharged from the mill. Thus only through long-term field measurement CH4 emission can be accurately estimated.

  10. Can persons with a history of multiple addiction treatment episodes benefit from technology delivered behavior therapy? A moderating role of treatment history at baseline.

    Science.gov (United States)

    Kim, Sunny Jung; Marsch, Lisa A; Acosta, Michelle C; Guarino, Honoria; Aponte-Melendez, Yesenia

    2016-03-01

    A growing line of research has shown positive treatment outcomes from technology-based therapy for substance use disorders (SUDs). However, little is known about the effectiveness of technology-based SUD interventions for persons who already had numerous prior SUD treatments. We conducted a secondary analysis on a 12-month trial with patients (N=160) entering methadone maintenance treatment (MMT). Patients were randomly assigned to either standard MMT treatment or a model in which half of standard counseling sessions were replaced with a computer-based intervention, called Therapeutic Education System (standard+TES). Four treatment history factors at baseline, the number of lifetime SUD treatment episodes, detoxification episodes, and inpatient/outpatient treatment episodes were categorized into three levels based on their tertile points, and analyzed as moderators. Dependent variables were urine toxicology results for opioid and cocaine abstinence for 52-weeks. The standard+TES condition produced significantly better opioid abstinence than standard treatment for participants with 1) a moderate or high frequency of lifetime SUD treatment episodes, and 2) those with all three levels (low, moderate and high) of detoxification and inpatient/outpatient treatment episodes, pspeople with 1) a moderate or high frequency of lifetime SUD treatment episodes, 2) a high level of detoxification episodes, and 3) a moderate or high level of inpatient treatment history, pstechnology-based behavioral therapy as part of treatment can be more effective than MMT alone, even among patients with a history of multiple addiction treatment episodes. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Treatment of imported severe malaria with artesunate instead of quinine--more evidence needed?

    Science.gov (United States)

    Cramer, Jakob P; López-Vélez, Rogelio; Burchard, Gerd D; Grobusch, Martin P; de Vries, Peter J

    2011-09-07

    Rapid and fast acting anti-malarials are essential to treat severe malaria. Quinine has been the only option for parenteral therapy until recently. While current evidence shows that intravenous artesunate is more effective than quinine in treating severe malaria in endemic countries, some questions remain regarding safety profiles and drug resistance. For imported severe malaria, additional unanswered questions are related to generalizability of the findings from endemic countries and to legal aspects, as there is no Good Manufacturing Practice-conform drug available yet. Here, the implications of existing evidence for the treatment of imported severe malaria are discussed.

  12. Treatment of imported severe malaria with artesunate instead of quinine - more evidence needed?

    Directory of Open Access Journals (Sweden)

    Grobusch Martin P

    2011-09-01

    Full Text Available Abstract Rapid and fast acting anti-malarials are essential to treat severe malaria. Quinine has been the only option for parenteral therapy until recently. While current evidence shows that intravenous artesunate is more effective than quinine in treating severe malaria in endemic countries, some questions remain regarding safety profiles and drug resistance. For imported severe malaria, additional unanswered questions are related to generalizability of the findings from endemic countries and to legal aspects, as there is no Good Manufacturing Practice-conform drug available yet. Here, the implications of existing evidence for the treatment of imported severe malaria are discussed.

  13. Anticancer Effect of AntiMalarial Artemisinin Compounds | Das ...

    African Journals Online (AJOL)

    Artemisinins seem to regulate key factors such as nuclear factor‑kappa B, survivin, NOXA, hypoxia‑inducible factor‑1α, and BMI‑1, involving multiple pathways that may affect drug response, drug interactions, drug resistance, and associated parameters upon normal cells. Newer synthetic artemisinins have been developed ...

  14. In vivo anti-malarial activity of hydroalcoholic extracts from ...

    African Journals Online (AJOL)

    Administrator

    of medicine is the emergence of the Peruvian (Cinchona) bark (Rubiaceae) coupled with its pharmacologically active substance, - the quinine. Quinine is a classic ... at optimum humidity for at least three days before being subjected to the experiments (2). All the experiments were carried out in a calm laboratory setting that ...

  15. interventional studies of anti-malarial drugs utilization in public

    African Journals Online (AJOL)

    DR. AMINU

    ABSTRACT. The best way to analyze drug utilization and evaluate impact of an intervention in health care institutions is to study the universal indicators, which are not dependent either on investigator or time of measurement. The aim of this study was to characterize the prescription pattern of public health institutions in ...

  16. In Vivo anti-malarial activities of Clerodendrum myricoides ...

    African Journals Online (AJOL)

    Background: Malaria caused by the parasite Plasmodium falciparum is an acute disease which kills an estimated 863,000 people per year according to the WHO report of 2009. The fight against malaria is faced with the occurrence of widespread resistance of P. falciparum. The search for plant-derived antimalarial drugs ...

  17. Interventional studies of anti-malarial drugs utilization in public ...

    African Journals Online (AJOL)

    The best way to analyze drug utilization and evaluate impact of an intervention in health care institutions is to study the universal indicators, which are not dependent either on investigator or time of measurement. The aim of this study was to characterize the prescription pattern of public health institutions in Kano, Nigeria ...

  18. Synthesis, and anti-malarial screening, of 1-diethylamino-4 ...

    African Journals Online (AJOL)

    Artemisinin and its derivatives have become antimalarial drugs of choice because they are effective against most stages in the life cycle of plasmodium and are safe for all, including pregnant women. World Health Organisation ... The target compound also had an LD50 of 330 mg/kg in mice by the oral route. A single dose ...

  19. Baseline Flowsheet Generation for the Treatment and Disposal of Idaho National Engineering and Environmental Laboratory Sodium Bearing Waste

    International Nuclear Information System (INIS)

    Barnes, C.M.; Lauerhass, L.; Olson, A.L.; Taylor, D.D.; Valentine, J.H.; Lockie, K.A.

    2002-01-01

    The High-Level Waste (HLW) Program at the Idaho National Engineering and Environmental Laboratory (INEEL) must implement technologies and processes to treat and qualify radioactive wastes located at the Idaho Nuclear Technology and Engineering Center (INTEC) for permanent disposal. This paper describes the approach and accomplishments to date for completing development of a baseline vitrification treatment flowsheet for sodium-bearing waste (SBW), including development of a relational database used to manage the associated process assumptions. A process baseline has been developed that includes process requirements, basis and assumptions, process flow diagrams, a process description, and a mass balance. In the absence of actual process or experimental results, mass and energy balance data for certain process steps are based on assumptions. Identification, documentation, validation, and overall management of the flowsheet assumptions are critical to ensuring an integrated, focused program. The INEEL HLW Program initially used a roadmapping methodology, developed through the INEEL Environmental Management Integration Program, to identify, document, and assess the uncertainty and risk associated with the SBW flowsheet process assumptions. However, the mass balance assumptions, process configuration and requirements should be accessible to all program participants. This need resulted in the creation of a relational database that provides formal documentation and tracking of the programmatic uncertainties related to the SBW flowsheet

  20. Differential item functioning (DIF) in the EORTC QLQ-C30: a comparison of baseline, on-treatment and off-treatment data.

    Science.gov (United States)

    Scott, Neil W; Fayers, Peter M; Aaronson, Neil K; Bottomley, Andrew; de Graeff, Alexander; Groenvold, Mogens; Gundy, Chad; Koller, Michael; Petersen, Morten A; Sprangers, Mirjam A G

    2009-04-01

    Differential item functioning (DIF) analyses can be used to explore translation, cultural, gender or other differences in the performance of quality of life (QoL) instruments. These analyses are commonly performed using "baseline" or pretreatment data. We previously reported DIF analyses to examine the pattern of item responses for translations of the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 QoL instrument, using only data collected prior to cancer treatment. We now compare the consistency of these results with similar analyses of on-treatment and off-treatment assessments and explore whether item relationships differ from those at baseline. Logistic regression DIF analyses were used to examine the translation of each item in each multi-item scale at the three time points, after controlling for the overall scale score and other covariates. The consistency of results at the three time points was explored. For most EORTC QLQ-C30 subscales, the DIF results were very consistent across the three time points. Results for the Nausea and Vomiting scale varied the most across assessments. The results indicated that DIF analyses were stable across each time point and that the same DIF effects were usually found regardless of the treatment status of the respondent.

  1. Assessment of the ecological potential of mine-water treatment wetlands using a baseline survey of macroinvertebrate communities

    International Nuclear Information System (INIS)

    Batty, L.C.; Atkin, L.; Manning, D.A.C.

    2005-01-01

    A baseline survey of macroinvertebrate populations in two mine-water treatment wetlands, one treating a net acidic spoil heap discharge and one a net alkaline ferruginous pumped mine water, was undertaken to assess the potential of these systems to provide habitats for faunal communities. Both wetlands were found to be impoverished in comparison to natural wetlands but did sustain a macroinvertebrate community that could support higher organisms. Wetland size and water quality in terms of pH, conductivity and metal concentrations were found to be important factors in determining the quality of the populations supported. Direct toxicity to organisms was unlikely to be the main cause of lower diversity, but the smothering of organisms via the precipitation of iron hydroxides particularly in the early parts of the treatment systems affected macroinvertebrate communities. The presence of areas of open water within the planted systems was found to be important for providing habitats for macroinvertebrates and this should be both a future design and maintenance consideration for environmental managers. - Mine-water treatment wetlands can be engineered to provide habitats for ecological communities

  2. Improving malaria recognition, treatment and referral practices by training caretakers in rural Nigeria.

    Science.gov (United States)

    Okeke, Theodora A

    2010-05-01

    A caretaker training programme was carried out in Ugwuogo-Nike, a rural area in south-east Nigeria, based on formative research within the community. A training of trainers workshop was organized for 30 leaders of women groups who subsequently trained other mothers in their group. Community information activities, which lasted for a period of eight months, included the use of posters, drama group and jingles. The programme was evaluated using the quantitative and qualitative methods that were employed at baseline, which included community survey and focus group discussions (FGDs). For the community survey, households with children under five years of age were identified and provided the sampling frame, from which 300 households were chosen using the systematic sampling method. The target population for the FGDs were caretakers of children under five years. Post-intervention evaluation of the programme showed significant (pmanagement of malaria and referral practices for severe malaria. Those who correctly reported that mosquitoes were the cause of malaria rose markedly from 39.7% to 88.7%. Knowledge of symptoms of mild and severe malaria also increased significantly. Only 1.5% of caretakers were aware of the correct dose of anti-malarial before intervention, but this increased to 41.5%. The impact of intervention brought about a dramatic change in the practice of taking severely ill children, especially those with convulsion, to a traditional healer. A minority (6.7%) of caretakers took a severely ill child to a traditional healer as against 60% pre-intervention. There was also a significant increase in use of formal health facilities for the treatment of severely ill children. The study findings support the view that training of mothers to recognize, treat appropriately and refer severe cases of malaria is feasible and may lead to a reduction in the incidence of severe disease.

  3. Malaria case management in Papua New Guinea following the introduction of a revised treatment protocol.

    Science.gov (United States)

    Pulford, Justin; Kurumop, Serah F; Ura, Yangta; Siba, Peter M; Mueller, Ivo; Hetzel, Manuel W

    2013-11-27

    This paper reports on the availability of diagnostic tools and recommended anti-malarials in the 12-month period immediately following the implementation of a new national malaria treatment protocol (NMTP) in Papua New Guinea (PNG). Health worker adherence to the new NMTP is also examined and comparisons made with previously reported pre-implementation findings. A countrywide cross-sectional survey in randomly selected primary health care facilities (n = 88). Data were collected via passive observation of the clinical case management of fever or suspected malaria patients and via an interviewer administered questionnaire completed with the officer in charge of each participating health care facility. Malaria rapid diagnostic tests (RDTs) and the new first-line anti-malarial medication, artemether-lumefantrine (AL), were available in 53.4% and 51.1% of surveyed heath facilities, respectively. However, they were more widely available in the larger health centres as compared to the smaller aid-posts (90.2% vs. 21.3% and 87.8% vs. 19.2%, respectively). Overall, 68.3% of observed fever cases (n = 445) were tested for malaria by RDT and 39% prescribed an anti-malarial, inclusive of 98.2% of RDT positive patients and 19.8% of RDT negative cases. The availability and use of malaria RDTs was greater in the current survey as compared to pre-implementation of the new NMTP (8.9% vs. 53.4% & 16.2% vs. 68.3%, respectively) as was the availability of AL (0% vs. 51.1%). The percentage of fever patients prescribed anti-malarials decreased substantially post implementation of the new NMTP (96.4% vs. 39.0%). PNG has achieved high coverage of malaria RDTs and AL at the health centre level, but these resources have yet to reach the majority of aid-posts. Malaria case management practice has substantially changed in the 12-month period immediately following the new NMTP, although full protocol adherence was rarely observed.

  4. Implementation, recruitment and baseline characteristics: A randomized trial of combined treatments for smoking cessation and weight control

    Directory of Open Access Journals (Sweden)

    Terry Bush

    2017-09-01

    Full Text Available Background: Two-thirds of treatment-seeking smokers are obese or overweight. Most smokers are concerned about gaining weight after quitting. The average smoker experiences modest post-quit weight gain which discourages many smokers from quitting. Although evidence suggests that combined interventions to help smokers quit smoking and prevent weight gain can be helpful, studies have not been replicated in real world settings. Methods: This paper describes recruitment and participant characteristics of the Best Quit Study, a 3-arm randomized controlled trial testing tobacco cessation treatment alone or combined with simultaneous or sequential weight management. Study participants were recruited via tobacco quitlines from August 5, 2013 to December 15, 2014. Results: Statistical analysis on baseline data was conducted in 2015/2016. Among 5082 potentially eligible callers to a tobacco quitline, 2540 were randomized (50% of eligible. Compared with individuals eligible but not randomized, those randomized were significantly more likely to be female (65.7% vs 54.5%, p < 0.01, overweight or obese (76.3% vs 62.5%, p < 0.01, more confident in quitting (p < 0.01, more addicted (first cigarette within 5 min: 50.0% vs 44.4%, p < 0.01, and have a chronic disease (28.6% vs. 24.4%, p < 0.01. Randomized groups were not statistically significantly different on demographics, tobacco or weight variables. Two-thirds of participants were female and white with a mean age of 43. Conclusions: Adding weight management interventions to tobacco cessation quitlines was feasible and acceptable to smokers. If successful for cessation and weight outcomes, a combined intervention may provide a treatment approach for addressing weight gain with smoking cessation through tobacco quitlines. Trial registration: Clinicaltrials.gov NCT01867983. Keywords: Smoking, Weight gain, Quitlines, Simultaneous, Sequential

  5. Baseline rationing

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter Raahave

    The standard problem of adjudicating conflicting claims describes a situation in which a given amount of a divisible good has to be allocated among agents who hold claims against it exceeding the available amount. This paper considers more general rationing problems in which, in addition to claims......, there exist baselines (to be interpreted as objective entitlements, ideal targets, or past consumption) that might play an important role in the allocation process. The model we present is able to accommodate real-life rationing situations, ranging from resource allocation in the public health care sector...... to international protocols for the reduction of greenhouse emissions, or water distribution in drought periods. We define a family of allocation methods for such general rationing problems - called baseline rationing rules - and provide an axiomatic characterization for it. Any baseline rationing rule within...

  6. Diabetes treatment patterns and goal achievement in primary diabetes care (DiaRegis - study protocol and patient characteristics at baseline

    Directory of Open Access Journals (Sweden)

    Deeg Evelin

    2010-09-01

    Full Text Available Abstract Background Patients with type 2 diabetes are at an increased risk for disease and treatment related complications after the initial approach of oral mono/dual antidiabetic therapy has failed. Data from clinical practice with respect to this patient group are however scarce. Therefore we set up a registry in primary care documenting the course and outcomes of this patient group. Methods Diabetes Treatment Patterns and Goal Achievement in Primary Diabetes Care (DiaRegis is a prospective, observational, German, multicenter registry including patients with type-2 diabetes in which oral mono/dual antidiabetic therapy has failed. Data were recorded at baseline and will be prospectively documented during visits at 6 ± 1, 12 ± 2 and 24 ± 2 months. The primary objective is to estimate the proportion of patients with at least 1 episode of severe hypoglycemia within one year. Results 313 primary care offices included 4,048 patients between June 2009 and March 2010 of which 3,810 patients fulfilled the in- and exclusion criteria. 46.7% of patients were female; patients had a median diabetes duration of 5.5 years and most were obese with respect to BMI or waist circumference. HbA1c at baseline was 7.4%, fasting plasma glucose 142 mg/dl and postprandial glucose 185 mg/dl. Co-morbidity in this patient population was substantial with 17.9% having coronary artery disease, 14.4% peripheral neuropathy, 9.9% heart failure and 6.0% peripheral arterial disease. 68.6% of patients received oral monotherapy, 31.4% dual oral combination therapy. The most frequent antidiabetic agent used as monotherapy was metformin (79.0% followed by sulfonylureas (14.8%. Conclusions DiaRegis is a large, prospective registry in primary diabetes care to document the course and outcomes of patients with type-2 diabetes in which the initial approach of oral mono/dual antidiabetic therapy has failed. The two year follow-up will allow for a prospective evaluation of these patients

  7. Evaluation of the use of baseline cortisol concentration as a monitoring tool for dogs receiving trilostane as a treatment for hyperadrenocorticism.

    Science.gov (United States)

    Cook, Audrey K; Bond, Karen G

    2010-10-01

    To determine whether a single measurement of cortisol concentration can be used to monitor dogs receiving trilostane for hyperadrenocorticism. Controlled drug efficacy trial. 103 client-owned dogs. Results of ACTH stimulation tests before and during trilostane treatment were evaluated. Each cortisol concentration after ACTH stimulation was classified as indicative of excessive, acceptable, or inadequate control of adrenal gland function, as outlined by the trilostane manufacturer. Baseline cortisol concentrations before and during trilostane treatment were evaluated; target variables were defined, and sensitivity, specificity, and predictive values were determined. Results of 103 and 342 ACTH stimulation tests before and during treatment were evaluated. In this population, baseline cortisol concentrations ≥ 1.3 µg/dL accurately excluded excessive suppression (defined by cortisol concentration after ACTH stimulation dogs. In addition, baseline cortisol concentrations ≤ 2.9 µg/dL correctly excluded inadequate control (defined by cortisol concentration after ACTH stimulation > 9.1 µg/dL) in 200 of 211 (95%) dogs. During trilostane treatment, baseline cortisol concentrations between 1.3 and either 2.9 µg/dL or ≤ 50% of the pretreatment baseline cortisol concentration correctly predicted acceptable control of adrenal gland function in 147 of 168 (88%) dogs. Evaluation of a baseline cortisol concentration collected 4 to 6 hours after trilostane administration in dogs with hyperadrenocorticism provided clinically useful information about control of adrenal gland function. Many dogs receiving trilostane may be adequately monitored without the expense and inconvenience of an ACTH stimulation test.

  8. Variation in pre-treatment count lead time and its effect on baseline estimates of cage-level sea lice abundance.

    Science.gov (United States)

    Gautam, R; Boerlage, A S; Vanderstichel, R; Revie, C W; Hammell, K L

    2016-11-01

    Treatment efficacy studies typically use pre-treatment sea lice abundance as the baseline. However, the pre-treatment counting window often varies from the day of treatment to several days before treatment. We assessed the effect of lead time on baseline estimates, using historical data (2010-14) from a sea lice data management programme (Fish-iTrends). Data were aggregated at the cage level for three life stages: (i) chalimus, (ii) pre-adult and adult male and (iii) adult female. Sea lice counts were log-transformed, and mean counts by lead time relative to treatment day were computed and compared separately for each life stage, using linear mixed models. There were 1,658 observations (treatment events) from 56 sites in 5 Bay Management Areas. Our study showed that lead time had a significant effect on the estimated sea lice abundance, which was moderated by season. During the late summer and autumn periods, counting on the day of treatment gave significantly higher values than other days and would be a more appropriate baseline estimate, while during spring and early summer abundance estimates were comparable among counts within 5 days of treatment. A season-based lead time window may be most appropriate when estimating baseline sea lice levels. © 2016 John Wiley & Sons Ltd.

  9. Malaria diagnosis and treatment practices following introduction of rapid diagnostic tests in Kibaha District, Coast Region, Tanzania.

    Science.gov (United States)

    Mubi, Marycelina; Kakoko, Deodatus; Ngasala, Billy; Premji, Zul; Peterson, Stefan; Björkman, Anders; Mårtensson, Andreas

    2013-08-26

    The success of the universal parasite-based malaria testing policy for fever patients attending primary health care (PHC) facilities in Tanzania will depend highly on health workers' perceptions and practices. The aim of this study was, therefore, to assess the present use of malaria diagnostics (rapid diagnostic tests (RDTs) and microscopy), prescription behaviour and factors affecting adherence to test results at PHC facilities in Kibaha District, Coast Region, Tanzania. Exit interviews were conducted with fever patients at PHC facilities and information on diagnostic test performed and treatment prescribed were recorded. Interviews with prescribers to assess their understanding, perceptions and practices related to RDTs were conducted, and health facility inventory performed to assess availability of staff, diagnostics and anti-malarial drugs. The survey was undertaken at ten governmental PHC facilities, eight of which had functional diagnostics. Twenty health workers were interviewed and 195 exit interviews were conducted with patients at the PHC facilities. Of the 168 patients seen at facilities with available diagnostics, 105 (63%) were tested for malaria, 31 (30%) of whom tested positive. Anti-malarial drugs were prescribed to all patients with positive test results, 14% of patients with negative results and 28% of patients not tested for malaria. Antibiotics were more likely to be prescribed to patients with negative test results compared to patients with positive results (81 vs 39%, p malaria (84 vs 69%, p = 0.01). Stock-outs of RDTs and staff shortage accounted for the low testing rate, and health worker perceptions were the main reason for non-adherence to test results. Anti-malarial prescription to patients with negative test results and those not tested is still practiced in Tanzania despite the universal malaria testing policy of fever patients. The use of malaria diagnostics was also associated with higher prescription of antibiotics among

  10. An Initial Investigation of Baseline Respiratory Sinus Arrhythmia as a Moderator of Treatment Outcome for Young Children Born Premature with Externalizing Behavior Problems

    Science.gov (United States)

    Bagner, Daniel M.; Graziano, Paulo A.; Jaccard, James; Sheinkopf, Stephen J.; Vohr, Betty R.; Lester, Barry M.

    2012-01-01

    The aim of the current study was to examine the moderating effect of baseline respiratory sinus arrhythmia (RSA) on Parent-Child Interaction Therapy (PCIT), a behavioral parent-training intervention, for young children born premature. In this pilot randomized controlled trial, 28 young children (mean age of 37.79 months), who were born < 37 weeks gestation and presented with elevated externalizing behavior problems, were randomly assigned to an immediate treatment or waitlist control group. RSA, which provides an approximate marker of individual differences in cardiac vagal tone, was measured during a baseline period. Past research has generally shown that higher levels of baseline RSA correlate with various positive psychological states (e.g., empathy, sustained attention), whereas lower levels of baseline RSA correlate with less optimal psychological states (e.g., higher externalizing behavior problems). Results indicated that baseline RSA significantly interacted with treatment condition in predicting changes in child disruptive behavior. Specifically, low levels of baseline RSA were associated with greater improvements in child disruptive behavior following PCIT. While acknowledging the caveats of measuring and interpreting RSA and the need to include a sympathetic-linked cardiac measure in future research, these findings provide preliminary evidence that children with lower capacity for emotion regulation receive even greater treatment gains. Future research should also examine the moderating effect of RSA in larger samples and explore the potential mediating role of RSA on behavioral parenting interventions. PMID:22697452

  11. Most Trial Eligibility Criteria and Patient Baseline Characteristics Do Not Modify Treatment Effect in Trials Using Targeted Therapies for Rheumatoid Arthritis

    DEFF Research Database (Denmark)

    Christensen, Anton Wulf; Tarp, Simon; Furst, Daniel E

    2015-01-01

    . Odds ratios (ORs) were calculated from the response rates and compared among the trial eligibility criteria/patient baseline characteristics of interest. Comparisons are presented as the Ratio of Odds Ratios (ROR). RESULTS: Sixty-two trials (19,923 RA patients) were included in the primary analyses...... using ACR20 response. Overall, targeted therapies constituted an effective treatment (OR 3.96 95% confidence interval (CI) 3.41 to 4.60). The majority of the trial eligibility criteria and patient baseline characteristics did not modify treatment effect. The added benefit of targeted therapies was lower......OBJECTIVE: To determine if variations in trial eligibility criteria and patient baseline characteristics could be considered effect modifiers of the treatment response when testing targeted therapies (biological agents and targeted synthetic disease modifying antirheumatic drugs (DMARDs...

  12. Baseline OCT measurements in the idiopathic intracranial hypertension treatment trial, part II: correlations and relationship to clinical features.

    Science.gov (United States)

    Auinger, Peggy; Durbin, Mary; Feldon, Steven; Garvin, Mona; Kardon, Randy; Keltner, John; Kupersmith, Mark J; Sibony, Patrick; Plumb, Kim; Wang, Jui-Kai; Werner, John S

    2014-11-04

    The accepted method to evaluate and monitor papilledema, Frisén grading, uses an ordinal approach based on descriptive features. Part I showed that spectral-domain optical coherence tomography (SD-OCT) in a clinical trial setting provides reliable measurement of the effects of papilledema on the optic nerve head (ONH) and peripapillary retina, particularly if a 3-D segmentation method is used for analysis.(1) We evaluated how OCT parameters are interrelated and how they correlate with vision and other clinical features in idiopathic intracranial hypertension (IIH) patients. A total of 126 subjects in the IIH Treatment Trial (IIHTT) OCT substudy had Cirrus SD-OCT optic disc and macula scans analyzed by using a 3-D segmentation algorithm to derive retinal nerve fiber layer (RNFL) thickness, total retinal thickness (TRT), retinal ganglion cell layer plus inner plexiform layer (GCL+IPL) thickness, and ONH volume. The SD-OCT parameter values were correlated with high- and low-contrast acuity, perimetric mean deviation, Frisén grading, and IIH features. At study entry, the average RNFL thickness, TRT, and ONH volume showed significant strong correlations (r ≥ 0.90) with each other. The same OCT parameters showed a strong (r > 0.76) correlation with Frisén grade and a mild (r > 0.24), but significant, correlation with lumbar puncture opening pressure. For all eyes at baseline, neither visual acuity (high or low contrast) nor mean deviation correlated with any OCT measure of swelling or GCL+IPL thickness. In newly diagnosed IIH, OCT demonstrated alterations of the peripapillary retina and ONH correlate with Frisén grading of papilledema. At presentation, OCT measures of papilledema, in patients with newly diagnosed IIH and mild vision loss, do not correlate with clinical features or visual dysfunction. (ClinicalTrials.gov number, NCT01003639.). Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  13. Analysis of Initial Baseline Clinical Parameters and Treatment Strategy Associated with Medication Failure in the Treatment of Benign Prostatic Hyperplasia in Korea

    Directory of Open Access Journals (Sweden)

    Hoon Choi

    2010-12-01

    Full Text Available Purpose To analyze the baseline clinical factors and medication treatment strategy used in cases with medication treatment failure of benign prostatic hyperplasia (BPH. Methods From January 2006 to December 2009, 677 BPH patients with at least 3 months of treatment with medication were enrolled. We analyzed clinical factors by medication failure (n=161 versus maintenance (n=516, by prostate size (less than 30 g, n=231; 30 to 50 g, n=244; greater than 50 g, n=202, and by prostate-specific antigen (PSA levels (less than 1.4 ng/mL, n=324; more than 1.4 ng/mL, n=353. Results Age, combination medication rate, PSA, and prostate volume were statistically different between the medication treatment failure and maintenance groups. By prostate size, the PSA and medication failure rates were relatively higher and the medication period was shorter in patients with a prostate size of more than 30 g. The combination medication rate was higher in patients with a prostate size of more than 50 g. The medication failure rate and prostate volume were higher in patients with a PSA level of more than 1.4 ng/mL. However, the combination treatment rate was not significantly different in patients with a PSA level lower than 1.4 ng/mL. Suggestive cutoffs for combination medication are a prostate volume of 34 g and PSA level of 1.9 ng/mL. Conclusions The clinical factors associated with medication failure were age, treatment type, and prostate volume. Combination therapy should be considered more in Korea in patients with a PSA level higher than 1.4 ng/mL and a prostate volume of between 30 and 50 g to prevent medication failure.

  14. Depression CBT treatment gains among HIV-infected persons with a history of injection drug use varies as a function of baseline substance use.

    Science.gov (United States)

    Labbe, Allison K; O'Cleirigh, Conall M; Stein, Michael; Safren, Steven A

    2015-01-01

    Depression and substance use, the most common comorbidities with HIV, are both associated with poor treatment outcomes and accelerated HIV disease progression. Though previous research has demonstrated short-term and follow-up success for cognitive behavioral therapy for adherence and depression (CBT-AD) on depression outcomes among patients with HIV in care and among patients with HIV in active substance abuse treatment for injection drug use (IDU), there is little information regarding possible moderating effects of active use versus abstinence on depression treatment gains. The present study aimed to examine recent substance use at treatment initiation as a moderator of the acute and maintenance effects of CBT-AD on depression. We used data from a two-arm, randomized controlled trial (N = 89) comparing CBT-AD to enhanced treatment as usual in individuals in treatment for IDU. To test whether depression at time of presentation affected outcomes, repeated-measures ANOVAs were conducted for two time frames: (1) acute phase (baseline to post-treatment) (acute) and (2) maintenance phase (baseline to 12-month follow-up). To further examine maintenance of gains, we additionally looked at post-treatment to 12-month follow-up. Depression scores derived from the clinical global impression for severity and the Montgomery-Asberg depression rating scale (MADRS) served as the primary outcome variables. Acute (baseline post treatment) moderation effects were found for those patients endorsing active drug use at baseline in the CBT-AD condition, who demonstrated the greatest reductions in MADRS scores at post-treatment (F[1,76] = 6.78, p = .01) and follow-up (F[1,61] = 5.46, p = .023). Baseline substance use did not moderate differences from post-treatment to 12-month follow-up as depression treatment gains that occurred acutely from baseline to post-treatment were maintained across both patients engaged in substance use and abstainers. We conclude that CBT

  15. Baseline blood immunological profiling differentiates between Her2– breast cancer molecular subtypes: implications for immunomediated mechanisms of treatment response

    Directory of Open Access Journals (Sweden)

    Tudoran O

    2015-11-01

    Full Text Available Oana Tudoran,1,2,* Oana Virtic,2,* Loredana Balacescu,1,2 Carmen Lisencu,3 Bogdan Fetica,4 Claudia Gherman,1 Ovidiu Balacescu,1 Ioana Berindan-Neagoe1,2,5 1Department of Functional Genomics and Experimental Pathology, The Oncology Institute “Prof Dr Ion Chiricuţă”, 2Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 3Department of Radiotherapy I, 4Department of Pathology, The Oncology Institute “Prof Dr Ion Chiricuţă”, 5Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania *These authors contributed equally to this work Purpose: Breast cancer patients’ response to treatment is highly dependent on the primary tumor molecular features, with triple-negative breast tumors having the worst prognosis of all subtypes. According to the molecular features, tumors stimulate the microenvironment to induce distinct immune responses, baseline immune activation being associated with higher likelihood of pathologic response. In this study, we investigated the deconvolution of the immunological status of triple-negative tumors in comparison with luminal tumors and the association with patients’ clinicopathological characteristics.Patients and methods: Gene expression of 84 inflammatory molecules and their receptors were analyzed in 40 peripheral blood samples from patients with Her2- primary breast cancer tumors. We studied the association of triple-negative phenotype with age, clinical stage, tumor size, lymph nodes, and menopausal status.Results: We observed that more patients with estrogen (ER/progesterone (PR-negative tumors had grade III, while more patients with ER/PR-positive tumors had grade II tumors. Gene expression analysis revealed a panel of 14 genes to have differential expression between the two groups: several interleukins: IL13, IL16, IL17C and IL17F, IL1A, IL3; interleukin receptors: IL10RB, IL5RA; chemokines: CXCL13 and CCL

  16. Rationale, design and baseline results of the Treatment Optimisation in Primary care of Heart failure in the Utrecht region (TOPHU) study : a cluster randomised controlled trial

    NARCIS (Netherlands)

    Valk, Mark J.; Hoes, Arno W.; Mosterd, Arend; Landman, Marcel A.; Broekhuizen, Berna D L; Rutten, Frans H.

    2015-01-01

    BACKGROUND: Heart failure (HF) is mainly detected and managed in primary care, but the care is considered suboptimal. We present the rationale, design and baseline results of the Treatment Optimisation in Primary care of Heart failure in the Utrecht region (TOPHU) study. In this study we assess the

  17. Evaluation of baseline cortisol, endogenous ACTH, and cortisol/ACTH ratio to monitor trilostane treatment in dogs with pituitary-dependent hypercortisolism.

    Science.gov (United States)

    Burkhardt, W A; Boretti, F S; Reusch, C E; Sieber-Ruckstuhl, N S

    2013-01-01

    The effectiveness of trilostane treatment is currently monitored by regular ACTH stimulation tests, which are time-consuming and expensive. Therefore, a monitoring system without a stimulation protocol and with less client expense would be preferable. The aim of our study was to evaluate if baseline cortisol, endogenous ACTH (ACTH) concentration or the baseline cortisol to ACTH ratio (cortisol/ACTH ratio) could replace the ACTH stimulation test. Forty trilostane-treated dogs with pituitary-dependent hypercortisolism (PDH) were included in this prospective study. A total of 148 ACTH stimulation tests and 77 ACTH concentrations and cortisol/ACTH ratios were analyzed. Control of cortisol release was classified according to cortisol concentration after ACTH administration as excessive (5.4 μg/dL; group 3). Baseline cortisol concentrations had considerable overlap between excessively, adequately, and inadequately controlled dogs. Only baseline cortisol >4.4 μg/dL (in 12% of tests) was a reliable diagnosis of inadequate control. Endogenous ACTH concentrations did not differ between groups. The overlap of the cortisol/ACTH ratio between groups was large. Correct classification was only possible if the cortisol/ACTH ratio was >15, which occurred in 4% of tests. To monitor trilostane treatment the ACTH stimulation test cannot be replaced by baseline cortisol, ACTH concentration, or the cortisol/ACTH ratio. Copyright © 2013 by the American College of Veterinary Internal Medicine.

  18. Gastrointestinal symptoms and association with medication use patterns, adherence, treatment satisfaction, quality of life, and resource use in osteoporosis: baseline results of the MUSIC-OS study.

    Science.gov (United States)

    Modi, A; Sen, S; Adachi, J D; Adami, S; Cortet, B; Cooper, A L; Geusens, P; Mellström, D; Weaver, J; van den Bergh, J P; Nguyen, A M; Sajjan, S

    2016-03-01

    The Medication Use Patterns, Treatment Satisfaction, and Inadequate Control of Osteoporosis Study (MUSIC-OS) is a prospective, observational study of women with osteoporosis in Europe and Canada. At baseline, patients with gastrointestinal symptoms reported lower adherence to osteoporosis treatment, treatment satisfaction, and health-related quality of life, than those without gastrointestinal symptoms. The aim of the study was to examine gastrointestinal (GI) symptoms and the association between GI symptoms and treatment adherence, treatment satisfaction, and health-related quality of life (HRQoL) among osteoporotic women in Europe and Canada. Baseline results are reported here for a prospective study which enrolled postmenopausal, osteoporotic women who were initiating (new users) or continuing (experienced users) osteoporosis treatment at study entry (baseline). A patient survey was administered at baseline and included the occurrence of GI symptoms during 6-month pre-enrolment, treatment adherence (adherence evaluation of osteoporosis (ADEOS), score 0-22), treatment satisfaction (Osteoporosis Treatment Satisfaction Questionnaire for Medications (OPSAT-Q), score 0-100) and HRQoL (EuroQol-5 dimension (EQ-5D) utility, score 0-1; OPAQ-SV, score 0-100). The association between GI symptoms and ADEOS (experienced users), OPSAT-Q (experienced users), and HRQoL (new and experienced users) was assessed by general linear models adjusted for patient characteristics. A total of 2959 patients (2275 experienced and 684 new users) were included. Overall, 68.1% of patients experienced GI symptoms in the past 6 months. Compared with patients without GI symptoms, patients with GI symptoms had lower mean baseline scores on most measures. The mean adjusted differences were ADEOS, -0.43; OPSAT-Q, -5.68; EQ-5D, -0.04 (new users) and -0.06 (experienced users), all P < 0.01. GI symptoms were also associated with lower OPAQ-SV domain scores: physical function, -4.17 (experienced

  19. Baseline characteristics and treatment patterns of patients with schizophrenia initiated on once-every-three-months paliperidone palmitate in a real-world setting.

    Science.gov (United States)

    Joshi, Kruti; Lafeuille, Marie-Hélène; Brown, Brianne; Wynant, Willy; Emond, Bruno; Lefebvre, Patrick; Tandon, Neeta

    2017-10-01

    Since May 2015, adult patients with schizophrenia adequately treated with once monthly paliperidone palmitate (PP1M) may be transitioned to once-every-three-months paliperidone palmitate (PP3M). This study aims to describe baseline characteristics and treatment patterns of patients with schizophrenia initiated on PP3M in a real-world setting. Pharmacy and medical claims from May 2014 to September 2016 for adult patients with schizophrenia initiated on PP3M (index date) in the Symphony Health Solutions database were analyzed. The cohort consisting of all patients and the one restricted to those transitioning from PP1M as per prescribing guideline recommendations were considered. Baseline characteristics were assessed during the 12 month baseline period. PP1M treatment patterns, proportion of days covered (PDC) by mental-health-related medications, and healthcare resource utilization (HRU) patterns were evaluated for each baseline quarter. PP3M treatment patterns were assessed post-index. Among the 1545 adult patients initiated on PP3M who formed the first cohort, 68.8% transitioned from PP1M based on prescribing guidelines and on an adaptation of the strict clinical trial protocol for PP1M to PP3M transition, forming the second cohort. In both cohorts, the proportion of patients with a PDC ≥80% for antipsychotics, antidepressants, anxiolytics, and mood stabilizers increased while the proportion of patients with ≥1 emergency room, inpatient, or outpatient visit decreased in baseline quarters closer to PP3M initiation. Among patients with ≥4 months of follow-up after the first dose, 85-88% had a second dose. Similarly, among those with ≥4 months of follow-up after the second dose, 87-90% received a third dose. Patients initiated on PP3M demonstrated decreased HRU and increased adherence in quarters closer to PP3M initiation, and were persistent on their PP3M treatment.

  20. Probability of treatment following acute decline in lung function in children with cystic fibrosis is related to baseline pulmonary function.

    Science.gov (United States)

    Morgan, Wayne J; Wagener, Jeffrey S; Yegin, Ashley; Pasta, David J; Millar, Stefanie J; Konstan, Michael W

    2013-10-01

    To determine whether the association between high forced expiratory volume in 1 second (FEV1) and increased rate of decline in FEV1 in children with cystic fibrosis could be due to less frequent intervention after acute declines (sudden decline events) in FEV1. Patients with cystic fibrosis aged 6-17 years enrolled in the Epidemiologic Study of Cystic Fibrosis were assessed for a sudden decline event, defined as a 10% relative decline in FEV1% predicted from an average of 3 consecutive stable baseline spirometries. The likelihood of therapeutic intervention within 14 days before and 56 days after this event was then related to their baseline FEV1% predicted age-specific decile using a logistic regression adjusting for age group (6-12 years, 13-17 years) and presence of Pseudomonas aeruginosa on respiratory culture. A total of 10 888 patients had at least 1 sudden decline event in FEV1. Patients in the highest FEV1 decile were significantly less likely than those in the lowest decile to receive intravenous antibiotics (OR, 0.14; 95% CI, 0.11-0.18; P < .001) or be hospitalized (OR, 0.18; 95% CI, 0.14-0.23; P < .001) following decline. Children and adolescents with high baseline lung function are less likely to receive a therapeutic intervention following an acute decline in FEV1, which may explain their greater rate of FEV1 decline. Copyright © 2013 Mosby, Inc. All rights reserved.

  1. Baseline Quality of Life and Risk of Stroke in the ALLHAT Study (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial).

    Science.gov (United States)

    Shams, Tanzila; Auchus, Alexander P; Oparil, Suzanne; Wright, Clinton B; Wright, Jackson; Furlan, Anthony J; Sila, Cathy A; Davis, Barry R; Pressel, Sara; Yamal, Jose-Miguel; Einhorn, Paula T; Lerner, Alan J

    2017-11-01

    The visual analogue scale is a self-reported, validated tool to measure quality of life (QoL). Our purpose was to determine whether baseline QoL predicted strokes in the ALLHAT study (Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial) and evaluate determinants of poststroke change in QoL. In the ALLHAT study, among the 33 357 patients randomized to treatment arms, 1525 experienced strokes; 1202 (79%) strokes were nonfatal. This study cohort includes 32 318 (97%) subjects who completed the baseline visual analogue scale QoL estimate. QoL was measured on a visual analogue scale and adjusted using a Torrance transformation (transformed QoL [TQoL]). Kaplan-Meier curves and adjusted proportional hazards analyses were used to estimate the effect of TQoL on the risk of stroke, on a continuous scale (0-1) and by quartiles (≤0.81, >0.81≤0.89, >0.89≤0.95, >0.95). We analyzed the change from baseline to first poststroke TQoL using adjusted linear regression. After adjusting for multiple stroke risk factors, the hazard ratio for stroke events for baseline TQoL was 0.93 (95% confidence interval, 0.89-0.98) per 0.1 U increase. The lowest baseline TQoL quartile had a 20% increased stroke risk (hazard ratio=1.20 [95% confidence interval, 1.00-1.44]) compared with the reference highest quartile TQoL. Poststroke TQoL change was significant within all treatment groups ( P ≤0.001). Multivariate regression analysis revealed that baseline TQoL was the strongest predictor of poststroke TQoL with similar results for the untransformed QoL. The lowest baseline TQoL quartile had a 20% higher stroke risk than the highest quartile. Baseline TQoL was the only factor that predicted poststroke change in TQoL. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00000542. © 2017 American Heart Association, Inc.

  2. Optimal price subsidies for appropriate malaria testing and treatment behaviour

    DEFF Research Database (Denmark)

    Hansen, Kristian Schultz; Lesner, Tine Hjernø; Østerdal, Lars Peter

    2016-01-01

    , ACT medicines, and cheap, less effective anti-malarials are sold. Assuming that the individual has certain beliefs of the accuracy of the RDT and the probability that the fever is malaria, the model predicts the diagnosis-treatment behaviour of the individual. Subsidies on RDTs and ACT are introduced...... to incentivize appropriate behaviour: choose an RDT before treatment and purchase ACT only if the test is positive. RESULTS: Solving the model numerically suggests that a combined subsidy on both RDT and ACT is cost minimizing and improves diagnosis-treatment behaviour of individuals. For certain beliefs......BACKGROUND: Malaria continues to be a serious public health problem particularly in Africa. Many people infected with malaria do not access effective treatment due to high price. At the same time many individuals receiving malaria drugs do not suffer from malaria because of the common practice...

  3. Low Baseline Interleukin-17A Levels Are Associated with Better Treatment Response at 12 Weeks to Tocilizumab Therapy in Rheumatoid Arthritis Patients

    Directory of Open Access Journals (Sweden)

    Sang Jin Lee

    2015-01-01

    Full Text Available T helper 17-related cytokines have been implicated in rheumatoid arthritis (RA pathogenesis. The study aimed to identify cytokines associated with the treatment response of RA patients to tocilizumab (TCZ, a humanized monoclonal antibody against the interleukin- (IL- 6 receptor. As an independent substudy of the 24-week, randomized, double-blinded CWP-TCZ301 trial of TCZ in RA patients with an inadequate response to disease-modifying antirheumatic drugs, serum levels of cytokines including tumor necrosis factor-alpha, IL-17A, IL-21, IL-23, IL-6, and soluble IL-6 receptor were measured. Baseline IL-17A levels were significantly lower in RA patients who achieved disease activity score 28 (DAS28 remission at 12 weeks of TCZ treatment, compared to patients not in remission. Patients were stratified into IL-17A low group and IL-17A high group. Significantly more patients in the IL-17A low group achieved remission as compared to the IL-17A high group (47.6 versus 17.4%, P=0.032. DAS28 improvement was significantly better in the IL-17A low group than in the IL-17A high group at 12 weeks (P=0.045 and 24 weeks (P=0.046 after adjustment. Other baseline cytokines were not associated with treatment response to TCZ. The data demonstrate that low baseline IL-17A levels are associated with better clinical response to TCZ treatment in RA patients.

  4. Treating nicotine dependence by targeting attention-deficit/ hyperactivity disorder (ADHD) with OROS methylphenidate: the role of baseline ADHD severity and treatment response.

    Science.gov (United States)

    Nunes, Edward V; Covey, Lirio S; Brigham, Gregory; Hu, Mei-Chen; Levin, Frances R; Somoza, Eugene C; Winhusen, Theresa M

    2013-10-01

    To determine whether treatment of attention-deficit/hyperactivity disorder (ADHD) with osmotic-release oral system (OROS) methylphenidate promotes abstinence from smoking among smokers with ADHD who have greater severity of ADHD symptoms at baseline or greater improvement in ADHD during treatment. This is a secondary analysis of data from a randomized, double-blind, 11-week trial conducted between December 2005 and January 2008 at 6 clinical sites; the original trial was sponsored by the National Drug Abuse Clinical Trials Network. Adult cigarette smokers (aged 18-55 years) who met DSM-IV criteria for ADHD were randomly assigned to OROS methylphenidate (72 mg/d) (n = 127) or matching placebo (n = 128). All participants received nicotine patches (21 mg/d) and weekly individual smoking cessation counseling. Logistic regression was used to model prolonged abstinence from smoking (ascertained by self-report and breath carbon monoxide testing) as a function of treatment, baseline ADHD Rating Scale-IV (ADHD-RS) score, change in ADHD-RS score during treatment, and their interactions. Treatment interacted with both ADHD-RS score at baseline (P = .01) and change in ADHD-RS score during treatment (P = .008). Among patients with higher ADHD-RS scores (> 36) at baseline and the most improvement in ADHD during treatment (ADHD-RS change score ≥ 24), 70.0% of those who took OROS methylphenidate achieved abstinence from smoking compared to 36.8% of those who took placebo (P = .02). In contrast, among patients with the lowest ADHD-RS baseline scores (≤ 30), 30.3% of those who took OROS methylphenidate achieved abstinence from smoking compared to 60.7% of those who took placebo (P = .02). OROS methylphenidate, in combination with nicotine patch, may be an effective treatment for nicotine dependence among smokers with more severe ADHD and more robust response of ADHD symptoms to medication. OROS methylphenidate may be counterproductive among smokers with lower severity of ADHD

  5. The RecordAF study: design, baseline data, and profile of patients according to chosen treatment strategy for atrial fibrillation

    DEFF Research Database (Denmark)

    Le Heuzey, Jean-Yves; Breithardt, Günter; Camm, John

    2010-01-01

    in 21 countries across Europe, America, and Asia; recruitment was completed in April 2008. The primary objectives were to prospectively assess the therapeutic success and clinical outcomes in rhythm- and rate-control strategies. The study design and patient baseline data are reported. A total of 5......The REgistry on Cardiac rhythm disORDers assessing the control of Atrial Fibrillation (RecordAF) is the first worldwide, 1-year observational, longitudinal study of the management of paroxysmal/persistent atrial fibrillation (AF) in recently diagnosed patients. The study was conducted at 532 sites......,814 patients with AF were registered, and 5,604 were eligible for evaluation. Rhythm- and rate-control strategies were applied to 55% and 45% of patients, respectively, at study inclusion. Rhythm-control patients mainly received class III agents (45%) or beta blockers (51%), except for sotalol, and rate...

  6. Simple, efficient estimators of treatment effects in randomized trials using generalized linear models to leverage baseline variables.

    Science.gov (United States)

    Rosenblum, Michael; van der Laan, Mark J

    2010-04-01

    Models, such as logistic regression and Poisson regression models, are often used to estimate treatment effects in randomized trials. These models leverage information in variables collected before randomization, in order to obtain more precise estimates of treatment effects. However, there is the danger that model misspecification will lead to bias. We show that certain easy to compute, model-based estimators are asymptotically unbiased even when the working model used is arbitrarily misspecified. Furthermore, these estimators are locally efficient. As a special case of our main result, we consider a simple Poisson working model containing only main terms; in this case, we prove the maximum likelihood estimate of the coefficient corresponding to the treatment variable is an asymptotically unbiased estimator of the marginal log rate ratio, even when the working model is arbitrarily misspecified. This is the log-linear analog of ANCOVA for linear models. Our results demonstrate one application of targeted maximum likelihood estimation.

  7. Baseline depression levels do not affect efficacy of cognitive-behavioral self-help treatment for insomnia

    NARCIS (Netherlands)

    Lancee, J.; van den Bout, J.; van Straten, A.; Spoormaker, V.I.

    2013-01-01

    Background: Cognitive-behavioral therapy can effectively treat insomnia (CBT-I). Randomized controlled trials have shown efficacy of self-help CBT-I, but unclear is whether excluding depressive patients boosted treatment effects. Method: We administered unsupported self-help CBT-I to insomnia

  8. Baseline depression levels do not affect efficacy of cognitive-behavioral self-help treatment for insomnia

    NARCIS (Netherlands)

    Lancee, J.; van den Bout, J.; van Straten, A.; Spoormaker, V.I.

    2013-01-01

    Background Cognitive-behavioral therapy can effectively treat insomnia (CBT-I). Randomized controlled trials have shown efficacy of self-help CBT-I, but unclear is whether excluding depressive patients boosted treatment effects. Method We administered unsupported self-help CBT-I to insomnia patients

  9. A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure: rationale, design, and baseline characteristics of BIOSTAT-CHF

    NARCIS (Netherlands)

    Voors, Adriaan A.; Anker, Stefan D.; Cleland, John G.; Dickstein, Kenneth; Filippatos, Gerasimos; van der Harst, Pim; Hillege, Hans L.; Lang, Chim C.; ter Maaten, Jozine M.; Ng, Leong; Ponikowski, Piotr; Samani, Nilesh J.; van Veldhuisen, Dirk J.; Zannad, Faiz; Zwinderman, Aeilko H.; Metra, Marco

    2016-01-01

    Despite major improvements in pharmacological and device treatments, heart failure remains a syndrome with high morbidity and mortality, poor quality of life, and high health-care costs. Given the extensive heterogeneity among patients with heart failure, substantial differences in the response to

  10. A systems BIOlogy Study to TAilored Treatment in Chronic Heart Failure : rationale, design, and baseline characteristics of BIOSTAT-CHF

    NARCIS (Netherlands)

    Voors, Adriaan A.; Anker, Stefan D.; Cleland, John G.; Dickstein, Kenneth; Filippatos, Gerasimos; van der Harst, Pim; Hillege, Hans L.; Lang, Chim C.; ter Maaten, Jozine M.; Ng, Leong; Ponikowski, Piotr; Samani, Nilesh J.; van Veldhuisen, Dirk J.; Zannad, Faiz; Zwinderman, Aeilko H.; Metra, Marco

    AimsDespite major improvements in pharmacological and device treatments, heart failure remains a syndrome with high morbidity and mortality, poor quality of life, and high health-care costs. Given the extensive heterogeneity among patients with heart failure, substantial differences in the response

  11. Multidisciplinary evaluation at baseline and during treatment improves the rate of compliance and efficacy of deferasirox in elderly myelodysplastic patients.

    Science.gov (United States)

    Del Corso, Lisette; Biale, Lucia; Parodi, Emanuele Luigi; Russo, Rodolfo; Filiberti, Rosa; Arboscello, Eleonora

    2017-04-01

    Deferasirox (DFX) is used to reduce iron levels in patients with myelodysplastic syndrome (MDS) who develop iron overload after chronic red blood cell infusions. However, DFX can be associated with renal and gastrointestinal toxicities, which may cause treatment interruption or discontinuation. This study aimed to determine the effectiveness and safety of DFX in patients with MDS. This multicenter, retrospective, observational study was conducted at two hospitals in Italy. Elderly patients with transfusion-dependent MDS received DFX for up to 12 months and were divided into two groups: group A comprised patients who were not under multidisciplinary assessment; group B comprised patients under multidisciplinary control. Treatment effectiveness was estimated by monitoring the serum ferritin (SF) levels throughout the study. Any treatment-related adverse events (AEs), clinically relevant analytical alterations, and reasons for treatment discontinuation were monitored. The study included 44 patients (13 female, 31 male; median age 77.0 years). At 3 months, SF levels decreased by ≥20 % in 29 and 31 % of patients in groups A and B, respectively, in 17 and 36 % of patients at 6 months, and in 22 and 58 % at 12 months. The most common AEs were diarrhea and increased serum creatinine, which were more frequent in group A. The discontinuation rate after renal AE was 15 and 5 % in groups A and B, respectively. Multidisciplinary evaluation can be an effective strategy for monitoring renal function in patients on DFX therapy, to improve treatment adherence and overall efficacy in elderly patients with MDS.

  12. Differential item functioning (DIF) in the EORTC QLQ-C30 : a comparison of baseline, on-treatment and off-treatment data

    NARCIS (Netherlands)

    Scott, Neil W.; Fayers, Peter M.; Aaronson, Neil K.; Bottomley, Andrew; de Graeff, Alexander; Groenvold, Mogens; Gundy, Chad; Koller, Michael; Petersen, Morten A.; Sprangers, Mirjam A. G.

    Introduction Differential item functioning (DIF) analyses can be used to explore translation, cultural, gender or other differences in the performance of quality of life (QoL) instruments. These analyses are commonly performed using "baseline" or pretreatment data. We previously reported DIF

  13. Differential item functioning (DIF) in the EORTC QLQ-C30: a comparison of baseline, on-treatment and off-treatment data

    DEFF Research Database (Denmark)

    Scott, Neil W.; Fayers, Peter M.; Aaronson, Neil K.

    2009-01-01

    Differential item functioning (DIF) analyses can be used to explore translation, cultural, gender or other differences in the performance of quality of life (QoL) instruments. These analyses are commonly performed using "baseline" or pretreatment data. We previously reported DIF analyses to examine...

  14. Differential item functioning (DIF) in the EORTC QLQ-C30: a comparison of baseline, on-treatment and off-treatment data

    NARCIS (Netherlands)

    Scott, Neil W.; Fayers, Peter M.; Aaronson, Neil K.; Bottomley, Andrew; de Graeff, Alexander; Groenvold, Mogens; Gundy, Chad; Koller, Michael; Petersen, Morten A.; Sprangers, Mirjam A. G.

    2009-01-01

    Introduction Differential item functioning (DIF) analyses can be used to explore translation, cultural, gender or other differences in the performance of quality of life (QoL) instruments. These analyses are commonly performed using "baseline" or pretreatment data. We previously reported DIF

  15. An Examination of Fluoxetine for the Treatment of Selective Mutism Using a Nonconcurrent Multiple-Baseline Single-Case Design Across 5 Cases.

    Science.gov (United States)

    Barterian, Justin A; Sanchez, Joel M; Magen, Jed; Siroky, Allison K; Mash, Brittany L; Carlson, John S

    2018-01-01

    This study examined the utility of fluoxetine in the treatment of 5 children, aged 5 to 14 years, diagnosed with selective mutism who also demonstrated symptoms of social anxiety. A nonconcurrent, randomized, multiple-baseline, single-case design with a single-blind placebo-controlled procedure was used. Parents and the study psychiatrist completed multiple methods of assessment including Direct Behavior Ratings and questionnaires. Treatment outcomes were evaluated by calculating effect sizes for each participant as an individual and for the participants as a group. Information regarding adverse effects with an emphasis on behavioral disinhibition and ratings of parental acceptance of the intervention was gathered. All 5 children experienced improvement in social anxiety, responsive speech, and spontaneous speech with medium to large effect sizes; however, children still met criteria for selective mutism at the end of the study. Adverse events were minimal, with only 2 children experiencing brief occurrences of minor behavioral disinhibition. Parents found the treatment highly acceptable.

  16. Efficacy of artesunate-amodiaquine for the treatment of acute uncomplicated falciparum malaria in southern Mauritania.

    Science.gov (United States)

    Ouldabdallahi, Mohamed; Alew, Ismail; Salem, Mohamed Salem Ould Ahmedou; Dit Dialaw Ba, Mamadou; Boukhary, Ali Ould Mohamed Salem; Khairy, Mohamed Lemine Ould; Aziz, Mohamed Boubacar Abdel; Ringwald, Pascal; Basco, Leonardo K; Niang, Saidou Doro; Lebatt, Sid Mohamed

    2014-12-16

    A regular evaluation of therapeutic efficacy in sentinel sites and a system of surveillance are required to establish treatment guidelines and adapt national anti-malarial drug policy to the rapidly changing epidemiology of drug-resistant malaria. The current anti-malarial treatment guideline in Mauritania, officially recommended since 2006, is based on artemisinin-based combination therapy. The aim of the present study was to evaluate clinical efficacy and tolerance of artesunate-amodiaquine, the first-line treatment for acute uncomplicated malaria, in Mauritanian paediatric and adult patients to validate its continued use in the country. Plasmodium falciparum-infected symptomatic patients aged > six months were enrolled in Kobeni and Timbedra in southern Mauritania in September to October 2013. Co-formulated artesunate-amodiaquine was administered at the recommended dose over three days. Patients were followed until day 28. Parasitological and clinical response was classified according to the standard 2009 World Health Organization protocol. A total of 130 patients (65 in Kobeni and 65 in Timbedra) were enrolled in the study. Seventeen patients (13.1%) were either excluded (before PCR correction) or lost to follow-up. Based on the per protocol analysis, artesunate-amodiaquine efficacy (i.e., the proportion of adequate clinical and parasitological response) was 96.6% in Kobeni and 98.2% in Timbedra before PCR correction. Late clinical failure was observed in two patients in Kobeni and one patient in Timbedra. After PCR correction, the efficacy rate in the two study sites was 98.2%. On day 3, all patients were afebrile and had negative smears. Treatment was well tolerated. Artesunate-amodiaquine is well tolerated and highly efficacious for the treatment of uncomplicated P. falciparum malaria. In the majority of patients, fever and parasitaemia were rapidly cleared before day 3. The results support the national anti-malarial drug guideline for a continued use of

  17. The choice of the noninferiority margin in clinical trials was driven by baseline risk, type of primary outcome, and benefits of new treatment.

    Science.gov (United States)

    Gayet-Ageron, Angèle; Agoritsas, Thomas; Rudaz, Sandrine; Courvoisier, Delphine; Perneger, Thomas

    2015-10-01

    To explore characteristics of clinical trials that influence the choice of the noninferiority margin (NIM) when planning the trial. We conducted an experimental survey among corresponding authors of randomized controlled trials indexed in MEDLINE. We described two hypothetical studies and asked the respondents' opinion on the largest loss of effectiveness that is clinically negligible (or the smallest lost of effectiveness that is clinically important in the superiority scenario). We randomly manipulated four study attributes in each vignette, using a factorial design. A total of 364 researchers participated. The values for NIMs were significantly lower than the differences to be detected in a superiority trial. The NIM was smaller when the primary outcome was mortality compared with treatment failure, when baseline risk in the control arm was lower, and when the advantage of the new treatment was a lower cost compared with having fewer side effects. In contrast, the population age group under study and the difficulty to recruit patients showed no effect on the choice of the NIM. In our experimental study, the factors associated with lower NIMs were mortality as a primary outcome, low baseline risk, and a less costly new treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Low-dose budesonide treatment reduces severe asthma-related events in patients with infrequent asthma symptoms at baseline

    DEFF Research Database (Denmark)

    Reddel, H. K.; Busse, W. W.; Pedersen, Søren

    2015-01-01

    .0 for Groups 0-1, >1-2, respectively. The rate of severe exacerbations identified by oral/systemic corticosteroid courses was lower for budesonide compared with placebo in all 3 symptom frequency groups (Figure). Patients treated with budesonide experienced significantly greater improvements in symptoms...... and significantly more symptom-free days compared with patients receiving placebo in all symptom frequency groups. CONCLUSIONS: Long-term, once-daily, low-dose budesonide treatment decreases the risk of SAREs and improves asthma symptoms in patients with mild, recent-onset asthma. These beneficial effects were seen...

  19. Evaluating the cognitive effects of donepezil 23 mg/d in moderate and severe Alzheimer’s disease: analysis of effects of baseline features on treatment response

    Science.gov (United States)

    2013-01-01

    Background Treatment of Alzheimer’s disease with acetylcholinesterase inhibitors can result in symptomatic benefits, but patients often show variable responses. The objective of this post hoc analysis was to investigate relationships between easily identifiable baseline characteristics/demographics and cognitive response in patients treated with either donepezil 23 mg/d or 10 mg/d and to identify factors potentially influencing response. Methods A post hoc analysis was conducted using data from a large, 24-week, randomized, double-blind, international study enrolling patients with moderate to severe Alzheimer’s disease (baseline Mini-Mental State Examination [MMSE], 0-20) (NCT 00478205). Cognitive changes in subgroups of patients based on selected baseline and demographic characteristics were compared using the least squares mean changes in Severe Impairment Battery scores at Week 24. Univariate and multivariate analyses were also performed. Results Donepezil 23 mg/d provided statistically significant incremental cognitive benefits over donepezil 10 mg/d irrespective of baseline functional severity, measured by scores on the Alzheimer’s Disease Cooperative Study-Activities of Daily Living-severe version (P donepezil 23 mg/d over 10 mg/d were seen in both subgroups when based on MMSE scores of 0-9 versus 10-20 (P  0.05). Statistically significant incremental cognitive benefits of donepezil 23 mg/d over 10 mg/d were also observed regardless of age, gender, weight, or prestudy donepezil 10 mg/d treatment duration (P donepezil 23 mg/d over 10 mg/d were achieved regardless of the patient’s age, gender, weight, duration of prior donepezil 10 mg/d, and functional severity. The influence of baseline cognitive severity on response seemed to be dependent on the level of impairment, with cognitive benefits of donepezil 23 mg/d over 10 mg/d most apparent in those patients at a more advanced stage of disease. These data may be useful

  20. A baseline audit of referral and treatment delivered to patients in the intermediate minor oral surgery service in Croydon PCT.

    Science.gov (United States)

    O'Neill, Eunan; Gallagher, Jennifer E; Kendall, Nick

    2012-01-01

    Patients attending for primary dental care may require oral surgery procedures beyond the capability of a generalist and thus need to be treated by a dentist with greater expertise. In the United Kingdom, it is increasingly accepted that such care may be provided in primary care settings by specialists or dentists with a special interest. In response to local pressures, an intermediate minor oral surgery (IMOS) service has been established in Croydon, south west London, to provide oral surgery treatment for non-urgent patients on referral. To audit the appropriateness and quality of oral surgery referrals after triage to an IMOS service in Croydon and to set standards for future audits on this topic. An audit tool was developed in line with the local referral guidelines and agreed with local stakeholders. Information on 501 (10%) triaged referrals to IMOS practices over a 24-month period was obtained through the referral management centre. A 10% sample of referrals per month to each practice was calculated and IMOS providers randomly selected the relevant patient records. Using an agreed audit pro forma, information on the indications for referral, treatment provided, and dates relating to patient management, in addition to the age and sex of patients, was collected from the IMOS providers by one investigator. Descriptive analysis of the data was performed. Of the 501 patient records that were examined, 99% of patients were treated in IMOS practices, with only three (less than 1%) patients being referred on to hospital consultant services. The largest proportion (237; 40%) of referrals was for the extraction of teeth considered to have special difficulty, followed by lower third molars (154; 26%). Almost one-third (159; 32%) of patients were referred for more than one procedure. One in eight (72; 13%) teeth removed by the IMOS providers were recorded as a simple extraction without medical complications. In general, patients were referred appropriately to the

  1. Treatment guided by rapid diagnostic tests for malaria in Tanzanian children: safety and alternative bacterial diagnoses

    Directory of Open Access Journals (Sweden)

    Sykes Alma

    2011-10-01

    Full Text Available Abstract Background WHO guidelines for the treatment of young children with suspected malaria have recently changed from presumptive treatment to anti-malarial treatment guided by a blood slide or malaria rapid diagnostic test (RDT. However, there is limited evidence of the safety of this policy in routine outpatient settings in Africa. Methods Children 3-59 months of age with a non-severe febrile illness and no obvious cause were enrolled over a period of one year in a malaria endemic area of Tanzania. Treatment was determined by the results of a clinical examination and RDT result, and blood culture and serum lactate were also collected. RDT-negative children were followed up over 14 days. Results Over the course of one year, 965 children were enrolled; 158 (16.4% were RDT-positive and treated with artemether-lumefantrine and 807 (83.4% were RDT-negative and treated with non-anti-malarial medicines. Compared with RDT-positives, RDT-negative children were on average younger with a lower axillary temperature and more likely to have a history of cough or difficulty in breathing. Six (0.6% children became RDT-positive after enrolment, all of whom were PCR-negative for Plasmodium falciparum DNA at enrolment. In addition, 12 (1.2% children were admitted to hospital, one with possible malaria, none of whom died. A bacterial pathogen was identified in 9/965 (0.9% children, eight of whom were RDT-negative and one was RDT-positive, but slide-negative. Excluding three children with Salmonella typhi, all of the children with bacteraemia were ≤12 months of age. Compared to double-read research slide results RDTs had a sensitivity of 97.8% (95%CI 96.9-98.7 and specificity of 96.3% (95%CI 96.3-98.4. Conclusions Use of RDTs to direct the use of anti-malarial drugs in young children did not result in any missed diagnoses of malaria although new infections soon after a consultation with a negative RDT result may undermine confidence in results. Invasive

  2. Malaria Treatment Policy Change and Implementation: The Case of Uganda

    Directory of Open Access Journals (Sweden)

    Miriam Nanyunja

    2011-01-01

    Full Text Available Malaria due to P. falciparum is the number one cause of morbidity and mortality in Uganda where it is highly endemic in 95% of the country. The use of efficacious and effective antimalarial medicines is one of the key strategies for malaria control. Until 2000, Chloroquine (CQ was the first-line drug for treatment of uncomplicated malaria in Uganda. Due to progressive resistance to CQ and to a combination of CQ with Sulfadoxine-Pyrimethamine, Uganda in 2004 adopted the use of ACTs as first-line drug for treating uncomplicated malaria. A review of the drug policy change process and postimplementation reports highlight the importance of managing the policy change process, generating evidence for policy decisions and availability of adequate and predictable funding for effective policy roll-out. These and other lessons learnt can be used to guide countries that are considering anti-malarial drug change in future.

  3. Malaria treatment policy change and implementation: the case of Uganda.

    Science.gov (United States)

    Nanyunja, Miriam; Nabyonga Orem, Juliet; Kato, Frederick; Kaggwa, Mugagga; Katureebe, Charles; Saweka, Joaquim

    2011-01-01

    Malaria due to P. falciparum is the number one cause of morbidity and mortality in Uganda where it is highly endemic in 95% of the country. The use of efficacious and effective antimalarial medicines is one of the key strategies for malaria control. Until 2000, Chloroquine (CQ) was the first-line drug for treatment of uncomplicated malaria in Uganda. Due to progressive resistance to CQ and to a combination of CQ with Sulfadoxine-Pyrimethamine, Uganda in 2004 adopted the use of ACTs as first-line drug for treating uncomplicated malaria. A review of the drug policy change process and postimplementation reports highlight the importance of managing the policy change process, generating evidence for policy decisions and availability of adequate and predictable funding for effective policy roll-out. These and other lessons learnt can be used to guide countries that are considering anti-malarial drug change in future.

  4. Baseline characteristics and concerns of female cancer patients/survivors seeking treatment at a Female Sexual Medicine Program.

    Science.gov (United States)

    Carter, Jeanne; Stabile, Cara; Seidel, Barbara; Baser, Raymond E; Gunn, Abigail R; Chi, Stephanie; Steed, Rebecca F; Goldfarb, Shari; Goldfrank, Deborah J

    2015-08-01

    The purpose of this study is to characterize patients seeking treatment at a Female Sexual Medicine and Women's Health Program and examine their sexual/vaginal health issues. Data from clinical assessment forms were extracted from 509 women referred to the Female Sexual Medicine and Women's Health Program during/after cancer treatment. The form consists of a Vaginal Assessment Scale (VAS), vaginal health items, patient-reported outcomes (PROs) (Sexual Activity Questionnaire [SAQ], Sexual Self-Schema Scale [SSS], Female Sexual Function Index [FSFI]), and exploratory items. Of 509 patients, 493 (97 %) completed PROs; 253 (50 %) received a pelvic examination. The majority had a history of breast (n = 260, 51 %), gynecologic (n = 184, 36 %), or colorectal/anal (n = 35, 7 %) cancer. Mean age was 51.2 years; 313 (62 %) were married/partnered. Approximately two thirds had elevated vaginal pH scores (5-6.5 [35 %] or 6.5+ [33 %]) and minimal (62 %) or no (5 %) vaginal moisture. Eighty-seven patients (44 %) experienced pain during their exam (23 % mild, 11 % moderate, 1.5 % severe, and 8.5 % not indicated). Fifty-three percent engaged in sexual activity with a partner; only 43 % felt confident about future sexual activity. Ninety-three percent were somewhat to very concerned/worried about sexual function/vaginal health. Approximately half had moderate/severe dryness (n = 133, 51 %) and dyspareunia (n = 120, 46 %). The mean SSS score was 60.7, indicating a slightly positive sexual self-view. However, 93.5 % (n = 429) had an FSFI score <26.55, suggesting sexual dysfunction. At initial consult, women reported vaginal dryness, pain, and sexual dysfunction. For many women, pelvic exams showed elevated vaginal pH, lack of moisture, and discomfort with the exam itself. Future analyses will examine changes over time.

  5. Evaluation of SMS reminder messages for altering treatment adherence and health seeking perceptions among malaria care-seekers in Nigeria.

    Science.gov (United States)

    Liu, Jenny X; Modrek, Sepideh

    2016-12-01

    In Nigeria, access to malaria diagnostics may be expanded if drug retailers were allowed to administer malaria rapid diagnostic tests (RDTs). A 2012 pilot intervention showed that short message service (SMS) reminder messages could boost treatment adherence to RDT results by 10-14% points. This study aimed to replicate the SMS intervention in a different population, and additionally test the effect of an expanded message about anticipated RDT access policy change on customers' acceptability for drug retailers' administration of RDTs. One day after being tested with an RDT, participants who purchased malaria treatment from drug shops were randomized to receive (1) a basic SMS reminder repeating the RDT result and appropriate treatment actions, (2) an expanded SMS reminder additionally saying that the 'government might allow pharmacists/chemists to do RDTs' or (3) no SMS reminders (i.e. control). Using regression analysis, we estimate intent-to-treat (ITT) and treatment effects on the treated for 686 study participants. Results corroborate previous findings that a basic SMS reminder increased treatment adherence [odds ratio (OR) = 1.53, 95% CI 0.96-2.44] and decreased use of unnecessary anti-malarials for RDT-negative adults [OR = 0.63, 95% CI 0.39-1.00]. The expanded SMS also increased adherence for adults [OR = 1.42, 95% CI 0.97-2.07], but the effects for sick children differed-the basic SMS did not have any measurable impact on treatment adherence [OR = 0.87, 95% CI 0.24-3.09] or use of unnecessary anti-malarials [OR = 1.27, 95% CI 0.32-1.93], and the expanded SMS actually led to poorer treatment adherence [OR = 0.26, 95% CI 0.10-0.66] and increased use of unnecessary anti-malarials [OR = 4.67, 95% CI 1.76-12.43]. Further, the targeted but neutral message in the expanded SMS lowered acceptance for drug retailers' administration of RDTs [OR = 0.55, 95% CI 0.10-2.93], counter to what we hypothesized. Future SMS interventions should

  6. Most Trial Eligibility Criteria and Patient Baseline Characteristics Do Not Modify Treatment Effect in Trials Using Targeted Therapies for Rheumatoid Arthritis: A Meta-Epidemiological Study.

    Directory of Open Access Journals (Sweden)

    Anton Wulf Christensen

    Full Text Available To determine if variations in trial eligibility criteria and patient baseline characteristics could be considered effect modifiers of the treatment response when testing targeted therapies (biological agents and targeted synthetic disease modifying antirheumatic drugs (DMARDs for rheumatoid arthritis (RA.We conducted a meta-epidemiological study of all trials evaluating a targeted therapy approved by regulatory authorities for treating RA. The database search was completed on December 11th 2013. Eligible trials reported ACR20 data at months 3-6 and used an add-on design. Odds ratios (ORs were calculated from the response rates and compared among the trial eligibility criteria/patient baseline characteristics of interest. Comparisons are presented as the Ratio of Odds Ratios (ROR.Sixty-two trials (19,923 RA patients were included in the primary analyses using ACR20 response. Overall, targeted therapies constituted an effective treatment (OR 3.96 95% confidence interval (CI 3.41 to 4.60. The majority of the trial eligibility criteria and patient baseline characteristics did not modify treatment effect. The added benefit of targeted therapies was lower in trials including "DMARD-naïve" patients compared with trials including "DMARD inadequate responders" (ROR = 0.45, 95%CI 0.31 to 0.66 and trials including "targeted therapy inadequate responders" (0.50, 95%CI 0.29 to 0.87, test for interaction: p = 0.0002. Longer mean disease duration was associated with a higher likelihood of responding to treatment (β = 1.05, 95%CI 1.00 to 1.11 OR's per year; p = 0.03. Analyses conducted using DAS28-remission as the outcome supported the above-mentioned findings.Our results suggest that a highly selective inclusion is not associated with greater treatment effect, as might otherwise be expected. The added benefit of a targeted therapy was lower in trials including patients who were DMARD-naïve and trials including patients with shorter disease durations.

  7. Baseline OCT measurements in the idiopathic intracranial hypertension treatment trial, part I: quality control, comparisons, and variability.

    Science.gov (United States)

    Auinger, Peggy; Durbin, Mary; Feldon, Steven; Garvin, Mona; Kardon, Randy; Keltner, John; Kupersmith, Mark; Sibony, Patrick; Plumb, Kim; Wang, Jui-Kai; Werner, John S

    2014-11-04

    Optical coherence tomography (OCT) has been used to investigate papilledema in single-site, mostly retrospective studies. We investigated whether spectral-domain OCT (SD-OCT), which provides thickness and volume measurements of the optic nerve head and retina, could reliably demonstrate structural changes due to papilledema in a prospective multisite clinical trial setting. At entry, 126 subjects in the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) with mild visual field loss had optic disc and macular scans, using the Cirrus SD-OCT. Images were analyzed by using the proprietary commercial and custom 3D-segmentation algorithms to calculate retinal nerve fiber layer (RNFL), total retinal thickness (TRT), optic nerve head volume (ONHV), and retinal ganglion cell layer (GCL) thickness. We evaluated variability, with interocular comparison and correlation between results for both methods. The average RNFL thickness > 95% of normal controls in 90% of eyes and the RNFL, TRT, ONH height, and ONHV showed strong (r > 0.8) correlations for interocular comparisons. Variability for repeated testing of OCT parameters was low for both methods and intraclass correlations > 0.9 except for the proprietary GCL thickness. The proprietary algorithm-derived RNFL, TRT, and GCL thickness measurements had failure rates of 10%, 16%, and 20% for all eyes respectively, which were uncommon with 3D-segmentation-derived measurements. Only 7% of eyes had GCL thinning that was less than fifth percentile of normal age-matched control eyes by both methods. Spectral-domain OCT provides reliable continuous variables and quantified assessment of structural alterations due to papilledema. (ClinicalTrials.gov number, NCT01003639.). Copyright 2014 The Association for Research in Vision and Ophthalmology, Inc.

  8. Baseline HCV Antibody Prevalence and Risk Factors among Drug Users in China's National Methadone Maintenance Treatment Program.

    Directory of Open Access Journals (Sweden)

    Changhe Wang

    Full Text Available Hepatitis C virus (HCV is the most common viral infection among injecting drug users worldwide. We aimed to assess HCV antibody prevalence and associated risk factors among clients in the Chinese national methadone maintenance treatment (MMT program.Data from 296,209 clients who enrolled in the national MMT program between March 2004 and December 2012 were analyzed to assess HCV antibody prevalence, associated risk factors, and geographical distribution.Anti-HCV screening was positive for 54.6% of clients upon MMT entry between 2004 and 2012. HCV antibody prevalence at entry declined from 66.8% in 2005 to 45.9% in 2012. The most significant predictors of HCV seropositivity were injecting drug use (adjusted odds ratio [AOR]: 8.34, 95% confidence interval [CI]: 8.17-8.52, p<0.0001 and a history of drug use ≥9 years (AOR: 2.01, 95% CI: 1.96-2.06, p<0.0001. Being female, of Uyghur or Zhuang ethnicity, and unmarried were identified as demographic risk factors (all p-values<0.0001. Of the 28 provincial-level divisions included in the study, we found that 5 divisions had HCV antibody prevalence above 70% and 20 divisions above 50%. The HCV screening rate within 6 months after MMT entry greatly increased from 30.4% in 2004 to 93.1% in 2012.The current HCV antibody prevalence remains alarmingly high among MMT clients throughout most provincial-level divisions in China, particularly among injecting drug users and females. A comprehensive prevention strategy is needed to control the HCV epidemic among MMT clients in China.

  9. Deployment and use of mobile phone technology for real-time reporting of fever cases and malaria treatment failure in areas of declining malaria transmission in Muheza district north-eastern Tanzania.

    Science.gov (United States)

    Francis, Filbert; Ishengoma, Deus S; Mmbando, Bruno P; Rutta, Acleus S M; Malecela, Mwelecele N; Mayala, Benjamin; Lemnge, Martha M; Michael, Edwin

    2017-08-01

    Early detection of febrile illnesses at community level is essential for improved malaria case management and control. Currently, mobile phone-based technology has been commonly used to collect and transfer health information and services in different settings. This study assessed the applicability of mobile phone-based technology in real-time reporting of fever cases and management of malaria by village health workers (VHWs) in north-eastern Tanzania. The community mobile phone-based disease surveillance and treatment for malaria (ComDSTM) platform, combined with mobile phones and web applications, was developed and implemented in three villages and one dispensary in Muheza district from November 2013 to October 2014. A baseline census was conducted in May 2013. The data were uploaded on a web-based database and updated during follow-up home visits by VHWs. Active and passive case detection (ACD, PCD) of febrile cases were done by VHWs and cases found positive by malaria rapid diagnostic test (RDT) were given the first dose of artemether-lumefantrine (AL) at the dispensary. Each patient was visited at home by VHWs daily for the first 3 days to supervise intake of anti-malarial and on day 7 to monitor the recovery process. The data were captured and transmitted to the database using mobile phones. The baseline population in the three villages was 2934 in 678 households. A total of 1907 febrile cases were recorded by VHWs and 1828 (95.9%) were captured using mobile phones. At the dispensary, 1778 (93.2%) febrile cases were registered and of these, 84.2% were captured through PCD. Positivity rates were 48.2 and 45.8% by RDT and microscopy, respectively. Nine cases had treatment failure reported on day 7 post-treatment and adherence to treatment was 98%. One patient with severe febrile illness was referred to Muheza district hospital. The study showed that mobile phone-based technology can be successfully used by VHWs in surveillance and timely reporting of fever

  10. Provider knowledge of treatment policy and dosing regimen with artemether-lumefantrine and quinine in malaria-endemic areas of western Kenya.

    Science.gov (United States)

    Watsierah, Carren A; Onyango, Rosebella O; Ombaka, James H; Abong'o, Benard O; Ouma, Collins

    2012-12-29

    Due to widespread anti-malarial drug resistance in many countries, Kenya included, artemisinin-based Combination Therapy (ACT) has been adopted as the most effective treatment option against malaria. Artemether-lumefantrine (AL) is the first-line ACT for treatment of uncomplicated malaria in Kenya, while quinine is preferred for complicated and severe malaria. Information on the providers' knowledge and practices prior to or during AL and quinine implementation is scanty. The current study evaluated providers' knowledge and practices of treatment policy and dosing regimens with AL and quinine in the public, private and not-for-profit drug outlets. A cross-sectional survey using three-stage sampling of 288 (126 public, 96 private and 66 not-for-profits) providers in drug outlets was conducted in western Kenya in two Plasmodium falciparum-endemic regions with varying malarial risk. Information on provider in-service training, knowledge (qualification, treatment policy, dosing regimen, recently banned anti-malarials) and on practices (request for written prescription, prescription of AL, selling partial packs and advice given to patients after prescription), was collected. Only 15.6% of providers in private outlets had received any in-service training on AL use. All (100%) in public and majority (98.4%) in not-for-profit outlets mentioned AL as first line-treatment drug. Quinine was mentioned as second-line drug by 47.9% in private outlets. A total of 92.0% in public, 57.3% in private and 78.8% in not-for-profit outlets stated correct AL dose for adults. A total of 85.7% of providers in public, 30.2% in private and 41.0% in not-for-profit outlets were aware that SP recommendations changed from treatment for mild malaria to IPTp in high risk areas. In-service training influenced treatment regimen for uncomplicated malaria (P = 0.039 and P = 0.039) and severe malaria (P < 0.0001 and P = 0.002) in children and adults, respectively. Most (82.3%) of private

  11. Provider knowledge of treatment policy and dosing regimen with artemether-lumefantrine and quinine in malaria-endemic areas of western Kenya

    Directory of Open Access Journals (Sweden)

    Watsierah Carren A

    2012-12-01

    Full Text Available Abstract Background Due to widespread anti-malarial drug resistance in many countries, Kenya included, artemisinin-based Combination Therapy (ACT has been adopted as the most effective treatment option against malaria. Artemether-lumefantrine (AL is the first-line ACT for treatment of uncomplicated malaria in Kenya, while quinine is preferred for complicated and severe malaria. Information on the providers’ knowledge and practices prior to or during AL and quinine implementation is scanty. The current study evaluated providers’ knowledge and practices of treatment policy and dosing regimens with AL and quinine in the public, private and not-for-profit drug outlets. Methods A cross-sectional survey using three-stage sampling of 288 (126 public, 96 private and 66 not-for-profits providers in drug outlets was conducted in western Kenya in two Plasmodium falciparum-endemic regions with varying malarial risk. Information on provider in-service training, knowledge (qualification, treatment policy, dosing regimen, recently banned anti-malarials and on practices (request for written prescription, prescription of AL, selling partial packs and advice given to patients after prescription, was collected. Results Only 15.6% of providers in private outlets had received any in-service training on AL use. All (100% in public and majority (98.4% in not-for-profit outlets mentioned AL as first line-treatment drug. Quinine was mentioned as second-line drug by 47.9% in private outlets. A total of 92.0% in public, 57.3% in private and 78.8% in not-for-profit outlets stated correct AL dose for adults. A total of 85.7% of providers in public, 30.2% in private and 41.0% in not-for-profit outlets were aware that SP recommendations changed from treatment for mild malaria to IPTp in high risk areas. In-service training influenced treatment regimen for uncomplicated malaria (P = 0.039 and P = 0.039 and severe malaria (P P = 0.002 in children and adults

  12. Assessment of early treatment response to neoadjuvant chemotherapy in breast cancer using non-mono-exponential diffusion models: a feasibility study comparing the baseline and mid-treatment MRI examinations

    Energy Technology Data Exchange (ETDEWEB)

    Bedair, Reem; Manavaki, Roido; Gill, Andrew B.; Abeyakoon, Oshaani; Gilbert, Fiona J. [University of Cambridge, Department of Radiology, School of Clinical Medicine, Cambridge (United Kingdom); Priest, Andrew N.; Patterson, Andrew J. [Cambridge University Hospitals NHS Foundation Trust, Department of Radiology, Addenbrookes Hospital, Cambridge (United Kingdom); McLean, Mary A. [Cambridge University Hospitals NHS Foundation Trust, Department of Radiology, Addenbrookes Hospital, Cambridge (United Kingdom); University of Cambridge, Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Cambridge (United Kingdom); Graves, Martin J. [University of Cambridge, Department of Radiology, School of Clinical Medicine, Cambridge (United Kingdom); Cambridge University Hospitals NHS Foundation Trust, Department of Radiology, Addenbrookes Hospital, Cambridge (United Kingdom); Griffiths, John R. [University of Cambridge, Li Ka Shing Centre, Cancer Research UK Cambridge Institute, Cambridge (United Kingdom)

    2017-07-15

    To assess the feasibility of the mono-exponential, bi-exponential and stretched-exponential models in evaluating response of breast tumours to neoadjuvant chemotherapy (NACT) at 3 T. Thirty-six female patients (median age 53, range 32-75 years) with invasive breast cancer undergoing NACT were enrolled for diffusion-weighted MRI (DW-MRI) prior to the start of treatment. For assessment of early response, changes in parameters were evaluated on mid-treatment MRI in 22 patients. DW-MRI was performed using eight b values (0, 30, 60, 90, 120, 300, 600, 900 s/mm{sup 2}). Apparent diffusion coefficient (ADC), tissue diffusion coefficient (D{sub t}), vascular fraction (Florin), distributed diffusion coefficient (DDC) and alpha (α) parameters were derived. Then t tests compared the baseline and changes in parameters between response groups. Repeatability was assessed at inter- and intraobserver levels. All patients underwent baseline MRI whereas 22 lesions were available at mid-treatment. At pretreatment, mean diffusion coefficients demonstrated significant differences between groups (p < 0.05). At mid-treatment, percentage increase in ADC and DDC showed significant differences between responders (49 % and 43 %) and non-responders (21 % and 32 %) (p = 0.03, p = 0.04). Overall, stretched-exponential parameters showed excellent repeatability. DW-MRI is sensitive to baseline and early treatment changes in breast cancer using non-mono-exponential models, and the stretched-exponential model can potentially monitor such changes. (orig.)

  13. Baseline characteristics and treatment of patients in prospective comparison of ARNI with ACEI to determine impact on global mortality and morbidity in heart failure trial (PARADIGM-HF).

    Science.gov (United States)

    McMurray, John J V; Packer, Milton; Desai, Akshay S; Gong, Jianjian; Lefkowitz, Martin; Rizkala, Adel R; Rouleau, Jean L; Shi, Victor C; Solomon, Scott D; Swedberg, Karl; Zile, Michael R

    2014-07-01

    To describe the baseline characteristics and treatment of the patients randomized in the PARADIGM-HF (Prospective comparison of ARNi with ACEi to Determine Impact on Global Mortality and morbidity in Heart Failure) trial, testing the hypothesis that the strategy of simultaneously blocking the renin-angiotensin-aldosterone system and augmenting natriuretic peptides with LCZ696 200 mg b.i.d. is superior to enalapril 10 mg b.i.d. in reducing mortality and morbidity in patients with heart failure and reduced ejection fraction. Key demographic, clinical and laboratory findings, along with baseline treatment, are reported and compared with those of patients in the treatment arm of the Studies Of Left Ventricular Dysfunction (SOLVD-T) and more contemporary drug and device trials in heart failure and reduced ejection fraction. The mean age of the 8442 patients in PARADIGM-HF is 64 (SD 11) years and 78% are male, which is similar to SOLVD-T and more recent trials. Despite extensive background therapy with beta-blockers (93% patients) and mineralocorticoid receptor antagonists (60%), patients in PARADIGM-HF have persisting symptoms and signs, reduced health related quality of life, a low LVEF (mean 29 ± SD 6%) and elevated N-terminal-proB type-natriuretic peptide levels (median 1608 inter-quartile range 886-3221 pg/mL). PARADIGM-HF will determine whether LCZ696 is more beneficial than enalapril when added to other disease-modifying therapies and if further augmentation of endogenous natriuretic peptides will reduce morbidity and mortality in heart failure and reduced ejection fraction. © 2014 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.

  14. Lack of Associations of CHRNA5-A3-B4 Genetic Variants with Smoking Cessation Treatment Outcomes in Caucasian Smokers despite Associations with Baseline Smoking.

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    Rachel F Tyndale

    Full Text Available CHRNA5-A3-B4 variants, rs16969968, rs588765 and rs578776, are consistently associated with tobacco consumption among smokers, but the association with smoking cessation is less consistent. Among the studies that reported significant associations with cessation, the effects were observed in smokers treated with placebo treatment in some studies and conversely in those receiving active pharmacological therapy (bupropion and nicotine replacement therapies in others. Thus, it remains unclear whether CHRNA5-A3-B4 is a useful marker for optimizing smoking cessation. Using data from 654 Caucasian smokers treated with placebo, nicotine patch or varenicline, we investigated whether CHRNA5-A3-B4 variants were associated with smoking cessation outcomes, and whether there were significant genotype-by-treatment or haplotype-by-treatment interactions. We observed no significant associations between CHRNA5-A3-B4 variants and smoking cessation, despite replicating previous associations with baseline tobacco consumption. At end of treatment the effect size on smoking cessation in the placebo, patch and varenicline groups for rs16969968 [GG vs. GA+AA] was OR = 0.66 (P = 0.23, OR = 1.01 (P = 0.99, and OR = 1.30 (P = 0.36 respectively, of rs588765 [CC vs. CT+TT] was OR = 0.96 (P = 0.90, OR = 0.84 (P = 0.58, and OR = 0.74 (P = 0.29 respectively, and for rs578776 [GG vs. GA+AA] on smoking cessation was OR = 1.02 (P = 0.95, OR = 0.75 (P = 0.35, and OR = 1.20 (P = 0.51 respectively. Furthermore, we observed no associations with cessation using the CHRNA5-A3-B4 haplotype (constructed using rs16969968 and rs588765, nor did we observe any significant genotype-by-treatment interactions, with or without adjusting for the rate of nicotine metabolism (all P>0.05. We also observed no significant genetic associations with 6 month or 12 month smoking abstinence. In conclusion, we found no association between CHRNA5-A3-B4 variants and smoking cessation rates in this clinical

  15. Use of Viremia to Evaluate the Baseline Case Fatality Ratio of Ebola Virus Disease and Inform Treatment Studies: A Retrospective Cohort Study.

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    Oumar Faye

    2015-12-01

    Full Text Available The case fatality ratio (CFR of Ebola virus disease (EVD can vary over time and space for reasons that are not fully understood. This makes it difficult to define the baseline CFRs needed to evaluate treatments in the absence of randomized controls. Here, we investigate whether viremia in EVD patients may be used to evaluate baseline EVD CFRs.We analyzed the laboratory and epidemiological records of patients with EVD confirmed by reverse transcription PCR hospitalized in the Conakry area, Guinea, between 1 March 2014 and 28 February 2015. We used viremia and other variables to model the CFR. Data for 699 EVD patients were analyzed. In the week following symptom onset, mean viremia remained stable, and the CFR increased with viremia, V, from 21% (95% CI 16%-27% for low viremia (V < 104.4 copies/ml to 53% (95% CI 44%-61% for intermediate viremia (104.4 ≤ V < 105.2 copies/ml and 81% (95% CI 75%-87% for high viremia (V ≥ 105.2 copies/ml. Compared to adults (15-44 y old [y.o.], the CFR was larger in young children (0-4 y.o. (odds ratio [OR]: 2.44; 95% CI 1.02-5.86 and older adults (≥ 45 y.o. (OR: 2.84; 95% CI 1.81-4.46 but lower in children (5-14 y.o. (OR: 0.46; 95% CI 0.24-0.86. An order of magnitude increase in mean viremia in cases after July 2014 compared to those before coincided with a 14% increase in the CFR. Our findings come from a large hospital-based study in Conakry and may not be generalizable to settings with different case profiles, such as with individuals who never sought care.Viremia in EVD patients was a strong predictor of death that partly explained variations in CFR in the study population. This study provides baseline CFRs by viremia group, which allow appropriate adjustment when estimating efficacy in treatment studies. In randomized controlled trials, stratifying analysis on viremia groups could reduce sample size requirements by 25%. We hypothesize that monitoring the viremia of hospitalized patients may inform the

  16. Treatment of malaria and related symptoms using traditional herbal medicine in Ethiopia.

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    Suleman, Sultan; Beyene Tufa, Takele; Kebebe, Dereje; Belew, Sileshi; Mekonnen, Yimer; Gashe, Fanta; Mussa, Seid; Wynendaele, Evelien; Duchateau, Luc; De Spiegeleer, Bart

    2018-03-01

    Medicinal plants have always been an integral part of different cultures in Ethiopia in the treatment of different illnesses including malaria and related symptoms. However, due to lack of proper documentation, urbanization, drought, acculturation and deforestation, there is an increased risk of losing this traditional knowledge. Hence, the use of the indigenous knowledge should be well documented and validated for potential future use. To gather and document information on medicinal plants which are used in the traditional treatment of malaria and related symptoms in Ethiopia. First, an ethnomedicinal survey of plants was conducted in 17 districts of Jimma zone, the Oromia national regional state of Ethiopia. Jimma zone is malarious and rich in natural flora. A total of 115 traditional healers were interviewed using a semi-structured questionnaire containing personal data of the respondents, and information on medicinal plants used to treat malaria and related symptoms. In addition, a literature search using Medline/PubMed, Google Scholar, ScienceDirect and HINARI was conducted on the indigenous use, in-vitro/in-vivo anti-malarial activity reports, and the chemical characterization of medicinal plants of Ethiopia used against malaria. From ethnomedicinal survey, a total of 28 species of plants used in the traditional treatment of malaria and related symptoms in Jimma Zone were collected, identified and documented. In addition, the literature search revealed that 124 medicinal plant species were reported to be traditionally used in the treatment of malaria in Ethiopia. From both ethnomedicinal survey and the literature search, Asteraceae and Fabaceae were the most represented families and Allium sativum L., Carica papaya L., Vernonia amygdalina Del., Lepidium sativum L. and Croton macrostachyus Del. were the most frequently reported plant species for their anti-malarial use. The dominant plant parts used in the preparation of remedies were leaves. About 54% of the

  17. Efficacy of chloroquine for the treatment of Plasmodium vivax in the Saharan zone in Mauritania.

    Science.gov (United States)

    Ould Ahmedou Salem, Mohamed Salem; Mohamed Lemine, Yeslim Ould; Deida, Jemila Mint; Lemrabott, Mohamed Aly Ould; Ouldabdallahi, Mohamed; Ba, Mamadou Dit Dialaw; Boukhary, Ali Ould Mohamed Salem; Khairy, Mohamed Lemine Ould; Abdel Aziz, Mohamed Boubacar; Ringwald, Pascal; Basco, Leonardo K; Niang, Saidou Doro; Lebatt, Sidi Mohamed

    2015-01-28

    In 2006, the Mauritanian Ministry of Health adopted a new therapeutic strategy based on the systematic use of artemisinin-based combination therapy (ACT), artesunate-amodiaquine and artemether-lumefantrine, for the first- and second-line treatment of uncomplicated malaria, respectively, regardless of Plasmodium spp. In the Saharan zone of the country, recent studies have shown that Plasmodium vivax largely predominates over Plasmodium falciparum. Anti-malarial drug response of P. vivax has not been evaluated in Mauritania. The aim of the present study was to evaluate the clinical efficacy and tolerance of chloroquine to treat P. vivax malaria in Mauritanian patients. Plasmodium vivax-infected patients aged > 6 months old were enrolled in Nouakchott and Atar in September-October 2013. Chloroquine was administered at the standard dose of 25 mg base/kg body weight over three days. Patients were followed until day 28, according to the standard 2009 World Health Organization protocol. A total of 128 patients (67 in Nouakchott and 61 in Atar) were enrolled in the study. Seven patients (5.5%) were either excluded or lost to follow-up. Based on the per protocol analysis, chloroquine efficacy (adequate clinical and parasitological response) was 100%. Treatment was well-tolerated. One patient was excluded on day 1 due to urticaria and treated with artesunate-amodiaquine. Although the current national treatment guideline recommends artesunate-amodiaquine for the first-line treatment of uncomplicated malaria, including P. vivax malaria, chloroquine may still have an important role to play in anti-malarial chemotherapy in Mauritania. Further epidemiological studies are required to map the distribution of P. vivax and P. falciparum in the country.

  18. Contrasting responses to interferon β-1b treatment in relapsing-remitting multiple sclerosis: Does baseline interleukin- 12p35 messenger RNA predict the efficacy of treatment?

    NARCIS (Netherlands)

    Boxel van-Dezaire, A.H.H.; Trigt van-Hoff, S.C.J.; Killestein, J.; Schrijver, H.M.; Houwelingen, J.C. van; Polman, C.H.; Nagelkerken, L.

    2000-01-01

    Interferon (IFN)-β treatment is effective in relapsing-remitting multiple sclerosis (RR-MS) via an as yet unidentified mechanism. In the present study, we investigated whether the expression of messenger RNA (mRNA) encoding the interleukin (IL)-12 subunits p40 and p35, IL-12 receptor chains, IL-18,

  19. Assessment of early treatment response to neoadjuvant chemotherapy in breast cancer using non-mono-exponential diffusion models: a feasibility study comparing the baseline and mid-treatment MRI examinations.

    Science.gov (United States)

    Bedair, Reem; Priest, Andrew N; Patterson, Andrew J; McLean, Mary A; Graves, Martin J; Manavaki, Roido; Gill, Andrew B; Abeyakoon, Oshaani; Griffiths, John R; Gilbert, Fiona J

    2017-07-01

    To assess the feasibility of the mono-exponential, bi-exponential and stretched-exponential models in evaluating response of breast tumours to neoadjuvant chemotherapy (NACT) at 3 T. Thirty-six female patients (median age 53, range 32-75 years) with invasive breast cancer undergoing NACT were enrolled for diffusion-weighted MRI (DW-MRI) prior to the start of treatment. For assessment of early response, changes in parameters were evaluated on mid-treatment MRI in 22 patients. DW-MRI was performed using eight b values (0, 30, 60, 90, 120, 300, 600, 900 s/mm 2 ). Apparent diffusion coefficient (ADC), tissue diffusion coefficient (D t ), vascular fraction (ƒ), distributed diffusion coefficient (DDC) and alpha (α) parameters were derived. Then t tests compared the baseline and changes in parameters between response groups. Repeatability was assessed at inter- and intraobserver levels. All patients underwent baseline MRI whereas 22 lesions were available at mid-treatment. At pretreatment, mean diffusion coefficients demonstrated significant differences between groups (p mono-exponential models, and the stretched-exponential model can potentially monitor such changes. • Baseline diffusion coefficients demonstrated significant differences between complete pathological responders and non-responders. • Increase in ADC and DDC at mid-treatment can discriminate responders and non-responders. • The ƒ fraction at mid-treatment decreased in responders whereas increased in non-responders. • The mono- and stretched-exponential models showed excellent inter- and intrarater repeatability. • Treatment effects can potentially be assessed by non-mono-exponential diffusion models.

  20. Prediction and treatment of asthma in preschool children at risk: study design and baseline data of a prospective cohort study in general practice (ARCADE

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    van Aalderen Wim MC

    2009-04-01

    Full Text Available Abstract Background Asthma is a difficult diagnosis to establish in preschool children. A few years ago, our group presented a prediction rule for young children at risk for asthma in general practice. Before this prediction rule can safely be used in practice, cross-validation is required. In addition, general practitioners face many therapeutic management decisions in children at risk for asthma. The objectives of the study are: (1 identification of predictors for asthma in preschool children at risk for asthma with the aim of cross-validating an earlier derived prediction rule; (2 compare the effects of different treatment strategies in preschool children. Design In this prospective cohort study one to five year old children at risk of developing asthma were selected from general practices. At risk was defined as 'visited the general practitioner with recurrent coughing (≥ 2 visits, wheezing (≥ 1 or shortness of breath (≥ 1 in the previous 12 months'. All children in this prospective cohort study will be followed until the age of six. For our prediction rule, demographic data, data with respect to clinical history and additional tests (specific immunoglobulin E (IgE, fractional exhaled nitric oxide (FENO, peak expiratory flow (PEF are collected. History of airway specific medication use, symptom severity and health-related quality of life (QoL are collected to estimate the effect of different treatment intensities (as expressed in GINA levels using recently developed statistical techniques. In total, 1,938 children at risk of asthma were selected from general practice and 771 children (40% were enrolled. At the time of writing, follow-up for all 5-year olds and the majority of the 4-year olds is complete. The total and specific IgE measurements at baseline were carried out by 87% of the children. Response rates to the repeated questionnaires varied from 93% at baseline to 73% after 18 months follow-up; 89% and 87% performed PEF and FENO

  1. Urban malaria treatment behaviour in the context of low levels of malaria transmission in Lagos, Nigeria.

    Science.gov (United States)

    Brieger, W R; Sesay, H R; Adesina, H; Mosanya, M E; Ogunlade, P B; Ayodele, J O; Orisasona, S A

    2001-01-01

    Urban malaria in West Africa is not well documented. While rapid urbanisation may create environmental conditions that favour mosquito breeding, urban pollution may inhibit the growth of Anopheles species. In 1996, the Basic Support for Institutionalizing Child Survival (BASICS) Project of the U.S. Agency for International Development (USAID) started building urban community health coalitions in Lagos, Nigeria, to empower communities to provide prompt treatment and appropriate prevention for major causes of childhood morbidity and mortality, including malaria, diarrhoeal disease, acute respiratory infections and vaccine preventable diseases. Intervention against malaria was predicated on national policies that assumed Nigeria was holo-endemic for malaria and that prompt treatment of febrile illness with anti-malarial drugs was an appropriate action. At the suggestion and with the assistance of another USAID programme, the Environmental Health Project (EHP), BASICS embarked on a rapid assessment of the epidemiological, entomological and sociological situation of malaria transmission and case management in three Lagos communities. During April and May 1998, blood film investigation of 916 children between the ages of 6 months and 5 years yielded a parasite prevalence rate of 0.9%. Night knockdown collections of mosquitoes in rooms yielded only C. quinquefasciatus and A. aegypti. The same results were obtained for night landing collections on human bait. Very low densities of A. gambiae larvae were found in breeding sites in Lagos Island (0.7) and Ajegunle (0.3). In contrast, community members, during focus group discussion identified malaria, in it various culturally defined forms, as a major health problem. Among the children examined clinically, 186 (20.3%) reported an illness, which they called "malaria" in the previous two weeks, and 180 had sought treatment for this illness. Data obtained from 303 shops in the area documented that a minimum of US dollars 4

  2. Severe delayed haemolytic anaemia associated with artemether-lumefantrine treatment of malaria in a Japanese traveller.

    Science.gov (United States)

    Hasegawa, Chihiro; Kudo, Masaharu; Maruyama, Haruhiko; Kimura, Mikio

    2018-03-01

    Delayed haemolytic anaemia has been reported in association with intravenous artesunate treatment in patients with severe Plasmodium falciparum malaria, and furthermore, oral artemisinin-based combination therapies including artemether-lumefantrine (AL) have also been incriminated. However, definite cases of delayed haemolytic anaemia associated with AL appear to be scarce, as reported cases were often treated concomitantly with other anti-malarials. In this study, we report a severe case of delayed haemolytic anaemia following AL alone in a Japanese traveller with severe parasitaemia caused by numerous P. falciparum parasites and a few P. vivax parasites. We also stress the need by further studies to differentiate between delayed haemolytic anaemia and blackwater fever, the latter being another malaria-related haemolytic condition, more clearly than they are now. Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  3. An assessment of anti-schistosomal treatment on physical work capacity.

    Science.gov (United States)

    Awad El Karim, M A; Collins, K J; Sukkar, M Y; Omer, A H; Amin, M A; Doré, C

    1981-04-01

    Acting as their own controls, village subjects from the Gezira are of the Sudan with relatively high levels of schistosomiasis infection were first tested in an exercise laboratory in Khartoum and the tests were then repeated after a period of about 1 yr during which time the subjects were treated with hycanthone and periodically monitored to ensure that they had remained free of the disease. In the meantime they were also given anti-malarial prophylaxis. Laboratory tests showed a significant improvement in physiological work capacity of up to 20% after treatment compared with untreated controls. An overall improvement in pulmonary function, particularly forced vital capacity, was observed as well as a significant increase in mean haemoglobin concentration by 1.1 g/100 ml of blood in the treated group. Apart from these improvements in physical working capacity, the treated subjects subjectively felt better after the exercise tests, as expressed by the disappearance of fatiguability.

  4. Treatment policy change to dihydroartemisinin-piperaquine contributes to the reduction of adverse maternal and pregnancy outcomes.

    Science.gov (United States)

    Poespoprodjo, Jeanne Rini; Fobia, Wendelina; Kenangalem, Enny; Lampah, Daniel A; Sugiarto, Paulus; Tjitra, Emiliana; Anstey, Nicholas M; Price, Richard N

    2015-07-15

    In Papua, Indonesia, maternal malaria is prevalent, multidrug resistant and associated with adverse outcomes for mother and baby. In March 2006, anti-malarial policy was revised for the second and third trimester of pregnancy to dihydroartemisinin-piperaquine (DHP) for all species of malaria. This study presents the temporal analysis of adverse outcomes in pregnancy and early life following this policy change. From April 2004 to May 2010, a standardized questionnaire was used to collect information from all pregnant women admitted to the maternity ward. A physical examination was performed on all live birth newborns. The relative risks (RR) and the associated population attributable risks (PAR) of adverse outcomes in women with a history of malaria treatment to the risk in those without a history of malaria during the current pregnancy were examined to evaluate the temporal trends before and after DHP deployment. Of 6,556 women enrolled with known pregnancy outcome, 1,018 (16%) reported prior anti-malarial treatment during their pregnancy. The proportion of women with malaria reporting treatment with DHP rose from 0% in 2004 to 64% (121/189) in 2010. In those with history of malaria during pregnancy, the increasing use of DHP was associated with a 54% fall in the proportion of maternal malaria at delivery and a 98% decrease in congenital malaria (from 7.1% prior to 0.1% after policy change). Overall policy change to more effective treatment was associated with an absolute 2% reduction of maternal severe anaemia and absolute 4.5% decrease in low birth weight babies. Introduction of highly effective treatment in pregnancy was associated with a reduction of maternal malaria at delivery and improved neonatal outcomes. Ensuring universal access to arteminisin combination therapy (ACT) in pregnancy in an area of multidrug resistance has potential to impact significantly on maternal and infant health.

  5. Gene Expression of Vitamin D Metabolic Enzymes at Baseline and in Response to Vitamin D Treatment in Thyroid Cancer Cell Lines

    Science.gov (United States)

    Bennett, Robert G.; Wakeley, Shannon E.; Hamel, Frederick G.; High, Robin R.; Korch, Christopher

    2014-01-01

    The association between vitamin D and thyroid cancer is unclear. It is unknown if CYP27A1 or CYP2R1 are present in normal thyroid or cancer cells and there is limited information regarding response to treatment with vitamin D. SV40 immortalized follicular cells (n-thy) and six thyroid cancer cell lines were treated with 10μM vitamin D3, 0.1μM 1,25(OH)2D3 or vehicle x 24 hours. CYP27A1, CYP2R1, CYP27B1, and CYP24A1 mRNA were measured using quantitative RT-PCR before and after treatment. Cell proliferation was also evaluated in TPC1 and C643 cells after treatment with D3, 25(OH)D3, and 1,25(OH)2D3. Baseline CYP27A1 and CYP27B1 mRNA were present in all cells, CYP2R1 was higher, and CYP24A1 mRNA was lower in cancer cell lines versus N-thy. TPC1 cells had increased CYP24A1 mRNA levels when treated with both D3 (3.49, pCYP27A1 and CYP2R1 in addition to CYP27B1, establishing the potential to metabolize D3 to 1,25(OH)2D3. Additionally, vitamin D3, 25(OH)D3, and 1,25(OH)2D3 all had an anti-proliferative effect on two thyroid cancer cell lines. PMID:22992568

  6. Effect of baseline Alberta Stroke Program Early CT Score on safety and efficacy of intra-arterial treatment: a subgroup analysis of a randomised phase 3 trial (MR CLEAN)

    NARCIS (Netherlands)

    Yoo, Albert J.; Berkhemer, Olvert A.; Fransen, Puck S. S.; van den Berg, Lucie A.; Beumer, Debbie; Lingsma, Hester F.; Schonewille, Wouter J.; Sprengers, Marieke E. S.; van den Berg, René; van Walderveen, Marianne A. A.; Beenen, Ludo F. M.; Wermer, Marieke J. H.; Nijeholt, Geert J. Lycklama À; Boiten, Jelis; Jenniskens, Sjoerd F. M.; Bot, Joseph C. J.; Boers, Anna M. M.; Marquering, Henk A.; Roos, Yvo B. W. E. M.; van Oostenbrugge, Robert J.; Dippel, Diederik W. J.; van der Lugt, Aad; van Zwam, Wim H.; Majoie, Charles B. L. M.

    2016-01-01

    Whether infarct size modifies intra-arterial treatment effect is not certain, particularly in patients with large infarcts. We examined the effect of the baseline Alberta Stroke Program Early CT Score (ASPECTS) on the safety and efficacy of intra-arterial treatment in a subgroup analysis of the

  7. Effect of baseline Alberta Stroke Program Early CT Score on safety and efficacy of intra-arterial treatment: a subgroup analysis of a randomised phase 3 trial (MR CLEAN)

    NARCIS (Netherlands)

    Yoo, A.J.; Berkhemer, O.A.; Fransen, P.S.; Berg, L.A. van den; Beumer, D.; Lingsma, H.F.; Schonewille, W.J.; Sprengers, M.E.; Berg, R. van den; Walderveen, M.A. van; Beenen, L.F.; Wermer, M.J.; Nijeholt, G.J.; Boiten, J.; Jenniskens, S.F.M.; Bot, J.C.; Boers, A.M.; Marquering, H.A.; Roos, Y.B.; Oostenbrugge, R.J. van; Dippel, D.W.; Lugt, A. van der; Zwam, W.H. van; Majoie, C.B.; et al.,

    2016-01-01

    BACKGROUND: Whether infarct size modifies intra-arterial treatment effect is not certain, particularly in patients with large infarcts. We examined the effect of the baseline Alberta Stroke Program Early CT Score (ASPECTS) on the safety and efficacy of intra-arterial treatment in a subgroup analysis

  8. Abriendo Puertas: baseline findings from an integrated intervention to promote prevention, treatment and care among FSW living with HIV in the Dominican Republic.

    Directory of Open Access Journals (Sweden)

    Yeycy Donastorg

    Full Text Available Female sex workers (FSW are often the focus of primary HIV prevention efforts. However, little attention has been paid to the prevention, treatment, and care needs of FSW living with HIV. Based on formative research, we developed an integrated model to promote prevention and care for FSW living with HIV in Santo Domingo, Dominican Republic, including (1 individual counseling and education; (2 peer navigation; (3 clinical provider training; and (4 community mobilization. We enrolled 268 FSW living with HIV into the intervention and conducted socio-behavioral surveys, sexually transmitted infection (STI testing, and viral load (VL assessments. We used multivariate logistic regression to identify behavioral and socio-demographic factors associated with detectable VL (>50 copies/mL and STI prevalence. Over half of all participants (51.9% had a detectable VL, even though most received HIV-related care in the last 6 months (85.1% and were currently on anti-retroviral treatment (ART (72.4%. Factors positively associated with a detectable VL included being 18-35 years of age (Adjusted Odds Ratio [AOR] 2.46, 95% CI 1.31-4.60, having ever used drugs (AOR 2.34, 95% CI 1.14-4.79, and having ever interrupted ART (AOR 3.09, 95% CI 1.44-6.59. Factors protective against having a detectable VL included being single (AOR 0.45, 95% 0.20-0.98 and being currently on ART (AOR 0.17, 95% CI 0.07-0.41. Nearly one-quarter (23.1% had an STI, which was associated with being single (AOR 3.21, 95% CI 1.27-8.11 and using drugs in the last 6 months (AOR 3.54, 95% CI 1.32-9.45. Being on ART was protective against STI (AOR 0.51, 95% CI 0.26-1.00. Baseline findings indicate significant barriers to VL suppression and STI prevention among FSW living with HIV and highlight gaps in the continuum of HIV care and treatment. These findings have important implications for both the individual health of FSW and population-level HIV transmission dynamics.

  9. Baseline Blood Pressure Effect on the Benefit and Safety of Intra-Arterial Treatment in MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands).

    Science.gov (United States)

    Mulder, Maxim J H L; Ergezen, Saliha; Lingsma, Hester F; Berkhemer, Olvert A; Fransen, Puck S S; Beumer, Debbie; van den Berg, Lucie A; Lycklama À Nijeholt, Geert; Emmer, Bart J; van der Worp, H Bart; Nederkoorn, Paul J; Roos, Yvo B W E M; van Oostenbrugge, Robert J; van Zwam, Wim H; Majoie, Charles B L M; van der Lugt, Aad; Dippel, Diederik W J

    2017-07-01

    High blood pressure (BP) is associated with poor outcome and the occurrence of symptomatic intracranial hemorrhage in acute ischemic stroke. Whether BP influences the benefit or safety of intra-arterial treatment (IAT) is not known. We aimed to assess the relation of BP with functional outcome, occurrence of symptomatic intracranial hemorrhage and effect of IAT. This is a post hoc analysis of the MR CLEAN (Multicenter Randomized Clinical Trial of Endovascular Treatment of Acute Ischemic Stroke in the Netherlands). BP was measured at baseline, before IAT or stroke unit admission. We estimated the association of baseline BP with the score on the modified Rankin Scale at 90 days and safety parameters with ordinal and logistic regression analysis. Effect of BP on the effect of IAT was tested with multiplicative interaction terms. Systolic BP (SBP) had the best correlation with functional outcome. This correlation was U-shaped; both low and high baseline SBP were associated with poor functional outcome. Higher SBP was associated with symptomatic intracranial hemorrhage (adjusted odds ratio, 1.25 for every 10 mm Hg higher SBP [95% confidence interval, 1.09-1.44]). Between SBP and IAT, there was no interaction for functional outcome, symptomatic intracranial hemorrhage, or other safety parameters; the absolute benefit of IAT was evident for the whole SBP range. The same was found for diastolic BP. BP does not affect the benefit or safety of IAT in patients with acute ischemic stroke caused by proximal intracranial vessel occlusion. Our data provide no arguments to withhold or delay IAT based on BP. URL: http://www.isrctn.com. Unique identifier: ISRCTN10888758. © 2017 American Heart Association, Inc.

  10. Sustainability of motor performance after robotic-assisted treadmill therapy in children: an open, non-randomized baseline-treatment study.

    Science.gov (United States)

    Borggraefe, I; Kiwull, L; Schaefer, J S; Koerte, I; Blaschek, A; Meyer-Heim, A; Heinen, F

    2010-06-01

    The aim of the study was to investigate the sustainability of motor improvements achieved after a three week trial of robotic assisted treadmill therapy in children and adolescents with central gait disorders within a follow up period of about six months. Open, non-randomized, baseline-treatment study. Fourteen patients (mean age 8.2+/-5.4) underwent a trial of 12 sessions of robotic-assisted treadmill therapy using the Lokomat over a period of three weeks. Outcome measures were the dimensions D (standing) and E (walking) of the Gross Motor Function Measure, the ten meter walking test and the six minute walking test. Outcome variables were evaluated immediately before and after the trial and at a follow up of about six months. Improvements after the trial in the dimension D from 49.5% to 54.4% (P=0.008) and from 38.9% to 42.3% (P=0.012) in the dimension E of the GMFM were seen and are within the same range of previously published results. The mean score at the follow up after six months was 56.8% and 43.3% for dimension D and E, respectively. Gait speed improved from 0.80 m/s to 1.01 m/s (P=0.006) after the trial and was 1.11 m/s at the follow-up visit at six months. Similar results were obtained for endurance. The improvements of motor function after a three-week trial of robotic-assisted treadmill therapy appear to be sustained after a mean period of six months.

  11. Long-term real-world entecavir therapy in treatment-naïve hepatitis B patients: base-line hepatitis B virus DNA and hepatitis B surface antigen levels predict virologic response.

    Science.gov (United States)

    Cho, Ju-Yeon; Sohn, Won; Sinn, Dong-Hyun; Gwak, Geum-Youn; Paik, Yong-Han; Choi, Moon Seok; Koh, Kwang Cheol; Paik, Seung Woon; Yoo, Byung Chul; Lee, Joon Hyeok

    2017-07-01

    Entecavir is a potent nucleoside analogue with high efficacy and barrier for resistance. We aimed to investigate the long-term efficacy and viral resistance rate of entecavir and explore the factors associated with virologic response, including quantitative hepatitis B surface antigen (qHBsAg) levels. One thousand and nine treatment-naïve chronic hepatitis B (CHB) patients were evaluated for cumulative rates of virologic response, biochemical response, and entecavir mutations. The role of baseline qHBsAg for virologic response was assessed in 271 patients with qHBsAg prior to entecavir treatment. The median duration of entecavir treatment was 26.5 months. The cumulative rate of virologic response at years 1, 3, and 5 were 79.0%, 95.6%, and 99.4%, respectively. The cumulative rate of entecavir resistance was 1.0% and 2.1% in years 3 and 5. Multivariate analysis identified baseline hepatitis B e antigen (HBeAg) negative status ( p response. Lower qHBsAg was an independent predictor of virologic response in patients with baseline qHBsAg. There were no serious adverse events during treatment. Long-term entecavir treatment of nucleos(t)ide-naïve CHB patients was associated with an excellent virologic response and a low rate of entecavir-resistant mutations at 5 years. Baseline HBV DNA load, qHBsAg levels, and HBeAg status were predictors of virologic response during entecavir treatment.

  12. Effectiveness of two intensive treatment methods for smoking cessation and relapse prevention in patients with coronary heart disease: study protocol and baseline description.

    Science.gov (United States)

    Berndt, Nadine; Bolman, Catherine; Lechner, Lilian; Mudde, Aart; Verheugt, Freek W A; de Vries, Hein

    2012-05-15

    There is no more effective intervention for secondary prevention of coronary heart disease than smoking cessation. Yet, evidence about the (cost-)effectiveness of smoking cessation treatment methods for cardiac inpatients that also suit nursing practice is scarce. This protocol describes the design of a study on the (cost-)effectiveness of two intensive smoking cessation interventions for hospitalised cardiac patients as well as first results on the inclusion rates and the characteristics of the study population. An experimental study design is used in eight cardiac wards of hospitals throughout the Netherlands to assess the (cost-)effectiveness of two intensive smoking cessation counselling methods both combined with nicotine replacement therapy. Randomization is conducted at the ward level (cross-over). Baseline and follow-up measurements after six and 12 months are obtained. Upon admission to the cardiac ward, nurses assess patients' smoking behaviour, ensure a quit advice and subsequently refer patients for either telephone counselling or face-to-face counselling. The counselling interventions have a comparable structure and content but differ in provider and delivery method, and in duration. Both counselling interventions are compared with a control group receiving no additional treatment beyond the usual care. Between December 2009 and June 2011, 245 cardiac patients who smoked prior to hospitalisation were included in the usual care group, 223 in the telephone counselling group and 157 in the face-to-face counselling group. Patients are predominantly male and have a mean age of 57 years. Acute coronary syndrome is the most frequently reported admission diagnosis. The ultimate goal of the study is to assess the effects of the interventions on smoking abstinence and their cost-effectiveness. Telephone counselling is expected to be more (cost-)effective in highly motivated patients and patients with high SES, whereas face-to-face counselling is expected to be

  13. Medicinal plants used by the people of Nsukka Local Government Area, south-eastern Nigeria for the treatment of malaria: An ethnobotanical survey.

    Science.gov (United States)

    Odoh, Uchenna E; Uzor, Philip F; Eze, Chidimma L; Akunne, Theophine C; Onyegbulam, Chukwuma M; Osadebe, Patience O

    2018-05-23

    Malaria is a serious public health problem especially in sub-Saharan African countries such as Nigeria. The causative parasite is increasingly developing resistance to the existing drugs. There is urgent need for alternative and affordable therapy from medicinal plants which have been used by the indigenous people for many years. This study was conducted to document the medicinal plant species traditionally used by the people of Nsukka Local Government Area in south-eastern Nigeria for the treatment of malaria. A total of 213 respondents, represented by women (59.2%) and men (40.8%), were interviewed using a semi-structured questionnaire. The results were analysed and discussed in the context of previously published information on anti-malarial and phytochemical studies of the identified plants. The survey revealed that 50 plant species belonging to 30 botanical families were used in this region for the treatment of malaria. The most cited families were Apocynaceae (13.3%), Annonaceae (10.0%), Asteraceae (10.0%), Lamiaceae (10.0%), Poaceae (10.0%), Rubiaceae (10.0%) and Rutaceae (10.0%). The most cited plant species were Azadirachta indica (11.3%), Mangifera indica (9.1%), Carica papaya (8.5%), Cymbopogon citratus (8.5%) and Psidium guajava (8.5%). The present findings showed that the people of Nsukka use a large variety of plants for the treatment of malaria. The identified plants are currently undergoing screening for anti-malarial, toxicity and chemical studies in our laboratory. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. Difference between observed and predicted glycated hemoglobin at baseline and treatment response to vildagliptin-based dual oral therapy in patients with type 2 diabetes.

    Science.gov (United States)

    Wang, Jun-Sing; Hung, Yi-Jen; Lu, Yung-Chuan; Tsai, Cheng-Lin; Yang, Wei-Shiung; Lee, Ting-I; Hsiao, Ya-Chun; Sheu, Wayne Huey-Herng

    2018-04-01

    We aimed to investigate the association of difference between observed and predicted glycated hemoglobin (dopHbA1c) and HbA1c reduction after vildagliptin-based oral therapy in patients with type 2 diabetes (T2D). This was a prospective observational study. Adults ≥ 20 years old with T2D and HbA1c ≧7% treated with oral anti-diabetic drugs (OADs) were eligible if their OADs were shifted to vildagliptin-based dual oral therapy. Fasting plasma glucose (FPG) and HbA1c were recorded at baseline, week 12, and week 24. To determine baseline dopHbA1c, a predicted HbA1c was calculated by inserting baseline FPG into a regression equation (HbA1c = FPG ∗ 0.0225 + 4.3806) developed from linear relationship between HbA1c and FPG in an independent cohort of 3239 outpatients with T2D (dopHbA1c = observed HbA1c - predicted HbA1c). Patients were assigned to low (≦0) or high (>0) dopHbA1c group according to their baseline dopHbA1c levels. The study endpoint was changes from baseline to week 24 in HbA1c levels. A total of 1224 patients were enrolled. Patients with a dopHbA1c >0 had a greater HbA1c reduction after vildagliptin-based dual oral therapy than those with a dopHbA1c ≦0 (-1.5 ± 2.0 vs. -0.4 ± 1.0%, p Baseline dopHbA1c was positively associated with HbA1c reduction from baseline to week 24 (β coefficient 0.883, 95% CI 0.811 to 0.955, p baseline dopHbA1c was associated with a greater HbA1c reduction after shifting to vildagliptin-based dual oral therapy. Copyright © 2018 Elsevier B.V. All rights reserved.

  15. Lamivudine monotherapy-based cART is efficacious for HBV treatment in HIV/HBV co-infection when baseline HBV DNA<20,000IU/ml

    Science.gov (United States)

    LI, Yijia; XIE, Jing; HAN, Yang; WANG, Huanling; ZHU, Ting; WANG, Nidan; LV, Wei; GUO, Fuping; QIU, Zhifeng; LI, Yanling; DU, Shanshan; SONG, Xiaojing; THIO, Chloe L; LI, Taisheng

    2016-01-01

    Background Although combination antiretroviral therapy (cART) including tenofovir (TDF)+lamivudine (3TC) or emtricitabine (FTC) is recommended for treatment of HIV/HBV co-infected patients, TDF is unavailable in some resource-limited areas. Some data suggest that 3TC monotherapy-based cART may be effective in patients with low pre-treatment HBV DNA. Methods Prospective study of 151 Chinese HIV/HBV co-infected subjects of whom 60 received 3TC-based cART and 91 received TDF+3TC-based cART. Factors associated with HBV DNA suppression at 24 and 48 weeks, including anti-HBV drugs, baseline HBV DNA, and baseline CD4 cell count, were evaluated overall and stratified by baseline HBV DNA using Poisson regression with a robust error variance. Results Baseline HBV DNA≥20,000 IU/ml was present in 48.3% and 44.0% of subjects in the 3TC and TDF groups, respectively (P=0.60). After 48 weeks of treatment, HBV DNA suppression rates were similar between these two groups (96.8% vs. 98.0% for 3TC and TDF+3TC, P>0.999) in subjects with baseline HBV DNAHBV DNA ≥20,000 IU/ml, TDF+3TC was associated with higher suppression rates (34.5% vs. 72.5% in 3TC and TDF+3TC groups, respectively, P=0.002). In stratified multivariate regression, TDF use (RR 1.98, P=0.010) and baseline HBV DNA (per 1 log increase in IU/ml, RR 0.74, PHBV DNA suppression only when baseline HBV DNA≥20,000IU/ml. Conclusion This study suggests that 3TC monotherapy-based cART is efficacious for HBV treatment through 48 weeks in HIV/HBV co-infection when baseline HBV DNA<20,000IU/ml. Studies with long-term follow-up are warranted to determine if this finding persists. PMID:26745828

  16. Program reference schedule baseline

    International Nuclear Information System (INIS)

    1986-07-01

    This Program Reference Schedule Baseline (PRSB) provides the baseline Program-level milestones and associated schedules for the Civilian Radioactive Waste Management Program. It integrates all Program-level schedule-related activities. This schedule baseline will be used by the Director, Office of Civilian Radioactive Waste Management (OCRWM), and his staff to monitor compliance with Program objectives. Chapter 1 includes brief discussions concerning the relationship of the PRSB to the Program Reference Cost Baseline (PRCB), the Mission Plan, the Project Decision Schedule, the Total System Life Cycle Cost report, the Program Management Information System report, the Program Milestone Review, annual budget preparation, and system element plans. Chapter 2 includes the identification of all Level 0, or Program-level, milestones, while Chapter 3 presents and discusses the critical path schedules that correspond to those Level 0 milestones

  17. Long Baseline Observatory (LBO)

    Data.gov (United States)

    Federal Laboratory Consortium — The Long Baseline Observatory (LBO) comprises ten radio telescopes spanning 5,351 miles. It's the world's largest, sharpest, dedicated telescope array. With an eye...

  18. The effect of baseline morphology and its change during treatment on the accuracy of Response Evaluation Criteria in Solid Tumours in assessment of liver metastases.

    Science.gov (United States)

    Schiavon, Gaia; Ruggiero, Alessandro; Bekers, Dave J; Barry, Peter A; Sleijfer, Stefan; Kloth, Jaqueline; Krestin, Gabriel P; Schöffski, Patrick; Verweij, Jaap; Mathijssen, Ron H J

    2014-03-01

    Tumour response assessment to therapy is crucial in oncology. We analysed the morphology of liver metastases (LM) in gastrointestinal stromal tumour (GIST) patients to determine whether uni-dimensional measurement of lesions by Response Evaluation Criteria in Solid Tumours (RECIST), accurately reflects lesion volume. The volumes of LM (n=139) from a GIST patient cohort were measured using computed tomography (CT) at baseline, 3, 6 and 12 months after commencement of imatinib therapy. Baseline measurements were obtained by two independent investigators and inter-observer agreement assessed using Bland-Altman plots. Actual lesion volumes (V(ACTUAL)) were measured and compared with volumes based on the RECIST measure (V(RECIST)), and with volumes based on three orthogonal measures (V(ELLIPSOID)) at several time-points. At baseline, the inter-observer bias for V(ACTUAL) was just 1.8%. V(RECIST) and V(ELLIPSOID) overestimated V(ACTUAL) by a mean of 35% and only 9% respectively (Pmorphology. The remainder demonstrated significant changes in morphology (from spheroidal to ellipsoidal and vice versa) over time, while the RECIST measure did not reflect such changes. The morphology of LM in GIST is rarely spherical (an underlying assumption for RECIST) and can change considerably during imatinib therapy. In this setting, measurements using RECIST do not reflect changes in size and morphology. Additionally, whilst V(ELLIPSOID) is a more suitable surrogate for volume estimation, it is still somewhat limited by the morphology and orientation of such lesions. Studies are warranted to further explore the clinical impact of these findings. Copyright © 2014 Elsevier Ltd. All rights reserved.

  19. Anti-malarial activity of a non-piperidine library of next-generation quinoline methanols

    Science.gov (United States)

    2010-01-01

    Background The clinical utility for mefloquine has been eroded due to its association with adverse neurological effects. Better-tolerated alternatives are required. The objective of the present study was the identification of lead compounds that are as effective as mefloquine, but exhibit physiochemical properties likely to render them less susceptible to passage across the blood-brain barrier. Methods A library of drug-like non-piperidine analogs of mefloquine was synthesized. These compounds are diverse in structure and physiochemical properties. They were screened in appropriate in vitro assays and evaluated in terms of their potential as lead compounds. The correlation of specific structural attributes and physiochemical properties with activity was assessed. Results The most potent analogs were low molecular weight unconjugated secondary amines with no heteroatoms in their side-chains. However, these compounds were more metabolically labile and permeable than mefloquine. In terms of physiochemical properties, lower polar surface area, lower molecular weight, more freely rotatable bonds and fewer H-bond acceptors were associated with greater potency. There was no such relationship between activity and LogP, LogD or the number of hydrogen bond donors (HBDs). The addition of an H-bond donor to the side-chain yielded a series of active diamines, which were as metabolically stable as mefloquine but showed reduced permeability. Conclusions A drug-like library of non-piperidine analogs of mefloquine was synthesized. From amongst this library an active lead series of less permeable, but metabolically stable, diamines was identified. PMID:20149249

  20. The molecular evolution of four anti-malarial immune genes in the Anopheles gambiae species complex

    Directory of Open Access Journals (Sweden)

    Simard Frederic

    2008-03-01

    Full Text Available Abstract Background If the insect innate immune system is to be used as a potential blocking step in transmission of malaria, then it will require targeting one or a few genes with highest relevance and ease of manipulation. The problem is to identify and manipulate those of most importance to malaria infection without the risk of decreasing the mosquito's ability to stave off infections by microbes in general. Molecular evolution methodologies and concepts can help identify such genes. Within the setting of a comparative molecular population genetic and phylogenetic framework, involving six species of the Anopheles gambiae complex, we investigated whether a set of four pre-selected immunity genes (gambicin, NOS, Rel2 and FBN9 might have evolved under selection pressure imposed by the malaria parasite. Results We document varying levels of polymorphism within and divergence between the species, in all four genes. Introgression and the sharing of ancestral polymorphisms, two processes that have been documented in the past, were verified in this study in all four studied genes. These processes appear to affect each gene in different ways and to different degrees. However, there is no evidence of positive selection acting on these genes. Conclusion Considering the results presented here in concert with previous studies, genes that interact directly with the Plasmodium parasite, and play little or no role in defense against other microbes, are probably the most likely candidates for a specific adaptive response against P. falciparum. Furthermore, since it is hard to establish direct evidence linking the adaptation of any candidate gene to P. falciparum infection, a comparative framework allowing at least an indirect link should be provided. Such a framework could be achieved, if a similar approach like the one involved here, was applied to all other anopheline complexes that transmit P. falciparum malaria.

  1. Effects of anti-malarial alkaloids on the sperm properties and blood ...

    African Journals Online (AJOL)

    STORAGESEVER

    2008-10-06

    Oct 6, 2008 ... saponins and quinine hydrochloride. Contraception, 50: 185-190. Heller CG, Clemont Y (1963). Spermatogenesis in man: An estimation of its duration. Science 140: 184-186. Isah AO, Ohaju-Obodo J, Isah EC, Ozemoya O (1997). Drug use in a. Nigerian City Hospital. Pharmacoepidemiol. Drug Safety, 6: ...

  2. Community participation during two mass anti-malarial administrations in Cambodia: lessons from a joint workshop

    NARCIS (Netherlands)

    Peto, Thomas J.; Debackere, Mark; Etienne, William; Vernaeve, Lieven; Tripura, Rupam; Falq, Gregoire; Davoeung, Chan; Nguon, Chea; Rekol, Huy; von Seidlein, Lorenz; Dondorp, Arjen M.; Sanann, Nou; Cheah, Phaik Yeong; de Smet, Martin; Pell, Christopher; Kindermans, Jean-Marie

    2018-01-01

    Two mass drug administrations (MDA) against falciparum malaria were conducted in 2015-16, one as operational research in northern Cambodia, and the other as a clinical trial in western Cambodia. During an April 2017 workshop in Phnom Penh the field teams from Medecins Sans Frontieres and the

  3. Anti-malarial activity of ethanolic leaf extract of Piliostigma thonningii ...

    African Journals Online (AJOL)

    STORAGESEVER

    2010-06-07

    Jun 7, 2010 ... control option for malaria, current research on vaccine development is still at preclinical stage and ... NIPRD/H/6268 has been deposited for future reference at the department's (MPR and TM) herbarium. .... more recently artemisinin derivatives have been identified using rodent malaria model (David et al., ...

  4. In-treatment midwall and endocardial fractional shortening predict cardiovascular outcome in hypertensive patients with preserved baseline systolic ventricular function: the Losartan Intervention For Endpoint reduction study

    DEFF Research Database (Denmark)

    Wachtell, Kristian; Gerdts, Eva; Palmieri, Vittorio

    2010-01-01

    Endocardial fractional shortening (EFS) and midwall shortening (MWS) are impaired in patients with left ventricular hypertrophy. However, it remains unknown whether improvement of left ventricular systolic function during treatment reduces cardiovascular morbidity and mortality in hypertensive...

  5. Patterns of Change in Collaboration Are Associated with Baseline Characteristics and Predict Outcome and Dropout Rates in Treatment of Multi-Problem Families. A Validation Study

    Directory of Open Access Journals (Sweden)

    Egon Bachler

    2017-07-01

    Full Text Available Objective: The present study validates the Multi-Problem Family (MPF-Collaboration Scale, which measures the progress of goal directed collaboration of patients in the treatment of families with MPF and its relation to drop-out rates and treatment outcome.Method: Naturalistic study of symptom and competence-related changes in children of ages 4–18 and their caregivers.Setting: Integrative, structural outreach family therapy.Measures: The data of five different groups of goal directed collaboration (deteriorating collaboration, stable low collaboration, stable medium collaboration, stable high collaboration, improving collaboration were analyzed in their relation to treatment expectation, individual therapeutic goals (ITG, family adversity index, severity of problems and global assessment of a caregiver’s functioning, child, and relational aspects.Results: From N = 810 families, 20% displayed stable high collaboration (n = 162 and 21% had a pattern of improving collaboration. The families with stable high or improving collaboration rates achieved significantly more progress throughout therapy in terms of treatment outcome expectancy (d = 0.96; r = 0.43, reaching ITG (d = 1.17; r = 0.50, family adversities (d = 0.55; r = 0.26, and severity of psychiatric symptoms (d = 0.31; r = 0.15. Furthermore, families with stable high or improving collaboration maintained longer treatments and had a bigger chance of finishing the therapy as planned. The odds of having a stable low or deteriorating collaboration throughout treatment were significantly higher for subjects who started treatment with low treatment expectation or high family-related adversities.Conclusion: The positive outcomes of homebased interventions for multi-problem families are closely related to “stable high” and an “improving” collaboration as measured with the MPF-Collaboration Scale. Patients who fall into these groups have a high treatment outcome expectancy and reduce

  6. Population Genetics and Drug Resistance Markers: An Essential for Malaria Surveillance in Pakistan

    International Nuclear Information System (INIS)

    Raza, A.; Beg, M.A.

    2013-01-01

    Plasmodium (P.) vivax is the prevalent malarial species accounting for 70% of malaria cases in Pakistan. However, baseline epidemiological data on P. vivax population structure and drug resistance are lacking from Pakistan. For population structure studies, molecular genetic markers, circumsporozoite protein (csp) and merozoite surface protein-1 (msp-1) are considered useful as these play an important role in P. vivax survival under immune and environmental pressure. Furthermore, these genes have also been identified as suitable candidates for vaccine development. While efforts for effective vaccine are underway, anti-malarial agents remain the mainstay for control. Evidence of resistance against commonly used anti-malarial agents, particularly Sulphadoxine-Pyrimethamine (SP) is threatening to make this form of control defunct. Therefore, studies on drug resistance are necessary so that anti-malarial treatment strategies can be structured and implemented accordingly by the Malaria Control Program, Pakistan. This review aims to provide information on genetic markers of P. vivax population structure and drug resistance and comment on their usefulness in molecular surveillance and control. (author)

  7. Rationing with baselines

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter Raahave

    2013-01-01

    We introduce a new operator for general rationing problems in which, besides conflicting claims, individual baselines play an important role in the rationing process. The operator builds onto ideas of composition, which are not only frequent in rationing, but also in related problems...... such as bargaining, choice, and queuing. We characterize the operator and show how it preserves some standard axioms in the literature on rationing. We also relate it to recent contributions in such literature....

  8. The TDAQ Baseline Architecture

    CERN Multimedia

    Wickens, F J

    The Trigger-DAQ community is currently busy preparing material for the DAQ, HLT and DCS TDR. Over the last few weeks a very important step has been a series of meetings to complete agreement on the baseline architecture. An overview of the architecture indicating some of the main parameters is shown in figure 1. As reported at the ATLAS Plenary during the February ATLAS week, the main area where the baseline had not yet been agreed was around the Read-Out System (ROS) and details in the DataFlow. The agreed architecture has: Read-Out Links (ROLs) from the RODs using S-Link; Read-Out Buffers (ROB) sited near the RODs, mounted in a chassis - today assumed to be a PC, using PCI bus at least for configuration, control and monitoring. The baseline assumes data aggregation, in the ROB and/or at the output (which could either be over a bus or in the network). Optimization of the data aggregation will be made in the coming months, but the current model has each ROB card receiving input from 4 ROLs, and 3 such c...

  9. PRODIACOR: a patient-centered treatment program for type 2 diabetes and associated cardiovascular risk factors in the city of Corrientes, Argentina: study design and baseline data.

    Science.gov (United States)

    Gagliardino, J J; Lapertosa, S; Villagra, M; Caporale, J E; Oliver, P; Gonzalez, C; Siri, F; Clark, Ch

    2007-07-01

    To implement a controlled clinical trial (PRODIACOR) in a primary care setting designed 1) to improve type 2 diabetes care and 2) to collect cost data in order to be able to measure cost-effectiveness of three system interventions (checkbook of indicated procedures, patient/provider feedback and complete coverage of medications and supplies) and physician and/or patient education to improve psychological, clinical, metabolic and therapeutic indicators. All three Argentinean health subsectors (public health, social security and the private, prepaid system) are participants in the study. Patients of participating physicians were randomly selected and assigned to one of four groups: control, provider education, patient education, and provider/patient education; the system interventions were provided to all four groups. Mean BMI was 29.8 kg/m(2); most subjects had blood pressure, fasting glucose and total cholesterol above targets recommended by international standards. Only 1% had had microalbuminuria measured, 57% performed glucose self-monitoring, 37% had had an eye examination and 31% a foot examination in the preceding year. Ten percent, 26% and 73% of people with hyperglycemia, hypertension and dyslipidemia, respectively, were not on medications. Most patients treated with either insulin or oral antidiabetic agents were on monotherapy as were those treated for hypertension and dyslipidemia. WHO-5 questionnaire scores indicated that 13% of the subjects needed psychological intervention. Baseline data show multiple deficiencies in the process and outcomes of care that could be targeted and improved by PRODIACOR intervention.

  10. Protocol and baseline data for a multi-year cohort study of the effects of different mass drug treatment approaches on functional morbidities from schistosomiasis in four African countries

    DEFF Research Database (Denmark)

    Shen, Ye; King, Charles H.; Binder, Sue

    2017-01-01

    Background The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) focus is on randomized trials of different approaches to mass drug administration (MDA) in endemic countries in Africa. Because their studies provided an opportunity to evaluate the effects of mass treatment...... in four parallel cohort studies. Methods In July 2009, SCORE hosted a discussion of the potential impact of MDA on morbidities due to Schistosoma infection that might be measured in the context of multi-year control. Candidate markers were reviewed and selected for study implementation. Baseline data were...... then collected from cohorts of children in four country studies: two in high endemic S. mansoni sites (Kenya and Tanzania), and two in high endemic S. haematobium sites (Niger and Mozambique), these cohorts to be followed prospectively over 5 years. Results At baseline, 62% of children in the S. mansoni sites...

  11. Retail sector distribution chains for malaria treatment in the developing world: a review of the literature.

    Science.gov (United States)

    Patouillard, Edith; Hanson, Kara G; Goodman, Catherine A

    2010-02-11

    In many low-income countries, the retail sector plays an important role in the treatment of malaria and is increasingly being considered as a channel for improving medicine availability. Retailers are the last link in a distribution chain and their supply sources are likely to have an important influence on the availability, quality and price of malaria treatment. This article presents the findings of a systematic literature review on the retail sector distribution chain for malaria treatment in low and middle-income countries. Publication databases were searched using key terms relevant to the distribution chain serving all types of anti-malarial retailers. Organizations involved in malaria treatment and distribution chain related activities were contacted to identify unpublished studies. A total of 32 references distributed across 12 developing countries were identified. The distribution chain had a pyramid shape with numerous suppliers at the bottom and fewer at the top. The chain supplying rural and less-formal outlets was made of more levels than that serving urban and more formal outlets. Wholesale markets tended to be relatively concentrated, especially at the top of the chain where few importers accounted for most of the anti-malarial volumes sold. Wholesale price mark-ups varied across chain levels, ranging from 27% to 99% at the top of the chain, 8% at intermediate level (one study only) and 2% to 67% at the level supplying retailers directly. Retail mark-ups tended to be higher, and varied across outlet types, ranging from 3% to 566% in pharmacies, 29% to 669% in drug shops and 100% to 233% in general shops. Information on pricing determinants was very limited. Evidence on the distribution chain for retail sector malaria treatment was mainly descriptive and lacked representative data on a national scale. These are important limitations in the advent of the Affordable Medicine Facility for Malaria, which aims to increase consumer access to artemisinin

  12. Retail sector distribution chains for malaria treatment in the developing world: a review of the literature

    Directory of Open Access Journals (Sweden)

    Hanson Kara G

    2010-02-01

    Full Text Available Abstract Background In many low-income countries, the retail sector plays an important role in the treatment of malaria and is increasingly being considered as a channel for improving medicine availability. Retailers are the last link in a distribution chain and their supply sources are likely to have an important influence on the availability, quality and price of malaria treatment. This article presents the findings of a systematic literature review on the retail sector distribution chain for malaria treatment in low and middle-income countries. Methods Publication databases were searched using key terms relevant to the distribution chain serving all types of anti-malarial retailers. Organizations involved in malaria treatment and distribution chain related activities were contacted to identify unpublished studies. Results A total of 32 references distributed across 12 developing countries were identified. The distribution chain had a pyramid shape with numerous suppliers at the bottom and fewer at the top. The chain supplying rural and less-formal outlets was made of more levels than that serving urban and more formal outlets. Wholesale markets tended to be relatively concentrated, especially at the top of the chain where few importers accounted for most of the anti-malarial volumes sold. Wholesale price mark-ups varied across chain levels, ranging from 27% to 99% at the top of the chain, 8% at intermediate level (one study only and 2% to 67% at the level supplying retailers directly. Retail mark-ups tended to be higher, and varied across outlet types, ranging from 3% to 566% in pharmacies, 29% to 669% in drug shops and 100% to 233% in general shops. Information on pricing determinants was very limited. Conclusions Evidence on the distribution chain for retail sector malaria treatment was mainly descriptive and lacked representative data on a national scale. These are important limitations in the advent of the Affordable Medicine Facility for

  13. Treatment with the first TNF inhibitor in rheumatoid arthritis patients in the Hellenic Registry of Biologic Therapies improves quality of life especially in young patients with better baseline functional status.

    Science.gov (United States)

    Boubouchairopoulou, Nadia; Flouri, Irini; Drosos, Alexandros A; Boki, Kyriaki; Settas, Loukas; Zisopoulos, Dimitrios; Skopouli, Fotini N; Papadopoulos, Ioannis; Iliopoulos, Alexios; Kyriopoulos, John; Boumpas, Dimitrios T; Athanasakis, Konstantinos; Sidiropoulos, Prodromos

    2016-01-01

    To assess in daily practice in patients with rheumatoid arthritis (RA) the effect of treatment with first tumour necrosis factor-α inhibitor (TNFi) in quality of life (Qol), disease activity and depict possible baseline predictors for gains in Qol. Patients followed prospectively by the Hellenic Registry of Biologic Therapies were analysed. Demographics were recorded at baseline, while RA-related characteristics at baseline and every 6 months. Paired t-tests were used to detect divergences between patient-reported (Health Assessment Questionnaire (HAQ), EuroQol (EQ-5D)) and clinical tools (Disease Activity Score-28 joints (DAS28)). Clinical versus self-reported outcomes were examined via cross-tabulation analysis. Multiple regression analysis was performed for identifying baseline predictors of improvements in QALYs. We analysed 255 patients (age (mean±SD) 57.1±13.0, disease duration 9.2±9.1 years, prior non-biologic disease-modifying anti-rheumatic drugs 2.3±1.2). Baseline EQ-5D, HAQ and DAS28 were 0.36 (0.28), 1.01 (0.72) and 5.9 (1.3), respectively, and were all significantly improved after 12 months (0.77 (0.35), 0.50 (0.66), 3.9 (1.5), respectively, p<0.05 for all). 90% of patients who improved from high to a lower DAS28 status (low-remission or moderate) had clinically important improvement in Qol (phi-coefficient=0.531,p<0.05). Independent predictors of gains in Qol were lower baseline HAQ, VAS global and younger age (adjusted R2=0.27). In daily practice TNFi improve both disease activity and Qol for the first 12 months of therapy. 90% of patients who improved from high to a lower DAS28 status had clinically important improvement in Qol. Younger patients starting with lower HAQ and VAS global are more likely to benefit.

  14. Efficacy and safety of azelaic acid (AzA) gel 15% in the treatment of post-inflammatory hyperpigmentation and acne: a 16-week, baseline-controlled study.

    Science.gov (United States)

    Kircik, Leon H

    2011-06-01

    Although there are few differences in the incidence and pathophysiology of acne across various races and ethnicities, there is some evidence that black patients may have larger sebaceous glands and increased sebum production. Of greater clinical relevance, patients with darker skin types are at increased risk for the development of post-inflammatory hyperpigmentation (PIH), which some find as or more troubling than acne itself. This common and bothersome sequelum of acne can be difficult to manage in this population. Topical azelaic acid gel is recognized to have anti-tyrosinase activity, suggesting it may be a suitable treatment option for mild-to-moderate acne with associated moderate-to-severe PIH. This pilot study demonstrates the efficacy of topical AzA gel 15% when applied twice daily for the reduction of both acne and PIH. J

  15. Space treatments of insecticide for control of dengue virus vector Aedes aegypti in southern Mexico. I. Baseline penetration trials in open field and houses.

    Science.gov (United States)

    Arrendondo-Jimenez, Juan I; Rivero, Norma E

    2006-06-01

    We studied the efficacy of space ultra-low volume treatments of 3 insecticides for the control of the dengue virus vector Aedes aegypti in southern Mexico. Insecticides tested were permethrin (Aqua-Reslin Super), d-phenothrin (Anvil), and cyfluthrin (Solfac), applied at rates of 10.87, 7.68, and 2 g/ha, respectively, by using London Fog, HP910-PHXL, or Micro-Gen pumps mounted on vehicles. Studies included 1) open field penetration tests and 2) house penetration tests. Open field tests indicated that Anvil and Solfac were more effective than Aqua-Reslin Super. In house tests, Anvil yielded the highest mosquito mortalities (>/=88%) of the three insecticides in the front porch, living room, bedroom, and backyard. Therefore, Anvil proved to be better than other insecticides evaluated to control Ae. aegypti in Chiapas, Mexico.

  16. 2017 Annual Technology Baseline

    Energy Technology Data Exchange (ETDEWEB)

    Cole, Wesley J [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Hand, M. M [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Eberle, Annika [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Beiter, Philipp C [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Kurup, Parthiv [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Turchi, Craig S [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Feldman, David J [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Margolis, Robert M [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Augustine, Chad R [National Renewable Energy Laboratory (NREL), Golden, CO (United States); Maness, Michael [Formerly NREL; O' Connor, Patrick [Oak Ridge National Laboratory

    2018-03-26

    Consistent cost and performance data for various electricity generation technologies can be difficult to find and may change frequently for certain technologies. With the Annual Technology Baseline (ATB), the National Renewable Energy Laboratory annually provides an organized and centralized set of such cost and performance data. The ATB uses the best information from the Department of Energy national laboratories' renewable energy analysts as well as information from the Energy Information Administration for fuel-based technologies. The ATB has been reviewed by experts and it includes the following electricity generation technologies: land-based wind, offshore wind, utility-scale solar photovoltaics (PV), commercial-scale solar PV, residential-scale solar PV, concentrating solar power, geothermal power, hydropower, coal, natural gas, nuclear, and conventional biopower. This webinar presentation introduces the 2017 ATB.

  17. Temporal distribution of baseline characteristics and association ...

    African Journals Online (AJOL)

    The first six months of HIV care and treatment are very important for long-term outcome. Early mortality (within 6 months of care initiation) undermines care and treatment goals. This study assessed the temporal distribution in baseline characteristics and early mortality among HIV patients at the University College Hospital, ...

  18. Types of adult attention-deficit hyperactivity disorder (ADHD): baseline characteristics, initial response, and long-term response to treatment with methylphenidate.

    Science.gov (United States)

    Reimherr, Fred W; Marchant, Barrie K; Gift, Thomas E; Steans, Tammy A; Wender, Paul H

    2015-06-01

    Much recent research describes the importance of emotional symptoms in ADHD. While there is no accepted system for including emotionality in diagnosing ADHD, the Wender-Reimherr Adult Attention Deficit Disorder Scale (WRAADDS) provides a tool to facilitate this. It assesses a range of adult ADHD symptoms which load on two factors: inattentive and emotional dysregulation. The consistently high inattentive factor was used to define significant elevation on the more variable emotional dysregulation factor (which contains four WRAADDS domains: hyperactivity/restlessness, temper, affective lability, and emotional over-reactivity) allowing the definition of two ADHD diagnostic types. We compared these two types on a broad range of adult subject characteristics, including response to methylphenidate (MPH) treatment assessed during two clinical trials. Marked impairment in three of the four emotional domains reflected a symptom severity level equivalent to that of the inattentive factor. 59 % met this threshold, defining them as ADHD emotion dysregulation presentation, as opposed to 41 % with ADHD inattentive presentation. Cluster analysis validated these groups by generating similar clusters with 85 % agreement regarding membership. ADHD emotional dysregulation presentation subjects showed more childhood ADHD symptoms, adult symptoms of oppositional defiant disorder, and evidence of personality disorder. Both types showed similar improvement during the double-blind MPH arm of the trials and during a 6-month open-label phase. Based on the presence of symptoms of emotional dysregulation, ADHD in adults can be conceptualized as two types. Impairment and comorbidity in adults with ADHD are largely concentrated in ADHD emotional dysregulation presentation patients.

  19. Investigations of morning and laboratory dream recall and content in depressive patients during baseline conditions and under antidepressive treatment with trimipramine.

    Science.gov (United States)

    Riemann, D; Löw, H; Schredl, M; Wiegand, M; Dippel, B; Berger, M

    1990-06-01

    REM sleep abnormalities like shortened REM (rapid eye movement) latency, prolongation of the first REM period and heightening of REM density often found in patients with a major depression have prompted an increasing number of studies investigating the neurobiology and neurophysiology of REM sleep in depressive patients, as well as in healthy humans and animals. On the other hand, since the early 1970s investigation of the psychological concomitant of REM sleep, i.e., dreaming, in depressive patients has been extremely sparse. The present study aimed at investigating morning and laboratory dream recall and content in patients with a major depressive disorder to shed more light on this neglected area. In short, morning as well as laboratory dream recall in depressive inpatients was drastically reduced. The low number of scorable dream reports collected did not reveal a heightened incidence of "masochistic" or "negative" content, indeed were rather mundane. In contrast, depressive outpatients (probably less depressed) had a higher rate of morning dream recall. Interestingly, antidepressive treatment with trimipramine (an antidepressant which does not suppress REM sleep) led to a positive influence on patients' mood that was paralleled by a change of dream mood in a positive direction.

  20. Comparison of non-radiographic axial spondyloarthritis and ankylosing spondylitis patients--baseline characteristics, treatment adherence, and development of clinical variables during three years of anti-TNF therapy in clinical practice.

    Science.gov (United States)

    Wallman, Johan K; Kapetanovic, Meliha C; Petersson, Ingemar F; Geborek, Pierre; Kristensen, Lars Erik

    2015-12-24

    The relationship between non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) is currently debated. Using observational data from the South Swedish Arthritis Treatment Group register, we thus aimed to compare clinical development and treatment adherence between nr-axSpA and AS patients during three years of anti-TNF (tumor necrosis factor) therapy in clinical practice, and to explore the impact of inflammatory activity measured by CRP (C-reactive protein) at treatment initiation. Nr-axSpA and AS patients (n = 86/238) in southern Sweden, commencing anti-TNF therapy 1999-2011, were followed during three years. Anti-TNF cessation was defined as stopping therapy, without restarting another anti-TNF agent within three months. Differences in the three year developments of patient's visual analogue scale (VAS) scores for global health and pain, EuroQol 5-Dimensions utility, evaluator's global disease activity assessment, CRP, and ESR (erythrocyte sedimentation rate) were assessed by repeated ANOVA. Anti-TNF adherence was compared by Log rank test and Cox regression. In a subanalysis, the same outcomes were studied after splitting both groups into patients with/without baseline CRP elevation. Nr-axSpA patients were more often female and had lower acute phase reactants at baseline. Apart from CRP, which remained lower in the nr-axSpA group throughout follow-up (p = 0.004), no between-group differences were detected regarding clinical developments (p >0.1 for all comparisons) or anti-TNF adherence (hazard ratio: 1.1 (95% CI 0.7 to 1.8) for the nr-axSpA vs. AS group) during three years. Elevated baseline CRP was similarly associated with superior clinical outcomes and treatment adherence in both groups. With the exception of constantly lower CRP levels in the nr-axSpA group, three years anti-TNF therapy resulted in similar clinical outcomes and treatment adherence in nr-axSpA and AS patients, thus strengthening the hypothesis that

  1. Biofuels Baseline 2008

    Energy Technology Data Exchange (ETDEWEB)

    Hamelinck, C.; Koper, M.; Berndes, G.; Englund, O.; Diaz-Chavez, R.; Kunen, E.; Walden, D.

    2011-10-15

    The European Union is promoting the use of biofuels and other renewable energy in transport. In April 2009, the Renewable Energy Directive (2009/28/EC) was adopted that set a 10% target for renewable energy in transport in 2020. The directive sets several requirements to the sustainability of biofuels marketed in the frame of the Directive. The Commission is required to report to the European Parliament on a regular basis on a range of sustainability impacts resulting from the use of biofuels in the EU. This report serves as a baseline of information for regular monitoring on the impacts of the Directive. Chapter 2 discusses the EU biofuels market, the production and consumption of biofuels and international trade. It is derived where the feedstock for EU consumed biofuels originally come from. Chapter 3 discusses the biofuel policy framework in the EU and major third countries of supply. It looks at various policy aspects that are relevant to comply with the EU sustainability requirements. Chapter 4 discusses the environmental and social sustainability aspects associated with EU biofuels and their feedstock. Chapter 5 discusses the macro-economic effects that indirectly result from increased EU biofuels consumption, on commodity prices and land use. Chapter 6 presents country factsheets for main third countries that supplied biofuels to the EU market in 2008.

  2. Malaria investigation and treatment of children admitted to county hospitals in western Kenya.

    Science.gov (United States)

    Amboko, Beatrice I; Ayieko, Philip; Ogero, Morris; Julius, Thomas; Irimu, Grace; English, Mike

    2016-10-18

    Up to 90 % of the global burden of malaria morbidity and mortality occurs in sub-Saharan Africa and children under-five bear a disproportionately high malaria burden. Effective inpatient case management can reduce severe malaria mortality and morbidity, but there are few reports of how successfully international and national recommendations are adopted in management of inpatient childhood malaria. A descriptive cross-sectional study of inpatient malaria case management practices was conducted using data collected over 24 months in five hospitals from high malaria risk areas participating in the Clinical Information Network (CIN) in Kenya. This study describes documented clinical features, laboratory investigations and treatment of malaria in children (2-59 months) and adherence to national guidelines. A total of 13,014 children had a malaria diagnosis on admission to the five hospitals between March, 2014 and February, 2016. Their median age was 24 months (IQR 12-36 months). The proportion with a diagnostic test for malaria requested was 11,981 (92.1 %). Of 10,388 patients with malaria test results documented, 8050 (77.5 %) were positive and anti-malarials were prescribed in 6745 (83.8 %). Malaria treatment was prescribed in 1613/2338 (69.0 %) children with a negative malaria result out of which only 52 (3.2 %) had a repeat malaria test done as recommended in national guidelines. Documentation of clinical features was good across all hospitals, but quinine remained the most prescribed malaria drug (47.2 % of positive cases) although a transition to artesunate (46.1 %) was observed. Although documented clinical features suggested approximately half of positive malaria patients were not severe cases artemether-lumefantrine was prescribed on admission in only 3.7 % cases. Despite improvements in inpatient malaria care, high rates of presumptive treatment for test negative children and likely over-use of injectable anti-malarial drugs were observed. Three

  3. Malaria investigation and treatment of children admitted to county hospitals in western Kenya

    Directory of Open Access Journals (Sweden)

    Beatrice I. Amboko

    2016-10-01

    Full Text Available Abstract Background Up to 90 % of the global burden of malaria morbidity and mortality occurs in sub-Saharan Africa and children under-five bear a disproportionately high malaria burden. Effective inpatient case management can reduce severe malaria mortality and morbidity, but there are few reports of how successfully international and national recommendations are adopted in management of inpatient childhood malaria. Methods A descriptive cross-sectional study of inpatient malaria case management practices was conducted using data collected over 24 months in five hospitals from high malaria risk areas participating in the Clinical Information Network (CIN in Kenya. This study describes documented clinical features, laboratory investigations and treatment of malaria in children (2–59 months and adherence to national guidelines. Results A total of 13,014 children had a malaria diagnosis on admission to the five hospitals between March, 2014 and February, 2016. Their median age was 24 months (IQR 12–36 months. The proportion with a diagnostic test for malaria requested was 11,981 (92.1 %. Of 10,388 patients with malaria test results documented, 8050 (77.5 % were positive and anti-malarials were prescribed in 6745 (83.8 %. Malaria treatment was prescribed in 1613/2338 (69.0 % children with a negative malaria result out of which only 52 (3.2 % had a repeat malaria test done as recommended in national guidelines. Documentation of clinical features was good across all hospitals, but quinine remained the most prescribed malaria drug (47.2 % of positive cases although a transition to artesunate (46.1 % was observed. Although documented clinical features suggested approximately half of positive malaria patients were not severe cases artemether-lumefantrine was prescribed on admission in only 3.7 % cases. Conclusions Despite improvements in inpatient malaria care, high rates of presumptive treatment for test negative children and likely

  4. Treatment Failure for Malaria in Vietnam

    Centers for Disease Control (CDC) Podcasts

    2017-06-05

    WHO malaria expert, Dr. Charlotte Rasmussen, discusses anti-malarial drug resistance in Vietnam.  Created: 6/5/2017 by National Center for Emerging and Zoonotic Infectious Diseases (NCEZID).   Date Released: 6/5/2017.

  5. Ethnomedicinal uses of plants for the treatment of malaria in Soon Valley, Khushab, Pakistan.

    Science.gov (United States)

    Shah, Amin; Rahim, Sarvat

    2017-03-22

    To best of our knowledge this is the first quantitative ethno-medicinal study with the aim of documenting the indigenous knowledge and practices of using plants for malarial therapy in Soon Valley, Khushab, Pakistan. In this Valley, malaria is among the major public health problems but, until now, the population still mostly relies on herbal medicine for treatment. Ethno-medicinal data were documented from 63 informants by using semi-structured questionnaires and interviewing the informants about their knowledge of plants regarding malaria and related symptoms. Documented data were evaluated using the quantitative ethno-botanical indices of frequency citation (FC), relative frequency of citation (RFC), percentage of respondents having knowledge (PRK) and Jaccard index (JI). A total of 70 plant species belonging to 62 genera and 34 families were recorded as anti-malarial in the study area. Solanaceae was found to be the most cited family with 7 species, followed by Fabaceae, Rutaceae and Lamiaceae with 5 species each. Ocimum americanum and Solanum incanum were the species with the highest relative frequency of citation (RFC =0.25 each) and percentage of respondents having knowledge (PRK =25.4% each), followed by Grewia tenax (RFC =0.23, PRK =23.8%), which indicates that these plants are the best species with anti-malarial properties. The most highly cited life form was found to be herbs (56%). The dominant plant part used in preparations were leaves (49%). The main mode of utilization was decoction (47%) followed by infusion (29%). In comparison, maximum similarity index is found in our study with JI (16.83) followed by (13.13). Similarity percentage of plants uses ranges from 0.81 to 16.83 while dissimilarity percentage varies from 0% to 17.65%. To the best of our knowledge seven plant species, viz. Withania coagulans, Fagonia cretica, Carthamus oxyacantha, Ehretia obtusifolia, Helianthus annuus, Olea ferruginea and Vitex trifolia, are reported from this region for

  6. Monitoring fever treatment behaviour and equitable access to effective medicines in the context of initiatives to improve ACT access: baseline results and implications for programming in six African countries

    Directory of Open Access Journals (Sweden)

    Littrell Megan

    2011-10-01

    Full Text Available Abstract Background Access to artemisinin-based combination therapy (ACT remains limited in high malaria-burden countries, and there are concerns that the poorest people are particularly disadvantaged. This paper presents new evidence on household treatment-seeking behaviour in six African countries. These data provide a baseline for monitoring interventions to increase ACT coverage, such as the Affordable Medicines Facility for malaria (AMFm. Methods Nationally representative household surveys were conducted in Benin, the Democratic Republic of Congo (DRC, Madagascar, Nigeria, Uganda and Zambia between 2008 and 2010. Caregivers responded to questions about management of recent fevers in children under five. Treatment indicators were tabulated across countries, and differences in case management provided by the public versus private sector were examined using chi-square tests. Logistic regression was used to test for association between socioeconomic status and 1 malaria blood testing, and 2 ACT treatment. Results Fever treatment with an ACT is low in Benin (10%, the DRC (5%, Madagascar (3% and Nigeria (5%, but higher in Uganda (21% and Zambia (21%. The wealthiest children are significantly more likely to receive ACT compared to the poorest children in Benin (OR = 2.68, 95% CI = 1.12-6.42; the DRC (OR = 2.18, 95% CI = 1.12-4.24; Madagascar (OR = 5.37, 95% CI = 1.58-18.24; and Nigeria (OR = 6.59, 95% CI = 2.73-15.89. Most caregivers seek treatment outside of the home, and private sector outlets are commonly the sole external source of treatment (except in Zambia. However, children treated in the public sector are significantly more likely to receive ACT treatment than those treated in the private sector (except in Madagascar. Nonetheless, levels of testing and ACT treatment in the public sector are low. Few caregivers name the national first-line drug as most effective for treating malaria in Madagascar (2%, the DRC (2%, Nigeria (4% and Benin (10

  7. Baseline ICIQ-UI score, body mass index, age, average birth weight, and perineometry duration as promising predictors of the short-term efficacy of Er:YAG laser treatment in stress urinary incontinent women: A prospective cohort study.

    Science.gov (United States)

    Fistonić, Ivan; Fistonić, Nikola

    2018-01-23

    A growing body of evidence indicates that a non-invasive erbium yttrium-aluminum-garnet (Er:YAG) laser may be an effective and highly tolerable treatment for stress urinary incontinence (SUI) in women. The primary objective was to identify pre-intervention predictors of short-term Er:YAG outcomes. The secondary objective was to identify patient segments with the best Er:YAG laser treatment short-term outcomes. A prospective cohort study performed in 2016 at Ob/Gyn Clinic, Zagreb, Croatia, recruited 85 female patients who suffered from SUI. The intervention was performed with a 2940 nm wave length Er:YAG laser (XS Dynamis, Fotona, Slovenia). Outcomes were absolute change in the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI SF) and a relative decrease in ICIQ-UI score of ≥30% 2-6 months after the intervention. Age and pre-intervention ICIQ-UI values were independent significant predictors of laser treatment efficacy for SUI. A decrease in ICIQ-UI score (minimum important difference, MID) of ≥30% was independently significantly associated with body mass index and ICIQ-UI values before the intervention. All patients with four or five positive predictors saw a clinically relevant decrease in ICIQ-UI of ≥30%. The total accuracy of the predictive model defined by the area under the curve was 0.83 (95%CI 0.74-0.91). At the cut-off ≥3 positive predictors, C-index was 0.80 (95%CI 0.71-0.90), positive predictive value was 0.97 (95%CI 0.87-0.99), and negative predictive value was 0.53 (95%CI 0.45-0.55). A relevant decrease in ICIQ-UI (MID) of ≥30% can be predicted based on age, body mass index, average birth weight, perineometer squeeze duration, and ICIQ-UI scores before the intervention. The association between Q-tip test and treatment outcome was moderated by age. Q-tip was a significant predictor for patients between 44 and 53 years of age. The best results should be expected in younger women with a body mass index of ≤23

  8. Trends in malaria case management following changes in the treatment policy to artemisinin combination therapy at the Mbakong Health Centre, Cameroon 2006-2012: a retrospective study.

    Science.gov (United States)

    Ndong, Ignatius C; Reenen, Mari van; Boakye, Daniel A; Mbacham, Wilfred F; Grobler, Anne F

    2015-10-01

    National malaria treatment policies are devised to guide health professionals and to facilitate diagnosis and case management. Following the recommendations of the WHO, Cameroon changed its malaria treatment policy from monotherapy to artemisinin-based combination therapy (ACT) as the first-line treatment for uncomplicated malaria. We report an investigation into trends of case management following this change in policy. Data was collected retrospectively, through consultation and perusal of laboratory and prescription registers of the Mbakong Health Centre. Analysis of data was done using SPSS and SAS Statistics. Data presented herein demonstrate that from 2006 to 2012, a total of 2484 (58.7%) of the total prescriptions included an anti-malarial, 1989 (47.0%) included an antibiotic and 1935(45.7%) included an antipyretic. The anti-malarials prescribed were Anti-malaria combination therapy (ACT) - 1216 (47.6%), quinine 1044 (40.8%) or SP 296 (11.6%). Of the 1216 patients prescribed an ACT, 441(36.3%) had a positive malaria parasite confirmation, 746 (61.3%) were negative for plasmodium. Overall, 29 patients (2.4%) were treated either with an ACT without any test performed. Quinine intake was recorded in 566 (54.2%) patients positive for plasmodium. ACT prescription increased from 23% in 2007 to between 44 and 45% in 2008-2009. During this period there was a corresponding drop in the prescription of quinine from 38% in 2007 to 13% in 2009 (r=-0.43, p>0.05). Sulphadoxine-Pyrimethamine (SP) was restrictively prescribed to women of childbearing age (97.0%) after 2008. Antibiotics prescription dropped from 53.7% to 39.3% from 2010 to 2012. The odds of being prescribed an antibiotic was significantly higher in patients with a malaria negative result compared to malaria positive patients (OR=6.12, CI 4.74-7.91, p<0.00001). Overall, there is an over treatment of malaria, thus departing from the WHO guidelines of appropriate treatment. Although there is an overall increase

  9. Modelling malaria treatment practices in Bangladesh using spatial statistics

    Directory of Open Access Journals (Sweden)

    Haque Ubydul

    2012-03-01

    Full Text Available Abstract Background Malaria treatment-seeking practices vary worldwide and Bangladesh is no exception. Individuals from 88 villages in Rajasthali were asked about their treatment-seeking practices. A portion of these households preferred malaria treatment from the National Control Programme, but still a large number of households continued to use drug vendors and approximately one fourth of the individuals surveyed relied exclusively on non-control programme treatments. The risks of low-control programme usage include incomplete malaria treatment, possible misuse of anti-malarial drugs, and an increased potential for drug resistance. Methods The spatial patterns of treatment-seeking practices were first examined using hot-spot analysis (Local Getis-Ord Gi statistic and then modelled using regression. Ordinary least squares (OLS regression identified key factors explaining more than 80% of the variation in control programme and vendor treatment preferences. Geographically weighted regression (GWR was then used to assess where each factor was a strong predictor of treatment-seeking preferences. Results Several factors including tribal affiliation, housing materials, household densities, education levels, and proximity to the regional urban centre, were found to be effective predictors of malaria treatment-seeking preferences. The predictive strength of each of these factors, however, varied across the study area. While education, for example, was a strong predictor in some villages, it was less important for predicting treatment-seeking outcomes in other villages. Conclusion Understanding where each factor is a strong predictor of treatment-seeking outcomes may help in planning targeted interventions aimed at increasing control programme usage. Suggested strategies include providing additional training for the Building Resources across Communities (BRAC health workers, implementing educational programmes, and addressing economic factors.

  10. Diagnosis and treatment based on quantitative PCR after controlled human malaria infection

    Directory of Open Access Journals (Sweden)

    Jona Walk

    2016-08-01

    Full Text Available Abstract Background Controlled human malaria infection (CHMI has become well-established in the evaluation of drugs and vaccines. Anti-malarial treatment is usually initiated when thick blood smears are positive by microscopy. This study explores the effects of using the more sensitive qPCR as the primary diagnostic test. Methods 1691 diagnostic blood samples were analysed by microscopy and qPCR from 115 volunteers (55 malaria naïve and 60 having received chemoprophylaxis and sporozoite immunization who were challenged by five mosquitoes infected with Plasmodium falciparum sporozoites of the NF54 strain. Results Retrospective analysis of different qPCR criteria for diagnosis and treatment, showed that once daily qPCR (threshold 100 parasites/ml had 99 % sensitivity and 100 % specificity, and shortened the median prepatent period from 10.5 to 7.0 days after CHMI when compared to twice daily measurement of thick blood smears (threshold 4000 parasites/ml. This is expected to result in a 78 % decrease of adverse events before initiation of treatment in future studies. Trial outcome related to infection and protective efficacy remained unchanged. Conclusion The use of qPCR as the primary diagnostic test in CHMI decreases symptoms as well as parasitaemia while obviating the need for twice daily follow-up. The implementation improves safety while reducing the clinical burden and costs without compromising the evaluation of protective efficacy.

  11. DairyBISS Baseline report

    NARCIS (Netherlands)

    Buizer, N.N.; Berhanu, Tinsae; Murutse, Girmay; Vugt, van S.M.

    2015-01-01

    This baseline report of the Dairy Business Information Service and Support (DairyBISS) project presents the findings of a baseline survey among 103 commercial farms and 31 firms and advisors working in the dairy value chain. Additional results from the survey among commercial dairy farms are

  12. Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity.

    Science.gov (United States)

    Staszewski, Vincent; Reece, Sarah E; O'Donnell, Aidan J; Cunningham, Emma J A

    2012-06-22

    Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way through infection prior to pregnancy can alter their immune response, with major consequences for offspring health and survival. In untreated maternal infections, maternally transferred protection suppressed parasitaemia and reduced pup mortality by 75 per cent compared with pups from naïve dams. However, when dams were treated with anti-malarial drugs, pups received fewer maternal antibodies, parasitaemia was only marginally suppressed, and mortality risk was 25 per cent higher than for pups from dams with full infections. We observed the same qualitative patterns across three different host strains and two parasite genotypes. This study reveals the role that within-host infection dynamics play in the fitness consequences of maternally transferred immunity. Furthermore, it highlights a potential trade-off between the health of mothers and offspring suggesting that anti-parasite treatment may significantly affect the outcome of infection in newborns.

  13. Drug treatment of malaria infections can reduce levels of protection transferred to offspring via maternal immunity

    Science.gov (United States)

    Staszewski, Vincent; Reece, Sarah E.; O'Donnell, Aidan J.; Cunningham, Emma J. A.

    2012-01-01

    Maternally transferred immunity can have a fundamental effect on the ability of offspring to deal with infection. However, levels of antibodies in adults can vary both quantitatively and qualitatively between individuals and during the course of infection. How infection dynamics and their modification by drug treatment might affect the protection transferred to offspring remains poorly understood. Using the rodent malaria parasite Plasmodium chabaudi, we demonstrate that curing dams part way through infection prior to pregnancy can alter their immune response, with major consequences for offspring health and survival. In untreated maternal infections, maternally transferred protection suppressed parasitaemia and reduced pup mortality by 75 per cent compared with pups from naïve dams. However, when dams were treated with anti-malarial drugs, pups received fewer maternal antibodies, parasitaemia was only marginally suppressed, and mortality risk was 25 per cent higher than for pups from dams with full infections. We observed the same qualitative patterns across three different host strains and two parasite genotypes. This study reveals the role that within-host infection dynamics play in the fitness consequences of maternally transferred immunity. Furthermore, it highlights a potential trade-off between the health of mothers and offspring suggesting that anti-parasite treatment may significantly affect the outcome of infection in newborns. PMID:22357264

  14. Program Baseline Change Control Procedure

    International Nuclear Information System (INIS)

    1993-02-01

    This procedure establishes the responsibilities and process for approving initial issues of and changes to the technical, cost, and schedule baselines, and selected management documents developed by the Office of Civilian Radioactive Waste Management (OCRWM) for the Civilian Radioactive Waste Management System. This procedure implements the OCRWM Baseline Management Plan and DOE Order 4700.1, Chg 1. It streamlines the change control process to enhance integration, accountability, and traceability of Level 0 and Level I decisions through standardized Baseline Change Proposal (BCP) forms to be used by the Level 0, 1, 2, and 3 Baseline Change Control Boards (BCCBs) and to be tracked in the OCRWM-wide Configuration Information System (CIS) Database.This procedure applies to all technical, cost, and schedule baselines controlled by the Energy System Acquisition Advisory Board (ESAAB) BCCB (Level 0) and, OCRWM Program Baseline Control Board (PBCCB) (Level 1). All baseline BCPs initiated by Level 2 or lower BCCBs, which require approval from ESAAB or PBCCB, shall be processed in accordance with this procedure. This procedure also applies to all Program-level management documents controlled by the OCRWM PBCCB

  15. 324 Building Baseline Radiological Characterization

    Energy Technology Data Exchange (ETDEWEB)

    R.J. Reeder, J.C. Cooper

    2010-06-24

    This report documents the analysis of radiological data collected as part of the characterization study performed in 1998. The study was performed to create a baseline of the radiological conditions in the 324 Building.

  16. Baseline restoration using current conveyors

    International Nuclear Information System (INIS)

    Morgado, A.M.L.S.; Simoes, J.B.; Correia, C.M.

    1996-01-01

    A good performance of high resolution nuclear spectrometry systems, at high pulse rates, demands restoration of baseline between pulses, in order to remove rate dependent baseline shifts. This restoration is performed by circuits named baseline restorers (BLRs) which also remove low frequency noise, such as power supply hum and detector microphonics. This paper presents simple circuits for baseline restoration based on a commercial current conveyor (CCII01). Tests were performed, on two circuits, with periodic trapezoidal shaped pulses in order to measure the baseline restoration for several pulse rates and restorer duty cycles. For the current conveyor based Robinson restorer, the peak shift was less than 10 mV, for duty cycles up to 60%, at high pulse rates. Duty cycles up to 80% were also tested, being the maximum peak shift 21 mV. The peak shift for the current conveyor based Grubic restorer was also measured. The maximum value found was 30 mV at 82% duty cycle. Keeping the duty cycle below 60% improves greatly the restorer performance. The ability of both baseline restorer architectures to reject low frequency modulation is also measured, with good results on both circuits

  17. The detection and treatment of Plasmodium falciparum malaria: Time for change

    Directory of Open Access Journals (Sweden)

    Nosten F

    2004-01-01

    Full Text Available In most countries where malaria is endemic, P. falciparum malaria is on the rise. This is primarily due to the spread of drug-resistant strains. Drug resistance is mediated by spontaneous changes in the parasite genome that allow resistant parasites to escape the action of the drugs. The spread of drug resistance increases the transmission of malaria parasites. The consequences for the populations at risk are profound both in terms of consequences for health and economy. In order to halt the progression of drug resistance, we need to change the way antimalarials are used. As in tuberculosis and HIV/AIDS, we must use a combination of drugs for the treatment of malaria. Taking into account the pharmacokinetic and pharmacodynamic properties of the various anti-malarial agents, artemisinin-based combination therapy (ACT seems to be the best option. This strategy should be used in conjunction with early diagnosis and appropriate vector control measures to achieve reduction in the emergence and spread of drug resistance.

  18. A retrospective evaluation of the quality of malaria case management at twelve health facilities in four districts in Zambia

    Directory of Open Access Journals (Sweden)

    Pascalina Chanda-Kapata

    2014-06-01

    Conclusions: Malaria case management was characterised by poor adherence to treatment guidelines. The non-adherence was mainly in terms of: inconsistent use of confirmatory tests (rapid diagnostic test or microscopy for malaria; prescribing anti-malarials which are not recommended (e.g. sulphadoxine-pyrimethamine and prescribing anti-malarials to cases testing negative. Innovative approaches are required to improve health worker adherence to diagnosis and treatment guidelines.

  19. Which method better evaluates the molecular response in newly diagnosed chronic phase chronic myeloid leukemia patients with imatinib treatment, BCR-ABL(IS) or log reduction from the baseline level?

    Science.gov (United States)

    Qin, Ya-Zhen; Jiang, Qian; Jiang, Hao; Li, Jin-Lan; Li, Ling-Di; Zhu, Hong-Hu; Lai, Yue-Yun; Lu, Xi-Jing; Liu, Yan-Rong; Jiang, Bin; Huang, Xiao-Jun

    2013-09-01

    The molecular response of chronic myeloid leukemia (CML) patients to tyrosine kinase inhibitor treatment can be evaluated either by BCR-ABL mRNA levels on international scale (IS) or by log reduction from the baseline level of the laboratory. Both methods were compared in 248 newly diagnosed chronic phase CML patients treated with imatinib. The major molecular responses (MMR) obtained by both methods predict progression-free survival (PFS, all Plog reduction method, had the same PFS as MMR patients identified by both methods. The molecular responses of patients at 3 and 6 months, as evaluated by the two methods, have similar predictive values on their cytogenetic responses at 12 months and on their molecular responses at 18 months. Both ≤ 10%(IS) and ≥ 1 log reduction at 3 months and ≤ 1%(IS) at 6 months were significantly associated with PFS (P=0.0011, 0.0090, and 0.0064). The percentages of patients with BCR-ABL(IS) of ≤ 1%, >1-10%, and of >10% at 3 months and 6 months in the German CML Study IV were similar with those with corresponding BCR-ABL(IS) in our center, but was significantly different with those evaluated by the log reduction method. Therefore, the molecular response evaluated by BCR-ABL(IS) has similar trends in PFS and in response prediction, but can better differentiate patients than that by the log reduction method. Furthermore, the IS method allows comparison among molecular response results from different laboratories. Crown Copyright © 2013. Published by Elsevier Ltd. All rights reserved.

  20. Developing RESRAD-BASELINE for environmental baseline risk assessment

    International Nuclear Information System (INIS)

    Cheng, Jing-Jy.

    1995-01-01

    RESRAD-BASELINE is a computer code developed at Argonne developed at Argonne National Laboratory for the US Department of Energy (DOE) to perform both radiological and chemical risk assessments. The code implements the baseline risk assessment guidance of the US Environmental Protection Agency (EPA 1989). The computer code calculates (1) radiation doses and cancer risks from exposure to radioactive materials, and (2) hazard indexes and cancer risks from exposure to noncarcinogenic and carcinogenic chemicals, respectively. The user can enter measured or predicted environmental media concentrations from the graphic interface and can simulate different exposure scenarios by selecting the appropriate pathways and modifying the exposure parameters. The database used by PESRAD-BASELINE includes dose conversion factors and slope factors for radionuclides and toxicity information and properties for chemicals. The user can modify the database for use in the calculation. Sensitivity analysis can be performed while running the computer code to examine the influence of the input parameters. Use of RESRAD-BASELINE for risk analysis is easy, fast, and cost-saving. Furthermore, it ensures in consistency in methodology for both radiological and chemical risk analyses

  1. Use of behavioral economics and social psychology to improve treatment of acute respiratory infections (BEARI): rationale and design of a cluster randomized controlled trial [1RC4AG039115-01]--study protocol and baseline practice and provider characteristics.

    Science.gov (United States)

    Persell, Stephen D; Friedberg, Mark W; Meeker, Daniella; Linder, Jeffrey A; Fox, Craig R; Goldstein, Noah J; Shah, Parth D; Knight, Tara K; Doctor, Jason N

    2013-06-27

    Inappropriate antibiotic prescribing for nonbacterial infections leads to increases in the costs of care, antibiotic resistance among bacteria, and adverse drug events. Acute respiratory infections (ARIs) are the most common reason for inappropriate antibiotic use. Most prior efforts to decrease inappropriate antibiotic prescribing for ARIs (e.g., educational or informational interventions) have relied on the implicit assumption that clinicians inappropriately prescribe antibiotics because they are unaware of guideline recommendations for ARIs. If lack of guideline awareness is not the reason for inappropriate prescribing, educational interventions may have limited impact on prescribing rates. Instead, interventions that apply social psychological and behavioral economic principles may be more effective in deterring inappropriate antibiotic prescribing for ARIs by well-informed clinicians. The Application of Behavioral Economics to Improve the Treatment of Acute Respiratory Infections (BEARI) Trial is a multisite, cluster-randomized controlled trial with practice as the unit of randomization. The primary aim is to test the ability of three interventions based on behavioral economic principles to reduce the rate of inappropriate antibiotic prescribing for ARIs. We randomized practices in a 2 × 2 × 2 factorial design to receive up to three interventions for non-antibiotic-appropriate diagnoses: 1) Accountable Justifications: When prescribing an antibiotic for an ARI, clinicians are prompted to record an explicit justification that appears in the patient electronic health record; 2) Suggested Alternatives: Through computerized clinical decision support, clinicians prescribing an antibiotic for an ARI receive a list of non-antibiotic treatment choices (including prescription options) prior to completing the antibiotic prescription; and 3) Peer Comparison: Each provider's rate of inappropriate antibiotic prescribing relative to top-performing peers is reported back to

  2. Use of behavioral economics and social psychology to improve treatment of acute respiratory infections (BEARI): rationale and design of a cluster randomized controlled trial [1RC4AG039115-01] - study protocol and baseline practice and provider characteristics

    Science.gov (United States)

    2013-01-01

    Background Inappropriate antibiotic prescribing for nonbacterial infections leads to increases in the costs of care, antibiotic resistance among bacteria, and adverse drug events. Acute respiratory infections (ARIs) are the most common reason for inappropriate antibiotic use. Most prior efforts to decrease inappropriate antibiotic prescribing for ARIs (e.g., educational or informational interventions) have relied on the implicit assumption that clinicians inappropriately prescribe antibiotics because they are unaware of guideline recommendations for ARIs. If lack of guideline awareness is not the reason for inappropriate prescribing, educational interventions may have limited impact on prescribing rates. Instead, interventions that apply social psychological and behavioral economic principles may be more effective in deterring inappropriate antibiotic prescribing for ARIs by well-informed clinicians. Methods/design The Application of Behavioral Economics to Improve the Treatment of Acute Respiratory Infections (BEARI) Trial is a multisite, cluster-randomized controlled trial with practice as the unit of randomization. The primary aim is to test the ability of three interventions based on behavioral economic principles to reduce the rate of inappropriate antibiotic prescribing for ARIs. We randomized practices in a 2 × 2 × 2 factorial design to receive up to three interventions for non-antibiotic-appropriate diagnoses: 1) Accountable Justifications: When prescribing an antibiotic for an ARI, clinicians are prompted to record an explicit justification that appears in the patient electronic health record; 2) Suggested Alternatives: Through computerized clinical decision support, clinicians prescribing an antibiotic for an ARI receive a list of non-antibiotic treatment choices (including prescription options) prior to completing the antibiotic prescription; and 3) Peer Comparison: Each provider’s rate of inappropriate antibiotic prescribing relative to top

  3. Free treatment, rapid malaria diagnostic tests and malaria village workers can hasten progress toward achieving the malaria related millennium development goals: the Médecins Sans Frontières experience from Chad, Sierra-Leone and Mali

    Directory of Open Access Journals (Sweden)

    Katie Tayler-Smith

    2011-02-01

    Full Text Available Halving the burden of malaria by 2015 and ensuring that 80% of people with malaria receive treatment is among the health related targets of the Millennium Development Goals (MDGs. Despite political momentum toward achieving this target, progress is slow and many with malaria (particularly in poor and rural communities in Africa are still without access to effective treatment. Finding ways to improve access to anti-malarial treatment in Africa is essential to achieve the malaria related and other MDG targets. During its work in Chad, Sierra Leone and Mali in the period 2004 to 2008, Médecins Sans Frontières showed that it was possible to significantly improve access to effective malaria treatment through: i the removal of health centre level user fees for essential healthcare for vulnerable population groups, ii the introduction of free community based treatment for children using malaria village workers to diagnose and treat simple malaria in communities where geographical and financial barriers limited access to effective malaria care, iii the improved diagnosis and treatment of malaria using rapid diagnosis tests and artemisinin based combination therapy, at both health facilities and in the community. This paper describes and discusses these strategies and their related impact.

  4. Baseline Report on HB2320

    Science.gov (United States)

    State Council of Higher Education for Virginia, 2015

    2015-01-01

    Staff provides this baseline report as a summary of its preliminary considerations and initial research in fulfillment of the requirements of HB2320 from the 2015 session of the General Assembly. Codified as § 23-7.4:7, this legislation compels the Education Secretary and the State Council of Higher Education for Virginia (SCHEV) Director, in…

  5. Gliotransmission modulates baseline mechanical nociception

    Directory of Open Access Journals (Sweden)

    Foley Jeannine C

    2011-12-01

    Full Text Available Abstract Pain is a physiological and adaptive process which occurs to protect organisms from tissue damage and extended injury. Pain sensation beyond injury, however, is a pathological process which is poorly understood. Experimental models of neuropathic pain demonstrate that reactive astrocytes contribute to reduced nociceptive thresholds. Astrocytes release "gliotransmitters" such as D-serine, glutamate, and ATP, which is extracellularly hydrolyzed to adenosine. Adenosine 1 receptor activation in the spinal cord has anti-nociceptive effects on baseline pain threshold, but the source of the endogenous ligand (adenosine in the spinal cord is unknown. In this study we used a transgenic mouse model in which SNARE-mediated gliotransmission was selectively attenuated (called dnSNARE mice to investigate the role of astrocytes in mediating baseline nociception and the development of neuropathic pain. Under baseline conditions, immunostaining in the dorsal horn of the spinal cord showed astrocyte-specific transgene expression in dnSNARE mice, and no difference in expression levels of the astrocyte marker GFAP and the microglia marker Iba1 relative to wild-type mice. The Von Frey filament test was used to probe sensitivity to baseline mechanical pain thresholds and allodynia following the spared nerve injury model of neuropathic pain. DnSNARE mice exhibit a reduced nociceptive threshold in response to mechanical stimulation compared to wild-type mice under baseline conditions, but nociceptive thresholds following spared nerve injury were similar between dnSNARE and wild-types. This study is the first to provide evidence that gliotransmission contributes to basal mechanical nociception.

  6. Plasmodium falciparum parasite population structure and gene flow associated to anti-malarial drugs resistance in Cambodia.

    Science.gov (United States)

    Dwivedi, Ankit; Khim, Nimol; Reynes, Christelle; Ravel, Patrice; Ma, Laurence; Tichit, Magali; Bourchier, Christiane; Kim, Saorin; Dourng, Dany; Khean, Chanra; Chim, Pheaktra; Siv, Sovannaroth; Frutos, Roger; Lek, Dysoley; Mercereau-Puijalon, Odile; Ariey, Frédéric; Menard, Didier; Cornillot, Emmanuel

    2016-06-14

    Western Cambodia is recognized as the epicentre of emergence of Plasmodium falciparum multi-drug resistance. The emergence of artemisinin resistance has been observed in this area since 2008-2009 and molecular signatures associated to artemisinin resistance have been characterized in k13 gene. At present, one of the major threats faced, is the possible spread of Asian artemisinin resistant parasites over the world threatening millions of people and jeopardizing malaria elimination programme efforts. To anticipate the diffusion of artemisinin resistance, the identification of the P. falciparum population structure and the gene flow among the parasite population in Cambodia are essential. To this end, a mid-throughput PCR-LDR-FMA approach based on LUMINEX technology was developed to screen for genetic barcode in 533 blood samples collected in 2010-2011 from 16 health centres in malaria endemics areas in Cambodia. Based on successful typing of 282 samples, subpopulations were characterized along the borders of the country. Each 11-loci barcode provides evidence supporting allele distribution gradient related to subpopulations and gene flow. The 11-loci barcode successfully identifies recently emerging parasite subpopulations in western Cambodia that are associated with the C580Y dominant allele for artemisinin resistance in k13 gene. A subpopulation was identified in northern Cambodia that was associated to artemisinin (R539T resistant allele of k13 gene) and mefloquine resistance. The gene flow between these subpopulations might have driven the spread of artemisinin resistance over Cambodia.

  7. Effect of selected anti-malarial drugs on the blood chemistry and brain serotonin levels in male rabbits.

    Science.gov (United States)

    Eigbibhalu, Ukpo Grace; Albert Taiwo, Ebuehi Osaretin; Douglass, Idiakheua Akhabue; Abimbola, Efunogbon Aderonke

    2013-01-01

    The effects of oral administration of sulfadoxine - pyrimethamine (SP), artesunate (A) and sulfadoxine - pyrimethamine - artesunate (SPA) on blood chemistry and brain serotonin in rabbits were investigated. Forty rabbits were divided into four groups of ten animals each. The group that served as the control received 2ml of distilled water while the other groups were received 1.25/25mg base/kg body weight of SP, 3.3mg/kg body weight of A and 1.25/25mg base/kg body weight of SP plus 3.3mg/kg body weight of A respectively by oral route daily for 3 days in a week for four weeks. At the end of each week of drug administration, three rabbits from each group were anaesthetized, blood was taken from the jugular veins using sterile needle and serum was extracted. The rabbits were sacrificed by decapitation; the liver and brain tissues were excised and homogenized. Total blood protein, cholesterol, triglyceride, albumin, creatinine and urea concentrations, creatine kinase, aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase, ALP activities were assayed using CX5 synchron autoanalyzer. The brain and liver serotonin levels were determined using high performance liquid chromatography (HPLC). There were no significant differences (P levels of rabbits administered SP, A and SPA were significantly higher as compared to the control throughout the duration of the study Data of the study indicate that oral administration of SP, A or SPA in rabbits do not affect blood chemistry, but affected brain serotonin levels and could alter some neural functions.

  8. Baseline Removal From EMG Recordings

    Science.gov (United States)

    2001-10-25

    Name(s) and Address(es) Departamento de Ingenieria Electra y Electronica Universidad Publica de Navarra Pamplona, Spain Performing Organization Report...Ingeniería Eléctrica y Electrónica, Universidad Pública de Navarra, Pamplona, Spain 2Servicio de Neurofisiología Clínica, Hospital Virgen del Camino...a time-varying baseline contamination. Acknowledgements: Work funded by the Departamento de Salud del Gobierno de Navarrra and by a Spanish MEC

  9. Diagnosis and treatment of malaria in peripheral health facilities in Uganda: findings from an area of low transmission in south-western Uganda

    Directory of Open Access Journals (Sweden)

    Clarke Siân

    2007-04-01

    Full Text Available Abstract Background Early recognition of symptoms and signs perceived as malaria are important for effective case management, as few laboratories are available at peripheral health facilities. The validity and reliability of clinical signs and symptoms used by health workers to diagnose malaria were assessed in an area of low transmission in south-western Uganda. Methods The study had two components: 1 passive case detection where all patients attending the out patient clininc with a febrile illness were included and 2 a longitudinal active malaria case detection survey was conducted in selected villages. A malaria case was defined as any slide-confirmed parasitaemia in a person with an axillary temperature ≥ 37.5°C or a history of fever within the last 24 hrs and no signs suggestive of other diseases. Results Cases of malaria were significantly more likely to report joint pains, headache, vomiting and abdominal pains. However, due to the low prevalence of malaria, the predictive values of these individual signs alone, or in combination, were poor. Only 24.8% of 1627 patients had malaria according to case definition and > 75% of patients were unnecessarily treated for malaria and few slide negative cases received alternative treatment. Conclusion In low-transmission areas, more attention needs to be paid to differential diagnosis of febrile illnesses In view of suggested changes in anti-malarial drug policy, introducing costly artemisinin combination therapy accurate, rapid diagnostic tools are necessary to target treatment to people in need.

  10. Community-based intermittent mass testing and treatment for malaria in an area of high transmission intensity, western Kenya: study design and methodology for a cluster randomized controlled trial.

    Science.gov (United States)

    Samuels, Aaron M; Awino, Nobert; Odongo, Wycliffe; Abong'o, Benard; Gimnig, John; Otieno, Kephas; Shi, Ya Ping; Were, Vincent; Allen, Denise Roth; Were, Florence; Sang, Tony; Obor, David; Williamson, John; Hamel, Mary J; Patrick Kachur, S; Slutsker, Laurence; Lindblade, Kim A; Kariuki, Simon; Desai, Meghna

    2017-06-07

    Most human Plasmodium infections in western Kenya are asymptomatic and are believed to contribute importantly to malaria transmission. Elimination of asymptomatic infections requires active treatment approaches, such as mass testing and treatment (MTaT) or mass drug administration (MDA), as infected persons do not seek care for their infection. Evaluations of community-based approaches that are designed to reduce malaria transmission require careful attention to study design to ensure that important effects can be measured accurately. This manuscript describes the study design and methodology of a cluster-randomized controlled trial to evaluate a MTaT approach for malaria transmission reduction in an area of high malaria transmission. Ten health facilities in western Kenya were purposively selected for inclusion. The communities within 3 km of each health facility were divided into three clusters of approximately equal population size. Two clusters around each health facility were randomly assigned to the control arm, and one to the intervention arm. Three times per year for 2 years, after the long and short rains, and again before the long rains, teams of community health volunteers visited every household within the intervention arm, tested all consenting individuals with malaria rapid diagnostic tests, and treated all positive individuals with an effective anti-malarial. The effect of mass testing and treatment on malaria transmission was measured through population-based longitudinal cohorts, outpatient visits for clinical malaria, periodic population-based cross-sectional surveys, and entomological indices.

  11. Integrated Baseline Review (IBR) Handbook

    Science.gov (United States)

    Fleming, Jon F.; Terrell, Stefanie M.

    2018-01-01

    The purpose of this handbook is intended to be a how-to guide to prepare for, conduct, and close-out an Integrated Baseline Review (IBR). It discusses the steps that should be considered, describes roles and responsibilities, tips for tailoring the IBR based on risk, cost, and need for management insight, and provides lessons learned from past IBRs. Appendices contain example documentation typically used in connection with an IBR. Note that these appendices are examples only, and should be tailored to meet the needs of individual projects and contracts.

  12. Baseline LAW Glass Formulation Testing

    Energy Technology Data Exchange (ETDEWEB)

    Kruger, Albert A. [USDOE Office of River Protection, Richland, WA (United States); Mooers, Cavin [The Catholic University of America, Washington, DC (United States). Vitreous State Lab.; Bazemore, Gina [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Pegg, Ian L. [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Hight, Kenneth [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Lai, Shan Tao [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Buechele, Andrew [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Rielley, Elizabeth [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Gan, Hao [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Muller, Isabelle S. [The Catholic University of America, Washington, DC (United States). Vitreous State Lab; Cecil, Richard [The Catholic University of America, Washington, DC (United States). Vitreous State Lab

    2013-06-13

    The major objective of the baseline glass formulation work was to develop and select glass formulations that are compliant with contractual and processing requirements for each of the LAW waste streams. Other objectives of the work included preparation and characterization of glasses with respect to the properties of interest, optimization of sulfate loading in the glasses, evaluation of ability to achieve waste loading limits, testing to demonstrate compatibility of glass melts with melter materials of construction, development of glass formulations to support ILAW qualification activities, and identification of glass formulation issues with respect to contract specifications and processing requirements.

  13. Treatment of imported severe malaria with artesunate instead of quinine--more evidence needed?

    NARCIS (Netherlands)

    Cramer, J.P.; López-Vélez, R.; Burchard, G.D.; Grobusch, M.P.; de Vries, P.J.

    2011-01-01

    Rapid and fast acting anti-malarials are essential to treat severe malaria. Quinine has been the only option for parenteral therapy until recently. While current evidence shows that intravenous artesunate is more effective than quinine in treating severe malaria in endemic countries, some questions

  14. FED baseline engineering studies report

    Energy Technology Data Exchange (ETDEWEB)

    Sager, P.H.

    1983-04-01

    Studies were carried out on the FED Baseline to improve design definition, establish feasibility, and reduce cost. Emphasis was placed on cost reduction, but significant feasibility concerns existed in several areas, and better design definition was required to establish feasibility and provide a better basis for cost estimates. Design definition and feasibility studies included the development of a labyrinth shield ring concept to prevent radiation streaming between the torus spool and the TF coil cryostat. The labyrinth shield concept which was developed reduced radiation streaming sufficiently to permit contact maintenance of the inboard EF coils. Various concepts of preventing arcing between adjacent shield sectors were also explored. It was concluded that installation of copper straps with molybdenum thermal radiation shields would provide the most reliable means of preventing arcing. Other design studies included torus spool electrical/structural concepts, test module shielding, torus seismic response, poloidal conditions in the magnets, disruption characteristics, and eddy current effects. These additional studies had no significant impact on cost but did confirm the feasibility of the basic FED Baseline concept.

  15. FED baseline engineering studies report

    International Nuclear Information System (INIS)

    Sager, P.H.

    1983-04-01

    Studies were carried out on the FED Baseline to improve design definition, establish feasibility, and reduce cost. Emphasis was placed on cost reduction, but significant feasibility concerns existed in several areas, and better design definition was required to establish feasibility and provide a better basis for cost estimates. Design definition and feasibility studies included the development of a labyrinth shield ring concept to prevent radiation streaming between the torus spool and the TF coil cryostat. The labyrinth shield concept which was developed reduced radiation streaming sufficiently to permit contact maintenance of the inboard EF coils. Various concepts of preventing arcing between adjacent shield sectors were also explored. It was concluded that installation of copper straps with molybdenum thermal radiation shields would provide the most reliable means of preventing arcing. Other design studies included torus spool electrical/structural concepts, test module shielding, torus seismic response, poloidal conditions in the magnets, disruption characteristics, and eddy current effects. These additional studies had no significant impact on cost but did confirm the feasibility of the basic FED Baseline concept

  16. Treatment outcome of intravenous artesunate in patients with severe malaria in the Netherlands and Belgium

    Directory of Open Access Journals (Sweden)

    Kreeftmeijer-Vegter Annemarie R

    2012-03-01

    Full Text Available Abstract Background Intravenous (IV artesunate is the treatment of choice for severe malaria. In Europe, however, no GMP-manufactured product is available and treatment data in European travellers are scarce. Fortunately, artesunate became available in the Netherlands and Belgium through a named patient programme. This is the largest case series of artesunate treated patients with severe malaria in Europe. Methods Hospitalized patients treated with IV artesunate between November 2007 and December 2010 in the Netherlands and Belgium were retrospectively evaluated. Patient characteristics, treatment and clinical outcome were recorded on a standardized form and mortality, parasite clearance times and the occurrence of adverse events were evaluated. Results Of the 68 treated patients, including 55 with severe malaria, two patients died (2/55 = 3.6%. The mean time to 50% parasite clearance (PCT50, 90% and 99% were 4.4 hours (3.9 - 5.2, 14.8 hours (13.0 - 17.2, and 29.5 hours (25.9 - 34.4 respectively. Artesunate was well tolerated. However, an unusual form of haemolytic anaemia was observed in seven patients. The relationship with artesunate remains uncertain. Conclusions Data from the named patient programme demonstrate that IV artesunate is effective and well-tolerated in European travellers lacking immunity. However, increased attention needs to be paid to the possible development of haemolytic anaemia 2-3 weeks after start of treatment. Treatment of IV artesunate should be limited to the period that IV treatment is required and should be followed by a full oral course of an appropriate anti-malarial drug.

  17. The impact of text message reminders on adherence to antimalarial treatment in northern Ghana: a randomized trial.

    Directory of Open Access Journals (Sweden)

    Julia R G Raifman

    Full Text Available BACKGROUND: Low rates of adherence to artemisinin-based combination therapy (ACT regimens increase the risk of treatment failure and may lead to drug resistance, threatening the sustainability of current anti-malarial efforts. We assessed the impact of text message reminders on adherence to ACT regimens. METHODS: Health workers at hospitals, clinics, pharmacies, and other stationary ACT distributors in Tamale, Ghana provided flyers advertising free mobile health information to individuals receiving malaria treatment. The messaging system automatically randomized self-enrolled individuals to the control group or the treatment group with equal probability; those in the treatment group were further randomly assigned to receive a simple text message reminder or the simple reminder plus an additional statement about adherence in 12-hour intervals. The main outcome was self-reported adherence based on follow-up interviews occurring three days after treatment initiation. We estimated the impact of the messages on treatment completion using logistic regression. RESULTS: 1140 individuals enrolled in both the study and the text reminder system. Among individuals in the control group, 61.5% took the full course of treatment. The simple text message reminders increased the odds of adherence (adjusted OR 1.45, 95% CI [1.03 to 2.04], p-value 0.028. Receiving an additional message did not result in a significant change in adherence (adjusted OR 0.77, 95% CI [0.50 to 1.20], p-value 0.252. CONCLUSION: The results of this study suggest that a simple text message reminder can increase adherence to antimalarial treatment and that additional information included in messages does not have a significant impact on completion of ACT treatment. Further research is needed to develop the most effective text message content and frequency. TRIAL REGISTRATION: ClinicalTrials.gov NCT01722734.

  18. The impact of text message reminders on adherence to antimalarial treatment in northern Ghana: a randomized trial.

    Science.gov (United States)

    Raifman, Julia R G; Lanthorn, Heather E; Rokicki, Slawa; Fink, Günther

    2014-01-01

    Low rates of adherence to artemisinin-based combination therapy (ACT) regimens increase the risk of treatment failure and may lead to drug resistance, threatening the sustainability of current anti-malarial efforts. We assessed the impact of text message reminders on adherence to ACT regimens. Health workers at hospitals, clinics, pharmacies, and other stationary ACT distributors in Tamale, Ghana provided flyers advertising free mobile health information to individuals receiving malaria treatment. The messaging system automatically randomized self-enrolled individuals to the control group or the treatment group with equal probability; those in the treatment group were further randomly assigned to receive a simple text message reminder or the simple reminder plus an additional statement about adherence in 12-hour intervals. The main outcome was self-reported adherence based on follow-up interviews occurring three days after treatment initiation. We estimated the impact of the messages on treatment completion using logistic regression. 1140 individuals enrolled in both the study and the text reminder system. Among individuals in the control group, 61.5% took the full course of treatment. The simple text message reminders increased the odds of adherence (adjusted OR 1.45, 95% CI [1.03 to 2.04], p-value 0.028). Receiving an additional message did not result in a significant change in adherence (adjusted OR 0.77, 95% CI [0.50 to 1.20], p-value 0.252). The results of this study suggest that a simple text message reminder can increase adherence to antimalarial treatment and that additional information included in messages does not have a significant impact on completion of ACT treatment. Further research is needed to develop the most effective text message content and frequency. ClinicalTrials.gov NCT01722734.

  19. 327 Building hazard baseline document

    International Nuclear Information System (INIS)

    STEFFEN, J.M.

    1999-01-01

    This document identifies the hazards in the 327 Building at the time that a facility walk through was performed during FY99, presents a PHA of stabilization and deactivation activities, and provides a basis for the hazard evaluation and accident analysis that will be developed in the 327 Building Basis for Interim Operation (BIO). Activities addressed in this hazard baseline document include: (1) Stabilization and deactivation activities in preparation for eventual decommissioning of the 327 Building and the routine handling, processing, and shipment of waste to support these activities. (2) 324/327 Building Minimum Safe Project engineering and maintenance activities to maintain the building and systems viable--especially the Safety SSCs--to allow stabilization, deactivation, and waste handling activities with a minimum of risk to workers, the public, and the environment

  20. Pinellas Plant Environmental Baseline Report

    Energy Technology Data Exchange (ETDEWEB)

    1997-06-01

    The Pinellas Plant has been part of the Department of Energy`s (DOE) nuclear weapons complex since the plant opened in 1957. In March 1995, the DOE sold the Pinellas Plant to the Pinellas County Industry Council (PCIC). DOE has leased back a large portion of the plant site to facilitate transition to alternate use and safe shutdown. The current mission is to achieve a safe transition of the facility from defense production and prepare the site for alternative uses as a community resource for economic development. Toward that effort, the Pinellas Plant Environmental Baseline Report (EBR) discusses the current and past environmental conditions of the plant site. Information for the EBR is obtained from plant records. Historical process and chemical usage information for each area is reviewed during area characterizations.

  1. Integrated Baseline Review (IBR) Handbook

    Science.gov (United States)

    Fleming, Jon F.; Kehrer, Kristen C.

    2016-01-01

    The purpose of this handbook is intended to be a how-to guide to prepare for, conduct, and close-out an Integrated Baseline Review (IBR). It discusses the steps that should be considered, describes roles and responsibilities, tips for tailoring the IBR based on risk, cost, and need for management insight, and provides lessons learned from past IBRs. Appendices contain example documentation typically used in connection with an IBR. Note that these appendices are examples only, and should be tailored to meet the needs of individual projects and contracts. Following the guidance in this handbook will help customers and suppliers preparing for an IBR understand the expectations of the IBR, and ensure that the IBR meets the requirements for both in-house and contract efforts.

  2. Environmental Baseline Survey, Real Property Transaction Between Nellis Air Force Base and the City of North Las Vegas for Construction of a Wastewater Treatment Facility, Clark County, Nevada. Phase 1

    Science.gov (United States)

    2007-12-06

    NWI Electronic Data CoverageNWI Quad at Target Property 32003C2180DAdditional Panels in search area: 32003C2200DFlood Plain Panel at Target Property...Response Plan. July 2006. Nellis AFB. 2006c. Environmental Baseline Survey for Leasing Nellis AFB Land for Construction & Operation of a Solar ...aeknowledsed thoy QXOcuted onme a.e their own f-ree and voluntary ~ct . .. .. • • II It" H • I II I~ .. I ,.,. o.c ll J 2v nl ’II APPENDIX G Terms and

  3. Hydrogeology baseline study Aurora Mine

    International Nuclear Information System (INIS)

    1996-01-01

    A baseline hydrogeologic study was conducted in the area of Syncrude's proposed Aurora Mine in order to develop a conceptual regional hydrogeologic model for the area that could be used to understand groundwater flow conditions. Geologic information was obtained from over 2,000 coreholes and from data obtained between 1980 and 1996 regarding water level for the basal aquifer. A 3-D numerical groundwater flow model was developed to provide quantitative estimates of the potential environmental impacts of the proposed mining operations on the groundwater flow system. The information was presented in the context of a regional study area which encompassed much of the Athabasca Oil Sands Region, and a local study area which was defined by the lowlands of the Muskeg River Basin. Characteristics of the topography, hydrology, climate, geology, and hydrogeology of the region are described. The conclusion is that groundwater flow in the aquifer occurs mostly in a westerly direction beneath the Aurora Mine towards its inferred discharge location along the Athabasca River. Baseflow in the Muskeg River is mostly related to discharge from shallow surficial aquifers. Water in the river under baseflow conditions was fresh, of calcium-carbonate type, with very little indication of mineralization associated with deeper groundwater in the Aurora Mine area. 44 refs., 5 tabs., 31 figs

  4. The California Baseline Methane Survey

    Science.gov (United States)

    Duren, R. M.; Thorpe, A. K.; Hopkins, F. M.; Rafiq, T.; Bue, B. D.; Prasad, K.; Mccubbin, I.; Miller, C. E.

    2017-12-01

    The California Baseline Methane Survey is the first systematic, statewide assessment of methane point source emissions. The objectives are to reduce uncertainty in the state's methane budget and to identify emission mitigation priorities for state and local agencies, utilities and facility owners. The project combines remote sensing of large areas with airborne imaging spectroscopy and spatially resolved bottom-up data sets to detect, quantify and attribute emissions from diverse sectors including agriculture, waste management, oil and gas production and the natural gas supply chain. Phase 1 of the project surveyed nearly 180,000 individual facilities and infrastructure components across California in 2016 - achieving completeness rates ranging from 20% to 100% per emission sector at < 5 meters spatial resolution. Additionally, intensive studies of key areas and sectors were performed to assess source persistence and variability at times scales ranging from minutes to months. Phase 2 of the project continues with additional data collection in Spring and Fall 2017. We describe the survey design and measurement, modeling and analysis methods. We present initial findings regarding the spatial, temporal and sectoral distribution of methane point source emissions in California and their estimated contribution to the state's total methane budget. We provide case-studies and lessons learned about key sectors including examples where super-emitters were identified and mitigated. We summarize challenges and recommendations for future methane research, inventories and mitigation guidance within and beyond California.

  5. 2016 Annual Technology Baseline (ATB)

    Energy Technology Data Exchange (ETDEWEB)

    Cole, Wesley; Kurup, Parthiv; Hand, Maureen; Feldman, David; Sigrin, Benjamin; Lantz, Eric; Stehly, Tyler; Augustine, Chad; Turchi, Craig; O' Connor, Patrick; Waldoch, Connor

    2016-09-01

    Consistent cost and performance data for various electricity generation technologies can be difficult to find and may change frequently for certain technologies. With the Annual Technology Baseline (ATB), National Renewable Energy Laboratory provides an organized and centralized dataset that was reviewed by internal and external experts. It uses the best information from the Department of Energy laboratory's renewable energy analysts and Energy Information Administration information for conventional technologies. The ATB will be updated annually in order to provide an up-to-date repository of current and future cost and performance data. Going forward, we plan to revise and refine the values using best available information. The ATB includes both a presentation with notes (PDF) and an associated Excel Workbook. The ATB includes the following electricity generation technologies: land-based wind; offshore wind; utility-scale solar PV; concentrating solar power; geothermal power; hydropower plants (upgrades to existing facilities, powering non-powered dams, and new stream-reach development); conventional coal; coal with carbon capture and sequestration; integrated gasification combined cycle coal; natural gas combustion turbines; natural gas combined cycle; conventional biopower. Nuclear laboratory's renewable energy analysts and Energy Information Administration information for conventional technologies. The ATB will be updated annually in order to provide an up-to-date repository of current and future cost and performance data. Going forward, we plan to revise and refine the values using best available information.

  6. Comparison of non-radiographic axial spondyloarthritis and ankylosing spondylitis patients - baseline characteristics, treatment adherence, and development of clinical variables during three years of anti-TNF therapy in clinical practice

    DEFF Research Database (Denmark)

    Wallman, Johan K; Kapetanovic, Meliha C; Petersson, Ingemar F

    2015-01-01

    BACKGROUND: The relationship between non-radiographic axial spondyloarthritis (nr-axSpA) and ankylosing spondylitis (AS) is currently debated. Using observational data from the South Swedish Arthritis Treatment Group register, we thus aimed to compare clinical development and treatment adherence ...... of constantly lower CRP levels in the nr-axSpA group, three years anti-TNF therapy resulted in similar clinical outcomes and treatment adherence in nr-axSpA and AS patients, thus strengthening the hypothesis that these diagnoses represent different aspects/phases of the same disease....

  7. 324 Building Baseline Radiological Characterization

    International Nuclear Information System (INIS)

    Reeder, R.J.; Cooper, J.C.

    2010-01-01

    This report documents the analysis of radiological data collected as part of the characterization study performed in 1998. The study was performed to create a baseline of the radiological conditions in the 324 Building. A total of 85 technical (100 square centimeter (cm 2 )) smears were collected from the Room 147 hoods, the Shielded Materials Facility (SMF), and the Radiochemical Engineering Cells (REC). Exposure rate readings (window open and window closed) were taken at a distance of 2.5 centimeters (cm) and 30 cm from the surface of each smear. Gross beta-gamma and alpha counts of each smear were also performed. The smear samples were analyzed by gamma energy analysis (GEA). Alpha energy analysis (AEA) and strontium-90 analysis were also performed on selected smears. GEA results for one or more samples reported the presence of manganese-54, cobalt-60, silver-108m antimony-125, cesium-134, cesium-137, europium-154, europium-155, and americium-241. AEA results reported the presence of plutonium-239/240, plutonium-238/ 241 Am, curium-243/244, curium-242, and americium-243. Tables 5 through 9 present a summary by location of the estimated maximum removable and total contamination levels in the Room 147 hoods, the SMF, and the REC. The smear sample survey data and laboratory analytical results are presented in tabular form by sample in Appendix A. The Appendix A tables combine survey data documented in radiological survey reports found in Appendix B and laboratory analytical results reported in the 324 Building Physical and Radiological Characterization Study (Berk, Hill, and Landsman 1998), supplemented by the laboratory analytical results found in Appendix C.

  8. Statistical baseline assessment in cardiotocography.

    Science.gov (United States)

    Agostinelli, Angela; Braccili, Eleonora; Marchegiani, Enrico; Rosati, Riccardo; Sbrollini, Agnese; Burattini, Luca; Morettini, Micaela; Di Nardo, Francesco; Fioretti, Sandro; Burattini, Laura

    2017-07-01

    Cardiotocography (CTG) is the most common non-invasive diagnostic technique to evaluate fetal well-being. It consists in the recording of fetal heart rate (FHR; bpm) and maternal uterine contractions. Among the main parameters characterizing FHR, baseline (BL) is fundamental to determine fetal hypoxia and distress. In computerized applications, BL is typically computed as mean FHR±ΔFHR, with ΔFHR=8 bpm or ΔFHR=10 bpm, both values being experimentally fixed. In this context, the present work aims: to propose a statistical procedure for ΔFHR assessment; to quantitatively determine ΔFHR value by applying such procedure to clinical data; and to compare the statistically-determined ΔFHR value against the experimentally-determined ΔFHR values. To these aims, the 552 recordings of the "CTU-UHB intrapartum CTG database" from Physionet were submitted to an automatic procedure, which consisted in a FHR preprocessing phase and a statistical BL assessment. During preprocessing, FHR time series were divided into 20-min sliding windows, in which missing data were removed by linear interpolation. Only windows with a correction rate lower than 10% were further processed for BL assessment, according to which ΔFHR was computed as FHR standard deviation. Total number of accepted windows was 1192 (38.5%) over 383 recordings (69.4%) with at least an accepted window. Statistically-determined ΔFHR value was 9.7 bpm. Such value was statistically different from 8 bpm (P<;10 -19 ) but not from 10 bpm (P=0.16). Thus, ΔFHR=10 bpm is preferable over 8 bpm because both experimentally and statistically validated.

  9. How much do Blantyre dispensers in hospital and community pharmacies know about the new malaria treatment guidelines?

    Science.gov (United States)

    Minyaliwa, Collins; Bandawe, Chiwoza; Mwale, Richman James

    2012-03-01

    To determine the knowledge of dispensers in hospital and community pharmacies within Blantyre on new malaria treatment guidelines. An interviewer administered questionnaire was used for data collection and the questions focused on the knowledge of dispensers on the new malaria treatment guidelines and whether the subjects were involved in the preparation or implementation of the guidelines or had undertaken any training on how to dispense the new anti-malarial medicines. None of the participants had been involved in the preparation of the treatment guidelines and only 45.5% of the participants had undertaken the pre-implementation training. Ninety percent of the interviewees had knowledge concerning the appropriate treatment of malaria in pregnancy. However, as many as 90.9% of the interviewed participants could not mention any possible five or more side-effects of LA and only 13.6% knew how to properly manage the possible effects. Only 27.3% knew the correct dose regimen of LA and none of them knew the condition of taking LA with a fatty meal for improved absorption. Lack of involvement of the pharmaceutical personnel working in hospital and community pharmacies, from the preparation of new malaria treatment guidelines to their implementation, inadequate training and qualifications of the dispensing personnel contributed to their lack of knowledge and skill on how to rationally dispense the medicines. Pharmaceutical personnel dispensing in the pharmacies need to be involved from the beginning in the preparation of treatment guidelines. Adequate training should be provided and followed by continuous professional education.

  10. 2016 Annual Technology Baseline (ATB) - Webinar Presentation

    Energy Technology Data Exchange (ETDEWEB)

    Cole, Wesley; Kurup, Parthiv; Hand, Maureen; Feldman, David; Sigrin, Benjamin; Lantz, Eric; Stehly, Tyler; Augustine, Chad; Turchi, Craig; Porro, Gian; O' Connor, Patrick; Waldoch, Connor

    2016-09-13

    This deck was presented for the 2016 Annual Technology Baseline Webinar. The presentation describes the Annual Technology Baseline, which is a compilation of current and future cost and performance data for electricity generation technologies.

  11. 40 CFR 1042.825 - Baseline determination.

    Science.gov (United States)

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Baseline determination. 1042.825... Provisions for Remanufactured Marine Engines § 1042.825 Baseline determination. (a) For the purpose of this... not valid. (f) Use good engineering judgment for all aspects of the baseline determination. We may...

  12. Determinants of delay in malaria treatment-seeking behaviour for under-five children in south-west Ethiopia: a case control study

    Directory of Open Access Journals (Sweden)

    Deribew Amare

    2010-11-01

    Full Text Available Abstract Background Prompt diagnosis and timely treatment of malaria within 24 hours after onset of first symptoms can reduce illness progression to severe stages and therefore, decrease mortality. The reason why mothers/caretakers delay in malaria diagnosis and treatment for under-five children is not well studied in Ethiopia. The objective of this study was to assess determinants of malaria treatment delay in under-five children in three districts of south-west Ethiopia. Methods A case control study was conducted from March 15 to April 20, 2010. Cases were under-five children who had clinical malaria and sought treatment after 24 hours of developing sign and symptom, and controls were under-five children who had clinical malaria and sought treatment within 24 hours of developing sign and symptom of malaria. Data were collected by trained enumerators using structured questionnaire. Data were entered in to Epi Info version 6.04 and analyzed using SPSS version 16.0. To identify determinants, multiple logistic regression was done. Results A total of 155 mothers of cases and 155 mothers of controls were interviewed. Mothers of children who were in a monogamous marriage (OR = 3.41, 95% CI: 1.39, 8.34, who complained about the side effects of anti-malarial drugs (OR = 4.96, 95% CI: 1.21, 20.36, who had no history of child death (OR = 3.50, 95% CI: 1.82, 6.42 and who complained about the higher cost of transportation to reach the health institutions (OR = 2.01, 95% CI: 1.17, 3.45 were more likely to be late for the treatment of malaria in under-five children. Conclusion Effective malaria control programmes should address reducing delayed presentation of children for treatment. Efforts to reduce delay should address transport cost, decentralization of services and increasing awareness of the community on early diagnosis and treatment.

  13. Determinants of delay in malaria treatment-seeking behaviour for under-five children in south-west Ethiopia: a case control study.

    Science.gov (United States)

    Getahun, Alemayehu; Deribe, Kebede; Deribew, Amare

    2010-11-11

    Prompt diagnosis and timely treatment of malaria within 24 hours after onset of first symptoms can reduce illness progression to severe stages and therefore, decrease mortality. The reason why mothers/caretakers delay in malaria diagnosis and treatment for under-five children is not well studied in Ethiopia. The objective of this study was to assess determinants of malaria treatment delay in under-five children in three districts of south-west Ethiopia. A case control study was conducted from March 15 to April 20, 2010. Cases were under-five children who had clinical malaria and sought treatment after 24 hours of developing sign and symptom, and controls were under-five children who had clinical malaria and sought treatment within 24 hours of developing sign and symptom of malaria. Data were collected by trained enumerators using structured questionnaire. Data were entered in to Epi Info version 6.04 and analyzed using SPSS version 16.0. To identify determinants, multiple logistic regression was done. A total of 155 mothers of cases and 155 mothers of controls were interviewed. Mothers of children who were in a monogamous marriage (OR = 3.41, 95% CI: 1.39, 8.34), who complained about the side effects of anti-malarial drugs (OR = 4.96, 95% CI: 1.21, 20.36), who had no history of child death (OR = 3.50, 95% CI: 1.82, 6.42) and who complained about the higher cost of transportation to reach the health institutions (OR = 2.01, 95% CI: 1.17, 3.45) were more likely to be late for the treatment of malaria in under-five children. Effective malaria control programmes should address reducing delayed presentation of children for treatment. Efforts to reduce delay should address transport cost, decentralization of services and increasing awareness of the community on early diagnosis and treatment.

  14. Schema therapy as treatment for adults with autism spectrum disorder and comorbid personality disorder : Protocol of a multiple-baseline case series study testing cognitive-behavioral and experiential interventions

    NARCIS (Netherlands)

    Vuijk, R.; Arntz, A.

    Background To our knowledge treatment of personality disorder (PD) comorbidity in adults with ASD is understudied and is still in its infancy. This study investigates the effectiveness of schema therapy for PD-psychopathology in adult patients with both ASD and PD. Methods/design Twelve adult

  15. Efficacy of artemether-lumefantrine, artesunate-amodiaquine, and dihydroartemisinin-piperaquine for treatment of uncomplicated Plasmodium falciparum malaria in Angola, 2015.

    Science.gov (United States)

    Plucinski, Mateusz M; Dimbu, Pedro Rafael; Macaia, Aleixo Panzo; Ferreira, Carolina Miguel; Samutondo, Claudete; Quivinja, Joltim; Afonso, Marília; Kiniffo, Richard; Mbounga, Eliane; Kelley, Julia S; Patel, Dhruviben S; He, Yun; Talundzic, Eldin; Garrett, Denise O; Halsey, Eric S; Udhayakumar, Venkatachalam; Ringwald, Pascal; Fortes, Filomeno

    2017-02-02

    Recent anti-malarial resistance monitoring in Angola has shown efficacy of artemether-lumefantrine (AL) in certain sites approaching the key 90% lower limit of efficacy recommended for artemisinin-based combination therapy. In addition, a controversial case of malaria unresponsive to artemisinins was reported in a patient infected in Lunda Sul Province in 2013. During January-June 2015, investigators monitored the clinical and parasitological response of children with uncomplicated Plasmodium falciparum infection treated with AL, artesunate-amodiaquine (ASAQ), or dihydroartemisinin-piperaquine (DP). The study comprised two treatment arms in each of three provinces: Benguela (AL, ASAQ), Zaire (AL, DP), and Lunda Sul (ASAQ, DP). Samples from treatment failures were analysed for molecular markers of resistance for artemisinin (K13) and lumefantrine (pfmdr1). A total of 467 children reached a study endpoint. Fifty-four treatment failures were observed: four early treatment failures, 40 re-infections and ten recrudescences. Excluding re-infections, the 28-day microsatellite-corrected efficacy was 96.3% (95% CI 91-100) for AL in Benguela, 99.9% (95-100) for ASAQ in Benguela, 88.1% (81-95) for AL in Zaire, and 100% for ASAQ in Lunda Sul. For DP, the 42-day corrected efficacy was 98.8% (96-100) in Zaire and 100% in Lunda Sul. All treatment failures were wild type for K13, but all AL treatment failures had pfmdr1 haplotypes associated with decreased lumefantrine susceptibility. No evidence was found to corroborate the specific allegation of artemisinin resistance in Lunda Sul. The efficacy below 90% of AL in Zaire matches findings from 2013 from the same site. Further monitoring, particularly including measurement of lumefantrine blood levels, is recommended.

  16. Implementation of a reference standard and proficiency testing programme by the World Wide Antimalarial Resistance Network (WWARN

    Directory of Open Access Journals (Sweden)

    Barnes Karen I

    2010-12-01

    Full Text Available Abstract Background The Worldwide Antimalarial Resistance Network (WWARN is a global collaboration to support the objective that anyone affected by malaria receives effective and safe drug treatment. The Pharmacology module aims to inform optimal anti-malarial drug selection. There is an urgent need to define the drug exposure - effect relationship for most anti-malarial drugs. Few anti-malarials have had their therapeutic blood concentration levels defined. One of the main challenges in assessing safety and efficacy data in relation to drug concentrations is the comparability of data generated from different laboratories. To explain differences in anti-malarial pharmacokinetics in studies with different measurement laboratories it is necessary to confirm the accuracy of the assay methods. This requires the establishment of an external quality assurance process to assure results that can be compared. This paper describes this process. Methods The pharmacology module of WWARN has established a quality assurance/quality control (QA/QC programme consisting of two separate components: 1. A proficiency testing programme where blank human plasma spiked with certified reference material (CRM in different concentrations is sent out to participating bioanalytical laboratories. 2. A certified reference standard programme where accurately weighed amounts of certified anti-malarial reference standards, metabolites, and internal standards are sent to participating bioanalytical and in vitro laboratories. Conclusion The proficiency testing programme is designed as a cooperative effort to help participating laboratories assess their ability to carry out drug analysis, resolve any potential problem areas and to improve their results - and, in so doing, to improve the quality of anti-malarial pharmacokinetic data published and shared with WWARN. By utilizing the same source of standards for all laboratories, it is possible to minimize bias arising from poor

  17. Integrated planning: A baseline development perspective

    International Nuclear Information System (INIS)

    Clauss, L.; Chang, D.

    1994-01-01

    The FEMP Baseline establishes the basis for integrating environmental activity technical requirements with their cost and schedule elements. The result is a path forward to successfully achieving the FERMCO mission. Specific to cost management, the FEMP Baseline has been incorporate into the FERMCO Project Control System (PCS) to provide a time-phased budget plan against which contractor performance is measured with an earned value management system. The result is the Performance Measurement Baseline (PMB), an important tool for keeping cost under control

  18. IPCC Socio-Economic Baseline Dataset

    Data.gov (United States)

    National Aeronautics and Space Administration — The Intergovernmental Panel on Climate Change (IPCC) Socio-Economic Baseline Dataset consists of population, human development, economic, water resources, land...

  19. Ethnobotanical survey on medicinal plants used by Guinean traditional healers in the treatment of malaria.

    Science.gov (United States)

    Traore, M S; Baldé, M A; Diallo, M S T; Baldé, E S; Diané, S; Camara, A; Diallo, A; Balde, A; Keïta, A; Keita, S M; Oularé, K; Magassouba, F B; Diakité, I; Diallo, A; Pieters, L; Baldé, A M

    2013-12-12

    The objective of the present study was to collect and document information on herbal remedies traditionally used for the treatment of malaria in Guinea. The survey was carried out from May 2008 to September 2010 and targeted traditional medical practitioners and herbalists. The questionnaire and oral interviews were based on the standardized model which was prepared by the "Centre de Recherche et de Valorisation des Plantes Médicinales (CRVPM) - Dubréka". A total of 258 people (141 males and 117 females) from which 150 traditional healers and 108 herbalists were interviewed. The age of informants ranged from 28 to 82 years old. 57% (149/258) of the interviewees were more than 50 years old. The respondents had good knowledge of the symptoms of malaria, and a fairly good understanding of the causes. One hundred thirteen plant species were recorded, out of which 109 were identified. They belonged to 84 genera and 46 families. The most frequently cited plants were Vismia guineensis, Parkia biglobosa, Nauclea latifolia, Harungana madagascariensis, Terminalia macroptera, Crossopteryx febrifuga, Terminalia albida, Annona senegalensis, and Nauclea pobeguinii. The leaves were most frequently used (80/113 species), followed by stem bark (38/113 species) and roots (4/113 species). The remedies were mostly prepared by decoction (111 species), followed by maceration (seven species). Only one species was prepared by infusion. The present study showed that traditional healers in Guinea have a consistent knowledge of antimalarial plants. Further research should be carried out to compare the anti-malarial activity of the different species, and to check if their use against malaria can be scientifically validated. © 2013 Published by Elsevier Ireland Ltd.

  20. Prevention & treatment of obstetrical complications in APS: Is hydroxychloroquine the Holy Grail we are looking for?

    Science.gov (United States)

    Meroni, Pier Luigi

    2016-12-01

    Pregnancy morbidity is part of the clinical spectrum of the anti-phospholipid syndrome (APS), with an important social and economical cost. Antiplatelet and anticoagulant agents are effective in preventing the clinical manifestations in the majority of the patients. However, a consistent proportion of the pregnant women present recurrences in spite of the standard therapy. Observational studies and anecdotal reports raised the issue of additional therapeutic strategies in these refractory cases. Among these, anti-malarials (AMs) and in particular hydroxychloroquine (HCQ) are becoming more and more popular in APS as well as in other systemic autoimmune rheumatic conditions. AMs display a pleiotropic activity spanning from immunomodulation effect to anti-inflammatory and anti-thrombotic activities, all of which potentially useful in APS. The well-known safety of HCQ in pregnancy encouraged its use in pregnant women with autoimmune rheumatic disorders including APS and observational reports suggested a protective effect on obstetrical recurrences. Since thrombosis does not seem to be the main pathogenic mechanism in obstetric APS, effectiveness of the treatment with HCQ should be related to other pharmacological effects rather than to the anti-platelet or anti-thrombotic activity of the molecule. Experimental models showed that HCQ may restore some defective biological functions induced by anti-phospholipid antibodies (aPL) on trophoblasts and a recent study reported a protective effect on in vivo aPL-mediated placental and foetal neurodevelopmental abnormalities. Although the rational behind the use of HCQ in obstetric APS is sound, the evidence from the real life is not conclusive and a critical appraisal through clinical trials is mandatory. Copyright © 2016. Published by Elsevier Ltd.

  1. Arc melter demonstration baseline test results

    Energy Technology Data Exchange (ETDEWEB)

    Soelberg, N.R.; Chambers, A.G.; Anderson, G.L.; Oden, L.L.; O`Connor, W.K.; Turner, P.C.

    1994-07-01

    This report describes the test results and evaluation for the Phase 1 (baseline) arc melter vitrification test series conducted for the Buried Waste Integrated Demonstration program (BWID). Phase 1 tests were conducted on surrogate mixtures of as-incinerated wastes and soil. Some buried wastes, soils, and stored wastes at the INEL and other DOE sites, are contaminated with transuranic (TRU) radionuclides and hazardous organics and metals. The high temperature environment in an electric arc furnace may be used to process these wastes to produce materials suitable for final disposal. An electric arc furnace system can treat heterogeneous wastes and contaminated soils by (a) dissolving and retaining TRU elements and selected toxic metals as oxides in the slag phase, (b) destroying organic materials by dissociation, pyrolyzation, and combustion, and (c) capturing separated volatilized metals in the offgas system for further treatment. Structural metals in the waste may be melted and tapped separately for recycle or disposal, or these metals may be oxidized and dissolved into the slag. The molten slag, after cooling, will provide a glass/ceramic final waste form that is homogeneous, highly nonleachable, and extremely durable. These features make this waste form suitable for immobilization of TRU radionuclides and toxic metals for geologic timeframes. Further, the volume of contaminated wastes and soils will be substantially reduced in the process.

  2. Mixed waste focus area technical baseline report. Volume 1

    International Nuclear Information System (INIS)

    1997-04-01

    The Department of Energy (DOE) established the Mixed Waste Characterization, Treatment, and Disposal Focus Area (MWFA) to develop and facilitate implementation of technologies required to meet the Department's commitments for treatment of mixed low-level and transuranic wastes. The mission of the MWFA is to provide acceptable technologies, developed in partnership with end-users, stakeholders, tribal governments, and regulators, that enable implementation of mixed waste treatment systems. To accomplish this mission, a technical baseline was established in 1996 that forms the basis for determining which technology development activities will be supported by the MWFA. This technical baseline is revised on an annual basis to reflect changes in the DOE Mixed Waste Management strategies, changes in the MWFA technical baseline development process, and MWFA accomplishments. This report presents the first revision to the technical baseline and the resulting prioritized list of deficiencies that the MWFA will address. This report also reflects a higher level of stakeholder involvement in the prioritization of the deficiencies. This document summarizes the data and the assumptions upon which this work was based, as well as information concerning the DOE Office of Environmental Management (EM) mixed waste technology development needs

  3. Application of mobile-technology for disease and treatment monitoring of malaria in the "Better Border Healthcare Programme"

    Directory of Open Access Journals (Sweden)

    Meankaew Pongthep

    2010-08-01

    Full Text Available Abstract Background The main objective of this study was to assess the effectiveness of integrating the use of cell-phones into a routine malaria prevention and control programme, to improve the management of malaria cases among an under-served population in a border area. The module for disease and treatment monitoring of malaria (DTMM consisted of case investigation and case follow-up for treatment compliance and patients' symptoms. Methods The module combining web-based and mobile technologies was developed as a proof of concept, in an attempt to replace the existing manual, paper-based activities that malaria staff used in treating and caring for malaria patients in the villages for which they were responsible. After a patient was detected and registered onto the system, case-investigation and treatment details were recorded into the malaria database. A follow-up schedule was generated, and the patient's status was updated when the malaria staff conducted their routine home visits, using mobile phones loaded with the follow-up application module. The module also generated text and graph messages for a summary of malaria cases and basic statistics, and automatically fed to predetermined malaria personnel for situation analysis. Following standard public-health practices, access to the patient database was strictly limited to authorized personnel in charge of patient case management. Results The DTMM module was developed and implemented at the trial site in late November 2008, and was fully functioning in 2009. The system captured 534 malaria patients in 2009. Compared to paper-based data in 2004-2008, the mobile-phone-based case follow-up rates by malaria staff improved significantly. The follow-up rates for both Thai and migrant patients were about 94-99% on Day 7 (Plasmodium falciparum and Day 14 (Plasmodium vivax and maintained at 84-93% on Day 90. Adherence to anti-malarial drug therapy, based on self-reporting, showed high completion

  4. Efficacy and tolerability of a new formulation of artesunate-mefloquine for the treatment of uncomplicated malaria in adult in Senegal: open randomized trial.

    Science.gov (United States)

    Tine, Roger C K; Faye, Babacar; Sylla, Khadime; Ndiaye, Jean L; Ndiaye, Magatte; Sow, Doudou; Lo, Aminata C; Abiola, Annie; Ba, Mamadou C; Gaye, Oumar

    2012-12-12

    Prompt treatment of malaria attacks with arteminisin-based combination therapy (ACT) is an essential tool for malaria control. A new co-blister tablet of artesunate-mefloquine (AM) with 25 mg/kg mefloquine has been developed for the management of uncomplicated malaria attacks. This non-inferiority randomized trial, was conducted to evaluate the efficacy and safety of the new formulation of AM in comparison to artemether-lumefantrine (AL) for the treatment of acute uncomplicated Plasmodium falciparum malaria in adults in Senegal. The study was carried out from September to December 2010 in two health centres in Senegal. The study end points included (i) PCR corrected adequate clinical and parasitological response (ACPR) at day 28, (ii) ACPR at days 42 and 63, (iii) parasites and fever clearance time, (iv) incidence of adverse events and patients biological profile at day 7 using the WHO 2003 protocol for anti-malarial drug evaluation. Overall, 310 patients were randomized to receive either AM (n = 157) or AL (n = 153). PCR corrected ACPR at day 28 was at 95.5% in the AM arm while that in the AL arm was at 96.7% (p = 0.83). Therapeutic efficacy was at 98.5% in the AM arm versus 98.2% in the AL group at day 42 (p = 1). At day 63, ACPR in the AM and AL arms was at 98.2% and 97.7%, respectively (p = 0.32). The two treatments were well tolerated with similar biological profile at day 7. However, dizziness was more frequent in the AM arm. Artesunate-mefloquine (25 mg/Kg mefloquine) is efficacious and well-tolerated for the treatment of uncomplicated P. falciparum malaria in adult patients.

  5. A randomized controlled pilot trial of azithromycin or artesunate added to sulfadoxine-pyrimethamine as treatment for malaria in pregnant women.

    Directory of Open Access Journals (Sweden)

    Linda Kalilani

    2007-11-01

    Full Text Available New anti-malarial regimens are urgently needed in sub-Saharan Africa because of the increase in drug resistance. We investigated the safety and efficacy of azithromycin or artesunate combined with sulfadoxine-pyrimethamine used for treatment of malaria in pregnant women in Blantyre, Malawi.This was a randomized open-label clinical trial, conducted at two rural health centers in Blantyre district, Malawi. A total of 141 pregnant women with uncomplicated Plasmodium falciparum malaria were recruited and randomly allocated to 3 treatment groups: sulfadoxine-pyrimethamine (SP; 3 tablets, 500 mg sulfadoxine and 25 mg pyrimethamine per tablet; SP plus azithromycin (1 g/dayx2 days; or SP plus artesunate (200 mg/dayx3 days. Women received two doses administered at least 4 weeks apart. Heteroduplex tracking assays were performed to distinguish recrudescence from new infections. Main outcome measures were incidence of adverse outcomes, parasite and fever clearance times and recrudescence rates. All treatment regimens were well tolerated. Two women vomited soon after ingesting azithromycin. The parasite clearance time was significantly faster in the SP-artesunate group. Recrudescent episodes of malaria were less frequent with SP-azithromycin [Hazard Ratio 0.19 (95% confidence interval 0.06 to 0.63] and SP-artesunate [Hazard Ratio 0.25 (95% confidence interval 0.10 to 0.65] compared with SP monotherapy. With one exception (an abortion in the SP-azithromycin group, all adverse pregnancy outcomes could be attributed to known infectious or obstetrical causes. Because of the small sample size, the effect on birth outcomes, maternal malaria or maternal anemia could not be evaluated.Both SP-artesunate and SP-azithromycin appeared to be safe, well tolerated and efficacious for the treatment of malaria during pregnancy. A larger study is needed to determine their safety and efficacy in preventing poor birth outcomes.ClinialTrials.gov NCT00287300.

  6. TWRS technical baseline database manager definition document

    International Nuclear Information System (INIS)

    Acree, C.D.

    1997-01-01

    This document serves as a guide for using the TWRS Technical Baseline Database Management Systems Engineering (SE) support tool in performing SE activities for the Tank Waste Remediation System (TWRS). This document will provide a consistent interpretation of the relationships between the TWRS Technical Baseline Database Management software and the present TWRS SE practices. The Database Manager currently utilized is the RDD-1000 System manufactured by the Ascent Logic Corporation. In other documents, the term RDD-1000 may be used interchangeably with TWRS Technical Baseline Database Manager

  7. Life Support Baseline Values and Assumptions Document

    Science.gov (United States)

    Anderson, Molly S.; Ewert, Michael K.; Keener, John F.

    2018-01-01

    The Baseline Values and Assumptions Document (BVAD) provides analysts, modelers, and other life support researchers with a common set of values and assumptions which can be used as a baseline in their studies. This baseline, in turn, provides a common point of origin from which many studies in the community may depart, making research results easier to compare and providing researchers with reasonable values to assume for areas outside their experience. This document identifies many specific physical quantities that define life support systems, serving as a general reference for spacecraft life support system technology developers.

  8. SSA FITARA Common Baseline Implementation Plan

    Data.gov (United States)

    Social Security Administration — This document describes the agency's plan to implement the Federal Information Technology Acquisition Reform Act (FITARA) Common Baseline per OMB memorandum M-15-14.

  9. Program cost and schedule baseline; Revision 2

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1991-11-01

    The purpose of this document is to establish quantitative expressions of proposed costs and schedule to serve as a basis for measurement of the Radioactive Waste Management Program performance. It identifies the components of the Program Cost and Schedule Baseline (PCSB) that will be subject to change control by the Executive Level (Level 0) and Program (Level 1) Change Control Boards (CCBs) and establishes their baseline values. This document also details PCSB reporting, monitoring, and corrective action requirements. The Program technical baseline contained in the Waste Management System Description (WMSD) and the Waste Management System Requirements (WMSR) documents provides the technical basis for the PCSB. The PCSB establishes baseline values for the Yucca Mountain Site Characterization Project cost and schedule through submittal of the license application to the Nuclear Regulatory Commission (NRC).

  10. Impact of rapid diagnostic tests for the diagnosis and treatment of malaria at a peripheral health facility in Western Uganda: an interrupted time series analysis.

    Science.gov (United States)

    Boyce, Ross M; Muiru, Anthony; Reyes, Raquel; Ntaro, Moses; Mulogo, Edgar; Matte, Michael; Siedner, Mark J

    2015-05-15

    The World Health Organization recommends that all suspected malaria cases receive a parasitological diagnosis prior to treatment with artemisinin-based combination therapy. A recent meta-analysis of clinical trials evaluating RDTs for the management of patients with fever found substantial reductions in anti-malarial prescriptions when health workers adhered to treatment protocols based on test results. However few studies have reported on the impact of RDTs on health systems outside research settings. The study comprised a retrospective interrupted time series analysis, comparing rates of malaria diagnosis, treatment, and resource utilization before and after introduction of RDTs at a peripheral health facility in rural Western Uganda. The use of malaria diagnostic tests was graphically depicted throughout the study period and fit regression models to identify correlates of three outcomes of interest: (1) length of stay (2) the proportion of patients referred to a higher-level health facility, and (3) administration of antibiotics. Over the course of the study period, 14,357 individuals underwent diagnostic testing for malaria with either a RDT (9,807) or microscopy (4,550). The proportion of patients with parasite-based diagnoses more than tripled to 34% after the introduction of RDTs. RDTs largely replaced microscopy as the diagnostic method of choice. Compared to patients admitted during the pre-RDT period, patients admitted to the health centre with malaria in the post-RDT period had significantly reduced odds of being referred to another health centre (AOR=0.49, P=0.038), receiving antibiotics (AOR=0.42, Pintroduction of RDTs for the diagnosis of malaria at a rural health facility in Uganda. The results show a reduction in referrals and shorter mean inpatient LOS even as antibiotics were prescribed less frequently. This change greatly increased laboratory throughput and the resultant proportion of patients receiving a parasite-based diagnosis.

  11. Technical baseline description for in situ vitrification laboratory test equipment

    International Nuclear Information System (INIS)

    Beard, K.V.; Bonnenberg, R.W.; Watson, L.R.

    1991-09-01

    IN situ vitrification (ISV) has been identified as possible waste treatment technology. ISV was developed by Pacific Northwest Laboratory (PNL), Richland, Washington, as a thermal treatment process to treat contaminated soils in place. The process, which electrically melts and dissolves soils and associated inorganic materials, simultaneously destroys and/or removes organic contaminants while incorporating inorganic contaminants into a stable, glass-like residual product. This Technical Baseline Description has been prepared to provide high level descriptions of the design of the Laboratory Test model, including all design modifications and safety improvements made to data. Furthermore, the Technical Baseline Description provides a basic overview of the interface documents for configuration management, program management interfaces, safety, quality, and security requirements. 8 figs

  12. Atorvastatin treatment is effective when used in combination with mefloquine in an experimental cerebral malaria murine model

    Directory of Open Access Journals (Sweden)

    Souraud Jean-Baptiste

    2012-01-01

    Full Text Available Abstract Background One of the major complications of Plasmodium falciparum infection is cerebral malaria (CM, which causes one million deaths worldwide each year, results in long-term neurological sequelae and the treatment for which is only partially effective. Statins are recognized to have an immunomodulatory action, attenuate sepsis and have a neuroprotective effect. Atorvastatin (AVA has shown in vitro anti-malarial activity and has improved the activity of mefloquine (MQ and quinine. Methods The efficiency of 40 mg/kg intraperitoneal AVA, alone or in association with MQ, was assessed in an experimental Plasmodium berghei ANKA rodent parasite model of CM and performed according to different therapeutic schemes. The effects on experimental CM were assessed through the evaluation of brain histopathological changes and neuronal apoptosis by TUNEL staining. Results AVA alone in the therapeutic scheme show no effect on survival, but the prophylactic scheme employing AVA associated with MQ, rather than MQ alone, led to a significant delay in mouse death and had an effect on the onset of CM symptoms and on the level of parasitaemia. Histopathological findings show a correlation between brain lesions and CM onset. A neuronal anti-apoptotic effect of AVA in the AVA + MQ combination was not shown. Conclusions The combination of AVA and MQ therapy led to a significant delay in mouse mortality. There were differences in the incidence, time to cerebral malaria and the level of parasitaemia when the drug combination was administered to mice. When used in combination with MQ, AVA had a relevant effect on the in vivo growth inhibition and clinical outcome of P. berghei ANKA-infected mice.

  13. Nonintrusive methodology for wellness baseline profiling

    Science.gov (United States)

    Chung, Danny Wen-Yaw; Tsai, Yuh-Show; Miaou, Shaou-Gang; Chang, Walter H.; Chang, Yaw-Jen; Chen, Shia-Chung; Hong, Y. Y.; Chyang, C. S.; Chang, Quan-Shong; Hsu, Hon-Yen; Hsu, James; Yao, Wei-Cheng; Hsu, Ming-Sin; Chen, Ming-Chung; Lee, Shi-Chen; Hsu, Charles; Miao, Lidan; Byrd, Kenny; Chouikha, Mohamed F.; Gu, Xin-Bin; Wang, Paul C.; Szu, Harold

    2007-04-01

    We develop an accumulatively effective and affordable set of smart pair devices to save the exuberant expenditure for the healthcare of aging population, which will not be sustainable when all the post-war baby boomers retire (78 millions will cost 1/5~1/4 GDP in US alone). To design an accessible test-bed for distributed points of homecare, we choose two exemplars of the set to demonstrate the possibility of translation of modern military and clinical know-how, because two exemplars share identically the noninvasive algorithm adapted to the Smart Sensor-pairs for the real world persistent surveillance. Currently, the standard diagnoses for malignant tumors and diabetes disorders are blood serum tests, X-ray CAT scan, and biopsy used sometime in the physical checkup by physicians as cohort-average wellness baselines. The loss of the quality of life in making second careers productive may be caused by the missing of timeliness for correct diagnoses and easier treatments, which contributes to the one quarter of human errors generating the lawsuits against physicians and hospitals, which further escalates the insurance cost and wasteful healthcare expenditure. Such a vicious cycle should be entirely eliminated by building an "individual diagnostic aids (IDA)," similar to the trend of personalized drug, developed from daily noninvasive intelligent databases of the "wellness baseline profiling (WBP)". Since our physiology state undulates diurnally, the Nyquist anti-aliasing theory dictates a minimum twice-a-day sampling of the WBP for the IDA, which must be made affordable by means of noninvasive, unsupervised and unbiased methodology at the convenience of homes. Thus, a pair of military infrared (IR) spectral cameras has been demonstrated for the noninvasive spectrogram ratio test of the spontaneously emitted thermal radiation from a normal human body at 37°C temperature. This invisible self-emission spreads from 3 microns to 12 microns of the radiation wavelengths

  14. Barriers to prompt and effective malaria treatment among the poorest population in Kenya

    Directory of Open Access Journals (Sweden)

    Okungu Vincent

    2010-05-01

    Full Text Available Abstract Background Prompt access to effective malaria treatment is central to the success of malaria control worldwide, but few fevers are treated with effective anti-malarials within 24 hours of symptoms onset. The last two decades saw an upsurge of initiatives to improve access to effective malaria treatment in many parts of sub-Saharan Africa. Evidence suggests that the poorest populations remain least likely to seek prompt and effective treatment, but the factors that prevent them from accessing interventions are not well understood. With plans under way to subsidize ACT heavily in Kenya and other parts of Africa, there is urgent need to identify policy actions to promote access among the poor. This paper explores access barriers to effective malaria treatment among the poorest population in four malaria endemic districts in Kenya. Methods The study was conducted in the poorest areas of four malaria endemic districts in Kenya. Multiple data collection methods were applied including: a cross-sectional survey (n = 708 households; 24 focus group discussions; semi-structured interviews with health workers (n = 34; and patient exit interviews (n = 359. Results Multiple factors related to affordability, acceptability and availability interact to influence access to prompt and effective treatment. Regarding affordability, about 40 percent of individuals who self-treated using shop-bought drugs and 42 percent who visited a formal health facility reported not having enough money to pay for treatment, and having to adopt coping strategies including borrowing money and getting treatment on credit in order to access care. Other factors influencing affordability were seasonality of illness and income sources, transport costs, and unofficial payments. Regarding acceptability, the major interrelated factors identified were provider patient relationship, patient expectations, beliefs on illness causation, perceived effectiveness of treatment, distrust in

  15. Evaluation of case management of uncomplicated malaria in Haiti: a national health facility survey, 2012.

    Science.gov (United States)

    Landman, Keren Z; Jean, Samuel E; Existe, Alexandre; Akom, Eniko E; Chang, Michelle A; Lemoine, Jean Frantz; Mace, Kimberly E

    2015-10-09

    Malaria is a public health concern in Haiti, although there are limited data on its burden and case management. National malaria guidelines updated in 2012 recommend treatment with chloroquine and primaquine. In December 2012, a nationally-representative cross-sectional survey of health facilities (HFs) was conducted to determine malaria prevalence among febrile outpatients and malaria case management quality at baseline before scale-up of diagnostics and case management training. Among all 833 HFs nationwide, 30 were selected randomly, in proportion to total HFs per region, for 2-day evaluations. Survey teams inventoried HF material and human resources. Outpatients of all ages were screened for temperature >37.5 °C or history of fever; those without severe symptoms were consented and enrolled. Providers evaluated and treated enrolled patients according to HF standards; the survey teams documented provider-ordered diagnostic tests and treatment decisions. Facility-based test results [microscopy and malaria rapid diagnostic tests (RDTs)] were collected from HF laboratories. Blood smears for gold-standard microscopy, and dried blood spots for polymerase chain reaction (PCR) were obtained. Malaria diagnostic capacity, defined as completing a test for an enrolled patient or having adequate resources for RDTs or microscopy, was present in 11 (37 %) HFs. Among 459 outpatients screened, 257 (56 %) were febrile, of which 193 (75 %) were eligible, and 153 (80 %) were enrolled. Among 39 patients with facility-level malaria test results available on the survey day, 11 (28 %) were positive, of whom 6 (55 %) were treated with an anti-malarial. Twenty-seven (95 %) of the 28 patients testing negative were not treated with an anti-malarial. Of 114 patients without test results available, 35 (31 %) were presumptively treated for malaria. Altogether, 42 patients were treated with an anti-malarial, one (2 %) according to Haiti's 2012 guidelines. Of 140 gold-standard smears, none

  16. Baseline methodologies for clean development mechanism projects

    International Nuclear Information System (INIS)

    Lee, M.K.; Shrestha, R.M.; Sharma, S.; Timilsina, G.R.; Kumar, S.

    2005-11-01

    The Kyoto Protocol and the Clean Development Mechanism (CDM) came into force on 16th February 2005 with its ratification by Russia. The increasing momentum of this process is reflected in more than 100 projects having been submitted to the CDM Executive Board (CDM-EB) for approval of the baselines and monitoring methodologies, which is the first step in developing and implementing CDM projects. A CDM project should result in a net decrease of GHG emissions below any level that would have resulted from other activities implemented in the absence of that CDM project. The 'baseline' defines the GHG emissions of activities that would have been implemented in the absence of a CDM project. The baseline methodology is the process/algorithm for establishing that baseline. The baseline, along with the baseline methodology, are thus the most critical element of any CDM project towards meeting the important criteria of CDM, which are that a CDM should result in 'real, measurable, and long term benefits related to the mitigation of climate change'. This guidebook is produced within the frame work of the United Nations Environment Programme (UNEP) facilitated 'Capacity Development for the Clean Development Mechanism (CD4CDM)' Project. This document is published as part of the projects effort to develop guidebooks that cover important issues such as project finance, sustainability impacts, legal framework and institutional framework. These materials are aimed to help stakeholders better understand the CDM and are believed to eventually contribute to maximize the effect of the CDM in achieving the ultimate goal of UNFCCC and its Kyoto Protocol. This Guidebook should be read in conjunction with the information provided in the two other guidebooks entitled, 'Clean Development Mechanism: Introduction to the CDM' and 'CDM Information and Guidebook' developed under the CD4CDM project. (BA)

  17. Geochemical baseline studies of soil in Finland

    Science.gov (United States)

    Pihlaja, Jouni

    2017-04-01

    The soil element concentrations regionally vary a lot in Finland. Mostly this is caused by the different bedrock types, which are reflected in the soil qualities. Geological Survey of Finland (GTK) is carrying out geochemical baseline studies in Finland. In the previous phase, the research is focusing on urban areas and mine environments. The information can, for example, be used to determine the need for soil remediation, to assess environmental impacts or to measure the natural state of soil in industrial areas or mine districts. The field work is done by taking soil samples, typically at depth between 0-10 cm. Sampling sites are chosen to represent the most vulnerable areas when thinking of human impacts by possible toxic soil element contents: playgrounds, day-care centers, schools, parks and residential areas. In the mine districts the samples are taken from the areas locating outside the airborne dust effected areas. Element contents of the soil samples are then analyzed with ICP-AES and ICP-MS, Hg with CV-AAS. The results of the geochemical baseline studies are published in the Finnish national geochemical baseline database (TAPIR). The geochemical baseline map service is free for all users via internet browser. Through this map service it is possible to calculate regional soil baseline values using geochemical data stored in the map service database. Baseline data for 17 elements in total is provided in the map service and it can be viewed on the GTK's web pages (http://gtkdata.gtk.fi/Tapir/indexEN.html).

  18. Baseline methodologies for clean development mechanism projects

    Energy Technology Data Exchange (ETDEWEB)

    Lee, M.K. (ed.); Shrestha, R.M.; Sharma, S.; Timilsina, G.R.; Kumar, S.

    2005-11-15

    The Kyoto Protocol and the Clean Development Mechanism (CDM) came into force on 16th February 2005 with its ratification by Russia. The increasing momentum of this process is reflected in more than 100 projects having been submitted to the CDM Executive Board (CDM-EB) for approval of the baselines and monitoring methodologies, which is the first step in developing and implementing CDM projects. A CDM project should result in a net decrease of GHG emissions below any level that would have resulted from other activities implemented in the absence of that CDM project. The 'baseline' defines the GHG emissions of activities that would have been implemented in the absence of a CDM project. The baseline methodology is the process/algorithm for establishing that baseline. The baseline, along with the baseline methodology, are thus the most critical element of any CDM project towards meeting the important criteria of CDM, which are that a CDM should result in 'real, measurable, and long term benefits related to the mitigation of climate change'. This guidebook is produced within the frame work of the United Nations Environment Programme (UNEP) facilitated 'Capacity Development for the Clean Development Mechanism (CD4CDM)' Project. This document is published as part of the projects effort to develop guidebooks that cover important issues such as project finance, sustainability impacts, legal framework and institutional framework. These materials are aimed to help stakeholders better understand the CDM and are believed to eventually contribute to maximize the effect of the CDM in achieving the ultimate goal of UNFCCC and its Kyoto Protocol. This Guidebook should be read in conjunction with the information provided in the two other guidebooks entitled, 'Clean Development Mechanism: Introduction to the CDM' and 'CDM Information and Guidebook' developed under the CD4CDM project. (BA)

  19. Scaling-up malaria treatment: a review of the performance of different providers.

    Science.gov (United States)

    Kamal-Yanni, Mohga M; Potet, Julien; Saunders, Philippa M

    2012-12-12

    Despite great progress towards malaria control, the disease continues to be a major public health problem in many developing countries, especially for poor women and children in remote areas. Resistance to artemisinin combination therapy (ACT) emerged in East Asia. Its spread would threaten the only effective malaria treatment currently available. Improvement in availability of diagnosis as part of malaria control has highlighted the fact that many fevers are not due to malaria. These fevers also need to be promptly diagnosed and adequately treated in order to improve public health outcomes in developing countries. This review looked for evidence for the most effective approach to deliver malaria treatment in developing countries, by public sector, formal and informal private sector, and community health workers (CHWs). The authors analysed 31 studies to assess providers based on six parameters: knowledge and practice of provider, diagnosis, referral practices, price of medicine, availability of ACT, and treatment coverage and impact on morbidity and mortality. The public sector has made progress in prevention and treatment in many countries, but facilities are inaccessible to some communities, and the sector suffers shortages of health workers and stock-outs of medicines. Despite wide outreach, the private sector, especially informal facilities, presents public health risks. This is due to an inability to diagnose and treat non-malarial fevers, and an innate motive to over-prescribe malaria treatment. The need to pay for treatment is a major factor in deterring poor women and children from accessing the medicines they need. A system that depends on ability to pay risks a repeat of the chloroquine story, where an effective and cheap anti-malarial drug was rendered useless partly due to under-treatment. CHWs have proved to be effective agents in providing correct diagnosis and treatment of malaria and other common fevers, even in remote areas. The evidence shows

  20. Scaling-up malaria treatment: a review of the performance of different providers

    Directory of Open Access Journals (Sweden)

    Kamal-Yanni Mohga M

    2012-12-01

    Full Text Available Abstract Background Despite great progress towards malaria control, the disease continues to be a major public health problem in many developing countries, especially for poor women and children in remote areas. Resistance to artemisinin combination therapy (ACT emerged in East Asia. Its spread would threaten the only effective malaria treatment currently available. Improvement in availability of diagnosis as part of malaria control has highlighted the fact that many fevers are not due to malaria. These fevers also need to be promptly diagnosed and adequately treated in order to improve public health outcomes in developing countries. Methods This review looked for evidence for the most effective approach to deliver malaria treatment in developing countries, by public sector, formal and informal private sector, and community health workers (CHWs. The authors analysed 31 studies to assess providers based on six parameters: knowledge and practice of provider, diagnosis, referral practices, price of medicine, availability of ACT, and treatment coverage and impact on morbidity and mortality. Results The public sector has made progress in prevention and treatment in many countries, but facilities are inaccessible to some communities, and the sector suffers shortages of health workers and stock-outs of medicines. Despite wide outreach, the private sector, especially informal facilities, presents public health risks. This is due to an inability to diagnose and treat non-malarial fevers, and an innate motive to over-prescribe malaria treatment. The need to pay for treatment is a major factor in deterring poor women and children from accessing the medicines they need. A system that depends on ability to pay risks a repeat of the chloroquine story, where an effective and cheap anti-malarial drug was rendered useless partly due to under-treatment. CHWs have proved to be effective agents in providing correct diagnosis and treatment of malaria and other

  1. Baseline factors affecting closure of venous leg ulcers.

    Science.gov (United States)

    Marston, William A; Ennis, William J; Lantis, John C; Kirsner, Robert S; Galiano, Robert D; Vanscheidt, Wolfgang; Eming, Sabine A; Malka, Marcin; Cargill, D Innes; Dickerson, Jaime E; Slade, Herbert B

    2017-11-01

    The objective of this study was to characterize factors associated with closure of venous leg ulcers (VLUs) in a pooled analysis of subjects from three randomized clinical trials. Closure of VLUs after treatment with HP802-247, an allogeneic living cell therapy consisting of growth-arrested human keratinocytes and fibroblasts, vs standard therapy with compression bandaging was evaluated in three phase 3 clinical trials of similar design. Two trials enrolled subjects with VLUs ranging from 2 cm 2 to 12 cm 2 in area with 12-week treatment periods; the third trial enrolled subjects with VLUs between >12 cm 2 and ≤36 cm 2 with a 16-week treatment period. The first trial went to completion but failed to demonstrate a benefit to therapy with HP802-247 compared with placebo, and because of this, the remaining trials were terminated before completion. On the basis of no differences in outcomes between groups, subjects from both HP802-247 and control groups were pooled across all three studies. Cox proportional hazards regression analysis was employed to evaluate factors associated with VLU closure. This analysis included data from 716 subjects with VLU. Factors evaluated for association with healing included age, gender, race, diabetes, glycated hemoglobin level, body mass index, treatment (HP802-247 vs compression alone), and ulcer characteristics including location and area and duration at baseline. In an initial model including all of these putative factors, the following were significant at the P < .10 level: diagnosis of diabetes mellitus, gender, wound location (ankle or leg), baseline wound area, and wound duration at baseline. In a final model including only these factors, all but diabetes mellitus were significant at the P < .05 level. Effect sizes were as follows (hazard ratio [95% confidence interval]): female gender (1.384 [1.134-1.690]), wound location on the leg (1.490 [1.187-1.871]), smaller wound area at baseline (0.907 [0.887-0.927]), and shorter

  2. Longitudinal change instead of baseline testosterone predicts depressive symptoms.

    Science.gov (United States)

    Kische, Hanna; Pieper, Lars; Venz, John; Klotsche, Jens; März, Winfried; Koch-Gromus, Uwe; Pittrow, David; Lehnert, Hendrik; Silber, Sigmund; Stalla, G K; Zeiher, Andreas M; Wittchen, Hans-Ulrich; Haring, Robin

    2018-03-01

    The association between total testosterone (T) and depression mostly relies on single sex hormone assessment and remains inconclusive. Thus, we investigated the comparative predictive performance of baseline T and change in T with development of depressive symptoms and incident depressive episodes. We used data from 6493 primary care patients (2653 men and 3840 women) of the DETECT study (Diabetes Cardiovascular Risk-Evaluation: Targets and Essential Data for Commitment of Treatment), including four-year follow-up, repeated immunoassay-based measurement of serum T and depressive symptoms assessed by the Depression Screening Questionnaire (DSQ). Cross-sectional and longitudinal associations of baseline T and one-year change in T with prevalent and incident depression were investigated using age- and multivariable-adjusted regression models. Baseline T showed no association with prevalent or incident depressive symptoms and episodes in both sexes. In men, a positive change in T (higher T at one-year follow-up compared to baseline) was associated with a lower burden of depressive symptoms (β-coefficient per unit change in T: -0.17; 95% CI: -0.31 to -0.04) and lower risk of incident depressive symptoms (odds ratio per unit change in T: 0.84; 95% CI: 0.72-0.98) at four-year follow-up. In women, the association of T change with incident depressive episodes was rendered non-significant after multivariable adjustment. The present study observed a sex-specific inverse association of T change, but not baseline T, with increased depressive symptom burden in men. Future studies should assess longitudinal changes in sex hormone status as predictor of adverse health outcomes related to low T. Copyright © 2017 Elsevier Ltd. All rights reserved.

  3. Waste management project technical baseline description

    International Nuclear Information System (INIS)

    Sederburg, J.P.

    1997-01-01

    A systems engineering approach has been taken to describe the technical baseline under which the Waste Management Project is currently operating. The document contains a mission analysis, function analysis, requirement analysis, interface definitions, alternative analysis, system definition, documentation requirements, implementation definitions, and discussion of uncertainties facing the Project

  4. On Internal Validity in Multiple Baseline Designs

    Science.gov (United States)

    Pustejovsky, James E.

    2014-01-01

    Single-case designs are a class of research designs for evaluating intervention effects on individual cases. The designs are widely applied in certain fields, including special education, school psychology, clinical psychology, social work, and applied behavior analysis. The multiple baseline design (MBD) is the most frequently used single-case…

  5. Waste management project technical baseline description

    Energy Technology Data Exchange (ETDEWEB)

    Sederburg, J.P.

    1997-08-13

    A systems engineering approach has been taken to describe the technical baseline under which the Waste Management Project is currently operating. The document contains a mission analysis, function analysis, requirement analysis, interface definitions, alternative analysis, system definition, documentation requirements, implementation definitions, and discussion of uncertainties facing the Project.

  6. Solid Waste Program technical baseline description

    Energy Technology Data Exchange (ETDEWEB)

    Carlson, A.B.

    1994-07-01

    The system engineering approach has been taken to describe the technical baseline under which the Solid Waste Program is currently operating. The document contains a mission analysis, function analysis, system definition, documentation requirements, facility and project bases, and uncertainties facing the program.

  7. National Cyberethics, Cybersafety, Cybersecurity Baseline Study

    Science.gov (United States)

    Education Digest: Essential Readings Condensed for Quick Review, 2009

    2009-01-01

    This article presents findings from a study that explores the nature of the Cyberethics, Cybersafety, and Cybersecurity (C3) educational awareness policies, initiatives, curriculum, and practices currently taking place in the U.S. public and private K-12 educational settings. The study establishes baseline data on C3 awareness, which can be used…

  8. Mercury baseline levels in Flemish soils (Belgium)

    International Nuclear Information System (INIS)

    Tack, Filip M.G.; Vanhaesebroeck, Thomas; Verloo, Marc G.; Van Rompaey, Kurt; Ranst, Eric van

    2005-01-01

    It is important to establish contaminant levels that are normally present in soils to provide baseline data for pollution studies. Mercury is a toxic element of concern. This study was aimed at assessing baseline mercury levels in soils in Flanders. In a previous study, mercury contents in soils in Oost-Vlaanderen were found to be significantly above levels reported elsewhere. For the current study, observations were extended over two more provinces, West-Vlaanderen and Antwerpen. Ranges of soil Hg contents were distinctly higher in the province Oost-Vlaanderen (interquartile range from 0.09 to 0.43 mg/kg) than in the other provinces (interquartile ranges from 0.7 to 0.13 and 0.7 to 0.15 mg/kg for West-Vlaanderen and Antwerpen, respectively). The standard threshold method was applied to separate soils containing baseline levels of Hg from the data. Baseline concentrations for Hg were characterised by a median of 0.10 mg Hg/kg dry soil, an interquartile range from 0.07 to 0.14 mg/kg and a 90% percentile value of 0.30 mg/kg. The influence of soil properties such as clay and organic carbon contents, and pH on baseline Hg concentrations was not important. Maps of the spatial distribution of Hg levels showed that the province Oost-Vlaanderen exhibited zones with systematically higher Hg soil contents. This may be related to the former presence of many small-scale industries employing mercury in that region. - Increased mercury levels may reflect human activity

  9. Chloroquine treatment enhances regulatory T cells and reduces the severity of experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Rodolfo Thomé

    Full Text Available BACKGROUND: The modulation of inflammatory processes is a necessary step, mostly orchestrated by regulatory T (Treg cells and suppressive Dendritic Cells (DCs, to prevent the development of deleterious responses and autoimmune diseases. Therapies that focused on adoptive transfer of Treg cells or their expansion in vivo achieved great success in controlling inflammation in several experimental models. Chloroquine (CQ, an anti-malarial drug, was shown to reduce inflammation, although the mechanisms are still obscure. In this context, we aimed to access whether chloroquine treatment alters the frequency of Treg cells and DCs in normal mice. In addition, the effects of the prophylactic and therapeutic treatment with CQ on Experimental Autoimmune Encephalomyelitis (EAE, an experimental model for human Multiple Sclerosis, was investigated as well. METHODOLOGY/PRINCIPAL FINDINGS: EAE was induced in C57BL/6 mice by immunization with myelin oligodendrocyte glycoprotein (MOG35-55 peptide. C57BL/6 mice were intraperitoneally treated with chloroquine. Results show that the CQ treatment provoked an increase in Treg cells frequency as well as a decrease in DCs. We next evaluated whether prophylactic CQ administration is capable of reducing the clinical and histopathological signs of EAE. Our results demonstrated that CQ-treated mice developed mild EAE compared to controls that was associated with lower infiltration of inflammatory cells in the central nervous system CNS and increased frequency of Treg cells. Also, proliferation of MOG35-55-reactive T cells was significantly inhibited by chloroquine treatment. Similar results were observed when chloroquine was administrated after disease onset. CONCLUSION: We show for the first time that CQ treatment promotes the expansion of Treg cells, corroborating previous reports indicating that chloroquine has immunomodulatory properties. Our results also show that CQ treatment suppress the inflammation in the CNS of

  10. CASA Uno GPS orbit and baseline experiments

    Science.gov (United States)

    Schutz, B. E.; Ho, C. S.; Abusali, P. A. M.; Tapley, B. D.

    1990-01-01

    CASA Uno data from sites distributed in longitude from Australia to Europe have been used to determine orbits of the GPS satellites. The characteristics of the orbits determined from double difference phase have been evaluated through comparisons of two-week solutions with one-week solutions and by comparisons of predicted and estimated orbits. Evidence of unmodeled effects is demonstrated, particularly associated with the orbit planes that experience solar eclipse. The orbit accuracy has been assessed through the repeatability of unconstrained estimated baseline vectors ranging from 245 km to 5400 km. Both the baseline repeatability and the comparison with independent space geodetic methods give results at the level of 1-2 parts in 100,000,000. In addition, the Mojave/Owens Valley (245 km) and Kokee Park/Ft. Davis (5409 km) estimates agree with VLBI and SLR to better than 1 part in 100,000,000.

  11. Baseline composition of solar energetic particles

    International Nuclear Information System (INIS)

    Meyer, J.

    1985-01-01

    We analyze all existing spacecraft observations of the highly variable heavy element composition of solar energetic particles (SEP) during non- 3 He-rich events. All data show the imprint of an ever-present basic composition pattern (dubbed ''mass-unbiased baseline'' SEP composition) that differs from the photospheric composition by a simple bias related to first ionization potential (FIP). In each particular observation, this mass-unbiased baseline composition is being distorted by an additional bias, which is always a monotonic function of mass (or Z). This latter bias varies in amplitude and even sign from observation to observation. To first order, it seems related to differences in the A/Z* ratio between elements (Z* = mean effective charge)

  12. Joint Multi-baseline SAR Interferometry

    Directory of Open Access Journals (Sweden)

    S. Tebaldini

    2005-12-01

    Full Text Available We propose a technique to provide interferometry by combining multiple images of the same area. This technique differs from the multi-baseline approach in literature as (a it exploits all the images simultaneously, (b it performs a spectral shift preprocessing to remove most of the decorrelation, and (c it exploits distributed targets. The technique is mainly intended for DEM generation at centimetric accuracy, as well as for differential interferometry. The problem is framed in the contest of single-input multiple-output (SIMO channel estimation via the cross-relations (CR technique and the resulting algorithm provides significant improvements with respect to conventional approaches based either on independent analysis of single interferograms or multi-baselines phase analysis of single pixels of current literature, for those targets that are correlated in all the images, like for long-term coherent areas, or for acquisitions taken with a short revisit time (as those gathered with future satellite constellations.

  13. Predicting Baseline for Analysis of Electricity Pricing

    Energy Technology Data Exchange (ETDEWEB)

    Kim, T. [Ulsan National Inst. of Science and Technology (Korea, Republic of); Lee, D. [Ulsan National Inst. of Science and Technology (Korea, Republic of); Choi, J. [Ulsan National Inst. of Science and Technology (Korea, Republic of); Spurlock, A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sim, A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Todd, A. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wu, K. [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2016-05-03

    To understand the impact of new pricing structure on residential electricity demands, we need a baseline model that captures every factor other than the new price. The standard baseline is a randomized control group, however, a good control group is hard to design. This motivates us to devlop data-driven approaches. We explored many techniques and designed a strategy, named LTAP, that could predict the hourly usage years ahead. The key challenge in this process is that the daily cycle of electricity demand peaks a few hours after the temperature reaching its peak. Existing methods rely on the lagged variables of recent past usages to enforce this daily cycle. These methods have trouble making predictions years ahead. LTAP avoids this trouble by assuming the daily usage profile is determined by temperature and other factors. In a comparison against a well-designed control group, LTAP is found to produce accurate predictions.

  14. Systematic errors in long baseline oscillation experiments

    Energy Technology Data Exchange (ETDEWEB)

    Harris, Deborah A.; /Fermilab

    2006-02-01

    This article gives a brief overview of long baseline neutrino experiments and their goals, and then describes the different kinds of systematic errors that are encountered in these experiments. Particular attention is paid to the uncertainties that come about because of imperfect knowledge of neutrino cross sections and more generally how neutrinos interact in nuclei. Near detectors are planned for most of these experiments, and the extent to which certain uncertainties can be reduced by the presence of near detectors is also discussed.

  15. OCRWM baseline management procedure for document identifiers

    International Nuclear Information System (INIS)

    1993-03-01

    This procedure establishes a uniform numbering system (document identifier) for all Program and project technical, cost, and schedule baselines, and selected management and procurement documents developed for and controlled by the Office of Civilian Radioactive Waste Management (OCRWM) for the Civilian Radioactive Waste Management System (CRWMS). The document identifier defined in this procedure is structured to ensure that the relational integrity between configuration items (CIs) and their associated documentation and software is maintained, traceable, categorical, and retrievable for the life of the program

  16. TWRS phase I privatization site environmental baseline and characterization plan

    Energy Technology Data Exchange (ETDEWEB)

    Shade, J.W.

    1997-09-01

    This document provides a plan to characterize and develop an environmental baseline for the TWRS Phase I Privatization Site before construction begins. A site evaluation study selected the former Grout Disposal Area of the Grout Treatment Facility in the 200 East Area as the TWRS Phase I Demonstration Site. The site is generally clean and has not been used for previous activities other than the GTF. A DQO process was used to develop a Sampling and Analysis Plan that would allow comparison of site conditions during operations and after Phase I ends to the presently existing conditions and provide data for the development of a preoperational monitoring plan.

  17. Do anti-malarials in Africa meet quality standards? The market penetration of non quality-assured artemisinin combination therapy in eight African countries.

    Science.gov (United States)

    Newton, Paul N; Hanson, Kara; Goodman, Catherine

    2017-05-25

    Quality of artemisinin-based combination therapy (ACT) is important for ensuring malaria parasite clearance and protecting the efficacy of artemisinin-based therapies. The extent to which non quality-assured ACT (non-QAACT), or those not granted global regulatory approval, are available and used to treat malaria in endemic countries is poorly documented. This paper uses national and sub-national medicine outlet surveys conducted in eight study countries (Benin, Kinshasa and Kantanga [Democratic Republic of the Congo, DRC], Kenya, Madagascar, Nigeria, Tanzania, Uganda and Zambia) between 2009 and 2015 to describe the non-QAACT market and to document trends in availability and distribution of non-QAACT in the public and private sector. In 2014/15, non-QAACT were most commonly available in Kinshasa (83%), followed by Katanga (53%), Nigeria (48%), Kenya (42%), and Uganda (33%). Non-QAACT accounted for 20% of the market share in the private sector in Kenya, followed by Benin and Uganda (19%), Nigeria (12%) and Zambia (8%); this figure was 27% in Katanga and 40% in Kinshasa. Public sector non-QAACT availability and distribution was much lower, with the exception of Zambia (availability, 85%; market share, 32%). Diverse generics and formulations were available, but non-QAACT were most commonly artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DHA PPQ), in tablet formulation, imported, and distributed in urban areas at either pharmacies or drug stores. The number of unique manufacturers supplying non-QAACT to each country ranged from 9 in Uganda to 92 in Nigeria. Addressing the availability and distribution of non-QAACT will require effective private sector engagement and evidence-based strategies to address provider and consumer demand for these products. Given the variation in non-QAACT markets observed across the eight study countries, active efforts to limit registration, importation and distribution of non-QAACT must be tailored to the country context, and will involve addressing complex and challenging aspects of medicine registration, private sector pharmaceutical regulation, local manufacturing and drug importation. These efforts may be critical not only to patient health and safety, but also to effective malaria control and protection of artemisinin drug efficacy in the face of spreading resistance.

  18. Efficacy comparison between anti-malarial drugs in Africans presenting with mild malaria in the Central Republic of Africa: a preliminary study

    Directory of Open Access Journals (Sweden)

    Nambei W.S.

    2005-03-01

    Full Text Available Drug resistance to Plasmodium falciparum contributes to major health problems in central Africa and, as a consequence, poverty. We have analyzed the efficacy of three currently available antimalarial drugs to treat symptomatic, uncomplicated P. falciparum malaria in semiimmune adults living in Bangui, Central Republic of Africa. 210 consecutive individuals were enrolled in the survey, of which 45 were excluded. Those having received dihydroartemisin proved significantly less parasitemic than those having received quinine per os or sulfadoxin-pyrimethamin (χ2 = 16.93 ; p < 0.05, and 75 % recovered in two days compared to 57 and 44 %, respectively. The 25 % who did not recover benefited from a second cure with dihydroartemisin, which proved 100 % efficient. The most accurate protocol remains to be established by analyzing clinical and parasitological data and taking into account the economics of the country.

  19. Prevalence of molecular markers of anti-malarial drug resistance in Plasmodium vivax and Plasmodium falciparum in two districts of Nepal

    DEFF Research Database (Denmark)

    Ranjitkar, Samir; Schousboe, Mette L; Thomsen, Thomas

    2011-01-01

    endemic areas. However, SP is still used against P. falciparum infections in low endemic areas while CQ is used in suspected cases in areas with lack of diagnostic facilities. This study examines the prevalence of molecular markers of P. falciparum and Plasmodium vivax CQ and SP resistance to determine...... if high levels of in vivo resistance are reflected at molecular level as well. METHODS: Finger prick blood samples (n=189) were collected from malaria positive patients from two high endemic districts and analysed for single nucleotide polymorphisms (SNPs) in the resistance related genes of P. falciparum...... on a few P. falciparum samples, the molecular level of CQ resistance in P. falciparum was high since nearly all parasites had the Pfcrt mutant haplotypes CVIET (55%) or SVMNT (42%), though frequency of Pfmdr1 wild type haplotype was relatively low (35%). Molecular levels of SP resistance in P. falciparum...

  20. The acceptability of mass administrations of anti-malarial drugs as part of targeted malaria elimination in villages along the Thai–Myanmar border

    Directory of Open Access Journals (Sweden)

    Ladda Kajeechiwa

    2016-09-01

    Full Text Available Abstract Background A targeted malaria elimination project, including mass drug administrations (MDA of dihydroartemisinin/piperaquine plus a single low dose primaquine is underway in villages along the Thailand Myanmar border. The intervention has multiple components but the success of the project will depend on the participation of the entire communities. Quantitative surveys were conducted to study reasons for participation or non-participation in the campaign with the aim to identify factors associated with the acceptance and participation in the mass drug administrations. Methods The household heads in four study villages in which MDAs had taken place previously were interviewed between January 2014 and July 2015. Results 174/378 respondents (46 % completed three rounds of three drug doses each, 313/378 (83 % took at least three consecutive doses and 56/378 (15 % did not participate at all in the MDA. The respondents from the two villages (KNH and TPN were much more likely to participate in the MDA than respondents from the other two villages (HKT and TOT. The more compliant villages KNH and TPN had both an appearance of cohesive communities with similar demographic and ethnic backgrounds. By contrast the villages with low participation were unique. One village was fragmented following years of armed conflict and many respondents gave little inclination to cooperate with outsiders. The other village with low MDA coverage was characterised by a high percentage of short-term residents with little interest in community interventions. A universal reason for non-participation in the MDA applicable to all villages was an inadequate understanding of the intervention. Conclusions It is unlikely that community engagement can unite fragmented communities in participating in an intervention, which benefits the community. Understanding the purpose and the reasons underlying the intervention is an important pre-condition for participation. In the absence of direct benefits and a complete understanding of the indirect benefits trust in the investigators is critical for participation.

  1. Mapping the genome of Plasmodium falciparum on the drug-like chemical space reveals novel anti-malarial targets and potential drug leads

    DEFF Research Database (Denmark)

    Jensen, Kasper; Plichta, Damian Rafal; Panagiotou, Gianni

    2012-01-01

    essential proteins and the effect of their perturbations on the metabolic network of P. falciparum, as well as indication of drug resistance emergence. Finally, we predict potential off-target effects on the human host with associations to cancer, neurological and dermatological disorders, based......The parasite Plasmodium falciparum is the main agent responsible for malaria. In this study, we exploited a recently published chemical library from GlaxoSmithKline (GSK) that had previously been confirmed to inhibit parasite growth of the wild type (3D7) and the multi-drug resistance (D2d) strains...... on integration of available chemical-protein and protein-protein interaction data. Our work suggests that a large number of the P. falciparum proteome is potentially druggable and could therefore serve as novel drug targets in the fight against malaria. At the same time, prioritized compounds from the GSK...

  2. Therapeutic indications and other use-case-driven updates in the drug ontology: anti-malarials, anti-hypertensives, opioid analgesics, and a large term request.

    Science.gov (United States)

    Hogan, William R; Hanna, Josh; Hicks, Amanda; Amirova, Samira; Bramblett, Baxter; Diller, Matthew; Enderez, Rodel; Modzelewski, Timothy; Vasconcelos, Mirela; Delcher, Chris

    2017-03-03

    The Drug Ontology (DrOn) is an OWL2-based representation of drug products and their ingredients, mechanisms of action, strengths, and dose forms. We originally created DrOn for use cases in comparative effectiveness research, primarily to identify historically complete sets of United States National Drug Codes (NDCs) that represent packaged drug products, by the ingredient(s), mechanism(s) of action, and so on contained in those products. Although we had designed DrOn from the outset to carefully distinguish those entities that have a therapeutic indication from those entities that have a molecular mechanism of action, we had not previously represented in DrOn any particular therapeutic indication. In this work, we add therapeutic indications for three research use cases: resistant hypertension, malaria, and opioid abuse research. We also added mechanisms of action for opioid analgesics and added 108 classes representing drug products in response to a large term request from the Program for Resistance, Immunology, Surveillance and Modeling of Malaria in Uganda (PRISM) project. The net result is a new version of DrOn, current to May 2016, that represents three major therapeutic classes of drugs and six new mechanisms of action. A therapeutic indication of a drug product is represented as a therapeutic function in DrOn. Adverse effects of drug products, as well as other therapeutic uses for which the drug product was not designed are dispositions. Our work provides a framework for representing additional therapeutic indications, adverse effects, and uses of drug products beyond their design. Our work also validated our past modeling decisions for specific types of mechanisms of action, namely effects mediated via receptor and/or enzyme binding. DrOn is available at: http://purl.obolibrary.org/obo/dron.owl . A smaller version without NDCs is available at: http://purl.obolibrary.org/obo/dron/dron-lite.owl.

  3. Therapeutic indications and other use-case-driven updates in the drug ontology: anti-malarials, anti-hypertensives, opioid analgesics, and a large term request

    OpenAIRE

    Hogan, William R.; Hanna, Josh; Hicks, Amanda; Amirova, Samira; Bramblett, Baxter; Diller, Matthew; Enderez, Rodel; Modzelewski, Timothy; Vasconcelos, Mirela; Delcher, Chris

    2017-01-01

    Background The Drug Ontology (DrOn) is an OWL2-based representation of drug products and their ingredients, mechanisms of action, strengths, and dose forms. We originally created DrOn for use cases in comparative effectiveness research, primarily to identify historically complete sets of United States National Drug Codes (NDCs) that represent packaged drug products, by the ingredient(s), mechanism(s) of action, and so on contained in those products. Although we had designed DrOn from the outs...

  4. Identification of Selective Inhibitors of the Plasmodium falciparum Hexose Transporter PfHT by Screening Focused Libraries of Anti-Malarial Compounds.

    Directory of Open Access Journals (Sweden)

    Diana Ortiz

    Full Text Available Development of resistance against current antimalarial drugs necessitates the search for novel drugs that interact with different targets and have distinct mechanisms of action. Malaria parasites depend upon high levels of glucose uptake followed by inefficient metabolic utilization via the glycolytic pathway, and the Plasmodium falciparum hexose transporter PfHT, which mediates uptake of glucose, has thus been recognized as a promising drug target. This transporter is highly divergent from mammalian hexose transporters, and it appears to be a permease that is essential for parasite viability in intra-erythrocytic, mosquito, and liver stages of the parasite life cycle. An assay was developed that is appropriate for high throughput screening against PfHT based upon heterologous expression of PfHT in Leishmania mexicana parasites that are null mutants for their endogenous hexose transporters. Screening of two focused libraries of antimalarial compounds identified two such compounds that are high potency selective inhibitors of PfHT compared to human GLUT1. Additionally, 7 other compounds were identified that are lower potency and lower specificity PfHT inhibitors but might nonetheless serve as starting points for identification of analogs with more selective properties. These results further support the potential of PfHT as a novel drug target.

  5. Base-line studies for DAE establishments

    International Nuclear Information System (INIS)

    Puranik, V.D.

    2012-01-01

    The Department of Atomic Energy has establishments located in various regions of the country and they include front-end fuel cycle facilities, nuclear power stations, back-end fuel cycle facilities and facilities for research and societal applications. These facilities handle naturally occurring radionuclides such as uranium, thorium and a variety of man-made radionuclides. These radionuclides are handled with utmost care so that they do not affect adversely the occupational workers or the members of public residing nearby. There is safety culture of the highest standard existing in all DAE establishments and it matches with the international standards. In addition, there is a perpetual environmental monitoring program carried out by the Environmental Survey Laboratories (ESLs) located at all DAE establishments. The environmental data generated by such program is studied regularly by experts to ensure compliance with the regulatory requirements. The regulatory requirements in the country are of international standards and ensure adequate protection of workers and members of public. In addition to such continued monitoring program and studies being carried out for the ongoing projects, base-line studies are carried out for all the new projects of the DAE. The purpose of the base-line studies is to establish a detailed base-line data set for a new DAE location well before the foundation stone is laid, so that the data collected when there is no departmental activity can be compared with the data generated later by the ESL. The data so generated is site specific and it varies from place to place depending upon the location of the site, e.g., inland or coastal, the presence of water bodies and pattern of irrigation, the geological characteristics of the location, the local culture and habits of the people, population density and urban or rural background. The data to be recorded as base-line data is generated over a period of at least one year covering all the seasons

  6. Pipeline integrity: ILI baseline data for QRA

    Energy Technology Data Exchange (ETDEWEB)

    Porter, Todd R. [Tuboscope Pipeline Services, Houston, TX (United States)]. E-mail: tporter@varco.com; Silva, Jose Augusto Pereira da [Pipeway Engenharia, Rio de Janeiro, RJ (Brazil)]. E-mail: guto@pipeway.com; Marr, James [MARR and Associates, Calgary, AB (Canada)]. E-mail: jmarr@marr-associates.com

    2003-07-01

    The initial phase of a pipeline integrity management program (IMP) is conducting a baseline assessment of the pipeline system and segments as part of Quantitative Risk Assessment (QRA). This gives the operator's integrity team the opportunity to identify critical areas and deficiencies in the protection, maintenance, and mitigation strategies. As a part of data gathering and integration of a wide variety of sources, in-line inspection (ILI) data is a key element. In order to move forward in the integrity program development and execution, the baseline geometry of the pipeline must be determined with accuracy and confidence. From this, all subsequent analysis and conclusions will be derived. Tuboscope Pipeline Services (TPS), in conjunction with Pipeway Engenharia of Brazil, operate ILI inertial navigation system (INS) and Caliper geometry tools, to address this integrity requirement. This INS and Caliper ILI tool data provides pipeline trajectory at centimeter level resolution and sub-metre 3D position accuracy along with internal geometry - ovality, dents, misalignment, and wrinkle/buckle characterization. Global strain can be derived from precise INS curvature measurements and departure from the initial pipeline state. Accurate pipeline elevation profile data is essential in the identification of sag/over bend sections for fluid dynamic and hydrostatic calculations. This data, along with pipeline construction, operations, direct assessment and maintenance data is integrated in LinaViewPRO{sup TM}, a pipeline data management system for decision support functions, and subsequent QRA operations. This technology provides the baseline for an informed, accurate and confident integrity management program. This paper/presentation will detail these aspects of an effective IMP, and experience will be presented, showing the benefits for liquid and gas pipeline systems. (author)

  7. SRP Baseline Hydrogeologic Investigation, Phase 3

    Energy Technology Data Exchange (ETDEWEB)

    Bledsoe, H.W.

    1988-08-01

    The SRP Baseline Hydrogeologic Investigation was implemented for the purpose of updating and improving the knowledge and understanding of the hydrogeologic systems underlying the SRP site. Phase III, which is discussed in this report, includes the drilling of 7 deep coreholes (sites P-24 through P-30) and the installation of 53 observation wells ranging in depth from approximately 50 ft to more than 970 ft below the ground surface. In addition to the collection of geologic cores for lithologic and stratigraphic study, samples were also collected for the determination of physical characteristics of the sediments and for the identification of microorganisms.

  8. SRP baseline hydrogeologic investigation, Phase 2

    Energy Technology Data Exchange (ETDEWEB)

    Bledsoe, H.W.

    1987-11-01

    As discussed in the program plan for the Savannah River Plant (SRP) Baseline Hydrogeologic Investigation, this program has been implemented for the purpose of updating and improving the current state of knowledge and understanding of the hydrogeologic systems underlying the Savannah River Plant (SRP). The objective of the program is to install a series of observation well clusters (wells installed in each major water bearing formation at the same site) at key locations across the plant site in order to: (1) provide detailed information on the lithology, stratigraphy, and groundwater hydrology, (2) provide observation wells to monitor the groundwater quality, head relationships, gradients, and flow paths.

  9. Spectrometer Baseline Control Via Spatial Filtering

    Science.gov (United States)

    Burleigh, M. R.; Richey, C. R.; Rinehart, S. A.; Quijada, M. A.; Wollack, E. J.

    2016-01-01

    An absorptive half-moon aperture mask is experimentally explored as a broad-bandwidth means of eliminating spurious spectral features arising from reprocessed radiation in an infrared Fourier transform spectrometer. In the presence of the spatial filter, an order of magnitude improvement in the fidelity of the spectrometer baseline is observed. The method is readily accommodated within the context of commonly employed instrument configurations and leads to a factor of two reduction in optical throughput. A detailed discussion of the underlying mechanism and limitations of the method are provided.

  10. Rationing in the presence of baselines

    DEFF Research Database (Denmark)

    Hougaard, Jens Leth; Moreno-Ternero, Juan D.; Østerdal, Lars Peter

    2013-01-01

    We analyze a general model of rationing in which agents have baselines, in addition to claims against the (insufficient) endowment of the good to be allocated. Many real-life problems fit this general model (e.g., bankruptcy with prioritized claims, resource allocation in the public health care...... sector, water distribution in drought periods). We introduce (and characterize) a natural class of allocation methods for this model. Any method within the class is associated with a rule in the standard rationing model, and we show that if the latter obeys some focal properties, the former obeys them...

  11. SRP baseline hydrogeologic investigation: Aquifer characterization

    Energy Technology Data Exchange (ETDEWEB)

    Strom, R.N.; Kaback, D.S.

    1992-03-31

    An investigation of the mineralogy and chemistry of the principal hydrogeologic units and the geochemistry of the water in the principal aquifers at Savannah River Site (SRS) was undertaken as part of the Baseline Hydrogeologic Investigation. This investigation was conducted to provide background data for future site studies and reports and to provide a site-wide interpretation of the geology and geochemistry of the Coastal Plain Hydrostratigraphic province. Ground water samples were analyzed for major cations and anions, minor and trace elements, gross alpha and beta, tritium, stable isotopes of hydrogen, oxygen, and carbon, and carbon-14. Sediments from the well borings were analyzed for mineralogy and major and minor elements.

  12. Baseline response rates affect resistance to change.

    Science.gov (United States)

    Kuroda, Toshikazu; Cook, James E; Lattal, Kennon A

    2018-01-01

    The effect of response rates on resistance to change, measured as resistance to extinction, was examined in two experiments. In Experiment 1, responding in transition from a variable-ratio schedule and its yoked-interval counterpart to extinction was compared with pigeons. Following training on a multiple variable-ratio yoked-interval schedule of reinforcement, in which response rates were higher in the former component, reinforcement was removed from both components during a single extended extinction session. Resistance to extinction in the yoked-interval component was always either greater or equal to that in the variable-ratio component. In Experiment 2, resistance to extinction was compared for two groups of rats that exhibited either high or low response rates when maintained on identical variable-interval schedules. Resistance to extinction was greater for the lower-response-rate group. These results suggest that baseline response rate can contribute to resistance to change. Such effects, however, can only be revealed when baseline response rate and reinforcement rate are disentangled (Experiments 1 and 2) from the more usual circumstance where the two covary. Furthermore, they are more cleanly revealed when the programmed contingencies controlling high and low response rates are identical, as in Experiment 2. © 2017 Society for the Experimental Analysis of Behavior.

  13. Baseline Estimation and Outlier Identification for Halocarbons

    Science.gov (United States)

    Wang, D.; Schuck, T.; Engel, A.; Gallman, F.

    2017-12-01

    The aim of this paper is to build a baseline model for halocarbons and to statistically identify the outliers under specific conditions. In this paper, time series of regional CFC-11 and Chloromethane measurements was discussed, which taken over the last 4 years at two locations, including a monitoring station at northwest of Frankfurt am Main (Germany) and Mace Head station (Ireland). In addition to analyzing time series of CFC-11 and Chloromethane, more importantly, a statistical approach of outlier identification is also introduced in this paper in order to make a better estimation of baseline. A second-order polynomial plus harmonics are fitted to CFC-11 and chloromethane mixing ratios data. Measurements with large distance to the fitting curve are regard as outliers and flagged. Under specific requirement, the routine is iteratively adopted without the flagged measurements until no additional outliers are found. Both model fitting and the proposed outlier identification method are realized with the help of a programming language, Python. During the period, CFC-11 shows a gradual downward trend. And there is a slightly upward trend in the mixing ratios of Chloromethane. The concentration of chloromethane also has a strong seasonal variation, mostly due to the seasonal cycle of OH. The usage of this statistical method has a considerable effect on the results. This method efficiently identifies a series of outliers according to the standard deviation requirements. After removing the outliers, the fitting curves and trend estimates are more reliable.

  14. Vegetation baseline report : Connacher great divide project

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2005-08-01

    This baseline report supported an application by Connacher Oil and Gas Ltd. to the Alberta Energy and Utilities Board (EUB) and Alberta Environment (AENV) for the Great Divide Steam Assisted Gravity Drainage (SAGD) Project. The goal of the report was to document the distribution and occurrence of ecosite phases and wetland classes in the project footprint as well as to document the distribution of rare plants; rare plant communities: and intrusive species and old growth communities, including species of management concern. A methodology of the baseline report was presented, including details of mapping and field surveys. Six vegetation types in addition to the disturbed land unit were identified in the project footprint and associated buffer. It was noted that all vegetation types are common for the boreal forest natural regions. Several species of management concern were identified during the spring rare plant survey, including rare bryophytes and non-native or invasive species. Mitigation was identified through a slight shift of the footprint, transplant of appropriate bryophyte species and implementation of a weed management plan. It was noted that results of future surveys for rare plants will be submitted upon completion. It was concluded that the effects of the project on existing vegetation is expected to be low because of the small footprint, prior disturbance history, available mitigation measures and conservation and reclamation planning. 27 refs., 5 tabs., 4 figs.

  15. Efficacy and safety of a fixed dose artesunate-sulphamethoxypyrazine-pyrimethamine compared to artemether-lumefantrine for the treatment of uncomplicated falciparum malaria across Africa: a randomized multi-centre trial

    Directory of Open Access Journals (Sweden)

    Djimdé Abdoulaye

    2009-04-01

    Full Text Available Abstract Background The efficacy of artemisinin-based combination therapy has already been demonstrated in a number of studies all over the world, and some of them can be regarded as comparably effective. Ease of administration of anti-malarial treatments with shorter courses and fewer tablets may be key determinant of compliance. Methods Patients with uncomplicated falciparum malaria and over six months of age were recruited in Cameroon, Mali, Rwanda and Sudan. 1,384 patients were randomly assigned to receive artesunate-sulphamethoxypyrazine-pyrimethamine (AS-SMP three-day (once daily for 3 days regimen (N = 476 or AS-SMP 24-hour (0 h, 12 h, 24 h regimen (N = 458 or artemether-lumefantrine (AL, the regular 6 doses regimen (N = 450. The primary objective was to demonstrate non-inferiority (using a margin of -6% of AS-SMP 24 hours or AS-SMP three days versus AL on the PCR-corrected 28-day cure rate. Results The PCR corrected 28-day cure rate on the intention to treat (ITT analysis population were: 96.0%(457/476 in the AS-SMP three-day group, 93.7%(429/458 in the AS-SMP 24-hour group and 92.0%(414/450 in the AL group. Likewise, the cure rates on the PP analysis population were high: 99.3%(432/437 in the AS-SMP three-day group, 99.5%(416/419 in the AS-SMP 24-hour group and 99.7(391/394% in the AL group. Most common drug-related adverse events were gastrointestinal symptoms (such as vomiting and diarrhea which were slightly higher in the AS-SMP 24-hour group. Conclusion AS-SMP three days or AS-SMP 24 hours are safe, are as efficacious as AL, and are well tolerated. Trial registration NCT00484900 http://www.clinicaltrials.gov.

  16. Patient baseline interpersonal problems as moderators of outcome in two psychotherapies for bulimia nervosa.

    Science.gov (United States)

    Gomez Penedo, Juan Martin; Constantino, Michael J; Coyne, Alice E; Bernecker, Samantha L; Smith-Hansen, Lotte

    2018-01-19

    We tested an aptitude by treatment interaction; namely, whether patients' baseline interpersonal problems moderated the comparative efficacy of cognitive-behavioral therapy (CBT) vs. interpersonal psychotherapy (IPT) for bulimia nervosa (BN). Data derived from a randomized-controlled trial. Patients reported on their interpersonal problems at baseline; purge frequency at baseline, midtreatment, and posttreatment; and global eating disorder severity at baseline and posttreatment. We estimated the rate of change in purge frequency across therapy, and the likelihood of attaining clinically meaningful improvement (recovery) in global eating disorder severity by posttreatment. We then tested the interpersonal problem by treatment interactions as predictors of both outcomes. Patients with more baseline overly communal/friendly problems showed steeper reduction in likelihood of purging when treated with CBT vs. IPT. Patients with more problems of being under communal/cold had similar reductions in likelihood of purging across both treatments. Patients with more baseline problems of being overly agentic were more likely to recover when treated with IPT vs. CBT, whereas patients with more problems of being under agentic were more likely to recover when treated with CBT vs. IPT. Interpersonal problems related to communion and agency may inform treatment fit among two empirically supported therapies for BN.

  17. Mujeres en accion: design and baseline data.

    Science.gov (United States)

    Keller, Colleen; Fleury, Julie; Perez, Adriana; Belyea, Michael; Castro, Felipe G

    2011-10-01

    The majority of programs designed to promote physical activity in older Hispanic women includes few innovative theory-based interventions that address cultural relevant strategies. The purpose of this report is to describe the design and baseline data for Mujeres en Accion, a physical activity intervention to increase regular physical activity, and cardiovascular health outcomes among older Hispanic women. Mujeres en Accion [Women in Action for Health], a 12 month randomized controlled trial to evaluate the effectiveness of a social support physical activity intervention in midlife and older Hispanic women. This study tests an innovative intervention, Mujeres en Accion, and includes the use of a theory-driven approach to intervention, explores social support as a theoretical mediating variable, use of a Promotora model and a Community Advisory group to incorporate cultural and social approaches and resources, and use of objective measures of physical activity in Hispanic women.

  18. The OPERA long baseline neutrino oscillation experiment

    International Nuclear Information System (INIS)

    Wilquet, G

    2008-01-01

    OPERA is a long baseline neutrino oscillation experiment designed to observe the appearance of vτ in a pure v μ beam in the parameter space indicated by the atmospheric neutrinos oscillation signal. The detector is situated in the underground LNGS laboratory under 3 800 water meter equivalent at a distance of 730 km from CERN where the CNGS neutrino beam to which it is exposed originates. It consists of two identical 0.68 kilotons lead/nuclear emulsion targets, each instrumented with a tracking device and complemented by a muon spectrometer. The concept and the status of the detector are described and the first results obtained with cosmic rays and during two weeks of beam commissioning in 2006 are reported

  19. Pentek concrete scabbling system: Baseline report

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1997-07-31

    The Pentek scabbling technology was tested at Florida International University (FIU) and is being evaluated as a baseline technology. This report evaluates it for safety and health issues. It is a commercially available technology and has been used for various projects at locations throughout the country. The Pentek concrete scabbling system consisted of the MOOSE{reg_sign}, SQUIRREL{reg_sign}-I, and SQUIRREL{reg_sign}-III scabblers. The scabblers are designed to scarify concrete floors and slabs using cross-section, tungsten carbide tipped bits. The bits are designed to remove concrete in 318 inch increments. The bits are either 9-tooth or demolition type. The scabblers are used with a vacuum system designed to collect and filter the concrete dust and contamination that is removed from the surface. The safety and health evaluation during the human factors assessment focused on two main areas: noise and dust.

  20. The WITCH Model. Structure, Baseline, Solutions.

    Energy Technology Data Exchange (ETDEWEB)

    Bosetti, V.; Massetti, E.; Tavoni, M.

    2007-07-01

    WITCH - World Induced Technical Change Hybrid - is a regionally disaggregated hard link hybrid global model with a neoclassical optimal growth structure (top down) and an energy input detail (bottom up). The model endogenously accounts for technological change, both through learning curves affecting prices of new vintages of capital and through R and D investments. The model features the main economic and environmental policies in each world region as the outcome of a dynamic game. WITCH belongs to the class of Integrated Assessment Models as it possesses a climate module that feeds climate changes back into the economy. In this paper we provide a thorough discussion of the model structure and baseline projections. We report detailed information on the evolution of energy demand, technology and CO2 emissions. Finally, we explicitly quantifiy the role of free riding in determining the emissions scenarios. (auth)

  1. An automated approach to configuration baseline documentation

    International Nuclear Information System (INIS)

    Blake, G.D.; Khan, M.A.

    1990-01-01

    This paper presents Public Service Electric and Gas Company's (PSE and G's) automated approach to configuration base-line documentation (CBD) for Salem units 1 and 2 and Hope Creek. The CBD project is a proactive project, similar to what is commonly termed a design basis documentation program in the nuclear utility industry. The data information management system (DIMS) element of the CBD project is expected to automate the CBD development, review/approval, control, maintenance, and distribution of CBD and the subsequent integration of the CBD into the day-to-day design processes of PSE and G's nuclear engineering department. The DIMS project scope emphasizes streamlined, swift, and accurate design information retrieval system hardware and software; proper and controlled screening of stored design information; legible storage of design information; and more efficient and user-friendly information handling. This paper discusses the selection and implementation of an integrated optical imaging and textual search technology

  2. Efficacy and tolerability of adjunct perampanel based on number of antiepileptic drugs at baseline and baseline predictors of efficacy: A phase III post-hoc analysis.

    Science.gov (United States)

    Glauser, Tracy; Laurenza, Antonio; Yang, Haichen; Williams, Betsy; Ma, Tony; Fain, Randi

    2016-01-01

    Perampanel is a selective, noncompetitive AMPA receptor antagonist with demonstrated efficacy and tolerability in partial seizures in patients aged ≥ 12 years in Phase III studies. Post-hoc analysis of these studies was conducted to determine the efficacy and tolerability of perampanel based on the number of concomitant antiepileptic drugs (AEDs) at baseline, as well as to examine which baseline characteristics, if any, were predictors of efficacy. Efficacy parameters were based on the number of baseline AEDs, and logistic regression analyses were used to evaluate the association of demographic and baseline clinical factors with probability of ≥ 50% reduction in seizure frequency. Patients on 1 AED at baseline were significantly more likely to have reduced seizure frequency (P<0.02) and improved 50% responder rate (P<0.02) than patients on 3 AEDs at baseline. Secondarily generalized seizures at baseline, unknown etiology, and use of concomitant non-inducer AEDs were also established as positive predictors of efficacy (50% responder rate; P<0.01). Patients with more AEDs at baseline were associated with greater use of inducers (P<0.01), which may result in decreased exposure of perampanel in these patients and lower efficacy. Patients with 1 AED at baseline had a significantly shorter time since diagnosis compared with patients in the 3 (P<0.01) AEDs group, as well as a lower median seizure frequency at baseline compared to patients on 3 AEDs (P<0.05), suggesting that the reduced efficacy of perampanel with 3 AEDs may also be associated with the greater severity of seizures in the patient groups. The incidence of adverse events in perampanel-treated patients was similar regardless of the number of AEDs at baseline. Greater efficacy is predicted for patients receiving fewer concomitant AEDs when starting perampanel, as well as for those receiving concomitant treatment with AEDs that are not CYP3A4 enzyme-inducers, compared to patients treated with multiple

  3. Integration report for SRC-I post-baseline environmental R and D

    Energy Technology Data Exchange (ETDEWEB)

    Yen, A.F.

    1984-06-01

    The Baseline Design for the wastewater treatment/reuse and solid-waste handling and disposal systems for the SRC-I Demonstration Plant was completed in 1982. Because of the ambitious construction schedule contemplated at that time, the design was not based on comprehensive design data. Consequently, since submission of the Baseline, ICRC has been generating experimental data to confirm and/or refine the Baseline Design. This report integrates all the environmental research and development (R and D) data generated during that period by many different R and D programs. 41 references, 29 figures, 32 tables.

  4. Drug coverage in treatment of malaria and the consequences for resistance evolution - evidence from the use of sulphadoxine/pyrimethamine

    Directory of Open Access Journals (Sweden)

    Malisa Allen L

    2010-07-01

    Full Text Available Abstract Background It is argued that, the efficacy of anti-malarials could be prolonged through policy-mediated reductions in drug pressure, but gathering evidence of the relationship between policy, treatment practice, drug pressure and the evolution of resistance in the field is challenging. Mathematical models indicate that drug coverage is the primary determinant of drug pressure and the driving force behind the evolution of drug resistance. These models show that where the basis of resistance is multigenic, the effects of selection can be moderated by high recombination rates, which disrupt the associations between co-selected resistance genes. Methods To test these predictions, dhfr and dhps frequency changes were measured during 2000-2001 while SP was the second-line treatment and contrasted these with changes during 2001-2002 when SP was used for first-line therapy. Annual cross sectional community surveys carried out before, during and after the policy switch in 2001 were used to collect samples. Genetic analysis of SP resistance genes was carried out on 4,950 Plasmodium falciparum infections and the selection pressure under the two policies compared. Results The influence of policy on the parasite reservoir was profound. The frequency of dhfr and dhps resistance alleles did not change significantly while SP was the recommended second-line treatment, but highly significant changes occurred during the subsequent year after the switch to first line SP. The frequency of the triple mutant dhfr (N51I,C59R,S108N allele (conferring pyrimethamine resistance increased by 37% - 63% and the frequency of the double A437G, K540E mutant dhps allele (conferring sulphadoxine resistance increased 200%-300%. A strong association between these unlinked alleles also emerged, confirming that they are co-selected by SP. Conclusion The national policy change brought about a shift in treatment practice and the resulting increase in coverage had a substantial

  5. 40 CFR 80.915 - How are the baseline toxics value and baseline toxics volume determined?

    Science.gov (United States)

    2010-07-01

    ... baseline toxics value if it can determine an applicable toxics value for every batch of gasoline produced... of gasoline batch i produced or imported between January 1, 1998 and December 31, 2000, inclusive. i = Individual batch of gasoline produced or imported between January 1, 1998 and December 31, 2000, inclusive. n...

  6. The London low emission zone baseline study.

    Science.gov (United States)

    Kelly, Frank; Armstrong, Ben; Atkinson, Richard; Anderson, H Ross; Barratt, Ben; Beevers, Sean; Cook, Derek; Green, Dave; Derwent, Dick; Mudway, Ian; Wilkinson, Paul

    2011-11-01

    On February 4, 2008, the world's largest low emission zone (LEZ) was established. At 2644 km2, the zone encompasses most of Greater London. It restricts the entry of the oldest and most polluting diesel vehicles, including heavy-goods vehicles (haulage trucks), buses and coaches, larger vans, and minibuses. It does not apply to cars or motorcycles. The LEZ scheme will introduce increasingly stringent Euro emissions standards over time. The creation of this zone presented a unique opportunity to estimate the effects of a stepwise reduction in vehicle emissions on air quality and health. Before undertaking such an investigation, robust baseline data were gathered on air quality and the oxidative activity and metal content of particulate matter (PM) from air pollution monitors located in Greater London. In addition, methods were developed for using databases of electronic primary-care records in order to evaluate the zone's health effects. Our study began in 2007, using information about the planned restrictions in an agreed-upon LEZ scenario and year-on-year changes in the vehicle fleet in models to predict air pollution concentrations in London for the years 2005, 2008, and 2010. Based on this detailed emissions and air pollution modeling, the areas in London were then identified that were expected to show the greatest changes in air pollution concentrations and population exposures after the implementation of the LEZ. Using these predictions, the best placement of a pollution monitoring network was determined and the feasibility of evaluating the health effects using electronic primary-care records was assessed. To measure baseline pollutant concentrations before the implementation of the LEZ, a comprehensive monitoring network was established close to major roadways and intersections. Output-difference plots from statistical modeling for 2010 indicated seven key areas likely to experience the greatest change in concentrations of nitrogen dioxide (NO2) (at least 3

  7. On baseline corrections and uncertainty in response spectrafor baseline variations commonly encountered in digital accelerograph records

    Science.gov (United States)

    Akkar, Sinan; Boore, David M.

    2009-01-01

    Most digital accelerograph recordings are plagued by long-period drifts, best seen in the velocity and displacement time series obtained from integration of the acceleration time series. These drifts often result in velocity values that are nonzero near the end of the record. This is clearly unphysical and can lead to inaccurate estimates of peak ground displacement and long-period spectral response. The source of the long-period noise seems to be variations in the acceleration baseline in many cases. These variations could be due to true ground motion (tilting and rotation, as well as local permanent ground deformation), instrumental effects, or analog-to-digital conversion. Very often the trends in velocity are well approximated by a linear trend after the strong shaking subsides. The linearity of the trend in velocity implies that no variations in the baseline could have occurred after the onset of linearity in the velocity time series. This observation, combined with the lack of any trends in the pre-event motion, allows us to compute the time interval in which any baseline variations could occur. We then use several models of the variations in a Monte Carlo procedure to derive a suite of baseline-corrected accelerations for each noise model using records from the 1999 Chi-Chi earthquake and several earthquakes in Turkey. Comparisons of the mean values of the peak ground displacements, spectral displacements, and residual displacements computed from these corrected accelerations for the different noise models can be used as a guide to the accuracy of the baseline corrections. For many of the records considered here the mean values are similar for each noise model, giving confidence in the estimation of the mean values. The dispersion of the ground-motion measures increases with period and is noise-model dependent. The dispersion of inelastic spectra is greater than the elastic spectra at short periods but approaches that of the elastic spectra at longer periods

  8. Shifting environmental baselines in the Red Sea.

    Science.gov (United States)

    Price, A R G; Ghazi, S J; Tkaczynski, P J; Venkatachalam, A J; Santillan, A; Pancho, T; Metcalfe, R; Saunders, J

    2014-01-15

    The Red Sea is among the world's top marine biodiversity hotspots. We re-examined coastal ecosystems at sites surveyed during the 1980s using the same methodology. Coral cover increased significantly towards the north, mirroring the reverse pattern for mangroves and other sedimentary ecosystems. Latitudinal patterns are broadly consistent across both surveys and with results from independent studies. Coral cover showed greatest change, declining significantly from a median score of 4 (1000-9999 m(2)) to 2 (10-99m(2)) per quadrat in 2010/11. This may partly reflect impact from coastal construction, which was evident at 40% of sites and has significantly increased in magnitude over 30 years. Beach oil has significantly declined, but shore debris has increased significantly. Although substantial, levels are lower than at some remote ocean atolls. While earlier reports have suggested that the Red Sea is generally healthy, shifting environmental baselines are evident from the current study. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Camera Trajectory fromWide Baseline Images

    Science.gov (United States)

    Havlena, M.; Torii, A.; Pajdla, T.

    2008-09-01

    Camera trajectory estimation, which is closely related to the structure from motion computation, is one of the fundamental tasks in computer vision. Reliable camera trajectory estimation plays an important role in 3D reconstruction, self localization, and object recognition. There are essential issues for a reliable camera trajectory estimation, for instance, choice of the camera and its geometric projection model, camera calibration, image feature detection and description, and robust 3D structure computation. Most of approaches rely on classical perspective cameras because of the simplicity of their projection models and ease of their calibration. However, classical perspective cameras offer only a limited field of view, and thus occlusions and sharp camera turns may cause that consecutive frames look completely different when the baseline becomes longer. This makes the image feature matching very difficult (or impossible) and the camera trajectory estimation fails under such conditions. These problems can be avoided if omnidirectional cameras, e.g. a fish-eye lens convertor, are used. The hardware which we are using in practice is a combination of Nikon FC-E9 mounted via a mechanical adaptor onto a Kyocera Finecam M410R digital camera. Nikon FC-E9 is a megapixel omnidirectional addon convertor with 180° view angle which provides images of photographic quality. Kyocera Finecam M410R delivers 2272×1704 images at 3 frames per second. The resulting combination yields a circular view of diameter 1600 pixels in the image. Since consecutive frames of the omnidirectional camera often share a common region in 3D space, the image feature matching is often feasible. On the other hand, the calibration of these cameras is non-trivial and is crucial for the accuracy of the resulting 3D reconstruction. We calibrate omnidirectional cameras off-line using the state-of-the-art technique and Mičušík's two-parameter model, that links the radius of the image point r to the

  10. LTC vacuum blasting machine (concrete): Baseline report

    International Nuclear Information System (INIS)

    1997-01-01

    The LTC shot blast technology was tested and is being evaluated at Florida International University (FIU) as a baseline technology. In conjunction with FIU's evaluation of efficiency and cost, this report covers the evaluation conducted for safety and health issues. It is a commercially available technology and has been used for various projects at locations throughout the country. The LTC 1073 Vacuum Blasting Machine uses a high-capacity, direct-pressure blasting system which incorporates a continuous feed for the blast media. The blast media cleans the surface within the contained brush area of the blast. It incorporates a vacuum system which removes dust and debris from the surface as it is blasted. The safety and health evaluation during the testing demonstration focused on two main areas of exposure: dust and noise. Dust exposure during maintenance activities was minimal, but due to mechanical difficulties dust monitoring could not be conducted during operation. Noise exposure was significant. Further testing for each of these exposures is recommended because of the outdoor environment where the testing demonstration took place. This may cause the results to be inaccurate. It is feasible that the dust and noise levels will be higher in an enclosed environment. In addition, other safety and health issues found were ergonomics, heat stress, tripping hazards, electrical hazards, lockout/tagout, and arm-hand vibration

  11. FAIR - Baseline technical report. Executive summary

    International Nuclear Information System (INIS)

    Gutbrod, H.H.; Augustin, I.; Eickhoff, H.; Gross, K.D.; Henning, W.F.; Kraemer, D.; Walter, G.

    2006-09-01

    This document presents the Executive Summary, the first of six volumes comprising the 2006 Baseline Technical Report (BTR) for the international FAIR project (Facility for Antiproton and Ion Research). The BTR provides the technical description, cost, schedule, and assessments of risk for the proposed new facility. The purpose of the BTR is to provide a reliable basis for the construction, commissioning and operation of FAIR. The BTR is one of the central documents requested by the FAIR International Steering Committee (ISC) and its working groups, in order to prepare the legal process and the decisions on the construction and operation of FAIR in an international framework. It provides the technical basis for legal contracts on contributions to be made by, so far, 13 countries within the international FAIR Consortium. The BTR begins with this extended Executive Summary as Volume 1, which is also intended for use as a stand-alone document. The Executive Summary provides brief summaries of the accelerator facilities, the scientific programs and experimental stations, civil construction and safety, and of the workproject structure, costs and schedule. (orig.)

  12. Cryogenics Testbed Laboratory Flange Baseline Configuration

    Science.gov (United States)

    Acuna, Marie Lei Ysabel D.

    2013-01-01

    As an intern at Kennedy Space Center (KSC), I was involved in research for the Fluids and Propulsion Division of the NASA Engineering (NE) Directorate. I was immersed in the Integrated Ground Operations Demonstration Units (IGODU) project for the majority of my time at KSC, primarily with the Ground Operations Demonstration Unit Liquid Oxygen (GODU L02) branch of IGODU. This project was established to develop advancements in cryogenic systems as a part of KSC's Advanced Exploration Systems (AES) program. The vision of AES is to develop new approaches for human exploration, and operations in and beyond low Earth orbit. Advanced cryogenic systems are crucial to minimize the consumable losses of cryogenic propellants, develop higher performance launch vehicles, and decrease operations cost for future launch programs. During my internship, I conducted a flange torque tracking study that established a baseline configuration for the flanges in the Simulated Propellant Loading System (SPLS) at the KSC Cryogenics Test Laboratory (CTL) - the testing environment for GODU L02.

  13. Beyond Baselines: Rethinking Priorities for Ocean Conservation

    Directory of Open Access Journals (Sweden)

    Lisa M. Campbell

    2009-06-01

    Full Text Available In 1995, Daniel Pauly identified a "shifting baselines syndrome" (SBS. Pauly was concerned that scientists measure ecosystem change against their personal recollections of the past and, based on this decidedly short-term view, mismanage fish stocks because they tolerate gradual and incremental elimination of species and set inappropriate recovery goals. As a concept, SBS is simple to grasp and its logic is compelling. Much current work in marine historical ecology is rationalized in part as a means of combating SBS, and the term has also resonated outside of the academy with environmental advocacy groups. Although we recognize both conceptual and operational merit in SBS, we believe that the ultimate impact of SBS on ocean management will be limited by some underlying and interrelated problematic assumptions about ecology and human-environment relations, and the prescriptions that these assumptions support. In this paper, we trace both assumptions and prescriptions through key works in the SBS literature and interrogate them via ecological and social science theory and research. We argue that an expanded discussion of SBS is needed, one that engages a broader range of social scientists, ecologists, and resource users, and that explicitly recognizes the value judgments inherent in deciding both what past ecosystems looked like and whether or not and how we might reconstruct them.

  14. Proguanil and cycloguanil are organic cation transporter and multidrug and toxin extrusion substrates

    NARCIS (Netherlands)

    Velden, M van der; Bilos, A.; Heuvel, J.M. van den; Rijpma, S.R.; Hurkmans, E.G.E.; Sauerwein, R.W.; Russel, F.G.M.; Koenderink, J.B.

    2017-01-01

    BACKGROUND: Malaria, HIV/AIDS, and tuberculosis endemic areas show considerable geographical overlap, leading to incidence of co-infections. This requires treatment with multiple drugs, potentially causing adverse drug-drug interactions (DDIs). As anti-malarials are generally positively charged at

  15. Ethnobotany of plants used as insecticides, repellents and ...

    African Journals Online (AJOL)

    An ethnobotanical study on plants used for the prevention and treatment of malaria was conducted to document the indigenous knowledge particularly associated with the use and conservation of anti-malarial, insecticide and insect repellent medicinal plants. In this study, five sampling sites were selected based on the ...

  16. ethnobotany of plants used as insecticides, repellents and anti

    African Journals Online (AJOL)

    ADMIN

    ABSTRACT: An ethnobotanical study on plants used for the prevention and treatment of malaria was conducted to document the indigenous knowledge particularly associated with the use and conservation of anti-malarial, insecticide and insect repellent medicinal plants. In this study, five sampling sites were selected ...

  17. Household beliefs about malaria testing and treatment in Western Kenya: the role of health worker adherence to malaria test results.

    Science.gov (United States)

    Saran, Indrani; Maffioli, Elisa M; Menya, Diana; O'Meara, Wendy Prudhomme

    2017-08-22

    Although use of malaria diagnostic tests has increased in recent years, health workers often prescribe anti-malarial drugs to individuals who test negative for malaria. This study investigates how health worker adherence to malaria case management guidelines influences individuals' beliefs about whether their illness was malaria, and their confidence in the effectiveness of artemisinin-based combination therapy (ACT). A survey was conducted with 2065 households in Western Kenya about a household member's treatment actions for a recent febrile illness. The survey also elicited the individual's (or their caregiver's) beliefs about the illness and about malaria testing and treatment. Logistic regressions were used to test the association between these beliefs and whether the health worker adhered to malaria testing and treatment guidelines. Of the 1070 individuals who visited a formal health facility during their illness, 82% were tested for malaria. ACT rates for malaria-positive and negative individuals were 89 and 49%, respectively. Overall, 65% of individuals/caregivers believed that the illness was "very likely" malaria. Individuals/caregivers had higher odds of saying that the illness was "very likely" malaria when the individual was treated with ACT, and this was the case both among individuals not tested for malaria [adjusted odds ratio (AOR) 3.42, 95% confidence interval (CI) [1.65 7.10], P = 0.001] and among individuals tested for malaria, regardless of their test result. In addition, 72% of ACT-takers said the drug was "very likely" effective in treating malaria. However, malaria-negative individuals who were treated with ACT had lower odds of saying that the drugs were "very likely" effective than ACT-takers who were not tested or who tested positive for malaria (AOR 0.29, 95% CI [0.13 0.63], P = 0.002). Individuals/caregivers were more likely to believe that the illness was malaria when the patient was treated with ACT, regardless of their test result

  18. Treatment

    Directory of Open Access Journals (Sweden)

    Safaa M. Raghab

    2013-08-01

    The main goal of this study is to utilize a natural low cost material “as an accelerator additive to enhance the chemical treatment process using Alum coagulant and the accelerator substances were Perlite and Bentonite. The performance of the chemical treatment was enhanced using the accelerator substances with 90 mg/l Alum as a constant dose. Perlite gave better performance than the Bentonite effluent. The removal ratio for conductivity, turbidity, BOD and COD for Perlite was 86.7%, 87.4%, 89.9% and 92.8% respectively, and for Bentonite was 83.5%, 85.0%, 86.5% and 85.0% respectively at the same concentration of 40 mg/l for each.

  19. 100-D Area technical baseline report

    International Nuclear Information System (INIS)

    Carpenter, R.W.

    1993-01-01

    This document is prepared in support of the 100 Area Environmental Restoration activity at the US Department of Energy's Hanford Site near Richland, Washington. It provides a technical baseline of waste sites located at the 100-D Area. The report is based on an environmental investigation undertaken by the Westinghouse Hanford Company (WHC) History Office in support of the Environmental Restoration Engineering Function and on review and evaluation of numerous Hanford Site current and historical reports, drawings, and photographs, supplemented by site inspections and employee interviews. No intrusive field investigation or sampling was conducted. All Hanford coordinate locations are approximate locations taken from several different maps and drawings of the 100-D Area. Every effort was made to derive coordinate locations for the center of each facility or waste site, except where noted, using standard measuring devices. Units of measure are shown as they appear in reference documents. The 100-D Area is made up of three operable units: 100-DR-1, 100-DR-2, and 100-DR-3. All three are addressed in this report. These operable units include liquid and solid waste disposal sites in the vicinity of, and related to, the 100-D and 100-DR Reactors. A fourth operable unit, 100-HR-3, is concerned with groundwater and is not addressed here. This report describes waste sites which include cribs, trenches, pits, french drains, retention basins, solid waste burial grounds, septic tanks, and drain fields. Each waste site is described separately and photographs are provided where available. A complete list of photographs can be found in Appendix A. A comprehensive environmental summary is not provided here but may be found in Hanford Site National Environmental Policy Act Characterization (Cushing 1988), which describes the geology and soils, meteorology, hydrology, land use, population, and air quality of the area

  20. Baseline Architecture of ITER Control System

    Science.gov (United States)

    Wallander, A.; Di Maio, F.; Journeaux, J.-Y.; Klotz, W.-D.; Makijarvi, P.; Yonekawa, I.

    2011-08-01

    The control system of ITER consists of thousands of computers processing hundreds of thousands of signals. The control system, being the primary tool for operating the machine, shall integrate, control and coordinate all these computers and signals and allow a limited number of staff to operate the machine from a central location with minimum human intervention. The primary functions of the ITER control system are plant control, supervision and coordination, both during experimental pulses and 24/7 continuous operation. The former can be split in three phases; preparation of the experiment by defining all parameters; executing the experiment including distributed feed-back control and finally collecting, archiving, analyzing and presenting all data produced by the experiment. We define the control system as a set of hardware and software components with well defined characteristics. The architecture addresses the organization of these components and their relationship to each other. We distinguish between physical and functional architecture, where the former defines the physical connections and the latter the data flow between components. In this paper, we identify the ITER control system based on the plant breakdown structure. Then, the control system is partitioned into a workable set of bounded subsystems. This partition considers at the same time the completeness and the integration of the subsystems. The components making up subsystems are identified and defined, a naming convention is introduced and the physical networks defined. Special attention is given to timing and real-time communication for distributed control. Finally we discuss baseline technologies for implementing the proposed architecture based on analysis, market surveys, prototyping and benchmarking carried out during the last year.

  1. 1993 baseline solid waste management system description

    International Nuclear Information System (INIS)

    Armacost, L.L.; Fowler, R.A.; Konynenbelt, H.S.

    1994-02-01

    Pacific Northwest Laboratory has prepared this report under the direction of Westinghouse Hanford Company. The report provides an integrated description of the system planned for managing Hanford's solid low-level waste, low-level mixed waste, transuranic waste, and transuranic mixed waste. The primary purpose of this document is to illustrate a collective view of the key functions planned at the Hanford Site to handle existing waste inventories, as well as solid wastes that will be generated in the future. By viewing this system as a whole rather than as individual projects, key facility interactions and requirements are identified and a better understanding of the overall system may be gained. The system is described so as to form a basis for modeling the system at various levels of detail. Model results provide insight into issues such as facility capacity requirements, alternative system operating strategies, and impacts of system changes (ie., startup dates). This description of the planned Hanford solid waste processing system: defines a baseline system configuration; identifies the entering waste streams to be managed within the system; identifies basic system functions and waste flows; and highlights system constraints. This system description will evolve and be revised as issues are resolved, planning decisions are made, additional data are collected, and assumptions are tested and changed. Out of necessity, this document will also be revised and updated so that a documented system description, which reflects current system planning, is always available for use by engineers and managers. It does not provide any results generated from the many alternatives that will be modeled in the course of analyzing solid waste disposal options; such results will be provided in separate documents

  2. The LBNO long-baseline oscillation sensitivities with two conventional neutrino beams at different baselines

    CERN Document Server

    Agarwalla, S.K.; Aittola, M.; Alekou, A.; Andrieu, B.; Antoniou, F.; Asfandiyarov, R.; Autiero, D.; Besida, O.; Balik, A.; Ballett, P.; Bandac, I.; Banerjee, D.; Bartmann, W.; Bay, F.; Biskup, B.; Blebea-Apostu, A.M.; Blondel, A.; Bogomilov, M.; Bolognesi, S.; Borriello, E.; Brancus, I.; Bravar, A.; Buizza-Avanzini, M.; Caiulo, D.; Calin, M.; Calviani, M.; Campanelli, M.; Cantini, C.; Cata-Danil, G.; Chakraborty, S.; Charitonidis, N.; Chaussard, L.; Chesneanu, D.; Chipesiu, F.; Crivelli, P.; Dawson, J.; De Bonis, I.; Declais, Y.; del Amo Sanchez, P.; Delbart, A.; Di Luise, S.; Duchesneau, D.; Dumarchez, J.; Efthymiopoulos, I.; Eliseev, A.; Emery, S.; Enqvist, T.; Enqvist, K.; Epprecht, L.; Erykalov, A.N.; Esanu, T.; Franco, D.; Friend, M.; Galymov, V.; Gavrilov, G.; Gendotti, A.; Giganti, C.; Gilardoni, S.; Goddard, B.; Gomoiu, C.M.; Gornushkin, Y.A.; Gorodetzky, P.; Haesler, A.; Hasegawa, T.; Horikawa, S.; Huitu, K.; Izmaylov, A.; Jipa, A.; Kainulainen, K.; Karadzhov, Y.; Khabibullin, M.; Khotjantsev, A.; Kopylov, A.N.; Korzenev, A.; Kosyanenko, S.; Kryn, D.; Kudenko, Y.; Kuusiniemi, P.; Lazanu, I.; Lazaridis, C.; Levy, J.M.; Loo, K.; Maalampi, J.; Margineanu, R.M.; Marteau, J.; Martin-Mari, C.; Matveev, V.; Mazzucato, E.; Mefodiev, A.; Mineev, O.; Mirizzi, A.; Mitrica, B.; Murphy, S.; Nakadaira, T.; Narita, S.; Nesterenko, D.A.; Nguyen, K.; Nikolics, K.; Noah, E.; Novikov, Yu.; Oprima, A.; Osborne, J.; Ovsyannikova, T.; Papaphilippou, Y.; Pascoli, S.; Patzak, T.; Pectu, M.; Pennacchio, E.; Periale, L.; Pessard, H.; Popov, B.; Ravonel, M.; Rayner, M.; Resnati, F.; Ristea, O.; Robert, A.; Rubbia, A.; Rummukainen, K.; Saftoiu, A.; Sakashita, K.; Sanchez-Galan, F.; Sarkamo, J.; Saviano, N.; Scantamburlo, E.; Sergiampietri, F.; Sgalaberna, D.; Shaposhnikova, E.; Slupecki, M.; Smargianaki, D.; Stanca, D.; Steerenberg, R.; Sterian, A.R.; Sterian, P.; Stoica, S.; Strabel, C.; Suhonen, J.; Suvorov, V.; Toma, G.; Tonazzo, A.; Trzaska, W.H.; Tsenov, R.; Tuominen, K.; Valram, M.; Vankova-Kirilova, G.; Vannucci, F.; Vasseur, G.; Velotti, F.; Velten, P.; Venturi, V.; Viant, T.; Vihonen, S.; Vincke, H.; Vorobyev, A.; Weber, A.; Wu, S.; Yershov, N.; Zambelli, L.; Zito, M.

    2014-01-01

    The proposed Long Baseline Neutrino Observatory (LBNO) initially consists of $\\sim 20$ kton liquid double phase TPC complemented by a magnetised iron calorimeter, to be installed at the Pyh\\"asalmi mine, at a distance of 2300 km from CERN. The conventional neutrino beam is produced by 400 GeV protons accelerated at the SPS accelerator delivering 700 kW of power. The long baseline provides a unique opportunity to study neutrino flavour oscillations over their 1st and 2nd oscillation maxima exploring the $L/E$ behaviour, and distinguishing effects arising from $\\delta_{CP}$ and matter. In this paper we show how this comprehensive physics case can be further enhanced and complemented if a neutrino beam produced at the Protvino IHEP accelerator complex, at a distance of 1160 km, and with modest power of 450 kW is aimed towards the same far detectors. We show that the coupling of two independent sub-MW conventional neutrino and antineutrino beams at different baselines from CERN and Protvino will allow to measure ...

  3. 10 CFR 850.20 - Baseline beryllium inventory.

    Science.gov (United States)

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Baseline beryllium inventory. 850.20 Section 850.20 Energy... Baseline beryllium inventory. (a) The responsible employer must develop a baseline inventory of the... inventory, the responsible employer must: (1) Review current and historical records; (2) Interview workers...

  4. Baseline Hearing Measurements in Alaskan Belugas

    Science.gov (United States)

    2013-09-30

    DE, Kiehl K, Pennington S, Wong S, Henry KR (1999) Killer whale (Orcinus orca) hearing: Auditory brainstem response and behavioral audiograms. J...Supin AY (2005) Behavioral and auditory evoked potential audiograms of a false killer whale (Pseudorca crassidens). J Acoust Soc Am 118:2688-2695...documented in older bottlenose dolphins and suggested in a false killer whale ; hearing loss has also been related to antibiotic treatment in belugas

  5. Intermittent preventive treatment for the prevention of malaria during pregnancy in high transmission areas

    Directory of Open Access Journals (Sweden)

    Massougbodji Achille

    2007-12-01

    Full Text Available Abstract Malaria in pregnancy is one of the major causes of maternal morbidity and adverse birth outcomes. In high transmission areas, its prevention has recently changed, moving from a weekly or bimonthly chemoprophylaxis to intermittent preventive treatment (IPTp. IPTp consists in the administration of a single curative dose of an efficacious anti-malarial drug at least twice during pregnancy – regardless of whether the woman is infected or not. The drug is administered under supervision during antenatal care visits. Sulphadoxine-pyrimethamine (SP is the drug currently recommended by the WHO. While SP-IPTp seems an adequate strategy, there are many issues still to be explored to optimize it. This paper reviewed data on IPTp efficacy and discussed how to improve it. In particular, the determination of both the optimal number of doses and time of administration of the drug is essential, and this has not yet been done. As both foetal growth and deleterious effects of malaria are maximum in late pregnancy women should particularly be protected during this period. Monitoring of IPTp efficacy should be applied to all women, and not only to primi- and secondigravidae, as it has not been definitively established that multigravidae are not at risk for malaria morbidity and mortality. In HIV-positive women, there is an urgent need for specific information on drug administration patterns (need for higher doses, possible interference with sulpha-based prophylaxis of opportunistic infections. Because of the growing level of resistance of parasites to SP, alternative drugs for IPTp are urgently needed. Mefloquine is presently one of the most attractive options because of its long half life, high efficacy in sub-Saharan Africa and safety during pregnancy. Also, efforts should be made to increase IPTp coverage by improving the practices of health care workers, the motivation of women and their perception of malaria complications in pregnancy. Because IPTp

  6. 1995 Baseline solid waste management system description

    International Nuclear Information System (INIS)

    Anderson, G.S.; Konynenbelt, H.S.

    1995-09-01

    This provides a detailed solid waste system description that documents the treatment, storage, and disposal (TSD) strategy for managing Hanford's solid low-level waste, low-level mixed waste, transuranic and transuranic mixed waste, and greater-than-Class III waste. This system description is intended for use by managers of the solid waste program, facility and system planners, as well as system modelers. The system description identifies the TSD facilities that constitute the solid waste system and defines these facilities' interfaces, schedules, and capacities. It also provides the strategy for treating each of the waste streams generated or received by the Hanford Site from generation or receipt through final destination

  7. Drug coverage in treatment of malaria and the consequences for resistance evolution--evidence from the use of sulphadoxine/pyrimethamine.

    Science.gov (United States)

    Malisa, Allen L; Pearce, Richard J; Abdulla, Salim; Mshinda, Hassan; Kachur, Patrick S; Bloland, Peter; Roper, Cally

    2010-07-05

    It is argued that, the efficacy of anti-malarials could be prolonged through policy-mediated reductions in drug pressure, but gathering evidence of the relationship between policy, treatment practice, drug pressure and the evolution of resistance in the field is challenging. Mathematical models indicate that drug coverage is the primary determinant of drug pressure and the driving force behind the evolution of drug resistance. These models show that where the basis of resistance is multigenic, the effects of selection can be moderated by high recombination rates, which disrupt the associations between co-selected resistance genes. To test these predictions, dhfr and dhps frequency changes were measured during 2000-2001 while SP was the second-line treatment and contrasted these with changes during 2001-2002 when SP was used for first-line therapy. Annual cross sectional community surveys carried out before, during and after the policy switch in 2001 were used to collect samples. Genetic analysis of SP resistance genes was carried out on 4,950 Plasmodium falciparum infections and the selection pressure under the two policies compared. The influence of policy on the parasite reservoir was profound. The frequency of dhfr and dhps resistance alleles did not change significantly while SP was the recommended second-line treatment, but highly significant changes occurred during the subsequent year after the switch to first line SP. The frequency of the triple mutant dhfr (N51I,C59R,S108N) allele (conferring pyrimethamine resistance) increased by 37% - 63% and the frequency of the double A437G, K540E mutant dhps allele (conferring sulphadoxine resistance) increased 200%-300%. A strong association between these unlinked alleles also emerged, confirming that they are co-selected by SP. The national policy change brought about a shift in treatment practice and the resulting increase in coverage had a substantial impact on drug pressure. The selection applied by first-line use

  8. Utilities and offsites design baseline. Outside Battery Limits Facility 6000 tpd SRC-I Demonstration Plant. Volume 1

    Energy Technology Data Exchange (ETDEWEB)

    None

    1984-05-25

    As part of the overall Solvent Refined Coal (SRC-1) project baseline being prepared by International Coal Refining Company (ICRC), the RUST Engineering Company is providing necessary input for the Outside Battery Limits (OSBL) Facilities. The project baseline is comprised of: design baseline - technical definition of work; schedule baseline - detailed and management level 1 schedules; and cost baseline - estimates and cost/manpower plan. The design baseline (technical definition) for the OSBL Facilities has been completed and is presented in Volumes I, II, III, IV, V and VI. The OSBL technical definition is based on, and compatible with, the ICRC defined statement of work, design basis memorandum, master project procedures, process and mechanical design criteria, and baseline guidance documents. The design basis memorandum is included in Paragraph 1.3 of Volume I. The baseline design data is presented in 6 volumes. Volume I contains the introduction section and utility systems data through steam and feedwater. Volume II continues with utility systems data through fuel system, and contains the interconnecting systems and utility system integration information. Volume III contains the offsites data through water and waste treatment. Volume IV continues with offsites data, including site development and buildings, and contains raw materials and product handling and storage information. Volume V contains wastewater treatment and solid wastes landfill systems developed by Catalytic, Inc. to supplement the information contained in Volume III. Volume VI contains proprietary information of Resources Conservation Company related to the evaporator/crystallizer system of the wastewater treatment area.

  9. Baseline CD4+ T lymphocyte cell counts, hepatitis B and C viruses ...

    African Journals Online (AJOL)

    Background: Ekiti State of Nigeria is known to have the lowest prevalence of HIV in Nigeria. University Teaching Hospital (UTH), Ado Ekiti was recently upgraded to serve as one of the three centres for HIV/AIDS referral, diagnosis and treatment in Ekiti State. We evaluated the baseline immunologic and biochemical ...

  10. Mixed Waste Focus Area integrated technical baseline report, Phase 1: Volume 1

    International Nuclear Information System (INIS)

    1996-01-01

    The Department of Energy (DOE) established the Mixed Waste Characterization, Treatment, and Disposal Focus Area (MWFA) to develop and facilitate implementation of technologies required to meet the Department's commitments for treatment of mixed low-level and transuranic wastes. The mission of the MWFA is to provide acceptable treatment systems, developed in partnership with users and with participation of stakeholders, tribal governments, and regulators, that are capable of treating DOE's mixed waste. These treatment systems include all necessary steps such as characterization, pretreatment, and disposal. To accomplish this mission, a technical baseline is being established that forms the basis for determining which technology development activities will be supported by the MWFA. The technical baseline is the prioritized list of deficiencies, and the resulting technology development activities needed to overcome these deficiencies. This document presents Phase I of the technical baseline development process, which resulted in the prioritized list of deficiencies that the MWFA will address. A summary of the data and the assumptions upon which this work was based is included, as well as information concerning the DOE Office of Environmental Management (EM) mixed waste technology development needs. The next phase in the technical baseline development process, Phase II, will result in the identification of technology development activities that will be conducted through the MWFA to resolve the identified deficiencies

  11. Predicting Intelligibility Gains in Individuals with Dysarthria from Baseline Speech Features

    Science.gov (United States)

    Fletcher, Annalise R.; McAuliffe, Megan J.; Lansford, Kaitlin L.; Sinex, Donal G.; Liss, Julie M.

    2017-01-01

    Purpose: Across the treatment literature, behavioral speech modifications have produced variable intelligibility changes in speakers with dysarthria. This study is the first of two articles exploring whether measurements of baseline speech features can predict speakers' responses to these modifications. Method: Fifty speakers (7 older individuals…

  12. A combination of baseline plasma immune markers can predict therapeutic response in multidrug resistant tuberculosis.

    Directory of Open Access Journals (Sweden)

    Selena Ferrian

    Full Text Available To identify plasma markers predictive of therapeutic response in patients with multidrug resistant tuberculosis (MDR-TB.Fifty HIV-negative patients with active pulmonary MDR-TB were analysed for six soluble analytes in plasma at the time of initiating treatment (baseline and over six months thereafter. Patients were identified as sputum culture positive or negative at baseline. Culture positive patients were further stratified by the median time to sputum culture conversion (SCC as fast responders (< 76 days or slow responders (≥ 76 days. Chest X-ray scores, body mass index, and sputum smear microscopy results were obtained at baseline.Unsupervised hierarchical clustering revealed that baseline plasma levels of IP-10/CXCL10, VEGF-A, SAA and CRP could distinguish sputum culture and cavitation status of patients. Among patients who were culture positive at baseline, there were significant positive correlations between plasma levels of CRP, SAA, VEGF-A, sIL-2Rα/CD40, and IP-10 and delayed SCC. Using linear discriminant analysis (LDA and Receiver Operating Curves (ROC, we showed that a combination of MCP-1/CCL2, IP-10, sIL-2Rα, SAA, CRP and AFB smear could distinguish fast from slow responders and were predictive of delayed SCC with high sensitivity and specificity.Plasma levels of specific chemokines and inflammatory markers measured before MDR-TB treatment are candidate predictive markers of delayed SCC. These findings require validation in a larger study.

  13. Baseline glucocorticoids are drivers of body mass gain in a diving seabird

    Science.gov (United States)

    Hennin, Holly; Berlin, Alicia; Love, Oliver P.

    2016-01-01

    Life-history trade-offs are influenced by variation in individual state, with individuals in better condition often completing life-history stages with greater success. Although resource accrual significantly impacts key life-history decisions such as the timing of reproduction, little is known about the underlying mechanisms driving resource accumulation. Baseline corticosterone (CORT, the primary avian glucocorticoid) mediates daily and seasonal energetics, responds to changes in food availability, and has been linked to foraging behavior, making it a strong potential driver of individual variation in resource accrual and deposition. Working with a captive colony of white-winged scoters (Melanitta fusca deglandi), we aimed to causally determine whether variation in baseline CORT drives individual body mass gains mediated through fattening rate (plasma triglycerides corrected for body mass). We implanted individuals with each of three treatment pellets to elevate CORT within a baseline range in a randomized order: control, low dose of CORT, high dose of CORT, then blood sampled and recorded body mass over a two-week period to track changes in baseline CORT, body mass, and fattening rates. The high CORT treatment significantly elevated levels of plasma hormone for a short period of time within the biologically relevant, baseline range for this species, but importantly did not inhibit the function of the HPA (hypothalamic–pituitary–adrenal) axis. Furthermore, an elevation in baseline CORT resulted in a consistent increase in body mass throughout the trial period compared to controls. This is some of the first empirical evidence demonstrating that elevations of baseline CORT within a biologically relevant range have a causal, direct, and positive influence on changes in body mass.

  14. Baseline glucocorticoids are drivers of body mass gain in a diving seabird.

    Science.gov (United States)

    Hennin, Holly L; Wells-Berlin, Alicia M; Love, Oliver P

    2016-03-01

    Life-history trade-offs are influenced by variation in individual state, with individuals in better condition often completing life-history stages with greater success. Although resource accrual significantly impacts key life-history decisions such as the timing of reproduction, little is known about the underlying mechanisms driving resource accumulation. Baseline corticosterone (CORT, the primary avian glucocorticoid) mediates daily and seasonal energetics, responds to changes in food availability, and has been linked to foraging behavior, making it a strong potential driver of individual variation in resource accrual and deposition. Working with a captive colony of white-winged scoters (Melanitta fusca deglandi), we aimed to causally determine whether variation in baseline CORT drives individual body mass gains mediated through fattening rate (plasma triglycerides corrected for body mass). We implanted individuals with each of three treatment pellets to elevate CORT within a baseline range in a randomized order: control, low dose of CORT, high dose of CORT, then blood sampled and recorded body mass over a two-week period to track changes in baseline CORT, body mass, and fattening rates. The high CORT treatment significantly elevated levels of plasma hormone for a short period of time within the biologically relevant, baseline range for this species, but importantly did not inhibit the function of the HPA (hypothalamic-pituitary-adrenal) axis. Furthermore, an elevation in baseline CORT resulted in a consistent increase in body mass throughout the trial period compared to controls. This is some of the first empirical evidence demonstrating that elevations of baseline CORT within a biologically relevant range have a causal, direct, and positive influence on changes in body mass.

  15. Functional Testing Protocols for Commercial Building Efficiency Baseline Modeling Software

    OpenAIRE

    Jump, David

    2014-01-01

    This document describes procedures for testing and validating proprietary baseline energy modeling software accuracy in predicting energy use over the period of interest, such as a month or a year. The procedures are designed according to the methodology used for public domain baselining software in another LBNL report that was (like the present report) prepared for Pacific Gas and Electric Company: ?Commercial Building Energy Baseline Modeling Software: Performance Metrics and Method Testing...

  16. Site Outcomes Baseline Multi Year Work Plan Volume 1, River Corridor Restoration Baseline

    International Nuclear Information System (INIS)

    Wintczak, T.M.

    2001-01-01

    The River Corridor Restoration volume is a compilation of Hanford Site scope, which excludes the approximately 194 km 2 Central Plateau. The River Corridor scope is currently contractually assigned to Fluor Hanford, Bechtel Hanford, inc., DynCorp, and Pacific Northwest National Laboratory, and others. The purpose of this project specification is to provide an overall scoping document for the River Corridor Restoration volume, and to provide a link with the overall Hanford Site River Corridor scope. Additionally, this specification provides an integrated and consolidated source of information for the various scopes, by current contract, for the River Corridor Restoration Baseline. It identifies the vision, mission, and goals, as well as the operational history of the Hanford Site, along with environmental setting and hazards

  17. Baseline inventory data recommendations for National Wildlife Refuges

    Data.gov (United States)

    Department of the Interior — The Baseline Inventory Team recommends that each refuge have available abiotic “data layers” for topography, aerial photography, hydrography, soils, boundaries, and...

  18. Coverage, adherence and costs of intermittent preventive treatment of malaria in children employing different delivery strategies in Jasikan, Ghana.

    Directory of Open Access Journals (Sweden)

    Edith Patouillard

    Full Text Available Intermittent preventive treatment of malaria in children (IPTc involves the administration of a course of anti-malarial drugs at specified time intervals to children at risk of malaria regardless of whether or not they are known to be infected. IPTc provides a high level of protection against uncomplicated and severe malaria, with monthly sulphadoxine-pyrimethamine plus amodiaquine (SP&AQ and sulphadoxine-pyrimethamine plus piperaquine being the most efficacious regimens. A key challenge is the identification of a cost-effective delivery strategy.A community randomized trial was undertaken in Jasikan district, Ghana to assess IPTc effectiveness and costs using SP&AQ delivered in three different ways. Twelve villages were randomly selected to receive IPTc from village health workers (VHWs or facility-based nurses working at health centres' outpatient departments (OPD or EPI outreach clinics. Children aged 3 to 59 months-old received one IPT course (three doses in May, June, September and October. Effectiveness was measured in terms of children covered and adherent to a course and delivery costs were calculated in financial and economic terms using an ingredient approach from the provider perspective.The economic cost per child receiving at least the first dose of all 4 courses was US$4.58 when IPTc was delivered by VHWs, US$4.93 by OPD nurses and US$ 5.65 by EPI nurses. The unit economic cost of receiving all 3 doses of all 4 courses was US$7.56 and US$8.51 when IPTc was delivered by VHWs or facility-based nurses respectively. The main cost driver for the VHW delivery was supervision, reflecting resources used for travelling to more remote communities rather than more intense supervision, and for OPD and EPI delivery, it was the opportunity cost of the time spent by nurses in dispensing IPTc.VHWs achieve higher IPTc coverage and adherence at lower costs than facility-based nurses in Jasikan district, Ghana.ClinicalTrials.gov NCT00119132.

  19. Routine delivery of artemisinin-based combination treatment at fixed health facilities reduces malaria prevalence in Tanzania: an observational study

    Directory of Open Access Journals (Sweden)

    Khatib Rashid A

    2012-04-01

    Full Text Available Abstract Background Artemisinin-based combination therapy (ACT has been promoted as a means to reduce malaria transmission due to their ability to kill both asexual blood stages of malaria parasites, which sustain infections over long periods and the immature derived sexual stages responsible for infecting mosquitoes and onward transmission. Early studies reported a temporal association between ACT introduction and reduced malaria transmission in a number of ecological settings. However, these reports have come from areas with low to moderate malaria transmission, been confounded by the presence of other interventions or environmental changes that may have reduced malaria transmission, and have not included a comparison group without ACT. This report presents results from the first large-scale observational study to assess the impact of case management with ACT on population-level measures of malaria endemicity in an area with intense transmission where the benefits of effective infection clearance might be compromised by frequent and repeated re-infection. Methods A pre-post observational study with a non-randomized comparison group was conducted at two sites in Tanzania. Both sites used sulphadoxine-pyrimethamine (SP monotherapy as a first-line anti-malarial from mid-2001 through 2002. In 2003, the ACT, artesunate (AS co-administered with SP (AS + SP, was introduced in all fixed health facilities in the intervention site, including both public and registered non-governmental facilities. Population-level prevalence of Plasmodium falciparum asexual parasitaemia and gametocytaemia were assessed using light microscopy from samples collected during representative household surveys in 2001, 2002, 2004, 2005 and 2006. Findings Among 37,309 observations included in the analysis, annual asexual parasitaemia prevalence in persons of all ages ranged from 11% to 28% and gametocytaemia prevalence ranged from Interpretation The introduction of ACT at

  20. Tank waste remediation system technical baseline summary description

    International Nuclear Information System (INIS)

    Raymond, R.E.

    1998-01-01

    This document is one of the tools used to develop and control the mission work as depicted in the included figure. This Technical Baseline Summary Description document is the top-level tool for management of the Technical Baseline for waste storage operations

  1. The 2014 ALMA Long Baseline Campaign : An Overview

    NARCIS (Netherlands)

    ALMA Partnership, [Unknown; Fomalont, E. B.; Vlahakis, C.; Corder, S.; Remijan, A.; Barkats, D.; Lucas, R.; Hunter, T. R.; Brogan, C. L.; Asaki, Y.; Matsushita, S.; Dent, W. R. F.; Hills, R. E.; Phillips, N.; Richards, A. M. S.; Cox, P.; Amestica, R.; Broguiere, D.; Cotton, W.; Hales, A. S.; Hiriart, R.; Hirota, A.; Hodge, J. A.; Impellizzeri, C. M. V.; Kern, J.; Kneissl, R.; Liuzzo, E.; Marcelino, N.; Marson, R.; Mignano, A.; Nakanishi, K.; Nikolic, B.; Perez, J. E.; Pérez, L. M.; Toledo, I.; Aladro, R.; Butler, B.; Cortes, J.; Cortes, P.; Dhawan, V.; Di Francesco, J.; Espada, D.; Galarza, F.; Garcia-Appadoo, D.; Guzman-Ramirez, L.; Humphreys, E. M.; Jung, T.; Kameno, S.; Laing, R. A.; Leon, S.; Mangum, J.; Marconi, G.; Nagai, H.; Nyman, L.-A.; Radiszcz, M.; Rodón, J. A.; Sawada, T.; Takahashi, S.; Tilanus, R. P. J.; van Kempen, T.; Vila Vilaro, B.; Watson, L. C.; Wiklind, T.; Gueth, F.; Tatematsu, K.; Wootten, A.; Castro-Carrizo, A.; Chapillon, E.; Dumas, G.; de Gregorio-Monsalvo, I.; Francke, H.; Gallardo, J.; Garcia, J.; Gonzalez, S.; Hibbard, J. E.; Hill, T.; Kaminski, T.; Karim, A.; Krips, M.; Kurono, Y.; Lopez, C.; Martin, S.; Maud, L.; Morales, F.; Pietu, V.; Plarre, K.; Schieven, G.; Testi, L.; Videla, L.; Villard, E.; Whyborn, N.; Alves, F.; Andreani, P.; Avison, A.; Barta, M.; Bedosti, F.; Bendo, G. J.; Bertoldi, F.; Bethermin, M.; Biggs, A.; Boissier, J.; Brand, J.; Burkutean, S.; Casasola, V.; Conway, J.; Cortese, L.; Dabrowski, B.; Davis, T. A.; Diaz Trigo, M.; Fontani, F.; Franco-Hernandez, R.; Fuller, G.; Galvan Madrid, R.; Giannetti, A.; Ginsburg, A.; Graves, S. F.; Hatziminaoglou, E.; Hogerheijde, M.; Jachym, P.; Jimenez Serra, I.; Karlicky, M.; Klaasen, P.; Kraus, M.; Kunneriath, D.; Lagos, C.; Longmore, S.; Leurini, S.; Maercker, M.; Magnelli, B.; Marti Vidal, I.; Massardi, M.; Maury, A.; Muehle, S.; Muller, S.; Muxlow, T.; O’Gorman, E.; Paladino, R.; Petry, D.; Pineda, J.; Randall, S.; Richer, J. S.; Rossetti, A.; Rushton, A.; Rygl, K.; Sanchez Monge, A.; Schaaf, R.; Schilke, P.; Stanke, T.; Schmalzl, M.; Stoehr, F.; Urban, S.; van Kampen, E.; Vlemmings, W.; Wang, K.; Wild, W.; Yang, Y.; Iguchi, S.; Hasegawa, T.; Saito, M.; Inatani, J.; Mizuno, N.; Asayama, S.; Kosugi, G.; Morita, K.-I.; Chiba, K.; Kawashima, S.; Okumura, S. K.; Ohashi, N.; Ogasawara, R.; Sakamoto, S.; Noguchi, T.; Huang, Y.-D.; Liu, S.-Y.; Kemper, F.; Koch, P. M.; Chen, M.-T.; Chikada, Y.; Hiramatsu, M.; Iono, D.; Shimojo, M.; Komugi, S.; Kim, J.; Lyo, A.-R.; Muller, E.; Herrera, C.; Miura, R. E.; Ueda, J.; Chibueze, J.; Su, Y.-N.; Trejo-Cruz, A.; Wang, K.-S.; Kiuchi, H.; Ukita, N.; Sugimoto, M.; Kawabe, R.; Hayashi, M.; Miyama, S.; Ho, P. T. P.; Kaifu, N.; Ishiguro, M.; Beasley, A. J.; Bhatnagar, S.; Braatz, J. A., III; Brisbin, D. G.; Brunetti, N.; Carilli, C.; Crossley, J. H.; D’Addario, L.; Donovan Meyer, J. L.; Emerson, D. T.; Evans, A. S.; Fisher, P.; Golap, K.; Griffith, D. M.; Hale, A. E.; Halstead, D.; Hardy, E. J.; Hatz, M. C.; Holdaway, M.; Indebetouw, R.; Jewell, P. R.; Kepley, A. A.; Kim, D.-C.; Lacy, M. D.; Leroy, A. K.; Liszt, H. S.; Lonsdale, C. J.; Matthews, B.; McKinnon, M.; Mason, B. S.; Moellenbrock, G.; Moullet, A.; Myers, S. T.; Ott, J.; Peck, A. B.; Pisano, J.; Radford, S. J. E.; Randolph, W. T.; Rao Venkata, U.; Rawlings, M. G.; Rosen, R.; Schnee, S. L.; Scott, K. S.; Sharp, N. K.; Sheth, K.; Simon, R. S.; Tsutsumi, T.; Wood, S. J.

    2015-01-01

    A major goal of the Atacama Large Millimeter/submillimeter Array (ALMA) is to make accurate images with resolutions of tens of milliarcseconds, which at submillimeter (submm) wavelengths requires baselines up to ∼15 km. To develop and test this capability, a Long Baseline Campaign (LBC) was carried

  2. Idaho National Laboratory’s Greenhouse Gas FY08 Baseline

    Energy Technology Data Exchange (ETDEWEB)

    Jennifer D. Morton

    2010-09-01

    s baseline GHG inventory: • Electricity is the largest contributor to INL’s GHG inventory, with over 50% of the net anthropogenic CO2e emissions • Other sources with high emissions were stationary combustion, fugitive emissions from the onsite landfill, mobile combustion (fleet fuels) and the employee commute • Sources with low emissions were contracted waste disposal, wastewater treatment (onsite and contracted) and fugitive emissions from refrigerants. This report details the methods behind quantifying INL’s GHG inventory and discusses lessons learned on better practices by which information important to tracking GHGs can be tracked and recorded. It is important to stress that the methodology behind this inventory followed guidelines that have not yet been formally adopted. Thus, some modification of the conclusions may be necessary as additional guidance is received. Further, because this report differentiates between those portions of the INL that are managed and operated by the Battelle Energy Alliance (BEA) and those managed by other contractors, it includes only that large proportion of Laboratory activities overseen by BEA. It is assumed that other contractors will provide similar reporting for those activities they manage, where appropriate.

  3. Idaho National Laboratory’s Greenhouse Gas FY08 Baseline

    Energy Technology Data Exchange (ETDEWEB)

    Jennifer D. Morton

    2011-06-01

    A greenhouse gas (GHG) inventory is a systematic attempt to account for the production and release of certain gasses generated by an institution from various emission sources. The gasses of interest are those which have become identified by climate science as related to anthropogenic global climate change. This document presents an inventory of GHGs generated during fiscal year (FY) 2008 by Idaho National Laboratory (INL), a Department of Energy (DOE)-sponsored entity, located in southeastern Idaho. Concern about the environmental impact of GHGs has grown in recent years. This, together with a desire to decrease harmful environmental impacts, would be enough to encourage the calculation of a baseline estimate of total GHGs generated at INL. Additionally, INL has a desire to see how its emissions compare with similar institutions, including other DOE national laboratories. Executive Order 13514 requires that federal agencies and institutions document reductions in GHG emissions in the future, and such documentation will require knowledge of a baseline against which reductions can be measured. INL's FY08 GHG inventory was calculated according to methodologies identified in federal GHG guidance documents using operational control boundaries. It measures emissions generated in three Scopes: (1) INL emissions produced directly by stationary or mobile combustion and by fugitive emissions, (2) the share of emissions generated by entities from which INL purchased electrical power, and (3) indirect or shared emissions generated by outsourced activities that benefit INL (occur outside INL's organizational boundaries but are a consequence of INL's activities). This inventory found that INL generated a total of 113,049 MT of CO2-equivalent emissions during FY08. The following conclusions were made from looking at the results of the individual contributors to INL's baseline GHG inventory: (1) Electricity (including the associated transmission and

  4. Therapeutic efficacy of artemether-lumefantrine combination in the treatment of uncomplicated malaria among children under five years of age in three ecological zones in Ghana

    Directory of Open Access Journals (Sweden)

    Abuaku Benjamin

    2012-11-01

    Full Text Available Abstract Background In 2008, artemether - lumefantrine (AL and dihydroartemisinin - piperaquine (DHAP were added to artesunate - amodiaquine (AS-AQ as first-line drugs for uncomplicated malaria in Ghana. The introduction of new drugs calls for continuous monitoring of these drugs to provide timely information on trends of their efficacy and safety to enhance timely evidence-based decision making by the National Malaria Control Programme. In this regard, the therapeutic efficacy of AL was monitored from September 2010 to April 2011 in four sentinel sites representing the three main ecological zones of the country. Methods The study was a one-arm prospective evaluation of clinical and parasitological responses to directly observed treatment for uncomplicated malaria among children aged 6 months to 59 months using the 2009 WHO protocol for surveillance of anti-malarial drug efficacy. Children recruited into the study received weight-based 20/120 mg AL at 0, 8, 24, 36, 48, and 60 hrs. Parasitaemia levels were assessed on days 2, 3, 7, 14, 21, 28, and at any time a study child was brought to the clinic with fever. Results A total of 175 children were enrolled into the study: 56 in the savanna zone, 78 in the forest zone and 41 in the coastal zone. Per-protocol analysis showed that the overall PCR-corrected cure rates on day 14 and day 28 were 96.5% (95% CI: 92.1, 98.6 and 95.4% (95% CI: 90.3, 98.0, respectively, with statistically significant differences between the ecological zones. The 90.4% day-28 cure rate observed in the savannah zone (95% CI: 78.2, 96.4 was significantly the lowest compared with 100% (95% CI: 93.2, 99.9 in the forest zone and 93.8% (95% CI: 77.8, 98.9 in the coastal zone (P = 0.017. Fever and parasite clearance were slower among children enrolled in the savannah zone. Gametocytaemia after day-3 post-treatment was rare in all the zones. Conclusions The study has shown that AL remains efficacious in Ghana with

  5. Extracting Baseline Electricity Usage Using Gradient Tree Boosting

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Taehoon [Ulsan Nat. Inst. of Sci. & Tech., Ulsan (South Korea); Lee, Dongeun [Ulsan Nat. Inst. of Sci. & Tech., Ulsan (South Korea); Choi, Jaesik [Ulsan Nat. Inst. of Sci. & Tech., Ulsan (South Korea); Spurlock, Anna [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Sim, Alex [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Todd, Annika [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Wu, Kesheng [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

    2016-05-05

    To understand how specific interventions affect a process observed over time, we need to control for the other factors that influence outcomes. Such a model that captures all factors other than the one of interest is generally known as a baseline. In our study of how different pricing schemes affect residential electricity consumption, the baseline would need to capture the impact of outdoor temperature along with many other factors. In this work, we examine a number of different data mining techniques and demonstrate Gradient Tree Boosting (GTB) to be an effective method to build the baseline. We train GTB on data prior to the introduction of new pricing schemes, and apply the known temperature following the introduction of new pricing schemes to predict electricity usage with the expected temperature correction. Our experiments and analyses show that the baseline models generated by GTB capture the core characteristics over the two years with the new pricing schemes. In contrast to the majority of regression based techniques which fail to capture the lag between the peak of daily temperature and the peak of electricity usage, the GTB generated baselines are able to correctly capture the delay between the temperature peak and the electricity peak. Furthermore, subtracting this temperature-adjusted baseline from the observed electricity usage, we find that the resulting values are more amenable to interpretation, which demonstrates that the temperature-adjusted baseline is indeed effective.

  6. Emotion-focused therapy for social anxiety disorder: Results from a multiple-baseline study.

    Science.gov (United States)

    Shahar, Ben; Bar-Kalifa, Eran; Alon, Eve

    2017-03-01

    The purpose of the present study was to evaluate the efficacy of emotion-focused therapy (EFT) for adults suffering from social anxiety disorder (SAD). Using a nonconcurrent multiple-baseline design, 12 patients (mean age = 26.75 years, SD = 5.15; 7 males) meeting criteria for SAD were treated with up to 28 sessions of EFT. EFT was based on an empathic relationship, 2-chair work for self-criticism, empty-chair work for unresolved feelings, and focusing. Patients were randomized to wait 4, 8, or 12 weeks between the intake and the first therapy session. Intake assessment included the MINI International Neuropsychiatric Interview (MINI; Sheehan et al. 1998), the clinician-administered Liebowitz Social Anxiety Scale (LSAS; Liebowitz, 1987), and various self-report questionnaires. The LSAS was also administered at the end of the baseline period and at posttreatment. The MINI was administered again at posttreatment. Self-reports were administered throughout the baseline, before each therapy session, and at 6-month and 12-month follow-ups. One patient dropped out prematurely. Of the 11 completers, 7 did not meet criteria for SAD at the end of treatment. Intent-to-treat analysis showed that LSAS scores did not change during baseline, significantly improved during treatment (Cohen's d = -2.37), and remained improved during follow-up. Mixed regression models showed that SAD symptoms and self-criticism did not change during baseline, significantly improved during treatment, and remained improved during follow-up. Self-reassurance improved significantly during the follow-up phase. This study provides initial evidence supporting the efficacy of EFT for SAD. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  7. Dynamic baseline detection method for power data network service

    Science.gov (United States)

    Chen, Wei

    2017-08-01

    This paper proposes a dynamic baseline Traffic detection Method which is based on the historical traffic data for the Power data network. The method uses Cisco's NetFlow acquisition tool to collect the original historical traffic data from network element at fixed intervals. This method uses three dimensions information including the communication port, time, traffic (number of bytes or number of packets) t. By filtering, removing the deviation value, calculating the dynamic baseline value, comparing the actual value with the baseline value, the method can detect whether the current network traffic is abnormal.

  8. Impact of baseline severity of aortic valve stenosis on effect of intensive lipid lowering therapy (from the SEAS study)

    DEFF Research Database (Denmark)

    Gerdts, Eva; Rossebø, Anne Bjørhovde; Pedersen, Terje Rolf

    2010-01-01

    Retrospective studies have suggested a beneficial effect of lipid-lowering treatment on the progression of aortic stenosis (AS) in milder stages of the disease. In the randomized, placebo-controlled Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study, 4.3 years of combined treatment...... with simvastatin 40 mg and ezetimibe 10 mg did not reduce aortic valve events (AVEs), while ischemic cardiovascular events (ICEs) were significantly reduced in the overall study population. However, the impact of baseline AS severity on treatment effect has not been reported. Baseline and outcomes data in 1...

  9. CryoSat SAR/SARin Level1b products: assessment of BaselineC and improvements towards BaselineD

    Science.gov (United States)

    Scagliola, Michele; Fornari, Marco; Bouffard, Jerome; Parrinello, Tommaso

    2017-04-01

    CryoSat was launched on the 8th April 2010 and is the first European ice mission dedicated to the monitoring of precise changes in the thickness of polar ice sheets and floating sea ice. Cryosat carries an innovative radar altimeter called the Synthetic Aperture Interferometric Altimeter (SIRAL), that transmits pulses at a high pulse repetition frequency thus making the received echoes phase coherent and suitable for azimuth processing. This allows to reach a significantly improved along track resolution with respect to traditional pulse-width limited altimeters. CryoSat is the first altimetry mission operating in SAR mode and continuous improvements in the Level1 Instrument Processing Facility (IPF1) are being identified, tested and validated in order to improve the quality of the Level1b products. The current IPF, Baseline C, was released in operation in April 2015 and the second CryoSat reprocessing campaign was jointly initiated, taking benefit of the upgrade implemented in the IPF1 processing chain but also of some specific configurations for the calibration corrections. In particular, the CryoSat Level1b BaselineC products generated in the framework of the second reprocessing campaign include refined information for what concerns the mispointing angles and the calibration corrections. This poster will thus detail thus the evolutions that are currently planned for the CryoSat BaselineD SAR/SARin Level1b products and the corresponding quality improvements that are expected.

  10. Information architecture. Volume 2, Part 1: Baseline analysis summary

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1996-12-01

    The Department of Energy (DOE) Information Architecture, Volume 2, Baseline Analysis, is a collaborative and logical next-step effort in the processes required to produce a Departmentwide information architecture. The baseline analysis serves a diverse audience of program management and technical personnel and provides an organized way to examine the Department`s existing or de facto information architecture. A companion document to Volume 1, The Foundations, it furnishes the rationale for establishing a Departmentwide information architecture. This volume, consisting of the Baseline Analysis Summary (part 1), Baseline Analysis (part 2), and Reference Data (part 3), is of interest to readers who wish to understand how the Department`s current information architecture technologies are employed. The analysis identifies how and where current technologies support business areas, programs, sites, and corporate systems.

  11. Baseline assessment of fish communities of the Flower Garden Banks

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — The work developed baseline information on fish and benthic communities within the Flower Garden Banks National Marine Sanctuary (FGBNMS). Surveys employed diving,...

  12. Continuous baseline growth and monitoring for guided wave SHM

    Science.gov (United States)

    Putkis, Osvaldas; Croxford, Anthony J.

    2013-05-01

    It has been shown by many authors that temperature effect compensation is a necessity for the realization of a reliable structural health monitoring (SHM) system. However, there exist practical issues related to the acquisition of baseline signals, required for temperature compensation methods to work effectively, such as degenerate baseline signals recorded at the same temperature and a long acquisition period before monitoring is started. An alternative approach for the acquisition of baseline signals is presented in this paper. The algorithm makes the acquisition an evolutionary process, integrated in the damage detection procedures. The algorithm is shown to be successful in generating a concise set of baselines that guarantees efficient performance of temperature compensation methods, leading to computation time and computer memory savings. Its capabilities in detecting simulated abrupt and slowly evolving damages have also been tested.

  13. Human Dimensions Baseline Assessment of th