[Factors associated with dissatisfaction with pharmacological treatment in patients with type 2 diabetes mellitus: A cross-sectional study]. / Factores asociados a la insatisfacción con el tratamiento farmacológico en pacientes con diabetes mellitus tipo 2: estudio transversal.

BACKGROUND AND OBJECTIVES: Diabetes is a chronic disease with a high impact on both health and Quality of Life Related to Health (QLRH). To evaluate the satisfaction of treatment in patients with type 2 diabetes mellitus through the Diabetes Treatment Satisfaction Questionnaire (DTSQ) and its relationship with sociodemographic variables, with antidiabetic medication and clinical-analytical variables. MATERIALS AND METHODS: This cross-sectional study was conducted in General University Hospital of San Juan de Alicante between September 2016 and December 2017. Two hundred thirty-two patients diagnosed with type 2 diabetes mellitus at least 1 year before inclusion, treated with antidiabetic medication were included. The Spanish version of the DTSQ scale was used to measure satisfaction with treatment. Factors associated with low satisfaction were analyzed by applying the Chi-square test for qualitative variables and Student-T for quantitative variables. To estimate magnitudes of association, logistic models were adjusted. RESULTS: Two hundred thirty-two patients were included in this study. 21.5% of the patients presented low satisfaction with the treatment. Patients who presented low satisfaction with treatment were associated with medications that could cause hypoglycemia (OR: 2.872 [1.195-6.903]), HbA1c levels higher than 7% (OR: 2.260 [1.005-5.083]) and drugs administered by the route oral (OR: 2.749 [1.233-6.131]). CONCLUSIONS: Patients with type 2 diabetes mellitus who had a lower score on the DTSQ questionnaire were associated with medications that produced hypoglycaemia, and with higher levels of HbA1c higher than 7%, and those who took oral medication.

[Analysis of two health attendance models for the non-hospital emergencies in Gipuzkoa: Retrospective study]. / Análisis de dos modelos asistenciales para la atención de las emergencias extrahospitalarias en Guipúzcoa: Estudio retrospectivo.

BACKGROUND AND OBJECTIVE: Out-of-hospital medical emergency services are defined as a functional organization that performs a set of sequential human and material activities. The objective of this study was to compare the mortality of patients attended by the out-of-hospital medical emergency services in 2 neighboring Spanish regions with different models of healthcare transport assistance for emergency care. MATERIAL AND METHOD: Retrospective observational cohort study, done between June 1, 2007 and December 31, 2008 in 2 regions of Gipuzkoa, Alto Deba (AD) and Bajo Deba (BD). The study variables were age, sex and place of exposure (AD/BD), heart rate, blood pressure, initial reason for the call defined by the European Resuscitation Council, unconsciousness and digestive bleeding. 3452 subjects were analyzed. RESULTS: The risk of in situ mortality in BD was 1.31 times higher than in AD (P=.050), that of hospital mortality in BD was 0.71 times lower than in AD (P=.011) and the risk of mortality at one year between counties and the combined mortality (in situ+hospital) did not contribute significant differences. CONCLUSIONS: Mortality (in situ+in-hospital, and one year aftercare) of patients treated by the out-of-hospital emergency medical services in AD (non-medicalized healthcare transport model) was similar to that of the BD region (mixed healthcare transport model).

Incubation period of COVID-19: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: The incubation period of COVID-19 helps to determine the optimal duration of the quarantine and inform predictive models of incidence curves. Several emerging studies have produced varying results; this systematic review aims to provide a more accurate estimate of the incubation period of COVID-19. METHODS: For this systematic review, a literature search was conducted using Pubmed, Scopus/EMBASE, and the Cochrane Library databases, covering all observational and experimental studies reporting the incubation period and published from 1 January 2020 to 21 March 2020.We estimated the mean and 95th percentile of the incubation period using meta-analysis, taking into account between-study heterogeneity, and the analysis with moderator variables. RESULTS: We included seven studies (n=792) in the meta-analysis. The heterogeneity (I2 83.0%, p<0.001) was significantly decreased when we included the study quality and the statistical model used as moderator variables (I2 15%). The mean incubation period ranged from 5.6 (95% CI: 5.2-6.0) to 6.7 days (95% CI: 6.0-7.4) according to the statistical model. The 95th percentile was 12.5 days when the mean age of patients was 60 years, increasing 1 day for every 10 years. CONCLUSION: Based on the published data reporting the incubation period of COVID-19, the mean time between exposure and onset of clinical symptoms depended on the statistical model used, and the 95th percentile depended on the mean age of the patients. It is advisable to record sex and age when collecting data in order to analyze possible differential patterns.

[Incubation period of COVID-19: A systematic review and meta-analysis]. / Período de incubación de la COVID-19: revisión sistemática y metaanálisis.

BACKGROUND AND OBJECTIVE: The incubation period of COVID-19 helps to determine the optimal duration of the quarantine and inform predictive models of incidence curves. Several emerging studies have produced varying results; this systematic review aims to provide a more accurate estimate of the incubation period of COVID-19. METHODS: For this systematic review, a literature search was conducted using Pubmed, Scopus/EMBASE, and the Cochrane Library databases, covering all observational and experimental studies reporting the incubation period and published from 1 January 2020 to 21 March 2020.We estimated the mean and 95th percentile of the incubation period using meta-analysis, taking into account between-study heterogeneity, and the analysis with moderator variables. RESULTS: We included seven studies (n = 792) in the meta-analysis. The heterogeneity (I2 83.0%, p < 0.001) was significantly decreased when we included the study quality and the statistical model used as moderator variables (I2 15%). The mean incubation period ranged from 5.6 (95% CI: 5.2 to 6.0) to 6.7 days (95% CI: 6.0 to 7.4) according to the statistical model. The 95th percentile was 12.5 days when the mean age of patients was 60 years, increasing 1 day for every 10 years. CONCLUSION: Based on the published data reporting the incubation period of COVID-19, the mean time between exposure and onset of clinical symptoms depended on the statistical model used, and the 95th percentile depended on the mean age of the patients. It is advisable to record sex and age when collecting data in order to analyze possible differential patterns.

Incubation period of COVID-19: A systematic review and meta-analysis. / Período de incubación de la COVID-19: revisión sistemática y metaanálisis.

BACKGROUND AND OBJECTIVE: The incubation period of COVID-19 helps to determine the optimal duration of the quarantine and inform predictive models of incidence curves. Several emerging studies have produced varying results; this systematic review aims to provide a more accurate estimate of the incubation period of COVID-19. METHODS: For this systematic review, a literature search was conducted using Pubmed, Scopus/EMBASE, and the Cochrane Library databases, covering all observational and experimental studies reporting the incubation period and published from 1 January 2020 to 21 March 2020.We estimated the mean and 95th percentile of the incubation period using meta-analysis, taking into account between-study heterogeneity, and the analysis with moderator variables. RESULTS: We included seven studies (n = 792) in the meta-analysis. The heterogeneity (I2 83.0%, p < 0.001) was significantly decreased when we included the study quality and the statistical model used as moderator variables (I2 15%). The mean incubation period ranged from 5.6 (95% CI: 5.2 to 6.0) to 6.7 days (95% CI: 6.0 to 7.4) according to the statistical model. The 95th percentile was 12.5 days when the mean age of patients was 60 years, increasing 1 day for every 10 years. CONCLUSION: Based on the published data reporting the incubation period of COVID-19, the mean time between exposure and onset of clinical symptoms depended on the statistical model used, and the 95th percentile depended on the mean age of the patients. It is advisable to record sex and age when collecting data in order to analyze possible differential patterns.

Validation of self-reported adherence in chronic patients visiting pharmacies and factors associated with the overestimation and underestimation of good adherence.

BACKGROUND: Studies validating indirect methods to identify nonadherence in chronic patients who visit pharmacies are lacking. The aim of this study was to validate self-reported adherence and assess the variables associated with both overestimation and underestimation of good adherence when using this method. MATERIALS AND METHODS: An observational, cross-sectional study was undertaken to validate self-reported adherence in 132 community pharmacies throughout Spain in 6237 chronic patients. The Morisky-Green test was used as the validation method and through a 2 × 2 table, the validity indicators, predictive values, and likelihood ratios were calculated. To assess the variables associated with both overestimation and underestimation of good adherence, multivariate logistic regression analysis and calculation of the area under the ROC curve were used to evaluate discriminatory capacity. RESULTS: Sensitivity was 27.8% (95% CI: 26.2-29.4) and specificity was 93.9% (95% CI: 93.1-94.7). Discrepancy analysis obtained a significant overestimation of good adherence (p < 0.001). The factors associated with overestimating good adherence were performing a mnemonic trick (p < 0.001), not self-medicating (p < 0.001), a high level of physical activity (p < 0.001), and an older age (p = 0.014). Factors associated with underestimation were self-medication (p < 0.001), desiring more information (p < 0.001), smoking (p = 0.014), not engaging in physical activity in the low (p = 0.006) or high (p < 0.001) categories, having a younger mean age (p = 0.007), and taking two to three (p = 0.029) or four or more (p < 0.001) chronic treatments. CONCLUSION: Self-reported adherence has good specificity but poor sensitivity. The associated profiles of the discrepancies were obtained to identify both good and poor adherence.

Waning protection of influenza vaccination during four influenza seasons, 2011/2012 to 2014/2015.

BACKGROUND: Concerns have been raised about intraseasonal waning of the protection conferred by influenza vaccination. METHODS: During four influenza seasons, we consecutively recruited individuals aged 18years or older who had received seasonal influenza vaccine and were subsequently admitted to the hospital for influenza infection, asassessed by reverse transcription polymerase chain reaction. We estimated the adjusted odds ratio (aOR) of influenza infection by date of vaccination, defined by tertiles, as early, intermediate or late vaccination. We used a test-negative approach with early vaccination as reference to estimate the aOR of hospital admission with influenza among late vaccinees. We conducted sensitivity analyses by means of conditional logistic regression, Cox proportional hazards regression, and using days between vaccination and hospital admission rather than vaccination date. RESULTS: Among 3615 admitted vaccinees, 822 (23%) were positive for influenza. We observed a lower risk of influenza among late vaccinees during the 2011/2012 and 2014/2015A(H3N2)-dominant seasons: aOR=0.68 (95% CI: 0.47-1.00) and 0.69 (95% CI: 0.50-0.95). We found no differences in the risk of admission with influenza among late versus early vaccinees in the 2012/2013A(H1N1)pdm09-dominant or 2013/2014B/Yamagata lineage-dominant seasons: aOR=1.18 (95% CI: 0.58-2.41) and 0.98 (95% CI: 0.56-1.72). When we restricted our analysis to individuals aged 65years or older, we found a statistically significant lower risk of admission with influenza among late vaccinees during the 2011/2012 and 2014/2015A(H3N2)-dominant seasons: aOR=0.61 (95% CI: 0.41-0.91) and 0.69 (95% CI: 0.49-0.96). We observed 39% (95% CI: 9-59%) and 31% (95% CI: 5-50%) waning of vaccine effectiveness among participants aged 65years or older during the two A(H3N2)-dominant seasons. Similar results were obtained in the sensitivity analyses. CONCLUSION: Waning of vaccine protection was observed among individuals aged 65years old or over in two A(H3N2)-dominant influenza seasons.

Analysing the concept of diagnostic inertia in hypertension: a cross-sectional study.

AIMS: The aim of this study was to quantify diagnostic inertia (DI) when the physician fails to diagnose hypertension and determine its associated factors. METHODS: This cross-sectional, observational study involved all patients without a diagnosis of hypertension who had their blood pressure (BP) measured at least three times during the second half of 2010 (N = 48,605). Patients with altered mean BP figures (≥ 140/90 mmHg) were considered to experience DI. Secondary variables: gender, atrial fibrillation, diabetes mellitus, dyslipidemia, cardiovascular disease, age and the physician having attended a cardiovascular training course (ESCARVAL). Associated factors were assessed by multivariate logistic regression analysis. RESULTS: Diagnostic inertia was present in 6450 patients (13.3%, 95% CI: 13.0-13.6%). Factors significantly associated with DI were: male gender (OR = 1.46, 95% CI: 1.37-1.55, p < 0.001), atrial fibrillation (OR = 0.73, 95% CI: 0.58-0.92, p = 0.007), the ESCARVAL cardiovascular course (OR = 0.88, 95% CI: 0.81-0.96, p = 0.005), diabetes mellitus (OR = 0.93, 95% CI: 0.87-0.99, p = 0.016), cardiovascular disease (OR = 0.77, 95% CI: 0.67-0.88, p < 0.001) and older age (years) (18-44→OR = 1; 45-59→OR = 12.45, 95% CI: 11.11-13.94; 60-74→OR = 18.11, 95% CI: 16.30-20.12; ≥ 75→OR = 20.43, 95% CI: 18.34-22.75; p < 0.001). The multivariate model had an area under the ROC curve of 0.81 (95% CI: 0.80-0.81, p < 0.001). CONCLUSIONS: This study will help clinical researchers differentiate between the two forms of DI (interpretation of a positive screening test and interpretation of positive diagnostic criteria). The results found here in patients with hypertension suggest that this problem is prevalent, and that a set of associated factors can explain the outcome well (AUC>0.80).

[Incidence and preventability of haemorrhagic strokes. Results of the Ebrictus register]. / Incidencia y evitabilidad de los ictus hemorragicos. Resultados del registro Ebrictus.

AIM: To determine the population incidence of intracerebral haemorrhage and its preventable incidence, associated risk factors and prognosis of death and disability. SUBJECTS AND METHODS: We examined a sample of 240 consecutive patients with a first episode of intracerebral haemorrhage between 1st April 2006 and 30th June 2015. The main variables are: NIHSS scale, comorbidity, pharmacological information, Barthel index, Rankin scale, time within therapeutic window, prognosis and destination on hospital discharge. The 'unnecessarily premature and sanitarily avoidable mortality' (MIPSE) classification was applied to define the cases as 'preventable incidence'. RESULTS: The rate of population incidence of haemorrhagic cerebrovascular disease was 23.5 cases per 100,000 inhabitants/year; an exponential increase occurred from the age of 55 years in males and 75 years in females. The rate ratio was 0.682. The preventable incidence would account for 66.6% of all the cases in those under 75 years of age and 22.7% in those aged 75 or over. The chances of survival and functional autonomy were significantly lower in females, and age, anticoagulant treatment, the presence of polymedication and treatment with serotonin reuptake inhibitor antidepressants were factors that were independent of the prognosis. CONCLUSIONS: The incidence of haemorrhagic cerebrovascular disease does not appear to be modified within the period, but just the opposite occurs with the factors associated according to sex and age. According to the MIPSE classification, the preventability of haemorrhagic cerebrovascular disease could be as high as 36%.

TITLE: Incidencia y evitabilidad de los ictus hemorragicos. Resultados del registro Ebrictus.Objetivo. Conocer la incidencia poblacional de la hemorragia intracerebral y su incidencia evitable, factores de riesgo asociados y pronostico de muerte y discapacidad. Sujetos y metodos. Muestra de 240 pacientes consecutivos con un primer episodio de hemorragia intracerebral entre el 1 de abril de 2006 y el 30 de junio de 2015. Las variables principales son: escala NIHSS, comorbilidad, informacion farmacologica, indice de Barthel, escala de Rankin, tiempo en rango terapeutico, pronostico y destino al alta hospitalaria. Se aplico la clasificacion 'mortalidad innecesariamente prematura y sanitariamente evitable' (MIPSE) para definir los casos como 'incidencia evitable'. Resultados. La tasa de incidencia poblacional de enfermedad cerebrovascular hemorragica fue de 23,5 casos por 100.000 habitantes/año; se produjo un incremento exponencial a partir de los 55 años en hombres y 75 años en mujeres. La razon de tasas fue de 0,682. La incidencia evitable significaria el 66,6% de todos los casos en los menores de 75 años y el 22,7% en aquellos con 75 o mas años. La probabilidad de supervivencia y la autonomia funcional fueron significativamente inferiores en las mujeres, y la edad, el tratamiento anticoagulante, la presencia de polimedicacion y el tratamiento con antidepresivos inhibidores de la recaptacion de serotonina fueron factores independientes del pronostico. Conclusiones. No parece que se modifique la incidencia de enfermedad cerebrovascular hemorragica en el periodo, pero si los factores asociados segun sexo y edad. Segun la clasificacion MIPSE, la evitabilidad de la enfermedad cerebrovascular hemorragica seria de hasta un 36%.

Differences in the management of hypertension, diabetes mellitus and dyslipidemia between obesity classes.

We did not find any paper that assessed clinical inertia in obese patients. Therefore, no paper has compared the clinical inertia rates between morbidly and nonmorbidly obese patients. A cross-sectional observational study was carried out. We analysed 8687 obese patients ⩾40 years of age who attended their health-care center for a checkup as part of a preventive program. The outcome was morbid obesity. Secondary variables were as follows: failure in the management of high blood pressure (HBP), high blood cholesterol (HBC) and high fasting blood glucose (HFBG); gender; personal history of hypertension, dyslipidemia, diabetes, smoking and cardiovascular disease; and age (years). We analysed the association between failures and morbid obesity by calculating the adjusted odds ratio (OR). Of 8687 obese patients, 421 had morbid obesity (4.8%, 95% confidence interval (CI): 4.4-5.3%). The prevalence rates for failures were as follows: HBP, 34.7%; HBC, 35.2%; and HFBG, 12.4%. Associated factors with morbid obesity related with failures were as follows: failure in the management of HBP (OR=1.42, 95% CI: 1.15-1.74, P=0.001); failure in the management of HBC (OR=0.73, 95% CI: 0.58-0.91, P=0.004); and failure in the management of HFBG (OR=2.24, 95% CI: 1.66-3.03, P<0.001). Morbidly obese patients faced worse management for HBP and HFBG, and better management for HBC. It would be interesting to integrate alarm systems to avoid this problem.

A Tool to Quickly Detect Short Hamstring Syndrome in Boys who Play Soccer.

UNLABELLED: There is a lack of studies of alternative techniques differing from the straight leg raise test (SLR) and the passive knee extension test (PKE) to diagnose short hamstring syndrome (SHS). We built a predictive model with simple parameters to diagnose SHS and implemented it in a mobile app. This cross-sectional study analyzed 85 Spanish boys aged 10-16 years who played soccer in 2012. OUTCOMES: SHS (SLR<70° and/or PKE>15°), and grade II SHS (SLR<60° and/or PKE≥35°). Secondary variables: toe-touch test (TT), body mass index (BMI), age, laterality and number of years registered as part of a federation. A risk table implemented in a mobile app was built to estimate the probability of SHS and grade II SHS according to secondary variables. The area under the ROC curve (AUC) was calculated and we constructed risk groups. Scoring factors for SHS: low TT, younger age and lower BMI. AUC: 0.89 (95% CI: 0.82-0.96, p<0.001). Scoring factors for grade II SHS: younger age, higher BMI, left footed and lower TT. AUC: 0.78 (95% CI: 0.68-0.88, p<0.001). We provide a tool with minimum material but with a high discriminatory power to quickly calculate whether a boy who plays soccer has SHS. The models need validation studies.

Early rehospitalization after hip fracture in elderly patients: risk factors and prognosis.

INTRODUCTION: Hip fracture usually occurs in older patients. These patients remain at risk for developing new medical complications even after discharge from the hospital. The objective of this study was to identify risk factors for hospital readmission 30 days after hip fracture and the prognosis of the readmitted patients. MATERIALS METHODS: A prospective, observational cohort study of 732 consecutive patients over 65 years surgically treated for hip fracture and discharged alive in 2010-2014 was conducted. The measurements were patient demographic characteristics, residential and discharge status, Katz Index, Merle D'aubigné Hip Score, Mini-Mental Test, comorbid conditions, Charlson Index, ASA group, type of fracture and repair, and postoperative complications. Patient characteristics were tested by bivariate and multivariate analyses. RESULTS: 8.3 % of patients were readmitted within 30 days (56.0 % of these within 2 weeks). Medical reasons were 13 times more frequent than surgical reasons. Diagnoses more prevalent for readmission were pulmonary disease, deep vein thrombosis, heart failure, and renal failure. Predictors of readmission were female gender (HR 1.9, 95 % CI 1.1-3.4), grade III-IV ASA (HR 2.1, 95 % CI 1.1-4.2), and pre-existing pulmonary disease (HR 5.3, 95 % CI 3.4-9.6). In-hospital mortality among readmitted patients was 22.9 %. In bivariate analyses, male gender, ASA III-IV, cognitive impairment, and more than two comorbidities were potential predictive factors for readmission, and in multivariate analysis only male gender and ASA III-IV. Mortality risk among readmitted patients was significantly higher compared to the in-hospital mortality in the overall cohort (OR 1.8, 95 % CI 1.5-2.3). CONCLUSIONS: Hospital readmissions after hip fracture were mainly due to medical complications and a fraction of these may be preventable. Readmission was associated with increased morbidity and mortality.

Debridement with prosthesis retention and antibiotherapy vs. two-stage revision for periprosthetic knee infection within 3 months after arthroplasty: a case-control study.

Sixty-four patients with periprosthetic infection within 3 months of index arthroplasty, of whom 39 underwent debridement with prosthesis retention and antibiotherapy (DPRA), and 25 underwent two-stage revision (2SR), were compared regarding control of infection and functional outcomes by use of Knee Society scores. Failure was defined as the need for subsequent surgery to control infection. The failure rate after DPRA was 61.5%, and that after 2SR was 12.0% (p 0.001). The failure risk was not significantly associated with the duration of symptoms (≤4 weeks). The only predictor of failure was isolation of Staphylococcus aureus or Staphylococcus epidermidis. Treatment with 2SR required fewer surgical operations, a shorter duration of hospitalization, and a shorter duration of treatment. All patients who required a second debridement ultimately underwent prosthesis removal. The functional outcome was significantly better for 2SR at the last follow-up.

Effectiveness of influenza vaccination programme in preventing hospital admissions, Valencia, 2014/15 early results.

Preliminary results for the 2014/15 season indicate low to null effect of vaccination against influenza A(H3N2)-related disease. As of week 5 2015, there have been 1,136 hospital admissions, 210 were due to influenza and 98% of subtype A strains were H3. Adjusted influenza vaccine effectiveness was 33% (range: 6-53%) overall and 40% (range: 13% to 59%) in those 65 years and older. Vaccination reduced by 44% (28-68%) the probability of admission with influenza.

Predictive models for all-cause and cardiovascular mortality in type 2 diabetic inpatients. A cohort study.

BACKGROUND: Many authors have analysed premature mortality in cohorts of type 2 diabetic patients, but no analyses have assessed mortality in hospitalised diabetic patients. AIM: To construct predictive models to estimate the likelihood of all-cause mortality and cardiovascular mortality in type 2 diabetic inpatients. DESIGN: Cohort study with follow-up from 2010 to 2014. METHODS: We evaluated mortality in a randomly selected cohort of 112 type 2 diabetic inpatients at the Hospital of Elda (Spain) in 2010-2012. OUTCOMES: all-cause mortality and cardiovascular mortality during the follow-up. Other variables: gender, age, depression, asthma/chronic obstructive pulmonary disease, hypertension, dyslipidemia, insulin, pills, smoking, walking, baseline blood glucose and creatinine. Predictive tables with risk groups were constructed to estimate the likelihood of all-cause mortality and cardiovascular mortality. Calculations were made of the area under the ROC curve (AUC). RESULTS: During the follow-up, 52 inpatients died (46.4%, 95% CI, confidence interval: 37.2-55.7%), 22 because of cardiovascular causes (19.6%, 95% CI: 12.3-27.0%). The mean follow-up time was 2.7 ± 1.5 years. The AUC for the all-cause mortality model was 0.84 (95% CI: 0.77-0.92, p < 0.001). Associated parameters: pills, smoking, walking, gender, insulin and age. The AUC for the cardiovascular mortality model was 0.79 (95% CI: 0.67-0.91, p < 0.001). Associated parameters: age, pills, walking, smoking, depression and insulin. CONCLUSIONS: This study provides tools to predict premature mortality in type 2 diabetic inpatients. However, before their general application they require joint validation by the internal medicine unit, emergency department, primary healthcare unit and endocrinology service to enable better prediction of the prognosis and more adequate decision-taking.

Suitability of antiplatelet therapy in hypertensive patients.

Antiplatelet therapy (AT) is indicated in hypertensive patients with increased cardiovascular risk. The literature about the adequate or inadequate prescription of AT is scarce. We conducted a prospective descriptive study to quantify therapeutic inertia and non-guideline-recommended prescription (NGRP) of AT (aspirinor clopidogrel or both), and to assess associated factors, calculating the adjusted odds ratios (ORs) from multivariate models. In 2007-2009, 712 primary health-care hypertensive patients in a Spanish region were enrolled. Inertia was defined as the lack of an AT prescription, despite being indicated by guidelines, whereas NGRP was defined as AT prescription when there was no guideline recommendation. We also recorded cardiovascular variables. Inertia and NGRP were quantified for primary and secondary prevention. Of 108 patients in secondary prevention, 53 had inertia (49.1%, 95% confidence interval (CI): 39.6-58.5%). Associated profile: female (OR=0.460, P=0.091), no dyslipidemia (OR=0.393, P=0.048), no coronary heart disease (OR=0.215, P=0.001) and high diastolic blood pressure (OR=1.076, P=0.016). In primary prevention, NGRP was present in 69 of 595 patients (11.6%, 95% CI: 9.0-14.2%). Associated profile: male (OR=1.610, P=0.089), smoking (OR=2.055, P=0.045), dyslipidemia (OR=3.227, P<0.001) and diabetes (OR=2.795, P<0.001). Although certain factors were clearly associated with these phenomena much still remains to be learnt.

[Effect on zebrafish neurodevelopment and neuroprotection of a polyphenolic extract olive seeds]. / Efecto sobre el neurodesarrollo y neuroprotección en pez cebra de un extracto polifenólico de huesos de aceituna.

OBJECTIVE: To determine the effect of a polyphenolic extract from olive pit on the development of the nervous system as well as its effect on pain induced by the neurotoxin kainic acid, taking the zebrafish as the animal model. MATERIAL AND METHODS: We analyse the effect of the extract at the maximum tolerated dose (100 mg/ml of polyphenols) on the cholinergic activity in zebrafish larvae (72 hours post-fertilization). Only fecundated eggs with no abnormalities are used. 6 eggs/bowl are incubated in a 24 bowls microplate in 2 ml of water with DMSO (0.1%) at 26 ± 1º C: a) neurodevelopment: water (control) and 100 mg/ml of extract, as an essay; b) neuroprotection: water and kainic acid (100 µM) (control) and 100 mg/ml of extract (essay). All incubations are in triplicate. After 72 h, incubations are examined and checked for any abnormalities. Larvae are homogenized and acetyl cholinesterase activity and protein concentration in supernatants is quantified. RESULTS: The quantity of protein and the morphologic appreciation is similar in all the essays, showing a standard development. Acetyl cholinesterase in fish larvae, with the polyphenolic extract is 162.2% (SD 44.2) compared to controls (100% of activity) (p < 0.01). Fish larvae treated with kainic acid and polyphenolic acid show 140.1% (SD 22.0) of activity, compared to those only incubated with the neurotoxin (100%) (p < 0.05). CONCLUSION: Polyphenols extracted from olive pit produce an increase in the cholinergic activity during the larvae neurodevelopment in the zebrafish as well as protection against the neurotoxin kainic acid.

Objetivo: Determinar el efecto de un extracto polifenólico de hueso de oliva en el desarrollo del sistema nervioso y frente al daño inducido mediante la neurotoxina ácido kaínico, utilizando como modelo animal el pez cebra. Material y métodos: Se analiza el efecto del extracto a la máxima dosis tolerada (100 mg/ml de polifenoles) sobre la actividad colinérgica en larvas de pez cebra (72 horas post-fertilización). Se utilizan únicamente huevos fecundados sin anomalías. Se incuban 6 huevos/pocillo en microplaca de 24 pocillos en 2 ml de agua con DMSO (0,1%) a 26 ± 1º C: a) neurodesarrollo: agua (control) y con 100 mg/ml de extracto, como ensayo; b) neuroprotección: agua y ácido kaínico (100 M) (control) y con 100 mg/ml de extracto (ensayo). Todas las incubaciones por triplicado. A las 72 h se examinan y verifica ausencia de anomalías. Las larvas se homogeneizan y en los sobrenadantes se cuantifica actividad acetilnolinesterasa y concentración proteínas. Resultados: La cantidad de proteína y apreciación morfológica es análoga en todos los ensayos, indicando mismo desarrollo. La acetilcolinesterasa en las larvas de pez, con el extracto polifenólico es del 162,2%(SD 44,2) respecto a controles (100% de actividad) (p < 0,01). Las larvas de pez tratadas con ácido kaínico y extracto polifenólico presentan el 140,1% (SD 22,0) de actividad, respecto a las incubadas únicamente con la neurotoxina (100%) (p < 0,05). Conclusión: Los polifenoles extraídos de los huesos de aceituna producen incremento de actividad colinérgica durante el neurodesarrollo larvario en el pez cebra y protección frente a la neurotoxina ácido kaínico.

[Anti-inflammatory activity of olive seed polyphenolic extract in the THP1-XBLUE-CD14 human monocytes cell line]. / Actividad antiinflamatoria de un extracto polifenólico de hueso de olivas en la línea celular de monocitos humanos THP1-XBLUE-CD14.

UNLABELLED: The aim of this study was to assess the anti-inflammatory activity of a polyphenolic extract from olive pits. MATERIAL AND METHODS: The THP1-XBlue-CD14 (invivogen) cellular line, 80,000 cells/well, was incubated and inflammation (activation of NF-kb) was produced with 0.1 mg/mL of LPS (lipopolysaccharide from E. coli) for 24 hours. We assessed the presence of the extract (10 and 50 mg/L, biologically safe concentrations) for 2 hours at 37º C, before (preventive effect) and after (therapeutic effect) the proinflammatory activation, and the activity of alkaline phosphatase, which is expressed under the control of the NF-kb transcriptional factor, was quantified by colorimetry. The percentage of activity of NF-kb as preventive effect and therapeutic effect was assessed by comparing it to control cultures of cells with LPS and without extract, which are considered 100% of NF-kb. RESULTS: The preventive anti-inflammatory capacity of the extract at 50 mg/L was 25.5% (95% CI: 16.8-34.2) and the therapeutic effect 34.9% (95% CI: 25.3-44.4) for the same concentration, without any significant activity at 10 mg/L. CONCLUSION: An activity of polyphenols extracted from olive pits is shown, both in preventing inflammation and therapeutically eliminating inflammation through inhibition of NF-kB factor previously activated by LPS at concentrations of 50 mg/L of polyphenols, which previously haven been shown to be safe.

El objetivo de este trabajo es evaluar la actividad antiinflamatoria de un extracto de naturaleza polifenólica de huesos de oliva. MATERIAL Y MÉTODOS: Se incubó la línea celular THP1- XBlue-CD14 (invivogen), 80.000 células/pocillo, provocando inflamación (activación de NF-kb) mediante 0.1 µg/ml LPS (lipopolisacárido de E. coli) durante 24 horas. Se evaluó la presencia del extracto (10 y 50 mg/l, concentraciones bioseguras) durante 2 horas a 37 ºC, previa (efecto preventivo) y posterior a la activación proinflamatoria (efecto terapéutico) y se cuantificó colorimétricamente la actividad de fosfatasa alcalina, que se expresa bajo el control del promotor del factor transcripcional de NF-kb. Se evalúa el % actividad de NF-kb en efecto preventivo y terapéutico respecto a cultivos control de células con LPS y sin extracto añadido, que se consideran 100% de NF-kb. RESULTADOS: La capacidad antiinflamatoria preventiva del extracto a 50 mg/l es del 25,5% (IC 95% 16,8-34,2) y el efecto terapéutico del 34,9% (IC 95% 25,3-44,4) para la misma concentración, no presentando actividad significativa a 10 mg/l. CONCLUSIÓN: Se muestra una actividad de los polifenoles extraídos de los huesos de aceitunas, tanto preventivo de la inflamación como terapéutico de eliminación de la inflamación a través de la inhibición del factor NF-kB previamente activado por LPS a concentraciones de 50 mg/l de polifenoles que previamente se han mostrado seguras.

A randomized clinical trial to determine the effect of angiotensin inhibitors reduction on creatinine clearance and haemoglobin in heart failure patients with chronic kidney disease and anaemia.

BACKGROUND: Chronic kidney disease is a common comorbidity in elderly patients with heart failure. Evidence supports the use of angiotensin inhibitors for patients with heart failure. However, there is little evidence with which to assess the risk and benefits of this treatment in elderly patients with renal dysfunction. OBJECTIVE: To determine the efficacy and safety of angiotensin inhibitor reduction in patients with heart failure, chronic kidney disease and anaemia. STUDY DESIGN: Open randomized controlled clinical trial. SETTING: Complexo Hospitalario Universitario A Coruña (Spain). PATIENTS: Patients ≥ 50 years old, with heart failure, haemoglobin (Hb) < 12 mg/dl and creatinine clearance <60 ml/min/1.73 m(2) admitted to hospital, in treatment with angiotensin inhibitors. Informed consent and Ethical Review Board approval were obtained. INTERVENTION: A 50% reduction of angiotensin inhibitor dose of the basal treatment on admission (n = 30) in the intervention group. Control group (n = 16) with the standard basal dose. MAIN OUTCOME MEASURE: Primary outcome was difference in Hb (gr/dl), creatinine clearance (ml/min/1.73 m(2) ) and protein C (mg/dl) between admission and 1-3 months after discharge. Secondary outcome was survival at 6-12 months after discharge. RESULTS: Patients in the intervention group experienced an improvement in Hb (10.62-11.47 g/dl), creatinine clearance (32.5 ml/min/1.73 m(2) to 42.9 ml/min/1.73 m(2) ), and a decrease in creatinine levels (1.98-1.68 mg/dl) and protein C (3.23 mg/dl to 1.37 mg/dl). There were no significant differences in these variables in the control group. Survival at 6 and 12 months in the intervention and control group was 86.7% vs. 75% and 69.3% vs. 50%, respectively. CONCLUSION: The reduction of the dose of angiotensin inhibitors in the intervention group resulted in an improvement in anaemia and kidney function, decreased protein C and an increased survival rate. TRIAL REGISTRATION: EudraCT: 2008-008480-10.