Podcasts about results median

N Engl J Med 1996;334:1349-1355Background Before 1990, the prevailing idea held that the negative inotropy of beta-blockers would harm patients with impaired systolic function. Yet part of the progression of systolic heart failure involved over stimulation of the sympathetic nervous system. Norepinephrine can exert adverse effects on the circulation, both directly and indirectly. Smaller trials of beta-blockers in systolic heart failure found trends for benefit with beta-blockers, however, a mortality benefit had not yet been proven. The U.S. Carvedilol Heart Failure Study aimed to study mortality in patients with heart failure with a reduced ejection fraction.Cardiology Trial's Substack remains free of industry ads because of your support. Thank you. Please consider becoming a free or paid subscriber.Patients The study enrolled 1094 patients with chronic heart failure symptoms for at least 3 months, LVEF ≤ 0.35%, at least 2 months of treatment with diuretics and an angiotensin-converting enzyme (ACE) inhibitor (if tolerated). Treatment with digoxin, hydralazine, or nitrates was permitted but not required.Exclusion criteria were extensive and important to understand. These included any recent major cardiac events or surgery within the previous 3 months, uncorrected valvular disease, active myocarditis, sustained VT or higher degrees of AV block not controlled by pacing, systolic blood pressure of more than 160 or less than 85 mm Hg or diastolic blood pressure of more than 100 mm Hg, clinically significant kidney or liver disease or use of calcium-channel blockers, adrenergic agonists/antagonists, or class IC/III antiarrhythmic agents. Patients receiving β-adrenergic agonists or antagonists (presumably for another indication) were not enrolled.Baseline Characteristics The results of this and other beta-blocker trials in heart failure will be clear. One of the most important points for translating this evidence to patients will be the baseline characteristics. It is vital to understand who these patients were.The mean age was 58 years and approximately 76% were male. Most patients had mild to moderate heart failure, with 53% in NYHA Class II, 44% in Class III, and only 3% in Class IV. The etiology of heart failure was nearly evenly split between coronary artery disease (47%) and nonischemic cardiomyopathy (53%). Patients had significantly impaired cardiac function with a mean LVEF of 0.23. The mean six-minute walk distance ranged from 386 to 390 meters. Hemodynamic parameters were relatively stable, with mean systolic blood pressure of 116 mmHg, and mean heart rate of 83-84 beats per minute. Most patients were receiving standard heart failure therapy at baseline, including digitalis (90-91%), loop diuretics (95%), and ACE inhibitors (95%), while approximately one-third (32%) were on direct-acting vasodilators.Trial Procedures Patients were assessed for eligibility during a 3-week screening period during which exercise capacity was assessed with a 6-minute walk test. Notable was that these were outpatients able to complete a 6-minute walk test. Enrollment was stratified to one of four treatment protocols on the basis of the patients' performance on the exercise test: patients able to walk between 426 and 550 m when tested were assigned to the mild-heart-failure protocol; those able to walk between 150 and 425 m were assigned either to the moderate-heart-failure protocol or to a dose-ranging protocol, depending on the location of the study center; and those able to walk only less than 150 m were assigned to the severe-heart-failure protocol.After this base-line testing, all patients received 6.25mg of carvedilol twice daily for two weeks in an open-label run-in period. Those who tolerated this initial dose were then randomized to receive either placebo (n=398) or carvedilol (n=696) on a double-blind basis, in addition to their usual medications.The allocation ratio (carvedilol:placebo) was 2:1 in the mild and severe heart failure protocols and 1:1 in the moderate heart failure protocol. The dose was gradually increased to target levels of 25-50mg twice daily over 2-10 weeks, followed by maintenance therapy for an additional 6 months (12 months for mild heart failure).Endpoints At the time of trial planning, the original intent was safety. That is, to show that carvedilol did not increase mortality. The original intent was to enroll 1100 patients. As smaller trials on beta-blockers were published, the statistical plan included the possibility of beta-blocker benefit. The trialists therefore planned two sided statistical analysis.Cumulative survival curves were constructed as time-to-first-event plots by Kaplan–Meier survivorship methods and differences between the curves were tested for significance by the log-rank statistic with use of a Cox proportional-hazards regression model (which included the protocol as a covariate).Results Median follow-up was only 6.5 months due to early termination for benefit. The patients mean total daily dose of carvedilol was 45±27 mg. Overall mortality was 7.8% in the placebo group vs. 3.2% in carvedilol group. The relative risk reduction from carvedilol vs placebo was 65% (95% CI, 39-80%; p

Background: Asthma and allergies are world-wide common chronic diseases among children and young people. Little information is available about the prevalence of these diseases in rural areas of Latin America. This study assesses the prevalence of symptoms of asthma and allergies among children in urban and rural areas at Oropeza Province in Bolivia. Methods: The Spanish version of the ISAAC standardized questionnaire and the ISAAC video questionnaire were implemented to 2584 children attending the fifth elementary grade in 36 schools in Oropeza province (response 91%). Lifetime, 12 months and severity prevalence were determined for asthma, rhinitis and eczema symptoms. Odds ratios (OR) with 95% confidence intervals (95% CI) were calculated adjusting for age using generalized linear mixed-effects models. Results: Median age of children was 11 years, 74.8% attended public schools, and 52.1% were female. While children attending urban schools had lower prevalence of self-reported wheeze in the written questionnaire (adjusted OR 0.6; 95% CI 0.4-1.9), they were more likely than children attending rural schools to report wheeze in the video questionnaire (aOR 2.1; 95% CI 1.0-2.6). They also reported more frequently severe rhinoconjunctivitis (aOR 2.8; 95% CI 1.2-6.6) and severe eczema symptoms (aOR 3.3; 95% CI 1.0-11.0). Conclusion: Overall in accordance with the hygiene hypothesis, children living in urban areas of Bolivia seem to have a higher prevalence of symptoms of asthma and allergies compared to children living in the country side. In order to develop primary prevention strategies, environmental factors need to be identified in future studies.

Background: In the present study factors affecting survival and toxicity in cerebral metastasized patients treated with stereotactic radiosurgery (SRS) were analyzed with special focus on radiation necrosis. Patients and methods: 340 patients with 1-3 cerebral metastases having been treated with SRS were retrospectively analyzed. Radiation necrosis was diagnosed by MRI und PET imaging. Univariate and multivariate analysis using a Cox proportional hazards regression model and log-rank test were performed to determine the prognostic value of treatment-related and individual factors for outcome and SRS-related complications. Results: Median overall survival was 282 days and median follow-up 721 days. 44% of patients received WBRT during the course of disease. Concerning univariate analysis a significant difference in overall survival was found for Karnofsky Performance Status (KPS

Background: The aim of this study was to analyze the long-term survival of AML patients with CEBPA mutations. Patients and methods: We investigated 88 AML patients with a median age of 61 years and (1) cytogenetically normal AML (CN-AML), (2) monoallelic (moCEBPA) or biallelic (biCEBPA) CEBPA mutation, and (3) intensive induction treatment. 60/88 patients have been described previously with a shorter follow-up. Results: Median follow-up time was 9.8 years (95% CI: 9.4-10.1 years) compared to 3.2 and 5.2 years in our former analyses. Patients with biCEBPA mutations survived significantly longer compared to those with moCEBPA (median overall survival (OS) 9.6 years vs. 1.7 years, p = 0.008). Patients

Background: To report an unplanned interim analysis of a prospective, one-armed, single center phase I/II trial (NCT01566123). Methods: Between 2007 and 2013, 27 patients (pts) with primary/recurrent retroperitoneal sarcomas (size > 5 cm, M0, at least marginally resectable) were enrolled. The protocol attempted neoadjuvant IMRT using an integrated boost with doses of 45-50 Gy to PTV and 50-56 Gy to GTV in 25 fractions, followed by surgery and IOERT (10-12 Gy). Primary endpoint was 5-year-LC, secondary endpoints included PFS, OS, resectability, and acute/late toxicity. The majority of patients showed high grade lesions (FNCLCC G1:18%, G2:52%, G3:30%), predominantly liposarcomas (70%). Median tumor size was 15 cm (6-31). Results: Median follow-up was 33 months (5-75). Neoadjuvant IMRT was performed as planned (median dose 50 Gy, 26-55) in all except 2 pts (93%). Gross total resection was feasible in all except one patient. Final margin status was R0 in 6 (22%) and R1 in 20 pts (74%). Contiguous-organ resection was needed in all grossly resected patients. IOERT was performed in 23 pts (85%) with a median dose of 12 Gy (10-20 Gy). We observed 7 local recurrences, transferring into estimated 3- and 5-year-LC rates of 72%. Two were located outside the EBRT area and two were observed after more than 5 years. Locally recurrent situation had a significantly negative impact on local control. Distant failure was found in 8 pts, resulting in 3-and 5-year-DC rates of 63%. Patients with leiomyosarcoma had a significantly increased risk of distant failure. Estimated 3-and 5-year-rates were 40% for PFS and 74% for OS. Severe acute toxicity (grade 3) was present in 4 pts (15%). Severe postoperative complications were found in 9 pts (33%), of whom 2 finally died after multiple re-interventions. Severe late toxicity (grade 3) was scored in 6% of surviving patients after 1 year and none after 2 years. Conclusion: Combination of neoadjuvant IMRT, surgery and IOERT is feasible with acceptable toxicity and yields good results in terms of LC and OS in patients with high-risk retroperitoneal sarcomas. Long term follow-up seems mandatory given the observation of late recurrences. Accrual of patients will be continued with extended follow-up.

Background: Asthma and allergies are world-wide common chronic diseases among children and young people. Little is known about prevalence and environmental and dietary risk factors of asthma and allergies among rural and urban school children in Bolivia. The aim of this study was to describe the prevalence, severity and risk factors associated with asthma, rhinoconjunctivitis, and eczema symptoms in children of school age in Oropeza Province – Bolivia. Methods: Overall, 2584 children (response 91%) attending fifth elementary grade in Oropeza province answered the written and the video questionnaire of the International Study on Asthma and Allergies in Childhood. Lifetime, 12 months and severity prevalence were determined for asthma, rhinoconjunctivitis and eczema symptoms. The associations between: environmental and dietary factors and symptoms of asthma, rhinoconjuctivitis and eczema symptoms were analysed using logistic regression analysis with adjustment for age, sex and place of living. Results: Median age of children was 11 years, 52% were female and 26% lived in rural areas. The prevalence of asthma symptoms was higher in the written (18%) than in the video questionnaire (6%). 22% of children reported symptoms of rhinoconjunctivitis and 9% eczema symptoms. Overall, rural children reported more frequently symptoms of asthma and allergies than urban children. Parental smoking (adjusted OR 1.3; 95%IC 1.0-1.6), presence of disease vectors at home (fourth quartile vs. first quartile: 1.5; 1.1-2.2) and farm animals (1.3; 1.0-1.6) were statistically significant predictors of asthma symptoms detected by the written questionnaire. The associations were similar for symptoms of rhinoconjunctivitis and eczema. A greater adherence to the Mediterranean Diet (MD) was inversely related with asthma symptoms in the video questionnaire (reference category: 1st quartile; second quartile 0.6; 0.3-0.9, third quartile 0.7; 0.4-1.2, fourth quartile 0.6; 0.3-1.0) Conclusion: Our results suggest that promoting a healthy diet and reducing exposure to modifiable risk factors like environmental tobacco smoke, precarious housing conditions and certain disease vectors would have a significant positive impact on asthma and allergies morbidity in children in this region.

Objectives: This study aimed to explore the period between onset of pain and hospital-admission (pain-to-admission time) in patients with acute pancreatitis (AP), to investigate the prognostic value and associated factors of this time, and to ascertain the knowledge about the pancreas in these patients. Methods: An analysis of a prospective multicenter study was done, which included 188 patients with AP. Results: Median pain-to-admission time was 27 hours (interquartile range, 6.0-72.0). Median pain-to-admission time was significantly shorter in intensive care unit (ICU) patients (10 hours) compared to non-ICU patients (36 hours) (P = 0.045). Short pain-to-admission time was associated with high pain level. Median pain level (0, no pain; 10, maximal pain) was 8.0 (interquartile range, 7.0-10.0). Older age correlated with lower pain level (r = -0.26; P = 0.002). Multiple logistic regression analysis including the admission values for serum lipase and C-reactive protein and the corresponding interactions to the pain-to-admission time showed substantial discriminative ability regarding ICU admission (concordance index, 0.706; P = 0.006). 86% (112/130) knew that they have a pancreas, 72% (81/112) of these patients knew that AP exists, and 56% (45/81) recognized that AP is potentially fatal. Conclusions: Knowledge about AP in hospitalized AP patients is poor. Serum lipase and C-reactive protein in dependency of the pain-to-admission time might be a suitable predictor for severity of AP.

Background: Re-irradiation is a reasonable second treatment option for patients with recurrent malignant glioma (MG) after previous radio(chemo) therapy. However, only limited data is available allowing for a precise selection of patients suitable for re-treatment in regard to safety and efficacy. Methods: Using the department database, 58 patients with two courses of percutaneous radiation were identified. Besides classical dose-volume histogram (DVH) parameters equivalent uniform dose (EUD) values were calculated for the tumor and organs at risk (OARs), retrospectively analyzed and correlated to survival outcome parameters. Cumulative EUD values were also calculated in all cases where previous OAR DVHs were available. Results: Median follow-up was 265 days and no relevant toxicity was observed after re-irradiation in our patient cohort during follow-up. Time interval between first and second irradiation was regularly above 6 months. As a conservative estimation of the cumulative EUD to the OARs, the EUDs of first and second irradiation were added. Median cumulative EUD to the optic chiasm was 48.8 Gy (range, 2.5-76.5 Gy), 57.4 Gy (range, 2.7-75.3 Gy) to the brainstem, 20.9/22.1 Gy (range, 0.0-68.3 Gy) to the right/left optic nerve and 73.8 Gy (range, 64.9-77.3 Gy) to the brain. No correlation between treated volume and survival was seen. Conclusions: This study provides retrospective estimates on cumulative doses at the OARs. EUD values are derived and may serve as reference for further studies, including planning studies where specific constraints are needed.

Background: This study compared manually delineated gross tumour volume (GTV) and automatically generated biological tumour volume (BTV) based on fluoro-deoxy-glucose (FDG) positron emission tomography (PET)/CT to assess the robustness of predefined PET algorithms for radiotherapy (RT) planning in routine clinical practice. Methods: RT-planning data from 20 consecutive patients (lung-(40%), oesophageal-(25%), gynaecological-(25%) and colorectal (10%) cancer) who had undergone FDG-PET/CT planning between 08/2010 and 09/2011 were retrospectively analysed, five of them underwent neoadjuvant chemotherapy before radiotherapy. In addition to manual GTV contouring, automated segmentation algorithms were applied-among these 38%, 42%, 47% and 50% SUVmax as well as the PERCIST total lesion glycolysis (TLG) algorithm. Different ratios were calculated to assess the overlap of GTV and BTV including the conformity index and the ratio GTV included within the BTV. Results: Median age of the patients was 66 years and median tumour SUVmax 9.2. Median size of the GTVs defined by the radiation oncologist was 43.7 ml. Median conformity indices were between 30.0-37.8%. The highest amount of BTV within GTV was seen with the 38% SUVmax algorithm (49.0%), the lowest with 50% SUVmax (36.0%). Best agreement was obtained for oesophageal cancer patients with a conformity index of 56.4% and BTV within GTV ratio of 71.1%. Conclusions: At present there is only low concordance between manually derived GTVs and automatically segmented FDG-PET/CT based BTVs indicating the need for further research in order to achieve higher volumetric conformity and therefore to get access to the full potential of FDG-PET/CT for optimization of radiotherapy planning.

Background: 15% of patients with severe endometriosis suffer from pain symptoms in spite of pharmacological and surgical treatments. In this retrospective study we aimed to assess the effectiveness of a combined therapy of Traditional Chinese medicine and hypnotherapy (systemic autoregulation therapy, SART) as a novel treatment for endometriosis-associated symptoms. Patients and Methods: 47 patients with severe endometriosis, which were treated with SART, were followed-up by standardized telephone interviews. Follow-up data were compared to baseline assessments. Results: Median follow-up time was 5 years. The median intensity of endometriosis-associated pain had decreased from 8 to 3 points on a 0-10 point visual analogue scale (p < 0.001). 18 patients (38%) were free of pain, and the number of patients using pain medication had decreased from 38 to 19 (from 81% to 40%). 17 out of the 31 women trying for a pregnancy (55%) showed a total of 21 births at follow-up. Exploratory analyses revealed that larger decreases in pain scores correlated significantly with longer treatment durations, suggesting a dose-response relationship. Conclusion: Treatment of endometriosis with a holistic approach of Chinese medicine and hypnotherapy may result in a substantial reduction of pain as well as increased birth rates in patients with therapy-refractory endometriosis. Randomized controlled studies to further investigate the effectiveness of SART are highly warranted.

Objective: To characterize clinical features, CSF biomarkers and genetic polymorphisms of patients suffering from a rapidly progressing subtype of Alzheimer's dementia (rpAD). Methods: Retrospective analyses of 32 neuropathologically confirmed cases differentially diagnosed as AD out of a group with rapidly progressive dementia. CSF biomarkers (14-3-3, tau, beta-amyloid 1-42) and genetic markers (PRNP codon 129, apolipoprotein E, ApoE, polymorphism) were determined. Results: Median survival was 26 months, age at onset 73 years. Biomarkers: mean beta-amyloid 1-42: 266 pg/ml, median tau: 491 pg/ml, 14-3-3 positive: 31%. Genetic polymorphisms showed a predominance of methionine homozygosity at PRNP codon 129 and a low frequency of ApoE4 (38%, no homozygous patients). Thirty-five symptoms were studied. Frequent symptoms were myoclonus (75%), disturbed gait (66%) and rigidity (50%). Discussion: rpAD is associated with a diversity of neurological signs even able to mimic Creutz feldt-Jakob disease. Biomarkers and genetic profile differ from those seen in classical AD. The findings on biomarkers, symptomatology and genetics may aid the differential diagnostic process. Copyright (C) 2010 S. Karger AG, Basel

Background: Evaluation of the protein osteopontin (OPN) as a potential new marker in comparison to melanoma inhibitory activity (MIA) for screening and detection of metastatic uveal melanoma. Methods: Plasma levels of 32 patients with uveal melanoma were analyzed for OPN and MIA by enzyme-linked immunosorbent assay (ELISA). Fourteen of these patients had clinically detectable liver metastases. Results: Median plasma concentration of OPN in patients with metastatic disease was 152.01 ng/ml compared to 47.39 ng/ml in patients without clinically detectable metastases (p < 0.001). The difference between the median MIA plasma levels in patients with (13.11 ng/ml) and patients without (5.64 ng/ml) metastatic disease was also statistically significant (p < 0.001). No correlation could be found between MIA or OPN levels and tumor height in patients without clinically detectable metastases. Conclusion: The proteins MIA and OPN seem to be promising tumor markers for the metastasis screening in patients with uveal melanoma. Copyright (C) 2009 S. Karger AG, Basel

Background/Aims: Liver transplantation (LTx) is the only established treatment in patients with end-stage primary biliary cirrhosis (PBC). Although short-term survival after LTx in this group of patients is usually good, few data exist on the long-term survival. The optimal timing of transplantation is difficult. Thus, the aims of this study were to assess the long-term survival of patients with PBC after LTx and to identify potential predictive factors for a positive outcome. Methods: Survival of 28 patients with PBC who underwent LTx between 1985 and July 1999 in a single center was studied by Kaplan-Meier analysis and was compared to predicted survival without LTx using established prognostic models for PBC, the Mayo and European risk scores. Potential prognostic parameters obtained before LTx were tested for correlation to survival. Rates of bone fractures as markers of hepatic osteodystrophy were compared before and after LTx. Results: Median follow-up after LTx was 90 months with a maximum of 140 months. Actuarial survival of patients with PBC was 89% after 1, 5, and 10 years and was significantly better than estimated survival without LTx after 1-7 years as calculated by the Mayo and European risk scores. Of several parameters tested, only serum bilirubin and the prognostic scores, but no other liver function tests obtained immediately prior to transplantation were significantly correlated with survival after LTx. The duration of intensive care after LTx was not associated with any parameters obtained before LTx. Bone fractures were diagnosed in 43% of patients of whom the vast majority were osteopenic before LTx as determined by osteodensitometry. Conclusion: Longterm survival of a well-defined group of patients with PBC was excellent after LTx and was inversely correlated with preoperative serum bilirubin levels as well as Mayo and European risk scores. Copyright (C) 2000 S. Karger AG. Basel.