Implementation fidelity trajectories of a health promotion program in multidisciplinary settings: managing tensions in rehabilitation care

Background

Although the importance of evaluating implementation fidelity is acknowledged, little is known about heterogeneity in fidelity over time. This study aims to generate insight into the heterogeneity in implementation fidelity trajectories of a health promotion program in multidisciplinary settings and the relationship with changes in patients’ health behavior.

Methods

This study used longitudinal data from the nationwide implementation of an evidence-informed physical activity promotion program in Dutch rehabilitation care. Fidelity scores were calculated based on annual surveys filled in by involved professionals (n?=?±?70). Higher fidelity scores indicate a more complete implementation of the program’s core components. A hierarchical cluster analysis was conducted on the implementation fidelity scores of 17 organizations at three different time points. Quantitative and qualitative data were used to explore organizational and professional differences between identified trajectories. Regression analyses were conducted to determine differences in patient outcomes.

Results

Three trajectories were identified as the following: ‘stable high fidelity’ (n?=?9), ‘moderate and improving fidelity’ (n?=?6), and ‘unstable fidelity’ (n?=?2). The stable high fidelity organizations were generally smaller, started earlier, and implemented the program in a more structured way compared to moderate and improving fidelity organizations. At the implementation period’s start and end, support from physicians and physiotherapists, professionals’ appreciation, and program compatibility were rated more positively by professionals working in stable high fidelity organizations as compared to the moderate and improving fidelity organizations (p?<?.05). Qualitative data showed that the stable high fidelity organizations had often an explicit vision and strategy about the implementation of the program. Intriguingly, the trajectories were not associated with patients’ self-reported physical activity outcomes (adjusted model β?=???651.6, t(613)?=???1032, p?=?.303).

Conclusions

Differences in organizational-level implementation fidelity trajectories did not result in outcome differences at patient-level. This suggests that an effective implementation fidelity trajectory is contingent on the local organization’s conditions. More specifically, achieving stable high implementation fidelity required the management of tensions: realizing a localized change vision, while safeguarding the program’s standardized core components and engaging the scarce physicians throughout the process. When scaling up evidence-informed health promotion programs, we propose to tailor the management of implementation tensions to local organizations’ starting position, size, and circumstances.

Trial registration

The Netherlands National Trial Register NTR3961. Registered 18 April 2013.

     

Different responses to DNA damage determine ageing differences between organs

Organs age differently, causing wide heterogeneity in multimorbidity, but underlying mechanisms are largely elusive. To investigate the basis of organ‐specific ageing, we utilized progeroid repair‐deficient Ercc1^{Δ /−} mouse mutants and systematically compared at the tissue, stem cell and organoid level two organs representing ageing extremes. Ercc1^{Δ /−} intestine shows hardly any accelerated ageing. Nevertheless, we found apoptosis and reduced numbers of intestinal stem cells (ISCs), but cell loss appears compensated by over‐proliferation. ISCs retain their organoid‐forming capacity, but organoids perform poorly in culture, compared with WT. Conversely, liver ages dramatically, even causing early death in Ercc1‐KO mice. Apoptosis, p21, polyploidization and proliferation of various (stem) cells were prominently elevated in Ercc1^{Δ /−} liver and stem cell populations were either largely unaffected (Sox9+), or expanding (Lgr5+), but were functionally exhausted in organoid formation and development in vitro. Paradoxically, while intestine displays less ageing, repair in WT ISCs appears inferior to liver as shown by enhanced sensitivity to various DNA‐damaging agents, and lower lesion removal. Our findings reveal organ‐specific anti‐ageing strategies. Intestine, with short lifespan limiting time for damage accumulation and repair, favours apoptosis of damaged cells relying on ISC plasticity. Liver with low renewal rates depends more on repair pathways specifically protecting the transcribed compartment of the genome to promote sustained functionality and cell preservation. As shown before, the hematopoietic system with intermediate self‐renewal mainly invokes replication‐linked mechanisms, apoptosis and senescence. Hence, organs employ different genome maintenance strategies, explaining heterogeneity in organ ageing and the segmental nature of DNA‐repair‐deficient progerias.     

Obesity in older adults is associated with an increased prevalence and incidence of pain

Cross-sectional studies suggest an association between BMI and pain. This prospective study investigated the associations of measured BMI and waist circumference with prevalent and incident pain in older adults. The study included participants of the Longitudinal Aging Study Amsterdam, aged 55-85 years at baseline (1992-1993). Pain was assessed using a subscale of the Nottingham Health Profile at baseline (N = 2,000), after 3 years (N = 1,478) and 6 years (N = 1,271) of follow-up. The overall prevalence of pain was 32.7% at baseline and increased significantly with higher quartiles of BMI or waist circumference. After adjustment for age, education, depression, smoking, physical activity, and chronic diseases, multiple logistic regression analyses showed odds ratios (ORs (95% confidence interval)) for prevalent pain of 2.16 (1.32-3.54) in men and 1.93 (1.26-2.95) in women comparing the highest with the lowest quartile of BMI. Of the participants without pain at baseline, those in the highest quartile of BMI had a twofold increased odds for incident pain after 3 years of follow-up. After 6 years of follow-up, ORs for incident pain were 2.34 (1.17-4.72) in men and 2.78 (1.36-5.70) in women. Additional adjustment for weight change did not change these associations. Similar results were found for the associations between waist circumference and pain. Exploring the reversed causal relation, analyses showed no significant associations between prevalent pain and weight gain. In conclusion, the prevalence of pain is higher among obese older men and women compared to their normal-weight peers. Furthermore, obese older adults are at increased odds to develop pain.     

Larger Thigh and Hip Circumferences Are Associated with Better Glucose Tolerance: The Hoorn Study

Objective: A higher waist‐to‐hip ratio, which can be due to a higher waist circumference, a lower hip circumference, or both, is associated with higher glucose levels and incident diabetes. A lower hip circumference could reflect either lower fat mass or lower muscle mass. Muscle mass might be better reflected by thigh circumference. The aim of this study was to investigate the contributions of thigh and hip circumferences, independent of waist circumference, to measures of glucose metabolism. Research Methods and Procedures: For this cross‐sectional study we used baseline data from the Hoorn Study, a population‐based cohort study of glucose tolerance among 2484 men and women aged 50 to 75. Glucose tolerance was assessed by a 75‐g oral glucose tolerance test; hemoglobin A_1c and fasting insulin were also measured. Anthropometric measurements included body mass index (BMI) and waist, hip, and thigh circumferences. Results: Stratified analyses and multiple linear regression showed that after adjustment for age, BMI, and waist circumference, thigh circumference was negatively associated with markers of glucose metabolism in women, but not in men. Standardized β values in women were ?0.164 for fasting, ?0.206 for post‐load glucose, ?0.190 for hemoglobin A_1c (all p < 0.001), and ?0.065 for natural log insulin levels (p = 0.061). Hip circumference was negatively associated with markers of glucose metabolism in both sexes (standardized betas ranging from ?0.093 to ?0.296, p < 0.05) except for insulin in men. Waist circumference was positively associated with glucose metabolism. Discussion: Thigh circumference in women and hip circumference in both sexes are negatively associated with markers of glucose metabolism independently of the waist circumference, BMI, and age. Both fat and muscle tissues may contribute to these associations.     

QDR 4500A DXA overestimates fat-free mass compared with criterion methods.

This study evaluated the accuracy with which the dual-energy X-ray absorptiometer (Hologic QDR 4500A) measured fat-free mass (FFM), fat mass (FM), and hydration of FFM. In a study of 58 men and women (ages 70-79 yr), the QDR 4500A was found to provide a systematically higher estimate of FFM and lower estimate of FM than a four-component model of body composition. A correction factor from this study was developed and applied to two other samples (n = 13 and 37). We found mean corrected levels of FFM and FM to be equivalent to that obtained by the four-component model or total body water. In addition, the hydration of the corrected FFM was closer to the established hydration level in adult samples and that obtained from the four-component model. These findings suggest that the current calibration of the fan-beam system of the Hologic QDR 4500A provides an overestimate of FFM and underestimate of FM compared with reference methods.     

One- and two-year change in body composition as measured by DXA in a population-based cohort of older men and women.

Changing body composition has been suggested as a pathway to explain age-related functional decline. No data are available on the expected changes in body composition as measured by dual-energy X-ray absorptiometry (DXA) in a population-based cohort of older persons. Body composition data at baseline, 1-yr follow-up, and 2-yr follow-up was measured by DXA in 2,040 well-functioning black and white men and women aged 70-79 yr, participants of the Health, Aging, and Body Composition Study. After 2 yr, a small decline in total body mass was observed (men: -0.3%, women: -0.4%). Among men, fat-free mass and appendicular lean soft tissue mass (ALST) decreased by -1.1 and -0.8%, respectively, which was masked by a simultaneous increase in total fat mass (+2.0%). Among women, a decline in fat-free mass was observed after 2 yr only (-0.6%) with no change in ALST and body fat mass. After 2 yr, the decline in ALST was greater in blacks than whites. Change in total body mass was associated with change in ALST (r = +0.58 to +0.70; P < 0.0001). Among participants who lost total body mass, men lost relatively more ALST than women, and blacks lost relatively more ALST than whites. In conclusion, the mean change in body composition after a 1- to 2-yr follow-up was 1-2% with a high interindividual variability. Loss of ALST was greater in men compared with women, and greater in blacks compared with whites, suggesting that men and blacks may be more prone to muscle loss.     

Lipopolysaccharide regions involved in the activation of Escherichia coli outer membrane protease OmpT.

OmpT is an integral outer membrane protease of Escherichia coli. Overexpression of OmpT in E. coli and subsequent in vitro folding of the produced inclusion bodies yielded protein with a native-like structure. However, enzymatically active protease was only obtained after addition of the outer membrane lipid lipopolysaccharide (LPS). OmpT is the first example of an enzyme that requires LPS for activity. In this study, we investigated the nature of this activation. Circular dichroism analysis showed that binding of LPS did not lead to large structural changes. Titration of OmpT with LPS and determining the resulting OmpT activity with a fluorimetric assay yielded a dissociation constant of 10-4 m for E. coli K-12 LPS. Determining the dissociation constants for different LPS chemotypes revealed that a fully acylated lipid A part is minimally required for activation of OmpT. The heptose-bound phosphates in the inner core region were also important for activation. The affinity for LPS was not dependent on the concentration of substrate, neither was affinity for the substrate influenced by the concentration of LPS. This indicated that LPS most likely does not act at the level of substrate binding. We hypothesize that LPS induces a subtle conformational change in the protein that is required for obtaining a native active site geometry.     

Role of caveolin-1 in fibrotic diseases

Fibrosis underlies the pathogenesis of numerous diseases and leads to severe damage of vital body organs and, frequently, to death. Better understanding of the mechanisms resulting in fibrosis is essential for developing appropriate treatment solutions and is therefore of upmost importance. Recent evidence suggests a significant antifibrotic potential of an integral membrane protein, caveolin-1. While caveolin-1 has been widely studied for its role in the regulation of cell signaling and endocytosis, its possible implication in fibrosis remains largely unclear. In this review we survey involvement of caveolin-1 in various cellular processes and highlight different aspects of its antifibrotic activity. We hypothesize that caveolin-1 conveys a homeostatic function in the process of fibrosis by (a) regulating TGF-β1 and its downstream signaling; (b) regulating critical cellular processes involved in tissue repair, such as migration, adhesion and cellular response to mechanical stress; and (c) antagonizing profibrotic processes, such as proliferation. Finally, we consider this homeostatic function of caveolin-1 as a possible novel approach in treatment of fibroproliferative diseases.     

L. plantarum,L. salivarius,and L. lactis Attenuate Th2 Responses and Increase Treg Frequencies in Healthy Mice in a Strain Dependent Manner

Many studies on probiotics are aimed at restoring immune homeostasis in patients to prevent disease recurrence or reduce immune-mediated pathology. Of equal interest is the use of probiotics in sub-clinical situations, which are characterized by reduced immune function or low-grade inflammation, with an increased risk of infection or disease as a consequence. Most mechanistic studies focus on the use of probiotics in experimental disease models, which may not be informative for these sub-clinical conditions. To gain better understanding of the effects in the healthy situation, we investigated the immunomodulatory effects of two Lactobacillus probiotic strains, i.e. L. plantarum WCFS1 and L. salivarius UCC118, and a non-probiotic lactococcus strain, i.e. L. lactis MG1363, in healthy mice. We studied the effect of these bacteria on the systemic adaptive immune system after 5 days of administration. Only L. plantarum induced an increase in regulatory CD103⁺ DC and regulatory T cell frequencies in the spleen. However, all three bacterial strains, including L. lactis, reduced specific splenic T helper cell cytokine responses after ex vivo restimulation. The effect on IFN-γ, IL5, IL10, and IL17 production by CD4⁺ and CD8⁺ T cells was dependent on the strain administered. A shared observation was that all three bacterial strains reduced T helper 2 cell frequencies. We demonstrate that systemic immunomodulation is not only observed after treatment with probiotic organisms, but also after treatment with non-probiotic bacteria. Our data demonstrate that in healthy mice, lactobacilli can balance T cell immunity in favor of a more regulatory status, via both regulatory T cell dependent and independent mechanisms in a strain dependent manner.     

Physiological tonicity improves human chondrogenic marker expression through nuclear factor of activated T-cells 5 <Emphasis Type="Italic">in vitro</Emphasis>

Introduction  

Chondrocytes experience a hypertonic environment compared with plasma (280 mOsm) due to the high fixed negative charge density of cartilage. Standard isolation of chondrocytes removes their hypertonic matrix, exposing them to nonphysiological conditions. During in vitro expansion, chondrocytes quickly lose their specialized phenotype, making them inappropriate for cell-based regenerative strategies. We aimed to elucidate the effects of tonicity during isolation and in vitro expansion on chondrocyte phenotype.