Characterisation of the autoinmune antibody repertoire of Parkinson's disease patients by systematic screening of protein arrays

Comunicaciones a congreso

Cost-effectiveness of 7-day-Holter monitoring alone or in combination with transthoracic echocardiography in patients with cerebral ischemia

Background and purpose Prolonged Holter monitoring of patients with cerebral ischemia increases the detection rate of paroxysmal atrial fibrillation (PAF); this leads to improved antithrombotic regimens aimed at preventing recurrent ischemic strokes. The aim of this study was to compare a 7-day-Holter monitoring (7-d-Holter) alone or in combination with prior selection via transthoracic echocardiography (TTE) to a standard 24-h-Holter using a cost-utility analysis. Methods: Lifetime cost, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICER) were estimated for a cohort of patients with acute cerebral ischemia and no contraindication to oral anticoagulation. A Markov model was developed to simulate the long-term course and progression of cerebral ischemia considering the different diagnostic algorithms (24-h-Holter, 7-d-Holter, 7-d-Holter after preselection by TTE). Clinical data for these algorithms were derived from the prospective observational Find-AF study (ISRCTN 46104198). Results: Predicted lifelong discounted costs were 33,837 € for patients diagnosed by the 7-d-Holter and 33,852 € by the standard 24-h-Holter. Cumulated QALYs were 3.868 for the 7-d-Holter compared to 3.844 for the 24-h-Holter. The 7-d-Holter dominated the 24-h-Holter in the base-case scenario and remained cost-effective in extensive sensitivity analysis of key input parameter with a maximum of 8,354 €/QALY gained. Preselecting patients for the 7-d-Holter had no positive effect on the cost-effectiveness. Conclusions: A 7-d-Holter to detect PAF in patients with cerebral ischemia is cost-effective. It increases the detection which leads to improved antithrombotic regimens; therefore, it avoids recurrent strokes, saves future costs, and decreases quality of life impairment. Preselecting patients by TTE does not improve cost-effectiveness

A dynamic network approach for the study of human phenotypes

The use of networks to integrate different genetic, proteomic, and metabolic datasets has been proposed as a viable path toward elucidating the origins of specific diseases. Here we introduce a new phenotypic database summarizing correlations obtained from the disease history of more than 30 million patients in a Phenotypic Disease Network (PDN). We present evidence that the structure of the PDN is relevant to the understanding of illness progression by showing that (1) patients develop diseases close in the network to those they already have; (2) the progression of disease along the links of the network is different for patients of different genders and ethnicities; (3) patients diagnosed with diseases which are more highly connected in the PDN tend to die sooner than those affected by less connected diseases; and (4) diseases that tend to be preceded by others in the PDN tend to be more connected than diseases that precede other illnesses, and are associated with higher degrees of mortality. Our findings show that disease progression can be represented and studied using network methods, offering the potential to enhance our understanding of the origin and evolution of human diseases. The dataset introduced here, released concurrently with this publication, represents the largest relational phenotypic resource publicly available to the research community.Comment: 28 pages (double space), 6 figure

Reconsidering Western core values of education and politics in a global context

Workshop presentation delivered at the Globethics.net International Conference "Building New Bridges Together: Ethics and Values at the Heart of Quality Education" held 17-19 October 2022, Geneva, Switzerland

Disease characteristics and treatment of patients with diabetes mellitus attending government health services in Indonesia, Peru, Romania and South Africa.

OBJECTIVE: To describe the characteristics and management of Diabetes mellitus (DM) patients from low- and middle-income countries (LMIC). METHODS: We systematically characterized consecutive DM patients attending public health services in urban settings in Indonesia, Peru, Romania and South Africa, collecting data on DM treatment history, complications, drug treatment, obesity, HbA1c, and cardiovascular risk profile; and assessing treatment gaps against relevant national guidelines. RESULTS: Patients (median 59 years, 62.9% female) mostly had type 2 diabetes (96%), half for >5 years (48.6%). Obesity (45.5%) and central obesity (females 84.8%; males 62.7%) were common. The median HbA1c was 8.7% (72 mmol/mol), ranging from 7.7% (61 mmol/mol; Peru) to 10.4% (90 mmol/mol; South Africa). Antidiabetes treatment included metformin (62.6%), insulin (37.8%), and other oral glucose-lowering drugs (34.8%). Disease complications included eyesight problems (50.4%), EGFR <60 ml/min (18.9%), heart disease (16.5%), and proteinuria (14.7%). Many had an elevated cardiovascular risk with elevated blood pressure (36%), LDL (71.0%), and smoking (13%), but few were taking antihypertensive drugs (47.1%), statins (28.5%) and aspirin (30.0%) when indicated. Few patients on insulin (8.0%), statins (8.4%) and antihypertensives (39.5%) reached treatment targets according to national guidelines. There were large differences between countries in terms of disease profile and medication use. CONCLUSION: DM patients in government clinics in four LMIC with considerable growth of DM have insufficient glycemic control, frequent macrovascular and other complications, and insufficient preventive measures for cardiovascular disease. These findings underline the need to identify treatment barriers and secure optimal DM care in such settings. This article is protected by copyright. All rights reserved

How universal is coverage and access to diagnosis and treatment for Chagas disease in Colombia? A health systems analysis

Limited access to Chagas disease diagnosis and treatment is a major obstacle to reaching the 2020 World Health Organization milestones of delivering care to all infected and ill patients. Colombia has been identified as a health system in transition, reporting one of the highest levels of health insurance coverage in Latin America. We explore if and how this high level of coverage extends to those with Chagas disease, a traditionally marginalised population. Using a mixed methods approach, we calculate coverage for screening, diagnosis and treatment of Chagas. We then identify supply-side constraints both quantitatively and qualitatively. A review of official registries of tests and treatments for Chagas disease delivered between 2008 and 2014 is compared to estimates of infected people. Using the Flagship Framework, we explore barriers limiting access to care. Screening coverage is estimated at 1.2% of the population at risk. Aetiological treatment with either benznidazol or nifurtimox covered 0.3-0.4% of the infected population. Barriers to accessing screening, diagnosis and treatment are identified for each of the Flagship Framework's five dimensions of interest: financing, payment, regulation, organization and persuasion. The main challenges identified were: a lack of clarity in terms of financial responsibilities in a segmented health system, claims of limited resources for undertaking activities particularly in primary care, non-inclusion of confirmatory test(s) in the basic package of diagnosis and care, poor logistics in the distribution and supply chain of medicines, and lack of awareness of medical personnel. Very low screening coverage emerges as a key obstacle hindering access to care for Chagas disease. Findings suggest serious shortcomings in this health system for Chagas disease, despite the success of universal health insurance scale-up in Colombia. Whether these shortcomings exist in relation to other neglected tropical diseases needs investigating. We identify opportunities for improvement that can inform additional planned health reforms. (C) 2017 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license

The ART Advantage: Health Care Utilization for Diabetes and Hypertension in Rural South Africa

The prevalence of diabetes and hypertension has increased in HIV-positive populations, but there is limited understanding of the role that antiretroviral therapy (ART) programs play in the delivery of services for these conditions. The aim of this study is to assess the relationship between ART use and utilization of health care services for diabetes and hypertension.Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa is a cohort of 5059 adults. The baseline study collects biomarker-based data on HIV, ART, diabetes, and hypertension and self-reported data on health care utilization. We calculated differences in care utilization for diabetes and hypertension by HIV and ART status and used multivariable logistic regressions to estimate the relationship between ART use and utilization of services for these conditions, controlling for age, sex, body mass index, education, and household wealth quintile.Mean age, body mass index, hypertension, and diabetes prevalence were lower in the HIV-positive population (all P < 0.001). Multivariable logistic regression showed that ART use was significantly associated with greater odds of blood pressure measurement [adjusted odds ratio (aOR) 1.27, 95% confidence interval (CI): 1.04 to 1.55] and blood sugar measurement (aOR 1.26, 95% CI: 1.05 to 1.51), counseling regarding exercise (aOR 1.57, 95% CI: 1.11 to 2.22), awareness of hypertension diagnosis (aOR 1.52, 95% CI: 1.12 to 2.05), and treatment for hypertension (aOR 1.63, 95% CI: 1.21 to 2.19).HIV-positive patients who use ART are more likely to have received health care services for diabetes and hypertension. This apparent ART advantage suggests that ART programs may be a vehicle for strengthening health systems for chronic care

Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers