Developing a Web Platform to Optimize the Self-Management of People Living with a Chronic Respiratory Disease.

Purpose: The purpose of this article is to describe the development of a new Web platform to optimize self-management after pulmonary rehabilitation (PR) for persons living with a chronic respiratory disease (CRD) and to present data on its usability. Method: The Web platform is informed by a theoretical framework of behaviour changes and concepts of self-management and self-efficacy. It uses breathing exercises and a logbook and is meant to be a self-management tool. Usability was tested for 8 months after PR with a group consisting of five patients with chronic obstructive pulmonary disease and one with pulmonary fibrosis. We evaluated adherence (e.g., number of exercise/weeks), quality of life, dyspnoea, and functional capacity. We measured frequency count for adherence and pre-post differences per patient for clinical outcomes. Results: Four participants' adherence was higher than 50% of completed exercises (72 exercise/weeks). Five of six participants showed maintenance of functional capacity (6-minute walk test) 8 months after PR. Four participants showed maintenance of their quality of life. Four participants showed a deterioration in dyspnoea on the Borg Scale of Perceived Exertion. Conclusions: We developed a new theory-informed Web platform to optimize self-management after PR for persons living with a CRD. The pilot Web platform appears to optimize adherence to self-management techniques and possibly stabilize people's health outcomes.

Objectif : décrire la création d'une nouvelle plateforme en ligne pour optimiser l'autogestion après la réadaptation pulmonaire (RP) des personnes vivant avec une maladie pulmonaire chronique et présenter des données sur sa facilité d'utilisation. Méthodologie : la plateforme repose sur une structure théorique de changements de comportement et de concepts d'autogestion et d'autoefficacité. Elle se veut un outil d'autogestion faisant appel à des exercices respiratoires et à un journal. Les chercheurs en ont évalué la facilité d'utilisation auprès d'un groupe de cinq patients atteints d'une maladie pulmonaire obstructive chronique et d'un patient atteint de fibrose pulmonaire pendant huit mois après la RP. Ils ont évalué l'adhésion (p. ex., nombre d'exercices par semaine), la qualité de vie, la dyspnée et la capacité fonctionnelle. Ils ont également mesuré la fréquence pour déterminer l'adhésion et la différence avant-après de chaque patient pour évaluer les résultats cliniques. Résultats : quatre participants ont présenté une adhésion supérieure à 50 % pour ce qui est des exercices complétés (72 exercices par semaine). Quatre des six participants avaient maintenu leur capacité fonctionnelle (test de marche de six minutes) huit mois après la RP, et quatre participants avaient maintenu leur qualité de vie. Cependant, quatre participants ont présenté une détérioration de leur dyspnée à l'échelle de Borg. Conclusion : les chercheurs ont créé une nouvelle plateforme reposant sur des critères théoriques pour optimiser l'autogestion après une RP chez les personnes vivant avec une maladie pulmonaire chronique. Le projet-pilote de plateforme en ligne semble optimiser l'adhésion aux techniques d'autogestion et pourrait stabiliser l'état de santé des patients.

Use and Effectiveness of Sperm Cryopreservation for Adolescents and Young Adults: A 37-Year Bicentric Experience.

Aim: Sperm cryopreservation (SCP) should be offered to every adolescent before gonadotoxic treatment, but experience in this age range is still relatively limited. The goal of this study is to assess how to optimize this procedure. Methods and Patients: One hundred thirty-three patients between 12 and 20 years old, who underwent SCP between 1980 and 2017, were included. Baseline data (age, indication for SCP, and semen parameters at freezing) and follow-up data (outcome of sperm straws and follow-up of sperm quality) were collected and analyzed. Results: SCP is feasible from the age of 12. Semen assessment parameters at this age were close to parameters of adults. However, we observed quantitative impairments in testicular tumors and qualitative impairments in leukemia and bone marrow failure. Four patients (3%) used their cryopreserved semen for medically assisted reproduction, 15 patients died (11.3%), 18 asked for destruction of their straws (13.5%), and nine samples were destroyed because of lack of news (6.8%). Very few patients underwent a sperm analysis after treatment. Conclusions: SCP is an efficient, still underused, procedure for adolescents and young adults. Cryopreserved sperm is rarely used and rarely destroyed, but studies with a longer follow-up are needed to better assess these observations. Follow-up with a specialist of reproductive medicine is valuable for better information of the patient.

Substrate selectivity of human cytochrome P450 2C9: importance of residues 476, 365, and 114 in recognition of diclofenac and sulfaphenazole and in mechanism-based inactivation by tienilic acid.

A series of six site-directed mutants of CYP 2C9 were constructed with the aim to better define the amino acid residues that play a critical role in substrate selectivity of CYP 2C9, particularly in three distinctive properties of this enzyme: (i) its selective mechanism-based inactivation by tienilic acid (TA), (ii) its high affinity and hydroxylation regioselectivity toward diclofenac, and (iii) its high affinity for the competitive inhibitor sulfaphenazole (SPA). The S365A mutant exhibited kinetic characteristics for the 5-hydroxylation of TA very similar to those of CYP 2C9; however, this mutant did not undergo any detectable mechanism-based inactivation by TA, which indicates that the OH group of Ser 365 could be the nucleophile forming a covalent bond with an electrophilic metabolite of TA in TA-dependent inactivation of CYP 2C9. The F114I mutant was inactive toward the hydroxylation of diclofenac; moreover, detailed analyses of its interaction with a series of SPA derivatives by difference visible spectroscopy showed that the high affinity of SPA to CYP 2C9 (K(s)=0.4 microM) was completely lost when the phenyl substituent of Phe 114 was replaced with the alkyl group of Ile (K(s)=190+/-20 microM), or when the phenyl substituent of SPA was replaced with a cyclohexyl group (K(s)=120+/-30 microM). However, this cyclohexyl derivative of SPA interacted well with the F114I mutant (K(s)=1.6+/-0.5 microM). At the opposite end, the F94L and F110I mutants showed properties very similar to those of CYP 2C9 toward TA and diclofenac. Finally, the F476I mutant exhibited at least three main differences compared to CYP 2C9: (i) big changes in the k(cat) and K(m) values for TA and diclofenac hydroxylation, (ii) a 37-fold increase of the K(i) value found for the inhibition of CYP 2C9 by SPA, and (iii) a great change in the regioselectivity of diclofenac hydroxylation, the 5-hydroxylation of this substrate by CYP 2C9 F476I exhibiting a k(cat) of 28min(-1). These data indicate that Phe 114 plays an important role in recognition of aromatic substrates of CYP 2C9, presumably via Pi-stacking interactions. They also provide the first experimental evidence showing that Phe 476 plays a crucial role in substrate recognition and hydroxylation by CYP 2C9.