How Healthcare Policies Affect Access And Quality Of Care

This thesis will outline healthcare systems in the United States, Canada, and Europe in order to understand how the policies of each system affect access to care and quality of care. The four policies outlined in this thesis include Social Health Insurance, Statutory Health Insurance, National Healthcare System, and National Health Insurance. This work attempts to summarize each healthcare system and the issues they face related to access and quality, in hopes of comparing the systems to learn from the strengths and weaknesses of each coverage model, and applying these findings to the United States

Route of transmission might influence the clinical expression of periodontal lesions in "Human immunodeficiency virus" positive patients

Background: Various routes have been reported with respect to the transmission of human immunodeficiency virus (HIV) from one individual to another. But it is not clear whether they alter the clinical expression of the disease. This study was conducted to know whether there exists any difference in the occurrence of periodontal lesions among untreated HIV subjects who acquired the disease either through intravenous drug abuse or sexual contact and to correlate those lesions with immune suppression as indicated by CD 4 T lymphocyte counts.Materials and Methods: In this cross-sectional study 213 HIV-positive subjects who had not started on Highly Active Anti Retroviral Therapy (HAART) were selected and divided into two groups intravenous drug users (IVDU) and non-IVDU (NIVDU). CD 4 T lymphocyte counts were evaluated and clinical examination was done to detect the presence of pathologic periodontal lesions.Results: Mean probing depth (PD) and clinical attachment level (CAL) are significantly higher in drug users than nondrug users. When periodontal lesions are compared with CD 4 cell counts, it is found that significant inverse relation exists between linear gingival erythema, necrotizing ulcerative periodontitis, and CD 4 counts, but only in nondrug users. Conclusion: An inverse correlation between linear gingival erythema, necrotizing ulcerative periodontitis, and CD 4 counts in NIVDU indicating their reliability as a marker for immune suppression. Periodontitis is more prevalent among drug users indicating some difference in disease expression among the groups

Non-Parametric Approximations for Anisotropy Estimation in Two-dimensional Differentiable Gaussian Random Fields

Spatially referenced data often have autocovariance functions with elliptical isolevel contours, a property known as geometric anisotropy. The anisotropy parameters include the tilt of the ellipse (orientation angle) with respect to a reference axis and the aspect ratio of the principal correlation lengths. Since these parameters are unknown a priori, sample estimates are needed to define suitable spatial models for the interpolation of incomplete data. The distribution of the anisotropy statistics is determined by a non-Gaussian sampling joint probability density. By means of analytical calculations, we derive an explicit expression for the joint probability density function of the anisotropy statistics for Gaussian, stationary and differentiable random fields. Based on this expression, we obtain an approximate joint density which we use to formulate a statistical test for isotropy. The approximate joint density is independent of the autocovariance function and provides conservative probability and confidence regions for the anisotropy parameters. We validate the theoretical analysis by means of simulations using synthetic data, and we illustrate the detection of anisotropy changes with a case study involving background radiation exposure data. The approximate joint density provides (i) a stand-alone approximate estimate of the anisotropy statistics distribution (ii) informed initial values for maximum likelihood estimation, and (iii) a useful prior for Bayesian anisotropy inference.Comment: 39 pages; 8 figure

Stopping Antiepileptic Drugs: When and Why?

After a patient has initiated an antiepileptic drug (AED) and achieved a sustained period of seizure freedom, the bias towards continuing therapy indefinitely can be substantial. Studies show that the rate of seizure recurrence after AED withdrawal is about two to three times the rate in patients who continue AEDs, but there are many benefits to AED withdrawal that should be evaluated on an individualized basis. AED discontinuation may be considered in patients whose seizures have been completely controlled for a prolonged period, typically 1 to 2 years for children and 2 to 5 years for adults. For children, symptomatic epilepsy, adolescent onset, and a longer time to achieve seizure control are associated with a worse prognosis. In adults, factors such as a longer duration of epilepsy, an abnormal neurologic examination, an abnormal EEG, and certain epilepsy syndromes are known to increase the risk of recurrence. Even in patients with a favorable prognosis, however, the risk of relapse can be as high as 20% to 25%. Before withdrawing AEDs, patients should be counseled about their individual risk for relapse and the potential implications of a recurrent seizure, particularly for safety and driving

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

NQO1-Dependent Redox Cycling of Idebenone: Effects on Cellular Redox Potential and Energy Levels

Short-chain quinones are described as potent antioxidants and in the case of idebenone have already been under clinical investigation for the treatment of neuromuscular disorders. Due to their analogy to coenzyme Q10 (CoQ10), a long-chain quinone, they are widely regarded as a substitute for CoQ10. However, apart from their antioxidant function, this provides no clear rationale for their use in disorders with normal CoQ10 levels. Using recombinant NAD(P)H:quinone oxidoreductase (NQO) enzymes, we observed that contrary to CoQ10 short-chain quinones such as idebenone are good substrates for both NQO1 and NQO2. Furthermore, the reduction of short-chain quinones by NQOs enabled an antimycin A-sensitive transfer of electrons from cytosolic NAD(P)H to the mitochondrial respiratory chain in both human hepatoma cells (HepG2) and freshly isolated mouse hepatocytes. Consistent with the substrate selectivity of NQOs, both idebenone and CoQ1, but not CoQ10, partially restored cellular ATP levels under conditions of impaired complex I function. The observed cytosolic-mitochondrial shuttling of idebenone and CoQ1 was also associated with reduced lactate production by cybrid cells from mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS) patients. Thus, the observed activities separate the effectiveness of short-chain quinones from the related long-chain CoQ10 and provide the rationale for the use of short-chain quinones such as idebenone for the treatment of mitochondrial disorders

Modeling Conformational Ensembles of Slow Functional Motions in Pin1-WW

Protein-protein interactions are often mediated by flexible loops that experience conformational dynamics on the microsecond to millisecond time scales. NMR relaxation studies can map these dynamics. However, defining the network of inter-converting conformers that underlie the relaxation data remains generally challenging. Here, we combine NMR relaxation experiments with simulation to visualize networks of inter-converting conformers. We demonstrate our approach with the apo Pin1-WW domain, for which NMR has revealed conformational dynamics of a flexible loop in the millisecond range. We sample and cluster the free energy landscape using Markov State Models (MSM) with major and minor exchange states with high correlation with the NMR relaxation data and low NOE violations. These MSM are hierarchical ensembles of slowly interconverting, metastable macrostates and rapidly interconverting microstates. We found a low population state that consists primarily of holo-like conformations and is a “hub” visited by most pathways between macrostates. These results suggest that conformational equilibria between holo-like and alternative conformers pre-exist in the intrinsic dynamics of apo Pin1-WW. Analysis using MutInf, a mutual information method for quantifying correlated motions, reveals that WW dynamics not only play a role in substrate recognition, but also may help couple the substrate binding site on the WW domain to the one on the catalytic domain. Our work represents an important step towards building networks of inter-converting conformational states and is generally applicable