BackgroundThe 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) Version 1.4 is a reliable and valid instrument to assess patients' satisfaction with medication, providing scores on four scales – side effects, effectiveness, convenience and global satisfaction. In naturalistic studies, administering the TSQM with the side effects domain could provoke the physician to assess the presence or absence of adverse events in a way that is clinically atypical, carrying the potential to interfere with routine medical care. As a result, an abbreviated 9-item TSQM (TSQM-9), derived from the TSQM Version 1.4 but without the five items of the side effects domain was created. In this study, an interactive voice response system (IVRS)-administered TSQM-9 was psychometrically evaluated among patients taking antihypertensive medication.MethodsA total of 3,387 subjects were invited to participate in the study from an online panel who self-reported taking a prescribed antihypertensive medication. The subjects were asked to complete the IVRS-administered TSQM-9 at the start of the study, along with the modified Morisky scale, and again within 7 to 14 days. Standard psychometric analyses were conducted; including Cronbach's alpha, intraclass correlation coefficients, structural equation modeling, Spearman correlation coefficients and analysis of covariance (ANCOVA).ResultsA total of 396 subjects completed all the study procedures. Approximately 50% subjects were male with a good racial/ethnic mix: 58.3% white, 18.9% black, 17.7% Hispanic and 5.1% either Asian or other. There was evidence of construct validity of the TSQM-9 based on the structural equation modeling findings of the observed data fitting the Decisional Balance Model of Treatment Satisfaction even without the side effects domain. TSQM-9 domains had high internal consistency as evident from Cronbach's alpha values of 0.84 and greater. TSQM-9 domains also demonstrated good test-retest reliability with high intraclass correlation coefficients exceeding 0.70. As expected, the TSQM-9 domains were able to differentiate between individuals who were low, medium and high compliers of medication, with moderate to high effect sizes. There was evidence of convergent validity with significant correlations with the medication adherence scale.ConclusionThe IVRS-administered TSQM-9 was found to be a reliable and valid measure to assess treatment satisfaction in naturalistic study designs, in which there is potential that the administration of the side effects domain of the TSQM would interfere with routine clinical care.

Experimental infection with mouse cytomegalovirus (MCMV) has been used to elucidate the intricate host-pathogen mechanisms that determine innate resistance to infection. Linkage analyses in F(2) progeny from MCMV-resistant MA/My (H2 (k)) and MCMV-susceptible BALB/c (H2 (d)) and BALB.K (H2 (k)) mouse strains indicated that only the combination of alleles encoded by a gene in the Klra (also called Ly49) cluster on chromosome 6, and one in the major histocompatibility complex (H2) on chromosome 17, is associated with virus resistance. We found that natural killer cell-activating receptor Ly49P specifically recognized MCMV-infected cells, dependent on the presence of the H2 (k) haplotype. This binding was blocked using antibodies to H-2D(k) but not antibodies to H-2K(k). These results are suggestive of a new natural killer cell mechanism implicated in MCMV resistance, which depends on the functional interaction of the Ly49P receptor and the major histocompatibility complex class I molecule H-2D(k) on MCMV-infected cells.

Airway damage and remodelling are important components of lung pathology progression in cystic fibrosis (CF). Although repair mechanisms are engaged to restore the epithelial integrity, these processes are obviously insufficient to maintain lung function in CF airways. Our aims were therefore to study how the basic cystic fibrosis transmembrane conductance regulator (CFTR) defect could impact epithelial wound healing and to determine if CFTR correction could improve it.Wound-healing experiments, as well as cell migration and proliferation assays, were performed to study the early phases of epithelial repair in human CF and non-CF airway cells. CFTR function was evaluated using CFTR small interferring (si)RNA and inhibitor GlyH101 in non-CF cells, and conversely after CFTR rescue with the CFTR corrector VRT-325 in CF cells.Wound-healing experiments first showed that airway cells from CF patients repaired slower than non-CF cells. CFTR inhibition or silencing in non-CF primary airway cells significantly inhibited wound closure. GlyH101 also decreased cell migration and proliferation. Interestingly, wild-type CFTR transduction in CF airway cell lines or CFTR correction with VRT-325 in CFBE-DF508 and primary CF bronchial monolayers significantly improved wound healing.Altogether our results demonstrated that functional CFTR plays a critical role in wound repair, and CFTR correction may represent a novel strategy to promote the airway repair processes in CF.

Chronic Pseudomonas aeruginosa lung infections are associated with progressive epithelial damage and lung function decline. In addition to its role in tissue injury, the persistent presence of P. aeruginosa-secreted products may also affect epithelial repair ability, raising the need for new antivirulence therapies. The purpose of our study was to better understand the outcomes of P. aeruginosa exoproducts exposure on airway epithelial repair processes to identify a strategy to counteract their deleterious effect. We found that P. aeruginosa exoproducts significantly decreased wound healing, migration, and proliferation rates, and impaired the ability of directional migration of primary non-cystic fibrosis (CF) human airway epithelial cells. Impact of exoproducts was inhibited after mutations in P. aeruginosa genes that encoded for the quorum-sensing (QS) transcriptional regulator, LasR, and the elastase, LasB, whereas impact was restored by LasB induction in ΔlasR mutants. P. aeruginosa purified elastase also induced a significant decrease in non-CF epithelial repair, whereas protease inhibition with phosphoramidon prevented the effect of P. aeruginosa exoproducts. Furthermore, treatment of P. aeruginosa cultures with 4-hydroxy-2,5-dimethyl-3(2H)-furanone, a QS inhibitor, abrogated the negative impact of P. aeruginosa exoproducts on airway epithelial repair. Finally, we confirmed our findings in human airway epithelial cells from patients with CF, a disease featuring P. aeruginosa chronic respiratory infection. These data demonstrate that secreted proteases under the control of the LasR QS system impair airway epithelial repair and that QS inhibitors could be of benefit to counteract the deleterious effect of P. aeruginosa in infected patients.-Ruffin, M., Bilodeau, C., Maillé, É., LaFayette, S. L., McKay, G. A., Trinh, N. T. N., Beaudoin, T., Desrosiers, M.-Y., Rousseau, S., Nguyen, D., Brochiero, E. Quorum-sensing inhibition abrogates the deleterious impact of Pseudomonas aeruginosa on airway epithelial repair.

Infused ICT may not provide adequate effectiveness in the real world. High ferritin levels seem to be associated with ICT noncompliance, likely in relation to the bothersome mode of administration and side effects. The total cost of ICT appears to well exceed that of drug alone.