Radiolabeled human monoclonal IgM for intracompartmental cancer therapy

Radioimmunotherapy (RIT) with i.v. administered radiolabeled IgG can selectively irradiate tumor cells in vivo. However, it only provides effective therapy for lymphomas. Intracompartmental RIT with radiolabeled human monoclonal IgM may allow curative treatment of solid tumors by increasing tumor deposition of radioactivity, reducing systemic toxicity and allowing repeated administration. This hypothesis was tested in nude mouse models with IgM radiolabeled with indium-111 $\rm(\sp{111}In)$ or yttrium-90 $\rm(\sp{90}Y).$ The use of two radioisotopes, $\rm\sp{111}In$ for imaging and $\rm\sp{90}Y$ for therapy, allow for more quantitative and cautious development of RIT.^ Radiolabled 2B12, an IgM reactive with human ovarian carcinomas was tested by i.v. and intraperitoneal (i.p.) administration in nude mice bearing i.p. nodules of a human ovarian carcinoma cell line (SKOV3 NMP2). Radiolabeled CR4E8, an IgM reactive with human squamous cell carcinomas was tested by i.v. and intralesional (i.l.) administration in nude mice bearing subcutaneous tumors of a human head and neck squamous cell carcinoma cell line (886). These two models were selected to test proof of concept. Radiolabeled irrelevant IgM (CH-1B9), and $\rm\sp{90}Y$-aggregate served as specificity controls. Biodistribution was performed by excising, weighing and then measuring the radioactivity of tumor and normal organs. Therapy was conducted with i.p. $\rm\sp{90}Y$-labeled 2B12 using both single and fractionated administration and with i.l. $\rm\sp{90}Y$-labeled CR4E8 using single administration. Mice were monitored for tumor response, survival and systemic toxicity.^ Intracompartmental administration of radiolabeled IgM produced immediate high and prolonged tumor deposition of radioactivity with low normal tissue uptake. In contrast, i.v. administration resulted in low tumor, but high liver and spleen uptake. Similar biodistributions were demonstrated for $\rm\sp{111}In$- and $\rm\sp{90}Y$-labeled IgM. Intraperitoneal therapy with $\rm\sp{90}Y$-labeled 2B12 increased survival by approximately 12 days for every 100 $\rm\mu Ci$ of activity without significant toxicity for single (0-300 $\rm\mu Ci)$ and fractionated (150-510 $\rm\mu Ci)$ administration. Intralesional therapy with $\rm\sp{90}Y$-labeled CR4E8 (150-400 $\rm\mu Ci)$ induced prolonged complete regressions. Significant local or systemic toxicity was not observed.^ Intracompartmental RIT with radiolabeled tumor-reactive human monoclonal IgM can selectively irradiate tumor cells. Intracompartmental radiolabled IgM can significantly extend the survival of treated mice with minimal toxicity. It deserves further development as a new cancer therapy. ^

Evidence of species-specific neighborhood effects in the dipterocarpaceae of a Bornean rain forest

Although accumulating evidence indicates that local intraspecific density-dependent effects are not as rare in species-rich communities as previously suspected, there are still very few detailed and systematic neighborhood analyses of species-rich communities. Here, we provide such an analysis with the overall goal of quantifying the relative importance of inter- and intraspecific interaction strength in a primary, lowland dipterocarp forest located at Danum, Sabah, Malaysia. Using data on 10 abundant overstory dipterocarp species from two 4-ha permanent plots, we evaluated the effects of neighbors on the absolute growth rate of focal trees (from 1986 to 1996) over increasing neighborhood radii (from 1 to 20 m) with multiple regressions. Only trees 10 cm to < 100 cm girth at breast height in 1986 were considered as focal trees. Among neighborhood models with one neighbor term, models including only conspecific larger trees performed best in five out of 10 species. Negative effects of conspecific larger neighbors were most apparent in large overstory species such as those of the genus Shorea. However, neighborhood models with separate terms and radii for heterospecific and conspecific neighbors accounted for more variability in absolute growth rates than did neighborhood models with one neighbor term. The conspecific term was significant for nine out of 10 species. Moreover, in five out of 10 species, trees without conspecific neighbors had significantly higher absolute growth rates than trees with conspecific neighbors. Averaged over the 10 species, trees without conspecific neighbors grew 32.4 cm(2) in basal area from 1986 to 1996, whereas trees with conspecific neighbors only grew 14.7 cm(2) in basal area, although there was no difference in initial basal area between trees in the two groups. Averaged across the six species of the genus Shorea, negative effects of conspecific larger trees were significantly stronger than for heterospecific larger neighbors. Thus, high local densities within neighborhoods of 20 m may lead to strong intraspecific negative and, hence, density-dependent, effects even in species rich communities with low overall densities at larger spatial scales. We conjecture that the strength of conspecific effects may be correlated with the degree of host specificity of ectomycorrhizae.

Is Living With Psychosis Demoralizing? Insight, Self-stigma, and Clinical Outcome Among People With Schizophrenia Across 1 Year

Lack of insight is a major target in the treatment of schizophrenia. However, insight may have undesirable effects on self-concept and motivation that can hinder recovery. This study aimed to examine the link between insight, self-stigma, and demoralization as predictors of symptoms and functioning. Insight, self-stigma, depressive and psychotic symptoms, and functioning were assessed among 133 outpatients with schizophrenia at baseline and 12 months later. The data were analyzed by hierarchical multiple linear regressions. More insight at baseline and an increase in self-stigma over 12 months predicted more demoralization at follow-up. Insight at baseline was not associated with any outcome variable, but self-stigma at baseline was related to poorer functioning and more positive symptoms at follow-up. More demoralization at baseline predicted poorer functioning 12 months later. Demoralization did not mediate the relationship between self-stigma at baseline and functioning after 1 year. Given the decisive role of self-stigma regarding recovery from schizophrenia, dysfunctional beliefs related to illness and the self should be addressed in treatment. Different psychotherapeutical approaches are discussed.

Gender differences in disordered eating and weight dissatisfaction in Swiss adults: Which factors matter?

Background Research results from large, national population-based studies investigating gender differences in weight dissatisfaction and disordered eating across the adult life span are still limited. Gender is a significant factor in relation to weight dissatisfaction and disordered eating. However, the reasons for gender differences in these conditions are still poorly understood. The aim of this study was to examine gender differences in weight dissatisfaction and disordered eating in the general Swiss adult population and to identify gender-specific risk factors. Methods The study population consisted of 18156 Swiss adults who completed the population-based Swiss Health Survey 2007. Self-reported weight dissatisfaction, disordered eating and associated risk factors were assessed. In order to examine whether determinants of weight dissatisfaction and disordered eating (dieting to lose weight, binge eating, and irregular eating) differ in men and women, multivariate logistic regressions were applied separately for women and men. Results Although more men than women were overweight, more women than men reported weight dissatisfaction. Weight category, smoking status, education, and physical activity were significantly associated with weight dissatisfaction in men and women. In women, nationality and age were also significant factors. Gender-specific risk factors such as physical activity or weight category were identified for specific disordered eating behaviours. Conclusions The results suggest that gender specific associations between predictors and disordered eating behaviour should be considered in the development of effective prevention programs against disordered eating.

Palynological richness and evenness: insights from the taxa accumulation curve

Palynology provides the opportunity to make inferences on changes in diversity of terrestrial vegetation over long time scales. The often coarse taxonomic level achievable in pollen analysis, differences in pollen production and dispersal, and the lack of pollen source boundaries hamper the application of diversity indices to palynology. Palynological richness, the number of pollen types at a constant pollen count, is the most robust and widely used diversity indicator for pollen data. However, this index is also influenced by the abundance distribution of pollen types in sediments. In particular, where the index is calculated by rarefaction analysis, information on taxonomic richness at low abundance may be lost. Here we explore information that can be extracted from the accumulation of taxa over consecutive samples. The log-transformed taxa accumulation curve can be broken up into linear sections with different slope and intersect parameters, describing the accumulation of new taxa within the section. The breaking points may indicate changes in the species pool or in the abundance of high versus low pollen producers. Testing this concept on three pollen diagrams from different landscapes, we find that the break points in the taxa accumulation curves provide convenient zones for identifying changes in richness and evenness. The linear regressions over consecutive samples can be used to inter- and extrapolate to low or extremely high pollen counts, indicating evenness and richness in taxonomic composition within these zones. An evenness indicator, based on the rank-order-abundance is used to assist in the evaluation of the results and the interpretation of the fossil records. Two central European pollen diagrams show major changes in the taxa accumulation curves for the Lateglacial period and the time of human induced land-use changes, while they do not indicate strong changes in the species pool with the onset of the Holocene. In contrast, a central Swedish pollen diagram shows comparatively little change, but high richness during the early Holocene forest establishment. Evenness and palynological richness are related for most periods in the three diagrams, however, sections before forest establishment and after forest clearance show high evenness, which is not necessarily accompanied by high palynological richness, encouraging efforts to separate the two.

Experimental, theoretical and numerical investigation of the nonlinear micromechanical properties of bone

Aging societies suffer from an increasing incidence of bone fractures. Bone strength depends on the amount of mineral measured by clinical densitometry, but also on the micromechanical properties of the bone hierarchical organization. A good understanding has been reached for elastic properties on several length scales, but up to now there is a lack of reliable postyield data on the lower length scales. In order to be able to describe the behavior of bone at the microscale, an anisotropic elastic-viscoplastic damage model was developed using an eccentric generalized Hill criterion and nonlinear isotropic hardening. The model was implemented as a user subroutine in Abaqus and verified using single element tests. A FE simulation of microindentation in lamellar bone was finally performed show-ing that the new constitutive model can capture the main characteristics of the indentation response of bone. As the generalized Hill criterion is limited to elliptical and cylindrical yield surfaces and the correct shape for bone is not known, a new yield surface was developed that takes any convex quadratic shape. The main advantage is that in the case of material identification the shape of the yield surface does not have to be anticipated but a minimization results in the optimal shape among all convex quadrics. The generality of the formulation was demonstrated by showing its degeneration to classical yield surfaces. Also, existing yield criteria for bone at multiple length scales were converted to the quadric formulation. Then, a computational study to determine the influence of yield surface shape and damage on the in-dentation response of bone using spherical and conical tips was performed. The constitutive model was adapted to the quadric criterion and yield surface shape and critical damage were varied. They were shown to have a major impact on the indentation curves. Their influence on indentation modulus, hardness, their ratio as well as the elastic to total work ratio were found to be very well described by multilinear regressions for both tip shapes. For conical tips, indentation depth was not a significant fac-tor, while for spherical tips damage was insignificant. All inverse methods based on microindentation suffer from a lack of uniqueness of the found material properties in the case of nonlinear material behavior. Therefore, monotonic and cyclic micropillar com-pression tests in a scanning electron microscope allowing a straightforward interpretation comple-mented by microindentation and macroscopic uniaxial compression tests were performed on dry ovine bone to identify modulus, yield stress, plastic deformation, damage accumulation and failure mecha-nisms. While the elastic properties were highly consistent, the postyield deformation and failure mech-anisms differed between the two length scales. A majority of the micropillars showed a ductile behavior with strain hardening until failure by localization in a slip plane, while the macroscopic samples failed in a quasi-brittle fashion with microcracks coalescing into macroscopic failure surfaces. In agreement with a proposed rheological model, these experiments illustrate a transition from a ductile mechanical behavior of bone at the microscale to a quasi-brittle response driven by the growth of preexisting cracks along interfaces or in the vicinity of pores at the macroscale. Subsequently, a study was undertaken to quantify the topological variability of indentations in bone and examine its relationship with mechanical properties. Indentations were performed in dry human and ovine bone in axial and transverse directions and their topography measured by AFM. Statistical shape modeling of the residual imprint allowed to define a mean shape and describe the variability with 21 principal components related to imprint depth, surface curvature and roughness. The indentation profile of bone was highly consistent and free of any pile up. A few of the topological parameters, in particular depth, showed significant correlations to variations in mechanical properties, but the cor-relations were not very strong or consistent. We could thus verify that bone is rather homogeneous in its micromechanical properties and that indentation results are not strongly influenced by small de-viations from the ideal case. As the uniaxial properties measured by micropillar compression are in conflict with the current literature on bone indentation, another dissipative mechanism has to be present. The elastic-viscoplastic damage model was therefore extended to viscoelasticity. The viscoelastic properties were identified from macroscopic experiments, while the quasistatic postelastic properties were extracted from micropillar data. It was found that viscoelasticity governed by macroscale properties has very little influence on the indentation curve and results in a clear underestimation of the creep deformation. Adding viscoplasticity leads to increased creep, but hardness is still highly overestimated. It was possible to obtain a reasonable fit with experimental indentation curves for both Berkovich and spherical indenta-tion when abandoning the assumption of shear strength being governed by an isotropy condition. These results remain to be verified by independent tests probing the micromechanical strength prop-erties in tension and shear. In conclusion, in this thesis several tools were developed to describe the complex behavior of bone on the microscale and experiments were performed to identify its material properties. Micropillar com-pression highlighted a size effect in bone due to the presence of preexisting cracks and pores or inter-faces like cement lines. It was possible to get a reasonable fit between experimental indentation curves using different tips and simulations using the constitutive model and uniaxial properties measured by micropillar compression. Additional experimental work is necessary to identify the exact nature of the size effect and the mechanical role of interfaces in bone. Deciphering the micromechanical behavior of lamellar bone and its evolution with age, disease and treatment and its failure mechanisms on several length scales will help preventing fractures in the elderly in the future.

Reversal of gender differences in Educational Attainment – historical analysis of the West German Case

Background information: During the late 1970s and the early 1980s, West Germany witnessed a reversal of gender differences in educational attainment, as females began to outperform males. Purpose: The main objective was to analyse which processes were behind the reversal of gender differences in educational attainment after 1945. The theoretical reflections and empirical evidence presented for the US context by DiPrete and Buchmann (Gender-specific trends in the value of education and the emerging gender gap in college completion, Demography 43: 1–24, 2006) and Buchmann, DiPrete, and McDaniel (Gender inequalities in education, Annual Review of Sociology 34: 319–37, 2008) are considered and applied to the West German context. It is suggested that the reversal of gender differences is a consequence of the change in female educational decisions, which are mainly related to labour market opportunities and not, as sometimes assumed, a consequence of a ‘boy’s crisis’. Sample: Several databases, such as the German General Social Survey, the German Socio-economic Panel and the German Life History Study, are employed for the longitudinal analysis of the educational and occupational careers of birth cohorts born in the twentieth century. Design and methods: Changing patterns of eligibility for university studies are analysed for successive birth cohorts and gender. Binary logistic regressions are employed for the statistical modelling of the individuals’ achievement, educational decision and likelihood for social mobility – reporting average marginal effects (AME). Results: The empirical results suggest that women’s better school achievement being constant across cohorts does not contribute to the explanation of the reversal of gender differences in higher education attainment, but the increase of benefits for higher education explains the changing educational decisions of women regarding their transition to higher education. Conclusions: The outperformance of females compared with males in higher education might have been initialised by several social changes, including the expansion of public employment, the growing demand for highly qualified female workers in welfare and service areas, the increasing returns of women’s increased education and training, and the improved opportunities for combining family and work outside the home. The historical data show that, in terms of (married) women’s increased labour market opportunities and female life-cycle labour force participation, the raising rates of women’s enrolment in higher education were – among other reasons – partly explained by their rising access to service class positions across birth cohorts, and the rise of their educational returns in terms of wages and long-term employment.

Health-related quality of life in young survivors of childhood cancer

PURPOSE Childhood cancer and its treatment may affect health-related quality of life (HRQoL) in childhood cancer survivors, but population-based studies in young survivors are scarce. We aimed to: (1) compare HRQoL between young survivors and population norms and (2) find factors that influence parent-reported HRQoL in survivors. METHODS As part of the Swiss Childhood Cancer Survivor Study, a questionnaire was mailed to parents of survivors aged 8-16 years, registered in the Swiss Childhood Cancer Registry, ≥5 years after diagnosis. We used the KIDSCREEN-27 instrument to compare self- and parent-reported HRQoL between survivors (N = 425) and standardized norms in the five dimensions of physical well-being, psychological well-being, autonomy, peers and school environment (mean = 50, SD = 10). We then used multivariable linear regressions to test the influence of socio-demographic and cancer-related factors on HRQoL. RESULTS Self-reported physical well-being was comparable to norms. Other HRQoL dimensions were higher than norms, with the highest mean = 52.2 (p < 0.001) for school environment. Parent-reported HRQoL in survivors was comparable to population norms; only physical well-being was lower (mean = 47.1, p < 0.001), and school environment was higher (mean = 51.1, p = 0.035). Parent-reported HRQoL was lower for survivors of CNS tumors (physical well-being: β = -5.27, p = 0.007; psychological well-being: β = -4.39, p = 0.044; peers β = -5.17, p = 0.028), survivors of neuroblastoma (psychological well-being β = -5.20, p = 0.047), and survivors who had had a relapse (physical well-being β = -5.41, p = 0.005). CONCLUSIONS Assessing HRQoL during follow-up care, with a focus on physical well-being, specific diagnoses (e.g., CNS tumor) and late complications (e.g., relapse) might help to early identify problems and offer support to survivors with reduced HRQoL.

Cancer's positive flip side: posttraumatic growth after childhood cancer.

BACKGROUND Surviving childhood cancer may result in positive psychological changes called posttraumatic growth (PTG). Knowing about the possibility of positive changes may facilitate survivors' reintegration in daily life. We aimed to (1) describe PTG in Swiss childhood cancer survivors including the most and the least common PTG phenomena on the subscale and item levels and (2) determine factors associated with PTG. METHOD Within the Swiss Childhood Cancer Survivor Study (SCCSS), we sent two questionnaires to childhood cancer survivors registered in the Swiss Childhood Cancer Registry (SCCR). Eligible survivors were diagnosed after 1990 at age ≤16 years, survived ≥5 years, and were aged ≥18 years at the time the second questionnaire was sent. We included the Posttraumatic Growth Inventory (PTGI) to assess five areas of PTG. We investigated the association of PTG with socio-demographic characteristics, self-reported late effects, and psychological distress, which were assessed in the SCCSS and clinical variables extracted from the SCCR. We used descriptive statistics to describe PTG and linear regressions to investigate factors associated with PTG. RESULTS We assessed PTG in 309 childhood cancer survivors. Most individuals reported to have experienced some PTG. The most endorsed change occurred in "relation with others," the least in "spiritual change." PTG was significantly higher in survivors with older age at diagnosis (p = 0.001) and those with a longer duration of treatment (p = 0.042), while it was lower in male survivors (p = 0.003). CONCLUSIONS Supporting experiences of PTG during follow-up may help survivors successfully return to daily life.

Hormonal and Clinical Predictors for Post-egg Retrieval Pain in Women Undergoing Assisted Reproductive Technology Procedures

OBJECTIVES The intensity of post-egg retrieval pain is underestimated, with few studies examining post-procedural pain and predictors to identify women at risk for severe pain. We evaluated the influence of pre-procedural hormonal levels, ovarian factors, as well as mechanical temporal summation (mTS) as predictors for post-egg retrieval pain in women undergoing in vitro fertilization (IVF). METHODS Eighteen women scheduled for ultrasound-guided egg retrieval under standardized anesthesia and post-procedural analgesia were enrolled. Pre-procedural mTS, questionnaires, clinical data related to anesthesia and the procedure itself, post-procedural pain scores and pain medication for breakthrough pain were recorded. Statistical analysis included Pearson product moment correlations, Mann-Whitney U tests and multiple linear regressions. RESULTS Average peak post-egg retrieval pain during the first 24 hours was 5.0±1.6 on an NRS scale (0=no pain, 10=worst pain imaginable). Peak post-egg retrieval pain was correlated with basal antimullerian hormone (AMH) (r=0.549, P=0.018), pre-procedural peak estradiol (r=0.582, P=0.011), total number of follicles (r=0.517, P=0.028) and number of retrieved eggs (r=0.510, P=0.031). Ovarian hyperstimulation syndrome (OHSS) (n=4) was associated with higher basal AMH (P=0.004), higher peak pain scores (P=0.049), but not with peak estradiol (P=0.13). The mTS did not correlate with peak post-procedural pain (r=0.266, P=0.286), or peak estradiol level (r=0.090, P=0.899). DISCUSSION Peak post-egg retrieval pain intensity was higher than anticipated. Our results suggest that post-egg retrieval pain can be predicted by baseline AMH, high peak estradiol, and OHSS. Further studies to evaluate intra- and post-procedural pain in this population are needed, as well as clinical trials to assess post-procedural analgesia in women presenting with high hormonal levels.

Temperature and precipitation effects on δ13C depth profiles in SOM under temperate beech forests

Enrichment of 13C in SOM with soil depth is related to interacting processes influenced by temperature and precipitation. Our objectives were to derive climate effects on patterns of vertical δ13C values of soil organic matter (SOM) while minimizing the effect of confounding variables. We investigated vertical changes in δ13C values of SOM in 1-cm depth intervals in silvicultural mature beech (Fagus sylvatica L.) forest ecosystems in northern Rhineland-Palatinate across gradients of MAT (7.9 to 9.7 °C mean annual temperature) and MAP (607 to 1085 mm mean annual precipitation) in winter 2011. Forest stands (n = 10) were chosen based on data sets provided by the Rhineland-Palatinate Forest Administration so that variations in these gradients occurred while other environmental factors like physico-chemical soil properties, tree species, stand age, exposition and precipitation (for the temperature gradient) or temperature (for the precipitation gradient) did not differ among study sites. From litter down to the mineral soil at 10 cm depth, soil organic carbon (SOC) content decreased (47.5 ± SE 0.1% to 2.5 ± 0.1%) while the δ13C values increased (− 29.4 ± 0.1‰ to − 26.1 ± 0.1‰). Litter of sites under higher MAP/lower MAT had lower δ13C values which was in line with literature data on climate driven plant physiological process. To compare the dimension of the vertical 13C enrichment, δ13C values were regressed linearly against log-transformed carbon contents yielding absolute values of these slopes (beta). Beta values ranged between 0.6 and 4.5 (range of r from − 0.7 to − 1.0; p < 0.01). Due to an assumed decay continuum and similar variations of δ13C values in litter and in 10 cm depth, we conclude that effects on isotope composition in the Oi layer continue vertically and therefore, δ13C values in litter do not solely control beta values. Beta values decreased with increasing MAT (r = − 0.83; p < 0.05). Reduced soil moisture and therefore both, reduced microbial activity and reduced downward transport of microbial cycled DOM (=13C enriched) might be responsible for less pronounced δ13C depth profiles in case of high temperatures. Greater C:N ratios (lower degradability) of the litter under higher temperatures likely contributed to these depth trends. Beta values increased with increasing MAP (r = 0.73; p < 0.05). We found decreasing C:N ratios in the mineral soil that possibly indicates higher decomposition under higher precipitation. Exclusion of the organic layers from linear regressions indicated a stronger impact of MAP on the development of δ13C depth profiles. Our results confirm temperature and precipitation effects on δ13C depth profiles and indicate stronger 13C enrichment under lower MAT/higher MAP. Therefore, time series of vertical δ13C depth profiles might provide insights into climate change effects.

The Dark Side of the Moon: Meta-analytical Impact of Recruitment Strategies on Risk Enrichment in the Clinical High Risk State for Psychosis

Background: The individual risk of developing psychosis after being tested for clinical high-risk (CHR) criteria (posttest risk of psychosis) depends on the underlying risk of the disease of the population from which the person is selected (pretest risk of psychosis), and thus on recruitment strategies. Yet, the impact of recruitment strategies on pretest risk of psychosis is unknown. Methods: Meta-analysis of the pretest risk of psychosis in help-seeking patients selected to undergo CHR assessment: total transitions to psychosis over the pool of patients assessed for potential risk and deemed at risk (CHR+) or not at risk (CHR−). Recruitment strategies (number of outreach activities per study, main target of outreach campaign, and proportion of self-referrals) were the moderators examined in meta-regressions. Results: 11 independent studies met the inclusion criteria, for a total of 2519 (CHR+: n = 1359; CHR−: n = 1160) help-seeking patients undergoing CHR assessment (mean follow-up: 38 months). The overall meta-analytical pretest risk for psychosis in help-seeking patients was 15%, with high heterogeneity (95% CI: 9%–24%, I 2 = 96, P < .001). Recruitment strategies were heterogeneous and opportunistic. Heterogeneity was largely explained by intensive (n = 11, β = −.166, Q = 9.441, P = .002) outreach campaigns primarily targeting the general public (n = 11, β = −1.15, Q = 21.35, P < .001) along with higher proportions of self-referrals (n = 10, β = −.029, Q = 4.262, P = .039), which diluted pretest risk for psychosis in patients undergoing CHR assessment. Conclusions: There is meta-analytical evidence for overall risk enrichment (pretest risk for psychosis at 38monhts = 15%) in help-seeking samples selected for CHR assessment as compared to the general population (pretest risk of psychosis at 38monhts=0.1%). Intensive outreach campaigns predominantly targeting the general population and a higher proportion of self-referrals diluted the pretest risk for psychosis.

Impact of hypertension on the outcome of patients admitted with acute coronary syndrome

OBJECTIVE The role of hypertension and its impact on outcome in patients with acute coronary syndrome (ACS) is still debated. This study aimed to compare the outcomes of hypertensive and nonhypertensive ACS patients. METHODS Using data of ACS patients enrolled in the Acute Myocardial Infarction in Switzerland Plus Registry from 1997 to 2013, characteristics at presentation and outcomes in hospital and after 1 year were analyzed. Hypertension was defined as previously diagnosed and treated by a physician. The primary endpoint was mortality. Data were analyzed using multiple logistic regressions. RESULTS Among 41 771 ACS patients, 16 855 (40.4%) were without and 24 916 (59.6%) with preexisting hypertension. Patients with preexisting hypertension had a more favorable in-hospital outcome [odds ratio (OR) in-hospital mortality 0.82, 95% confidence interval (CI) 0.73-0.93; P = 0.022]. The independent predictors of in-hospital mortality for patients with preexisting hypertension were age, Killip class greater than 2, Charlson Comorbidity Index greater than 1, no pretreatment with statins and lower admission systemic blood pressure. Preexisting hypertension was not an independent predictor of 1-year mortality in the subgroup of patients (n = 7801) followed: OR 1.07, 95% CI 0.78-1.47; P = 0.68. Independent predictors of mortality 1 year after discharge for the 4796 patients with preexisting hypertension were age, male sex and comorbidities. Angiotensin-converting enzyme inhibitors or angiotensin II receptor antagonists and statins prescribed at discharge improved the outcomes. CONCLUSION Outcome of ACS patients with preexisting hypertension was associated with an improved in-hospital prognosis after adjustment for their higher baseline risk. However, this effect was not long-lasting and does not necessarily mean a causal relationship exists. Short-term and long-term management of patients with hypertension admitted with ACS could be further improved.