Prospective registry of symptomatic severe aortic stenosis in octogenarians: a need for intervention.

OBJECTIVE To study the factors associated with choice of therapy and prognosis in octogenarians with severe symptomatic aortic stenosis (AS). STUDY DESIGN Prospective, observational, multicenter registry. Centralized follow-up included survival status and, if possible, mode of death and Katz index. SETTING Transnational registry in Spain. SUBJECTS We included 928 patients aged ≥80 years with severe symptomatic AS. INTERVENTIONS Aortic-valve replacement (AVR), transcatheter aortic-valve implantation (TAVI) or conservative therapy. MAIN OUTCOME MEASURES All-cause death. RESULTS Mean age was 84.2 ± 3.5 years, and only 49.0% were independent (Katz index A). The most frequent planned management was conservative therapy in 423 (46%) patients, followed by TAVI in 261 (28%) and AVR in 244 (26%). The main reason against recommending AVR in 684 patients was high surgical risk [322 (47.1%)], other medical motives [193 (28.2%)], patient refusal [134 (19.6%)] and family refusal in the case of incompetent patients [35 (5.1%)]. The mean time from treatment decision to AVR was 4.8 ± 4.6 months and to TAVI 2.1 ± 3.2 months, P < 0.001. During follow-up (11.2-38.9 months), 357 patients (38.5%) died. Survival rates at 6, 12, 18 and 24 months were 81.8%, 72.6%, 64.1% and 57.3%, respectively. Planned intervention, adjusted for multiple propensity score, was associated with lower mortality when compared with planned conservative treatment: TAVI Hazard ratio (HR) 0.68 (95% confidence interval [CI] 0.49-0.93; P = 0.016) and AVR HR 0.56 (95% CI 0.39-0.8; P = 0.002). CONCLUSION Octogenarians with symptomatic severe AS are frequently managed conservatively. Planned conservative management is associated with a poor prognosis.

Moderate-Vigorous Physical Activity across Body Mass Index in Females: Moderating Effect of Endocannabinoids and Temperament.

BACKGROUND Endocannabinoids and temperament traits have been linked to both physical activity and body mass index (BMI) however no study has explored how these factors interact in females. The aims of this cross-sectional study were to 1) examine differences among distinct BMI groups on daytime physical activity and time spent in moderate-vigorous physical activity (MVPA), temperament traits and plasma endocannabinoid concentrations; and 2) explore the association and interaction between MVPA, temperament, endocannabinoids and BMI. METHODS Physical activity was measured with the wrist-worn accelerometer Actiwatch AW7, in a sample of 189 female participants (43 morbid obese, 30 obese, and 116 healthy-weight controls). The Temperament and Character Inventory-Revised questionnaire was used to assess personality traits. BMI was calculated by bioelectrical impedance analysis via the TANITA digital scale. Blood analyses were conducted to measure levels of endocannabinoids and endocannabinoid-related compounds. Path-analysis was performed to examine the association between predictive variables and MVPA. RESULTS Obese groups showed lower MVPA and dysfunctional temperament traits compared to healthy-weight controls. Plasma concentrations of 2-arachidonoylglyceryl (2-AG) were greater in obese groups. Path-analysis identified a direct effect between greater MVPA and low BMI (b = -0.13, p = .039) and high MVPA levels were associated with elevated anandamide (AEA) levels (b = 0.16, p = .049) and N-oleylethanolamide (OEA) levels (b = 0.22, p = .004), as well as high Novelty seeking (b = 0.18, p<.001) and low Harm avoidance (b = -0.16, p<.001). CONCLUSIONS Obese individuals showed a distinct temperament profile and circulating endocannabinoids compared to controls. Temperament and endocannabinoids may act as moderators of the low MVPA in obesity.

Combined impact of healthy lifestyle factors on colorectal cancer: a large European cohort study.

BACKGROUND Excess body weight, physical activity, smoking, alcohol consumption and certain dietary factors are individually related to colorectal cancer (CRC) risk; however, little is known about their joint effects. The aim of this study was to develop a healthy lifestyle index (HLI) composed of five potentially modifiable lifestyle factors - healthy weight, physical activity, non-smoking, limited alcohol consumption and a healthy diet, and to explore the association of this index with CRC incidence using data collected within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. METHODS In the EPIC cohort, a total of 347,237 men and women, 25- to 70-years old, provided dietary and lifestyle information at study baseline (1992 to 2000). Over a median follow-up time of 12 years, 3,759 incident CRC cases were identified. The association between a HLI and CRC risk was evaluated using Cox proportional hazards regression models and population attributable risks (PARs) have been calculated. RESULTS After accounting for study centre, age, sex and education, compared with 0 or 1 healthy lifestyle factors, the hazard ratio (HR) for CRC was 0.87 (95% confidence interval (CI): 0.44 to 0.77) for two factors, 0.79 (95% CI: 0.70 to 0.89) for three factors, 0.66 (95% CI: 0.58 to 0.75) for four factors and 0.63 (95% CI: 0.54 to 0.74) for five factors; P-trend <0.0001. The associations were present for both colon and rectal cancers, HRs, 0.61 (95% CI: 0.50 to 0.74; P for trend <0.0001) for colon cancer and 0.68 (95% CI: 0.53 to 0.88; P-trend <0.0001) for rectal cancer, respectively (P-difference by cancer sub-site = 0.10). Overall, 16% of the new CRC cases (22% in men and 11% in women) were attributable to not adhering to a combination of all five healthy lifestyle behaviours included in the index. CONCLUSIONS Combined lifestyle factors are associated with a lower incidence of CRC in European populations characterized by western lifestyles. Prevention strategies considering complex targeting of multiple lifestyle factors may provide practical means for improved CRC prevention.

Association of irisin with fat mass, resting energy expenditure, and daily activity in conditions of extreme body mass index.

FNDC5/irisin has been recently postulated as beneficial in the treatment of obesity and diabetes because it is induced in muscle by exercise, increasing energy expenditure. However, recent reports have shown that WAT also secretes irisin and that circulating irisin is elevated in obese subjects. The aim of this study was to evaluate irisin levels in conditions of extreme BMI and its correlation with basal metabolism and daily activity. The study involved 145 female patients, including 96 with extreme BMIs (30 anorexic (AN) and 66 obese (OB)) and 49 healthy normal weight (NW). The plasma irisin levels were significantly elevated in the OB patients compared with the AN and NW patients. Irisin also correlated positively with body weight, BMI, and fat mass. The OB patients exhibited the highest REE and higher daily physical activity compared with the AN patients but lower activity compared with the NW patients. The irisin levels were inversely correlated with daily physical activity and directly correlated with REE. Fat mass contributed to most of the variability of the irisin plasma levels independently of the other studied parameters. Conclusion. Irisin levels are influenced by energy expenditure independently of daily physical activity but fat mass is the main contributing factor.

Efficacy of prescribed injectable diacetylmorphine in the Andalusian trial: Bayesian analysis of responders and non-responders according to a multi domain outcome index.

BACKGROUND The objective of this research was to evaluate data from a randomized clinical trial that tested injectable diacetylmorphine (DAM) and oral methadone (MMT) for substitution treatment, using a multi-domain dichotomous index, with a Bayesian approach. METHODS Sixty two long-term, socially-excluded heroin injectors, not benefiting from available treatments were randomized to receive either DAM or MMT for 9 months in Granada, Spain. Completers were 44 and data at the end of the study period was obtained for 50. Participants were determined to be responders or non responders using a multi-domain outcome index accounting for their physical and mental health and psychosocial integration, used in a previous trial. Data was analyzed with Bayesian methods, using information from a similar study conducted in The Netherlands to select a priori distributions. On adding the data from the present study to update the a priori information, the distribution of the difference in response rates were obtained and used to build credibility intervals and relevant probability computations. RESULTS In the experimental group (n = 27), the rate of responders to treatment was 70.4% (95% CI 53.287.6), and in the control group (n = 23), it was 34.8% (95% CI 15.354.3). The probability of success in the experimental group using the a posteriori distributions was higher after a proper sensitivity analysis. Almost the whole distribution of the rates difference (the one for diacetylmorphine minus methadone) was located to the right of the zero, indicating the superiority of the experimental treatment. CONCLUSION The present analysis suggests a clinical superiority of injectable diacetylmorphine compared to oral methadone in the treatment of severely affected heroin injectors not benefiting sufficiently from the available treatments. TRIAL REGISTRATION Current Controlled Trials ISRCTN52023186.

Pre-diagnostic concordance with the WCRF/AICR guidelines and survival in European colorectal cancer patients: a cohort study.

BACKGROUND Cancer survivors are advised to follow lifestyle recommendations on diet, physical activity, and body fatness proposed by the World Cancer Research Fund/American Institute of Cancer Research (WCRF/AICR) for cancer prevention. Previous studies have demonstrated that higher concordance with these recommendations measured using an index score (the WCRF/AICR score) was associated with lower cancer incidence and mortality. The aim of this study was to evaluate the association between pre-diagnostic concordance with WCRF/AICR recommendations and mortality in colorectal cancer (CRC) patients. METHODS The association between the WCRF/AICR score (score range 0-6 in men and 0-7 in women; higher scores indicate greater concordance) assessed on average 6.4 years before diagnosis and CRC-specific (n = 872) and overall mortality (n = 1,113) was prospectively examined among 3,292 participants diagnosed with CRC in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort (mean follow-up time after diagnosis 4.2 years). Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality. RESULTS The HRs (95% CIs) for CRC-specific mortality among participants in the second (score range in men/women: 2.25-2.75/3.25-3.75), third (3-3.75/4-4.75), and fourth (4-6/5-7) categories of the score were 0.87 (0.72-1.06), 0.74 (0.61-0.90), and 0.70 (0.56-0.89), respectively (P for trend <0.0001), compared to participants with the lowest concordance with the recommendations (category 1 of the score: 0-2/0-3). Similar HRs for overall mortality were observed (P for trend 0.004). Meeting the recommendations on body fatness and plant food consumption were associated with improved survival among CRC cases in mutually adjusted models. CONCLUSIONS Greater concordance with the WCRF/AICR recommendations on diet, physical activity, and body fatness prior to CRC diagnosis is associated with improved survival among CRC patients.

Prospective multicenter study of the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bloodstream infections.

The impact of antimicrobial resistance on clinical outcomes is the subject of ongoing investigations, although uncertainty remains about its contribution to mortality. We investigated the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bacteremia in a prospective multicenter (10 teaching hospitals) observational study of patients with monomicrobial bacteremia followed up for 30 days after the onset of bacteremia. The adjusted influence of carbapenem resistance on mortality was studied by using Cox regression analysis. Of 632 episodes, 487 (77%) were caused by carbapenem-susceptible P. aeruginosa (CSPA) isolates, and 145 (23%) were caused by carbapenem-resistant P. aeruginosa (CRPA) isolates. The median incidence density of nosocomial CRPA bacteremia was 2.3 episodes per 100,000 patient-days (95% confidence interval [CI], 1.9 to 2.8). The regression demonstrated a time-dependent effect of carbapenem resistance on mortality as well as a significant interaction with the Charlson index: the deleterious effect of carbapenem resistance on mortality decreased with higher Charlson index scores. The impact of resistance on mortality was statistically significant only from the fifth day after the onset of the bacteremia, reaching its peak values at day 30 (adjusted hazard ratio for a Charlson score of 0 at day 30, 9.9 [95% CI, 3.3 to 29.4]; adjusted hazard ratio for a Charlson score of 5 at day 30, 2.6 [95% CI, 0.8 to 8]). This study clarifies the relationship between carbapenem resistance and mortality in patients with P. aeruginosa bacteremia. Although resistance was associated with a higher risk of mortality, the study suggested that this deleterious effect may not be as great during the first days of the bacteremia or in the presence of comorbidities.

Prognosis Relevance of Serum Cytokines in Pancreatic Cancer.

The overall survival of patients with pancreatic ductal adenocarcinoma is extremely low. Although gemcitabine is the standard used chemotherapy for this disease, clinical outcomes do not reflect significant improvements, not even when combined with adjuvant treatments. There is an urgent need for prognosis markers to be found. The aim of this study was to analyze the potential value of serum cytokines to find a profile that can predict the clinical outcome in patients with pancreatic cancer and to establish a practical prognosis index that significantly predicts patients' outcomes. We have conducted an extensive analysis of serum prognosis biomarkers using an antibody array comprising 507 human cytokines. Overall survival was estimated using the Kaplan-Meier method. Univariate and multivariate Cox's proportional hazard models were used to analyze prognosis factors. To determine the extent that survival could be predicted based on this index, we used the leave-one-out cross-validation model. The multivariate model showed a better performance and it could represent a novel panel of serum cytokines that correlates to poor prognosis in pancreatic cancer. B7-1/CD80, EG-VEGF/PK1, IL-29, NRG1-beta1/HRG1-beta1, and PD-ECGF expressions portend a poor prognosis for patients with pancreatic cancer and these cytokines could represent novel therapeutic targets for this disease.

Prospective registry of symptomatic severe aortic stenosis in octogenarians: a need for intervention.

OBJECTIVE To study the factors associated with choice of therapy and prognosis in octogenarians with severe symptomatic aortic stenosis (AS). STUDY DESIGN Prospective, observational, multicenter registry. Centralized follow-up included survival status and, if possible, mode of death and Katz index. SETTING Transnational registry in Spain. SUBJECTS We included 928 patients aged ≥80 years with severe symptomatic AS. INTERVENTIONS Aortic-valve replacement (AVR), transcatheter aortic-valve implantation (TAVI) or conservative therapy. MAIN OUTCOME MEASURES All-cause death. RESULTS Mean age was 84.2 ± 3.5 years, and only 49.0% were independent (Katz index A). The most frequent planned management was conservative therapy in 423 (46%) patients, followed by TAVI in 261 (28%) and AVR in 244 (26%). The main reason against recommending AVR in 684 patients was high surgical risk [322 (47.1%)], other medical motives [193 (28.2%)], patient refusal [134 (19.6%)] and family refusal in the case of incompetent patients [35 (5.1%)]. The mean time from treatment decision to AVR was 4.8 ± 4.6 months and to TAVI 2.1 ± 3.2 months, P < 0.001. During follow-up (11.2-38.9 months), 357 patients (38.5%) died. Survival rates at 6, 12, 18 and 24 months were 81.8%, 72.6%, 64.1% and 57.3%, respectively. Planned intervention, adjusted for multiple propensity score, was associated with lower mortality when compared with planned conservative treatment: TAVI Hazard ratio (HR) 0.68 (95% confidence interval [CI] 0.49-0.93; P = 0.016) and AVR HR 0.56 (95% CI 0.39-0.8; P = 0.002). CONCLUSION Octogenarians with symptomatic severe AS are frequently managed conservatively. Planned conservative management is associated with a poor prognosis.

Prospective multicenter study of the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bloodstream infections.

The impact of antimicrobial resistance on clinical outcomes is the subject of ongoing investigations, although uncertainty remains about its contribution to mortality. We investigated the impact of carbapenem resistance on mortality in Pseudomonas aeruginosa bacteremia in a prospective multicenter (10 teaching hospitals) observational study of patients with monomicrobial bacteremia followed up for 30 days after the onset of bacteremia. The adjusted influence of carbapenem resistance on mortality was studied by using Cox regression analysis. Of 632 episodes, 487 (77%) were caused by carbapenem-susceptible P. aeruginosa (CSPA) isolates, and 145 (23%) were caused by carbapenem-resistant P. aeruginosa (CRPA) isolates. The median incidence density of nosocomial CRPA bacteremia was 2.3 episodes per 100,000 patient-days (95% confidence interval [CI], 1.9 to 2.8). The regression demonstrated a time-dependent effect of carbapenem resistance on mortality as well as a significant interaction with the Charlson index: the deleterious effect of carbapenem resistance on mortality decreased with higher Charlson index scores. The impact of resistance on mortality was statistically significant only from the fifth day after the onset of the bacteremia, reaching its peak values at day 30 (adjusted hazard ratio for a Charlson score of 0 at day 30, 9.9 [95% CI, 3.3 to 29.4]; adjusted hazard ratio for a Charlson score of 5 at day 30, 2.6 [95% CI, 0.8 to 8]). This study clarifies the relationship between carbapenem resistance and mortality in patients with P. aeruginosa bacteremia. Although resistance was associated with a higher risk of mortality, the study suggested that this deleterious effect may not be as great during the first days of the bacteremia or in the presence of comorbidities.

Psychiatric Status across Body Mass Index in a Mediterranean Spanish Population.

BACKGROUND Mental and body weight disorders are among the major global health challenges, and their comorbidity may play an important role in treatment and prevention of both pathologies. A growing number of studies have examined the relationship between psychiatric status and body weight, but our knowledge is still limited. OBJECTIVE The present study aims to investigate the cross-sectional relationships of psychiatric status and body mass index (BMI) in Málaga, a Mediterranean city in the South of Spain. MATERIALS AND METHODS A total of 563 participants were recruited from those who came to his primary care physician, using a systematic random sampling, non-proportional stratified by BMI categories. Structured clinical interviews were used to assess current Axes-I and II mental disorders according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR). BMI was calculated as weight (Kg) divided by square of height in meters (m2). Logistic regression was used to investigate the association between BMI and the presence of any mental disorder. BMI was introduced in the models using restricted cubic splines. RESULTS We found that high BMI values were directly associated with mood and adjustment disorders, and low BMI values were directly associated with avoidant and dependent personality disorders (PDs). We observed an inverse relationship between low BMI values and cluster A PDs. There were not significant relationships between anxiety or substance-related disorders and BMI. CONCLUSION Psychiatric status and BMI are related in a Mediterranean Spanish population. A multidisciplinary approach to both pathologies becomes increasingly more necessary.

A Lower Olfactory Capacity Is Related to Higher Circulating Concentrations of Endocannabinoid 2-Arachidonoylglycerol and Higher Body Mass Index in Women.

The endocannabinoid (eCB) system can promote food intake by increasing odor detection in mice. The eCB system is over-active in human obesity. Our aim is to measure circulating eCB concentrations and olfactory capacity in a human sample that includes people with obesity and explore the possible interaction between olfaction, obesity and the eCB system. The study sample was made up of 161 females with five groups of body mass index sub-categories ranging from under-weight to morbidly obese. We assessed olfactory capacity with the "Sniffin´Sticks" test, which measures olfactory threshold-discrimination-identification (TDI) capacity. We measured plasma concentrations of the eCBs 2-arachidonoylglycerol (2-AG) and N-arachidonoylethanolamine or anandamide (AEA), and several eCB-related compounds, 2-acylglycerols and N-acylethanolamines. 2-AG and other 2-acylglycerols fasting plasma circulating plasma concentrations were higher in obese and morbidly obese subjects. AEA and other N-acylethanolamine circulating concentrations were lower in under-weight subjects. Olfactory TDI scores were lower in obese and morbidly obese subjects. Lower TDI scores were independently associated with higher 2-AG fasting plasma circulating concentrations, higher %body fat, and higher body mass index, after controlling for age, smoking, menstruation, and use of contraceptives. Our results show that obese subjects have a lower olfactory capacity than non-obese ones and that elevated fasting plasma circulating 2-AG concentrations in obesity are linked to a lower olfactory capacity. In agreement with previous studies we show that eCBs AEA and 2-AG, and their respective congeners have a distinct profile in relation to body mass index. The present report is the first study in humans in which olfactory capacity and circulating eCB concentrations have been measured in the same subjects.