Phase III, two arm, multi-centre, open label, parallel-group randomised designed clinical investigation of the use of a personalised early warning decision support system to predict and prevent acute exacerbations of chronic obstructive pulmonary disease: 'Predict & Prevent AECOPD' - study protocol.

INTRODUCTION: With 65 million cases globally, chronic obstructive pulmonary disease (COPD) is the fourth leading cause of death and imposes a heavy burden on patients' lives and healthcare resources worldwide. Around half of all patients with COPD have frequent (≥2 per year) acute exacerbations of COPD (AECOPD). Rapid readmissions are also common. Exacerbations impact significantly on COPD outcomes, causing significant lung function decline. Prompt exacerbation management optimises recovery and delays the time to the next acute episode. METHODS/ANALYSIS: The Predict & Prevent AECOPD trial is a phase III, two arm, multi-centre, open label, parallel-group individually randomised clinical trial investigating the use of a personalised early warning decision support system (COPDPredict) to predict and prevent AECOPD. We aim to recruit 384 participants and randomise each individual in a 1:1 ratio to either standard self-management plans with rescue medication (RM) (control arm) or COPDPredict with RM (intervention arm).The trial will inform the future standard of care regarding management of exacerbations in COPD patients. The main outcome measure is to provide further validation, as compared with usual care, for the clinical effectiveness of COPDPredict to help guide and support COPD patients and their respective clinical teams in identifying exacerbations early, with an aim to reduce the total number of AECOPD-induced hospital admissions in the 12 months following each patient's randomisation. ETHICS AND DISSEMINATION: This study protocol is reported in accordance with the guidance set out in the Standard Protocol Items: Recommendations for Interventional Trials statement. Predict & Prevent AECOPD has obtained ethical approval in England (19/LO/1939). On completion of the trial and publication of results a lay findings summary will be disseminated to trial participants. TRIAL REGISTRATION NUMBER: NCT04136418.

Outcomes following acute poor-grade aneurysmal subarachnoid bleed - Is early definitive treatment better than delayed management?

BACKGROUND/OBJECTIVE: Patients with poor-grade subarachnoid bleed (World Federation of Neurosurgical Societies grades 4-5) often improve their neurocognitive function months after their ictus. However, it is essential to explore the timing of intervention and its impact on long-term outcome. We compared the long-term outcomes between immediate management within 24 h and delayed management after 24 h in patients following poor-grade subarachnoid bleed. METHODS: This was a retrospective population-based study, including patients with poor-grade subarachnoid bleed who received definitive management between 1 January 2011 and 31 December 2016 in a large tertiary neurocritical care unit. The primary outcome was adjusted odds ratio of favourable outcome (Glasgow Outcome Scale 4-5) for survivors at 12 months following discharge, as measured by the Glasgow Outcome Scale. The secondary outcomes included adjusted odds ratio of a favourable outcome at discharge, 3 months and 6 months following discharge and survival rate at 28 days, 3 months, 6 months and 12 months following haemorrhage. RESULTS: A total of 111 patients were included in this study: 53 (48%) received immediate management and 58 (52%) received delayed management. The mean time delay from referral to intervention was 14.9 ± 5.8 h in immediate management patients, compared to 79.6 ± 106.1 h in delayed management patients. At 12 months following discharge, the adjusted odds ratio for favourable outcome in immediate management versus delayed management patients was 0.96 (confidence interval (CI) = 0.17, 5.39; p = 0.961). At hospital discharge, 3 months and 6 months, the adjusted odds ratio for favourable outcome was 3.85 (CI = 1.38, 10.73; p = 0.010), 1.04 (CI = 0.22, 5.00; p = 0.956) and 0.98 (CI = 0.21, 4.58; p = 0.982), respectively. There were no differences in survival rate between the groups at 28 days, 3 months, 6 months and 12 months (71.7% in immediate management group vs. 82.8% in delayed management group at 12 months, p = 0.163). CONCLUSIONS: Immediate management and delayed management after poor-grade subarachnoid bleed are associated with similar morbidity and mortality at 12 months. Therefore, delaying intervention in poor-grade patients may be a reasonable approach, especially if time is needed to plan the procedure or stabilise the patient adequately.

Prevalence of peripapillary choroidal neovascular membranes (PPCNV) in an elderly UK population-the Bridlington eye assessment project (BEAP): a cross-sectional study (2002-2006).

PURPOSE: There is paucity of data on the epidemiology of peripapillary choroidal neovascularisartion (PPCNV). Our aim was to determine prevalence of PPCNV in the elderly UK population of Bridlington residents aged ≥65 years. METHODS: Eyes with PPCNV in the Bridlington eye assessment project (BEAP) database of 3475 participants were analysed. PPCNV outline was drawn, its area measured, and clock-hour involvement of disc circumference recorded. Location and shortest distance from the lesion edge to fovea were recorded. Masked grading for age-related maculopathy (ARM)/reticular pseudodrusen (RPD) within the ETDRS grid was assigned for each eye using a modified Rotterdam scale. Peripapillary retinal pigment epithelial (RPE) changes/drusen were recorded. Visual acuity (VA) and demographic details analysed separately were merged with grading data. RESULTS: PPCNV were identified in ten subjects, and were bilateral in two (20%), a population prevalence of 0.29%, and 0.06% bilaterality. Gender-specific prevalence were 0.36% and 0.19% for females and males, respectively. Age ranged from 66 to 85 years [mean 76.3 (SD 6.4)]. PPCNV were located nasal to disc in 41.7%, measuring 0.46-7.93 mm2 [mean 2.81 mm2 (SD 2.82)]. All PPCNV eyes had peripapillary RPE changes. One subject had no ARM, 1 angioid streaks, and 30% RPD. No direct foveal involvement, or reduced VA attributable to PPCNV was observed. CONCLUSION: PPCNV were infrequent in this population, more common in females, and often located nasal to the disc, without foveal extension. Peripapillary degenerative changes were universal, and strong association with ARM was observed in eyes with PPCNV. Typically, PPCNV were asymptomatic with VA preservation.

Prevalence of reticular pseudodrusen in an elderly UK Caucasian population-The Bridlington Eye Assessment Project (BEAP): a cross-sectional study (2002-2006).

AIMS: To determine prevalence, associations, and risk factors for reticular pseudodrusen (RPD) in a UK population. METHODS: Cross-sectional study of Bridlington residents aged ≥65 years. Masked grading of colour fundus photographs from 3549 participants. RPD presence, phenotype, and topography were recorded, demographic details were analysed, and prevalence was calculated. RESULTS: RPD was detected in 281 eyes (176 individuals) of 3476 participants (5.06%) with gradable images, and bilateral in 76.6%. Digital enhancement increased detection by 15.7%. Prevalence increased significantly with age from 1.18% (65-69 years) to 27.27% (≥90 years) (mean age 81.1, SD 6.01; OR 1.18, 95% CI 1.15-1.21, p value <0.001), was higher in females (5.9% vs 4.0%; OR 1.52, 95% CI 1.09-2.13, p = 0.014), and associated with diabetes (OR 1.97, CI 1.20-3.17, p = 0.005). History of antihypertension treatment appeared protective (OR 0.64, 95% CI 0.46-0.90, p = 0.009). RPD subtypes were dot in 18.5%, ribbon in 36.7%, and mixed in 36.3%. RPD were located outside the ETDRS grid in 88%, and most commonly in the outer superior subfield. Central grid involvement occurred in 12.1% of right and 14.3% of left eyes. RPD occurred in 25.9% of participants with grade 4 AMD in at least one eye. RPD was associated with visual dissatisfaction after controlling for age (OR 0.63, 95% CI 0.45-0.88, p = 0.007). CONCLUSION: RPD occur more commonly than previously reported, most frequently in the upper-outer macular subfield, but also within the central subfield, albeit with reduced frequency and altered morphology. RPD may be associated with visual dissatisfaction and diabetes, but are less frequent in persons receiving antihypertension therapy.

Interpreting the Tinnitus Questionnaire (German version): what individual differences are clinically important?

OBJECTIVE: Reporting of clinical significance is recommended because findings can be statistically significant without being relevant to patients. For aiding clinical interpretation of the Tinnitus Questionnaire (TQ), many investigators use a 5-point change cut-off as a minimal clinically important difference (MCID). But there are shortcomings in how this value was originally determined. DESIGN: The MCID was evaluated by analysing retrospective clinical data on the TQ (German version). Following recommended standards, multiple estimates were computed using anchor- and distribution-based statistical methods. These took into account not only patients' experience of clinical improvement, but also measurement reliability. STUDY SAMPLE: Pre- and post-intervention scores were assessed for 202 patients. RESULTS: Our six estimates ranged from 5 to 21 points in TQ change score from pre- to post- intervention. The 5-point TQ change score was obtained using a method that considered change between groups, and did not account for measurement error or bias. The size of the measurement error was considerable, and this comprises interpretation of individual patient change scores. CONCLUSIONS: To enhance confidence that a TQ change over time in individual patients is clinically meaningful, we advise at least the median MCID of 12 points.

Author Response to Sabour (2018), "Comment on Hall et al. (2017), 'How to Choose Between Measures of Tinnitus Loudness for Clinical Research? A Report on the Reliability and Validity of an Investigator-Administered Test and a Patient-Reported Measure Using Baseline Data Collected in a Phase IIa Drug Trial'".

PURPOSE: The authors respond to a letter to the editor (Sabour, 2018) concerning the interpretation of validity in the context of evaluating treatment-related change in tinnitus loudness over time. METHOD: The authors refer to several landmark methodological publications and an international standard concerning the validity of patient-reported outcome measurement instruments. RESULTS: The tinnitus loudness rating performed better against our reported acceptability criteria for (face and convergent) validity than did the tinnitus loudness matching test. CONCLUSION: It is important to distinguish between tests that evaluate the validity of measuring treatment-related change over time and tests that quantify the accuracy of diagnosing tinnitus as a case and non-case.

Assessing the impact of the introduction of an electronic hospital discharge system on the completeness and timeliness of discharge communication: a before and after study.

BACKGROUND: Hospital discharge summaries are a key communication tool ensuring continuity of care between primary and secondary care. Incomplete or untimely communication of information increases risk of hospital readmission and associated complications. The aim of this study was to evaluate whether the introduction of a new electronic discharge system (NewEDS) was associated with improvements in the completeness and timeliness of discharge information, in Nottingham University Hospitals NHS Trust, England. METHODS: A before and after longitudinal study design was used. Data were collected using the gold standard auditing tool from the Royal College of Physicians (RCP). This tool contains a checklist of 57 items grouped into seven categories, 28 of which are classified as mandatory by RCP. Percentage completeness (out of the 28 mandatory items) was considered to be the primary outcome measure. Data from 773 patients discharged directly from the acute medical unit over eight-week long time periods (four before and four after the change to the NewEDS) from August 2010 to May 2012 were extracted and evaluated. Results were summarised by effect size on completeness before and after changeover to NewEDS respectively. The primary outcome variable was represented with percentage of completeness score and a non-parametric technique was used to compare pre-NewEDS and post-NewEDS scores. RESULTS: The changeover to the NewEDS resulted in an increased completeness of discharge summaries from 60.7% to 75.0% (p < 0.001) and the proportion of summaries created under 24 h from discharge increased significantly from 78.0% to 93.0% (p < 0.001). Furthermore, five of the seven grouped checklist categories also showed significant improvements in levels of completeness (p < 0.001), although there were reduced levels of completeness for three items (p < 0.001). CONCLUSION: The introduction of a NewEDS was associated with a significant improvement in the completeness and timeliness of hospital discharge communication.

How to Choose Between Measures of Tinnitus Loudness for Clinical Research? A Report on the Reliability and Validity of an Investigator-Administered Test and a Patient-Reported Measure Using Baseline Data Collected in a Phase IIa Drug Trial.

PURPOSE: Loudness is a major auditory dimension of tinnitus and is used to diagnose severity, counsel patients, or as a measure of clinical efficacy in audiological research. There is no standard test for tinnitus loudness, but matching and rating methods are popular. This article provides important new knowledge about the reliability and validity of an audiologist-administered tinnitus loudness matching test and a patient-reported tinnitus loudness rating. METHOD: Retrospective analysis of loudness data for 91 participants with stable subjective tinnitus enrolled in a randomized controlled trial of a novel drug for tinnitus. There were two baseline assessments (screening, Day 1) and a posttreatment assessment (Day 28). RESULTS: About 66%-70% of the variability from screening to Day 1 was attributable to the true score. But measurement error, indicated by the smallest detectable change, was high for both tinnitus loudness matching (20 dB) and tinnitus loudness rating (3.5 units). Only loudness rating captured a sensation that was meaningful to people who lived with the experience of tinnitus. CONCLUSIONS: The tinnitus loudness rating performed better against acceptability criteria for reliability and validity than did the tinnitus loudness matching test administered by an audiologist. But the rating question is still limited because it is a single-item instrument and is probably able to detect only large changes (at least 3.5 points).

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.

Choosing which ear to implant in adult candidates with functional residual hearing.

This study examined whether audiologists consider the potential benefits of contralateral hearing aid use following cochlear implantation when recommending which ear to implant in UK adult candidates with residual hearing. Thirty-four audiologists from providers of adult implantation services completed a decision-choice experiment. Clinicians were willing to consider recommending that the poorer ear be implanted, provided it had been aided continuously, suggesting that their decision making seeks to preserve access to residual hearing in the non-implanted ear where possible. Future approaches to determining candidacy should therefore consider that a sub-set of patients may obtain additional benefit from this residual hearing following implantation.

A real-time electronic alert to improve detection of acute kidney injury in a large teaching hospital.

BACKGROUND: Acute kidney injury (AKI) is a common and serious problem in hospitalized patients. Early detection is critical for optimal management but in practice is currently inadequate. To improve outcomes in AKI, development of early detection tools is essential. METHODS: We developed an automated real-time electronic alert system employing algorithms which combined internationally recognized criteria for AKI [Risk, Injury, Failure, Loss, End-stage kidney disease (RIFLE) and Acute Kidney Injury Network (AKIN)]. All adult patients admitted to Nottingham University Hospitals were included. Where a patient's serum creatinine increased sufficiently to define AKI, an electronic alert was issued, with referral to an intranet-based AKI guideline. Incidence of AKI Stages 1-3, in-hospital mortality, length of stay and distribution between specialties is reported. RESULTS: Between May 2011 and April 2013, 59,921 alerts resulted from 22,754 admission episodes, associated with 15,550 different patients. Overall incidence of AKI for inpatients was 10.7%. Highest AKI stage reached was: Stage 1 in 7.2%, Stage 2 in 2.2% and Stage 3 in 1.3%. In-hospital mortality for all AKI stages was 18.5% and increased with AKI stage (12.5, 28.4, 35.7% for Stages 1, 2 and 3 AKI, respectively). Median length of stay was 9 days for all AKI. CONCLUSIONS: This is the first fully automated real time AKI e-alert system, using AKIN and RIFLE criteria, to be introduced to a large National Health Service hospital. It has provided one of the biggest single-centre AKI datasets in the UK revealing mortality rates which increase with AKI stage. It is likely to have improved detection and management of AKI. The methodology is transferable to other acute hospitals.

Preferred retinal locus profile during prolonged fixation attempts.

OBJECTIVE: The retinal area or location used during any fixation attempt defines the preferred retinal locus (PRL). It is presumed that during prolonged fixation attempts there may be various representative reference points within the PRL area. This study aims to clarify this presumption. DESIGN: Prospective, nonrandomized, observational case series. PARTICIPANTS: Sixty-five eyes of 41 patients from the University of Nottingham, Queen's Medical Centre Retina and Low Vision Clinics. METHODS: A total of 65 eyes of 41 patients from the University of Nottingham, Queen's Medical Centre Retina and Low Vision Clinics were assessed for PRL using the Macular Integrity Assessment (MAIA) microperimetry equipment (CenterVue, Padova, Italy). The MAIA allows automatic calculation for 2 points named PRL_initial (PRLi), which is calculated after the first 10 seconds of fixation, and PRL_final (PRLf), which is calculated after the completion of all fixation attempts during the microperimetry test. RESULTS: Estimates of PRLi and PRLf were produced for all patients. Forty-six (71%) eyes were classified as having stable fixation; 40 of the 46 eyes (87%) had both PRLs location over the fovea centralis. Nineteen of 65 eyes (29%) were classified as having unstable or relatively unstable fixation; different PRLi and PRLf locations were found in 18 (95%) of the 19 eyes, including 13 (68%) with central geographic atrophy secondary to dry age-related macular degeneration. The mean rate of change was 5.3 units in fixation per unit change in distance in both PRLi and PRLf. CONCLUSIONS: The representative points during prolonged fixation attempts may vary at different stages of fixation. This is reflected in the characteristics of fixation stability of the patients and presents a possible association with main pathology responsible for low vision.

The prevalence and nature of prescribing and monitoring errors in English general practice: a retrospective case note review.

BACKGROUND: Relatively little is known about prescribing errors in general practice, or the factors associated with error. AIM: To determine the prevalence and nature of prescribing and monitoring errors in general practices in England. DESIGN AND SETTING: Retrospective case-note review of unique medication items prescribed over a 12-month period to a 2% random sample of patients. Fifteen general practices across three primary care trusts in England. METHOD: A total of 6048 unique prescription items prescribed over the previous 12 months for 1777 patients were examined. The data were analysed by mixed effects logistic regression. The main outcome measures were prevalence of prescribing and monitoring errors, and severity of errors, using validated definitions. RESULTS: Prescribing and/or monitoring errors were detected in 4.9% (296/6048) of all prescription items (95% confidence interval [CI] = 4.4% to 5.5%). The vast majority of errors were of mild to moderate severity, with 0.2% (11/6048) of items having a severe error. After adjusting for covariates, patient-related factors associated with an increased risk of prescribing and/or monitoring errors were: age <15 years (odds ratio [OR] = 1.87, 95% CI = 1.19 to 2.94, P = 0.006) or >64 years (OR = 1.68, 95% CI = 1.04 to 2.73, P = 0.035), and higher numbers of unique medication items prescribed (OR = 1.16, 95% CI = 1.12 to 1.19, P<0.001). CONCLUSION: Prescribing and monitoring errors are common in English general practice, although severe errors are unusual. Many factors increase the risk of error. Having identified the most common and important errors, and the factors associated with these, strategies to prevent future errors should be developed, based on the study findings.

The diagnostic and prognostic value of tissue Doppler imaging during dobutamine stress echocardiography in end-stage renal disease.

OBJECTIVE: To determine whether a quantitative measurement of peak systolic velocity (PSV) during dobutamine stress echocardiography (DSE) detects severe coronary artery disease (CAD) and predicts mortality in patients with end-stage renal disease. METHODS: One hundred and forty renal transplant candidates had DSE and coronary angiography. DSE analysis was performed using conventional visual wall motion assessment, longitudinal PSV, and combining the two modalities. Failure of PSV to rise by more than 50% predicted an ischemic response. Significant CAD was defined as luminal stenosis greater than 70%. RESULTS: The number of positive DSE studies according to conventional, PSV, and combined criteria was 41 (30%), 42 (31%), and 46 (34%) respectively. Forty patients (29%) had significant CAD at angiography. The sensitivity, specificity, positive and negative predictive values for conventional DSE analysis were 84, 91, 86, and 90% respectively. The same values for PSV analysis were 86, 92, 86, and 91%, respectively. The same values for the combination of visual and PSV analysis were 88, 94, 87, and 92% respectively. The differences between the three methods were not statistically significant. Sensitivity for single-vessel CAD (P=0.05) and circumflex artery disease (P=0.05) diagnosis was higher with PSV compared with conventional DSE analysis. Failure of PSV to rise by more than 50% during DSE was associated with significantly increased mortality (P=0.001). CONCLUSION: A quantitative interpretation of DSE, based on the percentage rise of PSV during stress, accurately detects CAD and predicts prognosis in end-stage renal disease.

Evaluation of ischaemia-modified albumin as a marker of myocardial ischaemia in end-stage renal disease.

The early diagnosis of myocardial ischaemia is problematic in patients with ESRD (end-stage renal disease). The aim of the present study was to determine whether IMA (ischaemia-modified albumin) increases during dobutamine stress and detects myocardial ischaemia in patients with ESRD. A total of 114 renal transplant candidates were studied prospectively, and all received DSE (dobutamine stress echocardiography). IMA levels were taken at baseline and 1 h after cessation of DSE. A total of 35 patients (31%) had a positive DSE result. Baseline IMA levels were not significantly different in the DSE-positive and -negative groups. The increase in IMA was significantly higher in the DSE-positive group compared with those with no ischaemic response (26.5 +/- 19.1 compared with 8.2 +/- 9.6 kU/l respectively; P = 0.007; where kU is kilo-units). From ROC (receiver operator charactertistic) curve analysis, the optimal IMA increase to predict an ischaemic response was 20 kU/l, with a sensitivity of 81% and a specificity of 72% [area under the curve, 0.80 (95% confidence interval, 0.44-0.94); P = 0.03]. There were 18 deaths, ten of which were cardiac in nature over a follow up period of 2.25 +/- 0.71 years. An increase in IMA > or = 20 kU/l was associated with significantly worse survival (P = 0.02). In conclusion, IMA is a moderately accurate marker of myocardial ischaemia in ESRD. Patients with an increase in IMA > or = 20 kU/l during DSE had significantly worse survival.

Mitral annular calcification predicts mortality and coronary artery disease in end stage renal disease.

BACKGROUND: We sought to determine whether mitral annular calcification (MAC) predicts mortality and cardiac disease in a group of renal transplant candidates. METHODS: Hundred and forty patients were prospectively studied. All had echocardiography and coronary angiography. Significant coronary artery disease (CAD) was defined as luminal stenosis >70% by visual estimation in at least one coronary artery. RESULTS: There were 21 deaths over a follow-up period of 2.2+/-0.7 years. MAC occurred in 56 patients (40%) and was associated with higher mortality (p=0.04). Patients with MAC were older (p=or<0.001), had larger left ventricular (LV) end systolic (p=0.005) and LV end diastolic (p=0.04) diameter, larger left atrial diameter (p=0.001), lower LV fractional shortening (p=0.003), larger LV mass index (p=0.04) and higher mitral E/Ea ratio (p=0.03) compared to those without. Plasma calcium (p=0.002), phosphate (p=0.004), cardiac troponin T (p=0.03), N-terminal Pro-B-type natriuretic peptide (p=0.004) concentrations were higher in those with MAC but gender, total cholesterol, haemoglobin and creatinine were similar in the two groups. The proportion diabetic (p=0.03), on dialysis (p=0.05), with significant CAD (p=or<0.001), taking calcium containing phosphate binders (p=0.02) and Vitamin D3 (p=0.04) was significantly higher in those with MAC. Significant CAD (OR 12, 95% CI 3.25, p=0.001) was the only independent associate of MAC. CONCLUSIONS: MAC is associated with increased mortality and significant CAD in ESRD. These patients have increased LV cavity size, poorer LV systolic function, higher LV filling pressures compared to patients without MAC.

Echocardiography-based score to predict outcome after renal transplantation.

BACKGROUND: Given the high cardiac mortality of renal transplant recipients, identification of high-risk patients is important to offer appropriate treatment before transplantation. AIM: To determine patients with high mortality after renal transplantation despite selection according to current criteria. METHODS: Preoperative parameters were collected from 203 renal transplant recipients over a follow-up time of 3.6 (1.9) years. The primary end point was all-cause mortality. RESULTS: 22 deaths (11%) and 12 cardiac failures (6%) were observed. Non-survivors were older (p< or =0.001), had larger left ventricular end-systolic diameter (LVSD) (p< or =0.001) and end-diastolic diameter (p = 0.002), and lower ejection fraction (p< or =0.001). Left ventricular mass index (p = 0.001), maximal wall thickness (p = 0.006) and the proportion with mitral annular calcification (p = 0.001) were significantly higher in the non-survivors. The risk factors for ischaemic heart disease and exercise test data were not significantly different between the two groups. Four independent predictors of mortality after renal transplantation were identified: age > or =50 years (p = 0.002), LVESD > or =3.5 cm (p = 0.002), maximal wall thickness > or =1.4 cm (p = 0.014) and mitral annular calcification (p = 0.036). The 5-year survival estimates for 0, 1, 2 and 3 prognostic factors were 96%, 86%, 69% and 38%, respectively. No patient had four prognostic factors. In patients > or =50 years, the 5-year survival estimates for 0, 1 and 2 additional prognostic factors were 73%, 45% and 18%, respectively. CONCLUSION: In addition to selection according to current guidelines, age and three conventional echocardiography parameters may further improve risk stratification before renal transplantation.

Predicting the outcome of Legg-Calve-Perthes' disease in children under 6 years old.

PURPOSE: In this study, we investigated the outcome of Legg-Calve-Perthes disease in children presenting under 6 years old. Firstly, we wished to know the outcome in terms of femoral head deformity in this age group. Secondly, we investigated the potential for improvement in femoral head deformity with growth and remodelling after the Perthes lesion had healed. Thirdly, we assessed the ability of Herring's lateral pillar classification to predict femoral head deformity in this age group. METHODS: The outcome in this group was assessed using Stulberg's classification of femoral head deformity and compared to that for older children with Perthes seen at our institution over the same period. To investigate the potential for improvement of Stulberg grade with growth we assessed the hips at the stage of final healing (Waldenstrom IV) and again at skeletal maturity. To assess whether Herring's classification of lateral column collapse is predictive of deformity at this age we recorded the Herring class A, B or C at the time of maximum fragmentation and compared this to Stulberg grade. RESULTS: Out of a total of 127 children (131 hips) seen at our institution, 67 children (69 hips) presented before the age of 6 years. The number of Stulberg III and IV hips was 14 (20%) and 10 (15%), respectively. Chi-squared test of age against outcome confirmed that the younger children overall had a better outcome (P < 0.001). Stulberg grade did not improve predictably after the stage of final healing. Twenty-three hips graded as Stulberg III and IV at Waldenstrom IV were reassessed at skeletal maturity. Three changed from Stulberg III to IV and five changed from Stulberg IV to III, but none had improved to Stulberg I/II. Herring's classification was predictive of outcome, with 96% of Herring A hips having Stulberg I or II outcome, 61% of Herring B hips having Stulberg I or II outcome, while 60% of Herring C hips (18 hips) had significant femoral head deformity, and 10 hips Stulberg III and 6 hips Stulberg IV. CONCLUSIONS: Perthes in children presenting before 6 years of age can result in significant femoral head deformity which does not predictably improve with time. The risk of a poor outcome can be predicted by Herring's classification of lateral pillar collapse.

Quantification of [123I]FP-CIT SPECT brain images: an accurate technique for measurement of the specific binding ratio.

PURPOSE: A technique is described for accurate quantification of the specific binding ratio (SBR) in [(123)I]FP-CIT SPECT brain images. METHODS: Using a region of interest (ROI) approach, the SBR is derived from a measure of total striatal counts that takes into account the partial volume effect. Operator intervention is limited to the placement of the striatal ROIs, a task facilitated by the use of geometrical template regions. The definition of the image for the analysis is automated and includes transaxial slices within a "slab" approximately 44 mm thick centred on the highest striatal signal. The reference region is automatically defined from the non-specific uptake in the whole brain enclosed in the slab, with exclusion of the striatal region. A retrospective study consisting of 25 normal and 30 abnormal scans-classified by the clinical diagnosis reached with the scan support-was carried out to assess intra- and inter-operator variability of the technique and its clinical usefulness. Three operators repeated the quantification twice and the variability was measured by the coefficient of variation (COV). RESULTS: The COVs for intra- and inter-operator variability were 3% and 4% respectively. A cutoff approximately 4.5 was identified that separated normal and abnormal groups with a sensitivity, specificity and diagnostic concordance of 97%, 92% and 95% respectively. CONCLUSION: The proposed technique provides a reproducible and sensitive index. It is hoped that its independence from the partial volume effect will improve consistency in quantitative measurements between centres with different imaging devices and analysis software.