Early multimodal outcome prediction after cardiac arrest in patients treated with hypothermia.

OBJECTIVES: Therapeutic hypothermia and pharmacological sedation may influence outcome prediction after cardiac arrest. The use of a multimodal approach, including clinical examination, electroencephalography, somatosensory-evoked potentials, and serum neuron-specific enolase, is recommended; however, no study examined the comparative performance of these predictors or addressed their optimal combination. DESIGN: Prospective cohort study. SETTING: Adult ICU of an academic hospital. PATIENTS: One hundred thirty-four consecutive adults treated with therapeutic hypothermia after cardiac arrest. MEASUREMENTS AND MAIN RESULTS: Variables related to the cardiac arrest (cardiac rhythm, time to return of spontaneous circulation), clinical examination (brainstem reflexes and myoclonus), electroencephalography reactivity during therapeutic hypothermia, somatosensory-evoked potentials, and serum neuron-specific enolase. Models to predict clinical outcome at 3 months (assessed using the Cerebral Performance Categories: 5 = death; 3-5 = poor recovery) were evaluated using ordinal logistic regressions and receiving operator characteristic curves. Seventy-two patients (54%) had a poor outcome (of whom, 62 died), and 62 had a good outcome. Multivariable ordinal logistic regression identified absence of electroencephalography reactivity (p < 0.001), incomplete recovery of brainstem reflexes in normothermia (p = 0.013), and neuron-specific enolase higher than 33 μg/L (p = 0.029), but not somatosensory-evoked potentials, as independent predictors of poor outcome. The combination of clinical examination, electroencephalography reactivity, and neuron-specific enolase yielded the best predictive performance (receiving operator characteristic areas: 0.89 for mortality and 0.88 for poor outcome), with 100% positive predictive value. Addition of somatosensory-evoked potentials to this model did not improve prognostic accuracy. CONCLUSIONS: Combination of clinical examination, electroencephalography reactivity, and serum neuron-specific enolase offers the best outcome predictive performance for prognostication of early postanoxic coma, whereas somatosensory-evoked potentials do not add any complementary information. Although prognostication of poor outcome seems excellent, future studies are needed to further improve prediction of good prognosis, which still remains inaccurate.

No consistent association between processes-of-care and health-related quality of life among patients with diabetes : a missing link?

PURPOSE: Health-related quality of life (HRQoL) is considered a representative outcome in the evaluation of chronic disease management initiatives emphasizing patient-centered care. We evaluated the association between receipt of processes-of-care (PoC) for diabetes and HRQoL. METHODS: This cross-sectional study used self-reported data from non-institutionalized adults with diabetes in a Swiss canton. Outcomes were the physical/mental composites of the short form health survey 12 (SF-12) physical composite score, mental composite score (PCS, MCS) and the Audit of Diabetes-Dependent Quality of Life (ADDQoL). Main exposure variables were receipt of six PoC for diabetes in the past 12 months, and the Patient Assessment of Chronic Illness Care (PACIC) score. We performed linear regressions to examine the association between PoC, PACIC and the three composites of HRQoL. RESULTS: Mean age of the 519 patients was 64.5 years (SD 11.3); 60% were male, 87% reported type 2 or undetermined diabetes and 48% had diabetes for over 10 years. Mean HRQoL scores were SF-12 PCS: 43.4 (SD 10.5), SF-12 MCS: 47.0 (SD 11.2) and ADDQoL: -1.6 (SD 1.6). In adjusted models including all six PoC simultaneously, receipt of influenza vaccine was associated with lower ADDQoL (β=-0.4, p≤0.01) and foot examination was negatively associated with SF-12 PCS (β=-1.8, p≤0.05). There was no association or trend towards a negative association when these PoC were reported as combined measures. PACIC score was associated only with the SF-12 MCS (β=1.6, p≤0.05). CONCLUSIONS: PoC for diabetes did not show a consistent association with HRQoL in a cross-sectional analysis. This may represent an effect lag time between time of process received and health-related quality of life. Further research is needed to study this complex phenomenon.

Broad-scale adaptive genetic variation in alpine plants is driven by temperature and precipitation.

Identifying adaptive genetic variation is a challenging task, in particular in non-model species for which genomic information is still limited or absent. Here, we studied distribution patterns of amplified fragment length polymorphisms (AFLPs) in response to environmental variation, in 13 alpine plant species consistently sampled across the entire European Alps. Multiple linear regressions were performed between AFLP allele frequencies per site as dependent variables and two categories of independent variables, namely Moran's eigenvector map MEM variables (to account for spatial and unaccounted environmental variation, and historical demographic processes) and environmental variables. These associations allowed the identification of 153 loci of ecological relevance. Univariate regressions between allele frequency and each environmental factor further showed that loci of ecological relevance were mainly correlated with MEM variables. We found that precipitation and temperature were the best environmental predictors, whereas topographic factors were rarely involved in environmental associations. Climatic factors, subject to rapid variation as a result of the current global warming, are known to strongly influence the fate of alpine plants. Our study shows, for the first time for a large number of species, that the same environmental variables are drivers of plant adaptation at the scale of a whole biome, here the European Alps.

What is the influence of vaccination's routes on the regression of tumors located at mucosal sites?

Tumor-regressions following tumor-associated-antigen vaccination in animal models contrast with the limited clinical outcomes in cancer patients. Most animal studies however used subcutaneous-tumor-models and questions arise as whether these are relevant for tumors growing in mucosae; whether specific mucosal-homing instructions are required; and how this may be influenced by the tumor.

A step beyond--the relevance of depressed mood and mastery in the interplay between the number of social roles and alcohol use.

OBJECTIVES: The present study examines whether depressed mood and external control mediate or moderate the relationship between the number of social roles and alcohol use. PARTICIPANTS: The analysis was based on a national representative sample of 25- to 45-year-old male and female drinkers in Switzerland. METHOD: The influence of depressed mood and external control on the relationship between the number of social roles (parenthood, partnership, employment) and alcohol use was examined in linear structural equation models (mediation) and in multiple regressions (moderation) stratified by gender. All analyses were adjusted for age and education level. RESULTS: Holding more roles was associated with lower alcohol use, lower external control and lower depressed mood. The study did not find evidence of depressed mood or external control mediating the social roles-alcohol relationship. A moderation effect was identified among women only, whereby a protective effect of having more roles could not be found among those who scored high on external control. In general, a stronger link was observed between roles and alcohol use, while depressed mood and external control acted independently on drinking. With the exception of women with high external control, the study found no link between a higher number of social roles and greater alcohol use. CONCLUSION: Our results indicate that drinking behaviours are more strongly linked to external control and depressed mood than they are to the number of social roles. The study also demonstrates that in any effective alcohol prevention policy, societal actions that enable individuals to combine more social roles play a central role.

Is the impact of public investment neutral across the regional income distribution?: evidence from Mexico

This paper investigates the contribution of public investment to the reduction of regional inqualities, with a specific application to Mexico. We use quantile regressions to examine the impact of public investment on regional disparities according to the position of each region in the conditional distribution of regional income. Results confirm the hypothesis that regional inequalities can indeed be atrributed to the regional distribution of public investment, where the observed pattern shows that public investment mainly helped to reduce regional inequalities between the richest regions

Polymorphic mutations associated with the emergence of the multinucleoside/tide resistance mutations 69 insertion and Q151M.

BACKGROUND: We hypothesized that polymorphic mutations exist that are associated with the emergence of the multinucleoside resistance mutations (MNR), 69 insertion and Q151M. METHODS: The Swiss HIV Cohort Study was screened, and the frequencies of polymorphic mutations in HIV-1 (subtype B) were compared between patients detected with the 69 insertion (n = 17), Q151M (n = 29), ≥2 thymidine analogue mutations (TAM) 1 (n = 400) or ≥2 TAM 2 (n = 249). Logistic regressions adjusted for the antiretroviral treatment history were performed to analyze the association of the polymorphic mutations with MNR. RESULTS: The 69 insertion and TAM 1 were strongly associated and occurred in 94.1% (16 of 17) together. The 69 insertion seemed to emerge as a consequence of the TAM 1 pathway (median years until detection: 6.8 compared with 4.4 for ≥2 TAM 1, P Wilcoxon = 0.009). Frequencies of 8 polymorphic mutations (K43E, V60I, S68G, S162C, T165I, I202V, R211K, F214L) were significantly different between groups. Logistic regression showed that F214L and V60I were associated with the emergence of Q151M/TAM 2 opposed to 69 insertion/TAM 1. S68G, T165I, and I202V were associated with Q151M instead of TAM 2. CONCLUSIONS: Besides antiretroviral therapy, polymorphic mutations may contribute to the emergence of specific MNR mutations.

Predictors of onset of cannabis and other drug use in male young adults: results from a longitudinal study.

BACKGROUND: The use of cannabis and other illegal drugs is particularly prevalent in male young adults and is associated with severe health problems. This longitudinal study explored variables associated with the onset of cannabis use and the onset of illegal drug use other than cannabis separately in male young adults, including demographics, religion and religiosity, health, social context, substance use, and personality. Furthermore, we explored how far the gateway hypothesis and the common liability to addiction model are in line with the resulting prediction models. METHODS: The data were gathered within the Cohort Study on Substance Use Risk Factors (C-SURF). Young men aged around 20 years provided demographic, social, health, substance use, and personality-related data at baseline. Onset of cannabis and other drug use were assessed at 15-months follow-up. Samples of 2,774 and 4,254 individuals who indicated at baseline that they have not used cannabis and other drugs, respectively, in their life and who provided follow-up data were used for the prediction models. Hierarchical logistic stepwise regressions were conducted, in order to identify predictors of the late onset of cannabis and other drug use separately. RESULTS: Not providing for oneself, having siblings, depressiveness, parental divorce, lower parental knowledge of peers and the whereabouts, peer pressure, very low nicotine dependence, and sensation seeking were positively associated with the onset of cannabis use. Practising religion was negatively associated with the onset of cannabis use. Onset of drug use other than cannabis showed a positive association with depressiveness, antisocial personality disorder, lower parental knowledge of peers and the whereabouts, psychiatric problems of peers, problematic cannabis use, and sensation seeking. CONCLUSIONS: Consideration of the predictor variables identified within this study may help to identify young male adults for whom preventive measures for cannabis or other drug use are most appropriate. The results provide evidence for both the gateway hypothesis and the common liability to addiction model and point to further variables like depressiveness or practising of religion that might influence the onset of drug use.

Pain and beliefs after musuloskeletal trauma: Complex relationships during the first year of rehabilitation

Introduction.- Pain and beliefs have an influence on the patient's course in rehabilitation and their relationships are complex. The aim of this study was to understand the relationships between pain at admission and the evolution of beliefs during rehabilitation as well as the relationships between pain and beliefs one year after rehabilitation.Patients and methods.- Six hundred and thirty-one consecutive patients admitted in rehabilitation after musculoskeletal trauma, were included and assessed at admission, at discharge and one year after discharge. Pain was measured by VAS (Visual Analogical Scale) and beliefs by judgement on Lickert scales. Four kinds of beliefs were evaluated: fear of a severe origin of pain, fear of movement, fear of pain and feeling of distress (loss of control). The association between pain and beliefs was assessed by logistic regressions, adjusted for gender, age, native language, education and bio-psycho-social complexity.Results.- At discharge, 44% of patients felt less distressed by pain, 34% are reinsured with regard to their fear of a severe origin of pain, 38% have less fear of pain and 33% have less fear of movement. The higher the pain at admission, the higher the probability that the distress diminished, this being true up to a threshold (70 mm/100) beyond which there was a plateau. At one year, the higher the pain, the more dysfunctional the fears.Discussion.- The relationships between pain and beliefs are complex and may change all along rehabilitation. During hospitalization, one could hope that the patient would be reinsured and would gain self-control again, if pain does not exceed a certain threshold. After one year, high pain increases the risk of dysfunctional beliefs. For clinical practice, these data suggest to think in terms of the more accessible "entrance door", act against pain and/or against beliefs, adpated to each patient.

Diabetic patients who report receiving processes of diabetic care do not express a better quality of life

Background: Chronic disease management initiatives emphasize patient-centered care, and quality of life (QoL) is increasingly considered a representative outcome in that context. In this study we evaluated the association between receipt of processes of diabetic care and QoL. Methods: This cross-sectional population-based study (2011) used self-reported data from non-institutionalized, adult diabetics, recruited from randomly selected community pharmacies in Vaud. Outcomes included the physical and mental composites of the SF-36 (PCS, MCS) and the disease-specific Audit of Diabetes-Dependent QoL (ADDQoL). Main exposure variables were receipt of six diabetes processes-of care in the past 12 months. We also evaluated whether the association between care received and QoL was congruent with the chronic care model, when assessed by the Patient Assessment of Chronic Illness Care (PACIC). We used linear regressions to examine the association between process measures and the three composites of health-related QoL. Analyses were adjusted for age, gender, socioeconomic status, living companion, BMI, alcohol, smoking, physical activity, co-morbidities and diabetes mellitus (DM) characteristics (type, insulin use, complications, duration). Results: Mean age of the 519 diabetic patients was 64.4 years (SD 11.3), 60% were male and 73% had a living companion; 87% reported type 2 DM, half of respondents required insulin treatment, 48% had at least one DM complication, and 48% had DM over 10 years. Crude overall mean QoL scores were PCS: 43.4 (SD 10.5), MCS: 47.0 (SD 11.2) and ADDQoL: -1.56 (SD 1.6). In bivariate analyses, patients who received the influenza vaccine versus those who did not, had lower ADDQoL and PCS scores; there were no other indicator differences. In adjusted models including all processes, receipt of influenza vaccine was associated with lower ADDQoL (β= - 0.41, p=.01); there were no other associations between process indicators and QoL composites. There was no process association even when these were reported as combined measures of processes of care. PACIC score was associated only with the MCS (β= 1.57, p=.004). Conclusions: Process indicators for diabetes care did not show an association with QoL. This may represent an effect lag time between time of process received and quality of life; or that treatment may be related with inconvenience and patient worry. Further research is needed to explore these unexpected findings.

Negative impact of hypocaloric feeding and energy balance on clinical outcome in ICU patients

Résumé Introduction : Les patients nécessitant une prise en charge prolongée en milieu de soins intensifs et présentant une évolution compliquée, développent une réponse métabolique intense caractérisée généralement par un hypermétabolisme et un catabolisme protéique. La sévérité de leur atteinte pathologique expose ces patients à la malnutrition, due principalement à un apport nutritionnel insuffisant, et entraînant une balance énergétique déficitaire. Dans un nombre important d'unités de soins intensifs la nutrition des patients n'apparaît pas comme un objectif prioritaire de la prise en charge. En menant une étude prospective d'observation afin d'analyser la relation entre la balance énergétique et le pronostic clinique des patients avec séjours prolongés en soins intensifs, nous souhaitions changer cette attitude et démonter l'effet délétère de la malnutrition chez ce type de patient. Méthodes : Sur une période de 2 ans, tous les patients, dont le séjour en soins intensifs fut de 5 jours ou plus, ont été enrôlés. Les besoins en énergie pour chaque patient ont été déterminés soit par calorimétrie indirecte, soit au moyen d'une formule prenant en compte le poids du patient (30 kcal/kg/jour). Les patients ayant bénéficié d'une calorimétrie indirecte ont par ailleurs vérifié la justesse de la formule appliquée. L'âge, le sexe le poids préopératoire, la taille, et le « Body mass index » index de masse corporelle reconnu en milieu clinique ont été relevés. L'énergie délivrée l'était soit sous forme nutritionnelle (administration de nutrition entérale, parentérale ou mixte) soit sous forme non-nutritionnelle (perfusions : soluté glucosé, apport lipidique non nutritionnel). Les données de nutrition (cible théorique, cible prescrite, énergie nutritionnelle, énergie non-nutritionnelle, énergie totale, balance énergétique nutritionnelle, balance énergétique totale), et d'évolution clinique (nombre des jours de ventilation mécanique, nombre d'infections, utilisation des antibiotiques, durée du séjour, complications neurologiques, respiratoires gastro-intestinales, cardiovasculaires, rénales et hépatiques, scores de gravité pour patients en soins intensifs, valeurs hématologiques, sériques, microbiologiques) ont été analysées pour chacun des 669 jours de soins intensifs vécus par un total de 48 patients. Résultats : 48 patients de 57±16 ans dont le séjour a varié entre 5 et 49 jours (motif d'admission : polytraumatisés 10; chirurgie cardiaque 13; insuffisance respiratoire 7; pathologie gastro-intestinale 3; sepsis 3; transplantation 4; autre 8) ont été retenus. Si nous n'avons pu démontrer une relation entre la balance énergétique et plus particulièrement, le déficit énergétique, et la mortalité, il existe une relation hautement significative entre le déficit énergétique et la morbidité, à savoir les complications et les infections, qui prolongent naturellement la durée du séjour. De plus, bien que l'étude ne comporte aucune intervention et que nous ne puissions avancer qu'il existe une relation de cause à effet, l'analyse par régression multiple montre que le facteur pronostic le plus fiable est justement la balance énergétique, au détriment des scores habituellement utilisés en soins intensifs. L'évolution est indépendante tant de l'âge et du sexe, que du status nutritionnel préopératoire. L'étude ne prévoyait pas de récolter des données économiques : nous ne pouvons pas, dès lors, affirmer que l'augmentation des coûts engendrée par un séjour prolongé en unité de soins intensifs est induite par un déficit énergétique, même si le bon sens nous laisse penser qu'un séjour plus court engendre un coût moindre. Cette étude attire aussi l'attention sur l'origine du déficit énergétique : il se creuse au cours de la première semaine en soins intensifs, et pourrait donc être prévenu par une intervention nutritionnelle précoce, alors que les recommandations actuelles préconisent un apport énergétique, sous forme de nutrition artificielle, qu'à partir de 48 heures de séjour aux soins intensifs. Conclusions : L'étude montre que pour les patients de soins intensifs les plus graves, la balance énergétique devrait être considérée comme un objectif important de la prise en charge, nécessitant l'application d'un protocole de nutrition précoce. Enfin comme l'évolution à l'admission des patients est souvent imprévisible, et que le déficit s'installe dès la première semaine, il est légitime de s'interroger sur la nécessité d'appliquer ce protocole à tous les patients de soins intensifs et ceci dès leur admission. Summary Background and aims: Critically ill patients with complicated evolution are frequently hypermetabolic, catabolic, and at risk of underfeeding. The study aimed at assessing the relationship between energy balance and outcome in critically ill patients. Methods: Prospective observational study conducted in consecutive patients staying 5 days in the surgical ICU of a University hospital. Demographic data, time to feeding, route, energy delivery, and outcome were recorded. Energy balance was calculated as energy delivery minus target. Data in means+ SD, linear regressions between energy balance and outcome variables. Results: Forty eight patients aged 57±16 years were investigated; complete data are available in 669 days. Mechanical ventilation lasted 11±8 days, ICU stay 15+9 was days, and 30-days mortality was 38%. Time to feeding was 3.1 ±2.2 days. Enteral nutrition was the most frequent route with 433 days. Mean daily energy delivery was 1090±930 kcal. Combining enteral and parenteral nutrition achieved highest energy delivery. Cumulated energy balance was between -12,600+ 10,520 kcal, and correlated with complications (P<0.001), already after 1 week. Conclusion: Negative energy balances were correlated with increasing number of complications, particularly infections. Energy debt appears as a promising tool for nutritional follow-up, which should be further tested. Delaying initiation of nutritional support exposes the patients to energy deficits that cannot be compensated later on.

Prevalence of overweight and obesity in the Swiss population

Introduction: The latest data on prevalence of overweight (OW) and obesity (OB) in the general Swiss resident population rely on the Swiss Health Survey (SHS), a telephonic interview performed in 2007. However, body mass index (BMI) is underestimated when self-reported, leading to a misclassification of up to 60% of obese subjects. The last survey with measured BMI performed in the 3 linguistic regions of Switzerland dates back to 1977. We explored the regional prevalences of OW and OB by measured BMI in the general Swiss resident population. Methods: Cross-sectional population-based survey in the 3 linguistic regions of Switzerland in 2010-2011. Data on 1471 participants aged 15-95 years (712 men, 759 women) were available for the analysis. BMI was calculated from measured height and weight and categorized into 3 groups according to WHO classification: lean (<25 kg/m2), overweight (25-30 kg/m2) and obese (>= 30 kg/m2). Data on medication, smoking, education, physical activity and dietary habitudes were collected using a questionnaire. Results: The overall prevalence of OW and OB was 32.1% and 13.9%, respectively. OB prevalence was similar across the 3 linguistic regions (13.5% in German-, 15.6% in French- and 12.0% in Italian-speaking Switzerland, p = 0.40), unlike OW prevalence, which significantly differed in unadjusted analyses (35.4%, 29.1% and 25.4%, respectively, p = 0.005). In analyses including age, sex, smoking, physical activity and education as covariates, living in the Italian-speaking region was associated neither with BMI (linear regression) nor with OW or OB (logistic regressions) . Age (beta coefficient [SE]: 0.064[0.006] kg/m2 per year, p <0.001) and sex (-1.76 [0.23] kg/m2 in women, p <0.001) were significantly associated with BMI. Conclusions: Overweight and obesity affect nearly half of the Swiss population aged >15 years. We observed no significant differences across regions once we accounted for age, sex, education and lifestyle. Public health interventions addressing modifiable behavioral factors to reduce overweight and obesity in Switzerland can be expected to have substantial benefits.

Inferring landscape effects on dispersal from genetic distances: how far can we go?

Functional connectivity affects demography and gene dynamics in fragmented populations. Besides species-specific dispersal ability, the connectivity between local populations is affected by the landscape elements encountered during dispersal. Documenting these effects is thus a central issue for the conservation and management of fragmented populations. In this study, we compare the power and accuracy of three methods (partial correlations, regressions and Approximate Bayesian Computations) that use genetic distances to infer the effect of landscape upon dispersal. We use stochastic individual-based simulations of fragmented populations surrounded by landscape elements that differ in their permeability to dispersal. The power and accuracy of all three methods are good when there is a strong contrast between the permeability of different landscape elements. The power and accuracy can be further improved by restricting analyses to adjacent pairs of populations. Landscape elements that strongly impede dispersal are the easiest to identify. However, power and accuracy decrease drastically when landscape complexity increases and the contrast between the permeability of landscape elements decreases. We provide guidelines for future studies and underline the needs to evaluate or develop approaches that are more powerful.

Is the impact of public investment neutral across the regional income distribution?: evidence from Mexico

This paper investigates the contribution of public investment to the reduction of regional inqualities, with a specific application to Mexico. We use quantile regressions to examine the impact of public investment on regional disparities according to the position of each region in the conditional distribution of regional income. Results confirm the hypothesis that regional inequalities can indeed be atrributed to the regional distribution of public investment, where the observed pattern shows that public investment mainly helped to reduce regional inequalities between the richest regions

Recurrence of status epilepticus: Prognostic role and outcome predictors.

OBJECTIVE: Predictors of morbidity and mortality after status epilepticus (SE) have been studied extensively in hospital- and population-based cohorts. However, little attention has been directed toward SE recurrence after an incident episode. We investigated clinical and demographic characteristics of patients presenting SE recurrence and its specific prognostic role. METHODS: In this observational cohort study, we screened our prospective registry of consecutive adults with SE between April 2006 and February 2014. Demographic and clinical data were compared between incident and recurrent SE episodes; risk of SE recurrence was assessed through survival analysis, and the prognostic role of SE recurrence with multivariable logistic regressions. RESULTS: Of the incident cohort (509 patients), 68 (13%) experienced recurrent SE. The cumulative recurrence rate over 4 years was 32%. Recurrence risk was significantly reduced after an acute SE etiology (hazard ratio [HR] 0.5, 95% confidence interval [CI] 0.31-0.82; p = 0.005), and was borderline increased in women (HR 1.59, 95% CI 0.97-2.65; p = 0.06). Although recurrent SE episodes showed lower morbidity and mortality, prognosis was independently related to Status Epilepticus Severity Score (STESS) and potentially fatal etiology, but not to SE recurrence. SIGNIFICANCE: This study provides class III evidence that SE recurrence involves a significant proportion of patients, and that recurrence risk is independently associated with chronic etiology and to a lesser extent with female gender. However, contrary to underlying cause and SE severity, SE recurrence per se does not independently correlate with outcome. Early identification of patients at higher risk of SE recurrence may influence their management during follow-up.