Current tools for prediction of arteriovenous fistula outcomes

It remains challenging to accurately predict whether an individual arteriovenous fistula (AVF) will mature and be useable for haemodialysis vascular access. Current best practice involves the use of routine clinical assessment and ultrasonography complemented by selective venography and magnetic resonance imaging. The purpose of this literature review is to describe current practices in relation to pre-operative assessment prior to AVF formation and highlight potential areas for future research to improve the clinical prediction of AVF outcomes.

Fluid balance, intradialytic hypotension, and outcomes in critically ill patients undergoing renal replacement therapy: a cohort study

Introduction: In this cohort study, we explored the relationship between fluid balance, intradialytic hypotension and outcomes in critically ill patients with acute kidney injury (AKI) who received renal replacement therapy (RRT).

Methods: We analysed prospectively collected registry data on patients older than 16 years who received RRT for at least two days in an intensive care unit at two university-affiliated hospitals. We used multivariable logistic regression to determine the relationship between mean daily fluid balance and intradialytic hypotension, both over seven days following RRT initiation, and the outcomes of hospital mortality and RRT dependence in survivors.

Results: In total, 492 patients were included (299 male (60.8%), mean (standard deviation (SD)) age 62.9 (16.3) years); 251 (51.0%) died in hospital. Independent risk factors for mortality were mean daily fluid balance (odds ratio (OR) 1.36 per 1000 mL positive (95% confidence interval (CI) 1.18 to 1.57), intradialytic hypotension (OR 1.14 per 10% increase in days with intradialytic hypotension (95% CI 1.06 to 1.23)), age (OR 1.15 per five-year increase (95% CI 1.07 to 1.25)), maximum sequential organ failure assessment score on days 1 to 7 (OR 1.21 (95% CI 1.13 to 1.29)), and Charlson comorbidity index (OR 1.28 (95% CI 1.14 to 1.44)); higher baseline creatinine (OR 0.98 per 10 mu mol/L (95% CI 0.97 to 0.996)) was associated with lower risk of death. Of 241 hospital survivors, 61 (25.3%) were RRT dependent at discharge. The only independent risk factor for RRT dependence was pre-existing heart failure (OR 3.13 (95% CI 1.46 to 6.74)). Neither mean daily fluid balance nor intradialytic hypotension was associated with RRT dependence in survivors. Associations between these exposures and mortality were similar in sensitivity analyses accounting for immortal time bias and dichotomising mean daily fluid balance as positive or negative. In the subgroup of patients with data on pre-RRT fluid balance, fluid overload at RRT initiation did not modify the association of mean daily fluid balance with mortality.

Conclusions: In this cohort of patients with AKI requiring RRT, a more positive mean daily fluid balance and intradialytic hypotension were associated with hospital mortality but not with RRT dependence at hospital discharge in survivors.

Molecular markers for predicting recurrence, progression and outcomes of bladder cancer (do the poster boys need new posters

Purpose of review
Molecular markers for bladder cancer recurrence and
progression continue to drive many research programmes.
Translating the laboratory findings into the clinical environment
where these markers are used in clinical decision making has
proved problematic. In the clinical arena, stage and grade are
still the main focus for decisions about patient management.
There is however an evolution in bladder cancer research from
single-marker/single-pathway research to a more global
assessment of the tumour cell with DNA microarrays and
proteomics.
Recent findings
In the last year, DNA microarray assessment has revealed
several interesting molecular markers such as p33ING1 and
DEK. Parallel ‘conventional’ single-pathway research has
focused on new novel markers such as HER2/neu, survivin and
matrix metalloproteinase 2 (MMP-2). Molecular markers that
have a long-standing association with bladder cancer
progression such as p53, E-cadherin and Ki-67 have been
reviewed by both single-marker studies and by microarray
studies and their status remains important.
Summary
It is an exciting time in the molecular biology research of bladder
cancer as the focus changes to assess the global genetic and
protein expression within tumour cells. From such a wealth of
information it is likely that molecular markers will make the
translation from benchside to bedside.

Survey of new 2007 and 2011 Cochrane reviews found 37% of prespecified outcomes not reported

OBJECTIVES: To survey the outcomes used in Cochrane Reviews, as part of our work within the Core Outcome Measures in Effectiveness Trials Initiative.

STUDY DESIGN AND SETTING: A descriptive survey of Cochrane Reviews, divided by Cochrane Review Group (CRG), published in full for the first time in 2007 and 2011. Outcomes specified in the methods section of each review and outcomes reported in the results section of each review were of interest, in this exploration of the common use of outcomes and core outcome sets (COS).

RESULTS: Seven hundred eighty-eight reviews, specifying 6,127 outcomes, were included. When we excluded specified outcomes from the 86 reviews that did not include any studies, we found that 1,996 (37%) specified outcomes were not reported. Of the 361 new reviews with studies from 2011, 113 (31%) had a "summary of findings" table (SoF). Fifteen broad outcome categories were identified and used to manage the outcome data. We found consistency in the use of these categories across CRGs but inconsistency in outcomes within these categories.

CONCLUSION: COS have been used rarely in Cochrane Reviews, but the introduction of SoF makes the development and application of COS timelier than ever.

Hypofractionated radiotherapy versus conventionally fractionated radiotherapy for patients with intermediate-risk localised prostate cancer: 2-year patient-reported outcomes of the randomised, non-inferiority, phase 3 CHHiP trial

BACKGROUND: Patient-reported outcomes (PROs) might detect more toxic effects of radiotherapy than do clinician-reported outcomes. We did a quality of life (QoL) substudy to assess PROs up to 24 months after conventionally fractionated or hypofractionated radiotherapy in the Conventional or Hypofractionated High Dose Intensity Modulated Radiotherapy in Prostate Cancer (CHHiP) trial.

METHODS: The CHHiP trial is a randomised, non-inferiority phase 3 trial done in 71 centres, of which 57 UK hospitals took part in the QoL substudy. Men with localised prostate cancer who were undergoing radiotherapy were eligible for trial entry if they had histologically confirmed T1b-T3aN0M0 prostate cancer, an estimated risk of seminal vesicle involvement less than 30%, prostate-specific antigen concentration less than 30 ng/mL, and a WHO performance status of 0 or 1. Participants were randomly assigned (1:1:1) to receive a standard fractionation schedule of 74 Gy in 37 fractions or one of two hypofractionated schedules: 60 Gy in 20 fractions or 57 Gy in 19 fractions. Randomisation was done with computer-generated permuted block sizes of six and nine, stratified by centre and National Comprehensive Cancer Network (NCCN) risk group. Treatment allocation was not masked. UCLA Prostate Cancer Index (UCLA-PCI), including Short Form (SF)-36 and Functional Assessment of Cancer Therapy-Prostate (FACT-P), or Expanded Prostate Cancer Index Composite (EPIC) and SF-12 quality-of-life questionnaires were completed at baseline, pre-radiotherapy, 10 weeks post-radiotherapy, and 6, 12, 18, and 24 months post-radiotherapy. The CHHiP trial completed accrual on June 16, 2011, and the QoL substudy was closed to further recruitment on Nov 1, 2009. Analysis was on an intention-to-treat basis. The primary endpoint of the QoL substudy was overall bowel bother and comparisons between fractionation groups were done at 24 months post-radiotherapy. The CHHiP trial is registered with ISRCTN registry, number ISRCTN97182923.

FINDINGS: 2100 participants in the CHHiP trial consented to be included in the QoL substudy: 696 assigned to the 74 Gy schedule, 698 assigned to the 60 Gy schedule, and 706 assigned to the 57 Gy schedule. Of these individuals, 1659 (79%) provided data pre-radiotherapy and 1444 (69%) provided data at 24 months after radiotherapy. Median follow-up was 50·0 months (IQR 38·4-64·2) on April 9, 2014, which was the most recent follow-up measurement of all data collected before the QoL data were analysed in September, 2014. Comparison of 74 Gy in 37 fractions, 60 Gy in 20 fractions, and 57 Gy in 19 fractions groups at 2 years showed no overall bowel bother in 269 (66%), 266 (65%), and 282 (65%) men; very small bother in 92 (22%), 91 (22%), and 93 (21%) men; small bother in 26 (6%), 28 (7%), and 38 (9%) men; moderate bother in 19 (5%), 23 (6%), and 21 (5%) men, and severe bother in four (<1%), three (<1%) and three (<1%) men respectively (74 Gy vs 60 Gy, ptrend=0.64, 74 Gy vs 57 Gy, ptrend=0·59). We saw no differences between treatment groups in change of bowel bother score from baseline or pre-radiotherapy to 24 months.

INTERPRETATION: The incidence of patient-reported bowel symptoms was low and similar between patients in the 74 Gy control group and the hypofractionated groups up to 24 months after radiotherapy. If efficacy outcomes from CHHiP show non-inferiority for hypofractionated treatments, these findings will add to the growing evidence for moderately hypofractionated radiotherapy schedules becoming the standard treatment for localised prostate cancer.

FUNDING: Cancer Research UK, Department of Health, and the National Institute for Health Research Cancer Research Network.

Preoperative radial artery volume flow is predictive of arteriovenous fistula outcomes

Objective: Guidelines recommend the creation of a wrist radiocephalic arteriovenous fistula (RAVF) as initial hemodialysis vascular access. This study explored the potential of preoperative ultrasound vessel measurements to predict AVF failure to mature (FTM) in a cohort of patients with end-stage renal disease in Northern Ireland

.Methods: A retrospective analysis was performed of all patients who had preoperative ultrasound mapping of upper limb blood vessels carried out from August 2011 to December 2014 and whose AVF reached a functional outcome by March 2015.

Results: There were 152 patients (97% white) who had ultrasound mapping andan AVF functional outcome recorded; 80 (54%) had an upper arm AVF created, and 69 (46%) had a RAVF formed. Logistic regression revealed that female gender (odds ratio [OR], 2.5; 95% confidence interval [CI], 1.12-5.55; P = .025), minimum venous diameter (OR, 0.6; 95% CI, 0.39-0.95; P = .029), and RAVF (OR, 0.4; 95% CI, 0.18-0.89; P = .026) were associated with FTM. On subgroup analysis of the RAVF group, RAVFs with an arterial volume flow <50 mL/min were seven times as likely to fail as RAVFs with higher volume flows (OR, 7.0; 95% CI, 2.35-20.87; P < .001).

Conclusions: In this cohort, a radial artery flow rate <50 mL/min was associated with a sevenfold increased risk of FTM in RAVF, which to our knowledge has not been previously reported in the literature. Preoperative ultrasound mapping adds objective assessment in the clinical prediction of AVF FTM.

Learning outcomes tracking system (L.O.T.S):seeing student progress as term progresses

At QUB we have constructed a system that allows students to self-assess their capability on the fine grained learning outcomes for a module and to update their record as the term progresses. In the system each of the learning outcomes are linked to the relevant teaching session (lectures and labs) and to [online] resources that students can access at any time. Students can structure their own learning experience to their needs to attain the learning outcomes. The system keeps a history of the student’s record, allowing the lecturer to observe how the students’ abilities progress over the term and to compare it to assessment results. The system also keeps of any of the resource links that student has clicked on.

Systematic review of tools to measure outcomes for young children with autism spectrum disorder

BACKGROUND: The needs of children with autism spectrum disorder (ASD) are complex and this is reflected in the number and diversity of outcomes assessed and measurement tools used to collect evidence about children's progress. Relevant outcomes include improvement in core ASD impairments, such as communication, social awareness, sensory sensitivities and repetitiveness; skills such as social functioning and play; participation outcomes such as social inclusion; and parent and family impact.

OBJECTIVES: To examine the measurement properties of tools used to measure progress and outcomes in children with ASD up to the age of 6 years. To identify outcome areas regarded as important by people with ASD and parents.

METHODS: The MeASURe (Measurement in Autism Spectrum disorder Under Review) research collaboration included ASD experts and review methodologists. We undertook systematic review of tools used in ASD early intervention and observational studies from 1992 to 2013; systematic review, using the COSMIN checklist (Consensus-based Standards for the selection of health Measurement Instruments) of papers addressing the measurement properties of identified tools in children with ASD; and synthesis of evidence and gaps. The review design and process was informed throughout by consultation with stakeholders including parents, young people with ASD, clinicians and researchers.

RESULTS: The conceptual framework developed for the review was drawn from the International Classification of Functioning, Disability and Health, including the domains 'Impairments', 'Activity Level Indicators', 'Participation', and 'Family Measures'. In review 1, 10,154 papers were sifted - 3091 by full text - and data extracted from 184; in total, 131 tools were identified, excluding observational coding, study-specific measures and those not in English. In review 2, 2665 papers were sifted and data concerning measurement properties of 57 (43%) tools were extracted from 128 papers. Evidence for the measurement properties of the reviewed tools was combined with information about their accessibility and presentation. Twelve tools were identified as having the strongest supporting evidence, the majority measuring autism characteristics and problem behaviour. The patchy evidence and limited scope of outcomes measured mean these tools do not constitute a 'recommended battery' for use. In particular, there is little evidence that the identified tools would be good at detecting change in intervention studies. The obvious gaps in available outcome measurement include well-being and participation outcomes for children, and family quality-of-life outcomes, domains particularly valued by our informants (young people with ASD and parents).

CONCLUSIONS: This is the first systematic review of the quality and appropriateness of tools designed to monitor progress and outcomes of young children with ASD. Although it was not possible to recommend fully robust tools at this stage, the review consolidates what is known about the field and will act as a benchmark for future developments. With input from parents and other stakeholders, recommendations are made about priority targets for research.

FUTURE WORK: Priorities include development of a tool to measure child quality of life in ASD, and validation of a potential primary outcome tool for trials of early social communication intervention.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42012002223.

FUNDING: The National Institute for Health Research Health Technology Assessment programme.

How Good Am I? Crude Self-Assessment vs. Examination

With the new academic year structure encouraging more in-term assessment to replace end-of-year examinations one of the problems we face is assessing students and keeping track of individual student learning without overloading the students and staff with excessive assessment burdens.
In the School of Electronics, Electrical Engineering and Computer Science, we have constructed a system that allows students to self-assess their capability on a simple Yes/No/Don’t Know scale against fine grained learning outcomes for a module. As the term progresses students update their record as appropriately, including selecting a Learnt option to reflect improvements they have gained as part of their studies.
In the system each of the learning outcomes are linked to the relevant teaching session (lectures and labs) and to online resources that students can access at any time. Students can structure their own learning experience to their needs and preferences in order to attain the learning outcomes.
The system keeps a history of the student’s record, allowing the lecturer to observe how the students’ abilities progress over the term and to compare it to assessment results. The system also keeps of any of the resource links that student has clicked on and the related learning outcome.
The initial work is comparing the accuracy of the student self-assessments with their performance in the related questions in the traditional end-of-year examination.

The association between anticholinergic medication burden and health related outcomes in the ‘oldest old’: A systematic review of the literature

Background: Increased exposure to anticholinergic medication is problematic, particularly in those aged 80 years and older.

Objective: The aim of this systematic review was to identify tools used to quantify anticholinergic medication burden and determine the most appropriate tool for use in longitudinal research, conducted in those aged 80 years and older.

Methods: A systematic literature search was conducted across six electronic databases to identify existing tools. Data extraction was conducted independently by two researchers; studies describing the development of each tool were also retrieved and relevant data extracted. An assessment of quality was completed for all studies. Tools were assessed in terms of their measurement of the association between anticholinergic medication burden and a defined set of clinical outcomes, their development and their suitability for use in longitudinal research; the latter was evaluated on the basis of criteria defined as the key attributes of an ideal anticholinergic risk tool.

Results: In total, 807 papers were retrieved, 13 studies were eligible for inclusion and eight tools were identified. Included studies were classed as ‘very good’ or ‘good’ following the quality assessment analysis; one study was unclassified. Anticholinergic medication burden as measured in studies was associated with impaired cognitive and physical function, as well as an increased frequency of falls. The Drug Burden Index (DBI) exhibited most of the key attributes of an ideal anticholinergic risk tool.

Conclusion: This review identified the DBI as the most appropriate tool for use in longitudinal research focused on older people and their exposure to anticholinergic medication burden.