Guías actuales de práctica clínica en la diabetes mellitus tipo 2: ¿cómo aplicarlas en atención primaria?

Clinical practice guidelines should be drawn up with systematic methodology based on the best available evidence. Recommendations should be based on evaluation of the overall quality of the evidence and grading of the strength of recommendations. Consensus documents combine a review of the evidence with expert opinion in an attempt to reach some agreement in areas of uncertainty due to the lack of conclusive proof. The debate aroused by new treatments stimulates the production of documents advocating their use even when there are few long-term studies on their safety and efficacy.There are several methodologically rigorous international guidelines on diabetes (NGC, NICE, SIGN, CAD, ADA). The most recent debate has centered on the ADA-EASD treatment algorithm. In Spain, the production of clinical practice guidelines with analysis of the evidence and grading of recommendations remains scarce, although the most recent published guidelines show greater rigor. More common is the drafting of consensus documents by scientific societies with the aim of combining external evidence with experience and reflection. In Spain there are also organisms (such as GuíaSalud or Fisterra) that facilitate free access to guidelines drawn up by Spanish groups.     

Bioavailability and risk assessment of orally ingested polycyclic aromatic hydrocarbons

Polycyclic aromatic hydrocarbons (PAHs) are a family of toxicants that are ubiquitous in the environment. These contaminants generate considerable interest, because some of them are highly carcinogenic in laboratory animals and have been implicated in breast, lung, and colon cancers in humans. These chemicals commonly enter the human body through inhalation of cigarette smoke or consumption of contaminated food. Of these two pathways, dietary intake of PAHs constitutes a major source of exposure in humans. Although many reviews and books on PAHs have been published, factors affecting the accumulation of PAHs in the diet, their absorption following ingestion, and strategies to assess risk from exposure to these hydrocarbons following ingestion have received much less attention. This review, therefore, focuses on concentrations of PAHs in widely consumed dietary ingredients along with gastrointestinal absorption rates in humans. Metabolism and bioavailability of PAHs in animal models and the processes, which influence the disposition of these chemicals, are discussed. The utilitarian value of structure and metabolism in predicting PAH toxicity and carcinogenesis is also emphasized. Finally, based on intake, disposition, and tumorigenesis data, the exposure risk to PAHs from diet, and contaminated soil is presented. This information is expected to provide a framework for refinements in risk assessment of PAHs from a multimedia exposure perspective.     

Output congestion leads to compromised care in Peruvian public hospital neonatal units

Peru is moving toward a universal health insurance system, and it is facing important challenges in the provision of public health services. As more citizens gain access to health insurance, the flow of patients exceeds the capacity of public hospitals to provide care with quality. In this study we explore the relationship between technical efficiency and patient safety events in neonatal care units of Peru’s public hospitals. We use Data Envelope Analysis (DEA) with output congestion to assess the association between technical efficiency and patient safety events. We study 35 neonatal care units of public hospitals in Peru’s Social Security Health System, and identify two undesirable (risk-adjusted) safety outcomes: neonatal mortality and near-miss neonatal mortality. We found that for about half of hospital’s neonatal care units, technical efficiency is affected by output congestion. For those hospitals, patient safety is being compromised by receiving too many patients. Our results are consistent with public reports indicating that hospitals in the Peru’s Social Security Health System are overcrowded, affecting efficiency and jeopardizing quality of care. We found that most congested hospitals are located in the capital city and suburban areas, and are more likely to be hospitals with the lowest and the highest level of care. Our results call for improvements in the patient referral system and capacity expansion.     

Inhibition of Intestinal Pyrimidine Nucleoside Phosphorylases

The activity of 5-deoxy-5-fluorouridine (dFUR) depends on its activation to 5-fluorouracil (FU) by pyrimidine nucleoside phosphorylases. These enzymes are found in tumors and normal tissues, with the highest activity in the small intestines. The present study examined the inhibition of dFUR phosphorolysis in intestinal tissues. dFUR metabolism in intestinal homogenates was inhibited by uracil (U), uridine (UR), and thymidine (TdR), which are the normal substrates for the phosphorylases. Conversely dFUR reduced the metabolism of these inhibitors. A good agreement was found between the observed data and the computer-fitted data using the equations for competitive inhibition between dFUR and the inhibitors. In the absence of inhibitors, the V _max of dFUR phosphorolysis was 47.1 ± 4.9 µM/min and the apparent K _m was 910 ± 167 µM. The V _max was unaltered by the inhibitors, while the K _m was increased with increasing inhibitor concentrations. The maximal inhibition of dFUR metabolism by UR and TdR was about 80%. The K _i,'s were 372 µM for U, 87.2 µM for UR, and 112 µM for TdR and are orders of magnitude higher than their reported endogenous serum concentrations. The rate of dFUR phosphorolysis to FU in the intact intestinal epithelial crypt cells, indicated by the ratio of FU to dFUR in the intracellular fluid, was reduced by UR in a concentration-dependent fashion. These data indicate that the naturally occurring pyrimidines inhibit competitively the dFUR metabolism by the intestinal phosphorylases, that this inhibition occurs at concentrations much higher than the circulating endogenous levels, and that phosphorolysis is the major route of dFUR metabolism.     

Improved pharmacokinetic profile of lipophilic anti-cancer drugs using ανβ3-targeted polyurethane-polyurea nanoparticles

Glutathione degradable polyurethane-polyurea nanoparticles (PUUa NP) with a disulfide-rich multiwalled structure and a cyclic RGD peptide as a targeting moiety were synthesized, incorporating a very lipophilic chemotherapeutic drug named Plitidepsin. In vitro studies indicated that encapsulated drug maintained and even improved its cytotoxic activity while in vivo toxicity studies revealed that the maximum tolerated dose (MTD) of Plitidepsin could be increased three-fold after encapsulation. We also found that pharmacokinetic parameters such as maximum concentration (Cmax), area under the curve (AUC) and plasma half-life were significantly improved for Plitidepsin loaded in PUUa NP. Moreover, biodistribution assays in mice showed that RGD-decorated PUUa NP accumulate less in spleen and liver than non-targeted conjugates, suggesting that RGD-decorated nanoparticles avoid sequestration by macrophages from the reticuloendothelial system. Overall, our results indicate that polyurethane-polyurea nanoparticles represent a very valuable nanoplatform for the delivery of lipophilic drugs by improving their toxicological, pharmacokinetic and whole-body biodistribution profiles.     

The two component adjuvant IC31® potentiates the protective immunity induced by a dengue 2 recombinant fusion protein in mice

Here we evaluated the suitability of the synthetic adjuvant IC31^® to potentiate the protective capacity of PD5 protein (domain III of the envelope protein of dengue 2 virus fused to the carrier protein P64k). Unlike Alum, PD5 mixed with IC31^® induced complete protection against virus challenge in mice and increased IFN-γ secretion after in vitro re-stimulation. The induced antibody response was highly specific to the homologous serotype and showed both IgG1 and IgG2a subtypes. IC31^® is a promising adjuvant for PD5 recombinant protein based vaccination against dengue. Future work should address the suitability of PD5/IC31^® formulations in non-human primate models.     

Differences in disability-free life expectancy by gender and autonomous regions in Spain

BACKGROUND: Improvement of population health is the main aim and an important challenge for the health system. To monitor the population health indicators like disability-free life expectancy (DFLE) have been implemented. The purpose of this paper was to analyze the geographical distribution of DFLE according to autonomous regions in Spain. METHODS: Data of mortality, population and disability for the year 1999, provided by the National Institute of Statistics (INE), were used. To calculate DFLE by gender and region we used the Sullivan method that weights the expected time to live according to the status of disablement of the population. The standard error of DFLE, the expectation of disability and the proportion of time lived free of disability have also been estimated. RESULTS: In 1999 the DFLE at birth in Spain was 68.5 year for men and 72.2 years in women. Men lived proportionally more time free of disability than women (91% versus 87.7%) with an expectation of disability of 6.8 and 10.1 years respectively. Variability among regions was higher in DFLE than in life expectancy (LE). The regions with highest LE are not always those with the highest proportion of time lived without disability. CONCLUSIONS: Highest life expectancy does not always mean best health as it has been assumed currently. The DFLE indicator is a useful tool to show health status differences among the Spanish population.     

Anti-inflammatory actions of the heme oxygenase-1 pathway

Heme oxygenase 1 (HO-1) is induced by oxidative or nitrosative stress, cytokines and other mediators produced during inflammatory processes, likely as part of a defence system in cells exposed to stress to provide a negative feedback for cell activation and the production of mediators, which could modulate the inflammatory response. HO-1 activity results in the inhibition of oxidative damage and apoptosis, with significant reductions in inflammatory events including edema, leukocyte adhesion and migration, and production of inflammatory cytokines. HO-1 is induced by nitric oxide (NO) in different biological systems and can control the increased production of this mediator observed in many inflammatory situations. Regulatory interactions between HO-1 and cyclooxygenase (COX) pathways have also been reported. Modulation of signal transduction pathways by HO-1 or products derived from its activity, such as carbon monoxide (CO), may mediate the anti-inflammatory effects of this protein. Regulation of HO-1 activity may be a therapeutical strategy for a number of inflammatory conditions.     

Risk adjustment measures for mortality after hip fracture

OBJECTIVE: To assess factors associated to mortality in patients with hip fracture and to describe different risk adjustment measures. METHODS: Non-concurrent cohort study comprising 390 patients aged 50 years and more. Patients were identified from the Brazilian Unified Health System Hospital Information System, admitted for hip fracture surgery in a teaching hospital in Rio de Janeiro, southeastern Brazil, between 1995 and 2000. Data from medical records were collected and analyzed by logistic regression models to study 90-day mortality odds after admission according to patient and treatment profiles. Severity of illness classification indexes were estimated. RESULTS: Mortality rate was 7.4% and factors affecting mortality were age (OR=1.06; 95% CI: 1.02;1.11), number of co-morbidities (OR=1.44; 95% CI: 1.12;1.69), Charlson co-morbidity index (OR=6.67; 95% CI: 2.98;22.16) and time to surgery (OR=1.04; 95% CI: 1.02;1.07). CONCLUSIONS: Number of co-morbidities and Charlson co-morbidity index helped predicting the mortality rate.     

Cyanobacterium producing cylindrospermopsin cause histopathological changes at environmentally relevant concentrations in subchronically exposed tilapia (Oreochromis niloticus)

The acute toxicity of cylindrospermopsin (CYN) has been established in rodents, based on diverse intraperitoneal an oral exposure studies and more recently in fish. But no data have been reported in fish after subchronic exposure to cyanobacterial cells containing this cyanotoxin, so far. In this work, tilapia (Oreochromis niloticus) were exposed by immersion to lyophilized Aphanizomenon ovalisporum cells added to the aquaria using two concentration levels of CYN (10 or 100 μg CYN L^?1) and deoxy‐cylindrospermopsin (deoxy‐CYN) (0.46 or 4.6 μg deoxy‐CYN L^?1), during two different exposure times: 7 or 14 d. This is the first study showing damage in the liver, kidney, hearth, intestines, and gills of tilapia after subchronic exposure to cyanobacterial cells at environmental relevant concentrations. The major histological changes observed were degenerative processes and steatosis in the liver, membranous glomerulopathy in the kidney, myofibrolysis and edema in the heart, necrotic enteritis in the gastrointestinal tract, and hyperemic processes in gill lamellae and microhemorrhages. Moreover, these histopathological findings confirm that the extent of damage is related to the CYN concentration and length of exposure. Results from the morphometric study indicated that the average of nuclear diameter of hepatocytes and cross‐sections of proximal and distal convoluted tubules are useful to evaluate the damage induced by CYN in the main targets of toxicity. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 261–277, 2015.