Implementability of healthcare interventions: an overview of reviews and development of a conceptual framework

Background Implementation research may play an important role in reducing research waste by identifying strategies that support translation of evidence into practice. Implementation of healthcare interventions is influenced by multiple factors including the organisational context, implementation strategies and features of the intervention as perceived by people delivering and receiving the intervention. Recently, concepts relating to perceived features of interventions have been gaining traction in published literature, namely, acceptability, fidelity, feasibility, scalability and sustainability. These concepts may influence uptake of healthcare interventions, yet there seems to be little consensus about their nature and impact. The aim of this paper is to develop a testable conceptual framework of implementability of healthcare interventions that includes these five concepts. Methods A multifaceted approach was used to develop and refine a conceptual framework of implementability of healthcare interventions. An overview of reviews identified reviews published between January 2000 and March 2021 that focused on at least one of the five concepts in relation to a healthcare intervention. These findings informed the development of a preliminary framework of implementability of healthcare interventions which was presented to a panel of experts. A nominal group process was used to critique, refine and agree on a final framework. Results A total of 252 publications were included in the overview of reviews. Of these, 32% were found to be feasible, 4% reported sustainable changes in practice and 9% were scaled up to other populations and/or settings. The expert panel proposed that scalability and sustainability of a healthcare intervention are dependent on its acceptability, fidelity and feasibility. Furthermore, acceptability, fidelity and feasibility require re-evaluation over time and as the intervention is developed and then implemented in different settings or with different populations. The final agreed framework of implementability provides the basis for a chronological, iterative approach to planning for wide-scale, long-term implementation of healthcare interventions. Conclusions We recommend that researchers consider the factors acceptability, fidelity and feasibility (proposed to influence sustainability and scalability) during the preliminary phases of intervention development, evaluation and implementation, and iteratively check these factors in different settings and over time

A Chaperone Trap Contributes to the Onset of Cystic Fibrosis

Protein folding is the primary role of proteostasis network (PN) where chaperone interactions with client proteins determine the success or failure of the folding reaction in the cell. We now address how the Phe508 deletion in the NBD1 domain of the cystic fibrosis (CF) transmembrane conductance regulator (CFTR) protein responsible for cystic fibrosis (CF) impacts the binding of CFTR with cellular chaperones. We applied single ion reaction monitoring mass spectrometry (SRM-MS) to quantitatively characterize the stoichiometry of the heat shock proteins (Hsps) in CFTR folding intermediates in vivo and mapped the sites of interaction of the NBD1 domain of CFTR with Hsp90 in vitro. Unlike folding of WT-CFTR, we now demonstrate the presence of ΔF508-CFTR in a stalled folding intermediate in stoichiometric association with the core Hsps 40, 70 and 90, referred to as a ‘chaperone trap’. Culturing cells at 30 C resulted in correction of ΔF508-CFTR trafficking and function, restoring the sub-stoichiometric association of core Hsps observed for WT-CFTR. These results support the interpretation that ΔF508-CFTR is restricted to a chaperone-bound folding intermediate, a state that may contribute to its loss of trafficking and increased targeting for degradation. We propose that stalled folding intermediates could define a critical proteostasis pathway branch-point(s) responsible for the loss of function in misfolding diseases as observed in CF

Estudio de la formación de contaminantes fotoquímicos mediante la modelación matemática y sus efectos en la salud en el Valle de Aburra

IP 1210-13-234-98PONENCIA(S) EN CONGRESO: Numeral investigation of meteorologicalconditions leading to elevated ozone;concentrations in Medellin, Colombia / P. Sahm ... [et al.]. --En: International Conference on Urban Air;Quality and Saturn Workshop (3, 5 : 2001 Mar. 19-23 : Loutraki,Grecia). -- [s.l. : s.n.], 2001. -- p. ; 28;cm. -- Emission inventory in Medellin (Colombia) city : anaproximation /M.V. Toro ... [et al.]. -- En:;contaminantes atmosfericos en la ciudad de Medellin mediante factores de emision Corinar / M. Victoria Toro G.;... [et al.] -- En: Acodal -- Vol. 191 (2002); p. -- ISSN120798 -- Diagnostico de la calidad del aire en el;ancon sur del valle de Aburra / Maria Victoria Toro ... [et al.]'-- en: Contaminacion ambiental. -- Vol. 17,;no. 30-31 (2000); p. 93-103. -- ISSN 01200674.;International Conference on Urban Air Quality and Saturn Workshop (3, 5 :2001 Mar. 19-23 : Loutraki, Grecia).; [s.l. : s.n.], 2001. -- p. ; 28 cm. -- ARTICULO(S) EN REVISTA: Calculode la emision vehicular d

Concentrated Conditioned Media from Adipose Tissue Derived Mesenchymal Stem Cells Mitigates Visual Deficits and Retinal Inflammation Following Mild Traumatic Brain Injury

Blast concussions are a common injury sustained in military combat today. Inflammation due to microglial polarization can drive the development of visual defects following blast injuries. In this study, we assessed whether anti-inflammatory factors released by the mesenchymal stem cells derived from adipose tissue (adipose stem cells, ASC) can limit retinal tissue damage and improve visual function in a mouse model of visual deficits following mild traumatic brain injury. We show that intravitreal injection of 1 μL of ASC concentrated conditioned medium from cells pre-stimulated with inflammatory cytokines (ASC-CCM) mitigates loss of visual acuity and contrast sensitivity four weeks post blast injury. Moreover, blast mice showed increased retinal expression of genes associated with microglial activation and inflammation by molecular analyses, retinal glial fibrillary acidic protein (GFAP) immunoreactivity, and increased loss of ganglion cells. Interestingly, blast mice that received ASC-CCM improved in all parameters above. In vitro, ASC-CCM not only suppressed microglial activation but also protected against Tumor necrosis alpha (TNFα) induced endothelial permeability as measured by transendothelial electrical resistance. Biochemical and molecular analyses demonstrate TSG-6 is highly expressed in ASC-CCM from cells pre-stimulated with TNFα and IFNγ but not from unstimulated cells. Our findings suggest that ASC-CCM mitigates visual deficits of the blast injury through their anti-inflammatory properties on activated pro-inflammatory microglia and endothelial cells. A regenerative therapy for immediate delivery at the time of injury may provide a practical and cost-effective solution against the traumatic effects of blast injuries to the retina