Web-based self-management for patients with lymphoma:Assessment of the reach of intervention of a randomized controlled trial

Background: Randomized controlled trials (RCTs) often provide accurate estimates of the internal validity of an intervention but lack information on external validity (generalizability). We conducted an RCT on the effectiveness of a self-management intervention among patients with lymphoma in a population-based setting. Objective: The objectives of the current study were to describe the proportion of RCT participants compared to all patients invited to participate, and compare sociodemographic and clinical characteristics of RCT participants with all respondents, all patients invited to participate, and all patients selected from the Netherlands Cancer Registry (NCR) to determine the reach of the intervention. An additional objective was to assess differences on RCT outcome variables between RCT and paper respondents. Methods: Patients with lymphoma or chronic lymphocytic leukemia ≥18 years old at diagnosis from 13 hospitals in the Netherlands were selected from the population-based NCR, which routinely collects data on sociodemographic and clinical characteristics. Eligible patients were invited to participate in an RCT and complete a questionnaire. Web-based completion determined RCT enrollment, whereas paper respondents were followed observationally. Results: A total of 1193 patients were selected from the NCR, 892 (74.77%) of whom were invited to participate in the trial by their hematologist after verifying eligibility. Among those invited, 25.4% (227/892) completed the web-based questionnaire and were enrolled in the RCT. The RCT participants were younger and there was a higher proportion of men than nonparticipants (P<.001). In addition, 25.7% (229/892) of those invited opted to participate in the paper-based observational follow-up study. Compared with paper respondents, RCT participants were younger (P<.001), with a higher proportion of men (P=.002), and had higher education levels (P=.02). RCT participants more often wanted to receive all available information on their disease (P<.001), whereas paper respondents reported higher levels of emotional distress (P=.009). Conclusions: From a population-based sample of eligible patients, the participation rate in the RCT was approximately 25%. RCT participants may not be representative of the target population because of different sociodemographic and clinical characteristics. Since RCT participants represent a minority of the target population, RCT results should be interpreted with caution as patients in the RCT may be those least in need of a self-management intervention. Trial Registration: Netherlands Trial Register NTR5953; https://www.trialregister.nl/trial/579

Human α2β1HI CD133+VE epithelial prostate stem cells express low levels of active androgen receptor

Stem cells are thought to be the cell of origin in malignant transformation in many tissues, but their role in human prostate carcinogenesis continues to be debated. One of the conflicts with this model is that cancer stem cells have been described to lack androgen receptor (AR) expression, which is of established importance in prostate cancer initiation and progression. We re-examined the expression patterns of AR within adult prostate epithelial differentiation using an optimised sensitive and specific approach examining transcript, protein and AR regulated gene expression. Highly enriched populations were isolated consisting of stem (α(2)β(1)(HI) CD133(+VE)), transiently amplifying (α(2)β(1)(HI) CD133(-VE)) and terminally differentiated (α(2)β(1)(LOW) CD133(-VE)) cells. AR transcript and protein expression was confirmed in α(2)β(1)(HI) CD133(+VE) and CD133(-VE) progenitor cells. Flow cytometry confirmed that median (±SD) fraction of cells expressing AR were 77% (±6%) in α(2)β(1)(HI) CD133(+VE) stem cells and 68% (±12%) in α(2)β(1)(HI) CD133(-VE) transiently amplifying cells. However, 3-fold lower levels of total AR protein expression (peak and median immunofluorescence) were present in α(2)β(1)(HI) CD133(+VE) stem cells compared with differentiated cells. This finding was confirmed with dual immunostaining of prostate sections for AR and CD133, which again demonstrated low levels of AR within basal CD133(+VE) cells. Activity of the AR was confirmed in prostate progenitor cells by the expression of low levels of the AR regulated genes PSA, KLK2 and TMPRSS2. The confirmation of AR expression in prostate progenitor cells allows integration of the cancer stem cell theory with the established models of prostate cancer initiation based on a functional AR. Further study of specific AR functions in prostate stem and differentiated cells may highlight novel mechanisms of prostate homeostasis and insights into tumourigenesis

Advantages of the Ilizarov external fixation in the management of intra-articular fractures of the distal tibia

<p>Abstract</p> <p>Background</p> <p>Treatment of distal tibial intra-articular fractures is challenging due to the difficulties in achieving anatomical reduction of the articular surface and the instability which may occur due to ligamentous and soft tissue injury. The purpose of this study is to present an algorithm in the application of external fixation in the management of intra-articular fractures of the distal tibia either from axial compression or from torsional forces.</p> <p>Materials and methods</p> <p>Thirty two patients with intra-articular fractures of the distal tibia have been studied. Based on the mechanism of injury they were divided into two groups. Group I includes 17 fractures due to axial compression and group II 15 fractures due to torsional force. An Ilizarov external fixation was used in 15 patients (11 of group I and 4 of group II). In 17 cases (6 of group I and 11 of group II) a unilateral hinged external fixator was used. In 7 out of 17 fractures of group I an additional fixation of the fibula was performed.</p> <p>Results</p> <p>All fractures were healed. The mean time of removal of the external fixator was 11 weeks for group I and 10 weeks for group II. In group I, 5 patients had radiological osteoarthritic lesions (grade III and IV) but only 2 were symptomatic. Delayed union occurred in 3 patients of group I with fixed fibula. Other complications included one patient of group II with subluxation of the ankle joint after removal of the hinged external fixator, in 2 patients reduction found to be insufficient during the postoperative follow up and were revised and 6 patients had a residual pain. The range of ankle joint motion was larger in group II.</p> <p>Conclusion</p> <p>Intra-articular fractures of the distal tibia due to axial compression are usually complicated with cartilaginous problems and are requiring anatomical reduction of the articular surface. Fractures due to torsional forces are complicated with ankle instability and reduction should be augmented with ligament repair, in order to restore normal movement of talus against the mortise. Both Ilizarov and hinged external fixators are unable to restore ligamentous stability. External fixation is recommended only for fractures of the ankle joint caused by axial compression because it is biomechanically superior and has a lower complication rate.</p

Pathological chemotherapy response score is prognostic in tubo-ovarian high-grade serous carcinoma: A systematic review and meta-analysis of individual patient data

There is a need to develop and validate biomarkers for treatment response and survival in tubo-ovarian high-grade serous carcinoma (HGSC). The chemotherapy response score (CRS) stratifies patients into complete/near-complete (CRS3), partial (CRS2), and no/minimal (CRS1) response after neoadjuvant chemotherapy (NACT). Our aim was to review current evidence to determine whether the CRS is prognostic in women with tubo-ovarian HGSC treated with NACT.This article is freely available via Open Access. Click on the Publisher URL to access the full-text via the publisher's site

Phase III Study of the Value of Thalidomide Added to Melphalan Plus Prednisone in Elderly Patients With Newly Diagnosed Multiple Myeloma: The HOVON 49 Study

Purpose For several decades, the treatment of elderly patients with multiple myeloma (MM) has consisted of melphalan and prednisone (MP). The Dutch-Belgium Hemato-Oncology Cooperative Group (HOVON) investigated the efficacy of thalidomide added to MP (MP-T) in a randomized phase III trial. The objective of this study was to investigate the efficacy, toxicity, and effects on quality of life of MP-T. Patients and Methods A randomized phase III trial compared standard MP with MP-T (thalidomide 200 mg/d) in newly diagnosed patients with multiple myeloma older than age 65 years. Maintenance therapy with thalidomide 50 mg/d was administered to patients after MP-T until relapse. The primary end point was event-free survival (EFS); response rate, overall survival (OS), and progression-free survival (PFS) were secondary end points. Results An intent-to-treat analysis of 333 evaluable patients showed significantly higher response rates in MP-T-treated patients compared with MP-treated patients a response (>= partial response: 66% v 45%, respectively; P = very good partial response [VGPR]: 27% v 10%, respectively; P < .001). EFS was 13 months with MP-T versus 9 months with MP (P < .001). OS was 40 months with MP-T versus 31 months with MP (P = .05). Conclusion This study demonstrates that thalidomide improves the response rate and VGPR in elderly patients with newly diagnosed MM. MP-T also results in a better EFS, PFS, and OS

Out of hospital anticoagulant therapy in patients with acute pulmonary embolism is frequently practised but not perfect

Introduction: Traditionally, patients with pulmonary embolism (PE) are treated in-hospital until they reach an adequate international normalized ratio (INR). Analogous to patients with a deep venous thrombosis, therapy with low-molecular-weight heparin facilitates out of hospital treatment of PE. We retrospectively analysed the current practice of early anticoagulant therapy in 86 acute PE patients with emphasis on the occurrence and safety of outpatient treatment. Methods: Data were collected from two large regional teaching hospitals and from a specialized anticoagulation clinical, where patients were followed in the period after hospital discharge. The course of hospitalization and LMWH transitioning therapy and the quality of treatment in the first three months after diagnosis were compared between patients discharged before and patients discharged after reaching adequate INR. Results: Forty-four patients (51.2%) were discharged early, before reaching an adequate INR, and 42 patients (48.8%) were discharged after reaching adequate INR. Early discharged patients needed more time to reach adequate INR compared to other patients (13 versus 6 days). In 28 patients (32.6%), the LMWH transitioning therapy was stopped prematurely; 21 patients were from the early discharged group. During the first 3 months, the mean individual times below, in and above the INR range were equal between the two groups. Conclusion: Enhanced compliance to existing guidelines and tools, and further development of guidelines, with focus on intensification of monitoring of INR values in an outpatient setting and preventing premature discontinuation of transitioning therapy, are warranted for a safe and early discharge of stable patients with PE

Interim Analysis on a Dutch HOVON Multicenter Randomized Open Label Phase II Trial on 3 Rituximab Dosing Schemes In Chronic ITP Patients

Stemcel biology/Regenerative medicine (incl. bloodtransfusion