Ferritin measurement IN Donors-Effectiveness of iron Monitoring to diminish iron deficiency and low haemoglobin in whole blood donors (FIND'EM): study protocol for a stepped wedge cluster randomised trial.

BACKGROUND: Blood donors are at risk for reduced iron stores, because of which donor iron monitoring received increased attention in the last decade. Despite the importance for donor health, international consensus on an appropriate policy for iron monitoring is lacking. Therefore, we conduct a trial to evaluate to what extent ferritin-guided donation intervals are effective in increasing haemoglobin and ferritin levels, decreasing low-haemoglobin deferral, increasing donor return and improving the health of whole blood donors in the Netherlands. METHODS: Sanquin Blood Bank is implementing ferritin-guided donation intervals to prevent donors from increasing iron loss at repeated donations. Using a stepped wedge cluster randomised trial approach, the design involves a random crossover of 29 clusters of blood collection centres from the existing policy without ferritin measurements to a ferritin-guided donation interval policy. This new policy includes ferritin measurements for all new donors and at every 5th whole blood donation, extending donation intervals to 6 months if ferritin is 15-≤ 30 ng/mL and to 12 months if ferritin is < 15 ng/mL. We measure ferritin levels of whole blood donors from stored plasma samples and collect haemoglobin levels and information on low-haemoglobin deferral and donor return from the donor database before, during and after the implementation period. We measure donor health during and after the implementation period using questionnaires, assessing physical and mental wellbeing and iron deficiency- and donation-related symptoms. We use multilevel analyses to investigate differences in ferritin and haemoglobin levels, low-haemoglobin deferral rates, donor return and donor health from whole blood donors, between blood collection centres that have versus those that have not yet implemented the ferritin-guided donation interval policy. DISCUSSION: This stepped wedge cluster randomised trial will provide insight into the effectiveness of ferritin-guided donation intervals in lowering iron deficiency, decreasing donor deferrals due to low haemoglobin and improving donor health. We will evaluate a policy that is implemented nationwide in a real-life setting. Our study is therefore not limited to a small experimental setting and the results will guide policymakers seeking an appropriate policy for iron monitoring. TRIAL REGISTRATION: The Dutch trial registry NTR6738 . Registered on 29 September 2017. Retrospectively registered.

Lipid profile and carotid intima-media thickness in a prospective cohort of very preterm subjects at age 19 years: effects of early growth and current body composition.

Cardiovascular disease (CVD) risk is associated with prenatal and infancy growth. However, the relative importance of these time periods for the CVD risk is uncertain. To elucidate this, we tested in a very preterm cohort the effects of birth weight for gestational age and weight gain between birth and 3 mo post-term (early postnatal weight gain) and between 3 mo and 1 y post-term (late infancy weight gain) on the lipid profile and carotid intima-media thickness (CIMT) at age 19 y. A less favorable lipid profile was strongly associated with higher current body mass index (BMI), greater waist circumference, and greater absolute fat mass. CIMT was positively associated with current height, and with low-density lipoprotein (LDL) cholesterol and apolipoprotein B (ApoB) levels, and LDL/high-density lipoprotein (HDL) cholesterol and ApoB/apolipoprotein AI (ApoAI) ratios. Lipid profile and CIMT were unrelated to gestational age, birth weight standard deviation score (SDS) and early postnatal weight gain. CIMT was positively associated with late infancy weight gain, but the relationship disappeared after correction for current height. Our findings in 19 y olds born very preterm argue for an effect of current body composition, rather than of early growth, on the CVD risk. Attempts to reduce the CVD risk in this specific population should focus on weight reduction in young adulthood rather than on optimizing the early growth pattern.

Frequency and time course of reocclusion and restenosis in coronary artery occlusions after balloon angioplasty versus Wiktor stent implantation: results from the Mayo-Japan Investigation for Chronic Total Occlusion (MAJIC) trial.

BACKGROUND: Compared with balloon angioplasty, stent implantation has been shown to reduce restenosis and reocclusion after treatment of chronic total coronary artery occlusions (CTOs). However, little is known about the time course of restenosis and reocclusion after the 2 procedures. The purpose of this study was to examine the frequency and time course of restenosis and reocclusion after treatment of CTOs with balloon angioplasty and Wiktor stent implantation. METHODS AND RESULTS: A total of 221 patients with successfully recanalized CTOs were randomly assigned to either treatment with a coil stent implantation (Wiktor stent, n = 110) or standard balloon angioplasty (n = 111). Repeat angiography was performed the day after treatment and at 6 months. Patients undergoing balloon angioplasty showed 29.8% restenosis and 1.1% reocclusion the following day versus 2% restenosis and no reocclusion in stent patients the following day. The cumulative reocclusion rate was significantly lower in the stent group than in the balloon group at 6 months (2.1% versus 9.3%, P <.05). As a result of the more frequent need of target vessel revascularization (49.5% in the balloon group and 30.6% in the stent group, P <.005) and earlier final follow-up angiography in the balloon group, the frequency of angiographic restenosis at 6 months was similar in both groups (57.3% in the stent group and 54.5% in the balloon group). CONCLUSIONS: The frequency and time course of reocclusion and restenosis after balloon angioplasty and stent placement differ within 24 hours of the procedure and remain different on angiography at 6 months.

Variability of quantitative coronary angiography: an evaluation of on-site versus core laboratory analysis.

To assess the validity of locally performed off-line quantitative coronary angiography (QCA) measurement in clinical trials, we carried out a comparative study between on-site QCA analysis and analysis performed at an independent external core laboratory. One local operator analyzed the pre, post and follow-up angiograms of 116 patients participating in the Stenting in Small Coronary Arteries Study (SISCA) prior to final QCA analysis in the core laboratory. The mean values of the reference diameter (RD), minimal lumen diameter (MLD) and diameter stenosis (DS) showed acceptable agreement between study site and core laboratory. However, on the level of individuals the interobserver differences were large, affecting the outcome of restenosis rate significantly, and in a such way that the conclusions in the SISCA trial might have come out differently if a core laboratory had not been used. This emphasizes the importance of using independent core laboratories in coronary interventional trials.

Low restenosis rate of the NIR coronary stent: results of the Danish multicenter stent study (DANSTENT)--a randomized trial comparing a first-generation stent with a second-generation stent.

BACKGROUND: Larger studies evaluating the angiographic results of second-generation stents are scarce. The objectives of this study were to assess current standards of angiographic and clinical outcomes after implantation of the second-generation stainless steel stent, NIR (Medinol Ltd, Tel Aviv, Israel), and to compare the outcomes with those of the first-generation Palmaz-Schatz (PS) stent (Johnson & Johnson, Warren, NJ). METHODS: Patients having coronary artery lesions that could be covered by a stent of 15 mm in length were randomly assigned to receive the NIR or the PS. Procedural success, 6-month angiographic findings, and 1-year clinical outcomes were determined. RESULTS: In 424 patients included in the study, the overall procedural success rate was high (NIR 98%, PS 99%, P =.90). Follow-up angiography was conducted in 91% of the patients. The overall rate of angiographic restenosis was low in both groups (NIR 9.9%, PS 12.6%, P =.35). We found a low restenosis rate in vessels with a minimal lumen diameter >3.1 mm after the procedure, particularly in the NIR group (<6%). The rate of target lesion revascularization after 1 year did not differ (NIR 12%, PS 10%, P =.47). CONCLUSIONS: The angiographic and clinical outcomes after implantation of the second-generation stainless steel stent were not significantly better than those of the first-generation stent. The low restenosis rates, particularly in patients with the largest minimal lumen diameters after stent implantation, warrants circumspection when planning the evaluation of newer stent technologies that aim to further reduce coronary restenosis.

One core laboratory at two international sites, is that feasible? An inter-core laboratory and intra-observer variability study.

To assess the magnitude of differences in QCA outcomes between two cooperating core laboratories in a single trial, we have carried out an inter-core laboratory variability study. Two QCA experts at the Montreal Heart Institute and Heart Core Leiden both analyzed 32 lesions (pre- and post-intervention) in accordance with previously agreed upon standard operating procedures. One of the experts analyzed the whole image set twice to determine the intraobserver variability. The inter-core laboratory differences in the acute gain (n = 31 pairs) are non-significant. The systematic errors of the individual measurements (n = 63 analyses) show an excellent intraclass correlation coefficient of reliability (>75%), except for the stent length (67.7%). The corresponding random errors are small. In general, the intra-observer systematic and random errors are both slightly smaller than those for the inter-core laboratory study. QCA analyses in clinical trials can be carried out in core laboratories at two different locations if and only if highly standardized conditions are maintained.

A novel measurement technique to assess the effects of coronary brachytherapy in clinical trials.

This paper presents a novel measurement technique to assess the effects of coronary brachytherapy. This new technique is based upon the conventional quantitative coronary analysis (QCA) technique, which is accepted worldwide as an accurate and reliable analysis tool for clinical trials. This paper provides the definitions and main issues important for correct brachytherapy analysis. Based on these definitions, this novel technique is implemented as an extension of conventional QCA software, as a multisegmental analysis tool. It allows to follow the influence of radiation on restenosis, and the mutual relation between intervention devices. A pilot interobserver study was performed to assess the reliability and reproducibility of the brachytherapy analysis tool, using 15 patient cases. The validation results show that the segment lengths, minimum lumen diameter, and reference diameters of the user-defined and derived (sub)segments can be assessed reproducible. However, these good results can only be obtained, when strict and extensive image acquisition and image analysis protocols are followed. From this pilot validation study presented in this paper and only based on a small number of patients, we may conclude that the software can be applied to clinical trials.