Velocity of early BCR-ABL transcript elimination as an optimized predictor of outcome in chronic myeloid leukemia (CML) patients in chronic phase on treatment with imatinib

UNLABELLED Early assessment of response at 3 months of tyrosine kinase inhibitor treatment has become an important tool to predict favorable outcome. We sought to investigate the impact of relative changes of BCR-ABL transcript levels within the initial 3 months of therapy. In order to achieve accurate data for high BCR-ABL levels at diagnosis, beta glucuronidase (GUS) was used as a reference gene. Within the German CML-Study IV, samples of 408 imatinib-treated patients were available in a single laboratory for both times, diagnosis and 3 months on treatment. In total, 301 of these were treatment-naïve at sample collection. RESULTS (i) with regard to absolute transcript levels at diagnosis, no predictive cutoff could be identified; (ii) at 3 months, an individual reduction of BCR-ABL transcripts to the 0.35-fold of baseline level (0.46-log reduction, that is, roughly half-log) separated best (high risk: 16% of patients, 5-year overall survival (OS) 83% vs 98%, hazard ratio (HR) 6.3, P=0.001); (iii) at 3 months, a 6% BCR-ABL(IS) cutoff derived from BCR-ABL/GUS yielded a good and sensitive discrimination (high risk: 22% of patients, 5-year OS 85% vs 98%, HR 6.1, P=0.002). Patients at risk of disease progression can be identified precisely by the lack of a half-log reduction of BCR-ABL transcripts at 3 months.

Outcome of aplastic anaemia in children. A study by the severe aplastic anaemia and paediatric disease working parties of the European group blood and bone marrow transplant.

This study analysed the outcome of 563 Aplastic Anaemia (AA) children aged 0-12 years reported to the Severe Aplastic Anaemia Working Party database of the European Society for Blood and Marrow Transplantation, according to treatment received. Overall survival (OS) after upfront human leucocyte antigen-matched family donor (MFD) haematopoietic stem cell transplantation (HSCT) or immunosuppressive treatment (IST) was 91% vs. 87% (P 0·18). Event-free survival (EFS) after upfront MFD HSCT or IST was 87% vs. 33% (P 0·001). Ninety-one of 167 patients (55%) failed front-line IST and underwent rescue HSCT. The OS of this rescue group was 83% compared with 91% for upfront MFD HSCT patients and 97% for those who did not fail IST up-front (P 0·017). Rejection was 2% for MFD HSCT and HSCT post-IST failure (P 0·73). Acute graft-versus-host disease (GVHD) grade II-IV was 8% in MFD graft vs. 25% for HSCT post-IST failure (P < 0·0001). Chronic GVHD was 6% in MFD HSCT vs. 20% in HSCT post-IST failure (P < 0·0001). MFD HSCT is an excellent therapy for children with AA. IST has a high failure rate, but remains a reasonable first-line choice if MFD HSCT is not available because high OS enables access to HSCT, which is a very good rescue option.

Whole-Brain Susceptibility-Weighted Thrombus Imaging in Stroke: Fragmented Thrombi Predict Worse Outcome.

BACKGROUND AND PURPOSE The prevalence and clinical importance of primarily fragmented thrombi in patients with acute ischemic stroke remains elusive. Whole-brain SWI was used to detect multiple thrombus fragments, and their clinical significance was analyzed. MATERIALS AND METHODS Pretreatment SWI was analyzed for the presence of a single intracranial thrombus or multiple intracranial thrombi. Associations with baseline clinical characteristics, complications, and clinical outcome were studied. RESULTS Single intracranial thrombi were detected in 300 (92.6%), and multiple thrombi, in 24 of 324 patients (7.4%). In 23 patients with multiple thrombi, all thrombus fragments were located in the vascular territory distal to the primary occluding thrombus; in 1 patient, thrombi were found both in the anterior and posterior circulation. Only a minority of thrombus fragments were detected on TOF-MRA, first-pass gadolinium-enhanced MRA, or DSA. Patients with multiple intracranial thrombi presented with more severe symptoms (median NIHSS scores, 15 versus 11; P = .014) and larger ischemic areas (median DWI ASPECTS, 5 versus 7; P = .006); good collaterals, rated on DSA, were fewer than those in patients with a single thrombus (21.1% versus 44.2%, P = .051). The presence of multiple thrombi was a predictor of unfavorable outcome at 3 months (P = .040; OR, 0.251; 95% CI, 0.067-0.939). CONCLUSIONS Patients with multiple intracranial thrombus fragments constitute a small subgroup of patients with stroke with a worse outcome than patients with single thrombi.

Lordoplasty: midterm outcome of an alternative augmentation technique for vertebral fractures.

OBJECTIVE Vertebroplasty and balloon kyphoplasty are effective treatment options for osteoporotic vertebral compression fractures but are limited in correction of kyphotic deformity. Lordoplasty has been reported as an alternative, cost-effective, minimally invasive, percutaneous cement augmentation technique with good restoration of vertebral body height and alignment. The authors report on its clinical and radiological midterm results. METHODS A retrospective review was conducted of patients treated with lordoplasty from 2002 to 2014. Inclusion criteria were clinical and radiological follow-up evaluations longer than 24 months. Radiographs were accessed regarding initial correction and progressive loss of reduction. Complications and reoperations were recorded. Actual pain level, pain relief immediately after surgery, autonomy, and subjective impression of improvement of posture were assessed by questionnaire. RESULTS Sixty-five patients (46 women, 19 men, age range 38.9-86.2 years old) were treated with lordoplasty for 69 vertebral compression and insufficiency fractures. A significant correction of the vertebral kyphotic angle (mean 13°) and segmental kyphotic angle (mean 11°) over a mean follow-up of 33 months (range 24-108 months) was achieved (p < 0.001). On average, pain was relieved to 90% of the initial pain level. In 24% of the 65 patients a second spinal intervention was necessary: 16 distant (24.6%) and 7 adjacent (10.8%) new osteoporotic fractures, 4 instrumented stabilizations (6.2%), 1 new adjacent traumatic fracture (1.5%), and 1 distant microsurgical decompression (1.5%). Cement leakage occurred in 10.4% but was only symptomatic in 1 case. CONCLUSIONS Lordoplasty appeared safe and effective in midterm pain alleviation and restoration of kyphotic deformity in osteoporotic compression and insufficiency fractures. The outcomes of lordoplasty are consistent with other augmentation techniques.

Long-term Outcome After Monosegmental L4/5 Stabilization for Degenerative Spondylolisthesis With the Dynesys Device.

STUDY DESIGN Retrospective analysis of prospectively collected clinical data. OBJECTIVE To assess the long-term outcome of patients with monosegmental L4/5 degenerative spondylolisthesis treated with the dynamic Dynesys device. SUMMARY OF BACKGROUND DATA The Dynesys system has been used as a semirigid, lumbar dorsal pedicular stabilization device since 1994. Good short-term results have been reported, but little is known about the long-term outcome after treatment for degenerative spondylolisthesis at the L4/5 level. METHODS A total of 39 consecutive patients with symptomatic degenerative lumbar spondylolisthesis at the L4/5 level were treated with bilateral decompression and Dynesys instrumentation. At a mean follow-up of 7.2 years (range, 5.0-11.2 y), they underwent clinical and radiographic evaluation and quality of life assessment. RESULTS At final follow-up, back pain improved in 89% and leg pain improved in 86% of patients compared with preoperative status. Eighty-three percent of patients reported global subjective improvement. Ninety-two percent would undergo the surgery again. Eight patients (21%) required further surgery because of symptomatic adjacent segment disease (6 cases), late-onset infection (1 case), and screw breakage (1 case). In 9 cases, radiologic progression of spondylolisthesis at the operated segment was found. Seventy-four percent of operated segments showed limited flexion-extension range of <4 degrees. Adjacent segment pathology, although without clinical correlation, was diagnosed at the L5/S1 (17.9%) and L3/4 (28.2%) segments. In 4 cases, asymptomatic screw loosening was observed. CONCLUSIONS Monosegmental Dynesys instrumentation of degenerative spondylolisthesis at L4/5 shows good long-term results. The rate of secondary surgeries is comparable to other dorsal instrumentation devices. Residual range of motion in the stabilized segment is reduced, and the rate of radiologic and symptomatic adjacent segment degeneration is low. Patient satisfaction is high. Dynesys stabilization of symptomatic L4/5 degenerative spondylolisthesis is a possible alternative to other stabilization devices.

Spectral-domain optical coherence tomography study of macular structure as prognostic and determining factor for macular hole surgery outcome

Purpose: To evaluate postoperative spectral-domain optical coherence tomography findings after macular hole surgery. Methods: Retrospective, interventional, nonrandomized study. Overall, 164 eyes of 157 patients diagnosed with macular hole were operated on by vitrectomy and internal limiting membrane peeling. Preoperative and postoperative best-corrected visual acuity and spectral-domain optical coherence tomography images were obtained. Two groups were considered on the basis of the postoperative integrity of the back reflection line from the ellipsoid portion of the photoreceptor inner segment: group A (disruption of ellipsoid portion of the inner segment line, 60 eyes) and group B (restoration of ellipsoid portion of the inner segment line, 104 eyes). Results: Logarithm of the minimum angle of resolution best-corrected visual acuity improved significantly after the surgery of macular hole from a mean preoperative value of 0.79 ± 0.37 (range, 0.15–2.00) to a mean postoperative value of 0.35 ± 0.31 (range, 0.00–1.30) at the last follow-up visit (P < 0.01). Best-corrected visual acuity improved significantly in the 2 groups analyzed (all P < 0.01). A larger improvement was found in group B than in group A (P < 0.01). Conclusion: Ellipsoid portion of the inner segment line reconstruction seems to be a good prognostic factor for visual rehabilitation after macular hole surgery.

Bulgarian-Russian games in the energy sector: an outcome is getting closer. OSW Commentary No. 61, 2011-10-5

Bulgaria and Russia are entering the final phase of setting the conditions of their co-operation in the energy sector. A new gas contract is being negotiated because the currently applicable agreements will have expired by the end of 2012. The fate of two major energy projects – whose implementation depends on good co-operation between Sofia and Moscow: the Burgas– –Alexandroupolis oil pipeline and the construction of a Bulgarian nuclear power plant in Belene with Russian participation – is currently being decided. Another issue ever-present on the agenda is the future of the South Stream gas pipeline promoted by Russia, which is to run through Bulgarian territory. The outcome of all the aforementioned discussions and negotiations will determine for years the model of Bulgarian-Russian relations and may strongly affect the shape of the oil, gas and electricity markets in South-Eastern Europe.

Systematic review of outcome domains and instruments used in clinical trials of tinnitus treatments in adults

BACKGROUND: There is no evidence-based guidance to facilitate design decisions for confirmatory trials or systematic reviews investigating treatment efficacy for adults with tinnitus. This systematic review therefore seeks to ascertain the current status of trial designs by identifying and evaluating the reporting of outcome domains and instruments in the treatment of adults with tinnitus. METHODS: Records were identified by searching PubMed, EMBASE CINAHL, EBSCO, and CENTRAL clinical trial registries (ClinicalTrials.gov, ISRCTN, ICTRP) and the Cochrane Database of Systematic Reviews. Eligible records were those published from 1 July 2006 to 12 March 2015. Included studies were those reporting adults aged 18 years or older who reported tinnitus as a primary complaint, and who were enrolled into a randomised controlled trial, a before and after study, a non-randomised controlled trial, a case-controlled study or a cohort study, and written in English. Studies with fewer than 20 participants were excluded. RESULTS: Two hundred and twenty-eight studies were included. Thirty-five different primary outcome domains were identified spanning seven categories (tinnitus percept, impact of tinnitus, co-occurring complaints, quality of life, body structures and function, treatment-related outcomes and unclear or not specified). Over half the studies (55 %) did not clearly define the complaint of interest. Tinnitus loudness was the domain most often reported (14 %), followed by tinnitus distress (7 %). Seventy-eight different primary outcome instruments were identified. Instruments assessing multiple attributes of the impact of tinnitus were most common (34 %). Overall, 24 different patient-reported tools were used, predominantly the Tinnitus Handicap Inventory (15 %). Loudness was measured in diverse ways including a numerical rating scale (8 %), loudness matching (4 %), minimum masking level (1 %) and loudness discomfort level (1 %). Ten percent of studies did not clearly report the instrument used. CONCLUSIONS: Our findings indicate poor appreciation of the basic principles of good trial design, particularly the importance of specifying what aspect of therapeutic benefit is the main outcome. No single outcome was reported in all studies and there was a broad diversity of outcome instruments. PROSPERO REGISTRATION: The systematic review protocol is registered on PROSPERO (International Prospective Register of Systematic Reviews): CRD42015017525 . Registered on 12 March 2015 revised on 15 March 2016.

Six-month outcome for dysphagia following traumatic brain injury: Radiological assessment

The coexistence of a swallowing impairment, or dysphagia, can severely impact upon the medical condition and recovery of a child with traumatic brain injury (TBI; Logemann, Pepe, & Mackay, 1994). Despite this fact, there is limited data that provide evidence of the progression or outcome of dysphagia in the pediatric population post-TBI (Rowe, 1999). The present study aimed to (1) provide a prospective radiologically based profile of swallowing outcome and (2) determine the clinical significance of any persistent physiological swallowing deficits by investigating the presence/absence of any coexistent respiratory complications. Seven children with moderate/severe TBI were evaluated via an initial videofluoroscopic swallowing assessment (VFSS) at an average of 24.1 days postinjury, during the acute phase of management. A follow-up VFSS was conducted at an average of 7 months, 3 weeks postinjury. The physiological impairment, swallowing safety, swallowing efficiency, and functional swallowing outcomes of the acute phase post-TBI were compared with reassessment results at 6 months post-TBI. The presence/absence of lower respiratory tract infection/respiratory complications in the past 6 months postinjury were recorded.VFSS revealed a number of residual physiological oropharyngeal swallowing impairments and reduced swallowing efficiency. However, all participants presented with clinically safe and functional swallowing outcomes at 6 months post-TBI, with no recent history of respiratory complication. This study indicates good functional swallowing and respiratory outcomes for patients at 6-months post-TBI despite the presence of persistent physiological swallowing impairment.

Design of the low vision quality-of-life questionnaire (LVQOL) and measuring the outcome of low-vision rehabilitation

PURPOSE: To design and validate a vision-specific quality-of-life assessment tool to be used in a clinical setting to evaluate low-vision rehabilitation strategy and management. METHODS: Previous vision-related questionnaires were assessed by low-vision rehabilitation professionals and patients for relevance and coverage. The 74 items selected were pretested to ensure correct interpretation. One hundred and fifty patients with low vision completed the chosen questions on four occasions to allow the selection of the most appropriate items. The vision-specific quality of life of patients with low vision was compared with that of 70 age-matched and gender-matched patients with normal vision and before and after low-vision rehabilitation in 278 patients. RESULTS: Items that were unreliable, internally inconsistent, redundant, or not relevant were excluded, resulting in the 25-item Low Vision Quality-of-Life Questionnaire (LVQOL). Completion of the LVQOL results in a summed score between 0 (a low quality of life) and 125 (a high quality of life). The LVQOL has a high internal consistency (α = 0.88) and good reliability (0.72). The average LVQOL score for a population with low vision (60.9 ± 25.1) was significantly lower than the average score of those with normal vision (100.3 ± 20.8). Rehabilitation improved the LVQOL score of those with low vision by an average of 6.8 ± 15.6 (17%). CONCLUSIONS: The LVQOL was shown to be an internally consistent, reliable, and fast method for measuring the vision-specific quality of life of the visually impaired in a clinical setting. It is able to quantify the quality of life of those with low vision and is useful in determining the effects of low-vision rehabilitation. Copyright (C) 2000 Elsevier Science Inc.

Was it good for them? Reflections on the use of MENTOR and changes in course design using general performance measures

This paper considers the use of general performance measures in evaluating specific planning and design decisions in higher education and reflects on the students' learning process. Specifically, it concerns the use of the MENTOR multimedia computer aided learning package for helping students learn about OR as part of a general business degree. It includes the transfer of responsibility for a learning module to a new staff member and a change from a single tutor to a system involving multiple tutors. Student satisfaction measures, learning outcome measures and MENTOR usage patterns are examined in monitoring the effects of the changes in course delivery. The results raise some questions about the effectiveness of general performance measures in supporting specific decisions relating to course design and planning.

Methicillin-resistant Staphylococcus aureus bacteremia:epidemiology, outcome, and laboratory characteristics in a tertiary referral center in the UK

Objective: To analyze the recent epidemiology of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia in a UK tertiary referral center. Methods: We collected epidemiological and laboratory data on all cases of MRSA bacteremia from September 1, 2005 to December 31, 2007. Results: There were 195 clinically significant episodes. Most were hospital-acquired. Only one episode occurred in patients without a history of hospital admission in the previous 12 months. An intravascular device was the most common focus of infection (37%), with no identifiable source found in 35% of episodes. Twenty-eight percent of patients died within 30 days of bacteremia. Mortality was significantly higher in the absence of an identifiable focus. Failure to include an antibiotic active against MRSA in the empirical treatment was only significantly associated with death in patients showing signs of hemodynamic instability (p < 0.001). No isolates had a minimum inhibitory concentration to vancomycin above 1.5. mg/l and no heteroresistance to glycopeptide antibiotics (heteroresistant vancomycin-intermediate Staphylococcus aureus; hVISA) was detected. All isolates were sensitive to daptomycin, tigecycline, and linezolid. Conclusions: Despite improvement in infection control measures, medical devices remain the most common source of infection. Inappropriate empirical antibiotic usage is associated with a poor outcome in patients with signs of severe sepsis. Susceptibility to glycopeptides and newer antibiotics remains good. © 2010 International Society for Infectious Diseases.

TPEA good practice guide: lessons for cross-border MSP from transboundary planning in the European Atlantic

This Good Practice Guide is the outcome of a project co-funded by the European Commission (DG Mare) called Transboundary Planning in the European Atlantic (TPEA), which ran from December 2012 to May 2014. The aim of the project was to demonstrate approaches to transboundary maritime spatial planning (MSP) in the European Atlantic region. This is one of a series of projects exploring the opportunities and challenges of carrying out cross-border MSP in Europe’s regional seas, making connections with integrated coastal management (ICM). TPEA focused on two pilot areas: one involving Portugal and Spain and the other Ireland and the United Kingdom. Despite distinct identities in the region relating to different traditions of planning and stages of MSP implementation, TPEA worked towards a commonly-agreed approach to transboundary MSP and developed principles of cross-border working which it is hoped will be of wider benefit. This guide presents these principles, illustrated with examples from the TPEA project.

The Responsiveness, Content Validity, and Convergent Validity of the Measure Yourself Concerns and Wellbeing (MYCaW) Patient-Reported Outcome Measure

Objective Measure Yourself Concerns and Wellbeing (MYCaW) is a patient-centred questionnaire that allows cancer patients to identify and quantify the severity of their ‘Concerns’ and Wellbeing, as opposed to using a pre-determined list. MYCaW administration is brief and aids in prioritising treatment approaches. Our goal was to assess the convergent validity and responsiveness of MYCaW scores over time, the generalisability of the existing qualitative coding framework in different complementary and integrative healthcare settings and content validity. Methods Baseline and 6-week follow-up data (n=82) from MYCaW and FACIT-SpEx questionnaires were collected for a service evaluation of the ‘Living Well With The Impact of Cancer’ course at Penny Brohn Cancer Care. MYCaW construct validity was determined using Spearman's Rank Correlation test, and responsiveness indices assessed score changes over time. The existing qualitative coding framework was reviewed using a new dataset (n=158) and coverage of concern categories compared to items of existing outcome measures. Results Good correlation between MYCaW and FACIT-SpEx score changes were achieved (r= -0.57, p≥0.01). MYCaW Profile and Concern scores were highly responsive to change: SRM=1.02 and 1.08; effect size=1.26 and 1.22. MYCaW change scores showed the anticipated gradient of change according to clinically relevant degrees of change. Categories including ‘Spirituality’, ‘weight change’ and ‘practical concerns’ were added to the coding framework to improve generalisability. Conclusions MYCaW scores were highly responsive to change, allowing personalized patient outcomes to be quantified; the qualitative coding framework is generalisable across different oncology settings and has broader coverage of patient-identified concerns compared with existing cancer-related patient-reported outcome measures.