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.

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.

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.

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.).

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.

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.

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.

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.

A Large Intraperitoneal Residual Volume Hampers Adequate Volumetric Assessment of Osmotic Conductance to Glucose.

BACKGROUND: In end-stage renal disease patients treated with peritoneal dialysis (PD), the osmotic conductance to glucose (OCG) represents the intrinsic ability of the membrane to transport water in response to a crystalloid osmotic gradient. A progressive loss of OCG in long-term PD patients indicates the development of fibrosis in the peritoneal interstitium, and helps identify patients at risk for encapsulating peritoneal sclerosis. The double mini-peritoneal equilibration test (PET) has been proposed as a simple method to assess OCG using the difference in initial ultrafiltration rates generated by 2 successive dwells using 1.36% and 3.86% glucose-based, 1-h PET. However, the presence of a large peritoneal residual volume (RV) may potentially interfere with the correct evaluation of drained volumes, limiting the reliability of OCG assessed by the double mini-PET. METHODS: We retrospectively reviewed data from 53 peritoneal function tests in 35 consecutive PD patients starting PD at our center between March 2013 and March 2017. The test consisted of a uni-PET (double mini-PET combined with a 3.86%, 4-h PET) performed at PD start, then yearly. In addition to peritoneal solute transport rate and net ultrafiltration, the tests provided information about osmotic water transport (OCG, sodium sieving, and free-water transport) as well as the RV estimated from albumin dilution. RESULTS: Contrary to sodium sieving, net ultrafiltration, and free-water transport, OCG did not correlate with any of the other parameters of osmotic water transport. In multivariate regression analyses, the RV was identified as the only determinant of OCG, while it did not alter the robust association between sodium sieving/free-water transport and their respective determinants. Considering only baseline tests or the whole series of tests, the presence of a large intraperitoneal RV was associated with discrepant values between OCG and sodium sieving, and with an artificial increase in OCG. CONCLUSIONS: A large RV leads to significant overestimation of OCG using the double mini-PET, potentially reducing the ability of OCG to identify patients with progressive fibrosis in the peritoneal interstitium. On the other hand, sieving of the dialysate sodium, a biochemical surrogate for OCG, is independent of the RV and may therefore be more reliable. A call for caution is warranted in patients with a large RV to avoid misinterpretation of OCG values derived from the double mini-PET.

Enteric hyperoxaluria in chronic pancreatitis.

Chronic pancreatitis may lead to steatorrhea, enteric hyperoxaluria, and kidney damage. However, the prevalence and determinants of hyperoxaluria in chronic pancreatitis patients as well as its association with renal function decline have not been investigated.We performed an observational study. Urine oxalate to creatinine ratio was assessed on 2 independent random urine samples in consecutive adult patients with chronic pancreatitis followed at the outpatient clinic from March 1 to October 31, 2012. Baseline characteristics and annual estimated glomerular filtration rate (eGFR) change during follow-up were compared between patients with hyper- and normo-oxaluria.A total of 48 patients with chronic pancreatitis were included. The etiology of the disease was toxic (52%), idiopathic (27%), obstructive (11%), autoimmune (6%), or genetic (4%). Hyperoxaluria (defined as urine oxalate to creatinine ratio >32 mg/g) was found in 23% of patients. Multivariate regression analysis identified clinical steatorrhea, high fecal acid steatocrit, and pancreatic atrophy as independent predictors of hyperoxaluria. Taken together, a combination of clinical steatorrhea, steatocrit level >31%, and pancreatic atrophy was associated with a positive predictive value of 100% for hyperoxaluria. On the contrary, none of the patients with a fecal elastase-1 level >100 µg/g had hyperoxaluria. Longitudinal evolution of eGFR was available in 71% of the patients, with a mean follow-up of 904 days. After adjustment for established determinants of renal function decline (gender, diabetes, bicarbonate level, baseline eGFR, and proteinuria), a urine oxalate to creatinine ratio >32 mg/g was associated with a higher risk of eGFR decline.Hyperoxaluria is highly prevalent in patients with chronic pancreatitis and associated with faster decline in renal function. A high urine oxalate to creatinine ratio in patients with chronic pancreatitis is best predicted by clinical steatorrhea, a high acid steatocrit, and pancreatic atrophy. Further studies will need to investigate the mechanisms of renal damage in chronic pancreatitis and the potential benefits of therapies reducing oxaluria.

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.

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.

Simulation and comparison of progression-free survival among patients with non-squamous non-small-cell lung cancer receiving sequential therapy.

OBJECTIVES: In recent years, the treatment landscape in advanced non-squamous non-small-cell lung cancer (nsNSCLC) has changed. New therapies (e.g., bevacizumab indicated in first line) have become available and other therapies (e.g., pemetrexed in first line and second line) moved into earlier lines in the treatment paradigm. While there has been an expansion of the available treatment options, it is still a key research question which therapy sequence results in the best survival outcomes for patients with nsNSCLC. METHODS: A therapy-sequencing disease model that approximates treatment outcomes in up to five lines of treatment was developed for patients with nsNSCLC. The primary source of data for progression-free survival (PFS) and time to death was published pivotal trial data. All patients were treatment-naïve and in the PFS state, received first-line treatment with either bevacizumab-based therapy or doublet chemotherapy (including the option of pemetrexed + cisplatin). Patients would then progress to a subsequent line of therapy, remain in PFS or die. In case of progression, it was assumed that each survivor would receive a subsequent line of therapy, based on EMA licensed therapies. Weibull distribution curves were fitted to the data. RESULTS: All bevacizumab-based first-line therapy sequences analyzed achieved total PFS of around 15 months. Bevacizumab + carboplatin + paclitaxel (first line) → pemetrexed (second line) → erlotinib (third line) → docetaxel (fourth line) resulted in total mean PFS time of 15.7 months, for instance. Sequences with pemetrexed in combination with cisplatin in first line achieved total PFS times between 12.6 and 12.8 months with a slightly higher total PFS time achieved when assuming pemetrexed continuation therapy in maintenance after pemetrexed + cisplatin in first-line induction. Overall survival results followed the same trend as PFS. CONCLUSION: The model suggests that treatment-sequencing strategies starting with a bevacizumab-based combination in first line yield better survival outcomes than those starting with pemetrexed-based combinations, a result that is attributable to the possibility of one further line of treatment with first-line bevacizumab-based treatment sequences.

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.

Mapping algorithms from QLQ-C30 to EQ-5D utilities: no firm ground to stand on yet.

AIM: Over the last years several mapping or cross-walking algorithms for deriving utilities from QLQ-C30 scores have been published. However their external predictive accuracy has not yet been systematically compared. METHODS: We tested the external validity of previously published mapping algorithms to transform the European Organization for Research and Treatment of Cancer QLQ-C30 questionnaire responses to EQ-5D derived Utilities. RESULTS: When applied to different data sets, the currently published mapping showed a large variation between algorithms of the values of the mapped utilities, a low accuracy of the mapping compared to the observed EQ-5D utilities and no consistent performance between competing algorithms. DISCUSSION: Therefore direct mapping from QLQ-C30 profiles to EQ-5D utilities using published algorithms should be viewed cautiously.

A systematic review of the predictive value of (18)FDG-PET in esophageal and esophagogastric junction cancer after neoadjuvant chemoradiation on the survival outcome stratification.

PURPOSE: We studied the predictive value of [(18) F]fluorodeoxyglucose-positron emission tomography ((18)FDG-PET) for assessing disease-free (DFS) and overall survival (OS) in esophageal and esophagogastric junction cancer. MATERIALS AND METHODS: A literature search (PUBMED/MEDLINE, EMBASE, Cochrane) was performed to identify full papers with (18)FDG-PET and survival data, using indexing terms and free text words. Studies with >10 patients with locally advanced esophageal cancer, presenting sequential or at least one post-adjuvant treatment (18)FDG-PET data and Kaplan-Meier survival curves with >6 months median follow-up period were included. We performed a meta-analysis for DFS and OS using the hazard ratio (HRs) as outcome measure. Sources of heterogeneity study were also explored. RESULTS: We identified 26 eligible studies including a total of 1,544 patients (average age 62 years, 82% males). The TNM distribution was as follows: stage I 7%, II 24%, III 53% and IV 15%. The pooled HRs for complete metabolic response versus no response were 0.51 for OS (95% CI, 0.4-0.64; P < 0.00001) and 0.47 for DFS (95% CI, 0.38-0.57; P < 0.00001), respectively. No statistical heterogeneity was present. To explore sources of clinical heterogeneity, we also realised subgroup and regression analyses. Taken into account the moderate correlation between OS and DFS (ρ = 0.54), we used joint bivariate random regression model. These analyses did not show a statistically significant impact of study characteristics and PET modalities on the pooled outcome estimates. CONCLUSION: Despite methodological and clinical heterogeneity, metabolic response on (18)FDG-PET is a significant predictor of long-term survival data.

Pneumonia and influenza, and respiratory and circulatory hospital admissions in Belgium: a retrospective database study.

BACKGROUND: Influenza infections can lead to viral pneumonia, upper respiratory tract infection or facilitate co-infection by other pathogens. Influenza is associated with the exacerbation of chronic conditions like diabetes and cardiovascular disease and consequently, these result in acute hospitalizations. This study estimated the number, proportions and costs from a payer perspective of hospital admissions related to severe acute respiratory infections. METHODS: We analyzed retrospectively, a database of all acute inpatient stays from a non-random sample of eleven hospitals using the Belgian Minimal Hospital Summary Data. Codes from the International Classification of Diseases, Ninth Revision, Clinical Modification was used to identify and diagnose cases of pneumonia and influenza (PI), respiratory and circulatory (RC), and the related complications. RESULTS: During 2002-2007, we estimated relative hospital admission rates of 1.69% (20960/1237517) and 21.79% (269634/1237517) due to primary PI and RC, respectively. The highest numbers of hospital admissions with primary diagnosis as PI were reported for the elderly patient group (n = 10184) followed by for children below five years of age (n = 3451). Of the total primary PI and RC hospital admissions, 56.14% (11768/20960) and 63.48% (171172/269634) of cases had at least one possible influenza-related complication with the highest incidence of complications reported for the elderly patient group. Overall mortality rate in patients with PI and RC were 9.25% (1938/20960) and 5.51% (14859/269634), respectively. Average lengths of hospital stay for PI was 11.6 ± 12.3 days whereas for RC it was 9.1 ± 12.7 days. Annual average costs were 20.2 and 274.6 million Euros for PI and RC hospitalizations. Average cost per hospitalization for PI and RC were 5779 and 6111 Euros (2007), respectively. These costs increased with the presence of complications (PI: 7159, RC: 7549 Euros). CONCLUSION: The clinical and economic burden of primary influenza hospitalizations in Belgium is substantial. The elderly patient group together with children aged <18 years were attributed with the majority of all primary PI and RC hospitalizations. TRIAL REGISTRATION: Not applicable.

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.

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.

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.