Light-Driven Photoconversion of Squaramides with Implications in Anion Transport.

Simple, clean and fast photoconversion of aniline-derived squaramides was achieved by flashlight illumination. UV irradiation enabled the photochemical squaramide ring-opening to generate 1,2-bisketenes, which DMSO trapped as the nucleophilic oxidant. The only photoproducts isolated were 3,4-arylamino maleic anhydrides, which present conformational preferences very different from those of their parent squaramides. Similar photoconversion was achieved in MeOH. The UV-mediated time-dependent anion transport inhibition was demonstrated, establishing a new approach for modulating the transport abilities of AD-squaramides.

Cryopreservation of platelets treated with riboflavin and UV light and stored at -80°C for 1 year.

BACKGROUND: The combination of pathogen reduction technologies (PRTs) and cryopreservation can contribute to building a safe and durable platelet (PLT) inventory. Information about cryopreserved riboflavin and UV light-treated PLTs is scarce. STUDY DESIGN AND METHODS: Twenty-four buffy coat (BC) PLT concentrates were grouped into 12 type-matched pairs, pooled, and divided into 12 non-PRT-treated control units and 12 riboflavin and UV light PRT-treated test units. Both were cryopreserved with 5% DMSO and stored at -80°C for 1 year. The cryopreservation method used was designed to avoid the formation of aggregates. PLT variables (PLT recovery, swirling, pH, MPV, and LDH) and hemostatic function measured by thromboelastography (TEG) were analyzed before cryopreservation (day 1) and post-cryopreservation at day 14 and months 3, 6, and 12 of storage at -80°C. The analyses were carried out within 1-h post-thaw. RESULTS: No aggregates were found in either PLT group at any time. Swirling was observed in both groups. MPV increased and mean pH values decreased over time (p < .001), but the mean pH value was never below 6.4 in either group after 12 months of storage at -80°C. PLT recovery was good and clotting time became significantly shorter over the storage period in both groups (p < .001). CONCLUSION: Our cryopreservation and thawing method prevented aggregate formation in cryopreserved riboflavin-UV-light-treated PLTs, which exhibited good recovery, swirling, pH > 6.4, and procoagulant potential, as evidenced by a reduced clotting time after 12 months of storage at -80°C. The clinical relevance of these findings should be further investigated in clinical trials.

Haemostatic function measured by thromboelastography and metabolic activity of platelets treated with riboflavin and UV light.

BACKGROUND: Pathogen reduction technology (PRT) may damage platelet (PLT) components. To study this, metabolic activity and haemostatic function of buffy coat (BC) PLT concentrates, with or without riboflavin and UV light PRT treatment, were compared. MATERIAL AND METHODS: Twenty-four BC PLT concentrates, leukoreduced and diluted in additive solution, were grouped into 12 type-matched pairs, which were pooled and divided into 12 non-PRT-treated BC PLT concentrates (control units) and 12 riboflavin and UV PRT-treated BC PLT concentrates (test units). Haemostatic function and metabolic parameters were monitored by thrombelastography at days 1, 3, 7 and 14 post collection in both PLT groups. RESULTS: Loss of PLT discoid shape, glucose consumption, lactate production, and decrease in pH were greater in the PRT-treated PLTs than in control PLTs over time (p<0.001). PLT haemostatic function evaluated by clot strength was also significantly weaker in PRT-treated PLTs compared with the excellent clot quality of control PLTs at day 7 (maximum amplitude: 41.27 vs 64.27; p<0.001), and even at day 14 (21.16 vs 60.39; p<0.001) of storage. DISCUSSION: Pathogen reduction technology treatment accelerates and increases platelet storage lesion, resulting in glucose depletion, lactate accumulation, PLT acidification, and discoid shape loss. The clots produced by control PLTs at day 14 were still remarkably strong, whereas at day 7 PRT-treated PLTs produced weaker clots compared to the control group. Clinical trials investigating the efficacy of PRT-treated PLTs transfused at the end of the storage period (day 7), when the in vitro clot strength is weaker, are needed.

Ambient Intelligence Environment for Home Cognitive Telerehabilitation.

Higher life expectancy is increasing the number of age-related cognitive impairment cases. It is also relevant, as some authors claim, that physical exercise may be considered as an adjunctive therapy to improve cognition and memory after strokes. Thus, the integration of physical and cognitive therapies could offer potential benefits. In addition, in general these therapies are usually considered boring, so it is important to include some features that improve the motivation of patients. As a result, computer-assisted cognitive rehabilitation systems and serious games for health are more and more present. In order to achieve a continuous, efficient and sustainable rehabilitation of patients, they will have to be carried out as part of the rehabilitation in their own home. However, current home systems lack the therapist's presence, and this leads to two major challenges for such systems. First, they need sensors and actuators that compensate for the absence of the therapist's eyes and hands. Second, the system needs to capture and apply the therapist's expertise. With this aim, and based on our previous proposals, we propose an ambient intelligence environment for cognitive rehabilitation at home, combining physical and cognitive activities, by implementing a Fuzzy Inference System (FIS) that gathers, as far as possible, the knowledge of a rehabilitation expert. Moreover, smart sensors and actuators will attempt to make up for the absence of the therapist. Furthermore, the proposed system will feature a remote monitoring tool, so that the therapist can supervise the patients' exercises. Finally, an evaluation will be presented where experts in the rehabilitation field showed their satisfaction with the proposed system.

Oral anticoagulation in patients with atrial fibrillation and medical non-neoplastic disease in a terminal stage.

Many patients with non-neoplastic disease develop atrial fibrillation in advanced stages of their disease. The aim of this study is to determine the factors associated with the use of oral anticoagulants in patients with atrial fibrillation and non-neoplastic medical disease in a terminal stage, and whether their use is associated with a longer survival. Design is prospective, observational, multicentre study. Patients with atrial fibrillation and non-neoplastic disease (severe not reversible organ insufficiency) in a terminal stage were included between February 2009 and September 2010. A 6-month follow-up was carried out. We included 314 patients with a mean (SD) age of 82.6 (7.0) years. Their mean (SD) scores in CHADS2 and ATRIA scales were 3.4 (1.2) and 4.7 (2.0), respectively. Anticoagulants were prescribed to 112 (37.5 %) patients. The use of anticoagulants was associated with age (OR 0.96 95 % CI 0.93-0.99, p = 0.046) and to the Barthel index (OR 1.01 95 % CI 1.00-1.02; p = 0.034). After performing a propensity score matching analysis, 262 patients were included in the survival analysis. After 6 months, 133 (50.8 %) patients were dead. The mortality is higher among patients who are not treated with oral anticoagulants (57.1 vs. 39.4 %; p = 0.006), but it is independently associated only with the Barthel index score (HR 0.99 95 % CI 0.98-1.00; p = 0.039), delirium (HR 1.60, 95 % CI 1.08-2.36; p = 0.018), anorexia (HR 1.58 95 % CI 1.05-2.38; p = 0.027), and with the use of calcium channel blockers (HR 0.50 95 % CI 0.30-0.84; p = 0.009). In patients with atrial fibrillation and non-neoplastic disease in a terminal stage, the use of oral anticoagulants is not independently associated with a higher probability of survival.

Identifying Virtual 3D Geometric Shapes with a Vibrotactile Glove.

The emergence of off-screen interaction devices is bringing the field of virtual reality to a broad range of applications where virtual objects can be manipulated without the use of traditional peripherals. However, to facilitate object interaction, other stimuli such as haptic feedback are necessary to improve the user experience. To enable the identification of virtual 3D objects without visual feedback, a haptic display based on a vibrotactile glove and multiple points of contact gives users an enhanced sensation of touching a virtual object with their hands. Experimental results demonstrate the capacity of this technology in practical applications.

Perfil de prescripción farmacológica en pacientes con enfermedades crónicas no neoplásicas en fase avanzada / Drug prescription profile in patients with advanced chronic diseases

Objetivos. Analizar el perfil de prescripción farmacológica y los factores asociados a polifarmacia en pacientes con enfermedades crónicas no neoplásicas en fase avanzada. Material y métodos. Estudio observacional transversal, multicéntrico, realizado en 41 hospitales españoles (proyecto PALIAR). Se definió polifarmacia como el consumo habitual de 5 o más fármacos en los últimos 3 meses y polifarmacia excesiva cuando dicho número era de 10 o más. El grado de adherencia fue evaluado mediante una encuesta rellenada por el paciente o su cuidador. Se analizaron los factores relacionados con la polifarmacia y la no adherencia al tratamiento. Resultados. De 1.847 pacientes, completaron la encuesta 1.778 (96,2%). La edad media fue 78,74 ± 10 años. Los fármacos más prescritos fueron: antihipertensivos (82,6%), gastroprotectores (73,8%), antiagregantes/anticoagulantes (70,3%) y psicotrópicos (51,8%). La prevalencia de polifarmacia/polifarmacia-severa fue de 86,2-31,3% (consumo medio: 8 ± 3,5 fármacos). El 48,2% reconocía cometer errores en la toma: el 38,5% ocasionalmente y el 9,6% casi diariamente o siempre. La no-adherencia se relacionó con: cumplir criterios de paciente pluripatológico, > 3 ingresos en los últimos 3 meses, deterioro cognitivo y la toma de > 5 fármacos. La polifarmacia se asoció con cumplir criterios de paciente pluripatológico, puntuación ECOG < 3, edad < 85 años y > 3 ingresos en los últimos 3 meses. La polifarmacia severa se relacionó con cumplir criterios de paciente pluripatológico y > 3 ingresos en los últimos 3 meses. Conclusiones. La prevalencia de polifarmacia y errores en administración de fármacos en pacientes con enfermedades médicas avanzadas es elevada, por lo que es necesario desarrollar estrategias para mejorar la adherencia en esta población (AU)

Objectives. To analyze the prescription profile and the factors associated with multiple medications (polypharmacy) and non-adherence in patients with advanced chronic diseases. Material and methods. Longitudinal cross-sectional study including 41 Spanish hospitals (PALIAR project). Polypharmacy was defined as a prescribed treatment with five or more drugs, and excessive polypharmacy when the number was ten or more. The adherence was evaluated using a questionnaire completed by the patients or their caregivers. Description of drug prescription profile and analysis was performed on the risk factors associated with multiple medications and non-adherence. Results. The study included 1847 patients, and 1778 (96.2%) completed the questionnaire. Mean age was 78.74±10 years. Antihypertensives (82.6%), gastroprotectives (73.8%), anti-platelets/anticoagulants (70.3%), and psychotropic drugs (51.8%) were the most frequently prescribed drugs. Prevalence of polypharmacy/excessive polypharmacy was 86.2%/31.3%, with a mean of 8±3.5 drugs per patient. Errors in treatment compliance were detected in 48.2% of patients, but 38.5% and 9.6% referred to an occasional or almost daily failure, respectively. Factors associated with non-adherence were: to be a patient with multiple diseases, cognitive impairment, three or more 3 hospital admissions in the last three months, and having polypharmacy. Factors associated with polypharmacy were: to be a patient with multiple diseases, an ECOG score <3, age <85 years, and 3 or more hospital admissions. Factors associated with excessive polypharmacy were: to be a patient with multiple diseases and previous frequent hospital admissions. Conclusions. The prevalence of polypharmacy in patients with advanced chronic diseases is high, and mistakes in treatment compliance are frequent. Further studies with better defined objectives and more specific therapeutic limits are needed (AU)

[Drug prescription profile in patients with advanced chronic diseases]. / Perfil de prescripción farmacológica en pacientes con enfermedades crónicas no neoplásicas en fase avanzada.

OBJECTIVES: To analyze the prescription profile and the factors associated with multiple medications (polypharmacy) and non-adherence in patients with advanced chronic diseases. MATERIAL AND METHODS: Longitudinal cross-sectional study including 41 Spanish hospitals (PALIAR project). Polypharmacy was defined as a prescribed treatment with five or more drugs, and excessive polypharmacy when the number was ten or more. The adherence was evaluated using a questionnaire completed by the patients or their caregivers. Description of drug prescription profile and analysis was performed on the risk factors associated with multiple medications and non-adherence. RESULTS: The study included 1847 patients, and 1778 (96.2%) completed the questionnaire. Mean age was 78.74±10 years. Antihypertensives (82.6%), gastroprotectives (73.8%), anti-platelets/anticoagulants (70.3%), and psychotropic drugs (51.8%) were the most frequently prescribed drugs. Prevalence of polypharmacy/excessive polypharmacy was 86.2%/31.3%, with a mean of 8±3.5 drugs per patient. Errors in treatment compliance were detected in 48.2% of patients, but 38.5% and 9.6% referred to an occasional or almost daily failure, respectively. Factors associated with non-adherence were: to be a patient with multiple diseases, cognitive impairment, three or more 3 hospital admissions in the last three months, and having polypharmacy. Factors associated with polypharmacy were: to be a patient with multiple diseases, an ECOG score <3, age <85 years, and 3 or more hospital admissions. Factors associated with excessive polypharmacy were: to be a patient with multiple diseases and previous frequent hospital admissions. CONCLUSIONS: The prevalence of polypharmacy in patients with advanced chronic diseases is high, and mistakes in treatment compliance are frequent. Further studies with better defined objectives and more specific therapeutic limits are needed.

Development of a six-month prognostic index in patients with advanced chronic medical conditions: the PALIAR score.

CONTEXT: Efforts in developing useful tools to properly identify the end-of-life trajectory of patients with advanced medical diseases have been made, but the calibration and/or discriminative power of these tools has not been optimal. OBJECTIVES: Our objective was to develop a new, reliable prognostic tool to identify the probability of death within six months in patients with chronic medical diseases. METHODS: This was a multicenter, prospective, observational study in 41 Spanish hospitals, which included 1778 patients with one or more of the following: advanced conditions such as heart failure, respiratory failure, chronic renal failure, chronic liver disease, and/or chronic neurological disease. All patients were followed over six months. Each factor independently associated with death in the derivation cohort (884 patients from eastern areas of Spain) was assigned a prognostic weight, and the score was calculated by summing up the factors. The score's accuracy in the validation cohort (894 patients from western areas of Spain) was assessed by analyzing its calibration and discriminative power; we also calculated sensitivity, specificity, and positive and negative predictive values. RESULTS: Mortality in the derivation/validation cohorts was 37.6%/37.7%, respectively. We identified six independent predictors of mortality (≥85 years, three points; New York Heart Association Class IV/Stage 4 dyspnea on the modified Medical Research Council, 3.5 points; anorexia, 3.5 points; presence of pressure ulcer(s), three points; Eastern Cooperative Oncology Group Performance Status of three or more, four points; and albuminemia ≤2.5g/dL, four points). Mortality in the derivation/validation cohorts according to risk group was 20%/21.5% for patients with zero points; 33%/30.5% for those with 3-3.5 points; 46.3%/43% for those with four to seven points; and 67%/61% for those who reached 7.5 or more points, respectively. The calibration was good (Hosmer-Lemeshow test, P=0.39), as was the discriminative power (area under the receiver operating characteristic curve of 0.69 [0.66-0.72]). The sensitivity (85%), specificity (86%), positive and negative predictive values (64% and 80%, respectively) at 180 days were high. CONCLUSION: The PALIAR score is a precise and reliable tool for identifying the end-of-life trajectory in patients with advanced medical diseases.

Perianal versus endoanal application of glyceryl trinitrate 0.4% ointment in the treatment of chronic anal fissure: results of a randomized controlled trial. Is this the solution to the headaches?

BACKGROUND: Application of nitroglycerin (glyceryl trinitrate) ointment with perianal administration is a widely used treatment for chronic anal fissure. However, headache occurs after application in 20% to 70% patients and leads to withdrawal in 10% of patients. OBJECTIVE: The aim of the study was to investigate whether endoanal application of the ointment may lower the frequency of headaches without sacrificing effectiveness. compare the effects of perianal versus endoanal administration of nitroglycerin ointment on frequency of headache and rate of healing in the treatment of chronic anal fissure. DESIGN: This was a prospective randomized clinical trial (ClinicalTrial.gov, NCT01132391). SETTINGS AND PATIENTS: Study participants were consecutive patients with a diagnosis of chronic anal fissure treated at a university teaching hospital in Elche, Alicante, Spain. INTERVENTION: Patients were randomly assigned to receive perianal (n = 26) or endoanal (n = 26) administration of 0.4% nitroglycerin ointment (375 mg of ointment containing 1.5 mg of glyceryl trinitrate), applied every 12 hours over an 8-week period. MAIN OUTCOME MEASURES: The primary endpoint of the study was the number of patients with headache within 3 hours after application of the ointment, analyzed with the intention-to-treat principle. Intensity of headache pain was rated on a 10-point visual analog scale. Secondary endpoints included frequencies of fissure healing, anorectal pain, rectal bleeding, pruritus, and incontinence. RESULTS: Headaches were reported in 14 (54%) patients with perianal treatment and in 6 patients (23%) with anorectal treatment (p = 0.003). The median headache pain score was 6 (range, 0-10) in the perianal group and 4.5 (range, 0-10) in the endoanal group (p = 0.03). Disabling headaches led to crossover from perianal to endoanal treatment in 4 patients (15%), and from endoanal to perianal treatment in 1 patient (4%) (p = 0.004). Of the 4 patients who switched from perianal to endoanal treatment, 2 reported improvement in headaches and 2 stopped treatment. The patient who switched from endoanal to perianal treatment also showed no improvement and stopped treatment. The healing rate at 24-week follow-up was 62% (16 patients) with perianal treatment and 77% (20 patients) with endoanal treatment (p < 0.05). LIMITATIONS: Effects on sphincter pressure were not evaluated because manometric measurements were not available. CONCLUSIONS: Endoanal application significantly reduces the frequency of headaches due to treatment with 0.4% nitroglycerin ointment and results in a higher healing rate compared with perianal administration. However, roughly 1 in 4 patients still experiences headaches. Our data suggest that endoanal application may be a better option for treatment of anal fissure with nitroglycerin ointment.

Efectividad de la combinación de atorvastatina 10 mg más ezetimiba en el control de la hipercolesterolemia en atención primaria / Effectiveness of the combination of atorvastatin 10 mg plus ezetimibe in controlling hypercholesterolemia in primary care

Objetivos. Analizar la efectividad de atorvastatina 10 mg combinada con ezetimiba respecto a atorvastatina en altas dosis para el tratamiento de la hipercolesterolemia en pacientes de alto riesgo cardiovascular en atención primaria. Pacientes y método. Estudio transversal retrospectivo, de intervención en condiciones de uso habitual en pacientes hipercolesterolémicos con alto riesgo cardiovascular (diabéticos tipo II o postinfarto de miocardio y cifras de colesterol de las lipoproteínas de baja densidad [cLDL] > 100 mg/dl). Se incluyó un total de 102 pacientes (el 44,8% varones) con una media ± desviación estándar de edad de 60,9 ± 9,4 años. Un 61,4% eran diabéticos, el 52,1% había tenido episodio de cardiopatía isquémica. Recibieron tratamiento con atorvastatina 10 mg + ezetimiba 49 pacientes y 53 recibieron atorvastatina 40 mg/día durante 4 meses. Resultados. El cLDL, el colesterol total y los triglicéridos se redujeron significativamente con ambos tratamientos, si bien la combinación de ambos tratamientos redujo más rápidamente los parámetros lipídicos (2 meses; p < 0,05) que atorvastatina en altas dosis; a los 4 meses hubo reducciones de cLDL del 35,42% con la combinación de la estatina con ezetimiba y del 25,69% con la estatina sola; la reducción del cLDL fue de 57,58 ± 27,83 mg/dl y 58,33 ± 14,22 mg/dl a los 2 y 4 meses, respectivamente, con la combinación, frente a 16,4 ± 22,62 mg/dl y 40,14 ± 10,8 mg/dl con atorvastatina en altas dosis. A los 4 meses alcanzaron los objetivos terapéuticos de control de cLDL de acuerdo con las recomendaciones de la Adaptación Española de la Guía Europea de Prevención Cardiovascular de 2004 un 60,4% de los tratados con la combinación de fármacos y un 51,5% de los tratados con atorvastatina. Conclusiones. Ambos tratamientos se han mostrado efectivos en reducir las cifras de colesterol. Sin embargo, la combinación de atorvastatina en dosis de 10 mg y ezetimiba ha sido más efectiva y rápida que atorvastatina sola en altas dosis (AU)

Objectives. To analyze the effectiveness of atorvastatin 10 mg plus ezetimibe versus high-dose atorvastatin in the treatment of hypercholesterolemia in patients with high cardiovascular risk in primary care. Patients and method. We performed a retrospective, cross-sectional study of an intervention performed under conditions of normal use in hypercholesterolemic patients with high cardiovascular risk (type II diabetes or postmyocardial infarction and low density lipoprotein cholesterol [LDLc] values > 100 mg/dl). A total of 102 patients (44.8% men) with a mean age ± standard deviation of 60.9 ± 9.4 years were included. Of these, 61.4% were diabetic and 52.1% had had an episode of ischemic heart disease. Forty-nine patients received treatment with atorvastatin 10 mg plus ezetimibe and 53 received atorvastatin 40 mg/day for 4 months. Results. Values of LDLc, total cholesterol (TC) and triglycerides were significantly reduced with both treatments. However, the combined treatments produced a more rapid reduction in lipid parameters (2 months; p < 0.05) than did high-dose atorvastatin. At 4 months, a reduction in LDLc of 35.42% was found for the combination of atorvastatin plus ezetimibe versus 25.69% with atorvastatin alone; at 2 and 4 months, LDLc was reduced by 57.58 ± 27.83 mg/dl and 58.33 ± 14.22 respectively with the combined treatment compared with a decrease of 16.4 ± 22.62 and 40.14 ± 10.8 mg/dl with high-dose atorvastatin. At 4 months, the therapeutic targets for LDLc control, based on the recommendations of the Spanish adaptation of the European Guidelines on Cardiovascular Disease Prevention of 2004, had been achieved by 60.4% of patients receiving the combined treatment and by 51.5% of those treated with atorvastatin. Conclusions. Both treatments were effective in reducing cholesterol values. However, atorvastatin 10 mg and ezetimibe were faster and more effective than high-dose atorvastatin alone (AU)

A pharmacoeconomic evaluation of statins in the treatment of hypercholesterolaemia in the primary care setting in Spain.

BACKGROUND: Cardiovascular disease is one of the leading causes of death and it has been shown that primary prevention with the HMG-CoA reductase inhibitor (statin) lipid-lowering drugs can reduce cardiovascular events. Acquisition costs vary between statins and this may be an important consideration in the overall cost effectiveness (CE) of different options. OBJECTIVE: To perform a CE study of the main statins used in Spain for primary prevention of cardiovascular disease in patients with high cholesterol levels [corrected] STUDY DESIGN: The CE analysis was based on an open-label, prospective, naturalistic, randomised intervention study under usual care conditions in primary care settings in patients with high cholesterol levels (total cholesterol [TC] >240 mg/dL, low-density lipoprotein cholesterol [LDL-C] >160 mg/dL) and one or more cardiovascular risk factors. The analysis was conducted from the perspective of the Spanish National Health System; the year of costing was 2001. PATIENTS: A total of 161 patients (49.7% males), mean age 65 +/- 10.3 years, without evidence of cardiovascular disease were included in the study. Of those, 82.1% were hypertensive, 37.1% had diabetes mellitus and 17.9% were smokers. INTERVENTIONS: Forty-eight patients received oral atorvastatin 10 mg/day, 32 received fluvastatin 40 mg/day, 44 received simvastatin 20 mg/day and 37 patients received pravastatin 20 mg/day for 6 months. MAIN MEASUREMENTS AND RESULTS: After 6 months, the therapeutic goals of LDL-C control, according to the recommendations of the Spanish Society of Arteriosclerosis--Consensus-2000, were reached in 62.5%, 43.8%, 45.5% and 40.5% of patients treated with atorvastatin, fluvastatin, simvastatin and pravastatin, respectively. The average CE ratio, expressed as the cost in euros (euro) per patient achieving the therapeutic goals, was euros 424.3 for atorvastatin, euros 503.5 for fluvastatin, euros 527.0 for simvastatin and euros 683.4 for pravastatin. The incremental CE ratios for atorvastatin versus fluvastatin and simvastatin were euros 238.9 and euros 149.5, respectively, per additional patient reaching therapeutic goals. Atorvastatin, fluvastatin and simvastatin all dominated pravastatin. CONCLUSIONS: All the statins studied have been shown to be effective for reducing both TC and LDL-C levels. In this study, atorvastatin was the most efficient drug, with the best CE ratio (cost per patient reaching therapeutic goals). Atorvastatin was more effective and less costly than pravastatin, and when compared with fluvastatin or simvastatin the additional cost per additional patient achieving therapeutic goals was