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Using Molecular Markers to Help Predict Who Will Fail after Radical Prostatectomy  [PDF]
Gregory P. Swanson,David Quinn
Prostate Cancer , 2011, DOI: 10.1155/2011/290160
Abstract: Recent phase III trial data clearly demonstrate that adjuvant therapy can reduce recurrence and increase survival after prostatectomy for prostate cancer. There is great interest in being able to accurately predict who is at risk of failure to avoid treating those who may not benefit. The standard markers consisting of prostate specific antigen (PSA), Gleason score, and pathological stage are not very specific, so there is an unmet need for other markers to aid in prognostic stratification. Numerous studies have been conducted with various markers and more recently gene signatures, but it is unclear whether any of them are really useful. We conducted a comprehensive review of the literature to determine the current status of molecular markers in predicting outcome after radical prostatectomy. 1. Introduction Prostate specific antigen (PSA), stage (either clinical or pathological), and Gleason score are firmly established as prognostic indicators in prostate cancer. Individually and collectively, they predict for failure after radiation and surgery. The predictive value has been increased with more detailed information such as the addition of the detailed pathological findings of extraprostatic extension (EPE), positive margins, seminal vesicle involvement, and lymph node involvement. Various combinations of factors have been combined into tables, formulas, neural networks, and nomograms. While they are important tools in trying to predict failure, they are limited by the predictive ability of the factors themselves. For example, from a nomogram, a patient with a Gleason 7 (3 + 4) cancer with extraprostatic extension and positive margins, negative lymph nodes, negative seminal vesicles, and preoperative PSA of 8.2?ng/mL is predicted to have a 10-year recurrence rate of 20% [1]. Telling a patient that he has a 1 out of 5 chance of failing may or may not be reassuring. The absolute precision would be able to tell a patient whether he will fail (100%) or not (0%). The ultimate goal is to try to determine who will fail, not who may fail. The only way to try to approach that goal is with more precise markers than we currently have. One area of major promise in this regard is the greater individual cancer data that can be obtained from molecular markers. We already have seen an example of the benefit of a marker in prostate cancer. The addition of the biological marker PSA offers more precise information over stage and Gleason score alone. In breast cancer, the marker Her 2-neu has been shown to be not only an important prognostic marker, but also a target of
The WHO Collaborating Centre for Research and Control of Schistosomiasis at Niamey, Niger
Memórias do Instituto Oswaldo Cruz , 1997, DOI: 10.1590/S0074-02761997000500030
Abstract: the centre de recherche sur les méningites et les schistosomes (cermes) is a research institute depending on the organisation de coordination et de coopération pour la lutte contre les grandes endémies - a west african organization for public health - devoted to the studies on schistosomiasis and meningitis. the staff includes 32 persons with 11 scientists and one financial officer. the activities of the cermes involving schistosomiasis concern three research units: (a) ecology of human and animal schistosomiasis transmission; the cermes defined the different patterns of schistosomiasis transmission in niger (involving african dry savana); in this field, we have shown, (i) the existence of important variability in conditions of transmission of s. haematobium and, (ii) natural hybridization between parasitic species of the ruminants (s. bovis and s. curassoni) and genetic interaction between human and animal parasites; (b) definition of morbidity indicators usable for rapid assessment methods, for appraisal of the severity of the disease and for the evaluation of the efficiency of control methods; we have established the correlation between ultrasonographic data and some cheap and simple field indicators; (c) immune response and protective immunity induced by recombinant glutathion s-transferase (sm28, sb28 and sh28) in homologous and heterologous animal models including goats, sheep and non human primates (erythrocebus patas). in niger, we participate in all control programs against schistosomiasis to define control strategies, to supervise operations and to participate in their evaluation with external experts. international collaborations constitute a frame including four laboratories in africa and six laboratories in developed countries (europe and usa)
The WHO Collaborating Centre for Research and Control of Schistosomiasis at Niamey, Niger  [cached]
Chippaux J-P,Boulanger D,Brémond P,Campagne G
Memórias do Instituto Oswaldo Cruz , 1997,
Abstract: The Centre de Recherche sur les Méningites et les Schistosomes (CERMES) is a research institute depending on the Organisation de Coordination et de Coopération pour la lutte contre les Grandes Endémies - a West African Organization for Public Health - devoted to the studies on schistosomiasis and meningitis. The staff includes 32 persons with 11 scientists and one financial officer. The activities of the CERMES involving schistosomiasis concern three research units: (a) ecology of human and animal schistosomiasis transmission; the CERMES defined the different patterns of schistosomiasis transmission in Niger (involving African dry savana); in this field, we have shown, (i) the existence of important variability in conditions of transmission of S. haematobium and, (ii) natural hybridization between parasitic species of the ruminants (S. bovis and S. curassoni) and genetic interaction between human and animal parasites; (b) definition of morbidity indicators usable for rapid assessment methods, for appraisal of the severity of the disease and for the evaluation of the efficiency of control methods; we have established the correlation between ultrasonographic data and some cheap and simple field indicators; (c) immune response and protective immunity induced by recombinant glutathion S-transferase (Sm28, Sb28 and Sh28) in homologous and heterologous animal models including goats, sheep and non human primates (Erythrocebus patas). In Niger, we participate in all control programs against schistosomiasis to define control strategies, to supervise operations and to participate in their evaluation with external experts. International collaborations constitute a frame including four laboratories in Africa and six laboratories in developed countries (Europe and USA)
A cohort study to assess the new WHO Japanese encephalitis surveillance standards
Solomon,Tom; Thao,Thi Thu; Lewthwaite,Penny; Ooi,Mong How; Kneen,Rachel; Dung,Nguyen Minh; White,Nicholas;
Bulletin of the World Health Organization , 2008, DOI: 10.1590/S0042-96862008000300010
Abstract: objective: to assess the field-test version of the new who japanese encephalitis (je) surveillance standards. methods: we applied the clinical case definition of acute encephalitis syndrome (aes), laboratory diagnostic criteria and case classifications to patients with suspected central nervous system (cns) infections in southern viet nam. findings: of the 380 patients (149 children) recruited with suspected cns infections, 296 (96 children) met the aes case definition. 54 children were infected with je virus (jev), of whom 35 (65%) had aes, giving a sensitivity of 65% (95% ci: 56-73) and specificity of 39% (95% ci: 30-48). nine adults with jev presented with aes. 19 jev-infected children missed by surveillance included 10 with acute flaccid paralysis, two with flaccid hemiparesis and six with meningism only. altering the case definition to include limb paralysis and meningism improved sensitivity to 89% (95% ci: 83-95), while reducing specificity to 23% (95% ci: 15-30). six children that did not have aes on admission had reduced consciousness after admission. cerebrospinal fluid (csf) analysis diagnosed seven patients negative on serum analysis. five patients with neurological manifestations of dengue infection had jev antibodies in serum and would have been misdiagnosed had we not tested for dengue antibodies in parallel. conclusion: children infected with jev that presented with acute limb paralysis or neck stiffness only were missed by the surveillance standards, although some of them subsequently became encephalopathic. a footnote in the surveillance standards drawing attention to these presentations would be helpful. an acute csf sample is more sensitive and specific than an acute serum sample.
Pilot testing of WHO Child Growth Standards in Chandigarh: implications for India's child health programmes
Prinja,Shankar; Thakur,Jarnail Singh; Bhatia,Satpal Singh;
Bulletin of the World Health Organization , 2009, DOI: 10.1590/S0042-96862009000200013
Abstract: objective: to compare the prevalence of underweight as calculated from indian academy of paediatrics (iap) growth curves (based on the harvard scale) and the new who child growth standards. methods: we randomly selected 806 children under 6 years of age from 45 primary anganwadi (childcare) centres in chandigarh, punjab, india, that were chosen through multistage stratified random sampling. children were weighed, and their weight for age was calculated using iap curves and who growth references. nutritional status according to the who child growth standards was analysed using who anthro statistical software (beta version, 17 february 2006). the χ2 test was used to determine statistical significance at the 0.05 significance level. findings: the prevalence of underweight (z score less than -2) in the first 6 months of life was nearly 1.6 times higher when calculated in accordance with the new who standards rather than iap growth curves. for all ages combined, the estimated prevalence of underweight was 1.4 times higher when iap standards instead of the new who standards were used. similarly, the prevalence of underweight in both sexes combined was 14.5% higher when iap standards rather than the new who growth standards were applied (p < 0.001). by contrast, severe malnutrition estimated for both sexes were 3.8 times higher when the new who standards were used in place of iap standards (p < 0.001). conclusion: the new who growth standards will project a lower prevalence of overall underweight children and provide superior growth tracking than iap standards, especially in the first 6 months of life and among severely malnourished children.
Comparison of the Calibration Standards of Three Commercially Available Multiplex Kits for Human Cytokine Measurement to WHO Standards Reveals Striking Differences
Andreas Nechansky,Susanne Grunt,Ivan M. Roitt,Ralf Kircheis
Biomarker Insights , 2008,
Abstract: Serum parameters as indicators for the efficacy of therapeutic drugs are currently in the focus of intensive research. The induction of certain cytokines (or cytokine patterns) is known to be related to the status of the immune response e.g. in regulating the TH1/TH2 balance. Regarding their potential value as surrogate parameters in clinical trials and subsequently for the assignment of treatment effi cacy, the accurate and reliable determination of cytokines in patient serum is mandatory. Because serum samples are precious and limited, test methods—like the xMAP multiplex technology—that allow for the simultaneous determination of a variety of cytokines from only a small sample aliquot, can offer great advantages.We here have compared multiplex kits from three different manufactures and found striking differences upon standardizing using WHO standards for selected cytokines. We therefore extended our xMAP multiplex measurements investigations to an ex-vivo situation by testing serum samples and found that the cytokine amounts measured was critically influenced by the actual kit used. The presented data indicate that statements regarding the quantitive determination of cytokines—and therefore their use as biomarkers—in serum samples have to be interpreted with caution.
Implication of New WHO Growth Standards on Identification of Risk Factors and Estimated Prevalence of Malnutrition in Rural Malawian Infants  [PDF]
Marc-André Prost, Andreas Jahn, Sian Floyd, Hazzie Mvula, Eleneus Mwaiyeghele, Venance Mwinuka, Thomas Mhango, Amelia C. Crampin, Nuala McGrath, Paul E. M. Fine, Judith R. Glynn
PLOS ONE , 2008, DOI: 10.1371/journal.pone.0002684
Abstract: Background The World Health Organization (WHO) released new Child Growth Standards in 2006 to replace the current National Center for Health Statistics (NCHS) growth reference. We assessed how switching from the NCHS to the newly released WHO Growth Standards affects the estimated prevalence of wasting, underweight and stunting, and the pattern of risk factors identified. Methodology/Principal Findings Data were drawn from a village-informant driven Demographic Surveillance System in Northern Malawi. Children (n = 1328) were visited twice at 0–4 months and 11–15 months. Data were collected on the demographic and socio-economic environment of the child, health history, maternal and child anthropometry and child feeding practices. Weight-for-length, weight-for-age and length-for-age were derived in z-scores using the two growth references. In early infancy, prevalence estimates were 2.9, 6.1, and 8.5 fold higher for stunting, underweight, and wasting respectively using the WHO standards compared to NCHS reference (p<0.001 for all). At one year, prevalence estimates for wasting and stunting did not differ significantly according to reference used, but the prevalence of underweight was half that with the NCHS reference (p<0.001). Patterns of risk factors were similar with the two growth references for all outcomes at one year although the strength of association was higher with WHO standards. Conclusions/Significance Differences in prevalence estimates differed in magnitude but not direction from previous studies. The scale of these differences depends on the population's nutritional status thus it should not be assumed a priori. The increase in estimated prevalence of wasting in early infancy has implications for feeding programs targeting lactating mothers and ante-natal multiple micronutrients supplementation to tackle small birth size. Risk factors identified using WHO standards remain comparable with findings based on the NCHS reference in similar settings. Further research should aim to identify whether the young infants additionally diagnosed as malnourished by this new standard are more appropriate targets for interventions than those identified with the NCHS reference.
Recursive partitioning analysis of prognostic factors in WHO grade III glioma patients treated with radiotherapy or radiotherapy plus chemotherapy
Chul-Kee Park, Se-Hoon Lee, Jung Han, Chae-Yong Kim, Dong-Wan Kim, Sun Paek, Dong Kim, Dae Heo, Il Kim, Hee-Won Jung
BMC Cancer , 2009, DOI: 10.1186/1471-2407-9-450
Abstract: A total of 133 patients with anaplastic astrocytoma (AA, n = 56), anaplastic oligodendroglioma (AO, n = 67), or anaplastic oligoastrocytoma (AOA, n = 10) were included in the study. These patients were treated with either radiotherapy alone or radiotherapy followed by PCV chemotherapy after surgery. Five prognostic factors, including histological subsets, age, performance status, extent of resection, and treatment modality were incorporated into the RPA. The final nodes of RPA were grouped according to their survival times, and the Kaplan-Meier graphs are presented as the final set of prognostic groups.Four risk groups were defined based on the clinical prognostic factors excluding age, and split variables were all incorporated into the RPA. Survival analysis showed significant differences in mean survival between the different groups: 163.4 months (95% CI: 144.9-182.0), 109.5 months (86.7-132.4), 66.6 months (50.8-82.4), and 27.7 months (16.3-39.0), respectively, from the lowest to the highest risk group (p = 0.00).The present study shows that RPA grouping with clinical prognostic factors can successfully predict the survival of patients with WHO grade III glioma.Anaplastic astrocytoma (AA), anaplastic oligodendroglioma (AO), and anaplastic oligoastrocytoma (AOA) are defined as the major histological categories of WHO grade III gliomas, even though their classification based on the known molecular biology information remains controversial [1-4]. The relative survival rates at 5 years for AA and AO are 29.4% and 45.2%, respectively[5]. Although the increase is modest, standardized radiotherapy or chemotherapy has extended the survival period for patients with high-grade gliomas, suggesting the possible influence of prognostic factors such as age, performance status, symptom duration, tumor resection, histological type, and 1p/19q co-deletion [6-8]. However, most randomized trials pooled both grades III or IV astrocytic tumors and grade III oligodendroglial tumors as
Standard deviation of anthropometric Z-scores as a data quality assessment tool using the 2006 WHO growth standards: a cross country analysis
Mei,Zuguo; Grummer-Strawn,Laurence M;
Bulletin of the World Health Organization , 2007, DOI: 10.1590/S0042-96862007000600010
Abstract: objective: height- and weight-based anthropometric indicators are used worldwide to characterize the nutritional status of populations. based on the 1978 who/national center for health statistics (nchs) growth reference, the world health organization has previously indicated that the standard deviation (sd) of z-scores of these indicators is relatively constant across populations, irrespective of nutritional status. as such, the sd of z-scores can be used as quality indicators for anthropometric data. in 2006, who published new growth standards. here, we aim to assess whether the sd of height- and weight-based z-score indicators from the 2006 who growth standards can still be used to assess data quality. methods: we examined data on children aged 0-59 months from 51 demographic and health surveys (dhs) in 34 developing countries. we used 2006 growth standards to assign height-for-age z-scores (haz), weight-for-age z-scores (waz), weight-for-height z-scores (whz) and body-mass-index-for-age z-scores (bmiz). we also did a stratified analysis by age group. findings: the sd for all four indicators were independent of their respective mean z-scores across countries. overall, the 5th and 95th percentiles of the sd were 1.35 and 1.95 for haz, 1.17 and 1.46 for waz, 1.08 and 1.50 for whz and 1.08 and 1.55 for bmiz. conclusion: our results concur with the who assertion that sd is in a relatively small range for each indicator irrespective of where the z-score mean lies, and support the use of sd as a quality indicator for anthropometric data. however, the ranges of sds for all four indicators analysed were consistently wider than those published previously by who.
Malnutrition in Hospitalized Pediatric Patients: A Comparison of the National Turkish and World Health Organization (WHO) Child Growth Standards
Engin TUTA,Perran BORAN,Sedat ?KTEM,Gülnur TOKU?
Marmara Medical Journal , 2012,
Abstract: Objective: Malnutrition is known to be responsible for mortality especially in hospitalized children. Since there is a controversy regarding the criteria used to define malnutrition worldwide, the World Health Organization (WHO) has recommended using z-scores and has reported that the WHO child growth standards have worldwide validity. The aims of this study were to evaluate the prevalence of malnutrition in hospitalized pediatric patients and compare the Neyzi growth standards used in Turkey with the WHO standards.Patients and Methods: Weight-for-age, weight-for-height, and height-for-age were calculated separately in patients under five years old using the national Neyzi standards and the WHO 2006 standards. The weight-for-age- and height-for-age z-scores were also calculated, and malnutrition was defined as < -2 SD.Results: Among the 100 patients included in the study, 62 were male, and the mean age was 15.9±16.2 months. Twelve percent of the patients were classified as acute malnutrition, 13% were classified as chronic malnutrition, and 11% were underweight. The calculated mean weight-for-age and height-for-age z-scores were significantly different between the two growth standards (p<0.001).Conclusion: Although WHO has reported that the new WHO growth standards are applicable in all countries, there was a discrepancy between the WHO- and country-specific growth charts, and this presents a major problem for the evaluation of malnutrition. (Marmara Medical Journal 2012;25:128-32)
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