Cartilage repair: past and future – lessons for regenerative medicine

Since the first cell therapeutic study to repair articular cartilage defects in the knee in 1994, several clinical studies have been reported. An overview of the results of clinical studies did not conclusively show improvement over conventional methods, mainly because few studies reach level I of evidence for effects on middle or long term. However, these explorative trials have provided valuable information about study design, mechanisms of repair and clinical outcome and have revealed that much is still unknown and further improvements are required. Furthermore, cellular and molecular studies using new technologies such as cell tracking, gene arrays and proteomics have provided more insight in the cell biology and mechanisms of joint surface regeneration. Besides articular cartilage, cartilage of other anatomical locations as well as progenitor cells are now considered as alternative cell sources. Growth Factor research has revealed some information on optimal conditions to support cartilage repair. Thus, there is hope for improvement. In order to obtain more robust and reproducible results, more detailed information is needed on many aspects including the fate of the cells, choice of cell type and culture parameters. As for the clinical aspects, it becomes clear that careful selection of patient groups is an important input parameter that should be optimized for each application. In addition, the study outcome parameters should be improved. Although reduced pain and improved function are, from the patient's perspective, the most important outcomes, there is a need for more structure/tissue-related outcome measures. Ideally, criteria and/or markers to identify patients at risk and responders to treatment are the ultimate goal for these more sophisticated regenerative approaches in joint surface repair in particular, and regenerative medicine in general.     

Introduction of a collaborative quality improvement program in the French cystic fibrosis network: the PHARE-M initiative

Background

An agreement, signed in 2007 by the 49 French Cystic Fibrosis Centers, included a commitment to participate, within the next 5 years, in a care quality assessment and improvement program (QIP). The objective was to roll out in the French Cystic Fibrosis (CF) care network a QIP adapted from the US program for Accelerating Improvement in Cystic Fibrosis Care developed by The Dartmouth Institute Microsystem Academy (TDIMA) and customized by the US CF Foundation between 2002 and 2013.

Methods

The French national team at the Nantes-Roscoff CF Center of Expertise was trained at TDIMA and visited US CF centers involved in US Learning and Leadership Collaboratives (LLCs). It introduced the PHARE-M QIP in France by transposing the Action Guide and material. A PHARE-M LLC1 including seven centers, underwent two external assessments. Adjustments were made, then a PHARE-M LLC2 was rolled out at seven more centers in two regions. On-site coaching was strengthened. The teams’ satisfaction was assessed and further adjustments were made. In 2014, the program sought recognition as a continuing education program for healthcare professionals.

Results

Ninety-six trainees including 14 patients/parents from the 14 CFCs volunteered to participate, test and adapt the program during LLC1 and LLC2 sessions. Comparison of patient outcomes collected in the Registry report by CF center, reflection on potential best practices, selection by each team of an improvement theme, implementation of improvement actions, and exchanges between teams fostered the adhesion of the teams. The program strengthened quality of care, interdisciplinary functioning and collaboration with patients/parents at the centers. The satisfaction expressed by the teams increased over time. A post-PHARE-M cycle maintains the focus on continuous quality improvement (CQI). In 2015, PHARE-M was recognized as a continuing professional development program in healthcare.

Conclusions

The PHARE-M is a complex intervention in multidisciplinary teams working in a variety of hospital settings. A confluence of factors motivated teams to engage in the program. Involving Patient/Parent in quality improvement (QI) work and developing patient therapeutic education for self-management appeared to be complementary approaches to improve care. Incorporating the program into hospital continuing education insures its sustainability. Transparency of Patient Registry indicators per center published in a brief lapse of time is required to effectively support CQI. The impact of the PHARE-M on patient outcomes after 3 years is the subject of a research program funded by the French Ministry of Health whose results will be available in 2017.

     

The DIAMOND initiative: implementing collaborative care for depression in 75 primary care clinics

Background

The many randomized trials of the collaborative care model for improving depression in primary care have not described the implementation and maintenance of this model. This paper reports how and the degree to which collaborative care process changes were implemented and maintained for the 75 primary care clinics participating in the DIAMOND Initiative (Depression Improvement Across Minnesota–Offering a New Direction).

Methods

Each clinic was trained to implement seven components of the model and participated in ongoing evaluation and facilitation activities. For this study, assessment of clinical process implementation was accomplished via completion of surveys by the physician leader and clinic manager of each clinic site at three points in time. The physician leader of each clinic completed a survey measure of the presence of various practice systems prior to and one and two years after implementation. Clinic managers also completed a survey of organizational readiness and the strategies used for implementation.

Results

Survey response rates were 96% to 100%. The systems survey confirmed a very high degree of implementation (with large variation) of DIAMOND depression practice systems (mean of 24.4?±?14.6%) present at baseline, 57.0?±?21.0% at one year (P?=?<0.0001), and 55.9?±?21.3% at two years. There was a similarly large increase (and variation) in the use of various quality improvement strategies for depression (mean of 29.6?±?28.1% at baseline, 75.1?±?22.3% at one year (P?=?<0.0001), and 74.6?±?23.0% at two years.

Conclusions

This study demonstrates that under the right circumstances, primary care clinics that are prepared to implement evidence-based care can do so if financial barriers are reduced, effective training and facilitation are provided, and the new design introduces the specific mental models, new care processes, and workers and expertise that are needed. Implementation was associated with a marked increase in the number of improvement strategies used, but actual care and outcomes data are needed to associate these changes with patient outcomes and patient-reported care.

     

Bioremediation – prospects for the future application of innovative applied biological research

It has been estimated that there may be as much as 300 000 ha in the UK where contamination from previous industrial land use has occurred. The ‘Source‐Pathway‐Receptor’ model is used to evaluate these risks. Traditional engineering approaches have dominated remediation technology, but biological methods have become increasingly important in recent years. ‘Bioremediation’ has been defined as ‘the elimination, attenuation or transformation of polluting or contaminating substances by the use of biological processes’. Techniques to treat soil materials include biopiling, windrowing, landfarming and bioventing, all of which depend on microbiological degradation. However, increasingly it also includes the use of vegetation to take up and/or degrade contaminants (phytoremediation) or restrict contaminant movement (phytostabilisation). Phytoremediation can be encouraged by manipulation of the rhizosphere, using selected fungal isolates in a process now defined as phytobial remediation.     

Fleshy fruits – origins, niche shifts, and diversification

We examined shifts in fruit type, fleshy vs non-fleshy, in relation to habitat-related niche shifts, species richness, and historical distribution, in 50 phylogenetically independent plant lineages. Each lineage consisted of a sister-group pair of fleshy vs non-fleshy taxa and their outgroup. Niche shifts were assessed based on plant community characteristics. Two niche dimensions assumed to reflect community dynamics were derived: spatial predictability of disturbances and canopy closure. Phylogenetically independent origins of fleshy fruit types (1) were correlated with changes to habitats characterized by more shaded and spatially more unpredictable disturbances, (2) had an opposite effect on species richness in woody and herbaceous clades, enhancing species richness in woody clades, and (3) were continuously distributed over a period covering the last 70 million years. These results support the hypothesis that fleshy fruit evolution is driven by vegetation dynamics, and suggest that the strength of frugivore mediated selection on fleshy fruits increases when recruitment sites are spatially unpredictable and/or characterized by low light conditions.     

Searching for weeds – a GIS tool

Sampling for rare events, such as a new weed incursion, can be surprisingly efficient when adaptive, unequal probability survey designs are used. Spatially explicit habitat models and expert knowledge of weedy species can be used to identify areas of varied survey intensity. We introduce a GIS-based tool that can be used for designing such a survey. The user-friendly tool interfaces (behind the scenes) with the US Environmental Protection Agency’s spatially balanced sampling design functions in R. The functions ensure that the location of the sample points are spatially balanced while at the same time, allowing the user to specify survey intensity in area of special interest (preferred habitats, areas of high conservation value, areas of high public use, etc). We discuss the use of the GIS tool in a case study where we designed a 5-year weed monitoring plan for a local authority in New Zealand. The plan includes ‘over sample’ sites to replace any original sample sites that were impractical or costly to visit. Initial results include estimates of what proportion of the total region has weeds present and an estimate of weed density. More detailed results are produced for specified known weed hot spots, such as areas adjacent to roads and rivers. These estimates are available for all weed species, and for individual species. Because the system is GIS-based, spatial information is stored. Over time, as the weed surveillance and monitoring progresses, regional changes in weed distribution can be tracked, and species and locations that require more targeted weed management can be identified. Further results of such a probability-based design can be used to develop habitat models for predicting future distributions.