Performance-based payment (PBP) is increasingly advocated as a way to improve the performance of health systems in low-income countries. This study conducted a systematic review of the current ...literature on this topic and found that while it is a popular term, there was little consensus about the meaning or the use of the concept of PBP. Significant weaknesses in the current evidence base on the success of PBP initiatives were also found. The literature would be strengthened by multi-disciplinary case studies that present both the advantages and disadvantages of PBP, influential factors for success, and more details about the projects from which this evidence is drawn. Where possible, data from control facilities where PBP is not being implemented would be an important addition. This paper suggests a further agenda for research, including assessing optimal conditions for implementation of PBP schemes in less developed health systems, the impact of adopting measures of performance as targets, and the requirements for monitoring PBP adequately.
Hemoperfusion in Trauma Eldridge, Jack C; Wan, Yize I; Prowle, John R
Contributions to nephrology,
08/2023, Letnik:
200
Journal Article
Recenzirano
Major trauma care has seen significant improvements in early mortality, reflecting improvements in prehospital techniques for hemorrhage control and speed of access to specialized trauma centers. ...However, many patients then go on to die in the intensive care unit (ICU), and improvements in immediate trauma care are presenting intensivists with greater numbers of severely injured patients who might previously have died shortly after injury. It is theorized that, despite initial survival, these patients deteriorate due to massive release of damage associated molecular patterns (DAMPs) after traumatic and ischemic tissue injury. These trigger a vicious cycle of overactive pro- and anti-inflammatory pathways, leading to organ dysfunction and immunoparesis. Extracorporeal hemoperfusion, with its ability to adsorb both DAMPs and inflammatory mediators from the bloodstream, has the potential to break this cycle and could, in theory, then prevent early death or organ dysfunction in the ICU. However, currently, there has been little research around the indications for, and efficacy of, this therapy in the setting of polytrauma. Here we outline potential molecular targets, summarize existing exploratory studies, and suggest areas for future research required to establish the benefits of hemoperfusion as an adjunct therapy in major polytrauma.
Smoking is an established risk factor for a human papillomavirus (HPV) infection advancing to cervical precancer and cancer, but its role earlier in the natural history is less clear. Smoking is ...inversely associated with possessing HPV antibodies from a past infection suggesting that smoking may influence acquiring subsequent infections.
In a cohort of 1976 U.S. women, we evaluate whether reduced antibodies to HPV-16 is a mechanism for smoking's role on acquiring a subsequent HPV-16 infection, through the analytic technique of causal mediation analysis. We posit a causal model and estimate two counterfactually defined effects: a smoking impaired antibody-mediated indirect effect and a nonmediated direct effect representing all other potential mechanisms of smoking.
Compared to never smokers, current smokers had increased odds of HPV-16 infection by the antibody-mediated indirect effect (odds ratio OR = 1.29; 95% confidence interval CI: 1.11, 1.73); the estimated direct effect was very imprecise (OR = 0.57; 95% CI, 0.26–1.13). We observed a stronger estimated indirect effect among women who smoked at least half a pack of cigarettes daily (OR = 1.61, 95% CI, 1.27–2.15) than among women who smoked less than that threshold (OR = 1.09; 95% CI, 0.94–1.44).
This is the first study to directly test the mechanism underlying smoking as an HPV cofactor. The results support current smoking as a risk factor earlier in the natural history of HPV and are consistent with the hypothesis that smoking increases the risk of a subsequent infection by reducing immunity.
Translating relative risk estimates into absolute risks is important in evaluating the potential clinical and public health relevance of etiologic discoveries. Predicting high absolute risk is ...challenging, particularly for rare endpoints such as pancreatic cancer. Recent efforts to develop risk prediction models for pancreatic cancer have found moderate risk levels for very small parts of the population. A new approach in which clinical symptoms and medication use are evaluated in addition to information on risk factors is presented by Risch et al. in this issue of the Journal (Am J Epidemiol. 2015;182(1):26-34). The authors estimated absolute risks based on the relative risks obtained from their case-control study. Their absolute risk estimates were higher than those from previous approaches but remained restricted to a very small proportion of the general population. In the present commentary, we address issues of absolute risk stratification (particularly for rare diseases), specific analytic methods, and how actionable information will differ based on the disease and possible intervention. We suggest that moving from cancer-specific models to broader models used to predict risk for multiple outcomes can make risk prediction for rare diseases more effective. When considering translational goals, it is important to estimate absolute risk at the early stages of etiologic research. The results can be sobering but allow focusing on the most promising goals.
There is growing evidence that the metabolism is deeply intertwined with head and neck squamous cell carcinoma (HNSCC) progression and survival but little is known about circulating metabolite ...patterns and their clinical potential. We performed unsupervised hierarchical clustering of 209 HNSCC patients via pre-treatment plasma metabolomics to identify metabolic subtypes. We annotated the subtypes via pathway enrichment analysis and investigated their association with overall and progression-free survival. We stratified the survival analyses by smoking history. High-resolution metabolomics extracted 186 laboratory-confirmed metabolites. The optimal model created two patient clusters, of subtypes A and B, corresponding to 41% and 59% of the study population, respectively. Fatty acid biosynthesis, acetyl-CoA transport, arginine and proline, as well as the galactose metabolism pathways differentiated the subtypes. Relative to subtype B, subtype A patients experienced significantly worse overall and progression-free survival but only among ever-smokers. The estimated three-year overall survival was 61% for subtype A and 86% for subtype B; log-rank
= 0.001. The association with survival was independent of HPV status and other HNSCC risk factors (adjusted hazard ratio = 3.58, 95% CI: 1.46, 8.78). Our findings suggest that a non-invasive metabolomic biomarker would add crucial information to clinical risk stratification and raise translational research questions about testing such a biomarker in clinical trials.
Sensitivities of current directional dark matter search detectors using gas time projection chambers are now constrained by target mass. A ton-scale gas TPC detector will require large charge readout ...areas. We present a first demonstration of a novel ThGEM-Multiwire hybrid charge readout technology which combines the robust nature and high gas gain of Thick Gaseous Electron Multipliers with lower capacitive noise of a one-plane multiwire charge readout in SF6 target gas. Measurements performed with this hybrid detector show an ion drift velocity of 138±10 ms−1 in a reduced drift field E/N of 93 ×10−17 Vcm2 with an effective gas gain of 2470±160 in 20 Torr of pure SF6 target gas.
Integrating brain imaging with large scale omics data may identify novel mechanisms of mild cognitive impairment (MCI) and early Alzheimer's disease (AD). We integrated and analyzed brain magnetic ...resonance imaging (MRI) with cerebrospinal fluid (CSF) metabolomics to elucidate metabolic mechanisms and create a "metabolic map" of the brain in prodromal AD.
In 145 subjects (85 cognitively normal controls and 60 with MCI), we derived voxel-wise gray matter volume via whole-brain structural MRI and conducted high-resolution untargeted metabolomics on CSF. Using a data-driven approach consisting of partial least squares discriminant analysis, a multiomics network clustering algorithm, and metabolic pathway analysis, we described dysregulated metabolic pathways in CSF mapped to brain regions associated with MCI in our cohort.
The multiomics network algorithm clustered metabolites with contiguous imaging voxels into seven distinct communities corresponding to the following brain regions: hippocampus/parahippocampal gyrus (three distinct clusters), thalamus, posterior thalamus, parietal cortex, and occipital lobe. Metabolic pathway analysis indicated dysregulated metabolic activity in the urea cycle, and many amino acids (arginine, histidine, lysine, glycine, tryptophan, methionine, valine, glutamate, beta-alanine, and purine) was significantly associated with those regions (
< 0.05).
By integrating CSF metabolomics data with structural MRI data, we linked specific AD-susceptible brain regions to disrupted metabolic pathways involving nitrogen excretion and amino acid metabolism critical for cognitive function. Our findings and analytical approach may extend drug and biomarker research toward more multiomics approaches.
OBJECTIVES/GOALS: Cachexia is the involuntary and irreversible loss of muscle and fat and is a major cause of morbidity and mortality in head and neck cancer (HNC). It remains a poorly understood ...disease diagnosed by weight loss and a confluence of symptoms. We explored the metabolic and inflammatory mechanisms of cachexia symptoms via an multiomics network algorithm. METHODS/STUDY POPULATION: Prior to chemoradiotherapy, HNC subjects completed questionnaires and donated blood for untargeted (metabolites) and targeted (lipids and cytokines) assays. Metabolites and lipids were measured by liquid chromatography mass spectrometry. Cytokines were measured by multiplex assays. We plotted a multiomics network graph by estimating partial least squares correlations amongst metabolites, lipids, cytokines, and common cachexia symptoms—max percent weight loss over 1 year, baseline BMI, fatigue, performance, albumin, hemoglobin, and white blood cell count. To interpret the network, an algorithm identified highly correlated clusters of metabolites-lipids-cytokines-symptoms representing possible biological relatedness, which were functionally annotated via metabolic enrichment analysis. RESULTS/ANTICIPATED RESULTS: In 123 subjects (59 years of age, 72% male, 84% white, avg weight loss of 13%), we analyzed 186 metabolites, 54 lipids, 7 cytokines and 7 cachexia symptoms. We required a correlation >0.25 and P-value <.05 to be included in the network graph, resulting in 323 connections and 3 identified clusters. Max weight loss and baseline BMI were in a cluster enriched by unsaturated fatty acid biosynthesis (P<.0001) and arachidonic acid (P=.01) metabolic pathways but not linked to inflammation cytokines. The five other cachexia symptoms were in a cluster with 4 cytokines (C-reactive protein, interleukin 6, IL10, IL1, Tumor necrosis factor receptor 2) and enriched by aminoacyl tRNA (P<.01) and valine biosynthesis (P=.02). We observed no meaningful differences when we stratified the analysis by human papillomavirus. DISCUSSION/SIGNIFICANCE: Cachexia symptoms in head and neck cancer may be linked to specific metabolic dysregulation—weight loss and BMI were linked to fatty acids; fatigue, anemia and others were linked to amino acids and inflammation. This information may allow for the recognition of a cachexic-metabolic subtype or provide novel targets for metabolic intervention.
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