Editor's Choice - Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL) Prospective Cohort Study and the Generalisability of the BASIL-2 Randomised Controlled Trial

OBJECTIVE: The Bypass versus Angioplasty in Severe Ischaemia of the Leg-2 (BASIL-2) randomised controlled trial has shown that, for patients with chronic limb threatening ischaemia (CLTI) who require an infrapopliteal (IP) revascularisation a vein bypass (VB) first revascularisation strategy led to a 35% increased risk of major amputation or death when compared with a best endovascular treatment (BET) first revascularisation strategy. The study aims are to place the BASIL-2 trial within the context of the CLTI patient population as a whole and to investigate the generalisability of the BASIL-2 outcome data.METHODS: This was an observational, single centre prospective cohort study. Between 24 June 2014 and 31 July 2018, the BASIL Prospective Cohort Study (PCS) was performed which used BASIL-2 trial case record forms to document the characteristics, initial and subsequent management, and outcomes of 471 consecutive CLTI patients admitted to an academic vascular centre. Ethical approval was obtained, and all patients provided fully informed written consent. Follow up data were censored on 14 December 2022.RESULTS: Of the 238 patients who required an infrainguinal revascularisation, 75 (32%) had either IP bypass (39 patients) or IP BET (36 patients) outside BASIL-2. Seventeen patients were initially randomised to BASIL-2. A further three patients who did not have an IP revascularisation as their initial management were later randomised in BASIL-2. Therefore, 95/471 (20%) of patients had IP revascularisation (16% outside, 4% inside BASIL-2). Differences in amputation free survival, overall survival, and limb salvage between IP bypass and IP BET performed outside BASIL-2 were not subject to hypothesis testing due to the small sample size. Reasons for non-randomisation into the trial were numerous, but often due to anatomical and technical considerations.CONCLUSION: CLTI patients who required an IP revascularisation procedure and were subsequently randomised into BASIL-2 accounted for a small subset of the CLTI population as a whole. For a wide range of patient, limb, anatomical and operational reasons, most patients in this cohort were deemed unsuitable for randomisation in BASIL-2. The results of BASIL-2 should be interpreted in this context.</p

The INNs and outs of antibody nonproprietary names

An important step in drug development is the assignment of an International Nonproprietary Name (INN) by the World Health Organization (WHO) that provides healthcare professionals with a unique and universally available designated name to identify each pharmaceutical substance. Monoclonal antibody INNs comprise a –mab suffix preceded by a substem indicating the antibody type, e.g., chimeric (-xi-), humanized (-zu-), or human (-u-). The WHO publishes INN definitions that specify how new monoclonal antibody therapeutics are categorized and adapts the definitions to new technologies. However, rapid progress in antibody technologies has blurred the boundaries between existing antibody categories and created a burgeoning array of new antibody formats. Thus, revising the INN system for antibodies is akin to aiming for a rapidly moving target. The WHO recently revised INN definitions for antibodies now to be based on amino acid sequence identity. These new definitions, however, are critically flawed as they are ambiguous and go against decades of scientific literature. A key concern is the imposition of an arbitrary threshold for identity against human germline antibody variable region sequences. This leads to inconsistent classification of somatically mutated human antibodies, humanized antibodies as well as antibodies derived from semi-synthetic/synthetic libraries and transgenic animals. Such sequence-based classification implies clear functional distinction between categories (e.g., immunogenicity). However, there is no scientific evidence to support this. Dialog between the WHO INN Expert Group and key stakeholders is needed to develop a new INN system for antibodies and to avoid confusion and miscommunication between researchers and clinicians prescribing antibodies

The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy

Background: The ability to accurately predict operative duration has the potential to optimise theatre efficiency and utilisation, thus reducing costs and increasing staff and patient satisfaction. With laparoscopic cholecystectomy being one of the most commonly performed procedures worldwide, a tool to predict operative duration could be extremely beneficial to healthcare organisations. Methods: Data collected from the CholeS study on patients undergoing cholecystectomy in UK and Irish hospitals between 04/2014 and 05/2014 were used to study operative duration. A multivariable binary logistic regression model was produced in order to identify significant independent predictors of long (> 90 min) operations. The resulting model was converted to a risk score, which was subsequently validated on second cohort of patients using ROC curves. Results: After exclusions, data were available for 7227 patients in the derivation (CholeS) cohort. The median operative duration was 60 min (interquartile range 45–85), with 17.7% of operations lasting longer than 90 min. Ten factors were found to be significant independent predictors of operative durations > 90 min, including ASA, age, previous surgical admissions, BMI, gallbladder wall thickness and CBD diameter. A risk score was then produced from these factors, and applied to a cohort of 2405 patients from a tertiary centre for external validation. This returned an area under the ROC curve of 0.708 (SE = 0.013, p  90 min increasing more than eightfold from 5.1 to 41.8% in the extremes of the score. Conclusion: The scoring tool produced in this study was found to be significantly predictive of long operative durations on validation in an external cohort. As such, the tool may have the potential to enable organisations to better organise theatre lists and deliver greater efficiencies in care

Procedural and 12 month in-hospital costs of primary infra-popliteal bypass surgery, infra-popliteal best endovascular treatment, and major lower limb amputation for Chronic Limb Threatening Ischaemia.

BACKGROUND Chronic limb threatening ischaemia (CLTI) is a growing global problem due to the widespread use of tobacco and increasing prevalence of diabetes. Although the financial consequences are considerable, few studies have compared the relative cost-effectiveness of different CLTI management strategies. The Bypass versus Angioplasty in Severe Ischaemia of the Leg (BASIL)-2 trial is randomising CLTI patients to primary infra-popliteal (IP) vein bypass surgery (BS) or best endovascular treatment (BET) and includes a comprehensive within-trial cost-utility analysis. AIM To compare over a 12-month time horizon, the costs of primary IP BS, IP best endovascular treatment (BET), and major limb major amputation (MLLA) to inform the BASIL-2 cost-utility analysis. METHODS We compared procedural human resource (HR) costs and total in-hospital costs for the index admission, and over the following 12-months, in 60 consecutive patients undergoing primary IP BS (n=20), IP BET (n=20), or MLLA (10 transfemoral and 10 transtibial ) for CLTI within the BASIL prospective cohort study. RESULTS Procedural HR costs were greatest for BS (BS £2,551, 95% CI: £1,934-2,807 vs. MLLA £1,130 95% CI: £1,046-1,297 vs. BET £329, 95% CI: £242-390, p<.001, Kruskal-Wallis) due to longer procedure duration and greater staff requirement. With regard to the index admission, MLLA was the most expensive due to longer hospital stay (MLLA £13,320, 95% CI: £8,986-18,616 vs. BS £8,714, 95% CI: £6,097-11,973 vs. BET £4,813, 95% CI: £3,529-6,097, p<.001, Kruskal-Wallis). The total cost of the index admission and in-hospital care over the following 12-months remained least for BET (MLLA £26,327, 95% CI: £17,653-30,458 vs. BS £20,401, 95% CI: £12,071-23,926 vs. BET £12,298, 95% CI: £6,961-15,439, p<.001, Kruskal-Wallis). CONCLUSION Over a 12-month time horizon, MLLA and IP BS are more expensive than IP BET in terms of procedural HR costs and total in-hospital costs. These economic data together with quality of life data from BASIL-2 will inform the calculation of incremental cost-effectiveness ratios for different CLTI management strategies within the BASIL-2 cost-utility analysis

Impact of UK NICE Clinical Guidelines 168 and social deprivation on access to interventional treatment for symptomatic varicose vein and specialist referral for leg ulceration.

BACKGROUND UK National Institute for Health and Care Excellence (NICE) clinical guidelines (CG) 168, published in July 2013, aimed to improve the management of lower limb venous disease by newly recommending interventional treatment for all people affected by symptomatic varicose veins (VV) and specialist vascular referral for all people suffering from a leg ulcer (LU) that had been present for ≥2 weeks. This study aims to determine if CG168 has increased access to vascular services, particularly for the socially deprived, who might be expected to have greater need for such services. METHODS The study was performed in a highly multi-cultural, socio-economically diverse, mixed urban/suburban population of approximately 1.2 million people living in and around East Birmingham, UK. Index of multiple deprivation quintile (IMD-Q) was used as a measure of social deprivation to compare levels of social deprivation of people undergoing interventions for symptomatic VV or referred with an LU during 18-month periods before and after the publication of CG168. The referring general practitioner practices (GPPs) were also recorded. RESULTS There was no change in overall IMD-Q distribution before and after CG168 in terms of VV interventions. However, there was a non-significant increase in proportions of people classified as IMD-Q5 (the most deprived quintile). After CG168, fewer IMD-Q5 people with LU were referred, with a shift in referrals towards those from less socially deprived areas. More GPP referred people with both VV and LU after CG168, and those that referred patients before and after CG168 tended to refer more after CG168. CONCLUSIONS CG168 has increased VV interventions as well as the number referred with LU. However, this improvement in access to treatment and referral may have disproportionately favoured the more socio-economic privileged. Professional and public education is required to ensure that the beneficial impact of the CG168 recommendations are maximised and that those with the greatest health needs have equal access to evidence-based management of their venous disease