Development and Initial Validation of a Questionnaire to Measure Health-Related Quality of Life of Adults with Common Variable Immune Deficiency: The CVID_QoL Questionnaire.

BACKGROUND: Generic health status quality of life (QoL) instruments have been used in patients with common variable immune deficiency (CVID). However, by their nature, these tools may over- or underestimate the impact of diseases on an individual's QoL. OBJECTIVE: The objective of this study was to develop and validate a questionnaire to measure specific-health-related QoL for adults with CVID (CVID_QoL). METHODS: The 32-item content of the CVID_QoL questionnaire was developed using focus groups and individual patient interviews. Validation studies included 118 adults with CVID who completed Short Form-36, Saint George Respiratory Questionnaire, General Health Questionnaire-12, and EuroQol-5D questionnaire in a single session. Principal component and factor analysis solutions identified 3 scores to be similar in number and content for each solution. Validation of 3 factor scores was performed by construct validity. Reproducibility, reliability, convergent validity, and discriminant validity were evaluated. Matrices consisting of correlations between the 32 items in the CVID_QOL were calculated. RESULTS: Factor analysis identified 3 dimensions: emotional functioning (EF), relational functioning (RF), and gastrointestinal and skin symptoms (GSS). The instrument had good internal consistency (Cronbach's alpha, min. 0.74 for GSS, max. 0.84 for RF, n = 118) and high reproducibility (intraclass correlation coefficient, min. 0.79 for RF, max 0.90 for EF, n = 27). EF and RF scores showed good convergent validity correlating with conceptually similar dimensions of other study scales. Acute and relapsing infections had a significant impact on EF and RF. CONCLUSIONS: This study provides evidence of the reliability and construct validity of the CVID_QoL to identify QoL issues in patients with CVID that may not be addressed by generic instruments

Une approche pour la comparaison, du point de vue fonctionnement hydraulique, de propositions d'extension d'un réseau d'assainissement

Les outils informatiques développés dans le cadre de la conception des réseaux d'assainissement permettent de concevoir plusieurs solutions de réseaux pour un même problème. Il revient ensuite au décideur de choisir quelle solution retenir. Le problème qui se pose alors est la comparaison des propositions selon des critères économiques, écologiques, de fonctionnement, de maintenance, .... La difficulté vient du fait que certains de ces critères sont difficiles à évaluer. Nous présentons dans cet article une méthode permettant d'évaluer l'un de ces critères : le fonctionnement global d'un réseau d'assainissement suite à l'extension de ce dernier. Cette méthode est basée sur des simulations hydrauliques. Or ces simulations donnent des informations en chaque noeud du réseau (histogrammes de vitesses, débits ou hauteurs de charge) et non une indication sur la qualité de fonctionnement du réseau dans son ensemble. Il nous a donc fallu élaborer une technique d'agrégation permettant de passer de l'élément isolé (le tronçon) à l'ensemble organisé (le réseau). Cette technique d'agrégation utilise les notions de "période d'insuffisance" d'un tronçon qui est la période de retour d'une pluie pour laquelle ce tronçon dépasse un certain seuil de dysfonctionnement (dans notre cas, le débordement) et de sensibilité du tissu urbain à un dysfonctionnement hydraulique du réseau. Cette dernière notion est nécessaire car certains tronçons peuvent très bien déborder sans induire de désordres apparents s'ils ont, par exemple, une capacité d'écoulement faible et/ou s'ils se trouvent dans une zone non bâtie. Les informations nécessaires à l'utilisation de cette méthode étant souvent de qualité inégale en termes de précision, nous avons pris le parti de raisonner non sur des valeurs déterminées ais sur des classes d'appartenance modélisées sous forme de sous-ensembles flous.Software packages developed for the design of urban storm drainage networks allow several solutions to be proposed for the same problem. It then falls to the designer to choose which solution to use, the main problem being the evaluation of the efficiency (quality) of each solution. A multi-criteria approach represents one theoretical solution to the problem. This necessitates the determination of which criteria to use and how to evaluate them. In this paper, we present a method of evaluation of the criteria related directly to the functioning of an urban storm drainage network after its extension. This method is developed on the basis of hydraulic simulations of the network. These simulations produce results (histograms of discharge, water levels, rates of filling, hydraulic head, ...) for each pipe. Given these results, the designer must be able to assess whether the proposed solution is satisfactory, and then compare it with other solutions. The problem is therefore to be able to evaluate a complete network, whereas the results of conventional simulations present a fragmented and partial view of its functioning (pipe by pipe). A solution to this problem is proposed in the form of a tool, able to calculate a single combined value from the simulation results. The following calculation steps are proposed:1. First we model the effectiveness of each pipe. To do that, we determine the "return period of failure" of a pipe which is the return period of a rainfall for which the pipe passes a certain level of failure (in this paper, we take the level of failure as the state of overflow). The rainfall model used is the same one used for the design of the network. Then we attribute a numerical value (S) for the operation of a pipe according to its return period of failure by way of a satisfaction function. 2. Secondly we model the weighting given to each pipe. This weighting is constructed from the discharge capacity of the pipe and the sensitivity of the urban fabric (in proximity to the pipe) to system failure. The discharge capacity is calculated using Manning's formula on the basis of diameter, slope and internal roughness. The value of the coefficient (R), which indicates the sensitivity, necessitates a good knowledge of the urban fabric. Among the important variables related to this factor, we can identify the population density, the traffic density and the density of land use -DLU- (this variable is identified by the density of residential land use, the density of commercial land use, ...). We can then write R=f(density of population, density of traffic, DLU,...). Considering the difficulty of the identification of (f), we preferred to explore an expert approach. The rules have been identified from a bibliographical analysis and limited expertise. An example of theses rules is presented here : IF density of population is high and density of commercial land use is average THEN the degree of sensibility is average. The examination of the identified rules shows the use of words like low, average and high. To model this linguistic qualifying information, we have chosen fuzzy sets. Also the inferences of fuzzy information are treated by using operations of fuzzy logic. 3. Finally, we aggregate the results with the following equation:     nC=∑QaixRix∆Si  i=1where DSi=Si - Si' represents a measure of the effect of network modification upon the operation of the pipe i (Si and Si' are the effectiveness of the pipe respectively before and after the proposed modification), Qai is the discharge capacity of the pipe i, Ri is the coefficient of sensitivity of the area to failure associated with pipe i and C is a factor which quantifies the effect on the general operation of the network. With the coefficient C, the designer is now able to classify the different solutions of extension of an existing urban drainage network according to their impacts on its functioning and to introduce this classification order in a multi-criteria method

[Ca2+]i in human heart failure: a review and discussion of current areas of controversy.

Multiple abnormalities have been reported in the setting of human heart failure. It is unclear whether detected changes reflect adaptive alterations in myocardium subjected to increased and sustained hemodynamic overload or are pathogenic to the disease process. As a result of the observation that the primary defect in heart failure is decreased pump function, investigators have concentrated their efforts on determining systolic [Ca2+]i as a logical corollary and a causative mechanism for contractile dysfunction. A simple cause and effect relationship has therefore been proposed with regard to contractile dysfunction and [Ca2+]i. Yet some investigators have found no difference in peak systolic [Ca2+]i between failing and non-failing human myocardium, whereas others have found peak [Ca2+]i to be significantly reduced in failing hearts. Resting calcium concentrations have been reported either to be elevated in failing human myocardium or not different from non-failing human myocardium. Investigators should now appreciate that the force-calcium relationship is not a simple relationship. One must take into account the prolonged time course and slowed mobilization of [Ca2+]i as opposed to simply peak [Ca2+]i. When put in perspective of mechanisms and determinants of the Ca(2+)-force relationship, we begin to realize that failing human myocardium has the "potential" to generate normal levels of force. Only when stressed by [Ca2+]i overload and/or frequency perturbation does myocardium from patients with end-stage heart disease demonstrate contractile failure. Although [Ca2+]i availability and mobilization are likely to play a role in the systolic as well as diastolic dysfunction reported in human heart failure, it is likely that other mechanisms are involved as well (e.g., myocardial energetics). Myocardial energetics is directly related to [Ca2+]i and mobilization in failing human myocardium, because metabolites, e.g., ADP, inhibit pumps, such as sarcoplasmic reticulum Ca2+ ATPase activity. We therefore conclude that there is a role for intracellular calcium mobilization and myocardial energetics for systolic and diastolic dysfunction seen in human heart failure

Sterile Abscess in the Myocardium after Direct Intramyocardial Injection Related to Gene Therapy in a Swine Model

Cardiac gene therapy is one of the most promising approaches to cure patients with cardiac dysfunctions. Many ways of efficient gene transfer using viral vectors are tested, and some of them are already used in clinical settings. However, it is always important to be keenly alert to the possible complications when a new therapy is introduced. We present a case of myocardial sterile abscess in a swine model associated with a direct myocardial injection

Characterizing edge-wear in ceramic-on-ceramic acetabular cups

The use of fourth generation ceramic as an orthopaedic biomaterial has proved to be a very efficient and has gained popularity for primary hip surgery in the last 8-10 years. Cumulative percentage probability of revision after 7 years for uncemented CoC is 3.09% and for hybrid CoC is 2.00%, this compares favourably with traditional metal-on-UHMWPE uncemented at 3.05% and hybrid at 2.35% (12th Annual Report - NJR, 2015). Such ceramic-on-ceramic hip prostheses are being implanted in ever younger, more active patients, and yet very few long-term large cohort retrieval studies are yet to be carried out due to the survivorship of the implants. It has been seen in previous studies that levels of wear in ceramic-on-ceramic bearing surface can be of the order of 0.2 mm3/million cycles (Al-Hajjar, Fisher, Tipper, Williams, & Jennings, 2013). This is incredibly low when compared to studies that characterize wear in other bearing surface combinations. It has also been reported that an unusual stripe pattern of wear can occur in some in-vivo retrieved cups (Macdonald & Bankes, 2014) and it has further been postulated that this is caused by cup edge loading (Walter, Insley, Walter, & Tuke, 2004). The combined measurement challenge of stripe wear occurring at the edge of a low-wear ceramic-on-ceramic device is considerable, a solution to which is presented here. Current literature on wear measurement of such cases has been confined to in-vitro simulator studies and use of gravimetric measurement which by definition has limitations due to the lack of spacial characterisation. This paper details a novel method for measuring edge-wear in CoC acetabular liners. The method has been employed in an in-vitro study where it has been benchmarked against gravimetric measurements. These liners were measured on a CMM to determine the volume of material loss. The measurements were conducted as a blinded post-wear study akin to measurement of retrieved components. The most challenging part of this novel method was to create a reference geometry that replicates the free form edge surface of the ‘unworn’ cup using the residual post-wear surface. This was especially challenging due to the uncontrolled geometry at the cup edge and intersection of geometric features at this point. To achieve this, the geometry surrounding the wear patch was used to create a localized reference feature that minimised the effect of global form errors caused by hand polishing in the edge area. Furthermore, the reference geometry is compared with the measured surface to determine the linear penetration and volumetric wear loss. Result of this novel method can be seen in Fig 1 and Fig 2. The findings have been compared to gravimetric results and a bar graph comparing two results can be seen in Fig 3. Overall the accuracy of the method for this cohort was 0.03-0.2 mm3 when compared to gravimetric reference measurements. This compares very favourably with previously published wear measurement methods and gives confidence in the ability to measure such small measurement volumes over complex geometry

Role of antiseptics in the prevention and treatment of infections in nursing homes

Inadequate infection control, wound care, and oral hygiene protocols in nursing homes provide challenges to residents’ quality of life. Based on the outcomes from a focus group meeting and a literature search, this narrative review evaluates the current and potential roles of antiseptics within nursing home infection management procedures. We examine contemporary strategies and concerns within the management of meticillin-resistant Staphylococcus aureus (MRSA; including decolonization regimes), chronic wound care, and oral hygiene, and review the available data for the use of antiseptics, with a focus on povidone-iodine. Compared with chlorhexidine, polyhexanide, and silver, povidone-iodine has a broader spectrum of antimicrobial activity, with rapid and potent activity against MRSA and other microbes found in chronic wounds, including biofilms. As no reports of bacterial resistance or cross-resistance following exposure to povidone-iodine exist, it may be preferable for MRSA decolonization compared with mupirocin and chlorhexidine, which can cause resistant MRSA strains. Povidone-iodine oral products have greater efficacy against oral pathogens compared with other antiseptics such as chlorhexidine mouthwash, highlighting the clinical benefit of povidone-iodine in oral care. Additionally, povidone-iodine-based products, including mouthwash, have demonstrated rapid in vitro virucidal activity against SARS-CoV-2 and may help reduce its transmission if incorporated into nursing home coronavirus 2019 control protocols. Importantly, povidone-iodine activity is not adversely affected by organic material, such as that found in chronic wounds and the oral cavity. Povidone-iodine is a promising antiseptic agent for the management of infections in the nursing home setting, including MRSA decolonization procedures, chronic wound management, and oral care.N/