David Wellsted

Depression on Dialysis

Depression is the most common psychopathological condition among patients with end-stage renal disease (ESRD), yet it is still under-recognized and misdiagnosed. Depression reduces quality of life and has a negative clinical impact upon sufferers with chronic illness, including ESRD. This article discusses the negative effects of depression among the ESRD population treated with dialysis, the prevalence of the condition, the methodological issues involved with screening and treatment, and the possible psychological and somatic causes. There is a need to identify the prevalence of the disorder by effective methods, overcome the current issues surrounding depression assessment and to undertake trials of suitable treatments.

Long-Term Outcomes in Online Hemodiafiltration and High-Flux Hemodialysis : A Comparative Analysis

BACKGROUND AND OBJECTIVES Theoretical advantages exist of online hemodiafiltration (HDF) over high-flux hemodialysis (HD), but outcome data are scarce. Our objective was to compare outcomes between these modalities. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS We studied 858 incident patients in our incremental high-flux HD and online HDF program during an 18-yr period. We compared outcomes, including survival, in those who were treated predominantly with HDF (>50% sessions) and those with high-flux HD. Survival comparisons used a Cox model taking into account the time-varying proportion of time spent on HDF. All data were prospectively collected. RESULTS A total of 152,043 sessions were delivered as HDF and 291,222 as high-flux HD. A total of 232 (27%) patients were treated predominantly with HDF and 626 (73%) with high-flux HD. Total Kt/V, serum albumin, erythropoietin resistance index, and BP were similar in both groups up to 5 yr after HD initiation. Intradialytic hypotension was less frequent in the predominant HDF group. Predominant HDF treatment was associated with a reduced risk for death after correction for confounding variables. In a second Cox model, proportion of time spent on HDF predicted survival, such that patients who were treated solely by HDF would have a hazard for death of 0.66 compared with those who solely used high-flux HD. CONCLUSIONS We found no benefits of HDF over high-flux HD with respect to anemia management, nutrition, mineral metabolism, and BP control. The mortality benefit associated with HDF requires confirmation in large randomized, controlled trials. These data may contribute to their design.

Quality of Life and Survival in Patients with Advanced Kidney Failure Managed Conservatively or by Dialysis

BACKGROUND AND OBJECTIVES Benefits of dialysis in elderly dependent patients are not clearcut. Some patients forego dialysis, opting for conservative kidney management (CKM). This study prospectively compared quality of life and survival in CKM patients and those opting for dialysis. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Quality-of-life assessments (Short-Form 36, Hospital Anxiety and Depression Scale, and Satisfaction with Life Scale) were performed every 3 months for up to 3 years in patients with advanced, progressive CKD (late stage 4 and stage 5). RESULTS After 3 years, 80 and 44 of 170 patients had started or were planned for hemodialysis (HD) or peritoneal dialysis, respectively; 30 were undergoing CKM; and 16 remained undecided. Mean baseline estimated GFR ± SD was similar (14.0 ± 4.0 ml/min per 1.73 m(2)) in all groups but was slightly higher in undecided patients. CKM patients were older, more dependent, and more highly comorbid; had poorer physical health; and had higher anxiety levels than the dialysis patients. Mental health, depression, and life satisfaction scores were similar. Multilevel growth models demonstrated no serial change in quality-of-life measures except life satisfaction, which decreased significantly after dialysis initiation and remained stable in CKM. In Cox models controlling for comorbidity, Karnofsky performance scale score, age, physical health score, and propensity score, median survival from recruitment was 1317 days in HD patients (mean of 326 dialysis sessions) and 913 days in CKM patients. CONCLUSIONS Patients choosing CKM maintained quality of life. Adjusted median survival from recruitment was 13 months shorter for CKM patients than HD patients.

Colorectal Tumor Vascularity: Quantitative Assessment with Multidetector CT—Do Tumor Perfusion Measurements Reflect Angiogenesis?

PURPOSE To establish the relationships between quantitative perfusion computed tomography (CT) parameters-specifically, primary tumor blood flow, blood volume, transit time, and permeability surface-area product-and immunohistologic markers of angiogenesis in colorectal cancer. MATERIALS AND METHODS After institutional review board approval and informed patient consent were obtained for this prospective study, 23 patients (11 men, 12 women; mean age, 68.4 years; age range, 34.8-87.1 years) with colorectal adenocarcinoma underwent a 65-second perfusion CT examination, and tumor blood flow, blood volume, mean transit time, and permeability surface-area product were determined. After surgery, resected specimens were sectioned and stained immunohistochemically to identify CD34 for quantification of microvessel density (MVD), to identify smooth muscle actin for assessment of pericyte coverage index, to identify vascular endothelial growth factor (VEGF), and to identify glucose transporter protein (GLUT-1). Perfusion CT measurements were correlated with MVD, pericyte coverage index, VEGF expression, and GLUT-1 expression by using Pearson or Spearman rank correlation analysis, with significance assigned at the 5% level. RESULTS Mean blood flow, blood volume, transit time, and permeability surface-area product values were 72.1 mL/min/100 g of tissue +/- 28.4 (standard deviation), 6.2 mL/100 g of tissue +/- 1.4, 9.3 seconds +/- 3.9, and 13.9 mL/min/100 g of tissue +/- 3.2, respectively. Blood volume (r = 0.59, P = .002) and permeability surface-area product (r = 0.46, P = .03) correlated positively with MVD, but blood flow (r = 0.27, P = .22) and transit time (r = -0.18, P = .44) did not. There were no significant associations between any perfusion CT parameter and pericyte coverage index (r <or= 0.36, P > .05), VEGF score (rho <or= 0.30, P >or= .15), or GLUT-1 score (rho < 0.21, P >or= .33). CONCLUSION Tumor permeability surface-area product and blood volume correlate positively with MVD and may reflect the microvascularity of colorectal tumors.

Residual renal function improves outcome in incremental haemodialysis despite reduced dialysis dose

BACKGROUND AND METHODS The importance of residual renal function is well recognized in peritoneal dialysis but its role in haemodialysis (HD) has received much less attention. We studied 650 incident patients in our incremental high-flux HD programme over a 15-year period. Target total Kt/V urea (dialysis plus residual renal) was 1.2 per session and monitored monthly. Renal urea clearance (KRU) was estimated 1-3 monthly. RESULTS KRU declined during the first 5 years of HD from 3.1 +/- 1.9 at 3 months to 0.9 +/- 1.2 ml/min/1.73 m(2) at 5 years. The percentage of patients with KRU >or= 1 ml/min at these time points was 85% and 31%, respectively. Patients with KRU >or= 1 ml/min had a significantly lower mean creatinine (all time points), ultrafiltration requirement (all time points) and serum potassium (6, 12, 36 and 48 months). Nutritional parameters were also significantly better in respect to nPCR and serum albumin (6, 12, 24 and 36 months). Patients with KRU >or= 1 ml/min had significantly lower erythropoietin requirements and erythropoietin resistance indices (12, 24, 36 and 48 months). Mortality was significantly lower in patients with a KRU >or= 1 at 6, 12 and 24 months after HD initiation, this benefit being maintained after correcting for albumin, age, comorbidities, HDF use and renal diagnosis. Our unique finding was that these benefits occurred despite those with KRU >or= 1 ml/min having a significantly lower dialysis Kt/V at all time points. CONCLUSION The associations demonstrated suggest that residual renal function contributes significantly to outcome in HD patients and that efforts to preserve it are warranted. Comparative outcome studies should be controlled for residual renal function.

Quantitative Assessment of Colorectal Cancer Tumor Vascular Parameters by Using Perfusion CT: Influence of Tumor Region of Interest

PURPOSE To prospectively determine whether position and size of tumor region of interest (ROI) influence estimates of colorectal cancer vascular parameters at computed tomography (CT). MATERIALS AND METHODS After institutional review board approval and informed consent, 25 men and 22 women (mean age, 65.8 years) with colorectal adenocarcinoma underwent 65-second CT perfusion study. Blood volume, blood flow, and permeability-surface area product were determined for 40- or 120-mm(2) circular ROIs placed at the tumor edge and center and around (outlining) visible tumor. ROI analysis was repeated by two observers in different subsets of patients to assess intra- and interobserver variation. Measurements were compared by using analysis of variance; a difference with P = .002 was significant. RESULTS Blood volume, blood flow, and permeability-surface area product measurements were substantially higher at the edge than at the center for both 40- and 120-mm(2) ROIs. For 40-mm(2) ROI, means of the three measurements were 6.9 mL/100 g (standard deviation [SD], 1.4), 108.7 mL/100 g per minute (SD, 39.2), and 16.9 mL/100 g per minute (SD, 4.2), respectively, at the edge versus 5.1 mL/100 g (SD, 1.5), 56.3 mL/100 g per minute (SD, 33.1), and 13.9 mL/100 g per minute (SD, 4.6), respectively, at the center. For 120-mm(2) ROI, means of the three measurements were 6.6 mL/100 g (SD, 1.3), 96.7 mL/100 g per minute (SD, 42.5), and 16.3 mL/100 g per minute (SD, 5.6), respectively, at the edge versus 5.1 mL/100 g (SD, 1.4), 58.3 mL/100 g per minute (SD, 32.5), and 13.4 mL/100 g per minute (SD, 4.3) at the center (P < .0001). Measurements varied substantially depending on the ROI size; values for the ROI for outlined tumor were intermediate between those at the tumor edge and center. Inter- and intraobserver agreement was poor for both 40- and 120-mm(2) ROIs. CONCLUSION Position and size of tumor ROI and observer variation substantially influence ultimate perfusion values. ROI for outlined entire tumor is more reliable for perfusion measurements and more appropriate clinically than use of arbitrarily determined smaller ROIs.

Screening for depression while patients dialyse : an evaluation

BACKGROUND The lack of routine depression screening among the haemodialysis (HD) population may contribute to depression being under-recognised. While screening patients could be beneficial, the optimum screening procedure remains unclear. One method would be to screen HD patients while they receive their treatment. The purpose of this investigation was to determine whether the Beck Depression Inventory-II (BDI) could be administered while patients dialysed. METHODS Forty HD patients completed the BDI while dialysing and again at a time when off-dialysis. Level of agreement analysis (Bland and Altman) was undertaken to determine if the assessment condition influenced BDI scoring. The off-dialysis assessment also involved a short clinical interview that was compared with the BDI assessment. RESULTS There was a high level of agreement between the on- and off-dialysis assessments, but differences in response to the somatic items on the BDI scale were apparent between the conditions. The clinical interview revealed that 22% of the sample met the DSM-IV criteria for major depressive disorder. The optimal cut-off value for the BDI as determined by receiver operating characteristic curves was >or=16, with 88.9% sensitivity and 87.1% specificity. CONCLUSION The results indicate that the procedure of on-dialysis assessment using the BDI is a viable screening procedure. The practicality of employing this screening procedure may facilitate improved detection of depression in the dialysis population.

Illness representations are associated with fluid nonadherence among hemodialysis patients

OBJECTIVE Patients with end-stage renal disease are required to limit fluid and salt intake. We examined illness representations [common-sense model (CSM)] among a sample of hemodialysis (HD) patients, investigating whether fluid-adherent patients held illness representations different from those of nonadherent patients. We also explored the utility of illness perceptions in predicting fluid nonadherence after controlling for clinical parameters, including residual renal function (KRU). METHODS Illness perceptions were assessed [Revised Illness Perception Questionnaire (IPQ-R)] in 99 HD patients. Clinical parameters were collected and averaged over a 3-month period prior to and including the month of IPQ-R assessment. Depression scores, functional status, and comorbidity were also collected. Fluid nonadherence was defined using interdialytic weight gain (IDWG) and dry weight (ideal weight). Patients in the upper quartile of percent weight gain were defined as nonadherent (IDWG> or =3.21% dry weight). RESULTS Nonadherent patients had timeline perceptions significantly lower than those of adherent patients. Logistic regression models were computed in order to identify predictors of fluid nonadherence. After several demographic and clinical variables, including age, gender, and KRU, had been controlled for, lower consequence perceptions predicted nonadherence. CONCLUSIONS Illness representations appear to predict fluid nonadherence among HD patients. Extending the CSM to investigate specific perceptions surrounding treatment behaviors may be useful and merits attention in this setting.

The size, burden and cost of disorders of the brain in the UK

Aim: The aim of this paper is to increase awareness of the prevalence and cost of psychiatric and neurological disorders (brain disorders) in the UK. Method: UK data for 18 brain disorders were extracted from a systematic review of European epidemiological data and prevalence rates and the costs of each disorder were summarized (2010 values). Results: There were approximately 45 million cases of brain disorders in the UK, with a cost of €134 billion per annum. The most prevalent were headache, anxiety disorders, sleep disorders, mood disorders and somatoform disorders. However, the five most costly disorders (€ million) were: dementia: €22,164; psychotic disorders: €16,717; mood disorders: €19,238; addiction: €11,719; anxiety disorders: €11,687. Apart from psychosis, these five disorders ranked amongst those with the lowest direct medical expenditure per subject (<€3000). The approximate breakdown of costs was: 50% indirect costs, 25% direct non-medical and 25% direct healthcare costs. Discussion: The prevalence and cost of UK brain disorders is likely to increase given the ageing population. Translational neurosciences research has the potential to develop more effective treatments but is underfunded. Addressing the clinical and economic challenges posed by brain disorders requires a coordinated effort at an EU and national level to transform the current scientific, healthcare and educational agenda.

Illness Perceptions Predict Survival in Haemodialysis Patients

Background: Illness perceptions have been shown to be important determinants of functional and psychosocial outcomes, including quality of life and treatment adherence in end-stage renal disease patients. The aim of this prospective study was to determine whether haemodialysis patients’ illness perceptions impact upon survival. Methods: Haemodialysis patients from a UK renal service completed the Revised Illness Perception Questionnaire. Over the study period (May 2007 to December 2010), all-cause mortality was recorded as the endpoint. Results: 223 patients were followed up for a median of 15.9 months (min. 10 days, max. 42.7 months). The median dialysis vintage was 17.6 months (min. 4 days, max. 391.3 months). Treatment control perceptions demonstrated a significant association with mortality (HR = 0.91, 95% CI: 0.83–0.99, p = 0.03). After controlling for covariates, including age, albumin, extra renal comorbidity and depression scores, perception of treatment control remained a significant predictor of mortality (HR = 0.89, 95% CI: 0.80–0.99, p = 0.03). Conclusions: Patients’ perceptions of treatment control (dialysis therapy) predict survival independently of survival risk factors, including comorbidity. Studies are required to test whether psychological interventions designed to modify maladaptive illness perceptions influence clinical outcomes in this patient setting.