A realist process evaluation within the Facilitating Implementation of Research Evidence (FIRE) cluster randomised controlled international trial: an exemplar

Background

Facilitation is a promising implementation intervention, which requires theory-informed evaluation. This paper presents an exemplar of a multi-country realist process evaluation that was embedded in the first international randomised controlled trial evaluating two types of facilitation for implementing urinary continence care recommendations. We aimed to uncover what worked (and did not work), for whom, how, why and in what circumstances during the process of implementing the facilitation interventions in practice.

Methods

This realist process evaluation included theory formulation, theory testing and refining. Data were collected in 24 care home sites across four European countries. Data were collected over four time points using multiple qualitative methods: observation (372 h), interviews with staff (n?=?357), residents (n?=?152), next of kin (n?=?109) and other stakeholders (n?=?128), supplemented by facilitator activity logs. A combined inductive and deductive data analysis process focused on realist theory refinement and testing.

Results

The content and approach of the two facilitation programmes prompted variable opportunities to align and realign support with the needs and expectations of facilitators and homes. This influenced their level of confidence in fulfilling the facilitator role and ability to deliver the intervention as planned. The success of intervention implementation was largely dependent on whether sites prioritised their involvement in both the study and the facilitation programme. In contexts where the study was prioritised (including release of resources) and where managers and staff support was sustained, this prompted collective engagement (as an attitude and action). Internal facilitators’ (IF) personal characteristics and abilities, including personal and formal authority, in combination with a supportive environment prompted by managers triggered the potential for learning over time. Learning over time resulted in a sense of confidence and personal growth, and enactment of the facilitation role, which resulted in practice changes.

Conclusion

The scale and multi-country nature of this study provided a novel context to conduct one of the few trial embedded realist-informed process evaluations. In addition to providing an explanatory account of implementation processes, a conceptual platform for future facilitation research is presented. Finally, a realist-informed process evaluation framework is outlined, which could inform future research of this nature.

Trial registration

Current controlled trials ISRCTN11598502.

     

Polyamine deficiency alters EGF receptor distribution and signaling effectiveness in IEC-6 cells

Cell growth andmigration are essential processes for the differentiation, maintenance,and repair of the intestinal epithelium. Epidermal growth factor (EGF)is an important factor in the reorganization of the cytoskeletonrequired for both processes. Because we had previously foundsignificant changes in the cytoskeleton during polyamine deficiency, itwas of interest to know whether those changes could prevent EGF fromstimulating growth and migration. Polyamine biosynthesis in IEC-6 cellswas interrupted by treatment with -difluoromethylornithine (DFMO), aspecific inhibitor of ornithine decarboxylase, the primaryrate-limiting enzyme of polyamine biosynthesis. DFMO halted cellproliferation and inhibited cell migration, and neither function couldbe normally stimulated by EGF. Immunocytochemistry of the transferrinreceptor (used as a marker for the endocytic pathway) revealed anabnormal distribution of the EGF receptor (EGFR) 10 min after bindingEGF. Polyamine deficiency depleted the cells of interiormicrofilaments, thickened the actin cortex, and prevented the promptassociation of EGF-bound EGFR with actin. EGF-stimulated 170-kDaprotein tyrosine phosphorylation and the kinase activity of purifiedmembrane EGFR were reduced by 50%. Immunoprecipatated EGFR proteinconcentration, however, was not reduced by polyamine deficiency. All ofthese changes could be prevented by supplementation with putrescine.Cytoskeletal disruption, reduced EGFR phosphorylation and kinaseactivity, aberrant intracellular EGFR distribution, and delayedassociation with actin filaments suggest a partial explanation for thedependence of epithelial cell growth and migration on polyamines.

     

Genomic data reveal ancient microendemism in forest scorpions across the California Floristic Province

The California Floristic Province (CFP) in western North America is a globally significant biodiversity hotspot. Elucidating patterns of endemism and the historical drivers of this diversity has been an important challenge of comparative phylogeography for over two decades. We generated phylogenomic data using ddRADseq to examine genetic structure in Uroctonus forest scorpions, an ecologically restricted and dispersal‐limited organism widely distributed across the CFP north to the Columbia River. We coupled our genetic data with species distribution models (SDMs) to determine climatically suitable areas for Uroctonus both now and during the Last Glacial Maximum. Based on our analyses, Uroctonus is composed of two major genetic groups that likely diverged over 2 million years ago. Each of these groups itself contains numerous genetic groups that reveal a pattern of vicariance and microendemism across the CFP. Migration rates among these populations are low. SDMs suggest forest scorpion habitat has remained relatively stable over the last 21 000 years, consistent with the genetic data. Our results suggest tectonic plate rafting, mountain uplift, river drainage formation and climate‐induced habitat fragmentation have all likely played a role in the diversification of Uroctonus. The intricate pattern of genetic fragmentation revealed across a temporal continuum highlights the potential of low‐dispersing species to shed light on small‐scale patterns of biodiversity and the underlying processes that have generated this diversity in biodiversity hotspots.     

Epidemiological Characteristics of Strongyloidiasis in Inhabitants of Indigenous Communities in Borneo Island,Malaysia

Epidemiological study on strongyloidiasis in humans is currently lacking in Malaysia. Thus, a cross-sectional study was carried out to determine the prevalence of Strongyloides stercoralis infection among the inhabitants of longhouse indigenous communities in Sarawak. A single stool and blood sample were collected from each participant and subjected to microscopy, serological and molecular techniques. Five species of intestinal parasites were identified by stool microscopy. None of the stool samples were positive for S. stercoralis. However, 11% of 236 serum samples were seropositive for strongyloidiasis. Further confirmation using molecular technique on stool samples of the seropositive individuals successfully amplified 5 samples, suggesting current active infections. The prevalence was significantly higher in adult males and tended to increase with age. S. stercoralis should no longer be neglected in any intestinal parasitic survey. Combination of more than 1 diagnostic technique is necessary to increase the likelihood of estimating the ‘true’ prevalence of S. stercoralis.     

Surfactant protein D binds to Mycobacterium tuberculosis bacilli and lipoarabinomannan via carbohydrate-lectin interactions resulting in reduced phagocytosis of the bacteria by macrophages.

Surfactant protein-D (SP-D) is a collectin produced in the distal lung airspaces that is believed to play an important role in innate pulmonary immunity. Naive immunologic responses to Mycobacterium tuberculosis (M.tb) are especially important in the lung, since entry of this inhaled pathogen into the alveolar macrophage is a pivotal event in disease pathogenesis. Here we investigated SP-D binding to M.tb and the effect of this binding on the adherence of M. tb to human macrophages. These studies demonstrate specific binding of SP-D to M.tb that is saturable, calcium dependent, and carbohydrate inhibitable. In addition to purified SP-D, SP-D in bronchoalveolar lavage fluids from healthy donors and patients with alveolar proteinosis also binds to M.tb. Incubation of M.tb with SP-D results in agglutination of the bacteria. In contrast to its binding to M.tb, SP-D binds minimally to the avirulent Mycobacterium smegmatis. SP-D binds predominantly to lipoarabinomannan from the virulent Erdman strain of M.tb, but not the lipoarabinomannan from M. smegmatis. The binding of SP-D to Erdman lipoarabinomannan is mediated by the terminal mannosyl oligosaccharides of this lipoglycan. Incubation of M.tb with subagglutinating concentrations of SP-D leads to reduced adherence of the bacteria to macrophages (62.7% of control adherence +/- 3.3% SEM, n = 8), whereas incubation of bacteria with surfactant protein A leads to significantly increased adherence to monocyte-derived macrophages. These data provide evidence for specific binding of SP-D to M. tuberculosis and indicate that SP-D and surfactant protein A serve different roles in the innate host response to this pathogen in the lung.     

Targeting CoV-2 spike RBD and ACE-2 interaction with flavonoids of Anatolian propolis by in silico and in vitro studies in terms of possible COVID-19 therapeutics

Propolis is a multi-functional bee product rich in polyphenols. In this study, the inhibitory effect of Anatolian propolis against SARS-coronavirus-2 (SARS-CoV-2) was investigated in vitro and in silico. Raw and commercial propolis samples were used, and both samples were found to be rich in caffeic acid, p-coumaric acid, ferulic acid, t-cinnamic acid, hesperetin, chrysin, pinocembrin, and caffeic acid phenethyl ester (CAPE) at HPLC-UV analysis. Ethanolic propolis extracts (EPE) were used in the ELISA screening test against the spike S1 protein (SARS-CoV-2): ACE-2 interaction for in vitro study. The binding energy values of these polyphenols to the SARS-CoV-2 spike and ACE-2 protein were calculated separately with a molecular docking study using the AutoDock 4.2.6 program. In addition, the pharmacokinetics and drug-likeness properties of these eight polyphenols were calculated according to the SwissADME tool. The binding energy value of pinocembrin was highest in both receptors, followed by chrysin, CAPE, and hesperetin. Based on the in silico modeling and ADME (absorption, distribution, metabolism, and excretion) behaviors of the eight polyphenols, the compounds exhibited the potential ability to act effectively as novel drugs. The findings of both studies showed that propolis has a high inhibitory potential against the Covid-19 virus. However, further studies are now needed.     

Major discrepancy between phylogenetic hypotheses based on molecular and morphological criteria within the Order Haplosclerida (Phylum Porifera: Class Demospongiae)

Taxonomy within the sponge Order Haplosclerida remains somewhat contentious. Both morphology and biochemistry have been employed to help unravel the relationships of the Order with limited results perhaps because of the small number of reliable characters. We employed phylogenetic analysis of 750 base pairs of the 5′ end of the 28S rRNA gene to study relationships between 20 taxa within the Order. While preliminary (low number of taxa, one gene region) results suggested strong discrepancy to former phylogenies, there was no support for the monophyly of the Order and almost all morphologically defined genera appeared to be polyphyletic.     

Effects of Application Methods and Plastic Covers on Distribution of Cis- and Trans-1,3-Dichloropropene and Chloropicrin in Root Zone

This study examined the effects of three application methods (chisel injection, Avenger coulter injection, and drip irrigation) and two plastic films (polyethylene film [PE] and virtually impermeable film [VIF]) on distribution of cis- and trans- 1,3-dichloropropene (1,3-D) and chloropicrin (CP) in a Florida sandy soil after application of Telone C35 or Telone In-Line. Regardless of application method, VIF retained greater amounts of cis- and trans-1,3-D and CP in the root zone with longer residential time than PE. There was better retention of the three compounds in the root zone when applied with the Avenger coulter injection rig than chisel injection, especially in combination with VIF. Distribution of the three compounds in the root zone was less predictable when applied by drip irrigation. Following drip irrigation, more than 50% of the three compounds in the PE and VIF-covered beds was found near the end of the drip tapes in one experiment, whereas the distribution was much more uniform in the root zone in a second experiment. Among the three biologically active compounds, CP disappeared from the root zone more rapidly than cis- and trans-1,3-D, especially in the PE-covered beds.