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Zwolle, Netherlands

Van Den Brand J.A.J.G.,Radboud University Nijmegen | Van Dijk P.R.,Isala Clinics | Hofstra J.M.,Radboud University Nijmegen | Wetzels J.F.M.,Radboud University Nijmegen
Journal of the American Society of Nephrology | Year: 2014

Recently published Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend limiting the use of immunosuppressive drugs in idiopathic membranous nephropathy to patients at the highest risk of kidney failure. However, recommendations are based on natural history rather than direct assessment of a restrictive treatment strategy. Here, we describe the long-termoutcomes of treating a large cohort of patients with idiopathic membranous nephropathy according to a restrictive treatment policy. We analyzed data for 254 patients who visited our outpatient clinic between 1995 and 2009. All patients were treated with angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers. Immunosuppressive therapy was recommended in cases of deteriorating renal function or untreatable nephrotic syndrome. Primary outcomes for the present study were renal replacement therapy and death. Secondary outcomes included adverse events during follow-up and remission of proteinuria. In total, 124 patients (49%) received immunosuppressive therapy, which predominantly consisted of cyclophosphamide combined with steroids. Ten-year cumulative incidence rates were 3% for renal replacement therapy and 10% for death. Partial remission rates were 39%, 70%, and 83% after 1, 3, and 5 years, respectively; complete remission rateswere5%, 24%, and 38%at 1, 3, and 5 years, respectively. Aserious adverse event occurred in 23% of all patients. The most notable complications were infections (17%), leukopenia (18%), cardiovascular events (13%), and malignancies (8%). In conclusion, the use of a restrictive treatment strategy in this cohort of patients with idiopathic membranous nephropathy yielded favorable outcomes while limiting the number of patients exposed to toxic drugs. These results support current KDIGO guidelines. Copyright © 2014 by the American Society of Nephrology.

Joosten H.,University of Groningen | Van Eersel M.E.A.,University of Groningen | Gansevoort R.T.,University of Groningen | Bilo H.J.G.,Isala Clinics | And 2 more authors.
Stroke | Year: 2013

Background and Purpose-Cognitive decline occurs earlier than previously realized and is already evident at the age of 45. Because cardiovascular risk factors are established risk factors for cognitive decline in old age, we investigated whether cardiovascular risk factors are also associated with cognitive decline in young and middle-aged groups. Methods-The cross-sectional study included 3778 participants aged 35 to 82 years (mean age, 54 years) and free of cardiovascular disease and stroke. Cognitive function was measured with the Ruff Figural Fluency Test (RFFT; worst score, 0; best score, 175 points) and the Visual Association Test (VAT; worst score, 0; best score, 12 points). Overall cardiovascular risk was assessed with the Framingham Risk Score (FRS) for general cardiovascular disease (best score,-5; worst score, 33 points). Results-Mean RFFT score (SD) was 70 (26) points, median VAT score (interquartile range) was 10 (9-11) points, and mean FRS (SD) was 10 (6) points. Using linear regression analysis adjusting for educational level, RFFT was negatively associated with FRS. RFFT score decreased by 1.54 points (95% confidence interval,-1.66 to-1.44; P<0.001) per point increase in FRS. This negative association was not only limited to older age groups, but also found in the young (35-44 years). The main influencing components of the FRS were age (P<0.001), diabetes mellitus (P=0.001), and smoking (P<0.001). Similar results were found for VAT score as outcome measure. Conclusions-In this large population-based cohort, a worse overall cardiovascular risk profile was associated with poorer cognitive function. This association was already present in young adults aged 35 to 44 years. © 2013 American Heart Association, Inc.

Hofma S.H.,Medical Center Leeuwarden | Brouwer J.,Medical Center Leeuwarden | Velders M.A.,Medical Center Leeuwarden | Van'T Hof A.W.J.,Isala Clinics | And 4 more authors.
Journal of the American College of Cardiology | Year: 2012

Objectives: The goal of this study was to compare the efficacy and safety of second-generation everolimus-eluting stents (EES) with first-generation sirolimus-eluting stents (SES) in primary percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI). Background: Drug-eluting stents (DES) in AMI are still feared for possible late and very late stent thrombosis (ST). Newer-generation DES, with more hemocompatible polymers and improved healing, may show promise regarding increased efficacy of DES with improved safety. However, no randomized trials in AMI are available. Methods: A total of 625 patients with AMI were randomized (2:1) to receive EES or SES in the XAMI (XienceV Stent vs Cypher Stent in Primary PCI for Acute Myocardial Infarction) trial. Primary endpoint was major adverse cardiac events (MACE) at 1 year consisting of cardiac death, nonfatal AMI, or any target vessel revascularization. The study was powered for noninferiority of EES. Secondary endpoints comprised ST rates and MACE rate up to 3 years. Results: The MACE rate was 4.0% for EES and 7.7% for SES; the absolute difference was -3.7% (95% confidence interval: -8.28 to -0.03; p = 0.048) and relative risk was 0.52 (95% confidence interval: 0.27 to 1.00). One-year cardiac mortality was low at 1.5% for EES versus 2.7% for SES (p = 0.36), and 1-year incidence of definite and/or probable ST was 1.2% for EES versus 2.7% for SES (p = 0.21). Conclusions: In this all-comer, randomized, multicenter AMI trial, second-generation EES was noninferior to SES, and superiority for MACE was suggested. ST rate in EES at 1-year was low, but long-term follow-up and larger studies will have to show whether very late ST rates will also be improved in newer DES. (XienceV Stent vs Cypher Stent in Primary PCI for Acute Myocardial Infarction [XAMI]; NTR1123) © 2012 American College of Cardiology Foundation.

Mutsaerts M.A.Q.,University of Groningen | Kuchenbecker W.K.H.,Isala Clinics | Land J.A.,University of Groningen | Hoek A.,University of Groningen
Human Reproduction | Year: 2013

STUDY QUESTION: What are the dropout rates in lifestyle intervention programs (LIPs) for overweight and obese infertile women and can intervention- or patient-related baseline factors associated with dropout be identified in these women?SUMMARY ANSWERThe median dropout rate was 24% in overweight and obese infertile women who participated in a LIP; clinical useful intervention or patient-related factors associated with dropout could not be identified.WHAT IS KNOWN ALREADYOverweight and obese infertile women might improve their chance of conception when they improve their lifestyle and lose weight. Dropout from LIPs reduces the chance of losing considerable weight and is therefore considered to be an important limiting factor of the success of LIPs.STUDY DESIGN, SIZE, DURATIONThis systematic review included 15 studies published between January 1980 and December 2012.PARTICIPANTS/MATERIALS, SETTING, METHODSThe included studies investigated the effect of LIPs for overweight and obese infertile women with infertility. From these studies, dropout rates and intervention- and patient-related baseline factors associated with dropout, as well as weight loss and pregnancy rates, were recorded. MAIN RESULTS AND THE ROLE OF CHANCE: There were 15 studies identified, of which 10 reported dropout rates. The median dropout rate was 24% (range: 0-31%). Four studies reported baseline characteristics of women who dropped out, but modifiable predictors of dropout could not be identified. Weight loss and pregnancy rates were lower in women who dropped out than in women who completed the LIPs. LIMITATIONS, REASONS FOR CAUTION: There were limited numbers of studies investigating patient-related factors associated with dropout. The heterogeneity in the studies precluded us from drawing firm conclusions on the relation between the type of intervention and dropout. WIDER IMPLICATIONS OF THE FINDINGS: Dropout from LIPs is a major drawback because it predisposes to less weight loss and lower pregnancy rates. Identification of predictors of dropout is needed to identify overweight and obese infertile women who are prone for dropout. These women might benefit from extra support and monitoring, to potentially increasing adherence rates, weight loss and pregnancy chances. STUDY FUNDING/COMPETING INTEREST(S): M.A.Q.M. was supported by a research grant from the Dutch Organization for Health Research and Development (ZonMw). The department of obstetrics and gynaecology received research grants from Merck Sharpe and Dohme BV, feering pharmaceuticals, Merck Serono, the Netherlands. © 2013 The Author.

Cantineau A.E.P.,University of Groningen | Cohlen B.J.,Isala Clinics | Klip H.,Research Bureau | Heineman M.J.,University of Amsterdam
Human Reproduction | Year: 2011

Background: This multicenter, double-blinded RCT investigated the efficacy of GnRH antagonists in cycles with mild ovarian hyperstimulation (MOH) followed by IUI in subfertile women.MethodsCouples diagnosed with unexplained, male factor subfertility or associated with the presence of minimal or mild endometriosis were randomized with a computer-generated list of numbers by a third party in a double-blinded setting to receive either a GnRH antagonists or a placebo in 12 institutional or academic hospitals. All women were treated with recombinant FSH in a low-dose step-up regimen starting on Day 24 of the cycle. A GnRH antagonist was added when one or more follicles of 14 mm diameter or more were visualized. When at least one follicle reached a size of <18 mm, ovulation was induced by hCG injection. A single IUI was performed 3840 h later. Couples were offered a maximum of three consecutive cycles. The primary outcome of the trial was live births. Secondary outcomes were pregnancy rates, multiple pregnancy rates, miscarriages and ovarian hyperstimulation syndrome rate.ResultsA total of 233 couples were included from January 2006 to February 2009, starting 572 treatment cycles. Live birth rates were not significantly different between the group treated with GnRH antagonist (8.4; 23/275) and the placebo group (12; 36/297) (P 0.30). Three twin pregnancies occurred in the GnRH antagonist group and two twin pregnancies in the placebo group. Conclusions Adding a GnRH antagonist in cycles with MOH in an IUI program does not increase live birth rates.Dutch Trial Register no: NTR497. © 2011 The Author.

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