Non-technical skills of Norwegian medical students at different training sites: a comparative, observational cohort study.

PURPOSE: Mastering non-technical skills (NTS) is a fundamental part of the training of new physicians to perform effectively and safely in the medical practice environment. Ideally, they learn these skills during medical school. Decentralized medical education is being implemented increasingly worldwide. Two of the three training sites studied, Bodø (a regional hospital) and Finnmark (a rural local hospital), implemented decentralized medical education. The third training site was the main campus in Tromsø, located at an urban university hospital. The training in Finnmark emphasised training in non-technical skills using simulation to a larger extent than the two other university campuses. This study aimed to compare the NTS performance of medical students in their last year of education at three different training sites of the same university. METHODS: This blinded cohort study included students from the three training sites who participated in identical multi-professional simulations over a six-year period. Eight raters evaluated the video recordings of eight students from each training site using the Norwegian Medical Students Non-Technical Skills (NorMS-NTS) tool. The NorMS-NTS tool, which comprises four categories and 13 elements, assesses the NTS of Norwegian medical students and assigns an overall global score. Pairwise significant differences in the NTS performance levels between the training sites studied were assessed using Tukey's test. RESULTS: The overall NTS performance levels of the medical students from Finnmark (mean 4.5) were significantly higher than those of the students from Tromsø (mean 3.8) and Bodø (mean 3.5). Similarly, the NTS performance levels at category-level of the students in Finnmark were significantly higher than those of the students from Bodø and Tromsø. Except for one category, no significant differences were observed between the students from Bodø and Tromsø in terms of the overall or category-level NTS performance. CONCLUSION: The NTS performance levels of the medical students from Finnmark, which implements rural, decentralized medical education, were significantly higher than those of the students from Tromsø and Bodø.

Collecting evidence of validity for an assessment tool for Norwegian medical students' non-technical skills (NorMS-NTS): usability and reliability when used by novice raters.

BACKGROUND: The NorMS-NTS tool is an assessment tool for assessing Norwegian medical students' non-technical skills (NTS). The NorMS-NTS was designed to provide student feedback, training evaluations, and skill-level comparisons among students at different study sites. Rather than requiring extensive rater training, the tool should capably suit the needs of busy doctors as near-peer educators. The aim of this study was to examine the usability and preliminary assess validity of the NorMS-NTS tool when used by novice raters. METHODS: This study focused on the usability of the assessment tool and its internal structure. Three raters used the NorMS-NTS tool to individually rate the team leader, a medical student, in 20 video-recorded multi-professional simulation-based team trainings. Based on these ratings, we examined the tools' internal structure by calculating the intraclass correlation coefficient (ICC) (version 3.1) interrater reliability, internal consistency, and observability. After the rating process was completed, the raters answered a questionnaire about the tool's usability. RESULTS: The ICC agreement and the sum of the overall global scores for all raters were fair: ICC (3,1) = 0.53. The correlation coefficients for the pooled raters were in the range of 0.77-0.91. Cronbach's alpha for elements, categories and global score were mostly above 0.90. The observability was high (95%-100%). All the raters found the tool easy to use, none of the elements were redundant, and the written instructions were helpful. The raters also found the tool easier to use once they had acclimated to it. All the raters stated that they could use the tool for both training and teaching. CONCLUSIONS: The observed ICC agreement was 0.08 below the suggested ICC level for formative assessment (above 0.60). However, we know that the suggestion is based on the average ICC, which is always higher than a single-measure ICC. There are currently no suggested levels for single-measure ICC, but other validated NTS tools have single-measure ICC in the same range. We consider NorMS-NTS as a usable tool for formative assessment of Norwegian medical students' non-technical skills during multi-professional team training by raters who are new to the tool. It is necessary to further examine validity and the consequences of the tool to fully validate it for formative assessments.

Effect on bone anabolic markers of daily cheese intake with and without vitamin K2: a randomised clinical trial.

Background: Daily intake of 57 g Jarlsberg cheese has been shown to increase the total serum osteocalcin (tOC). Is this a general cheese effect or specific for Jarlsberg containing vitamin K2 and 1,4-dihydroxy-2naphtoic acid (DHNA)? Methods: 66 healthy female volunteers (HV) were recruited. By skewed randomisation (3:2), 41 HV were allocated to daily intake of 57 g Jarlsberg (J-group) and 25-50 g Camembert (C-group) in 6 weeks. After 6 weeks the C-group was switched to Jarlsberg. The study duration was 12 weeks with clinical investigations every 6 weeks. The main variables were procollagen type 1 N-terminal propeptide (PINP), tOC, carboxylated osteocalcin (cOC) and the osteocalcin ratio (RO) defined as the ratio between cOC and undercarboxylated osteocalcin (ucOC). Serum cross-linked C-telopeptide type I collagen (CTX), vitamin K2, lipids and clinical chemistry were used as secondary variables. Results: PINP, tOC, cOC, RO and vitamin K2 increased significantly (p<0.01) after 6 weeks in the J-group. PINP remained unchanged in the C-group. The other variables decreased slightly in the C-group but increased significantly (p≤0.05) after switching to Jarlsberg. No CTX-changes detected in neither of the groups.Serum lipids increased slightly in both groups. Switching to Jarlsberg, total cholesterol and low-density lipoprotein-cholesterol were significantly reduced (p≤0.05). Glycated haemoglobin (HbA1c), Ca++ and Mg++ were significantly reduced in the J-group, but unchanged in the C-group. Switching to Jarlsberg, HbA1c and Ca++ decreased significantly. Conclusion: The effect of daily Jarlsberg intake on increased s-osteocalcin level is not a general cheese effect. Jarlsberg contain vitamin K2 and DHNA which increases PINP, tOC, cOC and RO and decreases Ca++, Mg++ and HbA1c. These effects reflect increased bone anabolism and a possible reduced risk of adverse metabolic outcomes. Trial registration number: NCT04189796.

Positive effects on hematological and biochemical imbalances in patients with metastatic breast cancer stage IV, of BP-C1, a new anticancer substance.

UNLABELLED: A benzene-poly-carboxylic acid complex with cis-diammineplatinum(II) dihydrocholride, BP-C1 is currently used in clinical trials in treating metastatic breast cancer. BP-C1 controls tumor growth with a few mild side-effects, improving quality of life. METHODS: The data consisted of prospectively collected laboratory results from 47 patients in two controlled clinical trials of daily intramuscular injections of BP-C1 for 32 days. Study I was performed as an open, nonrandomized, Phase I dose-response, multicenter study with a three-level, between-patient, response surface pathway design. The second study was a randomized, double-blind, and placebo-controlled, multicenter study with a stratified semi-crossover design. RESULTS: Hemoglobin (Hb) and hematocrit (Hct) increased significantly (P<0.01) during BP-C1 treatment, while red blood cell (RBC) count increased but not significantly. The most pronounced increase in Hb, RBC, Hct, and white blood cell (WBC) was in anemic patients (P≤0.01). WBC count and neutrophils increased significantly (P=0.01) in the overall data. WBCs and neutrophils (P<0.01), eosinophils (P=0.05) and monocytes (P<0.01) increased significantly and markedly in patients with lowest baseline levels. Additionally, low levels of thrombocytes significantly increased. No changes in liver parameters, amylase, glucose, creatinine, or albumin, were detected except for albumin in the subgroup with low baseline levels, where levels increased significantly (P=0.04). An increase in K(+), Ca(2+), and PO4 (3-) was most pronounced in patients with low baseline levels (P≤0.02). A similar pattern detected for Mg(2+), prothrombin time (PT), coagulation factors II, VII, X (KFNT), and C-reactive protein (CRP), which increased significantly (P≤0.05) in the groups with the lowest values. CONCLUSION: Our findings support the safety profile of BP-C1 use in cancer patients. BP-C1 did not induce anemia, infection, bleeding, hepatic insufficiency or electrolyte imbalances. In contrast, BP-C1 corrected abnormalities. No hematological and biochemical toxicity was observed.

Two-year outcomes in thoracic transplant recipients after conversion to everolimus with reduced calcineurin inhibitor within a multicenter, open-label, randomized trial.

BACKGROUND: Use of the mammalian target of rapamycin inhibitor everolimus with an accompanying reduction in calcineurin inhibitor (CNI) exposure has shown promise in preserving renal function in maintenance thoracic transplant patients, but robust, long-term data are required. METHODS: In a prospective, open-label, multicenter study, thoracic transplant recipients more than or equal to 1 year posttransplant with mild-to-moderate renal insufficiency were randomized to continue their current CNI-based immunosuppression or convert to everolimus with predefined CNI exposure reduction. After a 12-month core trial, patients were followed up to month 24 after randomization. RESULTS: Of 245 patients who completed the month 12 visit, 235 patients (108 everolimus and 127 controls) entered the 12-month extension phase. At month 24, mean measured glomerular filtration rate had increased by 3.2±12.3 mL/min from the point of randomization in everolimus-treated patients and decreased by 2.4±9.0 mL/min in controls (P<0.001), a difference that was significant within both the heart and lung transplant subpopulations. During months 12 to 24, 5.6% of everolimus patients and 3.1% of controls experienced biopsy-proven acute rejection (P=0.76). There were no significant differences in the rate of adverse events or serious adverse events (including pneumonia) between groups during months 12 to 24. CONCLUSIONS: Converting maintenance thoracic transplant recipients to everolimus with low-exposure CNI results in a renal benefit that is sustained to 2 years postconversion, with significantly improved measured glomerular filtration rate in both heart and lung transplant patients. Despite reductions of more than 50% in CNI exposure, there was no marked loss of efficacy. The safety profile of the everolimus-based regimen was acceptable.

Effect of loss of regional fat assessed by DXA on insulin resistance and dyslipidaemia in obese men.

OBJECTIVE: To investigate the impact of reduction in total fat mass (FM) and regional FMs on indices of insulin resistance and dyslipidaemia in obese men (BMI > 30 kg/m²) after a 1-year weight loss (WL), and secondly, to examine the potential predictive effect of baseline insulin resistance on reduction in total and regional FMs. MATERIAL AND METHODS: In nine men with WL > 4 kg, body composition by DXA (dual X-ray absorptiometry) and indices of insulin resistance were assessed: fasting insulin, C-Peptide and HOMA-IR. Insulin sensitivity (QUICKI) and serum lipids were also assessed. RESULTS: Mean WL was 10.8%; Δ trunk and Δ leg FM were reduced by 30.1% and 21.3%, respectively, increasing leg/trunk FM ratio by 13.2%. Improvement in HOMA-IR was 63.1%, insulin 59.1%, and in QUICKI 17.4%. Loss of total FM, trunk FM, and increase in leg/trunk FM ratio were correlated with improvement in HOMA-IR (p < 0.001-0.05). Linear regression analysis of ln-transformed improvements in HOMA-IR was non-significantly related with losses of trunk FM and increases in leg/trunk FM ratio (p = 0.06). Multivariate analysis suggested improvements in fasting insulin and C-Peptide could be explained by leg/trunk FM ratio (R² = 0.60, p = 0.013, R² = 0.37, p = 0.012, respectively) and in HOMA-IR by trunk FM (R² = 0.42, p = 0.06). The loss of FM and change in FM distribution had no effect on serum lipids. CONCLUSION: Both loss of trunk FM and increase in leg/trunk FM ratio assessed by DXA contribute to the improvement in insulin resistance.

Effect of regional fat loss assessed by DXA on insulin resistance and dyslipidaemia in obese women.

OBJECTIVE: To investigate the impact of reduction in total fat mass (FM) and regional FMs on indices of insulin resistance and dyslipidaemia in obese women (BMI > 30 kg/m(2)) after a 1-year weight loss (WL) program; and, secondly, to investigate the potential predictive effect of baseline insulin resistance on reduction in total and regional FMs. MATERIAL AND METHODS: In 35 women with > 4 kg weight loss, body composition by DXA (dual X-ray absorptiometry), fasting insulin, C-Peptide, insulin resistance (HOMA-IR), insulin sensitivity (QUICKI), metabolic clearance rate (MCRestOGTT) and serum lipids were assessed. RESULTS: Mean WL was 9.6%; trunk and leg FM were reduced proportionally (14.9-14.7%). Improvement in HOMA-IR was 34.7%, insulin 30.7%, QUICKI 8.6% and MCRest OGTT 74%. The reduction in total, trunk and leg FM were similarly correlated with improvement in indices of insulin resistance (p < 0.001-0.05) and also with initial HOMA-IR (p = 0.000-0.02). In linear regressions improvement in HOMA-IR was similarly related with these FMs (p = 0.008), and initial HOMA predicted loss of trunk FM (p = 0.01). In multivariate analysis improvement in HOMA-IR was explained by loss of total FM (R(2) = 0.20, p = 0.004); improvement of QUICKI by loss of leg FM (R(2) = 0.33, p < 0.001). CONCLUSION: Loss of leg FM and trunk FM had similar importance for the improvement in insulin resistance. Baseline HOMA-IR predicted the potential for reduction in trunk FM.

Everolimus with reduced calcineurin inhibitor in thoracic transplant recipients with renal dysfunction: a multicenter, randomized trial.

BACKGROUND: The proliferation signal inhibitor everolimus offers the potential to reduce calcineurin inhibitor (CNI) exposure and alleviate CNI-related nephrotoxicity. Randomized trials in maintenance thoracic transplant patients are lacking. METHODS: In a 12-month, open-labeled, multicenter study, maintenance thoracic transplant patients (glomerular filtration rate > or =20 mL/min/1.73m and <90 mL/min/1.73 m) >1 year posttransplant were randomized to continue their current CNI-based immunosuppression or start everolimus with predefined CNI exposure reduction. RESULTS: Two hundred eighty-two patients were randomized (140 everolimus, 142 controls; 190 heart, 92 lung transplants). From baseline to month 12, mean cyclosporine and tacrolimus trough levels in the everolimus cohort decreased by 57% and 56%, respectively. The primary endpoint, mean change in measured glomerular filtration rate from baseline to month 12, was 4.6 mL/min with everolimus and -0.5 mL/min in controls (P<0.0001). Everolimus-treated heart and lung transplant patients in the lowest tertile for time posttransplant exhibited mean increases of 7.8 mL/min and 4.9 mL/min, respectively. Biopsy-proven treated acute rejection occurred in six everolimus and four control heart transplant patients (P=0.54). In total, 138 everolimus patients (98.6%) and 127 control patients (89.4%) experienced one or more adverse event (P=0.002). Serious adverse events occurred in 66 everolimus patients (46.8%) and 44 controls (31.0%) (P=0.02). CONCLUSION: Introduction of everolimus with CNI reduction offers a significant improvement in renal function in maintenance heart and lung transplant recipients. The greatest benefit is observed in patients with a shorter time since transplantation.

Cyclosporine C2 levels have impact on incidence of rejection in de novo lung but not heart transplant recipients: the NOCTURNE study.

BACKGROUND: Cyclosporine (CsA) absorption varies early after transplantation and can be accurately assessed by the area under the absorption curve (AUC). The 2-hour post-dose (C2) level of CsA in whole blood is reported to be a useful surrogate marker of CsA AUC in kidney and liver transplant monitoring, but should be further explored in thoracic organ recipients. METHODS: In a 12-month study we included de novo lung (n = 95) and heart (n = 96) recipients. All participants received cyclosporine (Sandimmun Neoral) monitored by C0 and blood was collected for analysis of C2 retrospectively. Abbreviated AUC (AUC(0-4)) was measured at 7 days and 3 months. Primary outcome was C2 relation to the frequency of acute cellular rejection (ACR) needing treatment and possible decline in measured glomerular filtration rate (mGFR). Recipients were divided into lower, middle and upper third C2 groups based on 2-week post-operative values (tertiles T1 to T3). RESULTS: C2 was the most robust substitute for AUC(0-4) in the group of patients studied. For lung, but not heart, recipients there were differences in mean number of ACRs (p = 0.05), incidence of any rejections (p = 0.04), mean number of any rejections (p = 0.001) and time to first rejection (p = 0.03) between T1 and T3. C2 did not predict reduction in mGFR. CONCLUSIONS: C2 is a sensitive predictor for ACR in lung, but not heart, recipients, C2 was not predictive of a decline in mGFR. This study suggests that management of lung recipients by C2 may diminish the number of ACRs.

Insulin resistance and dyslipidaemia in obese premenopausal and postmenopausal women matched for leg/trunk fat mass ratio.

OBJECTIVES: To investigate the influence of age, menopausal stage and selected hormonal factors on insulin resistance and dyslipidaemia in obese (BMI>30 kg/m(2)) pre- and postmenopausal women. MATERIAL AND METHODS: Thirty- eight pre- and postmenopausal women were matched one by one for leg/trunk fat mass (FM) ratio. Body composition and regional FM by dual X- ray absorptiometry (DXA), fasting glucose, insulin and C- peptide, insulin resistance by homeostasis model assessment (HOMA- IR), insulin sensitivity by quantitative insulin sensitivity check index (QUICKI) and metabolic clearance rate (MCRestOGTT), insulin secretion (HOMAsecr), serum lipids, oestradiol, SHBG, testosterone and testosterone index (total testosterone/SHBG), free thyroxine, free triiodothyronine, cortisol and IGF- 1 were assessed. RESULTS: HDL- cholesterol was higher (p=0.025) and total cholesterol/HDL- cholesterol ratio lower (p=0.026) in post- than in premenopausal women. No differences in parameters of insulin resistance or hormonal factors except oestradiol were found. In forward stepwise multiple regression analysis, cholesterol/HDL- cholesterol ratio was negatively predicted by age (R(2)=0.25, p=0.02) and HDL- cholesterol negatively (R(2)=0.16, p=0.013) predicted by belonging to the premenopausal group. MCRestOGTT was unfavourably predicted by IGF- 1 (R(2)=0.28, p=0.005) and testosterone (R(2)=0.36, p=0.048). Because of the relatively small number of subjects studied, interpretation of the results may to some extent have limited general validity. CONCLUSION: FM distribution is the major determinant of insulin resistance and dyslipidaemia, with only minor roles for menopausal status, age as such and age- related changes in hormonal factors in the regulation of glucose and lipid metabolism.

Leg fat mass as measured by dual X-ray absorptiometry (DXA) impacts insulin resistance differently in obese women versus men.

OBJECTIVE: To investigate the association between regional fat mass (FM) and insulin resistance and dyslipidaemia in obese women and men. MATERIAL AND METHODS: Body composition was measured by dual-energy X-ray absorptiometry (DXA) in 109 obese women and 113 obese men. Insulin resistance was measured by (HOMA-IR); insulin sensitivity was estimated by metabolic clearance rate (MCRestOGTT) and insulin secretion by HOMAsecr. Serum lipids were assessed. RESULTS: In women, leg FM was negatively (favourably) associated with HOMA-IR and cholesterol/HDL-cholesterol ratio (p<0.05). Trunk FM was positively (unfavourably) associated with HOMA-IR. Leg/trunk FM ratio was negatively associated with HOMA-IR (p<0.001), cholesterol/HDL-cholesterol ratio (p<0.001) and triglycerides (p<0.01); positively (favourably) with MCRestOGTT (p<0.01) and HDL-cholesterol (p<0.05). No associations were found in men. In women, multiple regression analysis demonstrated that leg/trunk FM ratio was the only explanatory FM for HOMA-IR and MCRestOGTT (R(2) = 0.23 and R(2) = 0.13, respectively; p<0.001), but postmenopausal status was also of importance (R(2) = 0.23, p = 0.019 and R(2) = 0.29, p = 0.015, respectively). CONCLUSIONS: Leg FM has a favourable influence on insulin resistance and dyslipidaemia in obese women, but not demonstrated in this cohort of obese men.

Low-dose GH improves exercise capacity in adults with GH deficiency: effects of a 22-month placebo-controlled, crossover trial.

Fifty-five patients with adult-onset GH deficiency (mean age, 49 years) were enrolled in a placebo-controlled, crossover study to investigate the effects of GH therapy on exercise capacity, body composition, and quality of life (QOL). GH and placebo were administered for 9 months each, separated by a 4-month washout period. GH therapy was individually dosed to obtain an IGF-I concentration within the normal range for age and sex. The final mean daily dose of GH was 1.2 IU/day for men and 1.8 IU/day for women. Mean IGF-I concentration at baseline was higher in men than in women (95+/-33 vs 68+/-41 microg/l respectively; P < 0.04) and increased to a similar level on GH therapy. Body fat mass was reduced by 1.9+/-2.9 kg and lean body mass was increased by 1.8+/-2.8 kg (P = 0.0001 for each) with GH treatment. Total and low-density cholesterol levels decreased. Absolute maximal oxygen uptake increased by 6% (P = 0.01), relative to body weight by 9% (P = 0.004), and there was a trend toward increased endurance performance by 7% (P = 0.07). There were no significant effects on QOL. In conclusion, treatment with a low, physiologic dose of GH produced positive effects on body composition and lipids and improved exercise capacity, likely to be of clinical relevance. No changes in QOL were seen, possibly because of a good QOL at baseline.

Supplementation with conjugated linoleic acid for 24 months is well tolerated by and reduces body fat mass in healthy, overweight humans.

After 12 mo in a randomized, double-blind, placebo-controlled trial of conjugated linoleic acid (CLA) supplementation (2 groups received CLA as part of a triglyceride or as the free fatty acid, and 1 group received olive oil as placebo), 134 of the 157 participants who concluded the study were included in an open study for another 12 mo. The goals of the extension study were to evaluate the safety [with clinical chemistry analyses and reported adverse events (AEs)] and assess the effects of CLA on body composition [body fat mass (BFM), lean body mass (LBM), bone mineral mass (BMM)], body weight, and BMI. All subjects were supplemented with 3.4g CLA/d in the triglyceride form. Circulating lipoprotein(a) and thrombocytes increased in all groups. There was no change in fasting blood glucose. Aspartate amino transferase, but not alanine amino transferase, increased significantly. Plasma total cholesterol and LDL cholesterol were reduced, whereas HDL cholesterol and triglycerides were unchanged. The AE rate decreased compared with the first 12 mo of the study. Body weight and BFM were reduced in the subjects administered the placebo during the initial 12 mo study (-1.6 +/- 3.2 and -1.7 +/- 2.8 kg, respectively). No fat or body weight changes occurred in the 2 groups given CLA during the initial 12 mo. LBM and BMM were not affected in any of the groups. Changes in body composition were not related to diet and/or training. In conclusion, this study shows that CLA supplementation for 24 mo in healthy, overweight adults was well tolerated. It confirms also that CLA decreases BFM in overweight humans, and may help maintain initial reductions in BFM and weight in the long term.

Conjugated linoleic acid supplementation for 1 y reduces body fat mass in healthy overweight humans.

BACKGROUND: Short-term trials showed that conjugated linoleic acid (CLA) may reduce body fat mass (BFM) and increase lean body mass (LBM), but the long-term effect of CLA was not examined. OBJECTIVE: The objective of the study was to ascertain the 1-y effect of CLA on body composition and safety in healthy overweight adults consuming an ad libitum diet. DESIGN: Male and female volunteers (n = 180) with body mass indexes (in kg/m(2)) of 25-30 were included in a double-blind, placebo-controlled study. Subjects were randomly assigned to 3 groups: CLA-free fatty acid (FFA), CLA-triacylglycerol, or placebo (olive oil). Change in BFM, as measured by dual-energy X-ray absorptiometry, was the primary outcome. Secondary outcomes included the effects of CLA on LBM, adverse events, and safety variables. RESULTS: Mean (+/- SD) BFM in the CLA-triacylglycerol and CLA-FFA groups was 8.7 +/- 9.1% and 6.9 +/- 9.1%, respectively, lower than that in the placebo group (P < 0.001). Subjects receiving CLA-FFA had 1.8 +/- 4.3% greater LBM than did subjects receiving placebo (P = 0.002). These changes were not associated with diet or exercise. LDL increased in the CLA-FFA group (P = 0.008), HDL decreased in the CLA-triacylglycerol group (P = 0.003), and lipoprotein(a) increased in both CLA groups (P < 0.001) compared with month 0. Fasting blood glucose concentrations remained unchanged in all 3 groups. Glycated hemoglobin rose in all groups from month 0 concentrations, but there was no significant difference between groups. Adverse events did not differ significantly between groups. CONCLUSION: Long-term supplementation with CLA-FFA or CLA-triacylglycerol reduces BFM in healthy overweight adults.

Activated factor 12 (FXIIa) predicts recurrent coronary events after an acute myocardial infarction.

BACKGROUND: Activated factor XII (FXIIa) is involved in vascular injury and repair, participating in inflammation, thrombosis, and fibrinolysis. We wanted to test the hypothesis that FXIIa may predict an acute coronary syndrome (ACS) after a myocardial infarction (MI) and to evaluate whether FXIIa is related to global markers of end-stage coagulation and inflammation, including fibrin monomer (FM) and ultrasensitive C-reactive protein (microCRP). METHODS: In a prospective study of 300 patients with acute MI, we evaluated the predictive value of FXIIa in blood samples drawn 4 to 6 days after admission. Cardiac death, re-MI, and troponin-T-positive unstable angina pectoris were registered during a median follow-up period of 1.5 years. RESULTS: In the upper quartile of FXIIa (Q4) (> or =2.23 ng/mL) 32.0% of patients had an ACS as compared with 16.9% of patients with FXIIa in the three lower quartiles (Q1-3, P =.008). Relative risk of recurrent ACS for patients with FXIIa in the Q4 as compared with Q1-3 was 1.89 (95% CI, 1.22 to 2.93). A secondary ACS occurred earlier in patients with FXIIa in the Q4 as compared with those with FXIIa in the Q1-3 (P =.0039). Conventional risk factors as potential confounders were not associated with time to event. FXIIa did not correlate with FM or microCRP, and the FM and microCRP levels were of a similar magnitude in the Q4 as compared with the Q1 and the Q1-3 of FXIIa. CONCLUSIONS: FXIIa predicts recurrent coronary events after MI. The prognostic ability of FXIIa was not reflected by markers of hypercoagulability or inflammation.

Safety and efficacy of Mangafodipir trisodium in patients with liver lesions and cirrhosis.

Mangafodipir trisodium (Mn-DPDP, Teslascan) is a well-tolerated liver contrast agent. Although the enhancement characteristics of the cirrhotic liver after Mangafodipir trisodium administration have been studied, at present there is no published data on the impact that cirrhosis might have on the safety and efficacy profiles of this agent. Our objective is to evaluate by means of a retrospective comparison the safety and efficacy of Mangafodipir trisodium in patients with underlying cirrhosis who were examined for suspicion of focal liver lesions. A total of 923 patients received Mangafodipir trisodium (5 micromol/kg) in 11 prospective randomized European clinical trials. Adverse events and discomfort were recorded and graded in all patients. The efficacy analyses were performed on the subsets consisting of 617 patients with independent lesion counts (detection), and on the subset with 399 patients with independent and onsite final lesion diagnosis (characterization). Of the 399 patients, 149 had histologic confirmation. One hundred eighty of 923 patients (19.5%) had cirrhosis. There were no main differences between cirrhotic and non-cirrhotic patients. Adverse events were observed in 64 patients (6.9%), 6.7% in the cirrhotic group and 7.0% in the non-cirrhotic group, a non-significant difference. Adverse events in most patients were mild or moderate. The presence and intensity of the events did not differ between groups. Discomfort was recorded in 79 patients (8.6%), equally distributed in cirrhotic (6.1%) and non-cirrhotic (9.2%) patients. Regarding lesion count, significantly more lesions were found in the post- than in the precontrast images in both the cirrhotic and non-cirrhotic groups ( p<0.0001). This increase was not influenced by the presence of liver cirrhosis ( p=0.94). Lesion characterization was significantly improved in cirrhotic patients after administration of Mangafodipir trisodium ( p=0.002) but not in non-cirrhotic patients ( p=0.13). Mangafodipir trisodium is a safe and well-tolerated useful contrast agent in patients with cirrhosis.