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Search Results: 1 - 10 of 1954 matches for " Pharmacometabolomics Research Network "
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Pharmacometabolomics of Response to Sertraline and to Placebo in Major Depressive Disorder – Possible Role for Methoxyindole Pathway
Hongjie Zhu, Mikhail B. Bogdanov, Stephen H. Boyle, Wayne Matson, Swati Sharma, Samantha Matson, Erik Churchill, Oliver Fiehn, John A. Rush, Ranga R. Krishnan, Eve Pickering, Marielle Delnomdedieu, Rima Kaddurah-Daouk, Pharmacometabolomics Research Network
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0068283
Abstract: Therapeutic response to selective serotonin (5-HT) reuptake inhibitors in Major Depressive Disorder (MDD) varies considerably among patients, and the onset of antidepressant therapeutic action is delayed until after 2 to 4 weeks of treatment. The objective of this study was to analyze changes within methoxyindole and kynurenine (KYN) branches of tryptophan pathway to determine whether differential regulation within these branches may contribute to mechanism of variation in response to treatment. Metabolomics approach was used to characterize early biochemical changes in tryptophan pathway and correlated biochemical changes with treatment outcome. Outpatients with MDD were randomly assigned to sertraline (n = 35) or placebo (n = 40) in a double-blind 4-week trial; response to treatment was measured using the 17-item Hamilton Rating Scale for Depression (HAMD17). Targeted electrochemistry based metabolomic platform (LCECA) was used to profile serum samples from MDD patients. The response rate was slightly higher for sertraline than for placebo (21/35 [60%] vs. 20/40 [50%], respectively, χ2(1) = 0.75, p = 0.39). Patients showing a good response to sertraline had higher pretreatment levels of 5-methoxytryptamine (5-MTPM), greater reduction in 5-MTPM levels after treatment, an increase in 5-Methoxytryptophol (5-MTPOL) and Melatonin (MEL) levels, and decreases in the (KYN)/MEL and 3-Hydroxykynurenine (3-OHKY)/MEL ratios post-treatment compared to pretreatment. These changes were not seen in the patients showing poor response to sertraline. In the placebo group, more favorable treatment outcome was associated with increases in 5-MTPOL and MEL levels and significant decreases in the KYN/MEL and 3-OHKY/MEL; changes in 5-MTPM levels were not associated with the 4-week response. These results suggest that recovery from a depressed state due to treatment with drug or with placebo could be associated with preferential utilization of serotonin for production of melatonin and 5-MTPOL.
Pharmacometabolomics Reveals Racial Differences in Response to Atenolol Treatment
William R. Wikoff, Reginald F. Frye, Hongjie Zhu, Yan Gong, Stephen Boyle, Erik Churchill, Rhonda M. Cooper-Dehoff, Amber L. Beitelshees, Arlene B. Chapman, Oliver Fiehn, Julie A. Johnson, Rima Kaddurah-Daouk, Pharmacometabolomics Research Network
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0057639
Abstract: Antihypertensive drugs are among the most commonly prescribed drugs for chronic disease worldwide. The response to antihypertensive drugs varies substantially between individuals and important factors such as race that contribute to this heterogeneity are poorly understood. In this study we use metabolomics, a global biochemical approach to investigate biochemical changes induced by the beta-adrenergic receptor blocker atenolol in Caucasians and African Americans. Plasma from individuals treated with atenolol was collected at baseline (untreated) and after a 9 week treatment period and analyzed using a GC-TOF metabolomics platform. The metabolomic signature of atenolol exposure included saturated (palmitic), monounsaturated (oleic, palmitoleic) and polyunsaturated (arachidonic, linoleic) free fatty acids, which decreased in Caucasians after treatment but were not different in African Americans (p<0.0005, q<0.03). Similarly, the ketone body 3-hydroxybutyrate was significantly decreased in Caucasians by 33% (p<0.0001, q<0.0001) but was unchanged in African Americans. The contribution of genetic variation in genes that encode lipases to the racial differences in atenolol-induced changes in fatty acids was examined. SNP rs9652472 in LIPC was found to be associated with the change in oleic acid in Caucasians (p<0.0005) but not African Americans, whereas the PLA2G4C SNP rs7250148 associated with oleic acid change in African Americans (p<0.0001) but not Caucasians. Together, these data indicate that atenolol-induced changes in the metabolome are dependent on race and genotype. This study represents a first step of a pharmacometabolomic approach to phenotype patients with hypertension and gain mechanistic insights into racial variability in changes that occur with atenolol treatment, which may influence response to the drug.
The Prevention Research Centers Healthy Aging Research Network
The Healthy Aging Research Network Writing Group
Preventing Chronic Disease , 2005,
Abstract: BackgroundThe Prevention Research Centers Healthy Aging Research Network (PRC–HAN), funded by the Centers for Disease Control and Prevention’s (CDC’s) Healthy Aging program, was created in 2001 to help develop partnerships and create a research agenda that promotes healthy aging. The nine universities that participate in the network use their expertise in aging research to collaborate with their communities and other partners to develop and implement health promotion interventions for older adults at the individual, organizational, environmental, and policy levels.ContextThe population of older adults in the United States is growing rapidly; approximately 20% of Americans will be aged 65 years or older by 2030. The health and economic impact of an aging society compel the CDC and the public health community to place increased emphasis on preventing unnecessary disease, disability, and injury among older Americans.MethodsThe PRC–HAN has a broad research agenda that addresses health-promoting skills and behaviors, disease and syndrome topics, and knowledge domains. The network chose physical activity for older adults as its initial focus for research and has initiated two networkwide projects: a comprehensive, multisite survey that collected information on the capacity, content, and accessibility of physical activity programs for older adults and a peer-reviewed publication that describes the role of public health in promoting physical activity among older adults. In addition to participating in the core research area, each network member works independently with its community committee on PRC–HAN activities.ConsequencesAs a result, the network is 1) expanding prevention research for older adults and their communities; 2) promoting the translation and dissemination of findings to key stakeholders; 3) strengthening PRC–HAN capacity through partnerships and expanded funding; and 4) stimulating the adoption of policies and programs by engaging policymakers, planners, and practitioners. In 2003, the PRC–HAN initiated an internal evaluation to better define the network’s contributions to healthy aging, formalize internal processes, and better equip itself to serve as a model for other PRC thematic networks. The PRC–HAN is conducting a pilot evaluation for eventual inclusion in the PRC national evaluation.InterpretationThe PRC–HAN has established itself as an effective research network to promote healthy aging. It has developed trust and mutual respect among participants, forged strong ties to local communities, and shown the ability to combine its expertise in
Building capacity for clinical research in developing countries: the INDOX cancer research network experience
Raghib Ali,Alexander Finlayson,on behalf of the INDOX Cancer Research Network
Global Health Action , 2012, DOI: 10.3402/gha.v5i0.17288
Abstract: Transnational Organisations increasingly prioritise the need to support local research capacity in low and middle income countries in order that local priorities are addressed with due consideration of contextual issues. There remains limited evidence on the best way in which this should be done or the ways in which external agencies can support this process.We present an analysis of the learning from the INDOX Research Network, established in 2005 as a partnership between the Institute of Cancer Medicine at the University of Oxford and India's top nine comprehensive cancer centres. INDOX aims to enable Indian centres to conduct clinical research to the highest international standards; to ensure that trials are developed to address the specific needs of Indian patients by involving Indian investigators from the outset; and to provide the training to enable them to design and conduct their own studies. We report on the implementation, outputs and challenges of simultaneously trying to build capacity and deliver meaningful research output.
Patterns of Use and Outcomes in Patients Treated with Etravirine in the HIV Research Network
Kelly Gebo,Cindy Voss,Joseph Mrus,HIV Research Network
AIDS Research and Treatment , 2013, DOI: 10.1155/2013/492831
Abstract: This observational analysis examined the clinical outcomes of patients receiving etravirine-(ETR-) based therapy, particularly with protease inhibitors (PIs) other than darunavir (DRV) and with raltegravir (RAL). Data included treatment-experienced adults in the HIV Research Network who began ETR-containing antiretroviral regimens in 2008–2010. The primary objective was to assess 6-month outcomes (durability, i.e., still on an ETR-containing regimen; change in CD4+ cell count and HIV-1 RNA <400?copies/mL). The cohort included 587 patients receiving ETR; 42% of ETR use was in patients not on DRV/ritonavir (r). Patients receiving ETR plus DRV/r had longer durability versus those on ETR plus a PI other than DRV/r at months 6 (91.2% versus 85.5%) and 12 (77.4% versus 65.2%), respectively. Patients on regimens with a PI other than DRV/r were the least likely to be receiving ETR at month 6 (85.5%) versus patients on other ETR-based regimens. Patients on regimens without a PI and without RAL had lower virologic suppression (month 6, 54.2%; month 12, 63.2%) versus patients on other ETR-based regimens. In a clinical care, nontrial setting, ETR was used in regimens without DRV/r. In this population, the 6-month response rates were similar and durable across all regimens, except when ETR was used without RAL and without a PI. 1. Introduction Aside from registrational trial data, there is limited information on the utilization and clinical outcomes of patients treated with etravirine-(ETR-) based therapy. To date, ETR has demonstrated high efficacy rates, as well as good tolerability and safety profiles [1, 2]. However, in most studies of ETR, including the Phase III trials, all patients also received darunavir/ritonavir (DRV/r). In the DUET 1 and DUET 2 trials, for example, 61% of patients receiving ETR 200?mg twice daily (bid) plus a background regimen that included DRV/r 600/100?mg bid achieved HIV-1 RNA <50 copies/mL at 48 weeks, compared with 40% of patients receiving placebo plus a background regimen that included DRV/r 600/100?mg bid [2]. Interestingly, in the GRACE (Gender, Race, And Clinical Experience) trial, which investigated the efficacy and safety of DRV/r plus an optimized background regimen that could include ETR in treatment-experienced patients, ETR use was associated with higher virologic response rates [3]. Despite encouraging data on the use of ETR plus DRV/r, limited data exist on the use of ETR with protease inhibitors (PIs) other than DRV/r, and with novel agents like raltegravir (RAL) [1, 4–6]. The few data that do exist are promising. The
A proposed approach in defining population-based rates of major injury from a trauma registry dataset: Delineation of hospital catchment areas (I)
Roxana Alexandrescu, Sarah J O'Brien, Ronan A Lyons, Fiona E Lecky, the Trauma Audit and Research Network
BMC Health Services Research , 2008, DOI: 10.1186/1472-6963-8-80
Abstract: We examined data from all hospitals reporting to TARN for continuity of numerator reporting; rates of completeness for patient postcodes, and clear denominator populations. We defined local market areas (>70% of patients originating from the same postcode district as the hospital). For relevant hospitals we assessed data quality: consistency of reporting, completeness of patient postcodes and for one selected hospital, North Staffordshire Royal Infirmary (NSRI), the capture rate of numerator data reporting. We used an established method based on patient flow to delineate market areas from hospitals discharges. We then assessed the potential competitors, and characterized these denominator areas. Finally we performed a denominator sensitivity analysis using a patient origin matrix based on Hospital Episodes Statistics (HES) to validate our approach.Sixteen hospitals met the data quality and patient flow criteria for numerator and denominator data, representing 12 hospital catchment areas across England. Data quality issues included fluctuations numbers of reported cases and poor completion of postcodes for some years. We found an overall numerator capture rate of 83.5% for the NSRI. In total we used 40,543 admissions to delineate hospital catchment areas. An average of 3.5 potential hospital competitors and 15.2 postcode districts per area were obtained. The patient origin matrix for NSRI confirmed the accuracy of the denominator/hospital catchment area from the patient flow analysis.Large national trauma registries, including TARN, hold suitable data for determining population-based injury rates. Patient postcodes from hospital discharge allow identification of denominator populations using a market area approach.In the United Kingdom, injury is the commonest cause of death in the first four decades of life and amongst the leading causes for ill-health. In 2004 in England and Wales 17,000 deaths due to injury (all causes) were registered. These represent only the ti
Prioritisation of patients on waiting lists for hip and knee arthroplasties and cataract surgery: Instruments validation
Alejandro Allepuz, Mireia Espallargues, Montse Moharra, Mercè Comas, Joan MV Pons, Research Group on Support Instruments – IRYSS Network
BMC Health Services Research , 2008, DOI: 10.1186/1472-6963-8-76
Abstract: Multicentre validation study which included orthopaedic surgeons and ophthalmologists from 10 hospitals. Participating doctors were asked to include all eligible patients placed in the waiting list for the procedures under study during the medical visit. Doctors assessed patients' priority through a visual analogue scale (VAS) and administered the prioritisation instrument. Information on socio-demographic data and health-related quality of life (HRQOL) (HUI3, EQ-5D, WOMAC and VF-14) was obtained through a telephone interview with patients. The correlation coefficients between the prioritisation instrument score and VAS and HRQOL were calculated. For the reliability study a self-administered questionnaire, which included hypothetic patients' scenarios, was sent via postal mail to the doctors. The priority of these scenarios was assessed through the prioritisation instrument. The intraclass correlation coefficient (ICC) between doctors was calculated.Correlations with VAS were strong for the AI (0.64, CI95%: 0.59–0.68) and for the CI (0.65, CI95%: 0.62–0.69), and moderate between the WOMAC and the AI (0.39, CI95%: 0.33–0.45) and the VF-14 and the CI (0.38, IC95%: 0.33–0.43). The results of the discriminant analysis were in general as expected. Inter-observer reliability was 0.79 (CI95%: 0.64–0.94) for the AI, and 0.79 (CI95%: 0.63–0.95) for the CI.The results show acceptable validity and reliability of the prioritisation instruments in establishing priority for surgery.Traditionally, the only explicit system to prioritise patients awaiting surgery has been the timing of the patient's inclusion in the waiting list, although various studies show how different factors may in practise influence the waiting period [1-3]. The lack of explicit prioritisation criteria that may cause patients with the same level of need to have very different waiting periods and the negative health effects of delay of surgery, further reinforce the necessity to develop instruments which enabl
Parenting and the decline of physical activity from age 9 to 15
RH Bradley, S McRitchie, RM Houts, P Nader, M O'Brien, the NICHD Early Child Care Research Network
International Journal of Behavioral Nutrition and Physical Activity , 2011, DOI: 10.1186/1479-5868-8-33
Abstract: Longitudinal analysis of 801 participants from 10 US sites in the NICHD Study of Early Child Care and Youth Development whose data included accelerometer-determined levels of moderate-to-vigorous physical activity (MVPA) between ages 9 and 15 years, as well as family process, BMI and demographic information. The sample included an even split of boys (49%) and girls (51%), was predominantly white (77%), and contained about 26% low income and 19% single parent families. The outcome measure was mean MVPA. It was based on 4 to 7 days of monitored physical activity.Boys with lower parental monitoring scores and more days of parental encouragement had significantly more minutes of MVPA at age 9 years. The effect of parental monitoring, however, was moderated by early puberty. High parental monitoring was associated with decreased activity levels for boys experiencing later puberty and increased activity for boy experiencing early puberty. Minutes of MVPA for boys living in the Midwest decreased at significantly faster rates than boys living in any other region; and boys in the South declined faster than boys in the West. Girls in the Midwest and South declined faster than girls in the West and Northeast. Among girls, more days of parental exercise and transportation to activities were associated with more MVPA per day at age 9. However, more parental transportation to activities and less monitoring was associated with faster linear declines in daughters' MVPA between the ages of 9 and 15 years. For girls who experienced puberty early, parental encouragement was associated with more MVPA.Parenting processes, such as monitoring and encouragement, as well as the parents' own level of physical activity, showed significant, but small, gender-specific associations with MVPA levels at age nine and the linear rate of decline in MVPA between ages 9 and 15.Several recent large-scale studies demonstrate a dramatic decline in moderate to vigorous physical activity during middle child
Brief Parenteral Nutrition Accelerates Weight Gain, Head Growth Even in Healthy VLBWs
Naho Morisaki, Mandy B. Belfort, Marie C. McCormick, Rintaro Mori, Hisashi Noma, Satoshi Kusuda, Masanori Fujimura, the Neonatal Research Network of Japan
PLOS ONE , 2014, DOI: 10.1371/journal.pone.0088392
Abstract: Introduction Whether parenteral nutrition benefits growth of very low birth weight (VLBW) preterm infants in the setting of rapid enteral feeding advancement is unclear. Our aim was to examine this issue using data from Japan, where enteral feeding typically advances at a rapid rate. Methods We studied 4005 hospitalized VLBW, very preterm (23–32 weeks' gestation) infants who reached full enteral feeding (100 ml/kg/day) by day 14, from 75 institutions in the Neonatal Research Network Japan (2003–2007). Main outcomes were weight gain, head growth, and extra-uterine growth restriction (EUGR, measurement <10th percentile for postmenstrual age) at discharge. Results 40% of infants received parenteral nutrition. Adjusting for maternal, infant, and institutional characteristics, infants who received parenteral nutrition had greater weight gain [0.09 standard deviation (SD), 95% CI: 0.02, 0.16] and head growth (0.16 SD, 95% CI: 0.05, 0.28); lower odds of EUGR by head circumference (OR 0.66, 95% CI: 0.49, 0.88). No statistically significant difference was seen in the proportion of infants with EUGR at discharge. SGA infants and infants who took more than a week until full feeding had larger estimates. Discussion Even in infants who are able to establish enteral nutrition within 2 weeks, deprivation of parenteral nutrition in the first weeks of life could lead to under nutrition, but infants who reached full feeding within one week benefit least. It is important to predict which infants are likely or not likely to advance on enteral feedings within a week and balance enteral and parenteral nutrition for these infants.
The Cost-Effectiveness and Value of Information of Three Influenza Vaccination Dosing Strategies for Individuals with Human Immunodeficiency Virus
Bohdan Nosyk, Behnam Sharif, Huiying Sun, Curtis Cooper, Aslam H. Anis, on behalf of the CIHR Canadian HIV Trials Network Influenza Vaccine Research Group
PLOS ONE , 2011, DOI: 10.1371/journal.pone.0027059
Abstract: Background Influenza vaccine immunogenicity is diminished in patients living with HIV/AIDS. We evaluated the cost-effectiveness and expected value of perfect information (EVPI) of three alternative influenza vaccine dosing strategies intended to increase immunogenicity in those patients. Methods A randomized, multi-centered, controlled, vaccine trial was conducted at 12 CIHR Canadian HIV Trials Network sites. Three dosing strategies with seasonal, inactivated trivalent, non-adjuvanted intramuscular vaccine were used in HIV infected adults: two standard doses over 28 days (Strategy A), two double doses over 28 days (Strategy B) and a single standard dose of influenza vaccine (Strategy C), administered prior to the 2008 influenza season. The comparator in our analysis was practice in the previous year, in which 82.8% of HIV/AIDS received standard-dose vaccination (Strategy D). A Markov cohort model was developed to estimate the monthly probability of Influenza-like Illness (ILI) over one influenza season. Costs and quality-adjusted life years, extrapolated to the lifetime of the hypothetical study cohorts, were estimated in calculating incremental cost-effectiveness ratios (ICER) and EVPI in conducting further research. Results 298 patients with median CD4 of 470 cells/μl and 76% with viral load suppression were randomized. Strategy C was the most cost-effective strategy for the overall trial population and for suppressed and unsuppressed individuals. Mean ICERs for Strategy A for unsuppressed patients could also be considered cost-effective. The level of uncertainty regarding the decision to implement strategy A versus C for unsuppressed individuals was high. The maximum acceptable cost of reducing decision uncertainty in implementing strategy A for individuals with unsuppressed pVL was $418,000 - below the cost of conducting a larger-scale trial. Conclusion Our results do not support a policy to implement increased antigen dose or booster dosing strategies with seasonal, inactivated trivalent, non-adjuvanted intramuscular vaccine for individuals with HIV in Canada. Trial Registration ClinicalTrials.gov NCT00764998.
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