The eTHINK Study: Cognitive and Behavioral Outcomes in Children with Hemophilia.

Objective: To assess cognitive, behavioral, and adaptive functions in children and young adults with hemophilia treated according to contemporary standards of care.

Study Design: Evolving Treatment of Hemophilia's Impact on Neurodevelopment, Intelligence, and Other Cognitive Functions (eTHINK) is a US-based, prospective, cross-sectional, observational study (September 2018 through October 2019). Males (aged 1-21 years) with hemophilia A or B of any severity, with or without inhibitors, were eligible.

Reassessing the Composition of Hybrid Orbitals in Contemporary VB Calculations.

Large variations in the ratios between the p and s components of individual hybrid orbitals that have been observed in contemporary ab initio VB calculations are reassessed, and links are established to specific energy terms that drive bond formation. It is demonstrated that the ratios between the p and s components for individual hybrid orbitals are not indicative of the overall hybridization status of the relevant atom, which exhibits only relatively small variations with the level of theory, irrespective of whether or not non-dynamical and dynamical electron correlation effects are accounted for. An alternative orbital representation that turns out to be far more consistent with the overall hybridization of the relevant atom is examined.

Magnetic Shielding Analysis of Bonding in [1.1.1]Propellane.

The bonding in [1.1.1]propellane, bicyclo[1.

Role of Dynamical Electron Correlation in the Differences in Bonding between CaAlH and MgAlH.

The most important factor behind the intriguing differences between the geometries of the M'AlH (M' = Mg, Ca) molecules is shown to be dynamical electron correlation and not intramolecular Coulombic interactions, as previously thought. Spin-coupled generalized valence bond (SCGVB) calculations reveal the different bonding situations in the two molecules at their optimal geometries but do not explain why these geometries differ so much; the solution to this conundrum comes instead from detailed analysis of coupled-cluster (CCSD(T)) energies at model and optimal geometries.

Spin-Coupled Generalized Valence Bond Theory: New Perspectves on the Electronic Structure of Molecules and Chemical Bonds.

Spin-Coupled Generalized Valence Bond (SCGVB) theory provides the foundation for a comprehensive theory of the electronic structure of molecules. SCGVB theory offers a compelling orbital description of the electronic structure of molecules as well as an efficient and effective zero-order wave function for calculations striving for quantitative predictions of molecular structures, energetics, and other properties. The orbitals in the SCGVB wave function are usually semilocalized, and for most molecules, they can be interpreted using concepts familiar to all chemists (hybrid orbitals, localized bond pairs, lone pairs, etc.

Impact of haemophilia on patients with mild-to-moderate disease: Results from the P-FiQ and B-HERO-S studies.

Introduction: Epidemiologic studies suggest that joint bleeding occurs in patients with mild-to-moderate haemophilia, including women and girls. However, most previous studies on the impacts of haemophilia focus on men with severe disease.

Aim: To identify unmet needs in men and women with mild-to-moderate haemophilia.

Identified unmet needs and proposed solutions in mild-to-moderate haemophilia: A summary of opinions from a roundtable of haemophilia experts.

Introduction: The experiences of patients with mild-to-moderate haemophilia differ from those of patients with severe haemophilia or those without a bleeding disorder and include a challenging diagnosis and variability in bleeding symptoms and treatment needs. In addition, there is a significant lack of data on mild-to-moderate haemophilia, and many unmet needs remain to be identified and addressed in this group of patients.

Methods: Challenges for these patients, including women with haemophilia, were identified during a roundtable meeting attended by a group of US-based experts including healthcare professionals (e.

Excited-State Aromaticity Reversals in Möbius Annulenes.

It is suggested that Möbius annulenes follow a rule similar to Baird's rule such that the 4 and 4 + 2 criteria for Möbius electronic ground-state aromaticity and antiaromaticity are reversed in the lowest triplet and first singlet excited electronic states. Support comes from an investigation of aromaticity in the ground (S), lowest triplet (T), and first singlet excited (S) electronic states of the Möbius-aromatic cyclononatetraenyl cation, CH, using isotropic magnetic shielding isosurfaces calculated with state-optimized complete-active-space self-consistent field wave functions constructed from gauge-including atomic orbitals. Examination of these isosurfaces demonstrates that while the S state of CH is aromatic, the T and S states are antiaromatic.

Are Multicentre Bond Indices and Related Quantities Reliable Predictors of Excited-State Aromaticity?

Systematic scrutiny is carried out of the ability of multicentre bond indices and the NOEL-based similarity index to serve as excited-state aromaticity criteria. These indices were calculated using state-optimized complete active-space self-consistent field wavefunctions for several low-lying singlet and triplet states of the paradigmatic molecules of benzene and square cyclobutadiene and the inorganic ring SN. The comparison of the excited-state indices with aromaticity trends for individual excited states suggested by the values of magnetic aromaticity criteria show that whereas the indices work well for aromaticity reversals between the ground singlet and first triplet electronic states, addressed by Baird's rule, there are no straightforward parallels between the two sets of data for singlet excited states.

Psychosocial Impact and Disease Management in Patients with Congenital Factor VII Deficiency.

Purpose: Congenital factor VII (FVII) deficiency is a rare bleeding disorder of variable phenotype with predominantly mucocutaneous bleeding. The aim of this study was to identify the burden of FVII deficiency on patients and caregivers through a better understanding of the management and psychosocial impact of this disease.

Materials And Methods: A rare disease specialty recruiter from Comprehensive Health Education Services recruited participants for this online survey, which was conducted from January 31 to March 12, 2019.

Disease Burden in Patients with Glanzmann's Thrombasthenia: Perspectives from the Glanzmann's Thrombasthenia Patient/Caregiver Questionnaire.

Purpose: Glanzmann's thrombasthenia (GT) is a rare bleeding disorder caused by a mutation in the αIIbβ3 integrin essential for optimal platelet function and hemostasis. The aim of this study was to identify the burden of GT on patients and caregivers through better understanding of the management and psychosocial impact of this disorder.

Patients And Methods: Participants for this online survey were recruited using a rare disease specialty recruiter from Comprehensive Health Education Services.

Hemophilia without prophylaxis: Assessment of joint range of motion and factor activity.

Background: Recurrent joint bleeding in hemophilia results in arthropathy and functional impairment. The relationship of arthropathy development and factor activity (FA) has not been reported in patients with FA levels <15%-20%.

Methods: During the Centers for Disease Control and Prevention Universal Data Collection, joint range-of-motion (ROM) measurements were taken at each comprehensive visit.

Resolving a puzzling anomaly in the spin-coupled generalized valence bond description of benzene.

In an earlier study of benzene, Small and Head-Gordon found that the spin-coupled generalized valence bond (SCGVB) wave function for the π system predicted a distorted (non-D ) geometry, one with alternating CC bond lengths. However, the variations in the energy were very small and the predictions were made using a very small basis set (STO-3G). We re-examined this prediction using a much larger basis set (aug-cc-pVTZ) to determine the dependence of the energy of benzene on the distortion angle, Δθ (Δθ = 0° corresponds to the D structure).

Awareness, Care and Treatment In Obesity maNagement to inform Haemophilia Obesity Patient Empowerment (ACTION-TO-HOPE): Results of a survey of US patients with haemophilia and obesity (PwHO) and their partners and caregivers.

Background: The ACTION study identified barriers to initiating and maintaining weight loss in patients with obesity; however, joint-related issues (pain, mobility and bleeding) may affect perceptions of patients with haemophilia and obesity (PwHO).

Aim: To identify patient and caregiver insights on the unique challenges of PwHO.

Methods: Following IRB approval, adults who self-identified as PwHO, spouses/partners of adult PwHO, and caregivers of adolescent PwHO (aged 12-17 years) completed an online survey between December 2017 and April 2018.

Awareness, Care and Treatment In Obesity maNagement to inform Haemophilia Obesity Patient Empowerment (ACTION-TO-HOPE): Results of a survey of US haemophilia treatment centre professionals.

Background: Despite the high prevalence of overweight and obesity in the United States, few studies have assessed the impact of obesity on haemophilia-specific outcomes or experiences/perceptions of healthcare providers (HCPs) treating haemophilia.

Aim: The Awareness, Care and Treatment In Obesity maNagement to inform Haemophilia Obesity Patient Empowerment (ACTION-TO-HOPE) study was designed to identify HCP insights on the unique challenges of patients with haemophilia and obesity/overweight (PwHO) and the barriers to chronic weight management.

Methods: An online survey collected data from haemophilia treatment centre-based HCPs.

Population Pharmacokinetic Modeling Of On-Demand And Surgical Use Of Nonacog Beta Pegol (N9-GP) And rFIXFc Based Upon The paradigm 7 Comparative Pharmacokinetic Study.

Aim/objective: Understanding pharmacokinetic (PK) differences between standard and extended half-life (EHL) products is important, particularly for factor IX (FIX), where differences are more significant than for factor VIII. Two single-dose PK trials showed N9-GP achieves higher FIX levels and greater area-under-the-curve than pdFIX, rFIX, and rFIXFc through higher recovery and longer terminal half-life. In paradigm 7, N9-GP demonstrated consistently favorable PK characteristics compared with rFIXFc.

Hemophilia and sexual health: results from the HERO and B-HERO-S studies.

Background: Sexual health plays a primary role in quality of life (QoL) for many people, including those with hemophilia; however, there is little information available about sexual relationships and satisfaction in patients with hemophilia.

Methods: To address this issue, the Hemophilia Experiences, Results and Opportunities (HERO) and the Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) studies included questions from the Male Sexual Health Questionnaire (MSHQ).

Results: Although these data were not statistically analyzed for comparisons between the 3 populations (HERO, HERO US only, and B-HERO-S), in general, participants in the HERO survey appeared to be more satisfied with their sexual relationship than participants in the B-HERO-S survey.

Neuropsychological function in children with hemophilia: A review of the Hemophilia Growth and Development Study and introduction of the current eTHINK study.

Almost all of what is known about neurologic and cognitive development in hemophilia derives from the Hemophilia Growth and Development Study, conducted during an era when treatment regimens and comorbidities differed significantly from the current environment. Results suggested hemophilia and human immunodeficiency virus had independent effects, and hemophilia negatively impacts academic achievement, attention, and behavior. The introduction of prophylaxis treatment in hemophilia has created the need for re-evaluation of the effects of hemophilia on neurodevelopment and cognition.

Thrombotic events with recombinant activated factor VII (rFVIIa) in approved indications are rare and associated with older age, cardiovascular disease, and concomitant use of activated prothrombin complex concentrates (aPCC).

Purpose: Recombinant activated factor VII (rFVIIa; NovoSeven RT; Novo Nordisk A/S, Bagsvaerd, Denmark) is approved in the United States for the treatment of bleeding and perioperative management in congenital hemophilia with inhibitors (CHwI), acquired hemophilia (AH), congenital factor VII (FVII) deficiency, and Glanzmann's thrombasthenia (GT) with refractoriness to platelets. The aim of the current analysis was to review clinical trials and registries pre- and post-licensure for each indication to establish the estimated rate of thrombosis and then to establish the association of all reported thrombotic events (TEs) with certain risk factors listed for many years in the prescribing information (PI).

Patients And Methods: A retrospective safety assessment of both clinical trials and registries used to support licensure and postmarketing surveillance was performed.

Correlations between patient-reported outcomes and self-reported characteristics in adults with hemophilia B and caregivers of children with hemophilia B: analysis of the B-HERO-S study.

Purpose: Pain, anxiety, depression, and other aspects of health-related quality of life (HRQoL) are important issues for people with hemophilia and caregivers of children with hemophilia. Patient-reported outcome (PRO) instruments may be used to assess aspects of HRQoL; however, the use of PROs in clinical management of patients with hemophilia is limited and inconsistent. The Bridging Hemophilia B Experiences, Results and Opportunities Into Solutions (B-HERO-S) study evaluated the impact of hemophilia B on HRQoL and other psychosocial aspects in affected adults and caregivers of children with hemophilia B.

Mild-severe hemophilia B impacts relationships of US adults and children with hemophilia B and their families: results from the B-HERO-S study.

Background: The B-HERO-S study evaluated the impact of mild to severe hemophilia B on the lives of affected adults and children. Here, we assessed the impact of hemophilia B on relationships.

Methods: US adults with hemophilia B and caregivers of affected children completed separate online surveys that included questions regarding impact of the disease on interpersonal relationships.

Nine questions on energy decomposition analysis.

The paper collects the answers of the authors to the following questions: Is the lack of precision in the definition of many chemical concepts one of the reasons for the coexistence of many partition schemes? Does the adoption of a given partition scheme imply a set of more precise definitions of the underlying chemical concepts? How can one use the results of a partition scheme to improve the clarity of definitions of concepts? Are partition schemes subject to scientific Darwinism? If so, what is the influence of a community's sociological pressure in the "natural selection" process? To what extent does/can/should investigated systems influence the choice of a particular partition scheme? Do we need more focused chemical validation of Energy Decomposition Analysis (EDA) methodology and descriptors/terms in general? Is there any interest in developing common benchmarks and test sets for cross-validation of methods? Is it possible to contemplate a unified partition scheme (let us call it the "standard model" of partitioning), that is proper for all applications in chemistry, in the foreseeable future or even in principle? In the end, science is about experiments and the real world. Can one, therefore, use any experiment or experimental data be used to favor one partition scheme over another? © 2019 Wiley Periodicals, Inc.

Continuous infusion of recombinant activated factor VII: a review of data in congenital hemophilia with inhibitors and congenital factor VII deficiency.

Introduction: Continuous infusion (CI) of clotting factors as a replacement therapy for perioperative hemostatic protection has been performed for many years, including with factors VIII and IX and recombinant activated factor VII (rFVIIa). This approach provides steady factor levels without requiring frequent administration of bolus doses.

Aim: To review safety, efficacy, and dosing data regarding CI of rFVIIa for hemostatic management of patients with congenital hemophilia with inhibitors (CHwI) or congenital factor VII deficiency (C7D).