Intravenous immunoglobulin and prednisolone to women with unexplained recurrent pregnancy loss after assisted reproductive technology treatment:a protocol for a randomised, double-blind, placebo-controlled trial

INTRODUCTION: Recurrent pregnancy loss (RPL), defined as two or more consecutive pregnancy losses in the first trimester, affects around 5% of fertile women. The underlying causes remain unknown in up to 60% of patients; however, most studies point at an immunological pathology in unexplained RPL, and therefore, an effective treatment may be immunomodulatory. This study aims to evaluate the effect of intravenous immunoglobulin (IVIg) and prednisolone on reproductive outcome and the immune system in women with unexplained RPL undergoing assisted reproductive technology treatment. METHODS AND ANALYSIS: This randomised, placebo-controlled trial with double-blinded randomisation to two parallel arms evaluate if immunomodulatory (active) treatment is superior to placebo in increasing the chance of ongoing pregnancy assessed at nuchal translucency scan in gestational weeks (GW) 11–13 after embryo transfer (ET) in 74 RPL patients with ≥2 pregnancy losses as its primary objective. The active treatment consists of IVIg (one infusion preferably 1–5 days before ET and in GW 5, 6 and 7) and prednisolone (5 mg/day from first day of menstrual bleeding until ET and 10 mg/day from ET to GW 8+0) while the comparator consists of intravenous human albumin (5%) and placebo tablets. Allocation is concealed for participants, caregivers, and investigators until trial termination and is performed in a 1:1 ratio. The secondary objective is to evaluate treatment safety, and the tertiary objective is exploration of the association between treatment, reproductive outcome after ET, and the lymphocyte subset distribution in peripheral blood collected before and after intravenous infusion(s). Excess biological material is stored in a biobank for future research. ETHICS AND DISSEMINATION: The North Denmark Region Committee on Health Research Ethics (N-20200066) approved this trial. The results will be published in peer-reviewed scientific journals and presented to relevant patient associations, at relevant academic conferences and to key stakeholders. TRIAL REGISTRATION NUMBER: NCT04701034

Pilot scale production of Hermetia illucens (L.) larvae and frass using former foodstuffs

The food and feed sector requires new sustainable sources of protein and innovative solutions for upcycling of food waste (former foodstuffs), which today is downcycled into energy or even wasted. This study aimed at evaluating the use of former foodstuff waste streams as feed substrate for Hermetia illucens (L.) larvae (black soldier fly larvae, BSFL) under long-term and semi-industrial conditions. Different foodstuff-based mixtures and different stocking BSFL densities were used during 20 batches, and quality and safety assessments were performed on the main outputs, namely BSFL production performance, frass impurities, larval and frass nutrient profiles and heavy metal content. About 1400 kg of former foodstuffs (fresh weight) were used to produce 239 kg BSFL and 230 kg frass. The production of BSFL reared on former foodstuffs was highly efficient, with feed conversion rates (FCR) ranging between 2.3 and 5.5 (dry matter basis). The optimization experiment revealed that former foodstuffs-based mixture and high larval density (10 larvae/cm2) lead to highly efficient (FCR: 2.6) and heavy metal-free production of BSFL and frass. The quality of the derived BSFL meal was high in terms of protein and amino acids. Furthermore, the quality of the technical frass was high in terms of N, P, and K levels and minimal packaging material residuals (<2.65%). This investigation suggests that nutrients in former foodstuffs can be successfully and safely recycled in production of BSFL

The Western Denmark Cardiac Computed Tomography Registry:a review and validation study

BACKGROUND: As a subregistry to the Western Denmark Heart Registry (WDHR), the Western Denmark Cardiac Computed Tomography Registry (WDHR-CCTR) is a clinical database established in 2008 to monitor and improve the quality of cardiac computed tomography (CT) in Western Denmark. OBJECTIVE: We examined the content, data quality, and research potential of the WDHR-CCTR. METHODS: We retrieved 2008–2012 data to examine the 1) content; 2) completeness of procedure registration using the Danish National Patient Registry as reference; 3) completeness of variable registration comparing observed vs expected numbers; and 4) positive predictive values as well as negative predictive values of 19 main patient and procedure variables. RESULTS: By December 31, 2012, almost 22,000 cardiac CTs with up to 40 variables for each procedure have been registered. Of these, 87% were coronary CT angiography performed in patients with symptoms indicative of coronary artery disease. Compared with the Danish National Patient Registry, the overall procedure completeness was 72%. However, an additional medical record review of 282 patients registered in the Danish National Patient Registry, but not in the WDHR-CCTR, showed that coronary CT angiographies accounted for only 23% of all nonregistered cardiac CTs, indicating >90% completeness of coronary CT angiographies in the WDHR-CCTR. The completeness of individual variables varied substantially (range: 0%–100%), but was >85% for more than 70% of all variables. Using medical record review of 250 randomly selected patients as reference standard, the positive predictive value for the 19 variables ranged from 89% to 100% (overall 97%), whereas the negative predictive value ranged from 97% to 100% (overall 99%). Stratification by center status showed consistently high positive and negative predictive values for both university (96%/99%) and nonuniversity centers (97%/99%). CONCLUSION: WDHR-CCTR provides ongoing prospective registration of all cardiac CTs performed in Western Denmark since 2008. Overall, the registry data have a high degree of completeness and validity, making it a valuable tool for clinical epidemiological research

Incidence and severity of paravalvular aortic regurgitation with multidetector computed tomography nominal area oversizing or undersizing after transcatheter heart valve replacement with the Sapien 3 : a comparison with the Sapien XT.

Objectives : This study sought to compare the influence of the extent of multidetector computed tomography (MDCT) area oversizing on the incidence of paravalvular aortic regurgitation (PAR) between the Sapien 3 and the Sapien XT transcatheter heart valve (THV) to define a new MDCT sizing guideline suitable for the Sapien 3 platform. Background : The inverse relationship of PAR occurrence and oversizing has been demonstrated for the Sapien XT but the incidence of PAR with comparable oversizing with the Sapien 3 is not known. Methods : Sixty-one prospectively enrolled patients who underwent transcatheter aortic valve replacement with the Sapien 3 THV were compared with 92 patients who underwent transcatheter aortic valve replacement with the Sapien XT THV. Patients were categorized depending on the degree of MDCT area oversizing percentage: undersizing (below 0%), 0% to 5%, 5% to 10%, and above 10%. The primary endpoint was mild or greater PAR on transthoracic echocardiography. Results : Mild or greater PAR was present in 19.7% of patients (12 of 61) in the Sapien 3 group and in 54.3% of patients (50 of 92) in the Sapien XT group (p 10% (p for interaction = 0.54). Moderate or severe PAR rates were also lower in the Sapien 3 group than in the Sapien XT group (3.3% vs. 13.0%, p = 0.04). In the Sapien 3 group, a MDCT area oversizing percentage value of =4.17% was identified as the optimal cutoff value to discriminate patients with or without mild or greater PAR. Conclusions : Our retrospective analysis suggests that the Sapien 3 THV displays significantly lower rates of PAR than does the Sapien XT THV. A lesser degree of MDCT area oversizing may be employed for this new balloon-expandable THV

Diagnosis of obstructive coronary artery disease using computed tomography angiography in patients with stable chest pain depending on clinical probability and in clinically important subgroups: meta-analysis of individual patient data

OBJECTIVE: To determine whether coronary computed tomography angiography (CTA) should be performed in patients with any clinical probability of coronary artery disease (CAD), and whether the diagnostic performance differs between subgroups of patients. DESIGN: Prospectively designed meta-analysis of individual patient data from prospective diagnostic accuracy studies. DATA SOURCES: Medline, Embase, and Web of Science for published studies. Unpublished studies were identified via direct contact with participating investigators. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Prospective diagnostic accuracy studies that compared coronary CTA with coronary angiography as the reference standard, using at least a 50% diameter reduction as a cutoff value for obstructive CAD. All patients needed to have a clinical indication for coronary angiography due to suspected CAD, and both tests had to be performed in all patients. Results had to be provided using 2×2 or 3×2 cross tabulations for the comparison of CTA with coronary angiography. Primary outcomes were the positive and negative predictive values of CTA as a function of clinical pretest probability of obstructive CAD, analysed by a generalised linear mixed model; calculations were performed including and excluding non-diagnostic CTA results. The no-treat/treat threshold model was used to determine the range of appropriate pretest probabilities for CTA. The threshold model was based on obtained post-test probabilities of less than 15% in case of negative CTA and above 50% in case of positive CTA. Sex, angina pectoris type, age, and number of computed tomography detector rows were used as clinical variables to analyse the diagnostic performance in relevant subgroups. RESULTS: Individual patient data from 5332 patients from 65 prospective diagnostic accuracy studies were retrieved. For a pretest probability range of 7-67%, the treat threshold of more than 50% and the no-treat threshold of less than 15% post-test probability were obtained using CTA. At a pretest probability of 7%, the positive predictive value of CTA was 50.9% (95% confidence interval 43.3% to 57.7%) and the negative predictive value of CTA was 97.8% (96.4% to 98.7%); corresponding values at a pretest probability of 67% were 82.7% (78.3% to 86.2%) and 85.0% (80.2% to 88.9%), respectively. The overall sensitivity of CTA was 95.2% (92.6% to 96.9%) and the specificity was 79.2% (74.9% to 82.9%). CTA using more than 64 detector rows was associated with a higher empirical sensitivity than CTA using up to 64 rows (93.4% v 86.5%, P=0.002) and specificity (84.4% v 72.6%, P<0.001). The area under the receiver-operating-characteristic curve for CTA was 0.897 (0.889 to 0.906), and the diagnostic performance of CTA was slightly lower in women than in with men (area under the curve 0.874 (0.858 to 0.890) v 0.907 (0.897 to 0.916), P<0.001). The diagnostic performance of CTA was slightly lower in patients older than 75 (0.864 (0.834 to 0.894), P=0.018 v all other age groups) and was not significantly influenced by angina pectoris type (typical angina 0.895 (0.873 to 0.917), atypical angina 0.898 (0.884 to 0.913), non-anginal chest pain 0.884 (0.870 to 0.899), other chest discomfort 0.915 (0.897 to 0.934)). CONCLUSIONS: In a no-treat/treat threshold model, the diagnosis of obstructive CAD using coronary CTA in patients with stable chest pain was most accurate when the clinical pretest probability was between 7% and 67%. Performance of CTA was not influenced by the angina pectoris type and was slightly higher in men and lower in older patients. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42012002780