79 research outputs found
A Systematic Review of Cost-of-Illness Studies of Multimorbidity
Objectives: The economic burden of multimorbidity is considerable. This review analyzed the methods of cost-of-illness (COI) studies and summarized the economic outcomes of multimorbidity. Methods: A systematic review (2000–2016) was performed, which was registered with Prospero, reported according to PRISMA, and used a quality checklist adapted for COI studies. The inclusion criteria were peer-reviewed COI studies on multimorbidity, whereas the exclusion criterion was studies focusing on an index disease. Extracted data included the definition, measure, and prevalence of multimorbidity; the number of included health conditions; the age of study population; the variables used in the COI methodology; the percentage of multimorbidity vs. total costs; and the average costs per capita. Results: Among the 26 included articles, 14 defined multimorbidity as a simple count of 2 or more conditions. Methodologies used to derive the costs were markedly different. Given different healthcare systems, OOP payments of multimorbidity varied across countries. In the 17 and 12 studies with cut-offs of ≥2 and ≥3 conditions, respectively, the ratios of multimorbidity to non-multimorbidity costs ranged from 2–16 to 2–10. Among the ten studies that provided cost breakdowns, studies with and without a societal perspective attributed the largest percentage of multimorbidity costs to social care and inpatient care/medicine, respectively. Conclusion: Multimorbidity was associated with considerable economic burden. Synthesising the cost of multimorbidity was challenging due to multiple definitions of multimorbidity and heterogeneity in COI methods. Count method was most popular to define multimorbidity. There is consistent evidence that multimorbidity was associated with higher costs
Tolerability of inhaled N-chlorotaurine in the pig model
<p>Abstract</p> <p>Background</p> <p>N-chlorotaurine, a long-lived oxidant produced by human leukocytes, can be applied in human medicine as an endogenous antiseptic. Its antimicrobial activity can be enhanced by ammonium chloride. This study was designed to evaluate the tolerability of inhaled N-chlorotaurine (NCT) in the pig model.</p> <p>Methods</p> <p>Anesthetized pigs inhaled test solutions of 1% (55 mM) NCT (n = 7), 5% NCT (n = 6), or 1% NCT plus 1% ammonium chloride (NH<sub>4</sub>Cl) (n = 6), and 0.9% saline solution as a control (n = 7), respectively. Applications with 5 ml each were performed hourly within four hours. Lung function, haemodynamics, and pharmacokinetics were monitored. Bronchial lavage samples for captive bubble surfactometry and lung samples for histology and electron microscopy were removed.</p> <p>Results</p> <p>Arterial pressure of oxygen (PaO<sub>2</sub>) decreased significantly over the observation period of 4 hours in all animals. Compared to saline, 1% NCT + 1% NH<sub>4</sub>Cl led to significantly lower PaO<sub>2 </sub>values at the endpoint after 4 hours (62 ± 9.6 mmHg vs. 76 ± 9.2 mmHg, p = 0.014) with a corresponding increase in alveolo-arterial difference of oxygen partial pressure (AaDO<sub>2</sub>) (p = 0.004). Interestingly, AaDO<sub>2 </sub>was lowest with 1% NCT, even lower than with saline (p = 0.016). The increase of pulmonary artery pressure (PAP) over the observation period was smallest with 1% NCT without difference to controls (p = 0.91), and higher with 5% NCT (p = 0.02), and NCT + NH<sub>4</sub>Cl (p = 0.05).</p> <p>Histological and ultrastructural investigations revealed no differences between the test and control groups. The surfactant function remained intact. There was no systemic resorption of NCT detectable, and its local inactivation took place within 30 min. The concentration of NCT tolerated by A549 lung epithelial cells <it>in vitro </it>was similar to that known from other body cells (0.25–0.5 mM).</p> <p>Conclusion</p> <p>The endogenous antiseptic NCT was well tolerated at a concentration of 1% upon inhalation in the pig model. Addition of ammonium chloride in high concentration provokes a statistically significant impact on blood oxygenation.</p
Targeting immune checkpoints potentiates immunoediting and changes the dynamics of tumor evolution
The cancer immunoediting hypothesis assumes the immune system sculpts the cancer genome. Here the authors show, in a mouse model, that neutral evolution outweighs the effects of immunoselection and that immune checkpoint blockade potentiates the immunoediting, switching the system to non-neutral evolution
The neurotoxic effects of vitamin A and retinoids
Vitamin A (retinol) and its congeners - the retinoids - participate in a panoply of biological events, as for instance cell differentiation, proliferation, survival, and death, necessary to maintain tissue homeostasis. Furthermore, such molecules may be applied as therapeutic agents in the case of some diseases, including dermatological disturbances, immunodeficiency, and cancer (mainly leukemia). In spite of this, there is a growing body of evidences showing that vitamin A doses exceeding the nutritional requirements may lead to negative consequences, including bioenergetics state dysfunction, redox impairment, altered cellular signaling, and cell death or proliferation, depending on the cell type. Neurotoxicity has long been demonstrated as a possible side effect of inadvertent consumption, or even under medical recommendation of vitamin A and retinoids at moderate to high doses. However, the exact mechanism by which such molecules exert a neurotoxic role is not clear yet. In this review, recent data are discussed regarding the molecular findings associated with the vitamin A-related neurotoxicity
Distribution Patterns of Lentic-Breeding Amphibians in Relation to Ultraviolet Radiation Exposure in Western North America
Dominância fiscal : uma investigação empírica sobre o caso brasileiro no período de 2003 a 2014
A estabilização econômica dos anos de 1990 e a adoção do tripé econômico, a partir de
1999, marcam o fim de um capítulo delicado da história brasileira; a partir de então, era
necessária a existência de certa sintonia de políticas monetária e fiscal para a
manutenção do controle dos diversos indicadores econômicos. Contudo, com essa
reciprocidade na política econômica, são incitadas discussões sobre a orientação do
governo na hora de definir suas prioridades nesse campo: as variáveis fiscais são
priorizadas e, por conseguinte, determinadas, forçando as monetárias a se ajustarem –
ou o contrário? A resposta para esse questionamento leva à discussão sobre a
dominância fiscal. Assim, esse trabalho visa verificar empiricamente, usando das
modelagens econométricas VAR e estudo de eventos, se há dominância fiscal ou
monetária na economia brasileira e se a eficácia da política monetária mudou na
transição do governo Lula para o governo Dilma. O resultado foi inconclusivo para o
governo Lula e indicou dominância fiscal no governo Dilma. Ainda verificou-se não
haver modificação na eficácia da política monetária.Economic stabilization, in the 1990s, and utilization of an economic tripod, after 1999,
represents the end of a delicate chapter in Brazilian history. Ever since, it was necessary
the existence of a certain agreement between monetary and fiscal politic, in order to
maintain under control a variety of economic indicators. However, this reciprocity (in
economic politic) starts discussions about the real government orientations when it
comes to define its priority on this subject: are the fiscal variables priorized, and then,
determined, forcing monetary variables to adjust themselves, or the opposite? The
answer to these questions emerge from the fiscal dominance discussion. This paper
intends to empiric verify, using econometric modeling VAR and event study, if there is
fiscal dominance or monetary in Brazilian economy and whether the effectiveness of
monetary politic has changed in the transition from Lula's government to the Dilma
government. The result was inconclusive for the Lula government and indicated fiscal
dominance in the Dilma government. There was still no change in the efficiency of the
monetary politic.CAPE
Protection of CpG islands against de novo DNA methylation during oogenesis is associated with the recognition site of E2f1 and E2f2
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