Formulation and development of paediatric orally disintegrating carbamazepine tablets.

Carbamazepine is a medicine used to manage epilepsy and partial or tonic-clonic seizures. This study aimed at formulating and obtaining carbamazepine orodispersible tablets for paediatric use at a 50 mg dose, with a diameter not greater than 6 mm and a tablet weight of 80 mg, through a direct compression process. The SeDeM pre-formulation/formulation method was used to define the characteristics of both carbamazepine and the selected excipients for direct compression. This study succeeded in formulating and obtaining the proposed tablets. Following the application of the SeDeM method, the tablets met the mass uniformity test and showed appropriate hardness values for orodispersible tablets. The tablets also met the United States Pharmacopeia (USP) test specifications at t = 60 min. The orodispersible tablets obtained may improve compliance with paediatric treatment with carbamazepine, ensuring the safety and effectiveness of the medicine.

[Cost-effectiveness analysis of fracture liaison services in Catalonia]. / Análisis de coste-efectividad de las Unidades de Coordinación de Fracturas en Cataluña.

OBJECTIVE: To assess the cost-effectiveness of Fracture Liaison Service (FLS) compared to the standard of care for secondary prevention of fragility fractures form the perspective of the Catalan Health Service. METHODS: Cost-utility assessment through a Markov model that simulated disease progression of a patients' cohort candidates to initiate antiosteoporotic treatment after a fragility fracture. A time horizon of 10 years and a 6-month duration per cycle was established. Clinical, economics and quality of life parameters were obtained from the literature and derived from four Catalan FLS. The Catalan Health Service perspective was adopted, considering direct health costs expressed in 2022 euros. A 3% discount rate was applied on costs and outcomes. Uncertainty was assessed through multiple sensitivity analyses. RESULTS: Compared to the standard of care, FLS would promote antiosteoporotic initiation and persistence, reducing the incidence and mortality associated with subsequent fragility fractures. This incremental clinical benefit was estimated at 0.055 years and 0.112 quality-adjusted life years (QALYs) per patient. A higher cost (€1,073.79 per patient) was estimated, resulting into an incremental cost-utility ratio of €9,602.72 per QALYs gained. The sensitivity analyses performed were consistent, corroborating the robustness and conservative approach of the base-case. CONCLUSIONS: The introduction of FLS for the secondary prevention of FF would represent a cost-effective strategy from the Catalan Health Service perspective.

Improvement of the Pour Plate Method by Separate Sterilization of Agar and Other Medium Components and Reduction of the Agar Concentration.

Although the pour plate method is widely employed in microbiological quality control, it has certain drawbacks, including having to melt the culture medium before seeding. In this study, the preparation of the culture medium was modified by using a lower concentration of agar (10 g/L), which was separated from the nutrients during sterilization. The new protocol was assessed in media frequently used in microbiological quality control of food, cosmetics, and pharmaceutical products, with tryptic soy agar (TSA), Sabouraud 4% dextrose agar (SDA), and violet red bile glucose agar (VRBG). In comparison with the conventionally produced media, the modifications significantly improved the growth of Saccharomyces cerevisiae in SDA, Staphylococcus aureus, Salmonella enterica subsp. enterica serovar Typhimurium, and Candida albicans in TSA and Escherichia coli ATCC 8739 and ATCC 25922 and S. Typhimurium in VRBG. The modified VRBG was also more selective for Pseudomonas aeruginosa. Regarding physicochemical properties, a significantly lower pH was observed in TSA and VRBG and lower strength values in TSA. Sterilizing agar separately from the other components of the medium and reducing the agar concentration to 10 g/L can improve microorganism growth and enhance the selectivity of differential media in the pour plate method. These modifications could facilitate the automation of this culture technique. IMPORTANCE In the era of rapid microbiological methods, there is a need to improve long-established culture techniques. Drawbacks of the pour plate method include having to melt each medium separately before seeding. For this technique, we demonstrate that separating the agar from the other components of commonly used media during sterilization and reducing the agar concentration to 10 g/L can enhance microbial growth. The new protocol could have advantages in routine laboratory practice because less agar is required and the same molten agar suspension can be used to prepare different media. Moreover, these modifications could facilitate the automation of the pour plate method.

[Management of severe accidental hypothermia]. / Manejo de la hipotermia accidental severa.

Accidental hypothermia is an environmental condition with basic principles of classification and resuscitation that apply to mountain, sea or urban scenarios. Along with coagulopathy and acidosis, hypothermia belongs to the lethal triad of trauma victims requiring critical care. A customized healthcare chain is involved in its management, extending from on site assistance to intensive care, cardiac surgery and/or the extracorporeal circulation protocols. A good classification of the degree of hypothermia preceding admission contributes to improve management and avoids inappropriate referrals between hospitals. The most important issue is to admit hypothermia victims in asystolia or ventricular fibrillation to those hospitals equipped with the medical technology which these special clinical scenarios require. This study attempts to establish the foundations for optimum management of accidental hypothermia from first emergency care on site to treatment in hospital including, resuscitation and rewarming with extracorporeal circulation.

Improvement of Mueller-Kauffman Tetrathionate-Novobiocin (MKTTn) enrichment medium for the detection of Salmonella enterica by the addition of ex situ-generated tetrathionate.

The detection of Salmonella in food is based on the use of a selective enrichment broth such as Muller-Kauffman Tetrathionate-Novobiocin (MKTTn), in which tetrathionate plays a key role by providing Salmonella with a growth advantage. As sodium tetrathionate is unstable, it is generated in situ by the addition of iodine (Lugol's solution) before seeding. This step is cumbersome as the solution is easily spilled, compromising the performance of the medium and hindering the work of technicians. The aim of this study was to optimize MKTTn broth by generating tetrathionate ex situ through an external reaction between iodine and thiosulphate followed by lyophilization. Quality control procedures were performed to compare the modified and original media, testing pure productivity (enrichment with 50-120 CFU of Salmonella Thyphimurium ATCC 14028 and Salmonella Enteritidis ATCC 13076 and plating on Xylose Lysine Deoxycholate agar, XLD), mixed productivity (50-120 CFU of Salmonella strains and Pseudomonas aeruginosa and Escherichia coli at ≥104 CFU and XLD plating) and selectivity (≥104 CFU of P. aeruginosa and Enterococcus faecalis and plating on Tryptone Casein Soy agar, TSA). The modified MKTTn medium (S/L) performed comparably with the original medium in terms of growth of both Salmonella strains (>300 colonies in XLD), alone or with P. aeruginosa and E. coli. Quantitative assays showed no statistically significant differences in the number of colonies grown on XLD after 10-5 dilution (p = 0.7015 with S. Thyphimurium ATCC 14028 and p = 0.2387 with S. Enteritidis ATCC 13076; ANOVA test). MKTTn medium (S/L) was also selective against E. coli (≤100 colonies) and E. faecalis (<10 colonies). These results suggest that adding tetrathionate as a lyophilisate (S/L) is a feasible alternative to the use of Lugol's solution for the preparation of MKTTn enrichment broth and does not affect the properties of the medium.

Erlotinib 'dosing-to-rash': a phase II intrapatient dose escalation and pharmacologic study of erlotinib in previously treated advanced non-small cell lung cancer.

BACKGROUND: To evaluate the anticancer activity of erlotinib in patients with previously treated, advanced non-small cell lung cancer (NSCLC) whose dose is increased to that associated with a maximal level of tolerable skin toxicity (i.e., target rash (TR)); to characterise the pharmacokinetics (PK) and pharmacodynamics (PD) of higher doses of erlotinib. METHODS: Patients initially received erlotinib 150 mg per day. The dose was successively increased in each patient to that associated with a TR. Anticancer activity was evaluated. Plasma, skin, and hair were sampled for PK and PD studies. RESULTS: Erlotinib dose escalation to 200-475 mg per day was feasible in 38 (90%) of 42 patients. Twenty-four (57%) patients developed a TR, but 19 (79%) did so at 150 mg per day. Five (12%) patients, all of whom developed a TR, had a partial response. Median progression-free survival (PFS) was 2.3 months (95% CI: 1.61, 4.14); median PFS was 3.5 months and 1.9 months, respectively, for patients who did and did not experience a TR (hazard ratio, 0.51; P=0.051). Neither rash severity nor response correlated with erlotinib exposure. CONCLUSION: Intrapatient dose escalation of erlotinib does not appreciably increase the propensity to experience a maximal level of tolerable skin toxicity, or appear to increase the anticancer activity of erlotinib in NSCLC.

CA 19-9 as a biomarker in advanced pancreatic cancer patients randomised to gemcitabine plus axitinib or gemcitabine alone.

BACKGROUND: Response assessment in advanced pancreatic cancer (APC) is difficult and predictive markers are needed. There are insufficient data on the value of carbohydrate antigen 19-9 (CA 19-9) and cytostatic-targeted therapies. Axitinib, a selective vascular endothelial growth factor (VEGF) receptors 1, 2, 3 inhibitor, may increase overall survival (OS) in APC. METHODS: We assessed serum CA 19-9, clinical outcomes and diastolic blood pressure (dBP) in APC patients receiving gemcitabine plus axitinib (Gem+A) or gemcitabine alone. RESULTS: In the total population (N=95), median OS was significantly longer in patients with baseline CA 19-9 values at or below the median than in those with values above it (12.2 months [95% confidence interval (CI), 8.6-16.6%] vs 5.0 months [95% CI, 3.9-5.7%]; P<0.0001). This also reached significance in the Gem+A arm (median OS, 12.5 months [95% CI, 8.6-16.6%] vs 4.9 months [95% CI, 3.6-5.6%]; P<0.0001). Patients with any dBP>90 mmHg had significantly longer OS than those who did not. However, there was no predictive significance of CA 19-9. CONCLUSION: Baseline CA 19-9 levels had prognostic value for OS, but caution is advised in interpreting CA 19-9 as a predictive biomarker for novel cytostatic agents such as VEGF-targeted therapies in phase II studies.

The effect of a multi-target protocol on cetacean detection and abundance estimation in aerial surveys.

A double-platform protocol was implemented in the Bay of Biscay and English Channel during the SCANS-III survey (2016). Two observation platforms using different protocols were operating on board a single aircraft: the reference platform (Scans), targeting cetaceans, and the 'Megafauna' platform, recording all the marine fauna visible at the sea surface (jellyfish to seabirds). We tested for a potential bias in small cetacean detection and density estimation when recording all marine fauna. At a small temporal scale (30 s, roughly 1.5 km), our results provided overall similar perception probabilities for both platforms. Small cetacean perception was higher following the detection of another cetacean within the previous 30 s in both platforms. The only prior target that decreased small cetacean perception during the subsequent 30 s was seabirds, in the Megafauna platform. However, at a larger scale (study area), this small-scale perception bias had no effect on the density estimates, which were similar for the two protocols. As a result, there was no evidence of lower performance regarding small cetacean population monitoring for the multi-target protocol in our study area. Because our study area was characterized by moderate cetacean densities and small spatial overlap of cetaceans and seabirds, any extrapolation to other areas or time requires caution. Nonetheless, by permitting the collection of cost-effective quantitative data for marine fauna, anthropogenic activities and marine litter at the sea surface, the multi-target protocol is valuable for optimizing logistical and financial resources to efficiently monitor biodiversity and study community ecology.

Sex-linked differences in pulse oxymetry.

The difference between genders has generated increasing interest in recent years. It is well known that women and men show differences in their respiratory system: different red blood cell counts, haemoglobin and 2,3-diphosphoglycerate plasma concentrations. Recently, further differences have been found in the ventilatory response to hypoxia and exercise and the evolution of some respiratory illnesses. In this study it was found that during rest at sea level, the haemoglobin oxygen saturation, as measured by pulse oxymetry, is slightly higher in women than in men (98.6 (SD 1.1)% versus 97.9 (SD 0.9)%; p = 0.001). These findings are consistent with other studies, which found gender differences in the transcutaneous or tissue PaO(2). The difference in oxygen saturation is not related to differences in ventilation. The disparity is modest and does not seem to produce great differences in the oxygen content of arterial blood, but combined with the different affinity of haemoglobin for oxygen or different metabolic rate, may play a role in the course of elite competition sports, high altitude ascents or the evaluation of critically ill patients. Further studies are needed to establish the degree, extent and clinical importance of these differences in the saturation of haemoglobin.

Erythrocyte membrane composition in patients with primary hypercholesterolemia.

There are conflicting results regarding the erythrocyte membrane cholesterol and phospholipid content in patients with primary hypercholesterolemia (PHC), due to methodological problems in obtaining haemoglobin-free ghosts. At the same time, the different units used and the fact that the cholesterol and phospholipids are not expressed in relation with integral protein membrane content, produces contradictory results. We have analysed in 33 patients with PHC (12 male, 31 female) aged 43+/-12 years and in 33 healthy normolipaemic volunteers (9 male, 24 female) aged 43+/-13 years plasma lipids, along with, erythrocyte membrane cholesterol, phospholipids and integral proteins. PHC patients showed increased erythrocyte membrane cholesterol: 0.36+/-0.15 mg/mg when compared with controls: 0.29+/-0.75 mg/mg; p=0.018. Phospholipid membrane content, although higher in the cases, did not reach statistical significance (PHC patients: 0.38+/-0.15 mg/mg vs. 0.33+/-0.72 mg/mg; p=0.098). The cholesterol/phospholipids ratio (Chol/Ph) was 0.99+/-0.22 in PHC patients versus 0.92+/-0.28 in controls; p=0.127. Our results suggest that there is a slight increase in erythrocyte membrane cholesterol in patients with PHC. Given the increasing importance of erythrocyte membrane cholesterol in the stability of the atheroma plaque due its possible contribution to the clinical signs of ischaemic heart disease, it seems relevant to determine this parameter in risk populations. Therefore, a simple and reproducible method needs to be standardised which would enable comparisons between laboratories and facilitate further studies aimed to it as a marker of acute coronary syndromes.

Is short-term amiodarone use post cardiac surgery a cause of acute respiratory failure?

AIM: It was believed that amiodarone-related adverse respiratory effects were found only when receiving amiodarone on a long-term basis, but several reports seem to contradict this hypothesis. The aim of this study was to evaluate, in an intensive care unit (ICU), the possibility of acute respiratory toxicity induced by short-term amiodarone administration following cardiac surgery. METHODS: We conducted a prospective clinical trial of 111 consecutive patients admitted to our ICU after cardiac surgery (basically, coronary artery bypass graft and/or valve surgery) and who received short-term prophylactic amiodarone treatment if they were considered at high risk of developing atrial fibrillation. We administered 900 mg/day intravenously for the first 2 days and 600 mg/day on the following days of the ICU stay. The oxygenation index (PaO2/FiO2 ratio) was evaluated at admission, and then 24 and 48 h postsurgery. RESULTS: One-hundred and two patients were included in the study (9 were excluded for bradycardia), and 25 received amiodarone treatment. The Parsonnet and APACHE II scores differed slightly between the treated and nontreated groups. There were no significant differences between the treated and nontreated groups with respect to left atrial pressure, the number of packed red cells transfused or the oxygenation index at admission and 24 and 48 h postsurgery. CONCLUSION: The short-term administration of amiodarone under the conditions of the present study does not seem to affect respiratory function.

An outbreak of hospital-acquired Klebsiella pneumoniae bacteraemia, including strains producing extended-spectrum beta-lactamase.

This study describes the clinical outcome of an outbreak of extended-spectrum beta-lactamase producing Klebsiella pneumoniae (ESBL-KP) bacteraemia. Ninety-two episodes of hospital-acquired K. pneumoniae bacteraemia were studied, 49 ESBL-KP and 43 non-ESBL-KP, from May 1993 to June 1995. Of these, 44 (90%) episodes of ESBL-KP vs. 20 (46%) episodes of non-ESBL-KP occurred in intensive care unit (ICU) patients. The incidence of K. pneumoniae bacteraemia (mainly due to ESBL-KP) increased in the ICU during the outbreak. A significant association was found between intravascular catheter-related bacteraemia and isolation of ESBL-KP [27 (56%) in the ESBL-KP group vs. 13 (30%) in the non-ESBL-KP group;P= 0.01]. The worst prognostic features were identified as age > 65 years (P= 0.02), septic shock (P< 0.001) and secondary bacteraemia (P= 0.04). High rates of resistance to beta-lactam/beta-lactamase inhibitors observed in our ESBL-KP isolates, as well as variable activity of aminoglycosides, restricts the empirical use of these antibiotics. Carbapenems should be the treatment of choice since they are uniformly active against these strains. Our study shows that ESBL-KP bacteraemia occurring in an epidemic ICU setting is mainly catheter-related. We did not find ESBL strains to be associated with a significantly poor outcome.

Risk factors for faecal carriage of Klebsiella pneumoniae producing extended spectrum beta-lactamase (ESBL-KP) in the intensive care unit.

In the course of an outbreak of extended-spectrum beta-lactamase-producing Klebsiella pneumoniae (ESBL-KP) in an intensive care unit (ICU), we conducted active surveillance to determine the risk factors for ESBL-KP faecal colonization of patients. We used weekly rectal samples during a four-month period. ESBL-KP was found in the faeces of 72 of 188 (38%) patients, and 42 (58%) of them were colonized within the first week of admission to the ICU. The probability of remaining free of faecal colonization was less than 20% at 30 days of ICU admission. The risk factors associated with ESBL-KP faecal colonization were clinical severity score at admission (P = 0.004), arterial catheterization (P = 0.002), total parenteral nutrition (P = 0.04), urinary catheterization (P = 0.01), mechanical ventilation (P < 0.001), and previous antibiotic therapy (P = 0.04). A logistic regression analysis identified duration of urinary catheterization (OR:3.5; 95% CI 1.2-10.3) and mechanical ventilation (OR:4.6; 95% CI 1.1-19.3) as independent risk factors for ESBL-KP faecal colonization. Our results suggest that in an ESBL-KP prevalent environment, manipulations that facilitate cross-infection are the most relevant in the acquisition of the micro-organism and risk increases throughout hospitalization.

Epidemiological significance of cutaneous, pharyngeal, and digestive tract colonization by multiresistant Acinetobacter baumannii in ICU patients.

The aim of this prospective study was to assess the relative epidemiological role of digestive tract colonization by Acinetobacter baumannii, in comparison with other body site colonizations, in patients admitted to intensive care units (ICUs). From January to May 1995, axillary, pharyngeal and rectal swabs were taken together within the first 48 h of admission, and then weekly during ICU stay. Seventy-three patients were included, 48 of them (66%) had axillary, pharyngeal, or rectal colonization with A. baumannii, nine (19%) of these 48 during the first 48 h and the remaining 28 (77%) during the first week. Twenty-one (29%) had clinical samples positive for A. baumannii and axillary, pharyngeal, or rectal colonization. In 15 of these 21 (71%), colonization on body sites occurred prior to isolation from clinical samples (mean seven days, range 1-20). Throughout admission, rates of detection of A. baumannii were 75% (36/48) for axillary or pharyngeal swabs and 77% (37/48) for rectal swabs. Combination of two body site swabs yielded culture positive rates of 90% (43/48) for axillary-pharyngeal or axillary-rectal sites, and 96% (46/48) for pharyngeal-rectal. Two epidemic clones were defined by antibiotype and pulsed-field gel electrophoresis (PFGE) of SmaI DNA digests in 48 isolates from 11 patients. We conclude that body sites of patients were a major reservoir for A. baumannii infections in the outbreak. This finding cases doubt on the value of selective decontamination of the digestive tract as an additional infection control measure in this kind of outbreak. The weekly performance of pharyngeal and rectal swabs appears to detect A. baumannii colonization early among ICU patients and enables barrier methods to be applied rapidly.

Intermittent hypobaric hypoxia stimulates erythropoiesis and improves aerobic capacity.

PURPOSE: The purpose of the study was to examine the effect of a very short intermittent exposure to moderate hypoxia in a hypobaric chamber on aerobic performance capacity at sea level and the erythropoietic response. The effects of hypobaric hypoxia alone and combined with low-intensity exercise were also compared. METHODS: Seventeen members of three high-altitude expeditions were exposed to intermittent hypoxia in a hypobaric chamber over 9 d at simulated altitude, which was progressively increased from 4000 to 5500 m in sessions ranging from 3 to 5 h x d(-1). One group (N = 7; HE group) combined passive exposure to hypoxia with low-intensity exercise on a cycle ergometer. Another group (N = 10; H group) was only exposed to passive hypoxia. Before and after the exposure to hypoxia, medical status, performance capacity, and complete hematological and hemorheological profile of subjects were evaluated. RESULTS: No significant differences were observed between the two groups (HE vs H) in any of the parameters studied, indicating that hypoxia alone was responsible for the changes. After the acclimation period, a significant increase in exercise time (mean difference: +3.9%; P < 0.01), and maximal pulmonary ventilation (+5.5%; P < 0.05) was observed during the maximal incremental test at sea level. Individual lactate-velocity curves significantly shifted to the right (P < 0.05), thus revealing an improvement of aerobic endurance. A significant increase was found in PCV (42.1-45.1%; P < 0.0001), RBC count (5.16 to 5.79 x 10(6) x mm(-3); P < 0.0001), reticulocytes (0.5 to 1.1%; P < 0.0001) and hemoglobin (Hb) concentration (14.2 to 16.7 g x dL(-1); P < 0.002). CONCLUSIONS: It was concluded that short-term hypobaric hypoxia can activate the erythropoietic response and improve the aerobic performance capacity in healthy subjects.

Increased blood ammonia in hypoxia during exercise in humans.

The effect of acute hypoxia on blood concentration of ammonia ([NH3]b) and lactate (la-]b) was studied during incremental exercise(IE), and two-step constant workload exercises (CE). Fourteen endurance-trained subjects performed incremental exercise on a cycle ergometer under normoxic (21% O2) and hypoxic (10.4% O2) conditions. Eight endurance-trained subjects performed two-step constant workload exercise at sea level and at a simulated altitude of 5000 m (hypobaric chamber, P(B)=405 Torr; P(O2)=85 Torr) in random order. In normoxia, the first step lasted 25 minutes at an intensity of 85 % of the individual ventilatory anaerobic threshold (AT(vent), ind) at sea level. This reduced workload was followed by a second step of 5 minutes at 115% of their AT(vent), ind. This test was repeated into a hypobaric chamber, at a simulated altitude of 5,000 m. The first step in hypoxia was at an intensity of 65 % of AT(vent), ind., whereas workload for the second step at simulated altitude was the same as that of the first workload in normoxia (85 % of AT(vent), ind). During IE, [NH3]b and [la-]b were significantly higher in hypoxia than in normoxia. Increases in these metabolites were highly correlated in each condition. The onset of [NH3]b and [la-]b accumulation occurred at different exercise intensity in normoxia (181W for lactate and 222W for ammonia) and hypoxia (100W for lactate and 140W for ammonia). In both conditions, during CE, [NH3]b showed a significant increase during each of the two steps, whereas [la-]b increased to a steady-state in the initial step, followed by a sharp increase above 4 mM x L(-1) during the second. Although exercise intensity was much lower in hypoxia than in normoxia, [NH3]b was always higher at simulated altitude. Thus, for the same workload, [NH3]b in hypoxia was significantly higher (p<0.05) than in normoxia. Our data suggest that there is a close relationship between [NH3]b and [la-]b in normoxia and hypoxia during graded intensity exercises. The accumulation of ammonia in blood is independent of that of lactate during constant intense exercise. Hypoxia increases the concentration of ammonia in blood during exercise.

Intermittent hypobaric hypoxia induces altitude acclimation and improves the lactate threshold.

The physiological responses to short-term intermittent exposure to hypoxia in a hypobaric chamber were evaluated. The exposure to hypoxia was compatible with normal daily activity. The ability of the hypoxia program to induce hematological and ventilatory adaptations leading to altitude acclimation and to improve physical performance capacity was tested. Six members of a high-altitude expedition were exposed to intermittent hypoxia and low-intensity exercise (in cycle-ergometer) in the INEFC-UB hypobaric chamber over 17 d, 3-5 h x d(-1), at simulated altitude of 4,000 m to 5,500 m. Following this hypoxia exposure program, significant increases were found in packed cell volume (41 to 44.6%; p<0.05), red blood cells count (4.607 to 4.968 10(6) cells x microL(-1); p<0.05), and hemoglobin concentration (14.8 to 16.4 g x dL(-1); p<0.05), thus implying an increase in the blood oxygen transport capacity. Significant differences in exercise blood lactate kinetics and heart rate were also observed. The lactate vs. exercise load curve shifted to the right and heart rate decreased, thus indicating an improvement of aerobic endurance. These results were associated with a significant increase in the ventilatory anaerobic threshold (p<0.05). Significant increases (p<0.05) in pulmonary ventilation, tidal volume, respiratory frequency, O2 uptake, CO2 output and ventilatory equivalents to oxygen (VE/Vo2) and carbon dioxide (VE/co2) were observed at the ventilatory threshold and within the transitional zone of the curves. We conclude that short-term intermittent exposure to moderate hypoxia, in combination with low-intensity exercise in a hypobaric chamber, is sufficient to improve aerobic capacity and to induce altitude acclimation.

Actividad física y factores de riesgo cardiovascular: evidencia de su interrelación a nivel nacional / Physical activity and cardiovascular risk factors: evidence of their interrelation nationwide

RESUMEN Antecedentes: En nuestro país la prevalencia de diabetes tipo 2 (DT2) y de factores de riesgo cardiovascular (FRCV) aumenta continuamente. Aunque el fenómeno se acompaña de adopción de estilos de vida no saludable que facilitan dicho crecimiento, es escasa la implementación de estrategias que puedan modificar la situación. Objetivo: Revisar la evidencia disponible sobre la magnitud del problema de la diabetes y los FRCV en nuestro país, su posible relación con la práctica de actividad física y potencial mecanismo de acción. Metodología: Evaluación de datos de la tercera Encuesta Nacional de Factores de Riesgo (ENFR) e información referida a factores que contribuyen al crecimiento de la prevalencia de DT2. Igualmente estrategias exitosas utilizadas a nivel mundial para su prevención. Resultados: El índice de masa corporal registrado en la población estudiada muestra un aumento del porcentaje de personas con sobrepeso/obesidad inverso a la práctica de actividad física. Igualmente los resultados de las pruebas de tolerancia a la glucosa oral muestran que sus alteraciones (prediabetes/diabetes) son menores entre quienes realizaban actividad física. El porcentaje de personas con valores de presión arterial dentro del rango normal al igual que de colesterol circulante (según valores meta de guías internacionales), es también significativamente menor entre quienes practicaban actividad física. Conclusión: La evidencia presentada demuestra objetivamente la necesidad/ventajas de implementar un programa de prevención primaria de diabetes a gran escala a nivel nacional para disminuir su crecimiento y la pertinencia de incluir la práctica de actividad física como estrategia de prevención tal como propone el PPDBA.

ABSTRACT Background: In our country, the prevalence of type 2 diabetes (DT2) and cardiovascular risk factors (CVRF) increases continuously. Although the phenomenon is accompanied by the adoption of unhealthy lifestyles that facilitate such growth, there is little implementation of strategies that can modify the situation. Objective: To review the available evidence on the magnitude of the problem of diabetes and CVRF in our country, its possible relationship with the practice of physical activity and potential mechanism of action. Methodology: Evaluation of data from the Third National Survey of Risk Factors (ENFR) and information referred to factors that promote the prevalence growth of T2D. Additionally, successful strategies have been used worldwide for its prevention. Results: The body mass index registered in the studied population shows an increase in the percentage of people with overweight/obesity inverse to the practice of physical activity. Likewise, the results of the oral glucose tolerance tests show that their alterations (prediabetes/ diabetes) are lower among those who performed physical activity. The percentage of people with blood pressure values within the normal range as well as circulating cholesterol (according to target values of international guidelines), is also significantly lower among those who practiced physical activity. Conclusion: The presented evidence objectively demonstrates the need/advantages of implementing a large-scale diabetes primary prevention program at the national level to.

Immunoconjugates against solid tumors: mind the gap.

The objective of immunoconjugate development is to combine the specificity of immunoglobulins with the efficacy of cytotoxic molecules. This therapeutic approach has been validated in hematologic malignancies; however, several obstacles to achieving efficacy in treating solid tumors have been identified. These include insufficient specificity of targets and poor antibody delivery, most specifically to the tumor core. Heterogeneous antigen expression, imperfect vascular supply, and elevated interstitial fluid pressure have been suggested as the factors responsible for the poor delivery of antibodies. Promising immunoconjugates are in development: immunoconjugates targeting the prostate-specific membrane antigen, trastuzumab-DM1, lorvotuzumab mertansine, and SS1P. Advances in cancer biology and antibody engineering may overcome some of the challenges. New small antibody formats, such as single-chain Fv, Fab, and diabodies, may improve penetration within tumor masses. Nevertheless, the cost of treatment might require justification in terms of demonstrable improvement in quality of life in addition to efficacy; further economic evaluation might be necessary before this approach can replace the current standards of care in clinical practice.