Impact on stable chest pain pathways of CT fractional flow reserve.

OBJECTIVES: To evaluate the impact of introducing CT fractional flow reserve (FFRCT) on stable chest pain pathways, concordance with National Institute for Health and Care Excellence (NICE) chest pain guidelines, resource usage and revascularisation of patients from a tertiary UK cardiac centre rapid access chest pain clinic (RACPC). METHODS: Single-centre before and after study comparing data from electronic records and Strategic Tracing Service of all RACPC patients attending between 1 July 2017 and 31 December 2017, and 1 August 2018 and 31 January 2019. RESULTS: Two hundred and sixty-eight and 287 patients (overall mean age 62 years, range 26-89 years, 48.3% male), were eligible for first-line CT coronary angiography (CTCA) pre-FFRCT and post-FFRCT, respectively. First-line CTCA use per NICE Guideline CG95 increased (50.6% pre-FFRCT vs 75.7% post-FFRCT, p<0.001). More patients reached pathway endpoint (revascularisation or assumed medical management) after one investigation (74.9% pre-FFRCT vs 84.9% post-FFRCT, p=0.005). There were fewer stress (22.8% pre-FFRCT vs 7.7% post-FFRCT, p<0.001) and rest (10.4% pre-FFRCT vs 4.2% post-FFRCT, p=0.007) myocardial perfusion scans and diagnostic-only angiograms (25.5% vs 13.7%, p<0.001). Despite fewer invasive procedures (29.3% pre-FFRCT vs 17.6% post-FFRCT, p=0.002), revascularisation rates remained similar (10.4% pre-FFRCT vs 8.8% post-FFRCT, p=0.561). Avoiding invasive investigations reduced inpatient admissions (39.0% pre-FFRCT vs 24.3% post-FFRCT, p<0.001). Time to revascularisation was unchanged (153.5 days pre-FFRCT vs 142.0 post-FFRCT, p=0.925). Unplanned hospital attendances, emergency admissions and adverse events were similar. CONCLUSIONS: FFRCT adoption was associated with greater compliance with NICE guidelines, reduced invasive diagnostic angiography, planned admissions and needing more than one test to reach a pathway endpoint.

Patent foramen ovale closure: A prospective UK registry linked to hospital episode statistics.

AIMS: PFO closure is a percutaneous intervention, which aims to reduce risk of recurrent stroke by preventing paradoxical embolism. The objective of this study was to measure procedural safety and longer-term effectiveness of PFO closure in a UK setting. METHODS AND RESULTS: Prospective registry data from patients with cryptogenic stroke eligible for PFO closure were collected for up to 2 years and linked to routine data sources for additional follow-up. Outcomes of interest included procedural success rate, health related quality of life, and longer-term death and neurological event rates. A total of 973 PFO closure procedures in 971 patients were included in analysis. Successful device implantation was achieved in 99.4 [95% CI 98.6 to 99.8]% of procedures, with one in-hospital death. During median follow-up of 758 (Q1:Q3 527:968) days, 33 patients experienced a subsequent neurological event, 76% of which were ischaemic in origin. Neurological event rate was 2.7 [95%CI 1.6 to 3.9]% at 1-year (n = 751) and 4.1 [95% CI 2.6 to 5.5]% at 2-years (n = 463) using Kaplan-Meier analysis. Improvements in patient quality of life (utility and visual analogue scale) were observed at 6-weeks and 6-months follow-up. CONCLUSION: Our observational study demonstrates that PFO closure for prevention of recurrent stroke is a relatively safe procedure but in routine clinical practice is associated with a slightly higher risk of recurrent neurological events than in randomised trials. We hypothesize that our study enrolled unselected patients with higher baseline risk, who were excluded from randomised trials, but who may benefit from a similar relative reduction in risk from the intervention.

Left atrial appendage occlusion in the UK: prospective registry and data linkage to Hospital Episode Statistics.

AIMS: Non-valvular atrial fibrillation (AF) greatly increases the risk of ischaemic stroke. For people with contraindications to oral anticoagulation, left atrial appendage occlusion (LAAO) provides a non-pharmacological management alternative. The aim of this study was to measure the procedural safety and longer-term effectiveness of LAAO for AF in a UK setting. METHODS AND RESULTS: This was a prospective, single-armed registry of patients with AF for whom anticoagulation was unsuitable. Registry data were collected between October 2014 and April 2018 and linked to routine data sources for follow-up. Data from 583 LAAO procedures were entered into the registry, of which 537 (from 525 patients) were eligible for inclusion (median CHA2DS2-VASc score 4). A closure device was successfully implanted in 93.4% of cases, with a procedural success rate (device implanted without major complication) of 88.9%. Five patients (1.0%) died in hospital. During follow-up [median 729 (Q1:Q3, 523:913) days] 45 patients experienced neurological events; 33 of which were ischaemic. The ischaemic neurological event rate was 3.3 (1.6-5.0)% at 1 year (n = 387) and 7.0 (4.3-9.6)% at 2 years (n = 196). There were significant improvements in overall patient health (via Visual Analogue Scale) measured at 6 weeks and 6 months, but no significant improvements observed in patient utility over time. CONCLUSION: The findings of our study suggest that LAAO is not without procedural risk, but that this risk may be justified in high-risk patients with AF who cannot take an anticoagulant. Moreover, the data do not provide support for more widespread use of LAAO as the complication rate was relatively high and would be difficult to justify in many patients with AF who tolerate anticoagulation.

Utility of Routine Laboratory Biomarkers to Detect COVID-19: A Systematic Review and Meta-Analysis.

No routine laboratory biomarkers perform well enough in diagnosing COVID-19 in isolation for them to be used as a standalone diagnostic test or to help clinicians prioritize patients for treatment. Instead, other diagnostic tests are needed. The aim of this work was to statistically summarise routine laboratory biomarker measurements in COVID-19-positive and -negative patients to inform future work. A systematic literature review and meta-analysis were performed. The search included names of commonly used, routine laboratory tests in the UK NHS, and focused on research papers reporting laboratory results of patients diagnosed with COVID-19. A random effects meta-analysis of the standardized mean difference between COVID-19-positive and -negative groups was conducted for each biomarker. When comparing reported laboratory biomarker results, we identified decreased white blood cell, neutrophil, lymphocyte, eosinophil, and platelet counts; while lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase were elevated in COVID-19-positive compared to COVID-19-negative patients. Differences were identified across a number of routine laboratory biomarkers between COVID-19-positive and -negative patients. Further research is required to identify whether routine laboratory biomarkers can be used in the development of a clinical scoring system to aid with triage of patients.

Safety, effectiveness and costs of percutaneous mitral valve repair: A real-world prospective study.

AIMS: Percutaneous mitral valve leaflet repair is a treatment option for some people with severe mitral valve regurgitation for whom conventional mitral valve surgery is clinically inappropriate. This study aimed to determine the safety, efficacy, and costs of percutaneous mitral valve leaflet repair, using the MitraClip device in a UK setting. METHODS AND RESULTS: This was a prospective, single-armed registry with a follow-up of 2 years that reported a range of procedural, clinical and patient-orientated outcomes. Registry data were linked to routine data sources to allow for more comprehensive follow up concerning mortality and healthcare resource use. The registry received data for 199 mainly elective patients with mixed mitral regurgitation aetiology. A MitraClip device was implanted in 187 patients (94%), with a procedural success rate of 86%, with 8% of patients having a serious in-hospital adverse event (including 5% mortality). Percutaneous mitral valve leaflet repair reduced mitral regurgitation from 100% MR grade ≥ 3+ to 7% at discharge. There were corresponding improvements in New York Heart Association functional class, reducing from 92% (class ≥ 3) at baseline to 18% at 6 weeks. There were significant improvements in generic and disease specific quality of life indicators up to 2 years. The all-cause mortality rate was estimated to be 12.7% (95% CI 7.5 to 17.7%) at 1 year. Percutaneous mitral valve leaflet repair was associated with reduced hospital readmissions and potential cost-savings in post-procedural care. CONCLUSION: This study shows that percutaneous mitral valve leaflet repair using MitraClip is a relatively safe and effective treatment in patients unable to tolerate surgery and has the potential to reduce ongoing healthcare costs in the UK.

Comparison of identifiable and non-identifiable data linkage: health technology assessment of MitraClip using registry, administrative and mortality datasets.

OBJECTIVES: The UK MitraClip registry was commissioned by National Health Service (NHS) England to assess real-world outcomes from percutaneous mitral valve repair for mitral regurgitation using a new technology, MitraClip. This study aimed to determine longitudinal patient outcomes by linking to routine datasets: Hospital Episode Statistics (HES) Admitted Patient Care (APC) and Office of National Statistics. METHODS: Two methods of linkage were compared, using identifiable (NHS number, date of birth, postcode, gender) and non-identifiable data (hospital trust, age in years, admission, discharge and operation dates, operation and diagnosis codes). Outcome measures included: matching success, patient demographics, all-cause mortality and subsequent cardiac intervention. RESULTS: A total of 197 registry patients were eligible for matching with routine administrative data. Using identifiable linkage, a total of 187 patients (94.9%) were matched with the HES APC dataset. However, 21 matched individuals (11.2%) had inconsistencies across the datasets (eg, different gender) and were subsequently removed, leaving 166 (84.3%) for analysis. Using non-identifiable data linkage, a total of 170 patients (86.3%) were uniquely matched with the HES APC dataset.Baseline patient characteristics were not significantly different between the two methods of data linkage. The total number of deaths (all causes) identified from identifiable and non-identifiable linkage methods was 37 and 40, respectively, and the difference in subsequent cardiac interventions identified between the two methods was negligible. CONCLUSIONS: Patients from a bespoke clinical procedural registry were matched to routine administrative data using identifiable and non-identifiable methods with equivalent matching success rates, similar baseline characteristics and similar 2-year outcomes.

Unmet clinical needs for COVID-19 tests in UK health and social care settings.

There is an urgent requirement to identify which clinical settings are in most need of COVID-19 tests and the priority role(s) for tests in these settings to accelerate the development of tests fit for purpose in health and social care across the UK. This study sought to identify and prioritize unmet clinical needs for COVID-19 tests across different settings within the UK health and social care sector via an online survey of health and social care professionals and policymakers. Four hundred and forty-seven responses were received between 22nd May and 15th June 2020. Hospitals and care homes were recognized as the settings with the greatest unmet clinical need for COVID-19 diagnostics, despite reporting more access to laboratory molecular testing than other settings. Hospital staff identified a need for diagnostic tests for symptomatic workers and patients. In contrast, care home staff expressed an urgency for screening at the front door to protect high-risk residents and limit transmission. The length of time to test result was considered a widespread problem with current testing across all settings. Rapid tests for staff were regarded as an area of need across general practice and dental settings alongside tests to limit antibiotics use.

How to Ease the Pain of Taking a Diagnostic Point of Care Test to the Market: A Framework for Evidence Development.

Bringing a diagnostic point of care test (POCT) to a healthcare market can be a painful experience as it requires the manufacturer to meet considerable technical, financial, managerial, and regulatory challenges. In this opinion article we propose a framework for developing the evidence needed to support product development, marketing, and adoption. We discuss each step in the evidence development pathway from the invention phase to the implementation of a new POCT in the healthcare system. We highlight the importance of articulating the value propositions and documenting the care pathway. We provide guidance on how to conduct care pathway analysis as little has been published on this. We summarize the clinical, economic and qualitative studies to be considered for developing evidence, and provide useful links to relevant software, on-line applications, websites, and give practical advice. We also provide advice on patient and public involvement and engagement (PPIE), and on product management. Our aim is to help device manufacturers to understand the concepts and terminology used in evaluation of in vitro diagnostics (IVDs) so that they can communicate effectively with evaluation methodologists, statisticians, and health economists. Manufacturers of medical tests and devices can use the proposed framework to plan their evidence development strategy in alignment with device development, applications for regulatory approval, and publication.

Novel optical assessments of tissue composition and viability using fluorescence spectroscopy and tissue oxygenation spectrophotometry in patients with systemic sclerosis: a pilot study.

OBJECTIVE: Patients with systemic sclerosis (SSc) experience significant morbidity and mortality, therefore, the development of tests to aid its early diagnosis are very important. The aim of this pilot study was to assess the diagnostic value of novel optical non-invasive skin fluorescence spectroscopy (FS) and tissue oxygen saturation (TOS) viability measurements in patients with established SSc. APPROACH: Two groups were studied, comprising 14 SSc patients and nine healthy controls (93% and 73% females, respectively). FS and TOS measurements were collected from three body sites: the forearm, chest, and calf. Fluorescence intensities at wavelengths attributed to collagen, elastin, and L-tryptophan were computed, with adjustment for melanin, and a normalised combined fluorescence score (NCFS) was determined. MAIN RESULTS: The NCFS was significantly higher (p < 0.001) and the combined TOS significantly lower (p < 0.001) in the SSc group. TOS measurements alone showed good classification accuracy (95.7%) at separating SSc from healthy control participants, with some clustering of values close to the 50% oxygenation level in both groups. When the composition and viability measures were combined and modelled using binary logistic regression, excellent results for the sample were obtained following leave one out cross validation (100%). SIGNIFICANCE: The results of this pilot study demonstrate the potential diagnostic utility of FS and TOS assessments in SSc patients and further work is now needed to validate these techniques prospectively in a larger group of SSc patients across the spectrum of the disease, and also patients with other types of vasculopathy and conditions that can cause skin fibrosis.

Quantification of differences between nailfold capillaroscopy images with a scleroderma pattern and normal pattern using measures of geometric and algorithmic complexity.

This study aimed to quantify and investigate differences in the geometric and algorithmic complexity of the microvasculature in nailfold capillaroscopy (NFC) images displaying a scleroderma pattern and those displaying a 'normal' pattern. 11 NFC images were qualitatively classified by a capillary specialist as indicative of 'clear microangiopathy' (CM), i.e. a scleroderma pattern, and 11 as 'not clear microangiopathy' (NCM), i.e. a 'normal' pattern. Pre-processing was performed, and fractal dimension (FD) and Kolmogorov complexity (KC) were calculated following image binarisation. FD and KC were compared between groups, and a k-means cluster analysis (n = 2) on all images was performed, without prior knowledge of the group assigned to them (i.e. CM or NCM), using FD and KC as inputs. CM images had significantly reduced FD and KC compared to NCM images, and the cluster analysis displayed promising results that the quantitative classification of images into CM and NCM groups is possible using the mathematical measures of FD and KC. The analysis techniques used show promise for quantitative microvascular investigation in patients with systemic sclerosis.

Gait analysis of fixed bearing and mobile bearing total knee prostheses during walking: do mobile bearings offer functional advantages?

BACKGROUND: Limited previous findings have detailed biomechanical advantages following implantation with mobile bearing (MB) prostheses after total knee replacement (TKR) surgery during walking. The aim of this study was to compare three dimensional spatiotemporal, kinematic, and kinetic parameters during walking to examine whether MBs offer functional advantages over fixed bearing (FB) designs. METHODS: Sixteen patients undergoing primary unilateral TKR surgery were randomised to receive either a FB (n=8) or MB (n=8) total knee prosthesis. Eight age and gender matched controls underwent the same protocol on one occasion. A 12 camera Vicon system integrated with four force plates was used. Patients were tested pre-surgery and nine months post-surgery. RESULTS: No significant differences between FB and MB groups were found at any time point in the spatiotemporal parameters. The MB group was found to have a significantly reduced frontal plane knee range of motion (ROM) at pre-surgery than the FB group (FB=14.92±4.02°; MB=8.87±4.82°), with the difference not observed post-surgery. No further significant kinematic or kinetic differences were observed between FB and MB groups. Fixed bearing and MB groups both displayed spatiotemporal, kinematic, and kinetic differences when compared to controls. Fixed bearing and MB groups differed from controls in six and five parameters at nine months post-surgery, respectively. CONCLUSIONS: No functional advantages were found in knees implanted with MB prostheses during walking, with both groups indicative of similar differences when compared to normal knee biomechanics following prosthesis implantation. LEVEL OF EVIDENCE: Level II.