Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation: results on health-related quality of life and symptom burden. The MANTRA-PAF trial.

AIMS: The Medical ANtiarrhythmic Treatment or Radiofrequency Ablation in Paroxysmal Atrial Fibrillation (MANTRA-PAF) trial assessed the long-term efficacy of an initial strategy of radiofrequency ablation (RFA) vs. antiarrhythmic drug therapy (AAD) as first-line treatment for patients with PAF. In this substudy, we evaluated the effect of these treatment modalities on the Health-Related Quality of Life (HRQoL) and symptom burden of patients at 12 and 24 months. METHODS AND RESULTS: During the study period, 294 patients were enrolled in the MANTRA-PAF trial and randomized to receive AAD (N = 148) or RFA (N = 146). Two generic questionnaires were used to assess the HRQoL [Short Form-36 (SF-36) and EuroQol-five dimensions (EQ-5D)], and the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) was used to evaluate the symptoms appearing during the trial. All comparisons were made on an intention-to-treat basis. Both randomization groups showed significant improvements in assessments with both SF-36 and EQ-5D, at 24 months. Patients randomized to RFA showed significantly greater improvement in four physically related scales of the SF-36. The three most frequently reported symptoms were breathlessness during activity, pronounced tiredness, and worry/anxiety. In both groups, there was a significant reduction in ASTA symptom index and in the severity of seven of the eight symptoms over time. CONCLUSION: Both AAD and RFA as first-line treatment resulted in substantial improvement of HRQoL and symptom burden in patients with PAF. Patients randomized to RFA showed greater improvement in physical scales (SF-36) and the EQ-visual analogue scale. CLINICAL TRIAL REGISTRATION: URL http://www.clinicaltrials.gov. Unique identifier: NCT00133211.

Restorative proctocolectomy for ulcerative colitis: development and validation of a new scoring system for pouch dysfunction and quality of life.

AIM: The purpose of this study was to develop and validate a pouch dysfunction score that could identify the aspects of function which have the greatest impact on quality of life as perceived by the patient. METHOD: All (n = 1757) patients having restorative proctocolectomy in Denmark between 1980 and 2010 were identified. Of these, 1229 were available for study and were sent a questionnaire on bowel function and quality of life (QoL) designed specifically for this study. Function was correlated with QoL in a multivariate model using ordinal logistic regression with QoL as a dependent variable. The pouch dysfunction score was developed from a randomly selected half of the study population and the validity was tested on the other half. RESULTS: 1047 (85%) patients returned the questionnaire. On multivariate analysis, the symptom domains of 'incomplete emptying', 'severity of urgency', 'number of bowel movements/24 h', 'major incontinence' and 'use of anti-diarrhoeal medication' were associated with reduced QoL. The score was divided into three categories including 'none', 'minor' and 'some/major' pouch dysfunction. The corresponding coefficients gave the score a range from 0 to 7.5. There was a highly significant difference (P < 0.001) in score between the categories. The area under the receiver operating curve was 0.81. CONCLUSION: Urgency, incomplete emptying, number of bowel movements/24 h, major incontinence and use of anti-diarrhoeal medication have a major impact on QoL. There was a high accuracy for the score, demonstrating its potential clinical usefulness in relating symptoms to QoL.

Liraglutide suppresses postprandial triglyceride and apolipoprotein B48 elevations after a fat-rich meal in patients with type 2 diabetes: a randomized, double-blind, placebo-controlled, cross-over trial.

AIMS: Postprandial triglyceridaemia is a risk factor for cardiovascular disease (CVD). This study investigated the effects of steady-state liraglutide 1.8 mg versus placebo on postprandial plasma lipid concentrations after 3 weeks of treatment in patients with type 2 diabetes mellitus (T2DM). METHODS: In a cross-over trial, patients with T2DM (n = 20, 18-75 years, BMI 18.5-40 kg/m²) were randomized to once-daily subcutaneous liraglutide (weekly dose escalation from 0.6 to 1.8 mg) and placebo. After each 3-week period, a standardized fat-rich meal was provided, and the effects of liraglutide on triglyceride (primary endpoint AUC(0-8h)), apolipoprotein B48, non-esterified fatty acids, glycaemic responses and gastric emptying were assessed. ClinicalTrials.gov ID: NCT00993304. FUNDING: Novo Nordisk A/S. RESULTS: After 3 weeks, mean postprandial triglyceride (AUC(0-8h) liraglutide/placebo treatment-ratio 0.72, 95% CI [0.62-0.83], p = 0.0004) and apolipoprotein B48 (AUC(0-8h) ratio 0.65 [0.58-0.73], p < 0.0001) significantly decreased with liraglutide 1.8 mg versus placebo, as did iAUC(0-8h) and C(max) (p < 0.001). No significant treatment differences were observed for non-esterified fatty acids. Mean postprandial glucose and glucagon AUC(0-8h) and C(max) were significantly reduced with liraglutide versus placebo. Postprandial gastric emptying rate [assessed by paracetamol absorption (liquid phase) and the ¹³C-octanoate breath test (solid phase)] displayed no treatment differences. Mean low-density lipoprotein and total cholesterol decreased significantly with liraglutide versus placebo. CONCLUSIONS: Liraglutide treatment in patients with T2DM significantly reduced postprandial excursions of triglyceride and apolipoprotein B48 after a fat-rich meal, independently of gastric emptying. Results indicate liraglutide's potential to reduce CVD risk via improvement of postprandial lipaemia.

Effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile and inflammation markers in metabolic syndrome -- a randomized study (SYSDIET).

BACKGROUND: Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and inflammatory markers in people with metabolic syndrome. METHODS: We conducted a randomized dietary study lasting for 18-24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m(-2) , 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4-week run-in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole-grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low-fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4-day food diaries and fatty acid composition of serum phospholipids. RESULTS: Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non-HDL cholesterol (-0.18, mmol L(-1) 95% CI -0.35; -0.01, P = 0.04), LDL to HDL cholesterol (-0.15, -0.28; -0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (-0.04, -0.07; -0.00, P = 0.025) favouring the Healthy diet. IL-1 Ra increased during the Control diet (difference -84, -133; -37 ng L(-1) , P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, -0.23, -0.41; -0.05, P = 0.012) were associated with IL-1 Ra. CONCLUSIONS: Healthy Nordic diet improved lipid profile and had a beneficial effect on low-grade inflammation.

PET hypoxia imaging with FAZA: reproducibility at baseline and during fractionated radiotherapy in tumour-bearing mice.

PURPOSE: Tumour hypoxia is linked to treatment resistance. Positron emission tomography (PET) using hypoxia tracers such as fluoroazomycin arabinoside (FAZA) may allow identification of patients with hypoxic tumours and the monitoring of the efficacy of hypoxia-targeting treatment. Since hypoxia PET is characterized by poor image contrast, and tumour hypoxia undergoes spontaneous changes and is affected by therapy, it remains unclear to what extent PET scans are reproducible. Tumour-bearing mice are valuable in the validation of hypoxia PET, but identification of a reliable reference tissue value (blood sample or image-derived muscle value) for repeated scans may be difficult due to the small size of the animal or absence of anatomical information (pure PET). Here tumour hypoxia was monitored over time using repeated PET scans in individual tumour-bearing mice before and during fractionated radiotherapy. METHODS: Mice bearing human SiHa cervix tumour xenografts underwent a PET scan 3 h following injection of FAZA on two consecutive days before initiation of treatment (baseline) and again following irradiation with four and ten fractions of 2.5 Gy. On the last scan day, mice were given an intraperitoneal injection of pimonidazole (hypoxia marker), tumours were collected and the intratumoral distribution of FAZA (autoradiography) and hypoxia (pimonidazole immunohistology) were determined in cryosections. RESULTS: Tissue section analysis revealed that the intratumoral distribution of FAZA was strongly correlated with the regional density of hypoxic (pimonidazole-positive) cells, even when necrosis was present, suggesting that FAZA PET provides a reliable measure of tumour hypoxia at the time of the scan. PET-based quantification of tumour tracer uptake relative to injected dose showed excellent reproducibility at baseline, whereas normalization using an image-derived nonhypoxic reference tissue (muscle) proved highly unreliable since a valid and reliable reference value could not be determined. The intratumoral distribution of tracer was stable at baseline as shown by a voxel-by-voxel comparison of the two scans (R = 0.82, range 0.72-0.90). During treatment, overall tracer retention changed in individual mice, but there was no evidence of general reoxygenation. CONCLUSION: Hypoxia PET scans are quantitatively correct and highly reproducible in tumour-bearing mice. Preclinical hypoxia PET is therefore a valuable and reliable tool for the development of strategies that target or modify hypoxia.

Effects of different fractions of whey protein on postprandial lipid and hormone responses in type 2 diabetes.

BACKGROUND/OBJECTIVES: Exacerbated postprandial lipid responses are associated with an increased cardiovascular risk. Dietary proteins influence postprandial lipemia differently, and whey protein has a preferential lipid-lowering effect. We compared the effects of different whey protein fractions on postprandial lipid and hormone responses added to a high-fat meal in type 2 diabetic subjects. SUBJECTS/METHODS: A total of 12 type 2 diabetic subjects ingested four isocaloric test meals in randomized order. The test meals contained 100 g of butter and 45 g of carbohydrate in combination with 45 g of whey isolate (iso-meal), whey hydrolysate (hydro-meal), α-lactalbumin enhanced whey (lac-meal) or caseinoglycomacropeptide enhanced whey (CGMP-meal). Plasma concentrations of triglyceride, retinyl palmitate, free fatty acid, insulin, glucose, glucagon, glucagon-like peptide 1 and glucose-dependent insulinotropic peptide were measured before and at regular intervals until 8-h postprandially. RESULTS: We found no statistical significant differences between meals on our primary variable triglyceride. The retinyl palmitate response was higher after the hydro-meal than after the iso- and lac-meal in the chylomicron-rich fraction (P=0.008) while no significant differences were found in the chylomicron-poor fraction. The hydro- and iso-meal produced a higher insulin response compared with the lac- and CGMP-meal (P<0.001). Otherwise no significant differences in the hormone responses were found in the incremental area under the curve over the 480-min period. CONCLUSIONS: A supplement of four different whey protein fractions to a fat-rich meal had similar effects on postprandial triglyceride responses in type 2 diabetic subjects. Whey isolate and whey hydrolysate caused a higher insulin response.

R-CHOEP-14 improves overall survival in young high-risk patients with diffuse large B-cell lymphoma compared with R-CHOP-14. A population-based investigation from the Danish Lymphoma Group.

BACKGROUND: Optimal treatment of young patients with high-risk diffuse large B-cell lymphoma (DLBCL) remains a matter of debate and requires improvement. The combination chemotherapy with cyclophosphamide, doxorubicin, vincristine and prednisone (CHOP) with addition of etoposide (CHOEP) has in other patient groups been shown to be effective. Further improvement has been accomplished with the use of rituximab in combination with the regimens every 2 weeks (R-CHOP-14, R-CHOEP-14). The aim of the present retrospective population-based study was to compare R-CHOP-14 with R-CHOEP-14 in a cohort of high-risk patients aged 18-60 years with two or more risk factors (stage III-IV, elevated lactate dehydrogenase levels, performance status 2-4). To our knowledge, this is the first study comparing these two regimens in this patient group. METHODS: We obtained data for the period 2004-2009 from the Danish Lymphoma Database. One hundred and fifty-nine patients were eligible to enter the study. Primary end point was overall survival (OS) and secondary end points were response to treatment, progression-free survival (PFS) and safety. RESULTS: Four-year OS was superior in the R-CHOEP-14 group: 75% compared with 62% for R-CHOP-14 (P=0.04). This superiority was also seen for PFS: 4-year PFS was 70% for the R-CHOEP-14 group compared with 58% for the R-CHOP-14 group (P=0.02). CONCLUSION: R-CHOEP-14 is a promising regimen for young patients with high-risk DLBCL with improved OS and PFS compared with R-CHOP-14.

Acute differential effects of milk-derived dietary proteins on postprandial lipaemia in obese non-diabetic subjects.

BACKGROUND/OBJECTIVES: Postprandial lipaemia is an established risk factor for atherosclerosis. To investigate the acute effect of four milk-derived dietary proteins (alpha-lactalbumin, whey isolate, caseinoglycomacropeptide and whey hydrolysate) on postprandial lipaemia, we have conducted a randomized, acute, single-blinded clinical intervention study with crossover design. SUBJECTS/METHODS: A total of 11 obese non-diabetic subjects (age: 44-74, BMI: 30-41.4 kg m(-2)) were included. On 4 different days the subjects ingested a high-fat meal with the following energy distribution: 66% energy from fat (100 g of butter), 15% of energy from carbohydrate (90 g of white wheat bread) and 19% of energy from protein (45 g of pure protein). Our primary variable was plasma triglyceride measured in the 8-h postprandial period. Secondarily, retinyl palmitate, non-esterified free fatty acids, glucose, insulin, glucagon, GLP-1 and GIP, active and total grehlin and cholecystokinin were measured. RESULTS: We observed no statistically significant (P=0.8) differences between meals on our primary variable that is, triglycerides. Whey hydrolysate was associated with a significantly (P=0.02) smaller postprandial suppression of non-esterified free fatty acids compared with the other dietary proteins. CONCLUSION: We did not observe significant differences in postprandial lipaemia to the four milk-derived dietary proteins. Whey hydrolysate caused less postprandial suppression of free fatty acids.

Atrial fibrillation and upper limb thromboembolectomy: a national cohort study.

BACKGROUND: The risk factors associated with, and the incidence of systemic embolism in patients with atrial fibrillation (AF) are poorly understood. OBJECTIVES: We studied the association between AF and upper limb thromboembolectomy involving brachial, ulnar or radial artery in a national cohort study that included all individuals aged 40-99 years with incident AF. METHODS: Data were retrieved from the Danish National Vascular Registry, the National Registry of Patients, the Danish Civil Registration System and Statistics Denmark. RESULTS: In total, 131,476 patients (68,042 men and 63,434 women) with AF without previous thromboembolectomy in the upper limb were registered. In the study cohort, 130 men underwent upper limb thromboembolectomy over 220,890 person-years of observation, whilst 275 women underwent thromboembolectomy over 197,777 patient-years. The incidence per 100,000 person-years was 58.9 (95% CI, 49.2-69.8) for men and 139.1 (95% CI, 123.1-156.5) for women. The relative risk of thromboembolectomy among patients with AF compared to the background population was 7.5 (95% CI, 6.3-8.9) for men, and 9.3 (95% CI, 8.3-10.5) for women. Women with AF had a relative thromboembolectomy risk of 1.8 (95% CI, 1.5-2.3) compared to men with AF. Among patients with AF, history of hypertension (HR 2.2-2.9), myocardial infarction (HR 2.9-3.9), heart failure (HR 1.6-1.9) and stroke (HR 2.2-3.8) were significantly associated with increased risk of thromboembolectomy in both men and women. CONCLUSIONS: AF substantially increases the risk of upper limb thromboembolectomy. This risk is higher with increasing age, female gender, and associated with hypertension, myocardial infarction, heart failure and stroke.

Upper-limb thrombo-embolectomy: national cohort study in Denmark.

OBJECTIVES: We investigated the incidence of thrombo-embolectomy in upper-limb and prognosis with respect to arm amputation, stroke and death. METHODS: We performed a national cohort study of individuals, aged 40-99 years, and undergoing first-time thrombo-embolectomy in the brachial, ulnar or radial artery in Denmark from 1990 to 2002. The data were retrieved from the National Vascular Registry and from the National Registry of Patients and the Civil Registration System. Patients were followed until 2006 to ascertain the occurrence of amputation and stroke and until 2007 with respect to death. RESULTS: In total, 1377 incident cases of thrombo-embolectomy were registered, comprising 504 (36.6%) males with a mean age of 72.0 (standard deviation (SD) 12.4) years and 873 (63.4%) females with a mean age of 77.2 (SD 11.7) years. Incidence was 3.3 (95% confidence interval (CI): 3.1-3.7) for males and 5.2 (95% CI: 4.9-5.6) for females per 100000 person-years. After thrombo-embolectomy, upper-limb amputation was performed in 11 (incidence 2.2%; 95% CI: 1.2-3.4) males and 31 (3.6%; 95% CI: 2.5-4.9) females. Age- and sex-specific risk of stroke was 2-16 times higher, and risk of death 3-11 times higher, than in the general population. CONCLUSIONS: Upper-limb thrombo-embolectomy is associated with an increased risk of limb amputation, stroke and death.

Warfarin for the prevention of systemic embolism in patients with non-valvular atrial fibrillation: a meta-analysis.

BACKGROUND: Warfarin for stroke prevention in patients with atrial fibrillation (AF) is well documented. However, it has not been examined in the prevention of systemic embolism. OBJECTIVES: To evaluate the efficacy of warfarin in preventing systemic embolism (embolism to limbs or viscera) in patients with AF. METHODS AND RESULTS: A combined Medline, Embase, Cochrane Library and SveMed+ search were made. Fifteen studies were included. Warfarin was better than antiplatelet agents for preventing systemic embolism with a 50% reduction of risk (odds ratio (OR) = 0.50, 95% CI 0.33 to 0.75) without increasing the risk of major bleeding (OR = 1.07; 95% CI 0.85 to 1.34). Warfarin compared with placebo resulted in a risk reduction of 71% (OR = 0.29; 95% CI 0.08 to 1.07) with higher risk of major bleeding with warfarin (OR = 3.01; 95% CI 1.31 to 6.92). Results of a comparison of warfarin with low-dose warfarin (OR = 1.52; 95% CI 0.40 to 5.81) or low-dose warfarin with aspirin (OR = 1.00; 95% CI 0.17 to 5.81) were inconclusive. CONCLUSIONS: Warfarin not only reduces the risk of stroke but is also better than placebo and antiplatelet agents in prevention of systemic embolism in patients with non-valvular AF. Warfarin increases the risk of major bleeding compared with placebo but not compared with antiplatelet agents.

Recovery of autonomic nervous activity after myocardial infarction demonstrated by short-term measurements of SDNN.

OBJECTIVE: Heart rate variability (HRV) has been demonstrated to be a risk factor after acute myocardial infarction (AMI). In the present study serial measurement of SDNN (standard deviation of the mean of qualified NN-interval) in short intervals was used to assess HRV changes after AMI, and determine the role of these as independent risk factors compared to clinical, arrhythmic, ischemic and anamnestic variables. Measurements from a normal healthy middle-aged male population were used as reference (n = 63). METHODS: SDNN from a five-minute period during day and night-time, respectively, was examined in 103 patients 1 week (n = 54), 1 month (n = 72) and 12-16 months (n = 54) after infarction. RESULTS: Day SDNN did not change during one-and-a-half years after AMI, and was significantly reduced compared with healthy males. Night SDNN, low after 1 week, with recovery 1 month after AMI, was significantly reduced compared with healthy males early, but not late after AMI. Thus, the study indicated during day-time a continuous abnormal sympathetic preponderance in the course of 16 months after AMI, and during night-time a gradual recovery of parasympathetic preponderance beginning early after AMI. CONCLUSION: One week after AMI day-time SDNN of <30 ms, and night-time SDNN of < 18 ms, age > or =60 years, and myocardial ischemia (Holter monitoring) were independent predictors of 9 years' mortality. One and 12-16 months after AMI reduced day and night-time SDNN had no prognostic implication.

[Prognosis after late versus early nonfatal myocardial infarction]. / Prognosen efter sent versus tidligt ikkedødeligt myokardiereinfarkt. DAVIT Study Group.

Many recent studies have identified nonfatal recurrent myocardial infarction (RNMI) as the most significant predictor for later outcome. Almost all of these studies have been based on the studies of RNMI in the first year after the index infarction. The prognosis after late RNMI has not been studied properly. In 3,867 nonselected patients below 76 years of age with an acute myocardial infarction we studied the prognosis after a first RNMI depending on the year of its occurrence after the index infarction. Mortality was estimated by the method of Kaplan-Meier and the differences were evaluated by means of the Tarone-Ware test. Four hundred and ninety-three (13.6%) patients had a first RNMI in the first, 151 (5.4%) in the second, 105 (4.2%) in the third, and 71 (3.8%) in the fourth year after the index infarction (group 1-4). One-year mortality rate after RNMI was 23.7% in the first group, 24.1% in the second, 17.5% in the third, and 22.8 in the fourth group. When all the groups were compared with each other no significant difference was found between the mortality rates (p = 0.12) or Standardised Mortality Rates. We concluded that late and early RNMIs have almost the same grave prognosis.

[Effect of specific physiotherapy on chronic pain, functional level and quality of life in osteoporosis. A prospective randomized single-blind placebo-controlled study]. / Effekt af specifik fysioterapi på kroniske smerter, funktionsniveau og livskvalitet ved osteoporose. En prospektiv randomiseret enkeltblindet placebokontrolleret undersøgelse.

Patients suffering from osteoporotic vertebral fractures are handicapped by pain and reduced quality of life. Our aim was to investigate the effect of a short training program for osteoporotic patients with regard to pain level, use of analgetics and quality of life. We performed a prospective randomized single-blinded placebo-controlled study. The training program included general training of balance and muscle strength and stabilization of the back. The participants were randomised to 10 weeks of ambulatory training. Controls and training participants were tested weekly by registration of pain level and analgetic intake. Questionnaires on daily level of function and quality of life were given at the start and after five and 10 weeks. After three months both groups filled out the questionnaires at home. The training group had a significant reduction in pain score and use of analgetics. The distribution of functional score improved during training. Quality of life score improved significantly throughout the study and after three months. In conclusion, this ambulatory training program is effective for training osteoporotic patients with moderately severe pain and the training should be continued.

Disrupted p53 function as predictor of treatment failure and poor prognosis in B- and T-cell non-Hodgkin's lymphoma.

Mutation of the p53 gene has been associated with treatment failure and poor outcome in various malignancies. It has been suggested that immunohistochemical analysis of p53 and p21Waf1, a downstream target, can be used to screen for p53 gene mutations. We determined the value of immunohistochemical screening for p53 gene mutations as a prognostic marker in a population-based group of B- and T-cell non-Hodgkin's lymphomas (NHLs). On the basis of p53 gene mutation status and immunohistochemically detected p53 and p21Waf1 expression in 34 lymphomas, we established an immunophenotype (delta p53) correlating with p53 gene mutation. The immunohistochemical analysis was extended to encompass 199 lymphomas from a population-based registry and was correlated with clinical parameters. Delta p53 showed 100% concordance with p53 gene mutation and was detected in 42 cases (21%). Multivariate analysis of advanced stage lymphomas showed that delta p53 was independently associated with treatment failure (relative risk, 3.8; P = 0.001). Delta p53 predicted poor survival when analyzing all patients (P = 0.0001), as well as B-cell (P = 0.04) and T-cell NHL (P = 0.000002). In multivariate analysis, delta p53 (relative risk, 2.2; P = 0.001) maintained prognostic significance. The impact on prognosis of delta p53 was highly significant in the low-intermediate-risk group (P = 0.00002). Comparing survival of the aggressive lymphoma patients in this group showed that the 8 delta p53 patients died within 1 year, whereas the median survival of the 28 non-delta p53 patients was 36 months. These results suggest that immunohistochemically assessed p53 status may predict treatment response and outcome in B- and T-cell NHL patients.

Clinical significance of cyclin-dependent kinase inhibitor p27Kip1 expression and proliferation in non-Hodgkin's lymphoma: independent prognostic value of p27Kip1.

The cyclin-dependent kinase inhibitor p27Kip1 is a negative cell cycle regulator linking extracellular growth-regulatory signals to the cell cycle machinery in G1. We investigated the pattern and prognostic value of p27Kip1 expression in a population-based group of 203 non-Hodgkin's lymphoma (NHL) patients. The expression of p27Kip1 was identified by immunohistochemistry and correlated with Ki-67 expression and clinical features. Correlation with outcome was determined using uni- and multivariate analysis stratified by clinical grade. Except for very aggressive NHL, there was a negative correlation between p27Kip1 and Ki-67 expression. Low expression of p27Kip1, defined as nuclear p27Kip1 expression in <40% of malignant cells, was predictive of poor survival in indolent and aggressive NHL. However, even in this regard, very aggressive lymphomas behaved differently as those with low p27Kip1 expression tended to do better. Likewise, a high proliferation rate (Ki-67 >40%) was associated with poor survival in indolent and aggressive lymphomas. Multivariate analysis using the proportional hazards model showed that only p27Kip1, and not Ki-67, maintained independent prognostic significance in indolent and aggressive lymphomas (relative risk = 2. 0; P = 0.0095). The low cost and simplicity of this standard immunohistochemistry analysis makes p27Kip1 a promising and suitable prognostic marker in routine diagnostic laboratories in a standard diagnostic panel.

Nonsteroidal anti-inflammatory drugs after acute myocardial infarction. DAVIT Study Group. Danish Verapamil Infarction Trial.

The effect of nonsteroid anti-inflammatory drugs (NSAIDs) after acute myocardial infarction was studied in a retrospective study of 88 patients who were receiving regular NSAID treatment at randomization in the Danish Verapamil Infarction Trial II. There were no significant differences in mortality or major events between NSAID-treated patients versus controls (1,687); however, in a multivariate analysis a nonsignificant beneficial trend in favor of NSAIDs was observed.

Temporal pattern of the effect of verapamil on myocardial reinfarction. DAVIT Study Group. Danish Verapamil Infarction Trial.

The purpose of this study was to compare the effects of verapamil on early versus late reinfarction after an index myocardial infarction. A total of 1775 consecutive patients < 76 years of age, with acute myocardial infarction, included in the Danish Verapamil Infarction Trial II, were followed for 18 months. Reinfarctions during the observation period were retrospectively divided into the 50% earliest occurring and the 50% latest occurring (early and late reinfarction, respectively). Cox regression analysis was applied to assess the significance of clinical baseline variables and treatment group (verapamil vs. placebo) on early, late, and total reinfarction. One hundred and ninety-one reinfarctions were registered during the 18-month observation: 96 in the first 5 months (early) and 95 in the last 13 months (late). On univariate analysis verapamil significantly reduced the rate of total reinfarction (P = 0.04, hazard ratio [HR] = 0.77; 95% confidence Interval [CI] 0.58-1.03) and early reinfarction (P = 0.007, HR 0.56; 95% CI 0.37-0.86), but not late reinfarction (P = 0.99, HR = 1.05; 95% CI 0.70-1.56). In a multivariate model, only the rate of early reinfarction was reduced by verapamil (P = 0.012, HR = 0.59, 95% CI 0.39-0.90). Additionally, predictors of early and late reinfarction were quite different in this model. After an index myocardial infarction verapamil reduces the rate of early but not late reinfarction.

Comparison of the prognosis after early versus late recurrent nonfatal myocardial infarction. DAVIT Study Group. Danish Verapamil Infarction Trial.

BACKGROUND: Recurrent nonfatal myocardial infarction (RNMI) is the most significant risk factor for later outcome after an index infarction. However, little is known about the prognosis after RNMIs that occur beyond the first year after the index infarction. METHODS AND RESULTS: In 3867 nonselected patients <76 years old with an acute myocardial infarction, we studied the rate of and prognosis after a first RNMI, depending on the year of its occurrence after the index infarction. Mortality rate was estimated by the method of Kaplan-Meier, and the differences were evaluated by means of the Tarone-Ware test. Four hundred ninety-three (13.6%) patients had a first RNMI in the first, 151 (5.4%) in the second, 105 (4.2%) in the third, and 71 (3.8%) in the fourth year after the index infarction (groups 1 through 4). One-year mortality rate after RNMI was 23.7% in the first group, 24.1% in the second group, 17.5% in the third group, and 22.8 in the fourth group. When all the groups were compared with each other, no significant difference was found between the mortality rates (p = 0.12) or standardized mortality rates. CONCLUSIONS: Late RNMIs have almost the same grave prognosis as do early RNMIs.

5993 survivors of suspected myocardial infarction. 10 year incidence of later myocardial infarction and subsequent mortality.

AIMS: To evaluate the 10-year incidence of later infarction and subsequent mortality, as well as predictors of later infarction, in patients with suspected myocardial infarction and alive on day 15 after admission. METHODS AND RESULTS: 5993 patients admitted with suspected myocardial infarction and alive on day 15 after admission were registered in The First Danish Verapamil Infarction Trial database in 1979-81. 2586 had definite infarction, 402 probable infarction and 3005 no infarction as they fulfilled 3, 2 and 1 criteria for infarction. They were followed for 10 years with respect to later infarction and death, i.e., including death after later infarction. The 10 year infarction rate after index admission was 48.8% in definite, 47.3% in probable and 24.6% in no infarction patients (P < 0.0001). The subsequent 10-year mortality was 82.3% in primary definite, 74.7% in primary probable, and 77.9% in primary no infarction patients (ns), Cox regression analysis with sex, age group, and definite, probable or no infarction as independent variables showed that females aged < 50 years without a primary infarction had the lowest hazard ratio (0.13 relative to males, aged 50-65 years with definite/probable infarction at index admission) for a later infarction, in contrast to the highest hazard ratio (1.17) for males aged > 65 years with definite or probable infarction. CONCLUSION: The 10-year infarction rate in patients with suspected myocardial infarction in whom the diagnosis is ruled out is lower than in those with definite or probable infarction, but the mortality after a later infarction is similar in all three groups.