Circulating immune-related proteins associated with immune checkpoint inhibitor efficacy in patients with pancreatic ductal adenocarcinoma.

BACKGROUND: Most patients with pancreatic ductal adenocarcinoma (PDAC) do not benefit from immune checkpoint inhibitor treatment. However, the phase II study CheckPAC (NCT02866383) showed a clinical benefit (CB) rate of 37% and a response rate of 14% in patients with metastatic PDAC receiving stereotactic radiation therapy and nivolumab with or without ipilimumab. Translational studies were initiated to characterize the patients who would benefit from this treatment. Here, we evaluated the association between treatment outcome and 92 circulating immuno-oncology-related proteins in patients from the CheckPAC trial. MATERIALS AND METHODS: The study included 78 patients with chemoresistant metastatic PDAC treated with nivolumab ± ipilimumab combined with radiotherapy. Proteins were measured in serum samples collected at baseline and on treatment with the use of the Olink Target 96 Immuno-Oncology panel. A cohort of 234 patients with metastatic PDAC treated with first-line chemotherapy were also included. RESULTS: High levels of Fas ligand (FASLG) and galectin 1 (Gal-1) and low levels of C-C motif chemokine 4 were associated with CB. High FASLG and Gal-1 were associated with longer progression-free survival in univariable analysis. In the multivariable Cox regression analysis, the association was significant for Gal-1 (P < 0.001) but not significant for FASLG (P = 0.06). A focused unsupervised hierarchal clustering analysis, including T-cell activation and immune checkpoint-related proteins, identified clusters of patients with higher CB rate and higher tumor expression of leukocyte or T-cell markers (CD3, CD45, granzyme B). Thirty-six proteins increased significantly during immunotherapy. Several proteins (including FASLG, checkpoint proteins, and immune activation markers) increased independently of response during immunotherapy but did not increase in the cohort of patients treated with chemotherapy. CONCLUSIONS: Circulating levels of immune-related proteins like FASLG and Gal-1 might be used to predict the efficacy of checkpoint inhibitors in patients with metastatic PDAC.

Waste LCA and the future.

Life cycle assessment (LCA) models quantifying the environmental aspects of waste management have become an integral part of waste management decision-making over the last two decades and have provided ample knowledge on both environmental benefits and drawbacks in the way we handle waste. Waste management and LCA modelling of waste management systems will soon be challenged by profound changes necessary in our societies and sectors to meet sustainable development goals. Foreseen changes in energy, material, and nutrient provision will directly and indirectly affect waste management in terms of its operation and goals. This study reflects on anticipated changes in society and industrial sectors and how these changes may affect waste management and LCA modelling of waste management systems in terms of waste input, the modelling of technologies and systems and exchanges of energy, materials, and nutrients, as well as how it may affect impact assessment and the interpretation of results. The study provides practical recommendations for LCA modelling of future waste management systems, which will hopefully lead to robust assessments that can support decision-making in an evolving society subject to great changes.

Dairy cattle welfare - the relative effect of legislation, industry standards and labelled niche production in five European countries.

The only common European Union (EU) legislation set up specifically to ensure the welfare of dairy cattle is for calves. As a consequence, there is wide diversity in how dairy cattle welfare is ensured in EU countries. A few countries have legal requirements for dairy cattle welfare, while in others, it is left to industry standards or niche production requirements, typically linked to various premium labels. In this paper, we compared animal welfare provisions in dairy cattle production across five countries with different combinations of legislative and other approaches: Denmark, Germany, the Netherlands, Sweden, and the United Kingdom. Firstly, we aimed to map the diversity of animal welfare initiatives. Secondly, we used the Benchmark method of expert valuations and weightings of the relative importance of individual welfare provisions. We found that Denmark and Sweden have the highest level of dairy cattle welfare provisions as measured by the Benchmark method, partly due to high legislative welfare requirements, followed by the United Kingdom, which has an extensive industry standard with very high uptake. Germany and the Netherlands, on the other hand, have lower levels of documented welfare provisions, and correspondingly a Benchmark score closer to a baseline defined by legal requirements at EU level. We also found differences in what elements of animal welfare were focussed on. Some initiatives emphasised fulfilling the social needs of cattle, while others focused more on space and freedom to move. Also, the countries with the highest Benchmark score had a relatively high level of production of organic and other specialty dairy products. We found the effect of national legislation or ambitious industry standards on dairy cattle welfare to be much larger than previous studies have found in either pigs or poultry. At a time when the EU is considering stepping up its efforts to improve animal welfare in terms of common minimum standards, the results of this study could have important policy implications. The diversity in the level of dairy cattle welfare standards found across countries may speak in favour of having shared minimum standards, both at EU level and globally. However, even among countries with a similar Benchmark score, we found a difference in the kinds of welfare provisions at work, which may make full harmonisation of standards more challenging.

Temporal Changes in Photoreducible Mercury, Photoreduction Rates, and the Role of Dissolved Organic Matter in Freshwater Lakes.

Total photoreducible mercury [Hg(II)RED] and photoreduction rates in the surface waters of four lakes in Kejimkujik National Park, Nova Scotia were measured monthly over a summer. The percent of THg that was photoreducible [%Hg(II)RED] decreased significantly in two of the four lakes from early to late summer: North Cranberry (maximum 42% to minimum 14%) and Big Dam East (maximum 51% to minimum 6%). Hg(II)RED was found to have a linear relationship with THg for all combined site data. THg and Hg(II)RED were found to have positive linear relationships with DOC concentrations (R2 = 0.97; n = 36; p < 0.01 and R2 = 0.75; n = 36; p < 0.01, respectively). A smaller proportion of THg was found to be photoreducible with increasing DOC concentration.

Effect of increasing dose level of a novel consensus bacterial 6-phytase variant on phytate degradation in broilers fed diets containing varied phytate levels.

1. The effect of increasing the dose level of a novel consensus bacterial 6-phytase variant on apparent ileal digestibility (AID) of phosphorus (P), phytic acid (inositol hexa-phosphate, IP6) and ileal IP6 degradation profile was studied in diets containing varying phytate-P (PP) levels.2. Ross 308, one-day-old males (n = 1,800) were allocated to cages (20 birds/cage, six cages/treatment) in a completely randomised design employing a 3 × 5 factorial arrangement (three PP levels: 2.45 (low) 2.95 (medium) and 3.45 g/kg (high); five dose levels of phytase (PhyG): 0, 500, 1,000, 2,000 and 4,000 FTU/kg). Phased diets were based on wheat, corn, soybean meal, rapeseed meal and rice bran (d 0 to 10; 2.60 g/kg digestible P, 7.6 g/kg calcium (Ca); d 11 to 21; 2.10 g/kg digestible P, 6.4 g/kg Ca). Ileal digesta was collected on d 21 for determination of P, IP6 and IP-esters content. Data were analysed by factorial ANOVA; means separation was achieved using Tukey's HSD test.3. Increasing PP reduced AID of IP6 and sum of IP3-6 (%) (P < 0.05) but absolute P-release (g/kg diet) above NC was increased (P < 0.05) at high vs. low PP. Increasing phytase dose exponentially increased (P < 0.001) AID IP6, sum of IP3-6 (%) and digestible IP3-6-P g/kg diet (P < 0.001). AID P was increased but there was an interaction with PP level (P < 0.001). Ileal accumulation of IP5-3-P was universally low with PhyG at ≥1,000 FTU/kg (<0.06 g/100 g DM). At 2,000 and 4,000 FTU/kg, AID IP6 was 97.2, 92.7, 92.6% and 100, 97.2, 97.1%, respectively, at low, medium and high PP. At 2,000 FTU/kg, phytate-P release estimated as the increase (above NC) in ileal digestible sum of IP3-6-P in the diet was 2.26, 2.59 and 3.10 g/kg in low, medium and high PP, respectively.4. The data demonstrated that the novel phytase was effective in breaking down phytate to low IP-esters in diets with varied PP content but the optimal dose level for maximising P-release may differ in diets with varying PP content.

Application of LCA modelling in integrated waste management.

Life cycle assessment (LCA) has been used in waste management for the last two decades and hundreds of journal papers have been published. The use of LCA in waste management has provided a much-improved holistic view of waste management including waste flows and potential environmental impacts. Although much knowledge has been obtained from LCA studies, there is still a need to use LCA models in integrated waste management. This paper describes six areas where LCA is expected to play a role in waste management in the future: 1) understanding an existing waste management system; 2) improving existing waste management systems; 3) comparing alternative technologies/ technology performance; 4) technology development/prospective technologies; 5) policy development/strategic development; and 6) reporting. Illustrative examples are provided for each application area.

Incidence of neuromyelitis optica spectrum disorder in the Central Denmark Region.

OBJECTIVES: Neuromyelitis optica (NMO)/NMO spectrum disorder (NMOSD) may be misdiagnosed as multiple sclerosis. The aim of this study was to (i) to measure AQP4-IgG in patients who fulfilled the clinical and radiological criteria of NMOSD in the Central Denmark Region and (ii) to estimate the incidence of NMOSD in the region, according to both the 2006 Wingerchuk criteria and the 2015 International Panel for NMO Diagnosis criteria. MATERIALS AND METHODS: Medical records of all patients diagnosed with a demyelinating disorder in the region from 1 January 2012 to 31 December 2013 were reviewed. Patients were classified as having (i) "NMO" if the 2006 criteria were met, (ii) "NMOSD with AQP4-IgG" or (iii) "NMOSD without/unknown AQP-IgG" if the new 2015 NMOSD criteria were met. Patients with core symptoms were invited to provide a blood sample for AQP4-IgG analysis with an enzyme-linked immunosorbent assay and a cell-based indirect immunofluorescence assay. RESULTS: In 191 patients with core symptoms, one met the 2015 NMOSD with AQP4-IgG criteria. Two patients met the 2006 NMO and 2015 NMOSD without/unknown AQP4-IgG criteria. Among 108 patients providing a blood sample, all were seronegative. The estimated incidence of NMO (2006 criteria) and NMOSD (2015 criteria) was 0.08 and 0.12 per 100 000 person-years, respectively. CONCLUSION: NMO/NMOSD is a rare disease in the Central Denmark Region, with a considerably lower incidence rate than previously estimated in a neighbouring region.

Accuracy of food photographs for quantifying food servings in a lunch meal setting among Danish children and adults.

BACKGROUND: Visual aids, such as food photographs, are widely used in estimating food quantities in dietary surveys. The present study aimed to assess how accurately Danish adults and children can estimate food portion sizes using 37 series of photographs illustrating four to six different portion sizes under real-life conditions; determine whether adults were more accurate than children; and estimate the error caused by using portion size photographs to estimate weights of foods consumed in macronutrient calculation. METHODS: Six hundred and twenty-two adults and 109 children were recruited in three workplace canteens and in two schools, respectively, to estimate their lunchtime portions based on photographs. Participants were instructed to keep the foods separated on their plate when taking lunch. Participants thereafter estimated their own portions by looking at the relevant series of photographs. The actual food portions were then weighed. RESULTS: The proportion of correct estimations was 42% overall (range 19-77%). The mean difference (%) between estimated and actual weight was 17% (range 1-111%). Small portion size photographs were more often used correctly compared to larger portion photographs. Children had as many correct estimations as adults, although they overestimated portions more. Participants using fractions of (or more than) one photograph to estimate the portion of a food had significantly larger errors. When calculating the macronutrient content of a weekly menu using the estimated portion sizes, protein had the largest error (29%). CONCLUSIONS: When used in a real-life situation, the portion size photographs validated in the present study showed a certain inaccuracy compared to the actual weights.

Human endogenous retroviruses in the aetiology of MS.

Several lines of investigation have provided strong indications for an association between the immune-mediated, neurologic disease multiple sclerosis (MS) and human endogenous retroviruses (HERVs). Whether the relationship is causal is yet to be established. Endogenous retroviruses are pathogenic-in other species than the human. Several aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been documented, both for cells in the periphery and in the central nervous system. Specific HERV-encoded genes and certain gene products (envelope proteins, Envs) appear strongly associated with the disease and have pathogenic potential. Most HERV sequences are non-functional, whereas some HERV loci have coding potential but remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, de-repression, and also involvement of retroviral restriction factors, is emerging. Disease intervention by means of antiretrovirals has potential as a novel therapeutic strategy in MS treatment; this is compounded by the apparently reduced risk of MS in HIV infection as a consequence of therapy. Extensive studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are needed.

PO-20 - Crosstalk between the lectin pathway and haemostasis in patients with pulmonary cancer.

INTRODUCTION: Recent research has focused on the complement system in cancer, including the lectin pathway of complement activation. Mannose-binding lectin (MBL), a key activator of the lectin pathway, can bind to tumor cell surfaces in vitro, and lectin pathway activation is increased in several types of cancer. The exact role of the complement system in cancer is currently discussed. However, one possible consequence of the increased complement activation could be contribution to the increased thrombosis risk which cancer patients experience. Proteins of the lectin pathway can activate coagulation and impair fibrinolysis in vitro, but the significance of this in a clinical setting is not well understood. AIM: We aim to investigate associations between lectin pathway and haemostatic activation in patients with lung cancer undergoing thoracoscopic surgery. MATERIALS AND METHODS: Patients with lung cancer (n=60) eligible for thoracoscopic tumor resection were included as part of a randomized controlled trial, the COPPVATS project (EudraCT no: 2012-002409-23), conducted at the Department of Thoracic Surgery, Aarhus University Hospital. Exclusion criteria were arterial or venous thrombosis within the last three months, other systemic disease than cancer, and anticoagulant treatment prior to inclusion. Blood samples were obtained the day before surgery, perioperatively, and on the 1st and 2nd postoperative days. Laboratory analyses on the complement system include MBL, MBL-associated protease (MASP)-1 and -2, MBL-MASP complex, ficolin-1, -2, and -3 and complement factor C3b. Haemostasis was evaluated with routine coagulation parameters (INR, APTT, fibrinogen, fibrin d-dimer), platelet function, and tissue factor-induced thrombin generation. RESULTS: Recruitment of the study subjects is concluded, and laboratory work is in progress. The complement analyses and data processing will be performed during early spring 2016, so that results will be ready for presentation on the conference. CONCLUSIONS: The present project will provide new knowledge on lectin pathway activation and the pathogenesis of thrombosis in cancer patients. In the long term, this will help improve the individual risk assessment and lead to new studies on thromboprophylaxis and treatment in conditions with increased complement activation.

Changes in the utilization of psychiatric hospital facilities in Denmark by patients diagnosed with schizophrenia from 1970 through 2012: The advent of 'revolving door' patients.

OBJECTIVE: The Danish psychiatric system has gone through several structural changes in the last four decades. The deinstitutionalization of the mental healthcare system was implemented in Denmark in the late 1970s with the intention of increasing out-patient treatment. One of the aims in the reorganization was to treat the patient in the local environment rather than during long-term hospitalization. This study focuses on the changes in the utilization of hospital facilities. METHOD: Using register data from secondary healthcare treatment of patients diagnosed with schizophrenia in Denmark 1970-2012, we analysed the development in the use of hospital facilities. RESULTS: Our major finding was a 220% increase between 1970 and 2012 in the total number of hospital admissions due to schizophrenia each year, while at the same time the number of annual schizophrenia bed days was reduced by 76%. Furthermore, the readmission rate within a year after discharge with a diagnosis of schizophrenia reached 70% in 2012 compared to 51% in 1970. Finally, the total bed occupancy continued to rise over the four decades and has exceeded 100% in several years since 1999. CONCLUSION: The findings indicate that the reorganization of the Danish mental healthcare system has created a problem of 'revolving door' schizophrenia patients' who since the 1970s have been increasingly hospitalized but for shorter periods. Possible explanations of the findings are premature discharge of patients with schizophrenia due to lack of beds or/and that community psychiatry has not been providing adequate relapse prevention.

Inflammatory myofibroblastic tumours of the respiratory system and the impact of the varying patterns.

Inflammatory fibroblastic tumours are very rare. They are mostly located in the respiratory system. We present three cases of patients with fibroblastic tumours. The diversity of inflammatory fibroblastic tumours in the respiratory system and the surgical considerations are discussed. Our recommendation is that treatment should include a complete resection to prevent local recurrence and malignant transformation, and follow-up review should reflect the procedure carried out, especially in terms of the anatomical location and the extent of the surgical procedure performed.

Early warning score predicts acute mortality in stroke patients.

OBJECTIVES: Clinical deterioration and death among patients with acute stroke are often preceded by detrimental changes in physiological parameters. Systematic and effective tools to identify patients at risk of deterioration early enough to intervene are therefore needed. The aim of the study was to investigate whether the aggregate weighted track and trigger system early warning score (EWS) can be used as a simple observational tool to identify patients at risk and predict mortality in a population of patients with acute stroke. MATERIALS AND METHODS: Patients admitted with acute stroke at the Copenhagen University Hospital, Nordsjaellands Hospital, Denmark, from May to September 2012 were enrolled in a retrospective cohort study (n = 274). Vital signs were measured immediately after admission and consistently during the hospitalization period. Based on the vital signs, a single composite EWS was calculated. Death within 30 days was used as outcome. Area under the receiver operating characteristics curve (AUROC) and a Kaplan-Meier curve were computed to examine the prognostic validity of EWS. RESULTS: A total of 24 patients (8.8%) died within 30 days. The prognostic performance was high for both the EWS at admission (AUROC 0.856; 95% CI 0.760-0.951; P-value < 0.001) and the maximal EWS measured (AUROC 0.949; 95% CI 0.919-0.980; P-value < 0.001). Mortality rates were lowest for admission EWS 0-1 (2%) and highest for admission EWS ≥ 5 (63%). CONCLUSIONS: Early warning score is a simple and valid tool for identifying patients at risk of dying after acute stroke. Readily available physiological parameters are converted to a single score, which can guide both nurses and physicians in clinical decision making and resource allocation.

Dietary exposure to volatile and non-volatile N-nitrosamines from processed meat products in Denmark.

Recent epidemiological studies show a positive association between cancer incidence and high intake of processed meat. N-nitrosamines (NAs) in these products have been suggested as one potential causative factor. Most volatile NAs (VNAs) are classified as probable human carcinogens, whereas the carcinogenicity for the majority of the non-volatile NA (NVNA) remains to be elucidated. Danish adults (15-75 years) and children (4-6 years) consume 20 g and 16 g of processed meat per day (95th percentile), respectively. The consumption is primarily accounted for by sausages, salami, pork flank (spiced and boiled) and ham. This consumption results in an exposure to NVNA of 33 and 90 ng kg bw(-1) day(-1) for adults and children, respectively. The exposure to VNA is significantly lower amounting to 0.34 and 1.1 ng kg bw(-1) day(-1) for adults and children, respectively. Based on a BMDL10 of 29 µg kg bw(-1) day(-1) a MOE value ≥17,000 was derived for the exposure to NA known to be carcinogenic (VNA including NSAR), indicating an exposure of low concern. The exposure to the NVNA is substantially higher and if found to be of toxicological significance the exposure may be of concern.

Second-generation antipsychotic effect on cognition in patients with schizophrenia--a meta-analysis of randomized clinical trials.

OBJECTIVE: To investigate the effect of second-generation antipsychotics on cognitive function in patients diagnosed with schizophrenia or schizoaffective disorder. METHOD: Multiple-treatments meta-analysis model. RESULTS: On cognitive composite score, sertindole was superior to clozapine, effect size (ES) 0.87; 95% CI: 0.12-1.63, quetiapine, ES 0.75; 95% CI: 0.00-1.49, and first-generation antipsychotics (FGAs), ES 0.89; 95% CI: 0.14-1.64. Analyses on each cognitive domain showed clozapine, ES 0.37; 95% CI: 0.00-0.74, olanzapine, ES 0.31; 95%CI: 0.02-0.59, quetiapine, ES 0.34; 95% CI: 0.03-0.64, and FGAs, ES 0.51; 95% CI: 0.18-0.83 performing poorer on verbal working memory than ziprasidone, as well as FGAs performing poorer than risperidone, ES 0.31; 95% CI: 0.04-0.58. On executive function, sertindole performed better than clozapine, ES 0.82; 95% CI: 0.06-1.58, olanzapine, ES 0.81; 95% CI: 0.07-1.55, quetiapine, ES 0.76; 95% CI: 0.02-1.51, ziprasidone, ES 0.90; 95% CI: 0.14-1.67, and FGAs, ES 0.83; 95% CI: 0.08-1.58. On processing speed, FGAs performed poorer than sertindole, ES 0.97; 95% CI: 0.02-1.91, and quetiapine, ES 0.36; 95% CI: 0.01-0.72. On long-term verbal working memory, clozapine performed poorer than olanzapine, ES 0.41; 95% CI: 0.06-0.76. On verbal fluency, FGAs performed poorer than olanzapine, ES 0.26; 95% CI: 0.01-0.50, and clozapine, ES 0.44; 95% CI: 0.06-0.81. Lastly, FGAs, ES 0.41; 95% CI: 0.04-0.78, and clozapine, ES 0.44; 95% CI: 0.05-0.83, performed poorer on visuospatial skill compared to olanzapine. CONCLUSION: The meta-analysis was able to detect some trends in the data analyzed, but did not show any drug having a uniform positive cognitive profile.

Cost-effectiveness of insulin degludec compared with insulin glargine in a basal-bolus regimen in patients with type 1 diabetes mellitus in the UK.

OBJECTIVE: The aim of this study was to evaluate the cost-effectiveness of insulin degludec (IDeg) vs insulin glargine (IGlar) as part of a basal-bolus treatment regimen in adults with T1DM, using a short-term economic model. METHODS: Data from two phase III clinical studies were used to populate a simple and transparent short-term model. The costs and effects of treatment with IDeg vs IGlar were calculated over a 12-month period. The analysis was conducted from the perspective of the UK National Health Service. Sensitivity analyses were conducted to assess the degree of uncertainty surrounding the results. The main outcome measure, the incremental cost-effectiveness ratio (ICER), was the cost per quality-adjusted life-year (QALY). RESULTS: IDeg is a cost-effective treatment option vs IGlar in patients with T1DM on a basal-bolus regimen. The base case ICER was estimated at £16,895/QALY, which is below commonly accepted thresholds for cost-effectiveness in the UK. Sensitivity analyses demonstrated that the ICER was stable to variations in the majority of input parameters. The parameters that exerted the most influence on the ICER were hypoglycemia event rates, daily insulin dose, and disutility associated with non-severe nocturnal hypoglycemic events. However, even under extreme assumptions in the majority of analyses the ICERs remained below the commonly accepted threshold of £20,000-£30,000 per QALY gained. CONCLUSIONS: This short-term modeling approach accommodates the treat-to-target trial design required by regulatory bodies, and focuses on the impact of important aspects of insulin therapy such as hypoglycemia and dosing. For patients with T1DM who are treated with a basal-bolus insulin regimen, IDeg is a cost-effective treatment option compared with IGlar. IDeg may be particularly cost-effective for sub-groups of patients, such as those suffering from recurrent nocturnal hypoglycemia and those with impaired awareness of hypoglycemia.

A comprehensive substance flow analysis of a municipal wastewater and sludge treatment plant.

The fate of total organic carbon, 32 elements (Al, Ag, As, Ba, Be, Br, Ca, Cd, Cl, Co, Cr, Cu, Fe, Hg, K, Li, Mg, Mn, Mo, N, Na, Ni, P, Pb, S, Sb, Se, Sn, Sr, Ti, V, and Zn) and 4 groups of organic pollutants (linear alkylbenzene sulfonates, bis(2-ethylhexyl)phthalate, polychlorinated biphenyl and polycyclic aromatic hydrocarbons) in a conventional wastewater treatment plant were assessed. Mass balances showed reasonable closures for most of the elements. However, gaseous emissions were accompanied by large uncertainties and show the limitation of mass balance based substance flow analysis. Based on the assessment, it is evident that both inorganic and organic elements accumulated in the sewage sludge, with the exception of elements that are highly soluble or degradable by wastewater and sludge treatment processes. The majority of metals and metalloids were further accumulated in the incineration ash, while the organic pollutants were effectively destroyed by both biological and thermal processes. Side streams from the sludge treatment process (dewatering and incineration) back to the wastewater treatment represented less than 1% of the total volume entering the wastewater treatment processes, but represented significant substance flows. In contrast, the contribution by spent water from the flue gas treatment process was almost negligible. Screening of human and eco-toxicity by applying the consensus-based environmental impact assessment method USEtox addressing 15 inorganic constituents showed that removal of inorganic constituents by the wastewater treatment plant reduced the toxic impact potential by 87-92%.

Prevalence of acute cardiac disorders in patients with suspected ST-segment elevation myocardial infarction and non-significant coronary artery disease.

BACKGROUND AND PURPOSE: We aimed to study the prevalence of acute cardiac disorders in patients with suspected ST-segment elevation myocardial infarction (STEMI) and non-significant coronary artery disease (CAD). METHODS: From January to October 2012 we consecutively included patients admitted with suspected STEMI and non-significant CAD (coronary artery stenosis diameter <50%). Patients were diagnosed with acute cardiac disorder in the presence of elevated cardiac biomarkers (troponin T >50ng/l or creatine kinase MB >4µg/l) or dynamic ECG changes (ST-segment changes or T-wave inversion). RESULTS: Of the 871 patients admitted with suspected STEMI, 11% (n=95) had non-significant CAD. Of these, 67% (n=64) had elevated cardiac biomarkers or dynamic ECG changes and were accordingly diagnosed with acute cardiac disorders. In the remaining 33% (n=31) of patients, cardiac biomarkers were normal and ECG changes remained stationary. CONCLUSIONS: Acute cardiac disorders were diagnosed in two thirds of patients with suspected STEMI and non-significant CAD.

Cognitive remediation combined with an early intervention service in first episode psychosis.

OBJECTIVE: This randomised clinical trial assessed the effects of a 16-week cognitive remediation programme (NEUROCOM) combined with an early intervention service (EIS) vs. EIS alone. METHOD: One hundred and seventeen patients with first episode psychosis were randomly assigned to 4 months cognitive remediation combined with EIS vs. EIS alone. Statistical analysis of effect was based on intention to treat. RESULTS: A total of 98 patients (83.8%) participated in post-training assessments at 4 months and 92 (78.6%) in 12-month follow-up assessments. No effects were found on the primary outcome measure functional capacity. At the post-training assessment, the intervention group had improved significantly on Rosenberg Self-Esteem Scale (Cohen's d=0.54, P=0.01), Positive and Negative Symptoms Scale (PANSS), General Psychopathology Scale (Cohen's d=0.51, P=0.05) and the verbal learning domain (Cohen's d=0.46, P=0.02). At follow-up assessment, the intervention group retained the significant improvements on the verbal learning domain (Cohen's d=0.58, P<0.05). Furthermore, significant improvements were observed on the working memory domain (Cohen's d=0.56, P=0.01) and PANSS positive symptoms (Cohen's d=0.44, P=0.04), while improvement on the composite score was marginally significant (Cohen's d=0.34, P=0.05). CONCLUSION: In accordance with other cognitive remediation programmes, this programme demonstrates some immediate and long-term effect on cognitive functioning, symptoms and self-esteem.