Integration of mental health screening and treatment into cystic fibrosis clinics: Evaluation of initial implementation in 84 programs across the United States

Background: A large‐scale epidemiological study of 6088 individuals with cystic fibrosis (CF) and 4102 caregivers in nine countries documented elevated symptoms of depression and anxiety, leading to international guidelines for annual screening and follow‐up. To facilitate national implementation, 84 CF programs funded a mental health coordinators (MHC). Implementation was evaluated after 1 year using the consolidated framework for implementation research (CFIR) to identify facilitators and barriers. Methods: A 45‐item internet survey was developed to assess relevant CFIR implementation steps. Surveys were completed in 2016. It assessed five domains tailored to study aims: (a) Intervention characteristics, (b) outer setting, (c) inner setting, (d) characteristics of individuals, and (e) process of implementation. Results: Response rate was 88%, with pediatric and adult programs equally represented. A majority of MHCs were social workers (54.1%) and psychologists (41.9%); 41% had joined the team in the past year. Facilitators across the five domains included universal uptake of screening tools, greater awareness and detection of psychological symptoms, reduced stigma, and positive feedback from patients and families. Barriers included limited staff time, space, and logistics. Discussion: This is the largest systematic effort to integrate mental health screening and treatment into the care of individuals with a serious, chronic illness and their caregivers. MHCs implementing screening, interpretation and follow‐up reported positive results, and significant barriers. This national implementation effort demonstrated that depression and anxiety can be efficiently evaluated and treated in a complex, chronic disease. Future efforts include recommending the addition of screening scores to national CF Registries and examining their effects on health outcomes

Effect of VX-770 in Persons with Cystic Fibrosis and the G551D- CFTR Mutation

A new approach in the treatment of cystic fibrosis involves improving the function of mutant cystic fibrosis transmembrane conductance regulator (CFTR). VX-770, a CFTR potentiator, has been shown to increase the activity of wild-type and defective cell-surface CFTR in vitro

Safety and efficacy of vanzacaftor–tezacaftor–deutivacaftor in adults with cystic fibrosis: randomised, double-blind, controlled, phase 2 trials

Background Elexacaftor–tezacaftor–ivacaftor has been shown to be safe and efficacious in people with cystic fibrosis and at least one F508del allele. Our aim was to identify a novel cystic fibrosis transmembrane conductance regulator (CFTR) modulator combination capable of further increasing CFTR-mediated chloride transport, with the potential for once-daily dosing. Methods We conducted two phase 2 clinical trials to assess the safety and efficacy of a once-daily combination of vanzacaftor–tezacaftor–deutivacaftor in participants with cystic fibrosis who were aged 18 years or older. A phase 2 randomised, double-blind, active-controlled study (VX18-561-101; April 17, 2019, to Aug 20, 2020) was carried out to compare deutivacaftor monotherapy with ivacaftor monotherapy in participants with CFTR gating mutations, following a 4-week ivacaftor monotherapy run-in period. Participants were randomly assigned to receive either ivacaftor 150 mg every 12 h, deutivacaftor 25 mg once daily, deutivacaftor 50 mg once daily, deutivacaftor 150 mg once daily, or deutivacaftor 250 mg once daily in a 1:1:2:2:2 ratio. The primary endpoint was absolute change in ppFEV1 from baseline at week 12. A phase 2 randomised, double-blind, controlled, proof-of-concept study of vanzacaftor–tezacaftor–deutivacaftor (VX18-121-101; April 30, 2019, to Dec 10, 2019) was conducted in participants with cystic fibrosis and heterozygous for F508del and a minimal function mutation (F/MF genotypes) or homozygous for F508del (F/F genotype). Participants with F/MF genotypes were randomly assigned 1:2:2:1 to receive either 5 mg, 10 mg, or 20 mg of vanzacaftor in combination with tezacaftor–deutivacaftor or a triple placebo for 4 weeks, and participants with the F/F genotype were randomly assigned 2:1 to receive either vanzacaftor (20 mg)–tezacaftor–deutivacaftor or tezacaftor–ivacaftor active control for 4 weeks, following a 4-week tezacaftor–ivacaftor run-in period. Primary endpoints for part 1 and part 2 were safety and tolerability and absolute change in ppFEV1 from baseline to day 29. Secondary efficacy endpoints were absolute change from baseline at day 29 in sweat chloride concentrations and Cystic Fibrosis Questionnaire-Revised (CFQ-R) respiratory domain score. These clinical trials are registered with ClinicalTrials.gov, NCT03911713 and NCT03912233, and are complete. Findings In study VX18-561-101, participants treated with deutivacaftor 150 mg once daily (n=23) or deutivacaftor 250 mg once daily (n=24) had mean absolute changes in ppFEV1 of 3·1 percentage points (95% CI –0·8 to 7·0) and 2·7 percentage points (–1·0 to 6·5) from baseline at week 12, respectively, versus –0·8 percentage points (–6·2 to 4·7) with ivacaftor 150 mg every 12 h (n=11); the deutivacaftor safety profile was consistent with the established safety profile of ivacaftor 150 mg every 12 h. In study VX18-121-101, participants with F/MF genotypes treated with vanzacaftor (5 mg)–tezacaftor–deutivacaftor (n=9), vanzacaftor (10 mg)–tezacaftor–deutivacaftor (n=19), vanzacaftor (20 mg)–tezacaftor–deutivacaftor (n=20), and placebo (n=10) had mean changes relative to baseline at day 29 in ppFEV1 of 4·6 percentage points (−1·3 to 10·6), 14·2 percentage points (10·0 to 18·4), 9·8 percentage points (5·7 to 13·8), and 1·9 percentage points (−4·1 to 8·0), respectively, in sweat chloride concentration of −42·8 mmol/L (–51·7 to –34·0), −45·8 mmol/L (95% CI –51·9 to –39·7), −49·5 mmol/L (–55·9 to –43·1), and 2·3 mmol/L (−7·0 to 11·6), respectively, and in CFQ-R respiratory domain score of 17·6 points (3·5 to 31·6), 21·2 points (11·9 to 30·6), 29·8 points (21·0 to 38·7), and 3·3 points (−10·1 to 16·6), respectively. Participants with the F/F genotype treated with vanzacaftor (20 mg)–tezacaftor–deutivacaftor (n=18) and tezacaftor–ivacaftor (n=10) had mean changes relative to baseline (taking tezacaftor–ivacaftor) at day 29 in ppFEV1 of 15·9 percentage points (11·3 to 20·6) and −0·1 percentage points (−6·4 to 6·1), respectively, in sweat chloride concentration of −45·5 mmol/L (−49·7 to −41·3) and −2·6 mmol/L (−8·2 to 3·1), respectively, and in CFQ-R respiratory domain score of 19·4 points (95% CI 10·5 to 28·3) and −5·0 points (−16·9 to 7·0), respectively. The most common adverse events overall were cough, increased sputum, and headache. One participant in the vanzacaftor–tezacaftor–deutivacaftor group had a serious adverse event of infective pulmonary exacerbation and another participant had a serious rash event that led to treatment discontinuation. For most participants, adverse events were mild or moderate in severity. Interpretation Once-daily dosing with vanzacaftor–tezacaftor–deutivacaftor was safe and well tolerated and improved lung function, respiratory symptoms, and CFTR function. These results support the continued investigation of vanzacaftor–tezacaftor–deutivacaftor in phase 3 clinical trials compared with elexacaftor–tezacaftor–ivacaftor. Funding Vertex Pharmaceuticals

Description of Exotic Nuclei with the Interacting Boson Model

International audienceEven—even nuclei in the A~100 mass region are investigated within the framework of the interacting boson model-1 (IBM-1). The study includes energy spectra and electric quadrupole transition properties of zirconium, molybdenum, ruthenium and palladium isotopes with neutron number N>=54. A global parametrization of the IBM-1 hamiltonian is found leading to a description of 301 collective levels in 30 nuclei with a root-mean-square deviation from the observed level energies of 119 keV. The geometric character of the nuclei can be visualized by plotting the potential energy surface V(beta,gamma) obtained from the IBM-1 hamiltonian in the classical limit. The parametrization established on the basis of known elements is then used to predict properties of the unknown, neutron-rich isotopes 106Zr, 112Mo, 116Ru and 120Pd

Description of nuclei in the A similar to 100 mass region with the interacting boson model

WOS: 000282276700020Even-even nuclei in the A similar to 100 mass region are investigated within the framework of the interacting boson model-1 (IBM-1). The study includes energy spectra and electric quadrupole transition properties of zirconium, molybdenum, ruthenium and palladium isotopes with neutron number N >= 52. A global parametrization of the IBM-1 Hamiltonian is found leading to a description of about 300 collective levels in 30 nuclei with a root-mean-square deviation from the observed level energies of 120 keV. The importance of the d(5/2) subshell closure at neutron number N = 56 is pointed out. The geometric character of the nuclei can be visualized by plotting the potential energy surface V (beta, gamma) obtained from the IBM-1 Hamiltonian in the classical limit. The parametrization established on the basis of known elements is used to predict properties of the unknown, neutron-rich isotopes (106)Zr, (112)Mo, (116)Ru and (122)Pd.Scientific and Technological Research Council of Turkey (TUBITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [107T557]; Agence Nationale de Recherche, FranceFrench National Research Agency (ANR) [ANR-07-BLAN-0256-03]This work was supported by the Scientific and Technological Research Council of Turkey (TUBITAK) under project no 107T557, and by the Agence Nationale de Recherche, France, under contract no ANR-07-BLAN-0256-03

Radiosynthesis and biodistribution of 99mTc-Sulfamethoxazole: a novel molecule for in-vivo infection imaging

The aim of this study was to prepare 99mTc-Sulfamethoxazole complex and evaluate its efficiency as an infection imaging agent. The Sulfamethoxazole was labeled with 99mTc and its biological efficacy as a potential radio tracer for Staphylococcus aureus infection was investigated in bacterially infected Albino Wistar rats. The radiolabeling yield was found to be 95 ± 3.07% and remained constant at more than 93 ± 0.1% even in serum for 240 min after radiolabeling. 99mTc-Sulfamethoxazole prepared with high yield localized well in the bacterially infected muscle of the rats. 99mTc-Sulfamethoxazole may be developed as a radiopharmaceutical agent to distinguish infection from inflammation by nuclear imaging. © 2017, Springer Science+Business Media, LLC

Influence of material and injection molding machine’s selection on the electricity consumption and environmental impact of the injection molding process: An experimental approach

Reducing energy consumption is an important issue for green manufacturing. In this paper, the specific energy consumption (SEC) of the injection molding process is analyzed. Results showed significant variations depending on the injected thermoplastic material and the type of injection molding machine (IMM) suggesting that IMM selection has a high relevance for the efficiency, cost and environmental impact of the process. The manufacturing of 36 plastic parts has been characterized by measuring the electricity consumption and obtaining the environmental impact, being this consumption its most important factor. A descending tendency for both is observed when high throughputs are obtained because the size of the IMM is more optimized. Conversely, the savings obtained by the all-electric IMMs are significant. This research could help engineers to properly select an IMM by taking into account the part weight, material and environmental criteria. Also, this study will be useful for life cycle assessment (LCA) practitioners. Real consumption data is presented, providing details about the materials, and relationships with the IMM that was used. The high variability suggests that if the injection molding process is relevant in a LCA study, its consumption must be analyzed in depth, preferably by measuring real consumptions in the factory