AQP1 Promoter Variant, Water Transport, and Outcomes in Peritoneal Dialysis.

BACKGROUND: Variability in ultrafiltration influences prescriptions and outcomes in patients with kidney failure who are treated with peritoneal dialysis. Variants in AQP1, the gene that encodes the archetypal water channel aquaporin-1, may contribute to that variability. METHODS: We gathered clinical and genetic data from 1851 patients treated with peritoneal dialysis in seven cohorts to determine whether AQP1 variants were associated with peritoneal ultrafiltration and with a risk of the composite of death or technique failure (i.e., transfer to hemodialysis). We performed studies in cells, mouse models, and samples obtained from humans to characterize an AQP1 variant and investigate mitigation strategies. RESULTS: The common AQP1 promoter variant rs2075574 was associated with peritoneal ultrafiltration. Carriers of the TT genotype at rs2075574 (10 to 16% of patients) had a lower mean (±SD) net ultrafiltration level than carriers of the CC genotype (35 to 47% of patients), both in the discovery phase (506±237 ml vs. 626±283 ml, P = 0.007) and in the validation phase (368±603 ml vs. 563±641 ml, P = 0.003). After a mean follow-up of 944 days, 139 of 898 patients (15%) had died and 280 (31%) had been transferred to hemodialysis. TT carriers had a higher risk of the composite of death or technique failure than CC carriers (adjusted hazard ratio, 1.70; 95% confidence interval [CI], 1.24 to 2.33; P = 0.001), as well as a higher risk of death from any cause (24% vs. 15%, P = 0.03). In mechanistic studies, the rs2075574 risk variant was associated with decreases in AQP1 promoter activity, aquaporin-1 expression, and glucose-driven osmotic water transport. The use of a colloid osmotic agent mitigated the effects of the risk variant. CONCLUSIONS: A common variant in AQP1 was associated with decreased ultrafiltration and an increased risk of death or technique failure among patients treated with peritoneal dialysis. (Funded by the Swiss National Science Foundation and others.).

Infectious Complications Associated to Buttonhole Cannulation of Native Arteriovenous Fistulas: A 22-year follow-up.

BACKGROUND AND HYPOTHESIS: Buttonhole cannulation of native arteriovenous fistulas (AVFs) appears associated with an increased infectious risk. We previously reported a dramatic increase in the incidence of infectious events after shift to buttonhole in an in-center hemodialysis unit, largely reduced after staff (re)education regarding strict respect of the procedure. We assessed the evolution over the following 12-years period in our center. METHODS: In this prospective follow-up of a previous, pre (rope-ladder)-post (buttonhole) comparison (2001-2010), all in-center hemodialysis patients with a native AVF were included from July 1st, 2010 to December 31st, 2022. Primary and secondary outcomes were infectious events (unexplained bacteraemia due to skin bacteria and/or local AVF infection) and complicated infectious events (metastatic infection, AVF surgery, death). Overall, the impact of several quality improvement strategies was tested according to the events rate over 6 periods: 1: Rope-ladder in all; 2: switch to buttonhole; 3: buttonhole in all, before workshops; 4: buttonhole in all, after workshops; 5: buttonhole withdrawal in problematic AVFs; 6: additional procedural changes. RESULTS: This extended observation period allowed adding 195,180 AVF-days to our previous report. Overall, 381,661 AVF-days (366 AVFs, 345 patients) were analysed. After an increase of the infectious events rate in 2012, the shift to rope-ladder in problematic AVFs during Period 5 did not have a significant impact. The incidence of infectious events decrease significantly during Period 6 compared to Periods 3, 4 and 5 [IRR 0.24 (95%CI 0.09-0.52) p=0.0001, IRR 0.22 (95%CI 0.09-0.47) p<0.0001, and IRR 0.29 (95%CI 0.11-0.66) p=0.001, respectively] and became eventually for the first time comparable to Period 1 [IRR 0.59 (95%CI 0.21-1.62) p=0.27]. CONCLUSION: The constant observance of reinforced hygiene protocols by trained staff and central coordination succeeded in significantly mitigating the infectious risk associated with buttonhole.

Estimating health related quality of life effects in vitiligo. Mapping EQ-5D-5 L utilities from vitiligo specific scales: VNS, VitiQoL and re-pigmentation measures using data from the HI-Light trial.

BACKGROUND: Vitiligo is reported to affect 2% of the world's population and has a significant impact on health related quality of life (HRQoL). The relationship between HRQoL and clinical outcomes used in vitiligo require further examination. Mapping condition specific measures of HRQoL: vitiligo specific quality of life instrument (VitiQoL), vitiligo noticeability scale (VNS) and vitiligo re-pigmentation scores (RPS) to the EQ-5D have not yet been reported. METHODS: Data collected from a randomised clinical trial (HI-Light) in vitiligo was used to develop mapping algorithms for the EQ-5D-5 L and the relationship between HRQoL, clinical outcomes and EQ-5D were investigated. Two EQ-5D-5 L value sets (Van Hout and Alava) using linear and non-linear models were considered. Logistic regression models were used to model the probability of vitiligo noticeability (VNS) in terms of RPS, EQ-5D and VitiQoL scores. RESULTS: Mapping from RPS appeared to perform better followed by VNS for the Alava crosswalks using polynomial models: Mean observed vs. predicted utilities of 0.9008 (0.005) vs. 0.8984 (0.0004) were observed for RPS. For VNS, mean observed vs. predicted utilities of 0.9008 (0.005) vs. 0.8939 (0.0003) were observed. For VitiQoL, mean observed vs. predicted utilities of 0.9008 (0.005) vs. 0.8912 (0.0002) were observed. For patients with the least re-pigmentation (RPS < 25%), a Total VitiQoL score of about 20 points gives around an 18% chance of vitiligo being no longer or a lot less noticeable. CONCLUSION: The algorithm based on RPS followed by VNS performed best. The relationship between effects from vitiligo specific HRQoL instruments and clinical RPS was established allowing for plausible clinically relevant differences to be identified, although further work is required in this area.

Podocyte Antigen Staining to Identify Distinct Phenotypes and Outcomes in Membranous Nephropathy: A Retrospective Multicenter Cohort Study.

RATIONALE & OBJECTIVE: Membranous nephropathy (MN) is characterized by the deposition of immune complexes along glomerular basement membranes. M-Type phospholipase A2 receptor (PLA2R), thrombospondin type 1 domain-containing 7A (THSD7A), exostosin 1 and 2 (EXT1/2), and neural epidermal growth factor-like 1 protein (NELL-1) have been identified as established or potential podocyte antigens in MN. We investigated the association of podocyte antigen staining with MN clinical phenotype and outcomes. STUDY DESIGN: Multicenter retrospective cohort study. SETTING & PARTICIPANTS: 177 consecutive patients with MN unrelated to lupus erythematosus, identified after screening of 3,875 native kidney biopsies performed in the Belgian UCLouvain Kidney Disease Network from 2000 through 2018. PREDICTOR: Positive immunostaining for podocyte antigens on archived kidney biopsy samples. OUTCOMES: Association with different phenotypes (baseline characteristics of patients and pathologic findings on kidney biopsy), time to cancer and to kidney failure. ANALYTICAL APPROACH: Kaplan-Meier estimates and Cox regression analyses to assess time to cancer and kidney failure. RESULTS: 177 patients were followed up for a median of 4.0 (IQR, 1.3-8.0) years. Diagnosis of PLA2R-positive (PLA2R+), THSD7A+, and double-negative (PLA2R-/THSD7A-) MN was made in 117 (66.1%), 6 (3.4%), and 54 (30.5%) patients, respectively. Progression to kidney failure was similar in all groups. Although the number of patients with THSD7A+MN was small, they showed a higher incidence (50%) and increased risk for developing cancer during follow-up (adjusted HR, 5.0 [95% CI, 1.4-17.9]; P=0.01). 8% and 5% of patients with double-negative MN stained positively for EXT1/2 and NELL-1, respectively. Most patients with EXT1/2+MN were women, had features of systemic autoimmunity, and showed glomerular C1q deposits. LIMITATIONS: Retrospective design; small number of patients in the THSD7A group; lack of evaluation of immunoglobulin G subclasses deposition. CONCLUSIONS: Our real-world data describe the relative prevalence of subgroups of MN and support the hypothesis that a novel classification of MN based on podocyte antigen staining may be clinically relevant.

Superior vena cava stenosis in haemodialysis patients with a tunnelled cuffed catheter: prevalence and risk factors.

Background: Although superior vena cava (SVC) stenosis may be a life-threatening complication of haemodialysis (HD) catheters, its prevalence and risk factors in HD patients are unknown. Our aim was to assess the prevalence and risk factors for SVC stenosis in HD patients with a tunnelled cuffed catheter (TCC) and to describe its clinical presentation. Methods: In this single-centre, retrospective cohort study, all in-centre chronic HD patients carrying a TCC (1 January 2008-31 December 2012) were included (n = 117 patients, 214 TCC, 80 911 catheter-days). SVC stenosis was defined as a diameter reduction >50% on phlebography or computed tomography. Imaging was triggered by clinical SVC stenosis syndrome or vascular access (VA)-related concerns. We recorded demographics, conditions potentially influencing catheter permeability (medications, carriage of thoracic devices), number of TCCs, total duration of TCC carriage, previous arteriovenous VA and last (in use at time of stenosis detection) TCC details (location, diameter and length). VAs created while a TCC was still used were also recorded. Results: An SVC stenosis was found in 11 patients (9.4%, 0.14/1000 catheter-days), which represents almost one-quarter of patients undergoing imaging, whatever the cause (11/45). Only two presented with clinically obvious SVC stenosis. The number of TCCs per patient was 2.64 ± 1.8 in the SVC stenosis group versus 1.75 ± 0.94 in the negative group (P = 0.13). On multivariate analysis (Poisson), diabetes {incidence rate ratio [IRR] 4.63 [confidence interval (CI) 1.2-17.8]; P = 0.02} and total duration of TCC carriage [IRR 1.47 (CI 1.2-1.8) per year; P = 0.001] were associated with SVC stenosis, whereas age had a slightly protective effect [IRR 0.96 (CI 0.91-1.01); P = 0.01]. Limitations are the retrospective design, detection and survivor bias. Conclusion: SVC stenosis is not a rare condition, is mostly asymptomatic in the absence of a peripheral VA, is strongly associated with diabetes and is promoted by long TCC carriage. Age is slightly protective.

Interstitial Fibrosis Restricts Osmotic Water Transport in Encapsulating Peritoneal Sclerosis.

Encapsulating peritoneal sclerosis (EPS) is a rare but severe complication of peritoneal dialysis (PD) characterized by extensive fibrosis of the peritoneum. Changes in peritoneal water transport may precede EPS, but the mechanisms and potential predictive value of that transport defect are unknown. Among 234 patients with ESRD who initiated PD at our institution over a 20-year period, 7 subsequently developed EPS. We evaluated changes in peritoneal transport over time on PD in these 7 patients and in 28 matched controls using 3.86% glucose peritoneal equilibration tests. Compared with long-term PD controls, patients with EPS showed early loss of ultrafiltration capacity and sodium sieving before the onset of overt EPS. Multivariate analysis revealed that loss of sodium sieving was the most powerful predictor of EPS. Compared with long-term PD control and uremic peritoneum, EPS peritoneum showed thicker submesothelial fibrosis, with increased collagen density and a greater amount of thick collagen fibers. Reduced osmotic conductance strongly correlated with the degree of peritoneal fibrosis, but not with vasculopathy. Peritoneal fibrosis was paralleled by an excessive upregulation of vascular endothelial growth factor and endothelial nitric oxide synthase, but the expression of endothelial aquaporin-1 water channels was unaltered. Our findings suggest that an early and disproportionate reduction in osmotic conductance during the course of PD is an independent predictor of EPS. This functional change is linked to specific alterations of the collagen matrix in the peritoneal membrane of patients with EPS, thereby validating the serial three-pore membrane/fiber matrix and distributed models of peritoneal transport.

Comprehensive cost analysis of sentinel node biopsy in solid head and neck tumors using a time-driven activity-based costing approach.

Head and neck cancer (HNC) is predominantly a locoregional disease. Sentinel lymph node (SLN) biopsy offers a minimally invasive means of accurately staging the neck. Value in healthcare is determined by both outcomes and the costs associated with achieving them. Time-driven activity-based costing (TDABC) may offer more precise estimates of the true cost. Process maps were developed for nuclear medicine, operating room and pathology care phases. TDABC estimates the costs by combining information about the process with the unit cost of each resource used. Resource utilization is based on observation of care and staff interviews. Unit costs are calculated as a capacity cost rate, measured as a Euros/min (2014), for each resource consumed. Multiplying together the unit costs and resource quantities and summing across all resources used will produce the average cost for each phase of care. Three time equations with six different scenarios were modeled based on the type of camera, the number of SLN and the type of staining used. Total times for different SLN scenarios vary between 284 and 307 min, respectively, with a total cost between 2794 and 3541€. The unit costs vary between 788€/h for the intraoperative evaluation with a gamma-probe and 889€/h for a preoperative imaging with a SPECT/CT. The unit costs for the lymphadenectomy and the pathological examination are, respectively, 560 and 713€/h. A 10 % increase of time per individual activity generates only 1 % change in the total cost. TDABC evaluates the cost of SLN in HNC. The total costs across all phases which varied between 2761 and 3744€ per standard case.

Cost comparison of open approach, transoral laser microsurgery and transoral robotic surgery for partial and total laryngectomies.

Activity-based costing is used to give a better insight into the actual cost structure of open, transoral laser microsurgery (TLM) and transoral robotic surgery (TORS) supraglottic and total laryngectomies. Cost data were obtained from hospital administration, personnel and vendor structured interviews. A process map identified 17 activities, to which the detailed cost data are related. One-way sensitivity analyses on the patient throughput, the cost of the equipment or operative times were performed. The total cost for supraglottic open (135-203 min), TLM (110-210 min) and TORS (35-130 min) approaches were 3,349 euro (3,193-3,499 euro), 3,461 euro (3,207-3,664 euro) and 5,650 euro (4,297-5,974 euro), respectively. For total laryngectomy, the overall cost were 3,581 euro (3,215-3,846 euro) for open and 6,767 euro (6,418-7,389 euro) for TORS. TORS cost is mostly influenced by equipment (54%) where the other procedures are predominantly determined by personnel cost (about 45%). Even when we doubled the yearly case-load, used the shortest operative times or a calculation without robot equipment costs we did not reach cost equivalence. TORS is more expensive than standard approaches and mainly influenced by purchase and maintenance costs and the use of proprietary instruments. Further trials on long-term outcomes and costs following TORS are needed to evaluate its cost-effectiveness.

An assessment of the external validity of mapping QLQ-C30 to EQ-5D preferences.

BACKGROUND: Although cancer-specific Health-related Quality-of-Life measures are commonly included in randomized clinical trials or other prospective non-randomized clinical studies, it is rare that preference-based instruments are used, which allow the calculation of a Utility weight suitable for estimating Quality-adjusted Life-Years gained. OBJECTIVE: To test the external validity of a previously published mapping algorithm to transform the EORTC QLQ-C30 questionnaire responses into EQ-5D-derived utilities by predicting EQ-5D utilities from QLQ-C30 scores. STUDY DESIGN AND METHODS: Comparative retrospective data analysis of four multicentre, prospective clinical trials in Breast, Multiple Myeloma, Non-Hodgkin Lymphoma and Non-Small-Cell Lung cancer patients with, respectively, 219, 172, 132 and 172 patients. Regression analysis of individual pairs of EQ-5D and QLQ-C30 scores. RESULTS: Although the internal predictive power of a previously published mapping equation was high, its external validity when tested on a set of unrelated external data sets in other cancers proved to underestimate both the mean and variance of the mapped EQ-5D utilities. Furthermore, it appears that the relationship between QLQ-C30 scores and EQ-5D values is not stable across the different data sets. CONCLUSIONS: Validation of the proposed algorithm in other external clinical data sets should be encouraged as well as the application of other more complex mapping methods to enhance accuracy of mapping. In the meanwhile, direct mapping from QLQ-C30 profiles to EQ-5D utilities using published algorithms should be performed with reservations.

Impact of thrice-weekly cotrimoxazole prophylaxis on creatinine and potassium plasma levels in kidney transplant recipients.

INTRODUCTION: Cotrimoxazole (CTX) 800/160 mg daily or thrice-weekly is recommended as prophylaxis of Pneumocystis jirovecii pneumonia in kidney transplant recipients. Cotrimoxazole 800/160 daily elevates plasma creatinine and potassium levels but whether the thrice-weekly regimen does so is unknown. METHODS: Medical records of 225 kidney transplant recipients at Cliniques Universitaires Saint-Luc were analyzed retrospectively. All received thrice-weekly CTX 800/160 for 6 months after transplantation. Monthly laboratory results, co-medications, and tacrolimus trough levels were compared. Standard statistical tests were used. RESULTS: One month after CTX stop, creatinine level decreased by 0.11 mg/dl (8%, p = 0.029). This contrasts with its stability in previous and subsequent months. No co-medication change accounted for this decrease. The decrease averaged 0.17 mg/dl (p < 0.01) in the highest initial creatinine tertile. The higher the initial creatinine level, the greater the decrease after CTX stop (p < 0.001), and urea levels remained stable after CTX stop. Potassium levels decreased by 0.09 mmol/L (p = 0.021) one month after CTX stop, and decreased by 0.23 mmol/L (p < 0.01) in the highest initial potassium level tertile. CONCLUSIONS: Our study pinpoints the impact of CTX 800/160 thrice-weekly on creatinine and potassium levels in kidney transplant recipients. This should be considered when interpreting the evolution of plasma creatinine over time, especially in patients with graft dysfunction. Thus, creatinine levels of cohorts with 6 months versus lifelong CTX require different interpretations.

Infectious complications following conversion to buttonhole cannulation of native arteriovenous fistulas: a quality improvement report.

BACKGROUND: Constant-site or buttonhole cannulation of native arteriovenous fistulas (AVFs) has gained in popularity compared with rope-ladder cannulation. However, cannulating nonhealed skin might increase the risk of (AVF-related) infectious events, as suggested by small reports. STUDY DESIGN: Quality improvement report. SETTING & PARTICIPANTS: All patients on in-center hemodialysis therapy using a native AVF from January 1, 2001, to June 30, 2010. QUALITY IMPROVEMENT PLAN: Shift to buttonhole cannulation between August 2004 and January 2005. Because the infectious event rate increased after the shift, educational workshops were held in May 2008 for all nurses, with review of every step of buttonhole protocol. OUTCOMES: Infectious events (unexplained bacteremia caused by skin bacteria and/or local AVF infection) and complicated infectious events (resulting in metastatic infection, death, or AVF surgery) were ascertained during 4 periods: (1) rope-ladder technique in all, (2) switch to buttonhole, (3) buttonhole in all before workshops, and (4) buttonhole in all after workshops. RESULTS: 177 patients (aged 70.4 ± 11.5 years) with 193 AVFs were analyzed, including 186,481 AVF-days. 57 infectious events occurred (0.31 events/1,000 AVF-days). The incidence of infectious events increased after the switch to the buttonhole method (0.17 [95% CI, 0.086-0.31], 0.11 [95% CI, 0.0014-0.63], and 0.43 [95% CI, 0.29-0.61] events/1,000 AVF-days in periods 1, 2, and 3, respectively; P = 0.003). This reached significance during only the second full year of buttonhole cannulation. During period 4, the incidence tended to decrease (0.34 events/1,000 AVF-days). Complicated infectious events (n = 12) were virtually restricted to period 3 (n = 11; 0.153 [95% CI, 0.076-0.273] events/1,000 AVF-days), with a significant decrease in period 4 (n = 1; 0.024 [95% CI, 0.001-0.118] events/1,000 AVF-days; RR for period 3 vs period 4, 6.37 [95% CI, 1.09-138.4]; P = 0.04). LIMITATIONS: Observational partly retrospective design. CONCLUSION: Intensive staff education regarding strict protocol for the buttonhole procedure was associated with a decrease in infectious events.

Economic impact of nonpersistence with antidepressant treatment in the adult population of Quebec: a comparative cost-effectiveness approach.

BACKGROUND: Although for the great majority of indications, practice guidelines recommend that antidepressants (ADs) be used for at least 6 months, premature discontinuation is very frequent in a "real-life" setting. Previous studies have assessed the economic impact of such nonpersistence, but differences across antidepressant products remain inadequately explored. OBJECTIVE: To compare treatment persistence and incremental cost/persistence ratios (ICPRs) across individual new ADs (selective serotonin reuptake inhibitors and atypical ADs) as well as the associated direct health-care costs in the adult population covered by the public drug program of Quebec. METHODS: A retrospective cohort study was conducted in 13,936 adults aged 18 to 64 years who started an AD treatment in 2003. Persistence was defined as treatment duration of at least 6 months regardless of whether a product switch had occurred. Economic impact was assessed over the first year of treatment through drug, medical services, hospitalization, and total health-care costs. Comparisons across products were conducted using the ICPR. RESULTS: Adjusting for confounders, treatment nonpersistence ranged from 60.4% (paroxetine) to 65.1% (citalopram). The product associated with the highest total health-care costs was citalopram (CDN$2653) and the lowest was venlafaxine (CDN$2168). Fluvoxamine had the lowest mean AD costs (CDN$215) and venlafaxine (CDN$309) the highest. CONCLUSIONS: Total health-care costs were similar across products except for citalopram, which was more costly. Comparisons based on the ICPR revealed that paroxetine, fluoxetine, and venlafaxine were more favorable than the other AD alternatives.

Cost-effectiveness analysis of FDG PET-CT in the management of pulmonary metastases from malignant melanoma.

OBJECTIVES: Most guidelines consider FDG PET-CT to detect occult extra-pulmonary disease prior to lung metastasectomy. A cost-effectiveness analysis, using a Markov model over a 10 year period, was performed to compare two different surveillance programs, either PET-CT or whole-body CT, in patients with suspected pulmonary metastasised melanoma. METHODS: Data from published studies provided probabilities for the model. Complication and care costs were obtained from standardised administrative databases from 19 hospitals identified by DRG codes (reported in 2009 Euros). For the cost calculation of PET-CT we performed a microcosting analysis. All costs and benefits were yearly discounted at respectively 3% and 1.5%. Outcomes included life-months gained (LMG) and the number of futile surgeries avoided. Cost-effectiveness ratios were in Euros per LMG. Univariate and probabilistic sensitivity analyses addressed uncertainty in all model parameters. RESULTS: The PET-CT strategy provided 86.29 LMG (95% CI: 81.50-90.88 LMG) at a discounted cost of euro3,974 (95% CI: euro1,339-12,303), while the conventional strategy provided 86.08 LMG (95% CI: 81.37-90.68 LMG) at a discounted cost of euro5,022 (95% CI: euro1,378-16,018). This PET-CT strategy resulted in a net saving of euro1,048 with a gain of 0.2 LMG. Based on PET-CT findings, 20% of futile surgeries could be avoided. CONCLUSION: Integrating PET-CT in the management of patients with high risk MM appears to be less costly and more accurate by avoiding futile thoracotomies in one of five patients as well as by providing a small survival benefit at 10 years.

Non-invasive Quantification of Fat Deposits in Skeletal Muscle Predicts Cardiovascular Outcome in Kidney Failure.

Fat accumulation in skeletal muscle was recently established as a major risk factor for cardiovascular disease (CVD) in the general population, but its relevance for patients with kidney failure is unknown. Here we examined the potential association between muscle radiation attenuation (MRA), a non-invasive indicator of fat deposits in muscle, and cardiovascular events in patients with kidney failure treated with peritoneal dialysis (PD) and investigated dynamic changes and determinants of MRA in this population. We retrospectively assessed MRA on computed tomography images collected yearly in 101 incident patients with kidney failure starting PD between January 2006 and December 2015. After a median of 21 months on dialysis, 34 patients had 58 non-fatal cardiovascular events, and 22 patients had died. Baseline MRA was associated with cardiovascular events during time on dialysis, and patients with higher MRA (reflecting lower amounts of fat in muscle) showed a reduced incidence of CVD, independently of traditional risk factors (adjusted HR, 0.91; 95% CI, 0.86-0.97, P = 0.006). Multivariate regression analysis identified old age, female gender, visceral fat area, and low residual urine volume as independent determinants of MRA. As compared with reference values from a healthy population, patients with kidney failure had lower MRA (i.e., increased fat accumulation), independently of age, gender, and body-mass index. The subset of patients who underwent kidney transplantation showed a significant increase in MRA after restoration of kidney function. These observations expand the association between ectopic fat accumulation and CVD to the population on dialysis, and suggest that kidney failure is reversibly associated with fatty muscle infiltration.

Activity-based costing evaluation of a [(18)F]-fludeoxyglucose positron emission tomography study.

OBJECTIVE: The aim of the study is to use the activity-based costing approach to give a better insight in the actual cost structure of a positron emission tomography procedure (FDG-PET) by defining the constituting components and by simulating the impact of possible resource or practice changes. METHODS: The cost data were obtained from the hospital administration, personnel and vendor interviews as well as from structured questionnaires. A process map separates the process in 16 patient- and non-patient-related activities, to which the detailed cost data are related. One-way sensitivity analyses shows to which degree of uncertainty the different parameters affect the individual cost and evaluate the impact of possible resource or practice changes like the acquisition of a hybrid PET/CT device, the patient throughput or the sales price of a 370MBq (18)F-FDG patient dose. RESULTS: The PET centre spends 73% of time in clinical activities and the resting time after injection of the tracer (42%) is the single largest departmental cost element. The tracer cost and the operational time have the most influence on cost per procedure. The analysis shows a total cost per FDG-PET ranging from 859 Euro for a BGO PET camera to 1142 Euro for a 16 slices PET-CT system, with a distribution of the resource costs in decreasing order: materials (44%), equipment (24%), wage (16%), space (6%) and hospital overhead (10%). CONCLUSIONS: The cost of FDG-PET is mainly influenced by the cost of the radiopharmaceutical. Therefore, the latter rather than the operational time should be reduced in order to improve its cost-effectiveness.

Role of PET in the initial staging of cutaneous malignant melanoma: systematic review.

PURPOSE: To calculate summary estimates of the diagnostic performance of fluorine 18 fluorodeoxyglucose (FDG) positron emission tomographic (PET) imaging in the initial staging of cutaneous malignant melanoma (CMM), following the new American Joint Committee on Cancer (AJCC) staging classification on per-patient and per-lesion bases. MATERIALS AND METHODS: MEDLINE, EMBASE, Web of Science, and Cochrane Database of Systematic Reviews databases, and reference lists of reviews and included papers were searched, without any language restrictions, for relevant articles published before March 2007. Two reviewers independently assessed study eligibility and methodologic quality by using the quality assessment of diagnostic accuracy studies checklist. A pooled random effect was estimated and a fixed coefficient regression model was used to explore the existing heterogeneity. RESULTS: Twenty-eight studies involving 2905 patients met the inclusion criteria. The pooled estimates of FDG PET for the detection of metastasis in the initial staging of CMM were sensitivity, 83% (95% confidence interval [CI]: 81%, 84%); specificity, 85% (95% CI: 83%, 87%); positive likelihood ratio (LR), 4.56 (95% CI: 3.12, 6.64); negative LR, 0.27 (95% CI: 0.18, 0.40); and diagnostic odds ratio, 19.8 (95% CI: 10.8, 36.4). Results from eight studies suggested that FDG PET was associated with 33% disease management changes (range, 15%-64%). CONCLUSION: There is good preliminary evidence that FDG PET is useful for the initial staging of patients with CMM, especially as adjunctive role in AJCC stages III and IV, to help detect deep soft-tissue, lymph node, and visceral metastases. FDG PET-computed tomographic imaging seemed to be more precise than PET alone, as suggested by four eligible studies. Further evaluation by using a well-designed prospective study, with clinical outcome-focused measures and cost effectiveness analysis, is needed to clarify the appropriate role of FDG PET in CMM staging. SUPPLEMENTAL MATERIAL: http://radiology.rsnajnls.org/cgi/content/full/249/3/836/DC1.

Activity-based costing evaluation of [18F]-fludeoxyglucose production.

INTRODUCTION: As healthcare expenses are escalating in many countries, the sector faces a new challenge of becoming more cost efficient. There is an urgent need for more accurate data on the costs of healthcare procedures. The cost of Positron Emission Tomography (PET) with [(18)F]-fludeoxyglucose ((18)F-FDG) studies is mainly influenced by the price of the radiopharmaceutical, which may vary throughout Europe from 300 to 500 Euro per patient dose (370 MBq). The aim of the current study is to conduct an activity-based costing (ABC) estimation of (18)F-FDG production in Europe to better identify the different cost components and to analyse their relative contribution to the total cost. MATERIALS AND METHODS: Financial data were collected on capital expense and global operating costs through interviews with industry experts, PET centre managers, evaluation of prior studies, and review of expenses incurred at the University Medical Centre in Groningen (The Netherlands). After mapping the activities, we divided the cost in five categories: wage, equipment, consumables, overhead and space costs. A sensitivity analysis was performed for key cost components, including the compliance with regulatory requirements. RESULTS: The critical factor for profitability was throughput. Including the European regulation procedure, the cost for 370 MBq (18)F-FDG patient dose, 3 h EOS without delivery cost, ranges between 155 and 177 Euro/dose for two production runs and between 210 and 237 Euro/dose for one production run. These costs are predominantly determined by personnel and equipment costs, although the cost for quality assurance increases steadily. CONCLUSION: The ABC analysis provides significant insight into the production cost components of (18)F-FDG through different operating configurations. Reductions in equipment prices, increased availability of radiopharmaceuticals, growth in demand, and improvements in reimbursement will all contribute to the financial viability of this imaging technique.

Preventing haemodialysis catheter-related bacteraemia with an antimicrobial lock solution: a meta-analysis of prospective randomized trials.

BACKGROUND: Catheter-related bacteraemia (CRB) is a major cause of morbidity and mortality in haemodialysis patients. Interdialytic locking of catheters with antimicrobial agents has recently been investigated for the prevention of CRB. We performed a meta-analysis of randomized controlled trials (RCT) to determine the efficacy of antimicrobial lock solutions (ALS) in the prevention of CRB in haemodialysis patients. METHODS: We collected from Medline, Web of Science, the Cochrane Library and major nephrology journals, all relevant references (January 1990-March 2007). We selected RCT comparing an ALS to a standard heparin lock in CRB prevention. We extracted data concerning study quality, patient characteristics and CRB incidence. The relative risk (RR) of CRB was calculated as Ln (CRB incidence control/CRB incidence experimental) using both a fixed- and a random-effects model. RESULTS: Eight studies were included, involving 829 patients, 882 catheters and 90 191 catheter-days. The use of an ALS significantly decreased the risk of CRB (RR 0.32; 95% CI 0.10-0.42). Borderline heterogeneity was observed in the fixed-effects model (Q = 14.42; P = 0.071). Despite the under-representation of small negative studies, the high number of additional trials necessary to reverse the final effect strengthens the confidence in the overall results. Subgroup analyses stratified by the presence of diabetes, duration of follow-up, biochemical markers, proportion of tunnelled cuffed catheters, intranasal mupirocin use and citrate use in the ALS did not show significant differences, except a higher efficacy of gentamicin-containing lock solutions (P = 0.003). CONCLUSIONS: The use of ALS reduces by about a factor 3 the risk of CRB in haemodialysis patients. The achieved absolute incidence is similar to the best-published figures (presumably related to stricter hygienic measures). The limited follow-up of the studies does not exclude the onset of adverse events or bacterial resistance with longer use of ALS.

The costs of colonoscopy in a Canadian hospital using a microcosting approach.

BACKGROUND: Colonoscopy has become accepted as one of the most effective methods of screening patients for colorectal cancer, and is used to remove the majority of colonic adenomas. OBJECTIVE: Because of the paucity of such estimates in the literature and the significant number of candidates for this procedure, the present study was performed to estimate the direct hospital costs of both diagnostic and therapeutic (polypectomy) colonoscopy. METHODS: A microcosting methodology was used to itemize the costs of colonoscopy. Variable and fixed costs were divided into labour, supplies, equipment and overhead costs. A third-party payer perspective was adopted. All costs are expressed in 2007 Canadian dollars. RESULTS: The cost of a diagnostic colonoscopy was $157 and the cost of a therapeutic colonoscopy was $199. Overhead costs represented approximately 30% of these amounts. When physician fees were added, these costs rose to $352 and $467, respectively. CONCLUSION: Because the overhead costs represent a large proportion of the total costs, allocation methods for these costs should be improved to allow for a more precise determination of the total costs of a colonoscopy. These estimates are useful when analyzing the cost-effectiveness of a strategy that uses colonoscopy when screening for colorectal cancer.

Direct Mapping of the QLQ-C30 to EQ-5D Preferences: A Comparison of Regression Methods.

BACKGROUND: Several mapping or cross-walking algorithms for deriving utilities from the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire for Cancer (EORTC QLQ-C30) scores have been published in recent years. However, the large majority used ordinary least squares (OLS) regression, which proved to be not very accurate because of the specifics of the quality-of-life measures. OBJECTIVE: Our objective was to compare regression methods that have been used to map EuroQol 5 Dimensions 3 Levels (EQ-5D-3L) utility values from the general EORTC QLQ-C30 using OLS as a benchmark while fixing the number of explanatory variables and to explore an alternative three-part model. METHODS: We conducted a regression analysis of predicted EQ-5D-3L utilities generated using data from an observational study in ambulatory patients with non-small-cell lung cancer in a Toronto hospital. Six alternative regression methods were compared with a simple OLS regression as benchmark. The six alternative regression models were Tobit, censored least absolute deviation, normal mixture, beta, zero-one inflated beta and a mix of piecewise OLS and logistic regression. RESULTS: The best predictive fit was obtained by a mix of OLS regression(s) for utilities lower than 1 with a cut-off point of 0.50 and a separate binary logistic regression for utilities equal to one. Zero-one inflated beta regression was also promising. However, OLS regression proved to be the most accurate for the mean. The prediction of utilities equal to one was poor in all regression approaches. CONCLUSIONS: Three-part regression methods that separately target low, medium and high (<0.50, 0.51-0.99 or 1) utilities seem to have better prediction power than OLS with EQ-5D-3L data, although OLS also seems quite robust. Exploration of three-part approaches compared with single (OLS) regression should be further tested in other similar datasets or using individual pooled data from various clinical or observational studies. The use of alternative goodness-of-fit measures for mapping studies and their influence on the choice of the best performing methods should also be investigated.