Contribution of copy number variants (CNVs) to congenital, unexplained intellectual and developmental disabilities in Lebanese patients

International audienceBackground: Chromosomal microarray analysis (CMA) is currently the most widely adopted clinical test for patients with unexplained intellectual disability (ID), developmental delay (DD), and congenital anomalies. Its use has revealed the capacity to detect copy number variants (CNVs), as well as regions of homozygosity, that, based on their distribution on chromosomes, indicate uniparental disomy or parental consanguinity that is suggestive of an increased probability of recessive disease. Results: We screened 149 Lebanese probands with ID/DD and 99 healthy controls using the Affymetrix Cyto 2.7 M and SNP6.0 arrays. We report all identified CNVs, which we divided into groups. Pathogenic CNVs were identified in 12.1% of the patients. We review the genotype/phenotype correlation in a patient with a 1q44 microdeletion and refine the minimal critical regions responsible for the 10q26 and 16q monosomy syndromes. Several likely causative CNVs were also detected, including new homozygous microdeletions (9p23p24.1, 10q25.2, and 8p23.1) in 3 patients born to consanguineous parents, involving potential candidate genes. However, the clinical interpretation of several other CNVs remains uncertain, including a microdeletion affecting ATRNL1. This CNV of unknown significance was inherited from the patient's unaffected-mother; therefore, additional ethnically matched controls must be screened to obtain enough evidence for classification of this CNV. Conclusion: This study has provided supporting evidence that whole-genome analysis is a powerful method for uncovering chromosomal imbalances, regardless of consanguinity in the parents of patients and despite the challenge presented by analyzing some CNVs

Variation of psychological and anthropometrics measures before and after dieting and factors associated with body dissatisfaction and quality of life in a Lebanese clinical sample

International audienceObjective: The primary objective of this study was to assess a change in the psychological states (stress, self-esteem, anxiety and depression), anthropometric measurements and physical/mental quality of life before and after diet in a sample of Lebanese subjects visiting a diet clinic. The secondary objectives included the evaluation of factors associated with body dissatisfaction, mental and physical quality of life (QOL) before the intervention of the diet program and the change in quality of life after this intervention among those participants. Methods: This cross-sectional study, conducted between May and August 2018, enrolled 62 participants recruited from three diet clinics. The QOL was measured using the 12-item Short Form Health Survey (SF-12) and the psychological states was measured using the following scales: The Rosenberg Self-esteem Scale, Perceived Stress Scale, Hamilton Anxiety Rating Scale and Hamilton Depression Rating Scale. Results: A significant reduction in body dissatisfaction, anxiety, waist, weight and body fat and a significant increase in the physical and mental quality of life was seen after diet compared to before it (p < 0.001 for all). No significant variation in perceived stress (p = 0.072), self-esteem (p = 0.885), and depression (p = 0.353) after diet were found. Higher BMI (β = 0.440) and higher anxiety (β = 0.132) were associated with higher body dissatisfaction scores, whereas higher self-esteem (β = − 0.818) was significantly associated with lower body dissatisfaction. Higher perceived stress (β = − 0.711), higher body dissatisfaction (β = − 0.480) and being a female (β = − 4.094) were associated with lower mental QOL. Higher Physical Activity Index was significantly associated with higher mental and physical QOL (β = 0.086 and β = 0.123 respectively). Conclusion: The results indicate the effectiveness of diet programs in enhancing the quality of life, psychological and anthropometric measures

Connaissances et compétences des pharmaciens communautaires et qualité de la pharmacothérapie des patients atteints d’insuffisance rénale chronique : Résultats provisoires du programme ProFiL

Résumé Objectif : Dans le cadre d’une analyse provisoire comprenant l’Hôpital de la Cité-de-la Santé de Laval et l’Hôpital Maisonneuve- Rosemont, évaluer les retombées d’un programme de formation et de liaison en néphrologie (ProFiL) sur les connaissances et compétences des pharmaciens, leurs pratiques cliniques et la qualité de la pharmacothérapie de leurs patients. Méthodologie : Des patients de cliniques de prédialyse et leur pharmacie ont été répartis aléatoirement dans les groupes ProFiL et Soins habituels. Les connaissances et compétences des pharmaciens ont été évaluées au moment de l’inclusion des patients dans l’étude et après une année. La qualité de la pharmacothérapie et les pratiques cliniques des pharmaciens ont été évaluées au cours des années précédant et suivant le recrutement. Résultats : Après un an de suivi, les pharmaciens ProFiL (n = 55) ont obtenu une amélioration plus importante de leurs scores de connaissances (différence avant-après entre les groupes : 5,6 % [IC 95 % : 0,08 % à 11,1 %]) et de compétences (10,8 % [5,5 % à 16,1 %]) que les pharmaciens du groupe Soins habituels (n = 27). Le nombre de problèmes liés à la pharmacothérapie des patients ProFiL (n = 117) est passé de 3,2 à 1,7 problèmes par patient, comparativement au groupe Soins habituels, qui n’est passé que de 2,6 à 2,1 par patient (n = 51), soit une diminution incrémentale de -1,1 problème par patient (-1,8 à -0,4), notamment pour les médicaments nécessitant un ajustement en insuffisance rénale chronique (-0,3 problème lié à la pharmacothérapie par patient [-0,5 à -0,02]) et l’adhésion au traitement (-0,5 problème lié à la pharmacothérapie par patient [-0,9 à -0,2]). Un nombre supérieur de recommandations aux patients et aux médecins, nommées opinions pharmaceutiques, et de refus d’exécuter une ordonnance ont été émis pour les patients ProFiL (0,4 opinion par patient versus 0,1 opinion par patient). Conclusion : Après une année, ProFiL améliore les connaissances et compétences des pharmaciens communautaires, leurs pratiques cliniques et la qualité de la pharmacothérapie de leurs patients. Abstract Objective: To evaluate the impact of a training and liaison program in nephrology (ProFil) on the knowledge and competencies of pharmacists, their clinical practice, and the quality of their patient pharmacotherapy. Methods: Patients in predialysis clinics in two academic medical centers and their community pharmacy were randomly assigned either to the ProFiL group or the Usual Care group. The knowledge and competencies of pharmacists were evaluated at the time of patient inclusion in the study and after one year. The quality of pharmacotherapy and the clinical practice of pharmacists were evaluated prior to and following patient recruitment. Results: After one year of follow-up, pharmacists from the ProFiL group (n=55) had significant improvement in their scores for knowledge (before-after difference between groups: 5.6% [CI 95 %: 0.08 % to 11.1 %]) and competency (10.8 % [5.5 % to 16.1 %]) than pharmacists in the Usual Care group (n=27). The number of drug-related problems in the ProFiL group patients (n=117) decreased from 3.2 to 1.7 problems per patient, compared to the patients in the Usual Care group where drug-related problems decreased from 2.6 to 2.1 per patient (n=51), an incremental decrease of -1.1 problems per patient (-1.8 to -0.4), primarily for medications requiring dosage adjustment in chronic renal failure (-0.3 drug-related problems per patient [-0.5 to -0.02]) and treatment adherence (-0.5 drug-related problems [-0.9 to -0.2]). A greater number of recommendations to patients and physicians, either as pharmaceutical opinions or refusal to fill a prescription, were made for patients in the ProFiL group (0.4 opinions per patient versus 0.1 opinions per patient). Conclusion: After one year, the ProFil program improved the knowledge and competencies of community pharmacists, their clinical practice, and the quality of patient pharmacotherapy. Key words: Chronic renal failure, community pharmacy, continuing education, drug-related problems, knowledge and competencies, pre-dialysis clinic

Aggravation de l’insuffisance rénale chronique et de ses facteurs de risque : Résultats provisoires du programme ProFiL

Résumé Objectif : Un essai clinique evalue presentement les retombees d’un Programme de formation et de liaison en nephrologie (ProFiL) sur la qualite de la pharmacotherapie de patients souffrant d’insuffisance renale chronique. L’objectif de cette analyse provisoire vise a evaluer la pertinence d’augmenter le nombre de patients a l’etude de maniere a pouvoir determiner les retombees du Programme sur l’aggravation de la fonction renale et de ses facteurs de risque. Méthodologie : Des patients de deux cliniques de predialyse (Hopital de la Cite-de-la-Sante de Laval et Hopital Maisonneuve- Rosemont) et leur pharmacie communautaire ont ete repartis aleatoirement dans les groupes ProFiL et Soins habituels et suivis pendant une annee. Les variables cliniques ont ete documentees au moment de l’inclusion des patients dans l’etude et un an plus tard. La comparaison de l’evolution des deux groupes a eu lieu a l’aide de modeles lineaires multivaries a effet mixte. Résultats : L’evolution du debit de filtration glomerulaire etait similaire dans les deux groupes. Une baisse additionnelle de -9,8 mmHg (IC 95 % : -15,8 a -3,7) de la tension arterielle systolique a ete observee dans le groupe ProFiL (n = 117) par rapport aux patients Soins habituels (n = 51). Parmi les patients diabetiques (n = 100), une reduction incrementale de l’hemoglobine glyquee de 0,4 % (IC 95 % : -0,9 a -0,1) a ete observee dans le groupe ProFiL alors que parmi les patients dyslipidemiques (n = 96), l’evolution du cholesterol-LDL etait similaire dans les deux groupes. Conclusion : Apres une annee, le Programme ProFiL a un effet positif sur le controle de la tension arterielle et de l’hemoglobine glyquee mais n’aurait pas d’effets significatifs sur le cholesterol-LDL et l’aggravation de l’insuffisance renale. Il n’est donc pas necessaire d’augmenter le nombre de patients recrutes. Abstract Objective: : A clinical trial is presently assessing the impact of a nephrology training and liaison program “ProFiL” on the quality of pharmacotherapy in patients with chronic renal failure. The objective of this interim analysis is to determine the usefulness of increasing the number of study patients to be able to assess the program’s impact on the progression of impaired renal function and of its risk factors. Methods: Patients from two predialysis clinics (Hopital de la Cite-de-la-Sante de Laval and Hopital Maisonneuve- Rosemont) and their community pharmacies were randomized to the ProFiL group or the usual care group and followed for one year. The clinical variables were recorded at study inclusion and one year later, and the changes in the two groups were compared using linear, mixed-effects multivariate models. Results: The changes in the glomerular filtration rate were similar in both groups. There was an additional decrease of -9.8 mm Hg (95% CI: -15.8 to -3.7) in systolic blood pressure in the ProFiL group (n = 117) compared to the patients receiving usual care (n = 51). In the diabetic patients (n = 100), an incremental reduction in the glycosylated hemoglobin concentration of 0.4% (95% CI: -0.9 to -0.1) was observed in the ProFiL group, while in the dyslipidemic patients (n = 96), the changes in the LDL cholesterol levels were similar in both groups. Conclusion: After one year, the ProFil program had a positive effect on blood pressure control and glycosylated hemoglobin control but did not appear to have a significant impact on LDL cholesterol or the progression of renal failure. Therefore, it is not necessary to increase the number of patients recruited. Key words: Chronic renal failure, community pharmacy, diabetes, dyslipidemia, predialysis, renal failure risk facto