97 research outputs found

    Neutrophil CD64 in early-onset neonatal sepsis

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    Background: Neonatal sepsis is a life threatening disease with an incidence of 3.5 to 8 cases per 1,000 live births; and mortality rate 16 to 30%. Cytokines, produced by monocytes, macrophages, and endothelial cells in response to infectious stimuli are important proinflammatory mediators in the early phases of the sepsis syndrome. Elevated serum levels of interleukin-6 (IL-6) had been found in both neonatal and adult sepsis. However, for neonatal sepsis, little is known about a group of molecules playing a central role in the innate immune system. Among them is the neutrophil CD64 which is expressed on neutrophil surface in many inflammatory conditions. Objective: To study the neutrophil CD64 expression in neonates with early onset sepsis and its relation to other laboratory markers as IL6, CRP, total leucocytic count and platelet count. Methods: This study comprised 30 neonates with a gestational age of 28 to 40 weeks with a picture of early onset neonatal sepsis within 48 hours of life admitted to neonatal care unit, Suzan Mubarak Hospital, El-Minia University, Egypt during the period from February, 2008 to January, 2009 and 20 healthy neonates age and sex matched as a control group. Neutrophil surface expression of CD64 was quantified with flow cytometry. We measured plasma IL6, C-reactive protein, complete blood count and blood culture. Results: Neutrophil CD64 expression was increased significantly in neonates with neonatal sepsis than controls (p=0.001). Cases with history of premature rupture of membranes (PROM) ≥48 hours, with positive blood culture or poor outcome had the highest levels of neutrophil CD64 expression (528±50.7, 558±58.4 and 560.9±43.9 relative fluorescence units (RFU) respectively). A significant positive correlation was found between CD64 levels and the levels of IL6 (r=0.71, p=0.001),C-reactive protein (r=0.74, p=0.001) and total leucocytic count (r=0.76 ,p=0.01) and negative correlation with gestational age (r=-0.92, p=0.001) and body weight (r=-0.92, p=0.006), but there was no correlation between it and platelet count (r=-0.32, p=0.08). Conclusion: Neutrophil CD64 expression is increased in neonates with early-onset neonatal sepsis and correlated well with other laboratory markers of sepsis.Keywords: Neonatal sepsis, Cytokines, Neutrophil CD64, IL6, PROMEgypt J Pediatr Allergy Immunol 2010;8(1):19-2

    DIFFERENT TOPICAL FORMULATIONS OF KETOROLAC TROMETHAMINE FOR ANTI-INFLAMMATORY APPLICATION AND CLINICAL EFFICACY

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    Ketorolac tromethamine (KT) is considered as a member of NSAIDs that used in treatment of rheumatoid arthritis. The main problems associated with the frequent administration of KT orally could be overcome by alternative routes as topical application. KT was formulated in different topical formulations such as gels, emulgels and creams. Sodium carboxymethylcellulose, carbopol 934 and pluronic F127 were used as polymers. In vitro permeation study through rat skin was carried out. The effect of different KT concentrations and the effect of skin penetration enhancer on the amount of KT permeated were investigated. Anti-inflammatory activity using commercial piroxicam gel for comparison was evaluated. The effectiveness and tolerability of the selected KT gel and piroxicam gel in osteoarthritis patients was also studied. The results obtained showed that, the flux of the drug increased with increasing its initial concentration. Using sodium lauryl sulfate as enhancer resulted in an improvement of KT permeation through rat skin. All formulations had the potential for local applications of KT as anti-inflammatory drug as compared to the control group. There was no significant difference in the efficacy between the selected KT gel and piroxicam gel for osteoarthritis patients. So KT gel may be used as another therapeutic option for the treatment of patients with osteoarthritis

    Cost-Savings Associated with Multi-Disciplinary Team Approach for Reducing Macrovascular and Microvascular Complications in Patients with Type 2 Diabetes: A Predictive Model

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    Abdulmajeed Alshowair,1 Saleh Altamimi,1 Faisal A Alruhaimi,1 Saad Alshahrani,2 Fatima Alsuwailem,3 Mona Alkhaldi,4 Haiam Abdalla,5 Fahad Hamad Alkhuraiji,6 Montaser Saad Alaqeel,6 Salman Sulaiman Almureef,7 Salman Alhawasy,8 Amro Abdel-Azeem3,9 1Community Health Excellence, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia; 2Academic and Training Affairs, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia; 3Population Health Management and Research, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia; 4Health Administration Office, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia; 5Model of Care, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia; 6Financial Affairs, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia; 7Cost Department, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia; 8Reporting Department, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia; 9Department of Community, Environmental and Occupational Medicine, Faculty of Medicine Zagazig University, Zagazig, EgyptCorrespondence: Amro Abdel-Azeem, Population Health Management and Research, Riyadh First Health Cluster Ministry of Health, Riyadh, Saudi Arabia, Tel +966547135224, Email [email protected]: This study aims to predict the expected cost savings associated with implementing a multidisciplinary team (MDT) approach to reduce macrovascular and microvascular complications among patients with type 2 diabetes mellitus (T2DM).Methods: This economic evaluation study was conducted in Riyadh First Health Cluster, Saudi Arabia as a predictive model conceptualized by the authors based on models used in previous studies, particularly the CORE Diabetes Model. Our model was designed based on 1) the level of glycemic control among 24,755 T2DM patients served by MDTs; 2) the expected incidence of diabetes-related complications without intervention; 3) the predicted risk reduction of developing diabetes-related complications with MDTs. Costs of complications and cost savings were then calculated and expressed as mean incremental annual cost savings adjusted for a 1% reduction in HbA1c, and a 10 mmHg reduction in systolic blood pressure (SBP).Results: Along with the expected reduction in all diabetes-related complications, the average incremental cost savings per diabetic patient is predicted to be ($38,878) with approximately ($11,108) in the year of complication onset and ($27,770) over the subsequent post-index 10-years. On adjustment of cost savings, the average incremental cost savings are predicted to be ($22,869) for each 1% reduction in HbA1c per diabetic patient and ($27,770) for every 10 mmHg reduction in SBP per diabetic patient.Conclusion: MDT as a model of care is effective in glycemic control among T2DM patients with a predicted significant reduction of all diabetes-related complications and in turn, a predicted significant cost savings.Keywords: cost-savings, multi-disciplinary team, complications, type 2 diabetes, predictive mode

    Preliminary safety and efficacy of first-line pertuzumab combined with trastuzumab and taxane therapy for HER2-positive locally recurrent or metastatic breast cancer (PERUSE).

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    BACKGROUND: Pertuzumab combined with trastuzumab and docetaxel is the standard first-line therapy for HER2-positive metastatic breast cancer, based on results from the phase III CLEOPATRA trial. PERUSE was designed to assess the safety and efficacy of investigator-selected taxane with pertuzumab and trastuzumab in this setting. PATIENTS AND METHODS: In the ongoing multicentre single-arm phase IIIb PERUSE study, patients with inoperable HER2-positive advanced breast cancer (locally recurrent/metastatic) (LR/MBC) and no prior systemic therapy for LR/MBC (except endocrine therapy) received docetaxel, paclitaxel or nab-paclitaxel with trastuzumab [8\u2009mg/kg loading dose, then 6\u2009mg/kg every 3\u2009weeks (q3w)] and pertuzumab (840\u2009mg loading dose, then 420\u2009mg q3w) until disease progression or unacceptable toxicity. The primary end point was safety. Secondary end points included overall response rate (ORR) and progression-free survival (PFS). RESULTS: Overall, 1436 patients received at least one treatment dose (initially docetaxel in 775 patients, paclitaxel in 589, nab-paclitaxel in 65; 7 discontinued before starting taxane). Median age was 54\u2009years; 29% had received prior trastuzumab. Median treatment duration was 16\u2009months for pertuzumab and trastuzumab and 4\u2009months for taxane. Compared with docetaxel-containing therapy, paclitaxel-containing therapy was associated with more neuropathy (all-grade peripheral neuropathy 31% versus 16%) but less febrile neutropenia (1% versus 11%) and mucositis (14% versus 25%). At this preliminary analysis (52 months' median follow-up), median PFS was 20.6 [95% confidence interval (CI) 18.9-22.7] months overall (19.6, 23.0 and 18.1\u2009months with docetaxel, paclitaxel and nab-paclitaxel, respectively). ORR was 80% (95% CI 78%-82%) overall (docetaxel 79%, paclitaxel 83%, nab-paclitaxel 77%). CONCLUSIONS: Preliminary findings from PERUSE suggest that the safety and efficacy of first-line pertuzumab, trastuzumab and taxane for HER2-positive LR/MBC are consistent with results from CLEOPATRA. Paclitaxel appears to be a valid alternative taxane backbone to docetaxel, offering similar PFS and ORR with a predictable safety profile. CLINICALTRIALS.GOV: NCT01572038

    Fusarium: more than a node or a foot-shaped basal cell

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    Recent publications have argued that there are potentially serious consequences for researchers in recognising distinct genera in the terminal fusarioid clade of the family Nectriaceae. Thus, an alternate hypothesis, namely a very broad concept of the genus Fusarium was proposed. In doing so, however, a significant body of data that supports distinct genera in Nectriaceae based on morphology, biology, and phylogeny is disregarded. A DNA phylogeny based on 19 orthologous protein-coding genes was presented to support a very broad concept of Fusarium at the F1 node in Nectriaceae. Here, we demonstrate that re-analyses of this dataset show that all 19 genes support the F3 node that represents Fusarium sensu stricto as defined by F. sambucinum (sexual morph synonym Gibberella pulicaris). The backbone of the phylogeny is resolved by the concatenated alignment, but only six of the 19 genes fully support the F1 node, representing the broad circumscription of Fusarium. Furthermore, a re-analysis of the concatenated dataset revealed alternate topologies in different phylogenetic algorithms, highlighting the deep divergence and unresolved placement of various Nectriaceae lineages proposed as members of Fusarium. Species of Fusarium s. str. are characterised by Gibberella sexual morphs, asexual morphs with thin- or thick-walled macroconidia that have variously shaped apical and basal cells, and trichothecene mycotoxin production, which separates them from other fusarioid genera. Here we show that the Wollenweber concept of Fusarium presently accounts for 20 segregate genera with clear-cut synapomorphic traits, and that fusarioid macroconidia represent a character that has been gained or lost multiple times throughout Nectriaceae. Thus, the very broad circumscription of Fusarium is blurry and without apparent synapomorphies, and does not include all genera with fusarium-like macroconidia, which are spread throughout Nectriaceae (e.g., Cosmosporella, Macroconia, Microcera). In this study four new genera are introduced, along with 18 new species and 16 new combinations. These names convey information about relationships, morphology, and ecological preference that would otherwise be lost in a broader definition of Fusarium. To assist users to correctly identify fusarioid genera and species, we introduce a new online identification database, Fusarioid-ID, accessible at www.fusarium.org. The database comprises partial sequences from multiple genes commonly used to identify fusarioid taxa (act1, CaM, his3, rpb1, rpb2, tef1, tub2, ITS, and LSU). In this paper, we also present a nomenclator of names that have been introduced in Fusarium up to January 2021 as well as their current status, types, and diagnostic DNA barcode data. In this study, researchers from 46 countries, representing taxonomists, plant pathologists, medical mycologists, quarantine officials, regulatory agencies, and students, strongly support the application and use of a more precisely delimited Fusarium (= Gibberella) concept to accommodate taxa from the robust monophyletic node F3 on the basis of a well-defined and unique combination of morphological and biochemical features. This F3 node includes, among others, species of the F. fujikuroi, F. incarnatum-equiseti, F. oxysporum, and F. sambucinum species complexes, but not species of Bisifusarium [F. dimerum species complex (SC)], Cyanonectria (F. buxicola SC), Geejayessia (F. staphyleae SC), Neocosmospora (F. solani SC) or Rectifusarium (F. ventricosum SC). The present study represents the first step to generating a new online monograph of Fusarium and allied fusarioid genera (www.fusarium.org)

    Use of multidimensional item response theory methods for dementia prevalence prediction : an example using the Health and Retirement Survey and the Aging, Demographics, and Memory Study

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    Background Data sparsity is a major limitation to estimating national and global dementia burden. Surveys with full diagnostic evaluations of dementia prevalence are prohibitively resource-intensive in many settings. However, validation samples from nationally representative surveys allow for the development of algorithms for the prediction of dementia prevalence nationally. Methods Using cognitive testing data and data on functional limitations from Wave A (2001-2003) of the ADAMS study (n = 744) and the 2000 wave of the HRS study (n = 6358) we estimated a two-dimensional item response theory model to calculate cognition and function scores for all individuals over 70. Based on diagnostic information from the formal clinical adjudication in ADAMS, we fit a logistic regression model for the classification of dementia status using cognition and function scores and applied this algorithm to the full HRS sample to calculate dementia prevalence by age and sex. Results Our algorithm had a cross-validated predictive accuracy of 88% (86-90), and an area under the curve of 0.97 (0.97-0.98) in ADAMS. Prevalence was higher in females than males and increased over age, with a prevalence of 4% (3-4) in individuals 70-79, 11% (9-12) in individuals 80-89 years old, and 28% (22-35) in those 90 and older. Conclusions Our model had similar or better accuracy as compared to previously reviewed algorithms for the prediction of dementia prevalence in HRS, while utilizing more flexible methods. These methods could be more easily generalized and utilized to estimate dementia prevalence in other national surveys
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