Cost-effectiveness of robotic-assisted surgery vs open surgery in the context of partial nephrectomy for small kidney tumors.

To evaluate the cost-effectiveness of robotic-assisted surgery compared to open surgery in the context of partial nephrectomy for small kidney tumor management. This is a retrospective study using data from 395 patients operated on by either robot-assisted surgery (RAPN) or by open partial nephrectomy (OPN); one hospital performed RAPN exclusively and the second hospital, OPN exclusively. Cost-effectiveness analysis was conducted from the perspective of the National Health Insurance System (NHIS) by considering the costs of the initial hospital stay and the cost of complications. Clinical outcome was defined by the avoidance of major complications during the 12 months postoperatively. Major complications were absent in 82% of patients in the OPN group and 93% of patients in the RAPN group, with 11% in favor of robotic assistance (p < 0.001). The average cost per patient, including the costs of complications, were, respectively, 9637 € and 8305 € for the OPN and RAPN groups. Robotic assistance was associated with a 1332 € lower cost (p < 0.001). The incremental cost-effectiveness ratio (ICER) is estimated at - 12,039 €. From the perspective of the public payer, robotic assistance was associated with a lower rate of postoperative complications and a lower average cost per patient. Robotic-assisted surgery was an efficient alternative to open surgery in partial nephrectomy. Trial registration number: NCT05089006 (October 22, 2021).

Prevalence of and Factors Associated with Respiratory Symptoms Among Patients with Inflammatory Bowel Disease: A Prospective Study.

BACKGROUND: No large, prospective study has investigated respiratory symptoms in patients with inflammatory bowel diseases. We aimed to describe the prevalence of and factors associated with respiratory symptoms in patients with inflammatory bowel disease. METHODS: In an observational, prospective, cross-sectional study, we evaluated the frequency of respiratory symptoms using a validated self-reporting questionnaire from February 2019 to February 2021 during routine follow-up outpatient visits of patients with inflammatory bowel disease followed in the Gastroenterology Department of the Nancy University Hospital. In case of a positive questionnaire, patients were systematically offered a consultation with a pulmonologist in order to investigate a potential underlying respiratory disease. RESULTS: There were 325 patients included, and 180 patients had a positive questionnaire (144 with Crohn's disease). Of the included patients, 165 (50.8%) presented with respiratory symptoms, with dyspnea being the most frequent symptom (102 patients). There were 102 patients (56.7%) who benefited from a consultation in the pulmonology department: 43 (42.2%) were diagnosed with a respiratory disease, mainly asthma (n = 13) or chronic obstructive pulmonary disease (n = 10). Fourteen patients (13.7%) had obstructive sleep apnea. A body mass index increase, being a smoker or ex-smoker, and having articular extra-intestinal manifestations were independently associated with a higher prevalence of respiratory symptoms. CONCLUSIONS: Half of patients with inflammatory bowel disease reported respiratory symptoms in our study. Patients with inflammatory bowel disease should be systematically screened, as pulmonary disease is frequently present in this population, with specific attention being given to smokers or ex-smokers and patients with extra-articular intestinal manifestations.

We conducted a large-scale, prospective study, finding a high prevalence of respiratory symptoms in patients with inflammatory bowel disease, which led to a variety of respiratory diseases, including asthma and obstructive pulmonary disease. Patients should therefore be systematically screened for pulmonary manifestations.

Cost-Effectiveness of Endovascular Treatment in Large Vessel Occlusion Stroke With Mild Prestroke Disability: Results From the HERMES Collaboration.

BACKGROUND: The clinical and economic benefit of endovascular treatment (EVT) in addition to best medical management in patients with stroke with mild preexisting symptoms/disability is not well studied. We aimed to investigate cost-effectiveness of EVT in patients with large vessel occlusion and mild prestroke symptoms/disability, defined as a modified Rankin Scale score of 1 or 2. METHODS: Data are from the HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials), which pooled patient-level data from 7 large, randomized EVT trials. We used a decision model consisting of a short-run model to analyze costs and functional outcomes within 90 days after the index stroke and a long-run Markov state transition model (cycle length of 12 months) to estimate expected lifetime costs and outcomes from a health care and a societal perspective. Incremental cost-effectiveness ratio and net monetary benefits were calculated, and a probabilistic sensitivity analysis was performed. RESULTS: EVT in addition to best medical management resulted in lifetime cost savings of $2821 (health care perspective) or $5378 (societal perspective) and an increment of 1.27 quality-adjusted life years compared with best medical management alone, indicating dominance of additional EVT as a treatment strategy. The net monetary benefits were higher for EVT in addition to best medical management compared with best medical management alone both at the higher (100 000$/quality-adjusted life years) and lower (50 000$/quality-adjusted life years) willingness to pay thresholds. Probabilistic sensitivity analysis showed decreased costs and an increase in quality-adjusted life years for additional EVT compared with best medical management only. CONCLUSIONS: From a health-economic standpoint, EVT in addition to best medical management should be the preferred strategy in patients with acute ischemic stroke with large vessel occlusion and mild prestroke symptoms/disability.

Significance of Baseline Ischemic Core Volume on Stroke Outcome After Endovascular Therapy in Patients Age ≥75 Years: A Pooled Analysis of Individual Patient Data From 7 Trials.

BACKGROUND: Age and infarct volume are strong predictors of outcome in patients with ischemic stroke who underwent endovascular therapy (EVT). We aimed to investigate the impact of ischemic core volume (ICV) on stroke outcome after EVT in elderly. METHODS: Using the HERMES (Highly Effective Reperfusion Using Multiple Endovascular Devices) collaboration, a patient-level meta-analysis of 7 randomized trials in which patients were enrolled from December 2010 to April 2015) dataset, we categorized patients into those aged <75 and ≥75 years. ICV was calculated on computed tomography perfusion or magnetic resonance diffusion-weighted imaging. The association between ICV and the benefit of EVT over best medical treatment on outcome (modified Rankin Scale [mRS] at 90 days) and an ICV threshold for high likelihood (≥90%) of very poor outcome (mRS score ≥5) after EVT were investigated. RESULTS: A total of 899 patients who had baseline ICV data, 247 patients aged ≥75 years, of which 118 were randomized in the EVT arm. Patients aged ≥75 years required smaller ICV to achieve mRS score ≤3 than those aged <75 years in the EVT arm (median 10.7 mL versus 23.9 mL, P<0.001). In patients aged ≥75 years, modeling of outcome in both treatment arms revealed potential loss of effect for EVT at ICV of ≥50 mL or ≥85 mL for achieving mRS score ≤3 or ≤4, respectively. Treatment effect of EVT was significant in ICV <50 mL for mRS ≤3 (odds ratio 2.38, 95% confidence interval 1.35-4.22). ICV ≥132 mL was a threshold for high likelihood of very poor outcome after EVT. However, EVT still predicted at least 30% rate of mRS ≤3 at 150 mL ICV if near-complete or complete reperfusion was achieved. CONCLUSIONS: Baseline ICV has an impact on stroke outcome after EVT in the elderly, but elderly patients with large ICV may still benefit from EVT if near-complete or complete reperfusion is achieved. Young patients seem to benefit from EVT regardless of ICV status.

Lack of Monitoring Is Associated with Risk of Acute Kidney Events among Patients with Inflammatory Bowel Disease.

Background: Although the iatrogenic risk of kidney failure is infrequent with treatment for inflammatory bowel disease (IBD), the repercussions for the patient could be major. The aim of this study was to assess the incidence of kidney events in IBD and to examine the protective effect of kidney function monitoring. Methods: In the French National Health Insurance database, 94,363 patients had a diagnosis of IBD between January 2010 and December 2016. By using a survival model with time-dependent covariates, we analyzed the time from inclusion in this IBD cohort to the first hospitalization for acute kidney impairment (AKI) according to patient characteristics, comorbidities, IBD phenotype and presence of monitoring. Results: A total of 693 patients were hospitalized for AKI, with an incidence of 1.36/1000 person−years (95% confidence interval [CI] 1.26−1.47). The incidence of AKI was lower than those without 5-aminosalicylic acid (5-ASA) use. Patients with 5-ASA use rarely had any lack of monitoring as compared with those not under 5-ASA use (3% vs. 17%). On multivariate analysis, lack of monitoring was associated with a substantial risk of AKI (hazard ratio 3.96, 95% CI [3.20−4.90], p < 0.0001). Conclusions: Increased frequency of monitoring is essential to identify nephropathy at an early stage and avoid the progression to chronic kidney disease.

The Economic, Medical and Psychosocial Consequences of Whole Genome Sequencing for the Genetic Diagnosis of Patients With Intellectual Disability: The DEFIDIAG Study Protocol.

Introduction: Like other countries, France has invested in a national medical genomics program. Among the four pilot research studies, the DEFIDIAG project focuses on the use of whole genome sequencing (WGS) for patients with intellectual disability (ID), a neurodevelopmental condition affecting 1-3% of the general population but due to a plethora of genes. However, the access to genomic analyses has many potential individual and societal issues in addition to the technical challenges. In order to help decision-makers optimally introduce genomic testing in France, there is a need to identify the socio-economic obstacles and leverages associated with the implementation of WGS. Methods and Analysis: This humanities and social sciences analysis is part of the DEFIDIAG study. The main goal of DEFIDIAG is to compare the percentage of causal genetic diagnoses obtained by trio WGS (including the patient and both parents) (WGST) to the percentage obtained using the minimal reference strategy currently used in France (Fragile-X testing, chromosomal microarray analysis, and gene panel strategy including 44 ID genes) for patients with ID having their first clinical genetics consultation. Additionally, four complementary studies will be conducted. First, a cost-effectiveness analysis will be undertaken in a subsample of 196 patients consulting for the first time for a genetic evaluation; in a blinded fashion, WGST and solo (index case, only) genomic analysis (WGSS) will be compared to the reference strategy. In addition, quantitative studies will be conducted: the first will estimate the cost of the diagnostic odyssey that could potentially be avoidable with first-line WGST in all patients previously investigated in the DEFIDIAG study; the second will estimate changes in follow-up of the patients in the year after the return of the WGST analysis compared to the period before inclusion. Finally, through semi-directive interviews, we will explore the expectations of 60 parents regarding genomic analyses. Discussion: Humanities and social sciences studies can be used to demonstrate the efficiency of WGS and assess the value that families associate with sequencing. These studies are thus expected to clarify trade-offs and to help optimize the implementation of genomic sequencing in France. Ethics Statement: The protocol was approved by the Ethics Committee Sud Méditerranée I (June 2019)-identification number: 2018-A00680-55 and the French data privacy commission (CNIL, authorization 919361). Clinical Trial Registration: (ClinicalTrials.gov), identifier (NCT04154891).

Direct transfer to angiosuite for patients with severe acute stroke treated with thrombectomy: the multicentre randomised controlled DIRECT ANGIO trial protocol.

INTRODUCTION: Mechanical thrombectomy (MT) increases functional independence in patients with acute ischaemic stroke with anterior circulation large vessel occlusion (LVO), and the probability to achieve functional independence decreases by 20% for each 1-hour delay to reperfusion. Therefore, we aim to investigate whether direct angiosuite transfer (DAT) is superior to standard imaging/emergency department-based management in achieving 90-day functional independence in patients presenting with an acute severe neurological deficit likely due to LVO and requiring emergent treatment with MT. METHODS AND ANALYSIS: DIRECT ANGIO (Effect of DIRECT transfer to ANGIOsuite on functional outcome in patient with severe acute stroke treated with thrombectomy: the randomised DIRECT ANGIO Trial) trial is an investigator-initiated, multicentre, prospective, randomised, open-label, blinded endpoint (PROBE) study. Eligibility requires a patient ≤75 years, pre-stroke modified Rankin Scale (mRS) 0-2, presenting an acute severe neurological deficit and admitted within 5 hours of symptoms onset in an endovascular-capable centre. A total of 208 patients are randomly allocated in a 1:1 ratio to DAT or standard management. The primary outcome is the rate of patients achieving a functional independence, assessed as mRS 0-2 at 90 days. Secondary endpoints include patients presenting confirmed LVO, patients eligible to intravenous thrombolysis alone, patients with intracerebral haemorrhage and stroke-mimics, intrahospital time metrics, early neurological improvement (reduction in National Institutes of Health Stroke Scale by ≥8 points or reaching 0-1 at 24 hours) and mRS overall distribution at 90 days and 12 months. Safety outcomes are death and intracerebral haemorrhage transformation. Medico-economics analyses include health-related quality of life and cost utility assessment. ETHICS AND DISSEMINATION: The DIRECT ANGIO trial was approved by the ethics committee of Ile de France 1. Study began in April 2020. Results will be published in an international peer-reviewed medical journal. TRIAL REGISTRATION NUMBER: NCT03969511.

Kidney function monitoring to prevent 5-aminosalicylic acid nephrotoxicity: What the gastroenterologist should know.

BACKGROUND: The kidney function monitoring is recommended in routine practice to detect 5-aminosalicylic acid (5-ASA) related nephrotoxicity, although is not standardized. The optimal monitoring is unknown, especially the best timing and which tests to perform. We summarized why, how, and when to perform the monitoring for patients treated with 5-ASA and provided an overview of the current guidelines on this topic. METHOD: Relevant studies on this topic were searched in PubMed, Embase, and Web of Science databases from July to August 2020. RESULTS: Serum creatinine, the estimated glomerular filtration rate, and 24-h proteinuria are the 3 main tests used for the monitoring in daily practice. Regarding the timing, several monitoring strategies have been proposed and guidelines are available too, but they provide conflicting information. To date, there is no medical evidence-based that one strategy is better than another. Comorbidities, chronic renal disease, use of nephrotoxic drugs or concomitant steroid therapy also impact the nephrotoxicity risk. Based on the literature review we proposed a kidney function monitoring strategy to guide physicians in clinical practice. CONCLUSION: A baseline assessment should be performed in all patients treated with 5-ASA. The monitoring should be carried out according to the other nephrotoxic factors. A tight monitoring may reduce morbidity and mortality of drug nephrotoxicity.

Effect of emergent carotid stenting during endovascular therapy for acute anterior circulation stroke patients with tandem occlusion: A multicenter, randomized, clinical trial (TITAN) protocol.

BACKGROUND AND HYPOTHESIS: There is no consensus on the optimal endovascular management of the extracranial internal carotid artery steno-occlusive lesion in patients with acute ischemic stroke due to tandem occlusion. We hypothesized that intracranial mechanical thrombectomy plus emergent internal carotid artery stenting (and at least one antiplatelet therapy) is superior to intracranial mechanical thrombectomy alone in patients with acute tandem occlusion. STUDY DESIGN: TITAN is an investigator-initiated, multicenter, prospective, randomized, open-label, blinded-endpoint (PROBE) study. Eligibility requires a diagnosis of acute ischemic stroke, pre-stroke modified Rankin Scale (mRS)≤2 (no upper age limit), National Institutes of Health Stroke Scale (NIHSS)≥6, Alberta Stroke Program Early Computed Tomography Score (ASPECTS)≥6, and tandem occlusion on the initial catheter angiogram. Tandem occlusion is defined as large vessel occlusion (intracranial internal carotid artery , M1 and/or M2 segment) and extracranial severe internal carotid artery stenosis ≥90% (NASCET) or complete occlusion. Patients are randomized in two balanced parallel groups (1:1) to receive either intracranial mechanical thrombectomy plus internal carotid artery stenting (and at least one antiplatelet therapy) or intracranial mechanical thrombectomy alone within 8 h of stroke onset. Up to 432 patients are randomized after tandem occlusion confirmation on angiogram. STUDY OUTCOMES: The primary outcome measure is complete reperfusion rate at the end of endovascular procedure, assessed as a modified Thrombolysis in Cerebral Infarction (mTICI) 3, and ≥4 point decrease in NIHSS at 24 h. Secondary outcomes include infarct growth, recurrent clinical ischemic event in the ipsilateral carotid territory, type and dose of antiplatelet therapy used, mRS at 90 (±15) days and 12 (±1) months. Safety outcomes are procedural complications, stent patency, intracerebral hemorrhage, and death. Economics analysis includes health-related quality of life, and costs utility comparison, especially with the need or not of endarterectomy. DISCUSSION: TITAN is the first randomized trial directly comparing two types of treatment in patients with acute ischemic stroke due to anterior circulation tandem occlusion, and especially assessing the safety and efficacy of emergent internal carotid artery stenting associated with at least one antiplatelet therapy in the acute phase of stroke reperfusion. TRIAL REGISTRATION: ClinicalTrials.gov NCT03978988.

Knowledge of 5-aminosalicylic acid nephrotoxicity and adherence to kidney function monitoring of patients with inflammatory bowel disease.

BACKGROUND AND AIM: 5-Aminosalicylic acid (5-ASA) nephrotoxicity is a rare and idiosyncratic condition in patients with inflammatory bowel disease (IBD), which may lead to end-stage kidney failure. Kidney function monitoring is recommended in clinical practice to prevent this complication. However, no data is available regarding the knowledge and adherence of patients with IBD to this monitoring. METHODS: As a part of routine practice, patients with IBD under treatment or previously treated with 5-ASA were systematically interviewed about knowledge of 5-ASA nephrotoxicity and adherence to kidney function monitoring. We reported here the experience among the first 103 consecutive patients seen in a French referral center. RESULTS: A total of 103 patients (93.2% ulcerative colitis, 5.8% Crohn's disease, and 1% unclassified colitis) were analyzed. Among them, 70% were informed about the need for kidney function monitoring, and in most cases, information was provided by their gastroenterologist (94.4%). The adherence rate to monitoring was very high (84.7%). Monitoring consisted of serum creatinine and estimated glomerular filtration rate in most cases (97.2%), while 24-h proteinuria was less frequently used (69.4%). These tests were performed twice or ≥3 times per year by 44.4 and 41.7% of patients, respectively. One case of isolated elevation of proteinuria related to 5-ASA treatment was observed. CONCLUSION: We reported for the first time that patients with IBD are well informed and adherent to kidney function monitoring of treatment with 5-ASA. The monitoring performed by their treating physician was generally in accordance with current recommendations.

Cost-effectiveness of four living-donor nephrectomy techniques from a hospital perspective.

BACKGROUND: In Europe, transplantation centres use different nephrectomy techniques: open surgery, and standard, hand-assisted and robot-assisted laparoscopies. Few studies have analysed the disparity in costs and clinical outcomes between techniques. Since donors are healthy patients expecting minimum pain and fast recovery, this study aimed to compare the cost-effectiveness of four nephrectomy techniques focusing on early surgical outcomes, an essential in the donation act. METHODS: A micro-costing approach was used to estimate the cost of implementation from a hospital perspective. Estimates took into account sterilization costs for multiple-use equipment, costs for purchasing single-use equipment, staff and analgesics. The study recruited donors in 20 centres in France. Quality of life by EuroQol-5D was assessed preoperatively, and 4 and 90 days post-operatively. Two effectiveness indicators were built: quality-of-life recovery and post-operative pain days averted (PPDA). The study was registered at ClinicalTrials.gov NCT02830568, on 10 June 2010. RESULTS: A total of 264 donors were included; they underwent open surgery (n = 65), and standard (n = 65), hand-assisted (n = 65) and robot-assisted laparoscopies (n = 69). Use of the nephrectomy techniques differed greatly in cost of implementation and immediate post-operative outcomes but not in clinical outcomes at 90 days. At 4 days, hand-assisted laparoscopy provided the lowest cost per quality-of-life recovery unit of effectiveness (%) and PPDA (days) (€2056/40.1%/2.3 days, respectively). Robot-assisted laparoscopy was associated with the best post-operative outcomes but with the highest cost (€3430/59.1%/2.6 days). CONCLUSION: Hand-assisted, standard and robot-assisted laparoscopies are cost-effective techniques compared with open surgery. Hand-assisted surgery is the most cost-effective procedure. Robot-assisted surgery requires more healthcare resource use but enables the best clinical outcome.

Cost-of-illness of inflammatory bowel disease patients treated with anti-tumour necrosis factor: A French large single-centre experience.

Background: No study has evaluated the direct annual costs of inflammatory bowel disease patients treated with anti-tumour necrosis factor therapy. Objectives: The purpose of this study was to identify annual direct costs and main cost drivers of anti-tumour necrosis factor-treated inflammatory bowel disease patients. Methods: All inflammatory bowel disease patients treated with infliximab or adalimumab at Nancy University Hospital were consecutively screened for inclusion from November 2016-February 2017. Data about hospitalisation, surgery, medication, outpatient visits, investigations and transport over the previous 12 months were retrospectively collected. Results: A total of 108 patients (n = 83 Crohn's disease; n = 25 ulcerative colitis) were included. The mean annual cost per patient was €15,775 (standard deviation €7221), with no difference between Crohn's disease and ulcerative colitis (p = 0.2). The main cost driver was medication, which accounted for 84% of the total direct cost. Hospitalisation and surgery represented 11% and 2% of the direct costs. History of switch to another anti-tumour necrosis factor treatment was identified as the only independent predictor of greater direct costs in the multivariate analysis (p = 0.0018). Conclusions: In a French tertiary referral centre, direct costs of anti-tumour necrosis factor therapy-treated patients were mainly driven by medication, while hospitalisation and surgery represented only a minor part of the costs. There was no difference between Crohn's disease and ulcerative colitis patients.

Impact of comorbidities and functional impairment on 5-year loss of health utility in patients with lower-limb osteoarthritis in the KHOALA cohort.

PURPOSE: To examine the respective and combined impact of "hypothetical" functional impairment (FI) and burden of comorbidities accrual on a 5-year risk of health utility (HU) loss in osteoarthritis (OA). METHODS: Participants of the Knee and Hip Osteoarthritis Long-term Assessment (KHOALA) study with a 5-year follow-up were included. FI, number of comorbidities and HU were measured annually by the WOMAC, Functional Comorbidity Index and Short-Form 6D, respectively. We estimated the population risk of HU loss (PRD: population risk difference, PRR: population risk ratio) under hypothetical FI and comorbidities using the parametric G-formula. Then, mediation analysis investigated the causal mechanism of comorbidities on HU through FI by estimating total, direct and indirect effects. RESULTS: We examined data from 767 patients (68.8% women; 61.6 years). The estimated 5-year risk of HU loss was 47.5% [41.9; 52.2] under natural course and 24.9% [15.5; 34.2] when imposing "Patient acceptable function and No comorbidity" corresponding to a PRD = - 22.6 [- 26.5; - 21.2] and a PRR = 0.5 [0.4; 0.6]. The estimated total risk of HU loss comparing "Two comorbidities" versus "No comorbidity" was significant without mediation effect of FI: Total = 10.1% [6.8; 12.9]; direct = 8.0% [2.7; 13.1]; indirect = 2.1% [- 2.0; 5.2]. CONCLUSIONS: FI and comorbidities are important and independent determinants of HU loss in patient with OA. Half of cases (50%) of HU loss during 5 years could be avoided by preventing comorbidities (30%) and limiting FI under patient acceptable function (20%). Caregivers should additionally pay close attention to the prevention and the treatment of comorbidities in routine management of OA.

Cost-Effectiveness of Thrombectomy in Patients With Acute Ischemic Stroke: The THRACE Randomized Controlled Trial.

BACKGROUND AND PURPOSE: The benefit of mechanical thrombectomy added to intravenous thrombolysis (IVT) in patients with acute ischemic stroke has been largely demonstrated. However, evidence of the economic incentive of this strategy is still limited, especially in the context of a randomized controlled trial. We aimed to analyze whether mechanical thrombectomy combined with IVT (IVMT) is cost-effective when compared with IVT alone. METHODS: Individual-level cost and outcome data were collected in the THRACE randomized controlled trial (Thrombectomie des Artères Cerébrales) including patients with acute ischemic stroke. Patients were assigned to receive IVT or IVMT. The primary outcomes were modified Rankin Scale score of functional independence at 90 days (score 0-2) and the EuroQol-5D quality-of-life score at 1 year. RESULTS: Treating acute ischemic stroke with IVMT (n=200) versus IVT (n=202) increased the rate of functional independence by 10.9% (53.0% versus 42.1%; P=0.028), at an increased cost of $2116 (€1909), with no significant difference in mortality (12% versus 13%; P=0.70) or symptomatic intracranial hemorrhage (2% versus 2%; P=0.71). The cost per one averted case of disability was estimated at $19 379 (€17 480). The incremental cost per one quality-adjusted life year gained was $14 881 (€13 423). On sensitivity analysis, the probability of cost-effectiveness with IVMT was 84.1% in terms of cases of averted disability and 92.2% in terms of quality-adjusted life years. CONCLUSIONS: Based on randomized trial data, this study demonstrates that IVMT used to treat acute ischemic stroke is cost-effective when compared with IVT alone. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01062698.