Summary Background Fludarabine-based chemoimmunotherapy with rituximab is frequently used in patients with indolent and mantle-cell lymphomas who relapse after alkylating chemotherapy. We aimed to ...compare the efficacy and safety of rituximab with bendamustine or fludarabine in patients with relapsed, indolent, non-Hodgkin lymphoma and mantle-cell lymphoma. Methods For this randomised, non-inferiority, open-label, phase 3 trial, we recruited patients from 55 centres in Germany, who were subsequently randomised centrally according to prespecified randomisation lists with permuted blocks of randomly variable block size to rituximab (375 mg/m2 , day 1) plus either bendamustine (90 mg/m2 , days 1 and 2) or fludarabine (25 mg/m2 , days 1–3) every 28 days for a maximum of six 28-day cycles. Patients were aged 18 years or older with a WHO performance status of 0–2 and had relapsed or refractory indolent or mantle-cell lymphoma; patients refractory to regimens that included rituximab, bendamustine, or purine analogue drugs were excluded. Patients were stratified by histological subtypes of lymphoma and by their latest previous therapies. Treatment allocation was not masked. The primary endpoint was progression-free survival and the final analysis was completed per protocol. Non-inferiority of bendamustine plus rituximab versus fludarabine plus rituximab was defined as a difference of less than 15% in 1-year progression-free survival. The protocol was amended in July, 2006, after approval of rituximab maintenance (375 mg/m2 every 3 months for up to 2 years), which was then given to patients achieving a response to either trial treatment. This study is registered with ClinicalTrials.gov , number NCT01456351 (closed to enrolment, follow-up is ongoing). Findings Between Oct 8, 2003, and Aug 5, 2010, we randomly assigned 230 patients to treatment groups (116 bendamustine plus rituximab, 114 fludarabine plus rituximab). 11 patients were excluded for protocol violations and were not followed up further (two in the bendamustine plus rituximab group and nine in the fludarabine plus rituximab group). Thus, 219 patients were included in the per-protocol analysis (114 bendamustine plus rituximab, 105 fludarabine plus rituximab). 1-year progression-free survival with bendamustine plus rituximab was 0·76 (95% CI 0·68–0·84) and 0·48 (0·39–0·58) with fludarabine plus rituximab (non-inferiority p<0·0001). At a median follow-up of 96 months (IQR 73·2–112·9), median progression-free survival with bendamustine plus rituximab was 34·2 months (95% CI 23·5–52·7) and 11·7 months (8·0–16·1) with fludarabine plus rituximab (hazard ratio HR 0·54 95% CI 0·38–0·72, log-rank test p<0·0001). Safety outcomes were similar in both groups, with 46 serious adverse events recorded (23 in the bendamustine plus rituximab group and 23 in the fludarabine plus rituximab group), most commonly myelosuppression and infections. Interpretation In combination with rituximab, bendamustine was more effective than fludarabine, suggesting that bendamustine plus rituximab may be the preferred treatment option for patients with relapsed indolent and mantle-cell lymphomas. Funding Roche Pharma AG, Ribosepharm GmbH, Mundipharma GmbH, Studiengruppe indolente Lymphome (StiL).
Abstract Context The goal of end-of-life (EOL) communication and decision making is to create a shared understanding about a person’s values and treatment preferences that will lead to a plan of care ...that is consistent with these values and preferences. Improvements in communication and decision making at the EOL have been identified as a high priority from a patient and family point of view. Objectives The purpose of this study was to develop quality indicators related to EOL communication and decision making. Methods We convened a multidisciplinary panel of experts to develop definitions, a conceptual framework of EOL communication and decision making, and quality indicators using a modified Delphi method. We generated a list of potential items based on literature review and input from panel members. Panel members rated the items using a seven-point Likert scale (1 = very little importance to 7 = extremely important) over four rounds of review until consensus was achieved. Results About 24 of the 28 panel members participated in all four rounds of the Delphi process. The final list of quality indicators comprised 34 items, divided into the four categories of our conceptual framework: Advance care planning (eight items), Goals of care discussions (13 items), Documentation (five items), and Organization/System aspects (eight items). Eleven items were rated “extremely important” (median score). All items had a median score of five (moderately important) or greater. Conclusion We have developed definitions, a conceptual framework, and quality indicators that researchers and health care decision makers can use to evaluate and improve the quality of EOL communication and decision making.
Objectives The purpose of this study was to assess the prognostic utility of lipoprotein(a) Lp(a) in individuals with coronary artery disease (CAD). Background Data regarding an association between ...Lp(a) and cardiovascular (CV) risk in secondary prevention populations are sparse. Methods Plasma Lp(a) was measured in 6,708 subjects with CAD from 3 studies; data were then combined with 8 previously published studies for a total of 18,978 subjects. Results Across the 3 studies, increasing levels of Lp(a) were not associated with the risk of CV events when modeled as a continuous variable (odds ratio OR: 1.03 per log-transformed SD, 95% confidence interval CI: 0.96 to 1.11) or by quintile (Q5:Q1 OR: 1.05, 95% CI: 0.83 to 1.34). When data were combined with previously published studies of Lp(a) in secondary prevention, subjects with Lp(a) levels in the highest quantile were at increased risk of CV events (OR: 1.40, 95% CI: 1.15 to 1.71), but with significant between-study heterogeneity (p = 0.001). When stratified on the basis of low-density lipoprotein (LDL) cholesterol, the association between Lp(a) and CV events was significant in studies in which average LDL cholesterol was ≥130 mg/dl (OR: 1.46, 95% CI: 1.23 to 1.73, p < 0.001), whereas this relationship did not achieve statistical significance for studies with an average LDL cholesterol <130 mg/dl (OR: 1.20, 95% CI: 0.90 to 1.60, p = 0.21). Conclusions Lp(a) is significantly associated with the risk of CV events in patients with established CAD; however, there exists marked heterogeneity across trials. In particular, the prognostic value of Lp(a) in patients with low cholesterol levels remains unclear.
Patients with known Crohn's disease (CD) and an acute onset of severe abdominal pain attending an emergency room frequently undergo contrast-enhanced emergency computed tomography (CT) for ...complication assessment. To assess small bowel changes, an additional dedicated imaging procedure such as magnetic resonance enterography (MRE) is regularly performed. Therefore, these patients undergo two imaging procedures, although the clinical and diagnostic value of such an approach is not known. In a retrospective study, we compared the diagnostic value of a conventional abdominal CT with a dedicated small bowel MRE to assess bowel wall changes as well as typical complications in patients with advanced CD.
We retrospectively evaluated 53 patients with CD having a conventional abdominal multidetector-CT (MD-CT) and MRE within 2 days. Image quality and bowel inflammation was analyzed for each bowel segment. Lymph nodes, abscesses, and fistulas were evaluated.
For small bowel and colon assessment, there was no significant difference for image quality between CT and MRE. Inflammation diagnosis was not significantly different between CT (69.4%) and MRE (71.4%). Colonic inflammation was diagnosed in 30.2% based on CT and 14.3% based on MRE. The difference for the detection of lymph nodes was significant (CT 49; MRE 27), whereas the differences between fistula (CT 25, MRE 27) or abscesses (CT and MRE 32) detection were not significant.
In patients with known advanced CD with acute abdominal pain conventional abdominal MD-CT, which is frequently performed as an emergency imaging procedure, is sufficient for bowel wall assessment. Based on our data, additional dedicated small bowel imaging such as MRE seems not to be necessary.
Finding ECG Readers in Clinical Practice Drew, Barbara J., RN, PhD; Dracup, Kathleen, RN, PhD; Childers, Rory, MD ...
Journal of the American College of Cardiology,
08/2014, Letnik:
64, Številka:
5
Journal Article
Recenzirano
Odprti dostop
...there is an ever-shrinking pool of cardiologists who have the expertise or desire to read ECGs.
The perioperative bleeding risk associated with therapeutic anticoagulation at cardiac implantable electronic device implantation has previously been demonstrated to vary by the specific ...anticoagulant used. Although uninterrupted anticoagulation with warfarin appears to be safe, heparin products have been shown to increase the risk of perioperative bleeding. However, the risk associated with cardiac implantable electronic device implantation with anticoagulation using dabigatran, a novel oral direct thrombin inhibitor, is not known. We performed a prospective observational study of patients receiving dabigatran for anticoagulation who underwent cardiac implantable electronic device implantation from June 2011 through May 2012. The study end points included thromboembolic and bleeding complications within 30 days of surgery. Major bleeding complications were defined as bleeding requiring surgical intervention, prolongation of hospitalization, and discontinuation of the anticoagulant or transfusion of blood products within 30 days of surgery. Minor bleeding complications included the development of a hematoma not requiring additional intervention. The thrombotic end points included stroke, transient ischemic attack, myocardial infarction, pulmonary embolism, and deep vein thrombosis. A total of 25 patients were identified for inclusion. During the index hospitalization, no thromboembolic or bleeding complications developed. No major bleeding complications occurred within 30 days of surgery. One minor bleeding event (4%) occurred within 30 days of surgery in 1 patient who was also receiving dual antiplatelet therapy. In conclusion, although no thromboembolic or major bleeding events were observed, additional studies are required to define the optimal antithrombotic management in the perioperative period.
To assess the safety and efficacy of different doses of RTH258 applied as single intravitreal administration compared with ranibizumab 0.5 mg in patients with neovascular age-related macular ...degeneration (AMD).
Six-month, phase 1/2, prospective, multicenter, double-masked, randomized, ascending single-dose, active-controlled, parallel-group study.
A total of 194 treatment-naive patients, aged ≥50 years, with primary subfoveal choroidal neovascularization secondary to AMD.
Patients received a single intravitreal injection of RTH258 0.5 mg (n = 11), 3.0 mg (n = 31), 4.5 mg (n = 47), or 6.0 mg (n = 44), or ranibizumab 0.5 mg (n = 61).
The primary efficacy end point was the change from baseline to month 1 in central subfield thickness (CSFT) measured by spectral-domain optical coherence tomography. The secondary efficacy end point was the duration of treatment effect measured as time from the initial injection to receipt of post-baseline therapy (PBT) guided by protocol-defined criteria. Adverse events (AEs) were recorded throughout the study.
RTH258 demonstrated noninferiority compared with ranibizumab in mean change in CSFT from baseline to month 1 for the 4.5- and 6.0-mg dose groups (margin: 40 μm, 1-sided alpha 0.05). The difference in CSFT change at month 1 comparison with ranibizumab was 22.86 μm (90% confidence interval CI, −9.28 to 54.99) and 19.40 μm (95% CI, −9.00 to 47.80) for RTH258 4.5 and 6 mg, respectively. The median time to PBT after baseline therapy was 60 and 75 days for patients in the RTH258 4.5- and 6.0-mg groups, respectively, compared with 45 days for ranibizumab. Changes in best-corrected visual acuity with RTH258 were comparable to those observed with ranibizumab. The most frequent AEs reported for the RTH258 groups were conjunctival hemorrhage, eye pain, and conjunctival hyperemia; the majority of these events were mild in intensity.
This first-in-human study of RTH258 demonstrated noninferiority in the change in CSFT at 1 month for the 4.5- and 6.0-mg doses compared with ranibizumab and an increase of 30 days in the median time to PBT for the 6.0-mg dose. There were no unexpected safety concerns, and the results support the continued development of RTH258 for the treatment of neovascular AMD.
A Novel Extracorporeal CO2 Removal System Burki, Nausherwan K., MD, PhD, FCCP; Mani, Raj Kumar, MD, FCCP; Herth, Felix J.F., MD, FCCP ...
Chest,
2013, Letnik:
143, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Background Hypercapnic respiratory failure in patients with COPD frequently requires mechanical ventilatory support. Extracorporeal CO2 removal (ECCO2 R) techniques have not been systematically ...evaluated in these patients. Methods This is a pilot study of a novel ECCO2 R device that utilizes a single venous catheter with high CO2 removal rates at low blood flows. Twenty hypercapnic patients with COPD received ECCO2 R. Group 1 (n = 7) consisted of patients receiving noninvasive ventilation with a high likelihood of requiring invasive ventilation, group 2 (n = 2) consisted of patients who could not be weaned from noninvasive ventilation, and group 3 (n = 11) consisted of patients on invasive ventilation who had failed attempts to wean. Results The device was well tolerated, with complications and rates similar to those seen with central venous catheterization. Blood flow through the system was 430.5 ± 73.7 mL/min, and ECCO2 R was 82.5 ± 15.6 mL/min and did not change significantly with time. Invasive ventilation was avoided in all patients in group 1 and both patients in group 2 were weaned; Pa CO2 decreased significantly ( P < .003) with application of the device from 78.9 ± 16.8 mm Hg to 65.9 ± 11.5 mm Hg. In group 3, three patients were weaned, while the level of invasive ventilatory support was reduced in three patients. One patient in group 3 died due to a retroperitoneal bleed following catheterization. Conclusions This single-catheter, low-flow ECCO2 R system provided clinically useful levels of CO2 removal in these patients with COPD. The system appears to be a potentially valuable additional modality for the treatment of hypercapnic respiratory failure. Trial registry ClinicalTrials.gov; No.: NCT00987740 and 01021605; URL: www.clinicaltrials.gov
We report the case of a 26-year-old female patient with Marfan syndrome and an aberrant right subclavian artery (ARSA) with associated Kommerell diverticulum. The patient presented with spontaneous ...acute dissection of the ARSA that showed fusiform dilation to 4 cm in diameter. Definitive treatment was performed using a two-stage hybrid endovascular technique, including extrathoracic bilateral upper extremity bypass and thoracic endovascular aortic repair with debranching of the right and left subclavian arteries. This was followed by coil and plug embolization to exclude the dissection and prevent subsequent endoleak.
The rapid technological developments of the past decade and the changes in echocardiographic practice brought about by these developments have resulted in the need for updated recommendations to the ...previously published guidelines for cardiac chamber quantification, which was the goal of the joint writing group assembled by the American Society of Echocardiography and the European Association of Cardiovascular Imaging. This document provides updated normal values for all four cardiac chambers, including three-dimensional echocardiography and myocardial deformation, when possible, on the basis of considerably larger numbers of normal subjects, compiled from multiple databases. In addition, this document attempts to eliminate several minor discrepancies that existed between previously published guidelines.
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