Capturing Patient Value in an Economic Evaluation

OBJECTIVE: Economic evaluations predominantly use generic outcomes, such as EuroQol-5 Dimension (EQ-5D), to assess the health status. However, because of the generic nature, they are less suitable to capture the quality of life of patients with specific conditions. Given the transition to patient-centered (remote) care delivery, this study aims to evaluate the possibility to use disease-specific measures in a cost-effectiveness analysis (CEA).METHODS: A real-life cohort from Maasstad Hospital (2020-2021) in the Netherlands, with 772 Rheumatoid Arthritis (RA) patients, was used to assess the cost-effectiveness of electronic consultations (e-consultations) compared with face-to-face consultations. The Incremental Cost-Effectiveness Ratio (ICER) based on the generic EQ-5D was compared with ICER's based on RA specific measures; Rheumatoid Arthritis Impact of Disease (RAID) and Health Assessment Questionnaire-Disability Index (HAQ-DI). To compare the cost-effectiveness of these different measures, HAQ-DI and RAID were expressed in QALYs via estimated conversion equations.CONCLUSIONS: The conventional ICER (e.g. EQ-5D) indicates that e-consultations are cost-effective with cost savings of - €161k per QALY gained for a prevalent RA cohort treated in a secondary trainee hospital. RA specific measures show similar results, with ICER's of - €163k per HAQ-DI(QALY) and - €223k per RAID(QALY) gained. RA specific measures capture patient-relevant domains and offer the opportunity to improve the assessment and treatment of the disease impact.DISCUSSION: Disease-specific patient-reported outcome measures (PROMs) offer a promising alternative for traditional measures in economic evaluations, capturing patient-relevant domains more comprehensively. As PROMs are increasingly applied in clinical practice, the next step entails modelling of a RA patient-wide conversion equation to implement PROMs in economic evaluations. This article is protected by copyright. All rights reserved.</p

The IMPACT study: A clustered randomized controlled trial to assess the effect of a referral algorithm for axial spondyloarthritis

BACKGROUND: A substantial number of patients with chronic low back pain (CLBP) have axial spondyloarthritis (axSpA), but early recognition of these patients is difficult for general practitioners (GPs). The Case Finding Axial Spondyloarthritis (CaFaSpA) referral strategy has shown to be able to identify patients with CLBP at risk for axSpA, but its impact on clinical daily practice is yet unknown. OBJECTIVE: To assess the effect of the CaFaSpA referral strategy on pain caused by disability in primary care patients with CLBP. METHODS: Within this clustered randomized controlled trial 93 general practices were randomized to either the CaFaSpA referral model (intervention) or usual primary care (control). In each group primary care patients between 18 and 45 years with CLBP were included. The primary outcome was disability caused by CLBP, measured with the Roland Morris Disability Questionnaire (RMDQ) at baseline and four months. Secondary outcome was the frequency of new axSpA diagnosis. Descriptive analyses were performed, and a linear mixed-effects model was used. RESULTS: In total 679 CLBP patients were included of which 333 patients were allocated to the intervention group and 346 to the control group. Sixty-four percent were female and mean age was 36.2 years. The mean RMDQ score at baseline was 8.39 in the intervention group and 8.61 in the control group. At four months mean RMDQ score was 7.65 in the intervention group and 8.15 in the control group. This difference was not statistically significant (p = 0.50). Six (8%) out of the 75 finally referred patients, were diagnosed with axSpA by their rheumatologist. CONCLUSIONS: The CaFaSpA referral strategy for axSpA did not have an effect on disability after four months caused by CLBP. However, the strategy is able to detect the axSpA patient within the large CLBP population sufficiently. Trial registration number: NCT01944163, Clinicaltrials.gov

The IMPACT study:A clustered randomized controlled trial to assess the effect of a referral algorithm for axial spondyloarthritis

Background A substantial number of patients with chronic low back pain (CLBP) have axial spondyloarthritis (axSpA), but early recognition of these patients is difficult for general practitioners (GPs). The Case Finding Axial Spondyloarthritis (CaFaSpA) referral strategy has shown to be able to identify patients with CLBP at risk for axSpA, but its impact on clinical daily practice is yet unknown. Objective To assess the effect of the CaFaSpA referral strategy on pain caused by disability in primary care patients with CLBP. Methods Within this clustered randomized controlled trial 93 general practices were randomized to either the CaFaSpA referral model (intervention) or usual primary care (control). In each group primary care patients between 18 and 45 years with CLBP were included. The primary outcome was disability caused by CLBP, measured with the Roland Morris Disability Questionnaire (RMDQ) at baseline and four months. Secondary outcome was the frequency of new axSpA diagnosis. Descriptive analyses were performed, and a linear mixed-effects model was used. Results In total 679 CLBP patients were included of which 333 patients were allocated to the intervention group and 346 to the control group. Sixty-four percent were female and mean age was 36.2 years. The mean RMDQ score at baseline was 8.39 in the intervention group and 8.61 in the control group. At four months mean RMDQ score was 7.65 in the intervention group and 8.15 in the control group. This difference was not statistically significant (p = 0.50). Six (8%) out of the 75 finally referred patients, were diagnosed with axSpA by their rheumatologist. Conclusions The CaFaSpA referral strategy for axSpA did not have an effect on disability after four months caused by CLBP. However, the strategy is able to detect the axSpA patient within the large CLBP population sufficiently

Current status and practical use of effluent biomarkers in peritoneal dialysis patients

Long-term peritoneal dialysis therapy can lead to alterations in the function and morphology of the peritoneal membrane. Assessment of the peritoneal dialysis membrane usually is done by investigating the transport of small solutes and fluid. Assessment of morphologic alterations and their development would require repetitive peritoneal biopsies that usually are not feasible. Peritoneal tissues are bathed in dialysis solutions during peritoneal dialysis and may secrete or shed substances that can be recovered in peritoneal effluent. These molecular effluent biomarkers may give insight into morphologic changes. In this review, established and emerging candidate biomarkers in peritoneal dialysis are discussed. Additionally, requirements, challenges, and clinical applications of effluent biomarkers in peritoneal dialysis are addresse

Peritoneal effluent MMP-2 and PAI-1 in encapsulating peritoneal sclerosis

Recently, the use of effluent matrix metalloproteinase 2 (MMP-2) and plasminogen activator inhibitor 1 (PAI-1) as potential biomarkers of peritoneal fibrosis has been demonstrated during longitudinal follow-up of incident peritoneal dialysis (PD) patients. This study focuses on effluent MMP-2 and PAI-1 as early diagnostic markers in the preceding years of patients who develop encapsulating peritoneal sclerosis (EPS). Diagnostic test study. PD patients who developed EPS were compared with controls using a 1:3 case-control design with a minimum PD duration of 57 months. Dialysate appearance rates of MMP-2 and PAI-1. EPS cases identified by 2 experienced nephrologists and a radiologist based on predefined criteria. 11 patients developed EPS within our center. The time course of MMP-2 appearance rates, studied by means of a linear repeated-measures model 4 years prior to the diagnosis of EPS, showed no difference between long-term controls and patients with EPS. In contrast, higher PAI-1 appearance rates were found in patients with EPS compared with controls (P=0.01). At a lag time of 1 year prior to EPS diagnosis, time-specific receiver operating characteristic curve analyses indicated a discriminative ability for PAI-1 appearance rate of 0.77 (95% CI, 0.63-0.91). A discriminative capacity was absent for those of MMP-2. Low event rate of EPS prevented independent validation in this single-center study. Elevated levels of PAI-1 appearance rates are present in patients who develop EPS, pointing to progressive peritoneal fibrosis and sclerosis. The PAI-1 appearance rate has fair discriminative capacity from 3 years prior to EPS diagnosis. Therefore, effluent PAI-1 may aid in monitoring peritoneal fibrosis and serve as a biomarker for EP

Can Free Water Transport Be Used as a Clinical Parameter for Peritoneal Fibrosis in Long-Term PD Patients?

Sodium sieving in peritoneal dialysis (PD) occurs in a situation with high osmotically-driven ultrafiltration rates. This dilutional phenomenon is caused by free water transport through the water channel aquaporin-1. It has recently been described that encapsulating peritoneal fibrosis is associated with impaired free water transport, despite normal expression of aquaporin-1. In this review, it will be argued that free water transport can be used for assessment of fibrotic peritoneal alterations, due to the water-binding capacity of collagen. Finally, the consequences for clinical practice will be discusse

Assessment of the size selectivity of peritoneal permeability by the restriction coefficient to protein transport

Transport of serum proteins from the circulation to peritoneal dialysate in peritoneal dialysis patients mainly focused on total protein. Individual proteins have hardly been studied. We determined serum and effluent concentrations of four individual proteins with a wide molecular weight range routinely in the standardised peritoneal permeability analysis performed yearly in all participating patients. These include β2-microglobulin, albumin, immunoglobulin G and α2-macroglobulin. The dependency of transport of these proteins on their molecular weight and diffusion coefficient led to the development of the peritoneal protein restriction coefficient (PPRC), which is the slope of the relation between the peritoneal clearances of these proteins and their free diffusion coefficients in water, when plotted on a double logarithmic scale. The higher the PPRC, the more size restriction to transport. In this review, we discuss the results obtained on the PPRC under various conditions, such as effects of various osmotic agents, vasoactive drugs, peritonitis and the hydrostatic pressure gradient. Long-term follow-up of patients shows an increase of the PPRC, the possible causes of which are discussed. Venous vasculopathy of the peritoneal microcirculation is the most likely explanation

Early Detection of Imminent Encapsulating Peritoneal Sclerosis: Free Water Transport, Selected Effluent Proteins, or Both?

BACKGROUND: No diagnostic tool or methodology is currently available for early detection of imminent encapsulating peritoneal sclerosis (EPS). The objective of this study was to investigate the predictive value of free water transport (FWT) and construct a panel of peritoneal effluent proteins for EPS alone or in combination with FWT. These parameters could be incorporated in the follow-up of peritoneal dialysis (PD) patients. METHODS: A case-control study, nested in a longitudinal PD patient cohort, was conducted. Time-specific areas under the receiver operating characteristic (ROC) curve were calculated for FWT and effluent biomarkers at a lag time up to 3 years before EPS diagnosis. Free water transport was combined with appearance rates (AR) of biomarkers to assess their clinical validity. RESULTS: Free water transport volume and AR of effluent biomarkers were investigated in 11 EPS patients and 34 long-term PD patients. Diagnostic performance was best for FWT (area under the curve [AUC] 0.94) followed by plasminogen activator inhibitor (PAI-1) AR. Throughout, diagnostic panels of FWT and AR of cancer antigen 125 (CA125), interleukin-6 (IL-6), or (PAI-1) yielded specificity estimates above 84%. The combination of FWT and PAI-1 AR identified the largest proportion of EPS patients at 1 year prior to diagnosis (sensitivity 100%, specificity 94%). CONCLUSION: Measurement of FWT is simple and has the highest predictive value for imminent EPS. The addition of effluent biomarkers provides an all-round insight into the state of the peritoneum. Our data indicate that combining FWT with either PAI-1, CA125, or IL-6 has the highest specificity. This is required to avoid unnecessary discontinuation of PD treatment

No Relation Between Peritoneal Fibrosis and Free Water Transport in a Rat Model

Free water transport (FWT) during peritoneal dialysis (PD) can easily be measured by Na+ kinetics. In long-term PD, FWT might reflect peritoneal fibrosis, but morphologic or functional relationships have not been investigated. Nonconventional dialysis solutions might be associated with better preservation of peritoneal tissues and function. We developed a long-term peritoneal exposure model in rats with impaired kidney function and investigated peritoneal morphology and function in that model after exposure to conventional and nonconventional solutions.Two studies were reanalyzed. Transport was assessed using a standard peritoneal permeability analysis adapted for the rat. Omental tissue was stained with picro-sirius red (PSR) for uniform quantification of fibrosis. A semiquantitative fibrosis score was also calculated.Rats (n = 9) exposed to a conventional solution for 16 weeks were compared with rats (n = 9) exposed to other solutions. Peritoneal transport parameters were similar, but the degree of fibrosis tended to be more severe in the conventional-solution group. Compared with the situation in humans, the contribution of FWT to ultrafiltration in rats was larger than that of small-pore fluid transport. No correlation between the percentage PSR positivity and FWT was observed. A marked difference in PSR positivity was found between the two studies.The long-term exposure model is not suitable for the study of relationships between FWT and peritoneal fibrosis. Quantitative assessment of the fibrosis is difficult