'Leaving my comfort zone'. A qualitative study of physiotherapists' experiences blending an eHealth psychosocial intervention with face-to-face physiotherapy.

BACKGROUND: Many physiotherapists do not feel adequately equipped to address psychosocial risk factors in people with complex pain states. Hence, a biopsychosocial blended intervention (Back2Action) was developed to assist physiotherapists to manage people with persistent spinal pain and coexisting psychosocial risk factors associated with the development or maintenance of persistent pain. OBJECTIVE: This study aimed to gain insight into the experiences of physiotherapists with this blended psychosocial intervention. DESIGN: and methods: This was an interpretative qualitative study with a reflexive thematic analysis of semi-structured interviews with physiotherapists (N = 15) who delivered Back2Action. The interview started with the grand-tour question: "What was your experience in using Back2Action?" Physiotherapist were encouraged to provide examples, and follow-up questions were posed to ensure a deeper understanding could be reached. RESULTS: Four themes were constructed: Physiotherapists became increasingly aware of (1) their own implicit expectations, biases and skills, and underlying treatment paradigms, and (2) the implicit expectations from their patients towards them. This led to (3) creating a deeper and stronger therapeutic alliance with the patient, but also (4) an understanding that implementation of a true biopsychosocial intervention - even if offered in a blended form - requires more practice, confidence and resources. CONCLUSIONS: Back2Action is considered a valuable treatment to deliver a biopsychosocial intervention in primary care. Considering the high level of knowledge, skills and competency of the participating physiotherapists, the perceived barriers may be more difficult to overcome for more junior physiotherapists.

How people with persistent pain experience in-person physiotherapy blended with biopsychosocial digital health - A qualitative study on participants' experiences with Back2Action.

Background: A blended intervention consisting of in-person physiotherapy and psychologically-informed digital health, called Back2Action, was developed to optimise the management of people with persistent spinal pain who also have psychosocial risk factors associated with the development or maintenance of persistent pain. This study aimed to gain insights in how participants experienced this blended intervention. Methods: A qualitative study using semi-structured interviews was conducted. Eleven people with persistent non-specific spinal pain who received the blended intervention within a randomised clinical trial were included. All interviews were recorded, transcribed verbatim and analysed independently by two researchers. Data were analysed using a thematic analysis. Results: The analysis identified four themes: (1) Experiencing a better understanding of the relationship between own physical and mental health; (2) Importance of the physiotherapist's active involvement in biopsychosocial blended care, which describes the crucial role of physiotherapists in supporting participants in this; (3) Appreciation of digital health, to better understand persistent pain and make meaningful lifestyle changes; and (4) Trials and triumphs, revealing gains such as better coping, but also challenges with implementation of changes into long-term routines. Conclusion: Participants of the blended intervention experienced positive changes in thoughts and behaviours, which highlights the feasibility and acceptability of the blended intervention as a more holistic treatment within pain management. The differences in personal preferences for receiving psychologically-informed digital health poses challenges for implementation of blended biopsychosocial care in evidence-based practice.

'Give me something meaningful': GPs perspectives on how to improve an audit and feedback report provided by health insurers - an exploratory qualitative study.

BACKGROUND: Audit and feedback (A&F) is a valuable quality improvement strategy, which can contribute to de-implementation of low-value care. In the Netherlands, all health insurers collaboratively provide A&F to general practitioners (GPs), the 'Primary Care Practice Report' (PCPR). Unfortunately, the use of this report by GPs is limited. This study examined the thoughts of GPs on the usability of the PCPR and GPs recommendations for improving the PCPR. METHOD: We used an interpretative qualitative design, with think-aloud tasks to uncover thoughts of GPs on the usability of the PCPR and semistructured interview questions to ask GPs' recommendations for improvement of the PCPR. Interviews were audiorecorded and transcribed ad verbatim. Data were analysed using thematic content analysis. RESULTS: We identified two main themes: 'poor usability of the PCPR', and 'minimal motivation to change based on the PCPR'. The GPs found the usability of the PCPR poor due to the feedback not being clinically meaningful, the data not being recent, individual and reliable, the performance comparators offer insufficient guidance to assess clinical performance, the results are not discussed with peers and the definitions and visuals are unclear. The GPs recommended improving these issues. The GPs motivation to change based on the PCPR was minimal. CONCLUSIONS: The GPs evaluated the PCPR as poorly usable and were minimally motivated to change. The PCPR seems developed from the perspective of the reports' commissioners, health insurers, and does not meet known criteria for effective A&F design and user-centred design. Importantly, the GPs did state that well-designed feedback could contribute to their motivation to improve clinical performance.Furthermore, the GPs stated that they receive a multitude of A&F reports, which they hardly use. Thus, we see a need for policy makers to invest in less, but more usable A&F reports.

Bioavailability of contaminants estimated from uptake rates into soil invertebrates.

It is often argued that the concentration of a pollutant inside an organism is a good indicator of its bioavailability, however, we show that the rate of uptake, not the concentration itself, is the superior predictor. In a study on zinc accumulation and toxicity to isopods (Porcellio scaber) the dietary EC(50) for the effect on body growth was rather constant and reproducible, while the internal EC(50) varied depending on the accumulation history of the animals. From the data a critical value for zinc accumulation in P. scaber was estimated as 53 microg/g/wk. We review toxicokinetic models applicable to time-series measurements of concentrations in invertebrates. The initial slope of the uptake curve is proposed as an indicator of bioavailability. To apply the dynamic concept of bioavailability in risk assessment, a set of representative organisms should be chosen and standardized protocols developed for exposure assays by which suspect soils can be evaluated.

Two metal-binding peptides from the insect Orchesella cincta (Collembola) as a result of metallothionein cleavage.

Metallothionein (MT) is an ubiquitous heavy metal-binding protein which has been identified in animals, plants, protists, fungi and bacteria. In insects, primary structures of MTs are known only for Drosophila and the collembolan, Orchesella cincta. The MT cDNA from O. cincta encodes a 77 amino acid protein with 19 cysteines. Isolations of the protein itself have demonstrated the presence of two smaller metal-binding peptides, whose amino acid sequences correspond to parts of the cDNA, and which apparently result from cleavage of the native protein. The present study was undertaken to complete the picture of cleavage sites within the MT protein by applying protein isolation techniques in combination with mass spectrometry and N-terminal sequence analysis. Further, recombinant expression allowed us to study the intrinsic stability of the MT and to perform in vitro cleavage studies. The results show that the MT from O. cincta is specifically cleaved at two sites, both after the amino acid sequence Thr-Gln (TQ). One of these sites is located in the N-terminal region and the other in the linker region between two putative metal-binding clusters. When expressed in Escherichia coli, the recombinant O. cincta MT can be isolated in an uncleaved form; however, this protein can be cleaved in vitro by the proteolytic activity of O. cincta. In combination with other studies, the results suggest that the length of the linker region is important for the stability of MT as a two domain metal-binding protein.

Biomarkers in terrestrial invertebrates for ecotoxicological soil risk assessment.

This review has served to present the most recent information on a selected series of biomarker studies undertaken on soil invertebrates during two extensive European-funded scientific consortia, BIOPRINT and BIOPRINT-II. The goals were to develop and validate methods for the analysis of markers of stress in a range of soil-dwelling organisms. We have discussed the potential and limitations of the following invertebrate biomarkers for soil risk assessment purposes: heat shock proteins, histological and ultrastructural markers, metallothioneins and metal-binding proteins, esterases, lysosomal integrity, and the novel biomarker histidine. The hsp response in soil invertebrates is especially suitable to indicate the effects of exposure to comparatively low concentrations for a range of toxicants and can be regarded as a biomarker of general stress. The application of MTs and other metal-binding proteins as biomarkers for exposure in soil invertebrates has been well described, and new methods are being developed for analyzing MT induction both at the protein and molecular level, and reliable and reproducible methods are now available. (Cd)-MT is well characterized for the springtails and its MT concentration is a useful biomarker for exposure as well as for effect. For snails, (Cd)-MT can accumulate in the midgut gland over extended periods of time and therefore its concentration is a biomarker not only for recent intoxication but also for events of cadmium exposure that snails may have experienced a long time before the measurement took place. Cellular and histological alterations can be regarded as reflecting the "health" state of a cell, which may be a measure for the presence of toxicants. Histopathological work on terrestrial invertebrates, however, is still scarce. Isozymes have been poorly studied in soil invertebrates despite their promising role as potential biomarkers in aquatic organisms. Among the large diversity of isozymes, the most well studied are esterases that are frequently used a biomarkers of exposure to various classes of pesticides. Many other isozymes offer potentials for biomarker research, such as glucosephosphate isomerase and phosphoglucomutase, both enzymes necessary for the glycolytic pathway. The lysosomal system has been identified as a particular target for the toxic effects of xenobiotics, although it has yet a limited application in soil invertebrates. This marker is nonspecific, responding equally sensitively to organic or inorganic contamination; however, if used in combination with an earthworm immnunocompetence assay such as total immunoactivity of the coelomocytes, then it is possible to be more specific as to the likely nature of contamination. Free histidine was positively correlated with increasing copper exposure and total copper burden in earthworms from a semifield study. Histidine may thus act as a biomarker of exposure. The transient responses and confounding factors of biomarkers obscure a proper interpretation of biomarker responses under field conditions. These factors are still very poorly understood and require more study. For risk assessment purposes it is recommended that the aforementioned biomarkers may show promise when included in a suite of biomarkers among different soil invertebrate species. It is recommended that a risk assessment protocol draw upon ranking of biomarker responses on a defined scale. It is also hoped that the problems outlined in this review will aid the direction of future research on soil invertebrate biomarkers.

Metallothionein-bound cadmium in the gut of the insect Orchesella cincta (Collembola) in relation to dietary cadmium exposure.

Metallothionein is considered to be a potential biomarker for heavy metal exposure in the terrestrial environment. However, limited information is available on metallothioneins from insects, a major class of terrestrial invertebrates. In this study we have quantified metallothioneins in the springtail Orchesella cincta by determining metallothionein-bound cadmium after separation of these proteins using gel filtration and reversed phase chromatography from total body homogenates of animals dietary exposed to different concentrations of cadmium. Furthermore, we have studied in more detail where cadmium and metallothionein-bound cadmium is located within this animal. The concentration of metallothionein-bound cadmium increases with the exposure concentration in the same way as the total internal concentration. Both reach a plateau at an exposure concentration of approximately 1.0 micromol Cd/dry food. Cadmium is primarily located within the gut of O. cincta and isolation of metallothionein from this organ gives results identical to isolations from total bodies. Based on this results an estimation of the metallothionein level at the highest exposure concentration results in a concentration of about 115 microg metallothionein/g fresh gut. The O. cincta metallothionein gives the possibility of using this protein as a biomarker for heavy metal exposure in soil insects.

Primary structure of a cadmium-induced metallothionein from the insect Orchesella cincta (Collembola).

The induction of metallothionein was studied in the springtail Orchesella cincta (Collembola), a species of insect living in forest soils. Upon dietary exposure to Cd, two Cd-binding, cysteine-rich peptides were isolated from whole-body homogenates, using gel filtration and reversed-phase FPLC. Mass spectrometric analysis revealed that the molecular masses of these peptides were 2989 Da and 4139 Da, respectively. Amino acid sequencing of the 2989-Da peptide resulted in a sequence typical for a metallothionein. Sequencing of the 4139-Da protein was unsuccessful, probably due to N-terminal blockage. Using different PCR techniques (3' and 5' RACE) with (degenerate) primers based on the identified amino acid sequence of the 2989 Da peptide, a metallothionein cDNA was isolated. The sequence of this cDNA potentially codes for a protein of 77 amino acids. The 2989 Da peptide corresponds to the C-terminal part of this protein. The 4139-Da protein is probably encoded by the N-terminal part of this protein. These results suggest that the identified peptides are products of one gene, and that the primary gene product is subject to post-translational processing. The deduced amino acid sequence of the O. cincta metallothionein shows low sequence similarity with metallothioneins from Drosophila. The similarity between O. cincta MT and MTs of invertebrates is not higher than that between O. cincta and vertebrates.

Early reproduction and increased reproductive allocation in metal-adapted populations of the terrestrial isopod Porcellio scaber.

Organisms inhabiting metal-contaminated areas can be stressed by metal exposure and are possibly subject to selection, resulting in increased metal tolerance and changes in growth and/or reproduction characteristics. In a previous study it was found that in the terrestrial isopod Porcellio scaber, sampled from the vicinity of a zine smelter, the body size was small and the brood size was large compared to isopods from a reference area. To assess whether these differences were due to genetic differentiation between strains, isopods collected from a reference wood, a zinc smelter area and a lead mine were cultured on non-polluted food, while growth, reproduction and metal concentrations were studied in first and second laboratory generations. The isopods from the three populations differed in age and weight at first reproduction, although there were hardly any differences in growth. The females of the mine and the smelter population started to reproduce earlier, at a lower weight, which resulted in fewer young per female. However, reproductive allocation (=wight of young relative to the weight of the mother) was higher in mine and smelter isopods. We conclude that the isopods at the metal-contaminated sites have been selected for early reproduction and increased reproductive allocation. The results indicate that populations inhabiting metal-polluted sites have probably undergone evolutionary changes. This study showed that growth and reproduction characteristics of different populations under laboratory conditions may provide information on selection processes in the field.

The possible role of metallothioneins in copper tolerance of Silene cucubalus.

Growth and copper-binding of a copper-tolerant and a copper-sensitive population of Silene cucubalus (L.) Wib. have been studied. The copper-tolerant plants showed a much lower uptake and a proportionally higher transport of copper from root to shoot. A copper-binding protein with an apparent Mr of 8500 resembling metallothionein has been isolated from the roots of copper-treated plants of the tolerant population. After 20 d, the protein was observed to be inducible upon copper supply in the copper-tolerant plants, but not yet in the sensitive ones. This could be an indication of a difference in metalregulated synthesis of the protein. Ion-exchange chromatography of the 8500 protein yielded a major copper-containing fraction eluting at high ionic strength. Other characteristics such as UV absorption and amino-acid composition resembled strongly those of metallothioneins. The involvement of metallothioneins in the detoxification of copper within Cu-tolerant plants is discussed in relation to other mechanisms.