scholarly journals An Oral Contraceptive Containing Estetrol 15 MG and Drospirenone 3 MG Has Limited Effects on Endocrine and Metabolic Parameters

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A728-A729
Author(s):  
Christine Klipping ◽  
Ingrid J M Duijkers ◽  
Maud Jost ◽  
Adriana Bastidas ◽  
Jean Michel F Foidart
Keyword(s):  
Carbohydrate Metabolism ◽  
User Satisfaction ◽  
Fetal Liver ◽  
Apolipoprotein A1 ◽  
Metabolic Parameters ◽  
Minor Effect ◽  
Total Cortisol ◽  
Venous Thromboembolic Events ◽  
Endocrine Parameters ◽  
The Impact

Abstract Background: Most combined oral contraceptives (COCs) contain ethinylestradiol (EE), an estrogen component known to increase the risk of venous thromboembolic events. Previous phase 2 trials have shown that Estetrol (E4), a naturally-occurring estrogen produced by the human fetal liver, in combination with Drospirenone (DRSP), inhibits ovulation and is associated with favorable vaginal bleeding, safety and tolerability profiles and high user satisfaction. When administered in doses up to 10 mg for less than 3 months, E4 either alone or in combination with DRSP showed limited effects on liver function as well as on metabolic and endocrine parameters. However, the impact of E4 15 mg/DRSP 3 mg, the selected dose for pregnancy prevention (hereafter referred to as E4/DRSP), on metabolic and endocrine parameters was never investigated. Methods: A randomized, open-label, controlled, three-arm parallel study was conducted in 101 healthy volunteers aged 18-50 years with a body mass index between 18.0 and 30.0 kg/m2. Of the randomized individuals, 98 subjects received either E4/DRSP (n=38), EE 30 µg/levonorgestrel (LNG) 150 µg (n=29) or EE 20 µg/DRSP 3 mg (n=31) COCs for six consecutive treatment cycles of 28 days. Endocrine and metabolic parameters were measured at baseline, cycle 3 and cycle 6. Results: FSH and LH decreased with both EE/LNG (-84% and -92%, respectively) and EE/DRSP (-64% and -90%, respectively), whereas E4/DRSP slightly increased FSH (31%) and had minor effect on LH (-8%). Total cortisol increased by more than 100% during treatment with EE/LNG (109%) and EE/DRSP (107%), while E4/DRSP only slightly increased total cortisol (26%). The effects of E4/DRSP, EE/LNG and EE/DRSP on other endocrine parameters including androstenedione (-31%, -49% and -40%) and free testosterone (-50%, -50% and -71%) were similar. Liver proteins, except CRP, increased from baseline in all treatment groups. The increase in angiotensinogen, CBG, and TBG levels was significantly lower for E4/DRSP (75%, 40% and 17%) in comparison with EE/LNG (170%, 152% and 37%) and EE/DRSP (207%, 140% and 70%). SHBG substantially increased for EE/DRSP (251%), while EE/LNG and E4/DRSP had limited effects on SHBG (74% and 55%, respectively). Triglycerides changed to a lesser extent for E4/DRSP (24%) compared to EE/DRSP (66%); EE/LNG increased triglycerides levels by 28%. Moreover, E4/DRSP had minimal impact on lipid parameters including HDL (4%), Apolipoprotein A1 (5%) and Apolipoprotein B (4%) compared to baseline, and no effects on carbohydrate metabolism. Conclusion: These data confirm that E4/DRSP has limited effects on liver proteins, lipid and carbohydrate metabolism, cortisol, and gonadotropins. The effect on other endocrine parameters, including suppression of ovarian steroids, was typical for a COC. In conclusion, combining E4 15 mg with DRSP 3 mg resulted in a different and potentially favorable metabolic profile.

scholarly journals Clinical implementation of a 3D4K-exoscope (Orbeye) in microneurosurgery

2021 ◽  
Author(s):  
Judith Rösler ◽  
Stefan Georgiev ◽  
Anna L. Roethe ◽  
Denny Chakkalakal ◽  
Güliz Acker ◽  
...  
Keyword(s):  
User Satisfaction ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Intraoperative Complications ◽  
Rank Test ◽  
User Group ◽  
Clinical Implementation ◽  
Physical Strain ◽  
Conventional Microscope ◽  
The Impact

AbstractExoscopic surgery promises alleviation of physical strain, improved intraoperative visualization and facilitation of the clinical workflow. In this prospective observational study, we investigate the clinical usability of a novel 3D4K-exoscope in routine neurosurgical interventions. Questionnaires on the use of the exoscope were carried out. Exemplary cases were additionally video-documented. All participating neurosurgeons (n = 10) received initial device training. Changing to a conventional microscope was possible at all times. A linear mixed model was used to analyse the impact of time on the switchover rate. For further analysis, we dichotomized the surgeons in a frequent (n = 1) and an infrequent (n = 9) user group. A one-sample Wilcoxon signed rank test was used to evaluate, if the number of surgeries differed between the two groups. Thirty-nine operations were included. No intraoperative complications occurred. In 69.2% of the procedures, the surgeon switched to the conventional microscope. While during the first half of the study the conversion rate was 90%, it decreased to 52.6% in the second half (p = 0.003). The number of interventions between the frequent and the infrequent user group differed significantly (p = 0.007). Main reasons for switching to ocular-based surgery were impaired hand–eye coordination and poor depth perception. The exoscope investigated in this study can be easily integrated in established neurosurgical workflows. Surgical ergonomics improved compared to standard microsurgical setups. Excellent image quality and precise control of the camera added to overall user satisfaction. For experienced surgeons, the incentive to switch from ocular-based to exoscopic surgery greatly varies.

Response and failure modes of biaxial warp-knitted flexible composite subject to low-velocity impact

2021 ◽  
pp. 152808372110154
Author(s):  
Ziyu Zhao ◽  
Tianming Liu ◽  
Pibo Ma
Keyword(s):  
Impact Energy ◽  
Linear Density ◽  
Failure Modes ◽  
Impact Response ◽  
Low Velocity Impact ◽  
Minor Effect ◽  
Low Velocity ◽  
Velocity Impact ◽  
Flexible Composites ◽  
The Impact

In this paper, biaxial warp-knitted fabrics were produced with different high tenacity polyester linear density and inserted yarns density. The low-velocity impact property of flexible composites made of polyurethane as matrix and biaxial warp-knitted fabric as reinforcement has been investigated. The effect of impactor shape and initial impact energy on the impact response of flexible composite is tested. The results show that the initial impact energy have minor effect on the impact response of the biaxial warp-knitted flexible composites. The impact resistance of flexible composite specimen increases with the increase of high tenacity polyester linear density and inserted yarns density. The damage morphology of flexible composite materials is completely different under different impactor shapes. The findings have theoretical and practical significance for the applications of biaxial warp-knitted flexible composite.

scholarly journals The impact of innovativeness on user satisfaction to use e-campus

2021 ◽  
Vol 1793 (1) ◽  
pp. 012020
Author(s):  
Hasiah bt. Mat Salleh ◽  
Fahmi Zaidi Abdul Razak
Keyword(s):  
User Satisfaction ◽  
The Impact

scholarly journals Elevated Mcl-1 perturbs lymphopoiesis, promotes transformation of hematopoietic stem/progenitor cells, and enhances drug resistance

Blood ◽  
2010 ◽  
Vol 116 (17) ◽  
pp. 3197-3207 ◽  
Author(s):  
Kirsteen J. Campbell ◽  
Mary L. Bath ◽  
Marian L. Turner ◽  
Cassandra J. Vandenberg ◽  
Philippe Bouillet ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Progenitor Cell ◽  
Fetal Liver ◽  
Cytotoxic Agents ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells ◽  
Fetal Liver Cells ◽  
Follicular Lymphomas ◽  
The Impact

Abstract Diverse human cancers with poor prognosis, including many lymphoid and myeloid malignancies, exhibit high levels of Mcl-1. To explore the impact of Mcl-1 overexpression on the hematopoietic compartment, we have generated vavP-Mcl-1 transgenic mice. Their lymphoid and myeloid cells displayed increased resistance to a variety of cytotoxic agents. Myelopoiesis was relatively normal, but lymphopoiesis was clearly perturbed, with excess mature B and T cells accumulating. Rather than the follicular lymphomas typical of vavP-BCL-2 mice, aging vavP-Mcl-1 mice were primarily susceptible to lymphomas having the phenotype of a stem/progenitor cell (11 of 30 tumors) or pre-B cell (12 of 30 tumors). Mcl-1 overexpression dramatically accelerated Myc-driven lymphomagenesis. Most vavP-Mcl-1/ Eμ-Myc mice died around birth, and transplantation of blood from bitransgenic E18 embryos into unirradiated mice resulted in stem/progenitor cell tumors. Furthermore, lethally irradiated mice transplanted with E13 fetal liver cells from Mcl-1/Myc bitransgenic mice uniformly died of stem/progenitor cell tumors. When treated in vivo with cyclophosphamide, tumors coexpressing Mcl-1 and Myc transgenes were significantly more resistant than conventional Eμ-Myc lymphomas. Collectively, these results demonstrate that Mcl-1 overexpression renders hematopoietic cells refractory to many cytotoxic insults, perturbs lymphopoiesis and promotes malignant transformation of hematopoietic stem and progenitor cells.

Validation of a Musculoskeletal Digital Assessment Routing Tool (DART): Protocol for a Pilot Randomised Crossover Non-Inferiority Trial (Preprint)

2021 ◽  
Author(s):  
Cabella Lowe ◽  
Harry Hanuman Sing ◽  
William Marsh ◽  
Dylan Morrissey
Keyword(s):  
Clinical Trials ◽  
Data Collection ◽  
Real World ◽  
User Satisfaction ◽  
Allocation Concealment ◽  
Trial Methodology ◽  
Primary Analysis ◽  
Digital Assessment ◽  
System Usability Scale ◽  
The Impact

BACKGROUND Musculoskeletal conditions account for 16% of global disability, resulting in a negative effect on millions of patients and an increasing burden on healthcare utilization. Digital technologies to improve health care outcomes and efficiency are considered a priority; however, innovations are rarely tested with sufficient rigor in clinical trials, the gold standard for clinical proof of safety and efficacy. We have developed a new musculoskeletal Digital Assessment Routing Tool (DART) that allows users to self-assess and be directed to the right care. DART requires validation in a real-world setting prior to implementation. OBJECTIVE This pilot study will assess the feasibility of a future trial by exploring key aspects of trial methodology, assess the procedures and collect exploratory data to inform the design of a definitive, randomized, crossover, non-inferiority trial to assess DART safety and effectiveness. METHODS We will collect data from 76 adult participants presenting to an NHS England GP practice with a musculoskeletal condition. Participants will complete both a DART assessment and a physiotherapist-led triage with the order determined by randomization. The primary analysis will involve an absolute agreement ICC (A,1) estimate with 95% confidence intervals between DART and the clinician for assessment outcomes sign-posting to condition management pathways. Data will be collected to allow analysis of participant recruitment and retention, randomization, allocation concealment, blinding, data collection process and bias. In addition, the impact of trial burden and potential barriers to intervention delivery will be considered. DART user satisfaction will be measured using the System Usability Scale. RESULTS A UK NHS ethics submission will be submitted during June 2021 and pending approval, recruitment will commence during August 2021 with data collection anticipated to last for 3 months. Results will be reported in a follow-up paper later in 2021. CONCLUSIONS This study will inform the design of a randomized controlled crossover non-inferiority study that will provide evidence concerning mHealth DART system clinical sign posting in an NHS setting prior to real-world implementation. Success should produce evidence of a safe, effective system with excellent usability, facilitating quicker and easier patient access to appropriate care while reducing the burden on primary and secondary care musculoskeletal services. This rigorous approach to mHealth system testing could be used as a guide for other developers of similar applications. CLINICALTRIAL This trial is registered with Clinical Trials number NCT04904029

Sign in / Sign up

Export Citation Format

Share Document