'Maze' not pathway: focus group exploration of patients' and public experiences of the UK NHS elective total joint arthroplasty pathway

Objective: To explore patient and public perceptions of planned improvements to the National Health Service (NHS) total joint arthroplasty (TJA) pathway. / Design: Three qualitative focus groups undertaken March–May 2018, as part of a mixed-methods evaluation of Getting It Right First Time. Transcripts were subject to framework analysis to identify thematic content between October 2018 and October 2021. / Setting: Elective TJA surgery in the English NHS. / Participants: Two focus groups including patients who had undergone TJA in the previous 2 years (group 1: n=5; group 2: n=4) and the other individuals who had not but were aged 60+ (group 3: n=5). Participants were recruited via community groups and patient panels. / Results: Fourteen individuals took part in the focus groups; all were aged over 60; seven (50%) were female and nine (64%) had undergone TJA surgery. Participants’ perspectives were categorised into themes and mapped onto stages of the TJA pathway. Although perioperative care is often the focus of improvement efforts, participants argued that the patient journey begins before individuals present to primary care. Participants had concerns about other aspects of the pathway, such as obtaining a surgical referral, with prereferral interventions aimed at potentially avoiding the need for surgery (ie, physiotherapy) being perceived as a mechanism to restrict access to secondary care. Patient experience was also conceptualised as a ‘maze’, rather than the logical, sequential process set out in clinical guidelines; exacerbated by a lack of information, knowledge and power imbalances. / Conclusion: The linear conceptualisation of the TJA pathway is at odds with patient experience. Improvement programmes focused on perioperative care fail to consider patient concerns and priorities. Patients should be directly involved in improvement programmes, to ensure that patient experience is optimised, as well as informing related processes and important outcomes of care

'Maze' not pathway: focus group exploration of patients' and public experiences of the UK NHS elective total joint arthroplasty pathway

OBJECTIVE: To explore patient and public perceptions of planned improvements to the National Health Service (NHS) total joint arthroplasty (TJA) pathway. DESIGN: Three qualitative focus groups undertaken March-May 2018, as part of a mixed-methods evaluation of Getting It Right First Time. Transcripts were subject to framework analysis to identify thematic content between October 2018 and October 2021. SETTING: Elective TJA surgery in the English NHS. PARTICIPANTS: Two focus groups including patients who had undergone TJA in the previous 2 years (group 1: n=5; group 2: n=4) and the other individuals who had not but were aged 60+ (group 3: n=5). Participants were recruited via community groups and patient panels. RESULTS: Fourteen individuals took part in the focus groups; all were aged over 60; seven (50%) were female and nine (64%) had undergone TJA surgery. Participants' perspectives were categorised into themes and mapped onto stages of the TJA pathway. Although perioperative care is often the focus of improvement efforts, participants argued that the patient journey begins before individuals present to primary care. Participants had concerns about other aspects of the pathway, such as obtaining a surgical referral, with prereferral interventions aimed at potentially avoiding the need for surgery (ie, physiotherapy) being perceived as a mechanism to restrict access to secondary care. Patient experience was also conceptualised as a 'maze', rather than the logical, sequential process set out in clinical guidelines; exacerbated by a lack of information, knowledge and power imbalances. CONCLUSION: The linear conceptualisation of the TJA pathway is at odds with patient experience. Improvement programmes focused on perioperative care fail to consider patient concerns and priorities. Patients should be directly involved in improvement programmes, to ensure that patient experience is optimised, as well as informing related processes and important outcomes of care

Higher plasma CXCL12 levels predict incident myocardial infarction and death in chronic kidney disease: findings from the Chronic Renal Insufficiency Cohort study

Aims Genome-wide association studies revealed an association between a locus at 10q11, downstream from CXCL12, and myocardial infarction (MI). However, the relationship among plasma CXCL12, cardiovascular disease (CVD) risk factors, incident MI, and death is unknown. Methods and Results We analysed study-entry plasma CXCL12 levels in 3687 participants of the Chronic Renal Insufficiency Cohort (CRIC) Study, a prospective study of cardiovascular and kidney outcomes in chronic kidney disease (CKD) patients. Mean follow-up was 6 years for incident MI or death. Plasma CXCL12 levels were positively associated with several cardiovascular risk factors (age, hypertension, diabetes, hypercholesterolaemia), lower estimated glomerular filtration rate (eGFR), and higher inflammatory cytokine levels (P \u3c 0.05). In fully adjusted models, higher study-entry CXCL12 was associated with increased odds of prevalent CVD (OR 1.23; 95% confidence interval 1.14, 1.33, P \u3c 0.001) for one standard deviation (SD) increase in CXCL12. Similarly, one SD higher CXCL12 increased the hazard of incident MI (1.26; 1.09,1.45, P \u3c 0.001), death (1.20; 1.09,1.33, P \u3c 0.001), and combined MI/death (1.23; 1.13–1.34, P \u3c 0.001) adjusting for demographic factors, known CVD risk factors, and inflammatory markers and remained significant for MI (1.19; 1.03,1.39, P = 0.01) and the combined MI/death (1.13; 1.03,1.24, P = 0.01) after further controlling for eGFR and urinary albumin:creatinine ratio. Conclusions In CKD, higher plasma CXCL12 was associated with CVD risk factors and prevalent CVD as well as the hazard of incident MI and death. Further studies are required to establish if plasma CXCL12 reflect causal actions at the vessel wall and is a tool for genomic and therapeutic trials

Signals of R-parity violating supersymmetry in neutrino scattering at muon storage rings

Neutrino oscillation signals at muon storage rings can be faked by supersymmetric (SUSY) interactions in an R-parity violating scenario. We investigate the $\tau$-appearance signals for both long-baseline and near-site experiments, and conclude that the latter is of great use in distinguishing between oscillation and SUSY effects. On the other hand, SUSY can cause a manifold increase in the event rate for wrong-sign muons at a long-baseline setting, thereby providing us with signatures of new physics.Comment: 7 pages LaTeX, 4 ps figures, accepted for publication in Phys. Rev.

Prehospital video triage of potential stroke patients in North Central London and East Kent: rapid mixed-methods service evaluation

Background In response to COVID-19, alongside other service changes, North Central London and East Kent implemented prehospital video triage: this involved stroke and ambulance clinicians communicating over FaceTime (Apple Inc., Cupertino, CA, USA) to assess suspected stroke patients while still on scene. Objective To evaluate the implementation, experience and impact of prehospital video triage in North Central London and East Kent. Design A rapid mixed-methods service evaluation (July 2020 to September 2021) using the following methods. (1) Evidence reviews: scoping review (15 reviews included) and rapid systematic review (47 papers included) on prehospital video triage for stroke, covering usability (audio-visual and signal quality); acceptability (whether or not clinicians want to use it); impact (on outcomes, safety, experience and cost-effectiveness); and factors influencing implementation. (2) Clinician views of prehospital video triage in North Central London and East Kent, covering usability, acceptability, patient safety and implementation: qualitative analysis of interviews with ambulance and stroke clinicians (n = 27), observations (n = 12) and documents (n = 23); a survey of ambulance clinicians (n = 233). (3) Impact on safety and quality: analysis of local ambulance conveyance times (n = 1400; April to September 2020). Analysis of national stroke audit data on ambulance conveyance and stroke unit delivery of clinical interventions in North Central London, East Kent and the rest of England (n = 137,650; July 2018 to December 2020). Results (1) Evidence: limited but growing, and sparse in UK settings. Prehospital video triage can be usable and acceptable, requiring clear network connection and audio-visual signal, clinician training and communication. Key knowledge gaps included impact on patient conveyance, patient outcomes and cost-effectiveness. (2) Clinician views. Usability – relied on stable Wi-Fi and audio-visual signals, and back-up processes for when signals failed. Clinicians described training as important for confidence in using prehospital video triage services, noting potential for ‘refresher’ courses and joint training events. Ambulance clinicians preferred more active training, as used in North Central London. Acceptability – most clinicians felt that prehospital video triage improved on previous processes and wanted it to continue or expand. Ambulance clinicians reported increased confidence in decisions. Stroke clinicians found doing assessments alongside their standard duties a source of pressure. Safety – clinical leaders monitored and managed potential patient safety issues; clinicians felt strongly that services were safe. Implementation – several factors enabled prehospital video triage at a system level (e.g. COVID-19) and more locally (e.g. facilitative governance, receptive clinicians). Clinical leaders reached across and beyond their organisations to engage clinicians, senior managers and the wider system. (3) Impact on safety and quality: we found no evidence of increased times from symptom onset to arrival at services or of stroke clinical interventions reducing in studied areas. We found several significant improvements relative to the rest of England (possibly resulting from other service changes). Limitations We could not interview patients and carers. Ambulance data had no historic or regional comparators. Stroke audit data were not at patient level. Several safety issues were not collected routinely. Our survey used a convenience sample. Conclusions Prehospital video triage was perceived as usable, acceptable and safe in both areas. Future research Qualitative research with patients, carers and other stakeholders and quantitative analysis of patient-level data on care delivery, outcomes and cost-effectiveness, using national controls. Focus on sustainability and roll-out of services. Study registration This study is registered as PROSPERO CRD42021254209. Funding This project was funded by the National Institute for Health and Care Research (NIHR) Health and Social Care Delivery Research programme and will be published in full in Health and Social Care Delivery Research; Vol. 10, No. 26. See the NIHR Journals Library website for further project information

Mixed methods evaluation of the Getting it Right First Time programme in elective orthopaedic surgery in England: an analysis from the National Joint Registry and Hospital Episode Statistics

OBJECTIVE: To evaluate the impact of the 'Getting it Right First Time' (GIRFT) national improvement programme in orthopaedics, which started in 2012. DESIGN: Mixed-methods study comprising statistical analysis of linked national datasets (National Joint Registry; Hospital Episode Statistics; Patient-Reported Outcomes); economic analysis and qualitative case studies in six National Health Service (NHS) Trusts. SETTING: NHS elective orthopaedic surgery in England. PARTICIPANTS: 736 088 patients who underwent primary hip or knee replacement at 126 NHS Trusts between 1 April 2009 and 31 March 2018, plus 50 NHS staff. INTERVENTION: Improvement bundle including 'deep dive' visits by senior clinician to NHS Trusts, informed by bespoke set of routine performance data, to discuss how improvements could be made locally. MAIN OUTCOME MEASURES: Number of procedures conducted by low volume surgeons; use of uncemented hip implants in patients >65; arthroscopy in year prior to knee replacement; hospital length of stay; emergency readmissions within 30 days; revision surgery within 1 year; health-related quality of life and functional status. RESULTS: National trends demonstrated substantial improvements beginning prior to GIRFT. Between 2012 and 2018, there were reductions in procedures by low volume surgeons (ORs (95% CI) hips 0.58 (0.53 to 0.63), knees 0.77 (0.72 to 0.83)); uncemented hip prostheses in >65 s (OR 0.56 (0.51 to 0.61)); knee arthroscopies before surgery (OR 0.48 (0.41 to 0.56)) and mean length of stay (hips -0.90 (-1.00 to -0.81), knees -0.74 days (-0.82 to -0.66)). The additional impact of visits was mixed and comprised an overall economic saving of £431 848 between 2012 and 2018, but this was offset by the costs of the visits. Staff reported that GIRFT's influence ranged from procurement changes to improved regional collaboration. CONCLUSION: Nationally, we found substantial improvements in care, but the specific contribution of GIRFT cannot be reliably estimated due to other concurrent initiatives. Our approach enabled additional analysis of the discrete impact of GIRFT visits

Eimeria species occurrence varies between geographic regions and poultry production systems and may influence parasite genetic diversity

Coccidiosis is one of the biggest challenges faced by the global poultry industry. Recent studies have highlighted the ubiquitous distribution of all Eimeria species which can cause this disease in chickens, but intriguingly revealed a regional divide in genetic diversity and population structure for at least one species, Eimeria tenella. The drivers associated with such distinct geographic variation are unclear, but may impact on the occurrence and extent of resistance to anticoccidial drugs and future subunit vaccines. India is one of the largest poultry producers in the world and includes a transition between E. tenella populations defined by high and low genetic diversity. The aim of this study was to identify risk factors associated with the prevalence of Eimeria species defined by high and low pathogenicity in northern and southern states of India, and seek to understand factors which vary between the regions as possible drivers for differential genetic variation. Faecal samples and data relating to farm characteristics and management were collected from 107 farms from northern India and 133 farms from southern India. Faecal samples were analysed using microscopy and PCR to identify Eimeria occurrence. Multiple correspondence analysis was applied to transform correlated putative risk factors into a smaller number of synthetic uncorrelated factors. Hierarchical cluster analysis was used to identify poultry farm typologies, revealing three distinct clusters in the studied regions. The association between clusters and presence of Eimeria species was assessed by logistic regression. The study found that large-scale broiler farms in the north were at greatest risk of harbouring any Eimeria species and a larger proportion of such farms were positive for E. necatrix, the most pathogenic species. Comparison revealed a more even distribution for E. tenella across production systems in south India, but with a lower overall occurrence. Such a polarised region- and system-specific distribution may contribute to the different levels of genetic diversity observed previously in India and may influence parasite population structure across much of Asia and Africa. The findings of the study can be used to prioritise target farms to launch and optimise appropriate anticoccidial strategies for long-term control

High PD-1/PD-L1 Checkpoint Interaction Infers Tumor Selection and Therapeutic Sensitivity to Anti-PD-1/PD-L1 Treatment

Many cancers are termed immunoevasive due to expression of immunomodulatory ligands. Programmed death ligand-1 (PD-L1) and cluster of differentiation 80/86 (CD80/86) interact with their receptors, programmed death receptor-1 (PD-1) and cytotoxic T-lymphocyte antigen-4 (CTLA-4), respectively, on tumor-infiltrating leukocytes eliciting immunosuppression. Immunotherapies aimed at blocking these interactions are revolutionizing cancer treatments, albeit in an inadequately described patient subset. To address the issue of patient stratification for immune checkpoint intervention, we quantitatively imaged PD-1/PD-L1 interactions in tumor samples from patients, employing an assay that readily detects these intercellular protein-protein interactions in the less than or equal to 10 nm range. These analyses across multiple patient cohorts demonstrated the intercancer, interpatient, and intratumoral heterogeneity of interacting immune checkpoints. The PD-1/PD-L1 interaction was not correlated with clinical PD-L1 expression scores in malignant melanoma. Crucially, among anti-PD-1-treated patients with metastatic non-small cell lung cancer, those with lower PD-1/PD-L1 interaction had significantly worsened survival. It is surmised that within tumors selecting for an elevated level of PD-1/PD-L1 interaction, there is a greater dependence on this pathway for immune evasion and hence, they exhibit more impressive patient response to intervention. SIGNIFICANCE: Quantitation of immune checkpoint interaction by direct imaging demonstrates that immunotherapy-treated patients with metastatic NSCLC with a low extent of PD-1/PD-L1 interaction show significantly worse outcome.This work was supported, in part, by Department of Education, Basque Government- IT1270-19, Elkartek grant (BG18), and the Spanish Ministry grant (MINECO) PROJECTS of EXCELLENCE (BFU2015-65625-P). P.J. Parker was supported by a core grant to the Francis Crick Institute, from Cancer Research UK (FC001130), the UK Medical Research Council (FC001130), and the Wellcome Trust (FC001130).Peer reviewe

A novel algorithmic approach to generate consensus treatment guidelines in adult Acute Myeloid Leukaemia

Induction therapy for acute myeloid leukaemia (AML) has changed with the approval of a number of new agents. Clinical guidelines can struggle to keep pace with an evolving treatment and evidence landscape and therefore identifying the most appropriate front-line treatment is challenging for clinicians. Here, we combined drug eligibility criteria and genetic risk stratification into a digital format, allowing the full range of possible treatment eligibility scenarios to be defined. Using exemplar cases representing each of the 22 identified scenarios, we sought to generate consensus on treatment choice from a panel of nine aUK AML experts. We then analysed >2500 real-world cases using the same algorithm, confirming the existence of 21/22 of these scenarios and demonstrating that our novel approach could generate a consensus AML induction treatment in 98% of cases. Our approach, driven by the use of decision trees, is an efficient way to develop consensus guidance rapidly and could be applied to other disease areas. It has the potential to be updated frequently to capture changes in eligibility criteria, novel therapies and emerging trial data. An interactive digital version of the consensus guideline is available

Oxidized LDL Receptor 1 (OLR1) as a Possible Link between Obesity, Dyslipidemia and Cancer

Recent studies have linked expression of lectin-like ox-LDL receptor 1 (OLR1) to tumorigenesis. We analyzed microarray data from Olr1 knockout (KO) and wild type (WT) mice for genes involved in cellular transformation and evaluated effects of OLR1 over-expression in normal mammary epithelial cells (MCF10A) and breast cancer cells (HCC1143) in terms of gene expression, migration, adhesion and transendothelial migration. Twenty-six out of 238 genes were inhibited in tissues of OLR1 KO mice; the vast majority of OLR1 sensitive genes contained NF-κB binding sites in their promoters. Further studies revealed broad inhibition of NF-kB target genes outside of the transformation-associated gene pool, with enrichment themes of defense response, immune response, apoptosis, proliferation, and wound healing. Transcriptome of Olr1 KO mice also revealed inhibition of de novo lipogenesis, rate-limiting enzymes fatty acid synthase (Fasn), stearoyl-CoA desaturase (Scd1) and ELOVL family member 6 (Elovl6), as well as lipolytic phospholipase A2 group IVB (Pla2g4b). In studies comparing MCF10A and HCC1143, the latter displayed 60% higher OLR1 expression. Forced over-expression of OLR1 resulted in upregulation of NF-κB (p65) and its target pro-oncogenes involved in inhibition of apoptosis (BCL2, BCL2A1, TNFAIP3) and regulation of cell cycle (CCND2) in both cell lines. Basal expression of FASN, SCD1 and PLA2G4B, as well as lipogenesis transcription factors PPARA, SREBF2 and CREM, was higher in HCC1143 cells. Over-expression of OLR1 in HCC1143 cells also enhanced cell migration, without affecting their adherence to TNFα-activated endothelium or transendothelial migration. On the other hand, OLR1 neutralizing antibody inhibited both adhesion and transmigration of untreated HCC1143 cells. We conclude that OLR1 may act as an oncogene by activation of NF-kB target genes responsible for proliferation, migration and inhibition of apoptosis and de novo lipogenesis genes