Self-perception of aging and vulnerability to adverse outcomes at the age of 65-70 years.

OBJECTIVES. This study examines the relationship between self-perception of aging and vulnerability to adverse outcomes in adults aged 65-70 years using data from a cohort of 1,422 participants in Lausanne, Switzerland. METHODS: A positive or negative score of perception of aging was established using the Attitudes Toward Own Aging subscale including 5 items of the Philadelphia Geriatric Center Morale Scale. Falls, hospitalizations, and difficulties in basic and instrumental activities of daily living (ADL) collected in the first 3 years of follow-up were considered adverse outcomes. The relationship between perception and outcomes were evaluated using multiple logistic regression models adjusting for chronic medical conditions, depressive feelings, living arrangement, and socioeconomic characteristics. RESULTS: The strongest associations of self-perception of aging with outcomes were observed for basic and instrumental ADL. Associations with falls and hospitalizations were not constant but could be explained by health characteristics. CONCLUSIONS: A negative self-perception of aging is an indicator of risk for future disability in ADL. Factors such as a low-economic status, living alone, multiple chronic medical conditions, and depressive feelings contribute to a negative self-perception of aging but do not explain the relationship with incident activities of daily living disability.

Job accessibility, employment and job-education mismatch in the metropolitan area of Barcelona

This paper analyses the effect of job accessibility by public and private transport on labour market outcomes in the metropolitan area of Barcelona. Beyond employment, we consider the effect of job accessibility on job-education mismatch, which represents a relevant aspect of job quality. We adopt a recursive system of equations that models car availability, employment and mismatch. Public transport accessibility appears as an exogenous variable in the three equations. Even though it may reflect endogenous residential sorting, falsification proofs suggest that the estimated effect of public transport accessibility is not entirely driven by the endogenous nature of residential decisions.

Outcome of intravenous thrombolysis in stroke patients weighing over 100 kg.

Background: Intravenous thrombolysis with alteplase for ischemic stroke is fixed at a maximal dose of 90 mg for safety reasons. Little is known about the clinical outcomes of stroke patients weighing >100 kg, who may benefit less from thrombolysis due to this dose limitation. Methods: Prospective data on 1,479 consecutive stroke patients treated with intravenous alteplase in six Swiss stroke units were analyzed. Presenting characteristics and the frequency of favorable outcomes, defined as a modified Rankin scale (mRS) score of 0 or 1, a good outcome (mRS score 0-2), mortality and symptomatic intracranial hemorrhage (SICH) were compared between patients weighing >100 kg and those weighing ≤100 kg. Results: Compared to their counterparts (n = 1,384, mean body weight 73 kg), patients weighing >100 kg (n = 95, mean body weight 108 kg) were younger (61 vs. 67 years, p < 0.001), were more frequently males (83 vs. 60%, p < 0.001) and more frequently suffered from diabetes mellitus (30 vs. 13%, p < 0.001). As compared with patients weighing ≤100 kg, patients weighing >100 kg had similar rates of favorable outcomes (45 vs. 48%, p = 0.656), good outcomes (58 vs. 64%, p = 0.270) and mortality (17 vs. 12%, p = 0.196), and SICH risk (1 vs. 5%, p = 0.182). After multivariable adjustment, body weight >100 kg was strongly associated with mortality (p = 0.007) and poor outcome (p = 0.007). Conclusion: Our data do not suggest a reduced likehood of favorable outcomes in patients weighing >100 kg treated with the current dose regimen. The association of body weight >100 kg with mortality and poor outcome, however, demands further large-scale studies to replicate our findings and to explore the underlying mechanisms.

Additive effects of HLA alleles and innate immune genes determine viral outcome in HCV infection.

BACKGROUND: Chronic HCV infection is a leading cause of liver-related morbidity globally. The innate and adaptive immune responses are thought to be important in determining viral outcomes. Polymorphisms associated with the IFNL3 (IL28B) gene are strongly associated with spontaneous clearance and treatment outcomes. OBJECTIVE: This study investigates the importance of HLA genes in the context of genetic variation associated with the innate immune genes IFNL3 and KIR2DS3. DESIGN: We assess the collective influence of HLA and innate immune genes on viral outcomes in an Irish cohort of women (n=319) who had been infected from a single source as well as a more heterogeneous cohort (Swiss Cohort, n=461). In the Irish cohort, a number of HLA alleles are associated with different outcomes, and the impact of IFNL3-linked polymorphisms is profound. RESULTS: Logistic regression was performed on data from the Irish cohort, and indicates that the HLA-A*03 (OR 0.36 (0.15 to 0.89), p=0.027) -B*27 (OR 0.12 (0.03 to 0.45), p=<0.001), -DRB1*01:01 (OR 0.2 (0.07 to 0.61), p=0.005), -DRB1*04:01 (OR 0.31 (0.12 to 0.85, p=0.02) and the CC IFNL3 rs12979860 genotypes (OR 0.1 (0.04 to 0.23), p<0.001) are significantly associated with viral clearance. Furthermore, DQB1*02:01 (OR 4.2 (2.04 to 8.66), p=0.008), KIR2DS3 (OR 4.36 (1.62 to 11.74), p=0.004) and the rs12979860 IFNL3 'T' allele are associated with chronic infection. This study finds no interactive effect between IFNL3 and these Class I and II alleles in relation to viral clearance. There is a clear additive effect, however. Data from the Swiss cohort also confirms independent and additive effects of HLA Class I, II and IFNL3 genes in their prediction of viral outcome. CONCLUSIONS: This data supports a critical role for the adaptive immune response in the control of HCV in concert with the innate immune response.

Preventive and therapeutic strategies in critically ill patients with highly resistant bacteria.

The antibiotic pipeline continues to diminish and the majority of the public remains unaware of this critical situation. The cause of the decline of antibiotic development is multifactorial and currently most ICUs are confronted with the challenge of multidrug-resistant organisms. Antimicrobial multidrug resistance is expanding all over the world, with extreme and pandrug resistance being increasingly encountered, especially in healthcare-associated infections in large highly specialized hospitals. Antibiotic stewardship for critically ill patients translated into the implementation of specific guidelines, largely promoted by the Surviving Sepsis Campaign, targeted at education to optimize choice, dosage, and duration of antibiotics in order to improve outcomes and reduce the development of resistance. Inappropriate antimicrobial therapy, meaning the selection of an antibiotic to which the causative pathogen is resistant, is a consistent predictor of poor outcomes in septic patients. Therefore, pharmacokinetically/pharmacodynamically optimized dosing regimens should be given to all patients empirically and, once the pathogen and susceptibility are known, local stewardship practices may be employed on the basis of clinical response to redefine an appropriate regimen for the patient. This review will focus on the most severely ill patients, for whom substantial progress in organ support along with diagnostic and therapeutic strategies markedly increased the risk of nosocomial infections.

Il canone del Novecento letterario italiano in Spagna

The essay offers a thorough analysis on the issue of the reception of XXth Century Italian Literature in Spain. The age af the avant-garde and the late Fifties are signalled as the decisive moments in the affirmation of such influence, whereas the Sixties mark the beginning of a declining phase, which had different outcomes in poetry and in narrative. In defining this complex trajectory, a wide range of cultural indicators have been used (such as: translations; anthologies; militant criticism; the influence upon individual writers or rather upon relevant reading communities etc.), and the limitations imposed by the specific cultural and epistemological expectations, considered in their well determined historical context, have also been observed.

Impact of the introduction of real-time therapeutic drug monitoring on empirical doses of carbapenems in critically ill burn patients.

PURPOSE: Adequate empirical antibiotic dose selection for critically ill burn patients is difficult due to extreme variability in drug pharmacokinetics. Therapeutic drug monitoring (TDM) may aid antibiotic prescription and implementation of initial empirical antimicrobial dosage recommendations. This study evaluated how gradual TDM introduction altered empirical dosages of meropenem and imipenem/cilastatin in our burn ICU. METHODS: Imipenem/cilastatin and meropenem use and daily empirical dosage at a five-bed burn ICU were analyzed retrospectively. Data for all burn admissions between 2001 and 2011 were extracted from the hospital's computerized information system. For each patient receiving a carbapenem, episodes of infection were reviewed and scored according to predefined criteria. Carbapenem trough serum levels were characterized. Prior to May 2007, TDM was available only by special request. Real-time carbapenem TDM was introduced in June 2007; it was initially available weekly and has been available 4 days a week since 2010. RESULTS: Of 365 patients, 229 (63%) received antibiotics (109 received carbapenems). Of 23 TDM determinations for imipenem/cilastatin, none exceeded the predefined upper limit and 11 (47.8%) were insufficient; the number of TDM requests was correlated with daily dose (r=0.7). Similar numbers of inappropriate meropenem trough levels (30.4%) were below and above the upper limit. Real-time TDM introduction increased the empirical dose of imipenem/cilastatin, but not meropenem. CONCLUSIONS: Real-time carbapenem TDM availability significantly altered the empirical daily dosage of imipenem/cilastatin at our burn ICU. Further studies are needed to evaluate the individual impact of TDM-based antibiotic adjustment on infection outcomes in these patients.

Three essays in behavioral and experimental economics

The present PhD dissertation consists of three papers, organized in chapters, in the field of behavioral economics. This discipline studies economic behavior of individuals subject to limitations, such as bounded self-interest and bounded willpower. The behavior studied in the present thesis ranges from the complex decision to register as an organ donor, decision¬making in the presence of uncertainty and the decision to give money to a charitable organization. The first chapter aims at testing the effectiveness of an active-decision (AD) mechanism on the decision to become an organ donor in Switzerland, using field experiments. We found that stimulating participants' reflection on the topic of organ donation had a negative effect on the decision to become an organ donor. Moreover, a non-binding commitment nudge reduces putting off the decision, but does not lead to donation rates higher than in the control group. The results suggest that AD may be far more limited than previously thought and raise doubts about the efficacy of engaging potential donors to reflect on the topic of organ donation. Beyond carrying for others, behavioral economics also recognizes that individuals do not evaluate outcomes in absolute terms but rather by comparing them to some reference levels, called reference points. Above the reference points, economic outcomes are perceived as gains, while below these levels the same outcomes are felt as losses. The last two chapters analyze the importance of reference points in the evaluation of economic outcomes. Using a laboratory experiment where subjects played two consecutive lotteries, Chapter 2 studies the speed of adjustment of the reference point. We find that varying the probability of winning the first lottery has no effect on subjects' risk behavior regarding the second lottery. This result indicates a very fast adjustment of the reference point to the latest information. Chapter 3 investigates whether reference points are relevant for charitable preferences. Using actual donation decisions of participants in a laboratory experiment, the results suggest that reference points are not crucial for shaping charitable giving. -- Cette thèse de doctorat consiste en trois articles, organisés en chapitres, dans le domaine de l'économie comportementale. Cette discipline étudie le comportement d'agents économiques sujets à des limitations, telles qu'un égoïsme limité et une volonté limitée. Le comportement étudié dans cette thèse va de la décision complexe de devenir donneur d'organes, la prise de décision en présence d'incertitude à la décision de donner de l'argent à une oeuvre caritative. Le premier chapitre vise à tester l'efficacité d'un mécanisme de « décision active » (active decision, AD) sur la décision de devenir donneur d'organes en Suisse, et ce en recourant à deux expériences hors-laboratoire. Les résultats montrent que stimuler la réflexion des participants sur le don d'organes a un effet négatif sur la décision de devenir donneur. De plus, un mécanisme qui encourage les participants à prendre une décision sur le champ réduit la tendance à procrastiner, mais ne mène pas à un taux de donneurs plus élevé par rapport à un groupe de contrôle. Les résultats suggèrent que le mécanisme AD est bien plus limité que ce qui a été supposé jusqu'à maintenant. De plus, ils suscitent le doute quant à l'efficacité de stimuler la réflexion de potentiels donneurs sur le sujet du don d'organes. En plus de se soucier des autres, l'économie comportementale admet également que les individus n'évaluent pas les résultats de façon absolue, mais en comparant ceux-ci à des niveaux de références, souvent appelés points de référence. Au-dessus de ces points de référence, les résultats sont perçus en tant que gains, tandis qu'en-dessous ces mêmes résultats sont considérés comme des pertes. Les deux derniers chapitres analysent l'importance des points de référence dans diverses situations. A l'aide d'une expérience en laboratoire dans laquelle les participants participent à deux loteries consécutives, le chapitre 2 étudie la vitesse d'ajustement du point de référence. Le résultat montre que varier la probabilité de gagner la première loterie n'a aucun effet sur le comportement en matière de risques concernant la deuxième loterie. Cela indique un ajustement très rapide du point de référence. Le chapitre 3 vise à déterminer si les points de référence ont un rôle majeur concernant les préférences caritatives. Les données relatives aux décisions de don des participants d'une expérience en laboratoire montrent que les points de référence n'influencent pas significativement le don caritatif.

Management of severe blunt hepatic injury in the era of computed tomography and transarterial embolization: A systematic review and critical appraisal of the literature.

BACKGROUND: During the last decade, the management of blunt hepatic injury has considerably changed. Three options are available as follows: nonoperative management (NOM), transarterial embolization (TAE), and surgery. We aimed to evaluate in a systematic review the current practice and outcomes in the management of Grade III to V blunt hepatic injury. METHOD: The MEDLINE database was searched using PubMed to identify English-language citations published after 2000 using the key words blunt, hepatic injury, severe, and grade III to V in different combinations. Liver injury was graded according to the American Association for the Surgery of Trauma classification on computed tomography (CT). Primary outcome analyzed was success rate in intention to treat. Critical appraisal of the literature was performed using the validated National Institute for Health and Care Excellence "Quality Assessment for Case Series" system. RESULTS: Twelve articles were selected for critical appraisal (n = 4,946 patients). The median quality score of articles was 4 of 8 (range, 2-6). Overall, the median Injury Severity Score (ISS) at admission was 26 (range, 0.6-75). A median of 66% (range, 0-100%) of patients was managed with NOM, with a success rate of 94% (range, 86-100%). TAE was used in only 3% of cases (range, 0-72%) owing to contrast extravasation on CT with a success rate of 93% (range, 81-100%); however, 9% to 30% of patients required a laparotomy. Thirty-one percent (range, 17-100%) of patients were managed with surgery owing to hemodynamic instability in most cases, with 12% to 28% requiring secondary TAE to control recurrent hepatic bleeding. Mortality was 5% (range, 0-8%) after NOM and 51% (range, 30-68%) after surgery. CONCLUSION: NOM of Grade III to V blunt hepatic injury is the first treatment option to manage hemodynamically stable patients. TAE and surgery are considered in a highly selective group of patients with contrast extravasation on CT or shock at admission, respectively. Additional standardization of the reports is necessary to allow accurate comparisons of the various management strategies. LEVEL OF EVIDENCE: Systematic review, level IV.

The use of beta-blockers is associated with the occurrence of acute kidney injury in severe alcoholic hepatitis.

BACKGROUND & AIMS: The beneficial effect of nonselective beta-blockers (NSBB) has recently been questioned in patients with end-stage cirrhosis. We analysed the impact of NSBB on outcomes in severe alcoholic hepatitis (AH). METHODS: This study was based on a prospective database of patients with severe, biopsy-proven AH. Patients admitted from July, 2006 to July, 2014 were retrospectively studied. Patients were divided into two groups (with and without NSBB) and assessed for the occurrence of Acute Kidney Injury (AKI) and transplant-free mortality during a 168-day follow-up period. RESULTS: One hundred thirty-nine patients were included, the mean Maddrey score was 71 ± 34 and 86 patients (61.9%) developed AKI. Forty-eight patients (34.5%) received NSBB. The overall 168-day transplant-free mortality was 50.5% (95%CI, 41.3-60.0%). The overall 168-day cumulative incidence of AKI was 61.9% (95%CI, 53.2-69.4%). When compared, patients with NSBB had a lower heart rate (65 ± 13 vs 92 ± 12, P < 0.0001) and a lower mean arterial pressure (MAP, 78 ± 3 vs 87 ± 5, P < 0.0001). Patients with NSBB had comparable MELD scores, Maddrey scores, and medical histories. The 168-day transplant-free mortality was 56.8% (95%CI, 41.3-69.7%) in patients with NSBB and 46.7% (95%CI, 35.0-57.6%) without NSBB (P = 0.25). The 168-day cumulative incidence of AKI was 89.6% (95%CI, 74.9-95.9%) with NSBB compared to 50.4% (95%CI: 39.0-60.7) for no NSBB (P = 0.0001). The independent factors predicting AKI were a higher MELD score and the presence of NSBB. CONCLUSIONS: The use of NSBB in patients with severe AH is independently associated with a higher cumulative incidence of AKI.

Embolic Strokes of Undetermined Source in the Athens Stroke Registry: an Outcome Analysis.

BACKGROUND AND PURPOSE: Information about outcomes in Embolic Stroke of Undetermined Source (ESUS) patients is unavailable. This study provides a detailed analysis of outcomes of a large ESUS population. METHODS: Data set was derived from the Athens Stroke Registry. ESUS was defined according to the Cryptogenic Stroke/ESUS International Working Group criteria. End points were mortality, stroke recurrence, functional outcome, and a composite cardiovascular end point comprising recurrent stroke, myocardial infarction, aortic aneurysm rupture, systemic embolism, or sudden cardiac death. We performed Kaplan-Meier analyses to estimate cumulative probabilities of outcomes by stroke type and Cox-regression to investigate whether stroke type was outcome predictor. RESULTS: 2731 patients were followed-up for a mean of 30.5±24.1months. There were 73 (26.5%) deaths, 60 (21.8%) recurrences, and 78 (28.4%) composite cardiovascular end points in the 275 ESUS patients. The cumulative probability of survival in ESUS was 65.6% (95% confidence intervals [CI], 58.9%-72.2%), significantly higher compared with cardioembolic stroke (38.8%, 95% CI, 34.9%-42.7%). The cumulative probability of stroke recurrence in ESUS was 29.0% (95% CI, 22.3%-35.7%), similar to cardioembolic strokes (26.8%, 95% CI, 22.1%-31.5%), but significantly higher compared with all types of noncardioembolic stroke. One hundred seventy-two (62.5%) ESUS patients had favorable functional outcome compared with 280 (32.2%) in cardioembolic and 303 (60.9%) in large-artery atherosclerotic. ESUS patients had similar risk of composite cardiovascular end point as all other stroke types, with the exception of lacunar strokes, which had significantly lower risk (adjusted hazard ratio, 0.70 [95% CI, 0.52-0.94]). CONCLUSIONS: Long-term mortality risk in ESUS is lower compared with cardioembolic strokes, despite similar rates of recurrence and composite cardiovascular end point. Recurrent stroke risk is higher in ESUS than in noncardioembolic strokes.

Clinical outcomes of lung transplant recipients with telomerase mutations.

BACKGROUND: Successful lung transplantation for patients with pulmonary fibrosis from telomerase mutations may be limited by systemic complications of telomerase dysfunction, including myelosuppression, cirrhosis, and malignancy. We describe clinical outcomes in 14 lung transplant recipients with telomerase mutations. METHODS: Subjects underwent lung transplantation between February 2005 and April 2014 at 5 transplant centers. Data were abstracted from medical records, focusing on outcomes reflecting post-transplant treatment effects likely to be complicated by telomerase mutations. RESULTS: The median age of subjects was 60.5 years (interquartile range = 52.0-62.0), 64.3% were male, and the mean post-transplant observation time was 3.2 years (SD ± 2.9). A mutation in telomerase reverse transcriptase was present in 11 subjects, a telomerase RNA component mutation was present in 2 subjects, and an uncharacterized mutation was present in 1 subject. After lung transplantation, 10 subjects were leukopenic and 5 did not tolerate lymphocyte anti-proliferative agents. Six subjects developed recurrent lower respiratory tract infections, 7 developed acute cellular rejection (A1), and 4 developed chronic lung allograft dysfunction. Eight subjects developed at least 1 episode of acute renal failure and 10 developed chronic renal insufficiency. In addition, 3 subjects developed cancer. No subjects had cirrhosis. At data censorship, 13 subjects were alive. CONCLUSIONS: The clinical course for lung transplant recipients with telomerase mutations is complicated by renal disease, leukopenia with intolerance of lymphocyte anti-proliferative agents, and recurrent lower respiratory tract infections. In contrast, cirrhosis was absent, acute cellular rejection was mild, and development of chronic lung allograft dysfunction was comparable to other lung transplant recipients. Although it poses challenges, lung transplantation may be feasible for patients with pulmonary fibrosis from telomerase mutations.

Prevalence of alcohol-impaired drivers based on random breath tests in a roadside survey

Sobriety checkpoints are not usually randomly located by traffic authorities. As such, information provided by non-random alcohol tests cannot be used to infer the characteristics of the general driving population. In this paper a case study is presented in which the prevalence of alcohol-impaired driving is estimated for the general population of drivers. A stratified probabilistic sample was designed to represent vehicles circulating in non-urban areas of Catalonia (Spain), a region characterized by its complex transportation network and dense traffic around the metropolis of Barcelona. Random breath alcohol concentration tests were performed during spring 2012 on 7,596 drivers. The estimated prevalence of alcohol-impaired drivers was 1.29 PER CENT, which is roughly a third of the rate obtained in non-random tests. Higher rates were found on weekends (1.90 PER CENT on Saturdays, 4.29 PER CENT on Sundays) and especially at night. The rate is higher for men (1.45 PER CENT) than for women (0.64 PER CENT) and the percentage of positive outcomes shows an increasing pattern with age. In vehicles with two occupants, the proportion of alcohol-impaired drivers is estimated at 2.62 PER CENT, but when the driver was alone the rate drops to 0.84 PER CENT, which might reflect the socialization of drinking habits. The results are compared with outcomes in previous surveys, showing a decreasing trend in the prevalence of alcohol-impaired drivers over time.

Waddlia chondrophila induces systemic infection, organ pathology, and elicits Th1-associated humoral immunity in a murine model of genital infection.

Waddlia chondrophila is a known bovine abortigenic Chlamydia-related bacterium that has been associated with adverse pregnancy outcomes in human. However, there is a lack of knowledge regarding how W. chondrophila infection spreads, its ability to elicit an immune response and induce pathology. A murine model of genital infection was developed to investigate the pathogenicity and immune response associated with a W. chondrophila infection. Genital inoculation of the bacterial agent resulted in a dose-dependent infection that spread to lumbar lymph nodes and successively to spleen and liver. Bacterial-induced pathology peaked on day 14, characterized by leukocyte infiltration (uterine horn, liver, and spleen), necrosis (liver) and extramedullary hematopoiesis (spleen). Immunohistochemistry demonstrated the presence of a large number of W. chondrophila in the spleen on day 14. Robust IgG titers were detected by day 14 and remained high until day 52. IgG isotypes consisted of high IgG2a, moderate IgG3 and no detectable IgG1, indicating a Th1-associated immune response. This study provides the first evidence that W. chondrophila genital infection is capable of inducing a systemic infection that spreads to major organs, induces uterus, spleen, and liver pathology and elicits a Th1-skewed humoral response. This new animal model will help our understanding of the mechanisms related to intracellular bacteria-induced miscarriages, the most frequent complication of pregnancy that affects one in four women.

Information Needs and Concerns of Patients with Inflammatory Bowel Disease: What Can We Learn from Participants in a Bilingual Clinical Cohort?

BACKGROUND: Inflammatory Bowel Disease (IBD) patients are confronted with needs and concerns related to their disease. AIM: To explore information expectations of patients included in a national bilingual IBD cohort in Switzerland (SIBDC). METHODS: This is a mixed-methods study, comprising 1) a semi-narrative survey sent to 1506 patients from the SIBDC and 2) two focus groups conducted with 14 patients to explore and assess the relevance of the survey's findings. Data collected within the framework of the SIBDC was used to characterize survey's responders. RESULTS: 728 patients (48%) replied to the survey: 52.5% females, 56% Crohn's disease (CD), 87% secondary/tertiary level educated, 70% full/part-time employed. On average, 47% of patients sought for information, regardless of the disease stage; 27% of them were dissatisfied with information received at the time of first symptoms. During flares, 43% were concerned about drugs and therapies; in remission, 57% had concerns on research and developments; 27% searched for information linked to daily disease management. Information-seeking increased when active disease, for CD with high levels of perceived stress (OR = 2.47; p = 0.003), and for all with higher posttraumatic stress symptoms. The focus groups confirmed a perceived lack of information about general functioning, disease course, treatments and their risks, extra-intestinal symptoms and manifestations. CONCLUSIONS: Information remains insufficient for IBD patients. Lack of information in specific domains can potentially cause stress and hinder detection of symptoms. Better information should be considered as a potentially important component in improving patients' outcomes in IBD.