Feasibility of delivering and evaluating stratified care integrated with telehealth (‘Rapid Stratified Telehealth’) for patients with low back pain: protocol for a feasibility and pilot randomised controlled trial

IntroductionLong waiting time is an important barrier to accessing recommended care for low back pain (LBP) in Australia’s public health system. This study describes the protocol for a randomised controlled trial (RCT) that aims to establish the feasibility of delivering and evaluating stratified care integrated with telehealth (‘Rapid Stratified Telehealth’), which aims to reduce waiting times for LBP.Methods and analysisWe will conduct a single-centre feasibility and pilot RCT with nested qualitative interviews. Sixty participants with LBP newly referred to a hospital outpatient clinic will be randomised to receive Rapid Stratified Telehealth or usual care. Rapid Stratified Telehealth involves matching the mode and type of care to participants’ risk of persistent disabling pain (using the Keele STarT MSK Tool) and presence of potential radiculopathy. ‘Low risk’ patients are matched to one session of advice over the telephone, ‘medium risk’ to telehealth physiotherapy plus App-based exercises, ‘high risk’ to telehealth physiotherapy, App-based exercises, and an online pain education programme, and ‘potential radiculopathy’ fast tracked to usual in-person care. Primary outcomes include the feasibility of delivering Rapid Stratified Telehealth (ie, acceptability assessed through interviews with clinicians and patients, intervention fidelity, appointment duration, App useability and online pain education programme usage) and evaluating Rapid Stratified Telehealth in a future trial (ie, recruitment rates, consent rates, lost to follow-up and missing data). Secondary outcomes include waiting times, number of appointments, intervention and healthcare costs, clinical outcomes (pain, function, quality of life, satisfaction), healthcare use and adverse events (AEs). Quantitative analyses will be descriptive and inform a future adequately-powered RCT. Interview data will be analysed using thematic analysis.Ethics and disseminationThis study has received approval from the Ethics Review Committee (RPAH Zone: X21-0221). Results will be published in peer-reviewed journals and presented at conferences.Trial registration numberACTRN12621001104842.

Management Approach Combining Prognostic Screening and Targeted Treatment for Patients with Low Back Pain Compared with Standard Physiotherapy: A Systematic Review & Meta-analysis

Introduction: Research evidence suggests that a stratified care management approach is better at improving clinical and economic outcomes for low back pain (LBP) patients compared with usual care in the short term. However, it is unclear if these health and economic benefits are sustainable in the longer term. The aim of this study was, therefore, to determine the effectiveness of stratified care compared with standard physiotherapy for LBP treatment. Methodology: A comprehensive search was undertaken of seven electronic databases (CINAHL, MEDLINE, Pedro, EMBASE, PsycINFO, Cochrane Register for Controlled Trials, and Web of Science with full text). Although no time limits were applied, studies were limited to English language publications and those involving human participants only. Study selection, data extraction, and appraisal of study were independently undertaken by both reviewers (CO and LE). Result: In total, 6842 patients (aged 18 years and above) were included in the eight trials reviewed; four were randomized controlled trials (RCTs) and four were non-RCTs. The pooled analysis of three studies (n = 2460) demonstrated a strong evidence in favor of stratified care over standard care at improving overall pain (Weighted Mean Difference (WMD) [random] 0.46 [95% CI 0.21, 0.71]; P < 0.0003), with overall effect (Z = 3.6) and (Roland-Morris disability questionnaire (RMDQ) scores (WMD [random] 0.71 [95% CI 0.05, 1.37]; P < 0.03), with overall effect (Z = 2.11) at three-, four-, and six-months’ follow-up periods. Conclusion: This current review demonstrated that a stratified care approach provides substantial clinical, economic, and health-related cost benefits in the medium- and high-risk subgroups compared with usual care. Further research is needed for longer-term benefits.

Population pharmacogenomics: an update on ethnogeographic differences and opportunities for precision public health

Both safety and efficacy of medical treatment can vary depending on the ethnogeographic background of the patient. One of the reasons underlying this variability is differences in pharmacogenetic polymorphisms in genes involved in drug disposition, as well as in drug targets. Knowledge and appreciation of these differences is thus essential to optimize population-stratified care. Here, we provide an extensive updated analysis of population pharmacogenomics in ten pharmacokinetic genes (CYP2D6, CYP2C19, DPYD, TPMT, NUDT15 and SLC22A1), drug targets (CFTR) and genes involved in drug hypersensitivity (HLA-A, HLA-B) or drug-induced acute hemolytic anemia (G6PD). Combined, polymorphisms in the analyzed genes affect the pharmacology, efficacy or safety of 141 different drugs and therapeutic regimens. The data reveal pronounced differences in the genetic landscape, complexity and variant frequencies between ethnogeographic groups. Reduced function alleles of CYP2D6, SLC22A1 and CFTR were most prevalent in individuals of European descent, whereas DPYD and TPMT deficiencies were most common in Sub-Saharan Africa. Oceanian populations showed the highest frequencies of CYP2C19 loss-of-function alleles while their inferred CYP2D6 activity was among the highest worldwide. Frequencies of HLA-B*15:02 and HLA-B*58:01 were highest across Asia, which has important implications for the risk of severe cutaneous adverse reactions upon treatment with carbamazepine and allopurinol. G6PD deficiencies were most frequent in Africa, the Middle East and Southeast Asia with pronounced differences in variant composition. These variability data provide an important resource to inform cost-effectiveness modeling and guide population-specific genotyping strategies with the goal of optimizing the implementation of precision public health.

Of Screening, Stratification, and Scores

Technological innovations including risk-stratification algorithms and large databases of longitudinal population health data and genetic data are allowing us to develop a deeper understanding how individual behaviors, characteristics, and genetics are related to health risk. The clinical implementation of risk-stratified screening programmes that utilise risk scores to allocate patients into tiers of health risk is foreseeable in the future. Legal and ethical challenges associated with risk-stratified cancer care must, however, be addressed. Obtaining access to the rich health data that are required to perform risk-stratification, ensuring equitable access to risk-stratified care, ensuring that algorithms that perform risk-scoring are representative of human genetic diversity, and determining the appropriate follow-up to be provided to stratification participants to alert them to changes in their risk score are among the principal ethical and legal challenges. Accounting for the great burden that regulatory requirements could impose on access to risk-scoring technologies is another critical consideration.

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.

Tryptophan and arginine metabolism is significantly altered at the time of admission in hospital for severe COVID-19 patients: findings from longitudinal targeted metabolomics analysis

The heterogeneity in severity and outcome of COVID-19 cases points out the urgent need for early molecular characterization of patients followed by risk-stratified care. The main objective of this study was to evaluate the fluctuations of serum metabolomic profiles of COVID-19 patients with severe illness during the different disease stages in a longitudinal manner. We demonstrate a distinct metabolomic signature in serum samples of 32 hospitalized patients at the acute phase compared to the recovery period, suggesting the tryptophan (tryptophan, kynurenine, and 3-hydroxy-DL-kynurenine) and arginine (citrulline and ornithine) metabolism as contributing pathways in the immune response to SARS-CoV-2 with a potential link to the clinical severity of the disease. In addition, we provide evidence for glutamine metabolism in M2 macrophages as a complementary process and contribution of phenylalanine and tyrosine in the molecular mechanisms underlying the severe course of the infection. In conclusion, our results provide several functional metabolic markers for disease progression and severe outcome with potential clinical application.

Testing Stratified Care for Musculoskeletal Pain in General Practice: Integrating Clinician Support and Intervention Design

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 from the initial stages of the programme. This paper details the steps in integrating the development of a clinician support package throughout the 6-year programme, to support GP engagement in delivering the STarT MSK intervention. Practical recommendations are made for future general practice interventions. Methods Clinician support was developed through an iterative, mixed methods approach. 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) and Behaviour Change Technique (BCT) taxonomy. Identified domains/BCTs 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 in enabling fidelity and, ultimately, a successful trial. Results highlighted that 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 also required to ensure ‘buy in’, and results indicated the importance of monitoring GP performance and providing regular feedback. 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.