Multifactorial approach and superior treatment efficacy in renal patients with the aid of nurse practitioners. Design of The MASTERPLAN Study [ISRCTN73187232]

BACKGROUND: Patients with chronic kidney disease (CKD) are at a greatly increased risk of developing cardiovascular disease. Recently developed guidelines address multiple risk factors and life-style interventions. However, in current practice few patients reach their targets. A multifactorial approach with the aid of nurse practitioners was effective in achieving treatment goals and reducing vascular events in patients with diabetes mellitus and in patients with heart failure. We propose that this also holds for the CKD population. DESIGN: MASTERPLAN is a multicenter randomized controlled clinical trial designed to evaluate whether a multifactorial approach with the aid of nurse-practicioners reduces cardiovascular risk in patients with CKD. Approximately 800 patients with a creatinine clearance (estimated by Cockcroft-Gault) between 20 to 70 ml/min, will be included. To all patients the same set of guidelines will be applied and specific cardioprotective medication will be prescribed. In the intervention group the nurse practitioner will provide lifestyle advice and actively address treatment goals. Follow-up will be five years. Primary endpoint is the composite of myocardial infarction, stroke and cardiovascular mortality. Secondary endpoints are cardiovascular morbidity, overall mortality, decline of renal function, change in markers of vascular damage and change in quality of life. Enrollment has started in April 2004 and the study is on track with 700 patients included on October 15th, 2005. This article describes the design of the MASTERPLAN study

Connective Tissue Growth Factor and IGF-I Are Produced by Human Renal Fibroblasts and Cooperate in the Induction of Collagen Production by High Glucose

Tubulointerstitial fibrosis is an important component in the development of diabetic nephropathy. Various renal cell types, including fibroblasts, contribute to the excessive matrix deposition in the kidney. Although transforming growth factor-beta (TGF-beta) has been thought to play a major role during fibrosis, other growth factors are also involved. Here we examined the effects of connective tissue growth factor (CTGF) and IGF-I on collagen type I and III production by human renal fibroblasts and their involvement in glucose-induced matrix accumulation. We have demonstrated that both CTGF and IGF-I expressions were increased in renal fibroblasts under hyperglycemic conditions, also in the absence of TGF-beta signaling. Although CTGF alone had no effect on collagen secretion, combined stimulation with IGF-I enhanced collagen accumulation. Furthermore, IGF-I also had a synergistic effect with glucose on the induction of collagens. Moreover, we observed a partial inhibition in glucose-induced collagen secretion with neutralizing anti-CTGF antibodies, thereby demonstrating for the first time the involvement of endogenous CTGF in glucose-induced effects in human renal fibroblasts. Therefore, the cooperation between CTGF and IGF-I might be involved in glucose-induced matrix accumulation in tubulointerstitial fibrosis and might contribute to the pathogenesis of diabetic nephropath

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS

Endoscopic sinus surgery in adult patients with Chronic Rhinosinusitis with nasal polyps (PolypESS) - statistical analysis plan for a multicentre randomised controlled trial

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) afflicts 2-4% of the population and comes with a long time burden of disease and high societal costs. The current treatment consists of medical treatment alone or in combination with endoscopic sinus surgery. No consensus exists on the right timing and extent of disease that warrants surgery. Furthermore, there is lack of clinical knowledge about the benefit of surgery over medication only. The current study evaluates the clinical effectiveness and cost-effectiveness of endoscopic sinus surgery in addition to medical treatment versus medication alone in the adult patient group with nasal polyps (CRSwNP). Methods: The PolypESS trial is designed as a prospective, randomised, multicentre trial in adult patients with CRSwNP selected for primary or revision endoscopic sinus surgery by their otorhinolaryngologist. Patients are randomly assigned to endoscopic sinus surgery in addition to medication or medical therapy only. This paper details the statistical analysis plan (SAP) of this trial and was submitted before outcome data were available. Results: The primary outcome of the trial is disease-specific Health-Related Quality of Life quantified by the SNOT-22 at 12-months follow-up. Secondary outcomes consist of generic and disease-specific Health-Related Quality of Life, objective signs of disease and adverse events of treatment. Subgroup analyses will be performed to verify if treatment effects differ among patient phenotypes. Analyses will be completed according to this pre-specified SAP. The main analysis will be performed as a standard ITT analysis. Discussion: The PolypESS trial will show whether addition of endoscopic sinus surgery to medical treatment improves the disease-specific Health-Related Quality of Life quantified by the SNOT-22 at 12-months follow-up. Unforeseen deviations from the SAP at the time of analysis will be motivated and discussed in the final publication of the primary outcome of this study.</jats:p

Effect of absolute blood volume measurement-guided fluid management on the incidence of intradialytic hypotension-associated events: a randomised controlled trial

BackgroundUltrafiltration to target weight during haemodialysis is complicated by intradialytic hypotension-associated adverse events (IHAAEs) in 10–30% of dialysis treatments. IHAAEs are caused by critical reductions in absolute blood volume (ABV), due to the interaction of ultrafiltration, refill and compensatory mechanisms. Non-randomised studies have suggested that ABV-guided treatment, using an indicator dilution technique employing the blood volume monitor on the dialysis machine, could reduce the incidence of IHAAEs.MethodsWe performed an open-label randomised controlled trial. Patients were randomly assigned to adjustment of target weight guided by ABV measurements or standard care. The primary outcome was the change in the incidence of IHAAEs from baseline, defined as the percentage of treatment episodes in a 4-week period where the patient had a systolic blood pressure ResultsA total of 56 patients were randomised, of whom 29 were allocated to ABV-guided treatment and 27 to standard care. Overall baseline incidence of IHAAEs was 26.0%. ABV-guided treatment significantly reduced the incidence of IHAAEs compared with standard care, with a mean change from baseline of −9.6% [95% confidence interval (CI) −17.3 to −1.8) versus 2.4% (95% CI −2.3–7.2). The adjusted difference between the groups was 10.5% (95% CI 1.3–19.8; P = .026). ABV measurement had moderate agreement with other methods to estimate blood volume. The sensitivity for the previously suggested threshold of a post-dialysis normalised blood volume of 65 ml/kg was observed to be 74% in this study.ConclusionsABV-guided volume management significantly reduced IHAAEs compared with standard care. The clinical relevance of the previously suggested threshold of 65 ml/kg cannot be firmly concluded on the basis of our results. If confirmed in a larger trial, this intervention could potentially change dialysis practice and impact patient care in a clinically meaningful way.Prevention, Population and Disease management (PrePoD)Public Health and primary car