Integrating clinician support with intervention design as part of a programme testing stratified care for musculoskeletal pain in general practice.

BACKGROUND: Stratified care involves subgrouping patients based on key characteristics, e.g. prognostic risk, and matching these subgroups to early treatment options. The STarT-MSK programme developed and tested a new stratified primary care intervention for patients with common musculoskeletal (MSK) conditions in general practice. Stratified care involves changing General Practitioners' (GPs) behaviour, away from the current 'stepped' care approach to identifying early treatment options matched to patients' risk of persistent pain. Changing healthcare practice is challenging, and to aid the successful delivery of stratified care, education and support for GPs was required. This paper details the iterative development of a clinician support package throughout the lifespan of the programme, to support GPs in delivering the stratified care intervention. We argue that clinician support is a crucial aspect of the intervention itself, which is often overlooked. METHODS: Qualitative research with patients and GPs identified barriers and facilitators to the adoption of stratified care, which were mapped onto the Theoretical Domains Framework (TDF). Identified domains were 'translated' into an educational paradigm, and an initial version of the support package developed. This was further refined following a feasibility and pilot RCT, and a finalised support package was developed for the main RCT. RESULTS: The clinician support package comprised face-to-face sessions combining adult-learning principles with behaviour change theory in a multimethod approach, which included group discussion, simulated consultations, patient vignettes and model consultation videos. Structured support for GPs was crucial to facilitate fidelity and, ultimately, a successful trial. Clinician support is a two-way process- the study team can learn from and adapt to specific local factors and issues not previously identified. The support from senior clinicians was required to ensure 'buy in'. Monitoring of GP performance, provision of regular feedback and remedial support are important aspects of effective clinician support. CONCLUSION: Designing effective clinician support from the onset of trial intervention design, in an evidence-based, theory-informed manner, is crucial to encourage active engagement and intervention fidelity within the trial, enabling the delivery of a robust and reliable proof-of-principle trial. We offer practical recommendations for future general practice interventions.

Sustaining voluntary recycling programmes in a country transitioning to an integrated solid waste management system.

Many developing countries are transitioning to integrated solid waste management systems that will likely have a recycling component for making them sustainable. There are several approaches to recycling, one being waste separation at the household level. Such an approach relies critically on the willingness of households to engage in source-separation. Many studies on recycling have been based on self-reported information on the willingness of households to participate in recycling programmes, should they be established; only few studies have been able to test what these intentions are by actual measurements of participation. The type of measurement for gauging success should be able to compare achievements against alternative approaches. This study is of particular interest to transitioning countries because it reports on a recycling programme in a small community that, even though voluntary in nature, has so far been sustained for almost three years. Available data on the amount of recycled beverage containers retrieved over a six-month period was analysed to assess the performance of the programme. A survey of households was performed among the community to understand the factors that may be contributing to such longevity. It was found that a major driver is the internal motivation of most of the community households for caring and preserving the environment. This is a necessary but not sufficient requirement, for it is doubtful whether the programme could have been sustained without an effective education programme and a system to make the process of retrieval easy. The education programme importantly linked recycling as a solution to an environmental problem plaguing the community. Moreover, the improvement in the environmental quality once the programme started was positive feedback to their recycling efforts. However, the ease at which recycled items could have been deposited was found to be the most essential factor. Inasmuch as the quantity of retrievals was a measure of the continued interest in recycling, a reliable estimate of the achieved fraction of beverage waste retrieval rates could not have been obtained with the most recent national waste characterization information. The reasons for this are explained.

Dendritic cells overcome Cre/Lox induced gene deficiency by siphoning cytosolic material from surrounding cells.

In a previous report, keratinocytes were shown to share their gene expression profile with surrounding Langerhans cells (LCs), influencing LC biology. Here, we investigated whether transferred material could substitute for lost gene products in cells subjected to Cre/Lox conditional gene deletion. We found that in human Langerin-Cre mice, epidermal LCs and CD11b+CD103+ mesenteric DCs overcome gene deletion if the deleted gene was expressed by neighboring cells. The mechanism of material transfer differed from traditional antigen uptake routes, relying on calcium and PI3K, being susceptible to polyguanylic acid inhibition, and remaining unaffected by inflammation. Termed intracellular monitoring, this process was specific to DCs, occurring in all murine DC subsets tested and human monocyte-derived DCs. The transferred material was presented on MHC-I and MHC-II, suggesting a role in regulating immune responses.

Last Glacial Maximum pattern effects reduce climate sensitivity estimates.

Here, we show that the Last Glacial Maximum (LGM) provides a stronger constraint on equilibrium climate sensitivity (ECS), the global warming from increasing greenhouse gases, after accounting for temperature patterns. Feedbacks governing ECS depend on spatial patterns of surface temperature ("pattern effects"); hence, using the LGM to constrain future warming requires quantifying how temperature patterns produce different feedbacks during LGM cooling versus modern-day warming. Combining data assimilation reconstructions with atmospheric models, we show that the climate is more sensitive to LGM forcing because ice sheets amplify extratropical cooling where feedbacks are destabilizing. Accounting for LGM pattern effects yields a median modern-day ECS of 2.4°C, 66% range 1.7° to 3.5°C (1.4° to 5.0°C, 5 to 95%), from LGM evidence alone. Combining the LGM with other lines of evidence, the best estimate becomes 2.9°C, 66% range 2.4° to 3.5°C (2.1° to 4.1°C, 5 to 95%), substantially narrowing uncertainty compared to recent assessments.

Risk-based stratified primary care for common musculoskeletal pain presentations: qualitative findings from the STarT MSK cluster randomised controlled trial.

BACKGROUND: The STarT MSK cluster randomised controlled trial (RCT) investigated the clinical- and cost-effectiveness of risk-based stratified primary care versus usual care for patients with back, neck, shoulder, knee or multi-site pain. Trial quantitative results showed risk-based stratified care was not superior to usual care for patients' clinical outcomes, but the intervention led to some changes in GP clinical decision-making. This paper reports a linked qualitative study exploring how risk-based stratified care was perceived and used in the trial, from the perspectives of clinicians and patients. METHODS: Semi-structured interviews were conducted with 27 patients, and focus groups and interviews with 20 clinicians (GPs and physiotherapists) in the intervention arm of the trial. Data were analysed thematically and findings explored using Normalisation Process Theory (NPT) and the COM-B model. MAIN FINDINGS: Risk-based stratified care (subgrouping and matching treatments) was found to have 'coherence' (i.e. made sense) to several clinicians and patients, in that it was well-integrated in practice, and supported clinical decision-making. However, for some GPs stratified care was less 'meaningful', as the risk-stratification tool did not fit with usual ways of consulting and added to already time-pressured consultations. GPs reported giving more patients written information/advice due to easier access to electronic information leaflets through the trial template and were motivated to refer patients to physiotherapy as they believed the trial resulted in faster physiotherapy access (although this was not the case). Patients and clinicians reported that risk-based stratified care influenced conversations in the consultation, prompting greater attention to psychosocial factors, and facilitating negotiation of treatment options. Physiotherapists saw benefits in receiving information about patients' risk subgroup on referral forms. CONCLUSION: These findings provide context for interpreting some of the trial outcomes, particularly in relation to changes in clinical decision-making when risk-based stratified care was used. Findings also indicate potential reasons for lack of GP engagement with risk-based stratified care. Positive outcomes were identified that were not captured in the quantitative data, specifically that risk-based stratified care positively influenced some GP-patient conversations and facilitated negotiation of treatment options. TRIAL REGISTRATION: ISRCTN15366334 (26/04/2016).

Attitudes and perceptions of rheumatologists regarding consultation skills training for specialist trainees: a qualitative study.

Within rheumatology specialty training, direct observation and formal assessment of consultation skills rarely occur. This study explored the attitudes and perceptions of rheumatology specialist registrars (SpRs) and consultants regarding consultation skills training and potential barriers to its successful implementation in the context of specialist training. Semi-structured interviews with rheumatology consultants and focus groups with rheumatology SpRs were conducted in four UK deanery regions. All participants value consultation skills training and believe it requires observation of trainees consulting. The skills of consultant trainers in providing feedback on consulting skills are sometimes sub-optimal. Direct, real time observation of trainees is difficult and happens infrequently. Recording consultations is a potentially attractive alternative. Important issues regarding the successful implementation of videotaped consultations include time constraints, consistency in the assessment of consultation skills, and expertise in providing constructive feedback that is individualised and tailored to the trainee's learning needs.

Computer-Based Stratified Primary Care for Musculoskeletal Consultations Compared With Usual Care: Study Protocol for the STarT MSK Cluster Randomized Controlled Trial.

BACKGROUND: Musculoskeletal (MSK) pain is a major cause of pain and disability. We previously developed a prognostic tool (Start Back Tool) with demonstrated effectiveness in guiding primary care low back pain management by supporting decision making using matched treatments. A logical next step is to determine whether prognostic stratified care has benefits for a broader range of common MSK pain presentations. OBJECTIVE: This study seeks to determine, in patients with 1 of the 5 most common MSK presentations (back, neck, knee, shoulder, and multisite pain), whether stratified care involving the use of the Keele Start MSK Tool to allocate individuals into low-, medium-, and high-risk subgroups, and matching these subgroups to recommended matched clinical management options, is clinical and cost-effective compared with usual nonstratified primary care. METHODS: This is a pragmatic, two-arm parallel (stratified vs nonstratified care), cluster randomized controlled trial, with a health economic analysis and mixed methods process evaluation. The setting is UK primary care, involving 24 average-sized general practices randomized (stratified by practice size) in a 1:1 ratio (12 per arm) with blinding of trial statistician and outcome data collectors. Randomization units are general practices, and units of observation are adult MSK consulters without indicators of serious pathologies, urgent medical needs, or vulnerabilities. Potential participant records are tagged and individuals invited using a general practitioner (GP) point-of-consultation electronic medical record (EMR) template. The intervention is supported by an EMR template (computer-based) housing the Keele Start MSK Tool (to stratify into prognostic subgroups) and the recommended matched treatment options. The primary outcome using intention-to-treat analysis is pain intensity, measured monthly over 6 months. Secondary outcomes include physical function and quality of life, and an anonymized EMR audit to capture clinician decision making. The economic evaluation is focused on the estimation of incremental quality-adjusted life years and MSK pain-related health care costs. The process evaluation is exploring a range of potential factors influencing the intervention and understanding how it is perceived by patients and clinicians, with quantitative analyses focusing on a priori hypothesized intervention targets and qualitative approaches using focus groups and interviews. The target sample size is 1200 patients from 24 general practices, with >5000 MSK consultations available for anonymized medical record data comparisons. RESULTS: Trial recruitment commenced on May 18, 2018, and ended on July 15, 2019, after a 14-month recruitment period in 24 GP practices. Follow-up and interview data collection was completed in February 2020. CONCLUSIONS: This trial is the first attempt, as far as we know, at testing a prognostic stratified care approach for primary care patients with MSK pain. The results of this trial should be available by the summer of 2020. TRIAL REGISTRATION: ISRCTN Registry ISRCTN15366334; http://www.isrctn.com/ISRCTN15366334. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/17939.

Impact of recreation on recreational water quality of a small tropical stream.

A study was conducted to determine the possible influence of recreation on microbiological water quality of a tropical stream. Microbiological water quality was measured at several recreational sites along the stream and a separate experiment was conducted to look at the effect of sediment resuspension on microbiological water quality. Microbiological quality of the water in the stream was generally poor and varied widely with faecal coliform and Escherichia coli levels ranging from 1 to > 16,000 and 14 to 9615 organisms 100 ml(-1) respectively. Levels of faecal coliforms were higher in the wet (median = 700 organisms 100 ml(-1)) than the dry (median = 500 organisms 100 ml(-1)) season while the reverse was true for E. coli (median = 300 and 220 organisms 100 ml(-1) in the wet and dry seasons respectively). Recreational activity resulted in reduced water quality: sites with recreation had poorer water quality than those without; water quality was generally poorer when there were high numbers of recreational users. Wading resulted in a 4-fold increase in mean E. coli densities and a 3-fold increase in total suspended sediments in the overlying water suggesting that the increases were due to suspension of bacteria from the sediments. We conclude that water quality monitoring methodology for assessing recreational water quality should be amended to factor in the effects of wading since environmental strains of bacteria can be pathogenic and thus represent a human health threat.

Enhancement of intestinal absorption of 2-methyl cytidine prodrugs.

The purpose of this study was to investigate the in vivo absorption enhancement of a nucleoside (phosphoramidate prodrug of 2'-methyl-cytidine) anti-viral agent of proven efficacy by means of intestinal permeation enhancers. Natural nucleosides are hydrophilic molecules that do not rapidly penetrate cell membranes by diffusion and their absorption relies on specialized transporters. Therefore, the oral absorption of nucleoside prodrugs and the target organ concentration of the biologically active nucleotide can be limited due to poor permeation across the intestinal epithelium. In the present study, the specificity, concentration dependence, and effect of four classes of absorption promoters, i.e. fatty acids, steroidal detergents, mucoadhesive polymers, and secretory transport inhibitors, were evaluated in a rat in vivo model. Sodium caprate and alpha-tocopheryl-polyethyleneglycol-1000-succinate (TPGS) showed a significant effect in increasing liver concentration of nucleotide (5-fold). These results suggested that both excipients might be suited in a controlled release matrix for the synchronous release of the drug and absorption promoter directly to the site of absorption and highlights that the effect is strictly dependent on the absorption promoter dose. The feasibility of such a formulation approach in humans was evaluated with the aim of developing a solid dosage form for the peroral delivery of nucleosides and showed that these excipients do provide a potential valuable tool in pre-clinical efficacy studies to drive discovery programs forward.