Comparison of microsatellite instability and chromosomal instability in predicting survival of patients with T3N0 colorectal cancer.

BACKGROUND: At least 2 apparently independent mechanisms, microsatellite instability (MSI) and chromosomal instability, are implicated in colorectal tumorigenesis. Their respective roles in predicting clinical outcomes of patients with T3N0 colorectal cancer remain unknown. METHODS: Eighty-eight patients with a sporadic T3N0 colon or rectal adenocarcinoma were followed up for a median of 67 months. For chromosomal instability analysis, Ki-ras mutations were determined by single-strand polymerase chain reaction, and p53 protein staining was studied by immunohistochemistry. For MSI analysis, DNA was amplified by polymerase chain reaction at 7 microsatellite targets (BAT25, BAT26, D17S250, D2S123, D5S346, transforming growth factor receptor II, and BAX). RESULTS: Overall 5-year survival rate was 72%. p53 protein nuclear staining was detected in 39 patients (44%), and MSI was detected in 21 patients (24%). MSI correlated with proximal location (P <.001) and mucinous content (P <.001). In a multivariate analysis, p53 protein expression carried a significant risk of death (relative risk = 4.0, 95% CI = 1.6 to 10.1, P =.004). By comparison, MSI was not a statistically significant prognostic factor for survival in this group (relative risk = 2.2, 95% CI = 0.6 to 7.3, P =.21). CONCLUSIONS: p53 protein overexpression provides better prognostic discrimination than MSI in predicting survival of patients with T3N0 colorectal cancer. Although MSI is associated with specific clinicopathologic parameters, it did not predict overall survival in this group. Assessment of p53 protein expression by immunocytochemistry provides a simple means to identify a subset of T3N0 patients with a 4-times increased risk for death.

Bienestar social e impuesto sobre la renta

El presente artículo pretende ampliar el modelo original de SANDMO (Journal of Public Economics, 1981 , Vol. 16), relativo a evasión e imposición óptima, en dos direcciones. De un lado, haciendo extensivo el marco de preferencias redistributivas hacia otros objetivos sociales distintos del utilitarista; asimismo, permitiendo el que los sujetos no defraudadores puedan diferir entre sí, de acuerdo con la bibliografía más corriente sobre el tema, por razón de la capacidad productiva que posean en el mercado de trabajo. Dichas modificaciones, además de deslindar los aspectos de aversión al riesgo de lo que propiamente es el grado de concavidad de la función de bienestar, facilitan una más completa descripción del modo como operan los factores que inciden en la conducta del contribuyente.

Bivalirudin for patients with acute coronary syndromes

Background: Current guidelines for patients with moderate- or high-risk acute coronary syndromes recommend an early invasive approach with concomitant antithrombotic therapy, including aspirin, clopidogrel, unfractionated or low-molecular-weight heparin, and glycoprotein IIb/IIIa inhibitors. We evaluated the role of thrombin-specific anticoagulation with bivalirudin in such patients. Methods: We assigned 13,819 patients with acute coronary syndromes to one of three antithrombotic regimens: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. The primary end points were a composite ischemia end point (death, myocardial infarction, or unplanned revascularization for ischemia), major bleeding, and the net clinical outcome, defined as the combination of composite ischemia or major bleeding. Results: Bivalirudin plus a glycoprotein IIb/IIIa inhibitor, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with noninferior 30-day rates of the composite ischemia end point (7.7% and 7.3%, respectively), major bleeding (5.3% and 5.7%), and the net clinical outcome end point (11.8% and 11.7%). Bivalirudin alone, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with a noninferior rate of the composite ischemia end point (7.8% and 7.3%, respectively; P = 0.32; relative risk, 1.08; 95% confidence interval [CI], 0.93 to 1.24) and significantly reduced rates of major bleeding (3.0% vs. 5.7%; P<0.001; relative risk, 0.53; 95% CI, 0.43 to 0.65) and the net clinical outcome end point (10.1% vs. 11.7%; P = 0.02; relative risk, 0.86; 95% CI, 0.77 to 0.97). Conclusions: In patients with moderate- or high-risk acute coronary syndromes who were undergoing invasive treatment with glycoprotein IIb/IIIa inhibitors, bivalirudin was associated with rates of ischemia and bleeding that were similar to those with heparin. Bivalirudin alone was associated with similar rates of ischemia and significantly lower rates of bleeding. (ClinicalTrials.gov number, NCT00093158.)

Abolishing mammography screening programs?

Biller-Andorno and Jüni (2014), in a widely debated commentary published in the May 22 issue of the New England Journal of Medicine, accept the concept that mammography every 2 years from age 50 can decrease breast cancer mortality by 20%, that is, from five to four deaths per 1000 women over a 10-year period. Both the absolute and the relative risk of breast cancer death may vary depending on the baseline mortality rates in various populations and on the impact of screening mammography in reducing breast cancer mortality, which may well vary around the 20% estimate adopted. We accept, therefore, that there are still uncertainties in the absolute and relative impact of mammography screening on breast cancer mortality, given the different study schemes and mammography intervals, the differences in populations, and the continuous improvements in technology (Warner, 2011; Independent UK Panel on Breast Cancer Screening, 2012). We also agree on the observation that mammography has an appreciable impact on breast cancer mortality (Bosetti et al., 2012), but clearly a much smaller one on total mortality.

Status epilepticus: impact of therapeutic coma on outcome.

OBJECTIVES: Therapeutic coma is advocated in guidelines for management of refractory status epilepticus; this is, however, based on weak evidence. We here address the specific impact of therapeutic coma on status epilepticus outcome. DESIGN: Retrospective assessment of a prospectively collected cohort. SETTING: Academic hospital. PATIENTS: Consecutive adults with incident status epilepticus lasting greater than or equal to 30 minutes, admitted between 2006 and 2013. MEASUREMENTS AND MAIN RESULTS: We recorded prospectively demographics, clinical status epilepticus features, treatment, and outcome at discharge and retrospectively medical comorbidities, hospital stay, and infectious complications. Associations between potential predictors and clinical outcome were analyzed using multinomial logistic regressions. Of 467 patients with incident status epilepticus, 238 returned to baseline (51.1%), 162 had new disability (34.6%), and 67 died (14.3%); 50 subjects (10.7%) were managed with therapeutic coma. Therapeutic coma was associated with poorer outcome in the whole cohort (relative risk ratio for new disability, 6.86; 95% CI, 2.84-16.56; for mortality, 9.10; 95% CI, 3.17-26.16); the effect was more important in patients with complex partial compared with generalized convulsive or nonconvulsive status epilepticus in coma. Prevalence of infections was higher (odds ratio, 3.81; 95% CI, 1.66-8.75), and median hospital stay in patients discharged alive was longer (16 d [range, 2-240 d] vs 9 d [range, 1-57 d]; p < 0.001) in subjects managed with therapeutic coma. CONCLUSIONS: This study provides class III evidence that therapeutic coma is associated with poorer outcome after status epilepticus; furthermore, it portends higher infection rates and longer hospitalizations. These data suggest caution in the straightforward use of this approach, especially in patients with complex partial status epilepticus.

Reasons to use e-cigarettes and associations with other substances among adolescents in Switzerland.

BACKGROUND: The objectives of this research were to describe the main reason(s) why adolescents use electronic cigarettes, to assess how e-cigarette experimenters and users differ based on personal characteristics, and to determine whether its use is associated with the use of other substances among a representative sample of youths in Switzerland. METHODS: A representative sample of 621 youths (308 females) was divided into never users (n=353), experimenters (Only once, n=120) and users (Several times, n=148) of e-cigarettes. Groups were compared on socio-demographic data and current smoking, alcohol misuse and cannabis use. Reasons for e-cigarette use were compared between experimenters and users. A multinomial regression was performed using never users as the reference category. RESULTS: Forty-three percent had ever tried e-cigarettes, and the main reason was curiosity. Compared to never users, experimenters were more likely to be out of school (Relative Risk Ratio [RRR]: 2.68) and to misuse alcohol (RRR: 2.08), while users were more likely to be male (RRR: 2.75), to be vocational students (RRR: 2.30) or out of school (RRR: 3.48) and to use any of the studied substances (tobacco, RRR: 5.26; alcohol misuse, RRR: 2.71; cannabis use, RRR: 30.2). CONCLUSIONS: Although often still part of adolescent experimentation, e-cigarettes are becoming increasingly popular among adolescents and they should become part of health providers' standard substance use screening. As health providers (and especially paediatricians) do not seem to have high levels of knowledge and, consequently, little comfort in discussing e-cigarettes, training in this domain should be available to them.

Riscos dos exames radiográficos em recém-nascidos internados em um hospital público de Belo Horizonte, MG

OBJETIVO: Os objetivos deste trabalho são: a) avaliar os procedimentos radiográficos e estimar o valor do kerma no ar na superfície de entrada nos recém-nascidos prematuros submetidos a exames de tórax e abdome, realizados no setor de neonatologia de um hospital público de Belo Horizonte; b) estimar as doses nos órgãos e os respectivos riscos de ocorrência de câncer nesses órgãos em decorrência das exposições à radiação. MATERIAIS E MÉTODOS: Foram analisados os prontuários dos pacientes internados no setor de neonatologia desse hospital durante o período de maio a setembro de 2004, anotando-se os dados antropométricos, data de internação/alta, exames de raios X realizados. O kerma no ar na superfície de entrada foi determinado a partir do rendimento do tubo de raios X e dos parâmetros de irradiação utilizados nos exames. As doses nos órgãos foram estimadas com o software PCXMC e o risco, durante o restante da expectativa de vida, com o software IREP. RESULTADOS: O valor médio do kerma no ar na superfície de entrada por exame foi abaixo do nível de referência da publicação da Comunidade Européia. Para o paciente mais severamente irradiado, os órgãos mais suscetíveis à ocorrência de câncer foram fígado, mama e estômago, com valores máximos de excess relative risk, respectivamente, de 3,4%, 2,3% e 1,7%. CONCLUSÃO: Foi constatada a necessidade de otimização dos procedimentos radiográficos com vista à diminuição do risco para os recém-nascidos, que apesar de ser considerado baixo (comparativamente ao benefício), deve ser sempre diminuído para valores tão baixos quanto razoavelmente exeqüíveis.

External Validation of the Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale (ISAN) Score for Predicting Stroke-Associated Pneumonia in the Athens Stroke Registry.

BACKGROUND AND PURPOSE: The Prestroke Independence, Sex, Age, National Institutes of Health Stroke Scale (ISAN) score was developed recently for predicting stroke-associated pneumonia (SAP), one of the most common complications after stroke. The aim of the present study was to externally validate the ISAN score. METHODS: Data included in the Athens Stroke Registry between June 1992 and December 2011 were used for this analysis. Inclusion criteria were the availability of all ISAN score variables (prestroke independence, sex, age, National Institutes of Health Stroke Scale score). Receiver operating characteristic curves and linear regression analyses were used to determine the discriminatory power of the score and to assess the correlation between actual and predicted pneumonia in the study population. Separate analyses were performed for patients with acute ischemic stroke (AIS) and intracerebral hemorrhage (ICH). RESULTS: The analysis included 3204 patients (AIS: 2732, ICH: 472). The ISAN score demonstrated excellent discrimination in patients with AIS (area under the curve [AUC]: .83 [95% confidence interval {CI}: .81-.85]). In the ICH group, the score was less effective (AUC: .69 [95% CI: .63-.74]). Higher-risk groups of ISAN score were associated with an increased relative risk of SAP; risk increase was more prominent in the AIS population. Predicted pneumonia correlated very well with actual pneumonia (AIS group: R(2) = .885; β-coefficient = .941, P < .001; ICH group: R(2) = .880, β-coefficient = .938, P < .001). CONCLUSIONS: In our external validation in the Athens Stroke Registry cohort, the ISAN score predicted SAP very accurately in AIS patients and demonstrated good discriminatory power in the ICH group. Further validation and assessment of clinical usefulness would strengthen the score's utility further.

Indirect comparison meta-analysis of two enoxaparin regimens in patients undergoing major orthopaedic surgery. Impact on the interpretation of thromboprophylactic effects of new anticoagulant drugs.

Two enoxaparin dosage regimens are used as comparators to evaluate new anticoagulants for thromboprophylaxis in patients undergoing major orthopaedic surgery, but so far no satisfactory direct comparison between them has been published. Our objective was to compare the efficacy and safety of enoxaparin 3,000 anti-Xa IU twice daily and enoxaparin 4,000 anti-Xa IU once daily in this clinical setting by indirect comparison meta-analysis, using Bucher's method. We selected randomised controlled trials comparing another anticoagulant, placebo (or no treatment) with either enoxaparin regimen for venous thromboembolism prophylaxis after hip or knee replacement or hip fracture surgery, provided that the second regimen was assessed elsewhere versus the same comparator. Two authors independently evaluated study eligibility, extracted the data, and assessed the risk of bias. The primary efficacy outcome was the incidence of venous thomboembolism. The main safety outcome was the incidence of major bleeding. Overall, 44 randomised comparisons in 56,423 patients were selected, 35 being double-blind (54,117 patients). Compared with enoxaparin 4,000 anti-Xa IU once daily, enoxaparin 3,000 anti-Xa IU twice daily was associated with a reduced risk of venous thromboembolism (relative risk [RR]: 0.53, 95% confidence interval [CI]: 0.40 to 0.69), but an increased risk of major bleeding (RR: 2.01, 95% CI: 1.23 to 3.29). In conclusion, when interpreting the benefit-risk ratio of new anticoagulant drugs versus enoxaparin for thromboprophylaxis after major orthopaedic surgery, the apparently greater efficacy but higher bleeding risk of the twice-daily 3,000 anti-Xa IU enoxaparin regimen compared to the once-daily 4,000 anti-Xa IU regimen should be taken into account.

A systematic review of ultrasound-guided methods for brachial plexus blockade.

We systematically reviewed 25 randomised controlled trials of ultrasound-guided brachial plexus blockade that recruited 1948 participants: either one approach vs another (axillary, infraclavicular or supraclavicular); or one injection vs multiple injections. There were no differences in the rates of successful blockade with approach, relative risk (95% CI): axillary vs infraclavicular, 1.0 (1.0-1.1), p = 0.97; axillary vs supraclavicular, 1.0 (1.0-1.1), p = 0.68; and infraclavicular vs supraclavicular, 1.0 (1.0-1.1), p = 0.32. There was no difference in the rate of successful blockade with the number of injections, relative risk (95% CI) 1.0 (1.0-1.0), p = 0.69, for one vs multiple injections. The rate of procedural paraesthesia was less with one injection than multiple injections, relative risk (95% CI) 0.6 (0.4-0.9), p = 0.004.

An update on EMU sovereign yield spread drivers in times of crisis: A panel data analysis

We empirically investigate the determinants of EMU sovereign bond yield spreads with respect to the German bund. Using panel data techniques, we examine the role of a wide set of potential drivers. To our knowledge, this paper presents one of the most exhaustive compilations of the variables used in the literature to study the behaviour of sovereign yield spreads and, in particular, to gauge the effect on these spreads of changes in market sentiment and risk aversion. We use a sample of both central and peripheral countries from January 1999 to December 2012 and assess whether there were significant changes after the outbreak of the euro area debt crisis. Our results suggest that the rise in sovereign risk in central countries can only be partially explained by the evolution of local macroeconomic variables in those countries.

An update on EMU sovereign yield spread drivers in times of crisis: A panel data analysis

We empirically investigate the determinants of EMU sovereign bond yield spreads with respect to the German bund. Using panel data techniques, we examine the role of a wide set of potential drivers. To our knowledge, this paper presents one of the most exhaustive compilations of the variables used in the literature to study the behaviour of sovereign yield spreads and, in particular, to gauge the effect on these spreads of changes in market sentiment and risk aversion. We use a sample of both central and peripheral countries from January 1999 to December 2012 and assess whether there were significant changes after the outbreak of the euro area debt crisis. Our results suggest that the rise in sovereign risk in central countries can only be partially explained by the evolution of local macroeconomic variables in those countries.

The effectiveness of vocationally oriented multidisciplinary rehabilitation (ASLAK®) amongst public sector employees

In Finland, vocationally oriented medical rehabilitation (ASLAK®) is a common preventive rehabilitation measure with the primary goal of preserving and improving work ability. The ASLAK® programme has been used for almost 30 years, although limited data exist on its effectiveness. The aims of this study were to determine whether the increased risk of work disability predicts the participants’ likelihood to be granted ASLAK® rehabilitation and to assess the effectiveness of the programme in decreasing the risk of work disability and modifying health-risk behaviours. This study is a part of the on-going Finnish Public Sector Study conducted by the Finnish Institute of Occupational Health. Data on 53 416 employees (81% women) were gathered from employers’ records, national health registers and repeated survey responses. During the 5-year follow-up, increased levels of the risk factors for work disability did not predict participation in the rehabilitation programme. During the 2.8-year followup (range 0.04–5.0 years), the risk of long-term work disability (sick leave >90 days or retirement) overall or, more specifically, due to musculoskeletal or mental diseases did not differ between the rehabilitants who participated in ASLAK® in 1997–2005 and their propensity score matched controls. There was no evidence of ASLAK® being effective in changing participants’ health-risk behaviours or in improving perceived general or mental health. The results suggest that potential participant recognition, mainly taking place in occupational health care, may fail to identify those with a higher risk of work disability. No evidence on the effectiveness of the programme was found in the study cohort when measured by the selected indicators.

Ultrasonografic changes in the axillary vein of patients with lymphedema after mastectomy

OBJECTIVE: To determine the prevalence of sonographic abnormalities (SA) in the axillary vein of patients with and without post-mastectomy lymphedema. METHODS: We studied a sample of 80 women, divided into two equal groups, with and without lymphedema, with B mode ultrasound, color and pulsed Doppler. The primary variable, SA, is defined as change in the venous diameter, parietal thickening, intraluminal images, compressibility, parietal collapse at inspiration and feature of the axillary venous flow on the operated side. Secondary variables were: stage of lymphedema, surgical technique, number of radio and chemotherapy sessions, limb volume, weight and age. The differences between the proportions in the groups were determined using the Chi-square test and / or Fisher's test. For continuous variables, we used the Mann-Whitney Test. To estimate the magnitude of the associations, we used the prevalence rate of SA in both groups as a measure of frequency, and as a measure of association, the prevalence ratio (PR) obtained as a function of relative risk (RR) and estimated by the test Mantel-Haenszel homogeneity test. We adopted the statistical significance level of 5% (p < 0.05). RESULTS: only the criterion "parietal thickening" was strongly associated with the lymphedema group (p = 0.001). The prevalence of SA was 55% in patients with lymphedema and 17.5% in the group without it, with difference in prevalence of 37.5%. CONCLUSION: the prevalence of SA was higher in patients undergoing mastectomy with lymphedema than in those without lymphedema.

Prospektiteoria ja sijoitusten hajauttaminen

Tämä tutkielma replikoi vuonna 1979 tehtyä Prospect Theory: An Analysis of Decision under Risk tutkimusta. Tutkielman tarkoituksena on tutkia odotetun hyödyn teorian ja prospektiteorian välistä eroa. Lisäksi tutkielmassa pyritään tutkimaan onko vastaajien vastauksilla yhteyttä heidän hajauttamiseensa ulkomaisiin sijoituskohteisiin. Kysymykset ovat suoraan replikoituja lukuun ottamatta viimeistä kysymystä, joka on tutkielman laatijan oma kysymys. Vastaukset on kerätty pörssiyhtiöiden yhtiökokouksissa Suomessa keväällä 2011 ja Lappeenrannan teknillisen yliopiston opiskelijoiden keskuudessa.