Risk stratification of patients with chronic kidney disease: Results of screening strategies incorporating clinical risk scoring and dobutamine stress echocardiography

Background Cardiac disease is the principal cause of death in patients with chronic kidney disease (CKD). Ischemia at dobutamine stress echocardiography (DSE) is associated with adverse events in these patients. We sought the efficacy of combining clinical risk evaluation with DSE. Methods We allocated 244 patients with CKD (mean age 54 years, 140 men, 169 dialysis-dependent at baseline) into low- and high-risk groups based on two disease-specific scores and the Framingham risk model. All underwent DSE and were further stratified according to DSE results. Patients were followed over 20 +/- 14 months for events (death, myocardial infarction, acute coronary syndrome). Results There were 49 deaths and 32 cardiac events. Using the different clinical scores, allocation of high risk varied from 34% to 79% of patients, and 39% to 50% of high-risk patients had an abnormal DSE. In the high-risk groups, depending on the clinical score chosen, 25% to 44% with an abnormal DSE had a cardiac event, compared with 8% to 22% with a.normal DSE. Cardiac events occurred in 2.0%, 3.1 %, and 9.7% of the low-risk patients, using the two disease-specific and Framingham scores, respectively, and DSE results did not add to risk evaluation in this subgroup. Independent DSE predictors of cardiac events were a lower resting diastolic blood pressure, angina during the test, and the combination of ischemia with resting left ventricular dysfunction. Conclusion In CKD patients, high-risk findings by DSE can predict outcome. A stepwise strategy of combining clinical risk scores with DSE for CAD screening in CKD reduces the number of tests required and identifies a high-risk subgroup among whom DSE results more effectively stratify high and low risk.

Characterisation of the signalment, clinical and survival characteristics of 41 cats with mast cell neoplasia

Mast cell tumours (MCTs) are relatively common tumours of cats, and are the second most common cutaneous tumours in cats in the USA. While the primary splenic form of the disease is far less common, it is usually associated with more severe clinical signs. Signalment, clinical and survival characteristics of mast cell neoplasia were characterised in 41 cats. The most common tumour location was cutaneous/ subcutaneous head and trunk. Stage la was the most common tumour stage at first diagnosis (n = 20), followed by stage 4 (both stage 4a and stage 4b; n = 10). Of 22 cats that underwent excisional biopsy, mast cell neoplasia recurred in four cats during the study period. Three of the 41 cats presented with simultaneous cutaneous and either splenic or lymph node tumours. A comparison between cats with only cutaneous tumours (n = 30) and those with tumours involving the spleen or lymph nodes (n = 11) showed longer survival times for the cutaneous-only group (P = 0.031). Twelve of the 41 cats died of mast cell neoplasia during the study period. When a subgroup of cats with only cutaneous tumours (no lymph node or visceral involvement) were divided according to whether there were multiple (five or more) tumours (n = 6) or a single tumour (n = 19), cats with single tumours survived longer than those with multiple tumours (P = 0.001). Solitary cutaneous feline MCTs without spread to the lymph nodes usually manifest as benign disease with a relatively protracted course. However, multiple cutaneous tumours, recurrent tumours and primary splenic disease should receive a guarded prognosis due to the relatively short median survival times associated with these forms of the disease. (C) 2006 ESFM and AAFR Published by Elsevier Ltd. All rights reserved.

Dosing of gentamicin in patients with end-stage renal disease receiving hemodialysis

The aim of this study was to evaluate dosing schedules of gentamicin in patients with end-stage renal disease and receiving hemodialysis. Forty-six patients were recruited who received gentamicin while on hemodialysis. Each patient provided approximately 4 blood samples at various times before and after dialysis for analysis of plasma gentamicin concentrations. A population pharmacokinetic model was constructed using NONMEM (version 5). The clearance of gentamicin during dialysis was 4.69 L/h and between dialysis was 0.453 L/h. The clearance between dialysis was best described by residual creatinine clearance (as calculated using the Cockcroft and Gault equation), which probably reflects both lean mass and residual clearance mechanisms. Simulation from the final population model showed that predialysis dosing has a higher probability of achieving target maximum concentration (C-max) concentrations (> 8 mg/L) within acceptable exposure limits (area under the concentration-time curve [AUC] values > 70 and < 120 mg.h/L per 24 hours) than postdialysis dosing.

The production of clinical dextran using membrane processes

Clinical dextran is used as a blood volume expander. The British Pharmacopeia (BP) specification for this product requires the amount of dextran below 12,000 MW and above 98,000 MW to be strictly controlled. Dextran is presently fractionated industrially using ethanol precipitation. The aim of this work was to develop an ultrafiltration system which could replace the present industrial process. Initially these molecular weight (MW) bands were removed using batch ultrafiltration. A large number of membranes were tested. The correct BP specification could be achieved using these membranes but there was a significant loss of saleable material. To overcome this problem a four stage ultrafiltration cascade (UFC) was used. This work is the first known example of a UFC being used to remove both the high and low MW dextran. To remove the high MW material it was necessary to remove 90% of the MW distribution and retain the remaining 10%. The UFC significantly reduced the amount of dialysate required. To achieve the correct specification below 12,000 MW, the UFC required only 2.5 - 3.0 diavolumes while the batch system required 6 - 7. The UFC also improved the efficiency of the fractionation process. The UFC could retain up to 96% of the high MW material while the batch system could only retain 82.5% using the same number of diavolumes. On average the UFC efficiency was approximately 10% better than the equivalent batch system. The UFC was found to be more predictable than the industrial process and the specification of the final product was easier to control. The UFC can be used to improve the fractionation of any polymer and also has several other potential uses including enzyme purification. A dextransucrase bioreactor was also developed. This preliminary investigation highlighted the problems involved with the development of a successful bioreactor for this enzyme system.

The fractionation of dextran polymer by ultrafiltration to yield clinical products

A review of ultrafiltration (UF) theory and equipment has been made. Dextran is fractionated industrially by ethanol precipitation, which is a high energy intensive process. The aims of this work were to investigate the fractionation of dextran using UF and to compare the efficiency and costs of UF fractionation with ethanol fractionation. This work is the continuation of research conducted at Aston, which was concerned with the fractionation of dextran using gel permeation chromatography (GPC) and hollow fibre UF membranes supplied by Amicon Ltd. Initial laboratory work centred on determining the most efficient make and configuration of membrane. UF membranes of the Millipore cassette configuration, and the DDS flat-sheet configuration, were examined for the fracationation of low molecular weight (MW) dextran. When compared to Amicon membranes, these membranes were found to be inferior. DDS membranes of 25 000 and 50 000 MW cut-offs were shown to be capable of fractionating high MW dextran with the same efficiency as GPC. The Amicon membranes had an efficiency comparable to that of ethanol fractionation. To increase this efficiency a theoretical UF membrane cascade was adopted to utilize favourable characteristics encountered in batch mode membrane experiments. The four stage cascade used recycled permeates in a counter- current direction to retentate flow, and was operated 24 hours per day controlled by a computer. Using 5 000 MW cut-off membranes the cascade improved the batch efficiency by at least 10% for a fractionation at 6 000 MW. Economic comparisons of ethanol fractionation, combined GPC and UF fractionation, and UF fractionation of dextran were undertaken. On an economic basis GPC was the best method for high MW dextran fractionation. When compared with a plant producing 100 tonnes pa of clinical dextran, by ethanol fractionation, a combined GPC and UF cascade fractionation could produce savings on operating costs and an increased dextran yield of 5%.

Herbal medicines:physician's recommendation and clinical evaluation of St.John's Wort for depression

Why some physicians recommend herbal medicines while others do not is not well understood. We undertook a survey designed to identify factors, which predict recommendation of herbal medicines by physicians in Malaysia. About a third (206 out of 626) of the physicians working at the University of Malaya Medical Centre ' were interviewed face-to-face, using a structured questionnaire. Physicians were asked about their personal use of, recommendation of, perceived interest in and, usefulness and safety of herbal medicines. Using logistic regression modelling we identified personal use, general interest, interest in receiving training, race and higher level of medical training as significant predictors of recommendation. St. John's wort is one of the most widely used herbal remedies. It is also probably the most widely evaluated herbal remedy with no fewer than 57 randomised controlled trials. Evidence from the depression trials suggests that St. John's wort is more effective than placebo while its comparative efficacy to conventional antidepressants is not well established. We updated previous meta-analyses of St. John's wort, described the characteristics of the included trials, applied methods of data imputation and transformation for incomplete trial data and examined sources of heterogeneity in the design and results of those trials. Thirty randomised controlled trials, which were heterogeneous in design, were identified. Our meta-analysis showed that St. John's wort was significantly more effective than placebo [pooled RR 1.90 (1.54-2.35)] and [Pooled WMD 4.09 (2.33 to 5.84)]. However, the remedy was similar to conventional antidepressant in its efficacy [Pooled RR I. 0 I (0.93 -1.10)] and [Pooled WMD 0.18 (- 0.66 to 1.02). Subgroup analyses of the placebo-controlled trials suggested that use of different diagnostic classifications at the inclusion stage led to different estimates of effect. Similarly a significant difference in the estimates of efficacy was observed when trials were categorised according to length of follow-up. Confounding between the variables, diagnostic classification and length of trial was shown by loglinear analysis. Despite extensive study, there is still no consensus on how effective St. lohn's wort is in depression. However, most experts would agree that it has some effect. Our meta-analysis highlights the problems associated with the clinical evaluation of herbal medicines when the active ingredients are poorly defined or unknown. The problem is compounded when the target disease (e.g. depression) is also difficult to define and different instruments are available to diagnose and evaluate it.

Gram-positive infections in patients with end-stage renal disease

Gram-positive microorganisms, specifically coagulase-negative staphylococci are the most common species recovered from clinical culture specimens of patients with end-stage renal disease. The propensity of coagulase-negative staphylococci (CNS) to cause infection in this patient group has been widely debated. However, it is still unclear how this usually avirulent commensal microorganism produces infection that contributes to high rates of morbidity and mortality in patients with end-stage renal disease. The aim of this thesis was to investigate the rate, geographical distribution, molecular and phenotypic mechanisms of Gram-positive microorganisms associated with infection in renal dialysis patients. In addition, it sought to assess the value of early serological diagnosis of dialysis catheter-associated infection and the effect of antimicrobial treatment regimens on the faecal carriage of enteric microorganisms. In this study, the incidence of haemodialysis catheter-associated infection was established with the Meditrend audit tool. This tool was used to assess the infection outcomes of catheter insertion and management procedures until the catheter was explanted. Introduction of a catheter management protocol decreased the incidence of catheter-related infection. Staphylococcal species recovered from episodes of haemodialysis catheter-associated infection and continuous ambulatory peritoneal dialysis (CAPD)-associated peritonitis were genotyped by determination of macrorestriction profiles with pulsed-field gel electrophoresis. This highlighted horizontal transfer of microorganisms between different patients and the environment. The phenotypic characteristics of these strains were also investigated to determine characteristics that could be used as markers for dialysis catheter-associated infection. The expression of elastase, lipase and esterase by CNS was significantly associated with infection. A rapid enzyme-linked immunosorbent assay incorporating a novel staphylococcal antigen (lipid S) was used to evaluate the early detection of anti-staphylococcal immunoglobulin gamma in patient sera. The comparison of culture positive and culture negative patients demonstrated a steady state of immune activation in both groups. However anti-lipid S serum antibody titres > 1000 were found to be a predictor of infection. The effect on faecal carriage of vancomycin resistant enterococci (VRE) and Clostridium difficile toxins in patients treated with CAPD when empiric cephalosporin therapy was substituted for piperacillin/tazobactam was investigated. The introduction of piperacillin/tazobactam demonstrated a decrease in the faecal carriage of VRE.

Statistical guidelines for clinical studies of human vision

Citation information: Armstrong RA, Davies LN, Dunne MCM & Gilmartin B. Statistical guidelines for clinical studies of human vision. Ophthalmic Physiol Opt 2011, 31, 123-136. doi: 10.1111/j.1475-1313.2010.00815.x ABSTRACT: Statistical analysis of data can be complex and different statisticians may disagree as to the correct approach leading to conflict between authors, editors, and reviewers. The objective of this article is to provide some statistical advice for contributors to optometric and ophthalmic journals, to provide advice specifically relevant to clinical studies of human vision, and to recommend statistical analyses that could be used in a variety of circumstances. In submitting an article, in which quantitative data are reported, authors should describe clearly the statistical procedures that they have used and to justify each stage of the analysis. This is especially important if more complex or 'non-standard' analyses have been carried out. The article begins with some general comments relating to data analysis concerning sample size and 'power', hypothesis testing, parametric and non-parametric variables, 'bootstrap methods', one and two-tail testing, and the Bonferroni correction. More specific advice is then given with reference to particular statistical procedures that can be used on a variety of types of data. Where relevant, examples of correct statistical practice are given with reference to recently published articles in the optometric and ophthalmic literature.

Flexible tactile digital feedback for clinical applications

Trauma and damage to the delicate structures of the inner ear frequently occurs during insertion of electrode array into the cochlea. This is strongly related to the excessive manual insertion force of the surgeon without any tool/tissue interaction feedback. The research is examined tool-tissue interaction of large prototype scale (12.5:1) digit embedded with distributive tactile sensor based upon cochlear electrode and large prototype scale (4.5:1) cochlea phantom for simulating the human cochlear which could lead to small scale digit requirements. This flexible digit classified the tactile information from the digit-phantom interaction such as contact status, tip penetration, obstacles, relative shape and location, contact orientation and multiple contacts. The digit, distributive tactile sensors embedded with silicon-substrate is inserted into the cochlea phantom to measure any digit/phantom interaction and position of the digit in order to minimize tissue and trauma damage during the electrode cochlear insertion. The digit is pre-curved in cochlea shape so that the digit better conforms to the shape of the scala tympani to lightly hug the modiolar wall of a scala. The digit have provided information on the characteristics of touch, digit-phantom interaction during the digit insertion. The tests demonstrated that even devices of such a relative simple design with low cost have potential to improve cochlear implants surgery and other lumen mapping applications by providing tactile feedback information by controlling the insertion through sensing and control of the tip of the implant during the insertion. In that approach, the surgeon could minimize the tissue damage and potential damage to the delicate structures within the cochlear caused by current manual electrode insertion of the cochlear implantation. This approach also can be applied diagnosis and path navigation procedures. The digit is a large scale stage and could be miniaturized in future to include more realistic surgical procedures.

Cardiac dysfunction and cell damage across clinical stages of severity in growth-restricted fetuses

Objective - The purpose of this study was to assess cardiac function and cell damage in intrauterine growth-restricted (IUGR) fetuses across clinical Doppler stages of deterioration. Study Design - One hundred twenty appropriate-for-gestational-age and 81 IUGR fetuses were classified in stages 1/2/3 according umbilical artery present/absent/reversed end-diastolic blood flow, respectively. Cardiac function was assessed by modified-myocardial performance index, early-to-late diastolic filling ratios, cardiac output, and cord blood B-type natriuretic peptide; myocardial cell damage was assessed by heart fatty acid–binding protein, troponin-I, and high-sensitivity C-reactive protein. Results - Modified-myocardial performance index, blood B-type natriuretic peptide, and early-to-late diastolic filling ratios were increased in a stage-dependent manner in IUGR fetuses, compared with appropriate-for-gestational-age fetuses. Heart fatty acid–binding protein levels were higher in IUGR fetuses at stage 3, compared with control fetuses. Cardiac output, troponin-I, and high-sensitivity C-reactive protein did not increase in IUGR fetuses at any stage. Conclusion - IUGR fetuses showed signs of cardiac dysfunction from early stages. Cardiac dysfunction deteriorates further with the progression of fetal compromise, together with the appearance of biochemical signs of cell damage.

Understanding the dynamics of information technology implementation: The case of clinical information systems

The ultimate intent of this dissertation was to broaden and strengthen our understanding of IT implementation by emphasizing research efforts on the dynamic nature of the implementation process. More specifically, efforts were directed toward opening the "black box" and providing the story that explains how and why contextual conditions and implementation tactics interact to produce project outcomes. In pursuit of this objective, the dissertation was aimed at theory building and adopted a case study methodology combining qualitative and quantitative evidence. Precisely, it examined the implementation process, use and consequences of three clinical information systems at Jackson Memorial Hospital, a large tertiary care teaching hospital.^ As a preliminary step toward the development of a more realistic model of system implementation, the study proposes a new set of research propositions reflecting the dynamic nature of the implementation process.^ Findings clearly reveal that successful implementation projects are likely to be those where key actors envision end goals, anticipate challenges ahead, and recognize the presence of and seize opportunities. It was also found that IT implementation is characterized by the systems theory of equifinality, that is, there are likely several equally effective ways to achieve a given end goal. The selection of a particular implementation strategy appears to be a rational process where actions and decisions are largely influenced by the degree to which key actors recognize the mediating role of each tactic and are motivated to action. The nature of the implementation process is also characterized by the concept of "duality of structure," that is, context and actions mutually influence each other. Another key finding suggests that there is no underlying program that regulates the process of change and moves it form one given point toward a subsequent and already prefigured end. For this reason, the implementation process cannot be thought of as a series of activities performed in a sequential manner such as conceived in stage models. Finally, it was found that IT implementation is punctuated by a certain indeterminacy. Results suggest that only when substantial efforts are focused on what to look for and think about, it is less likely that unfavorable and undesirable consequences will occur. ^

Modulating membership grades to gain consensus for fuzzy set uncertainty values in a clinical decision support system

This paper deals with a very important issue in any knowledge engineering discipline: the accurate representation and modelling of real life data and its processing by human experts. The work is applied to the GRiST Mental Health Risk Screening Tool for assessing risks associated with mental-health problems. The complexity of risk data and the wide variations in clinicians' expert opinions make it difficult to elicit representations of uncertainty that are an accurate and meaningful consensus. It requires integrating each expert's estimation of a continuous distribution of uncertainty across a range of values. This paper describes an algorithm that generates a consensual distribution at the same time as measuring the consistency of inputs. Hence it provides a measure of the confidence in the particular data item's risk contribution at the input stage and can help give an indication of the quality of subsequent risk predictions. © 2010 IEEE.

The clinical utility of FibroScan(®) as a noninvasive diagnostic test for liver disease.

An important aspect of managing chronic liver disease is assessing for evidence of fibrosis. Historically, this has been accomplished using liver biopsy, which is an invasive procedure associated with risk for complications and significant sampling and observer error, limiting the accuracy for determination of fibrosis stage. Hence, several serum biomarkers and imaging methods for noninvasive assessment of liver fibrosis have been developed. In this article, we review the current literature on an important noninvasive imaging modality to measure tissue elastography (FibroScan(®)). This ultrasound-based technique is now increasingly available in many countries and has been shown to be a reliable and safe noninvasive means of assessing disease severity in chronic liver disease of varying etiology.

Influence of diabetes on natriuretic peptide thresholds in screening for Stage B heart failure

CONTEXT: Natriuretic peptide (NP) has been shown to be an effective screening tool to identify patients with Stage B heart failure and to have clinical value in preventing heart failure progression. The impact of associated metabolic confounders on the screening utility of NP needs clarification.

OBJECTIVE: To assess the impact of diabetes mellitus (DM) on NP screening for asymptomatic Stage B heart failure.

MATERIALS AND METHODS: The study population consisted of 1368 asymptomatic patients with cardiovascular risk factors recruited from general practice as part of the STOP-HF trial. B-type NP (BNP) was quantified at point-of-care.

RESULTS: BNP was found to be as accurate for detecting Stage B heart failure in DM patients compared to non-DM patients (AUC 0.75 [0.71,0.78] and 0.77 [0.72,0.82], respectively). However, different BNP thresholds are required to achieve the same level of diagnostic sensitivity in DM compared with non-DM patients. To achieve 80% sensitivity a difference of 5-ng/L lower is required for patients with DM.

CONCLUSION: Although a significantly different BNP threshold is detected for patients with DM, the BNP concentration difference is small and unlikely to warrant a clinically different diagnostic threshold.