3-year clinical outcomes of A Singapore VenaSeal™ real world post-market evaluation Study (ASVS) for varicose vein ablation.

INTRODUCTION: Medium-term clinical outcome data are lacking for cyanoacrylate glue (CAG) ablation for symptomatic varicose veins, especially from the Asian population. OBJECTIVES: Aim was to determine the 3-year symptomatic relief gained from using the VenaSeal™ device to close refluxing truncal veins from the Singaporean ASVS prospective registry. METHODS: The revised Venous Clinical Severity Score (rVCSS) and three quality of life (QoL) questionnaires were completed to assess clinical improvement in venous disease symptoms along with a dedicated patient satisfaction survey. 70 patients (107 limbs; 40 females; mean age of 60.9 ± 13.6 years) were included at 3 years. RESULTS: At 3 years, rVCSS showed sustained improvement from baseline (5.00 to 0.00; p < 0.001) and 51/70 (72.9%) had improvement by at least 2 or more CEAP categories. Freedom from reintervention was 90% and 85.7% patients were extremely satisfied with the treatment outcome. No further reports of further hypersensitivity reactions after one year. CONCLUSION: The 3-year follow-up results of the ASVS registry demonstrated continued and sustained clinical efficacy with few reinterventions following CAG embolization in Asian patients with chronic venous insufficiency. TRIAL REGISTRATION: ClinicalTrials.gov Registration: NCT03893201.

The impact of elective surgery postponement during COVID-19 on emergency bellwether procedures in a large tertiary centre in Singapore.

The coronavirus disease 2019 (COVID-19) pandemic drove many healthcare systems worldwide to postpone elective surgery to increase healthcare capacity, manpower, and reduce infection risk to staff. The aim of this study was to assess the impact of an elective surgery postponement policy in response to the COVID-19 pandemic on surgical volumes and patient outcomes for three emergency bellwether procedures. A retrospective cohort study of patients who underwent any of the three emergency procedures [Caesarean section (CS), emergency laparotomy (EL), and open fracture (OF) fixation] between 1 January 2018 and 31 December 2021 was conducted using clinical and surgical data from electronic medical records. The volumes and outcomes of each surgery were compared across four time periods: pre-COVID (January 2018-January 2020), elective postponement (February-May 2020), recovery (June-November 2020), and postrecovery (December 2020-December 2021) using Kruskal-Wallis test and segmented negative binomial regression. There was a total of 3886, 1396, and 299 EL, CS, and OF, respectively. There was no change in weekly volumes of CS and OF fixations across the four time periods. However, the volume of EL increased by 47% [95% confidence interval: 26-71%, P = 9.13 × 10-7) and 52% (95% confidence interval: 25-85%, P = 3.80 × 10-5) in the recovery and postrecovery period, respectively. Outcomes did not worsen throughout the four time periods for all three procedures and some actually improved for EL from elective postponement onwards. Elective surgery postponement in the early COVID-19 pandemic did not affect volumes of emergency CS and OF fixations but led to an increase in volume for EL after the postponement without any worsening of outcomes.

Frameworks for measuring population health: A scoping review.

INTRODUCTION: Many regions in the world are using the population health approach and require a means to measure the health of their population of interest. Population health frameworks provide a theoretical grounding for conceptualization of population health and therefore a logical basis for selection of indicators. The aim of this scoping review was to provide an overview and summary of the characteristics of existing population health frameworks that have been used to conceptualize the measurement of population health. METHODS: We used the Population, Concept and Context (PCC) framework to define eligibility criteria of frameworks. We were interested in frameworks applicable for general populations, that contained components of measurement of health with or without its antecedents and applied at the population level or used a population health approach. Eligible reports of eligible frameworks should include at least domains and subdomains, purpose, or indicators. We searched 5 databases (Pubmed, EMBASE, Web of Science, NYAM Grey Literature Report, and OpenGrey), governmental and organizational sites on Google and websites of selected organizations using keywords from the PCC framework. Characteristics of the frameworks were summarized descriptively and narratively. RESULTS: Fifty-seven frameworks were included. The majority originated from the US (46%), Europe (23%) and Canada (19%). Apart from 1 framework developed for rural populations and 2 for indigenous populations, the rest were for general urban populations. The numbers of domains, subdomains and indicators were highly variable. Health status and social determinants of health were the most common domains across all frameworks. Different frameworks had different priorities and therefore focus on different domains. CONCLUSION: Key domains common across frameworks other than health status were social determinants of health, health behaviours and healthcare system performance. The results in this review serve as a useful resource for governments and healthcare organizations for informing their population health measurement efforts.

Implementation of Prediction Models in the Emergency Department from an Implementation Science Perspective-Determinants, Outcomes, and Real-World Impact: A Scoping Review.

STUDY OBJECTIVE: Prediction models offer a promising form of clinical decision support in the complex and fast-paced environment of the emergency department (ED). Despite significant advancements in model development and validation, implementation of such models in routine clinical practice remains elusive. This scoping review aims to survey the current state of prediction model implementation in the ED and to provide insights on contributing factors and outcomes from an implementation science perspective. METHODS: We searched 4 databases from their inception to May 20, 2022: MEDLINE (through PubMed), Embase, Scopus, and CINAHL. Articles that reported implementation outcomes and/or contextual determinants under the Reach, Effectiveness, Adoption, Implementation Maintenance (RE-AIM)/Practical, Robust, Implementation, and Sustainability Model (PRISM) framework were included. Characteristics of studies, models, and results of the RE-AIM/PRISM domains were summarized narratively. RESULTS: Thirty-six reports on 31 implementations were included. The most common prediction models implemented were early warning scores. The most common implementation strategies used were training stakeholders, infrastructural changes, and using evaluative or iterative strategies. Only one report examined ED patients' perspectives, whereas the rest were focused on the experience of health care workers or organizational stakeholders. Key determinants of successful implementation include strong stakeholder engagement, codevelopment of workflows and implementation strategies, education, and usability. CONCLUSION: Examining ED prediction models from an implementation science perspective can provide valuable insights and help guide future implementations.

Intervention with selution SLR™ Agent Balloon for Endovascular Latent Limus therapy for failing AV Fistulas (ISABELLA) Trial: Protocol for a pilot clinical study and pre-clinical results.

BACKGROUND: The aim of this pilot clinical study is to evaluate the safety and efficacy of the Selution Sustained Limus Release (SLR)™ sirolimus-coated balloon (M.A. MedAlliance SA, Nyon, Switzerland) for improving the patency of failing arterio-venous fistulas (AVF) in hemodialysis patients. We also present herein a pre-clinical pharmacokinetic and safety evaluation of Selution™ to justify its first use in hemodialysis patients for endovascular access salvage. METHODS AND RESULTS: This is an investigator-initiated prospective single-center, non-blinded single-arm trial. Forty patients with clinically significant de novo or recurrent stenoses in a mature AVF circuit will be recruited. All stenotic lesions will be prepared with high pressure non-compliant conventional balloon angioplasty (CBA) prior to deployment of the Sustained-Release Selution™ sirolimus drug-eluting balloon. The primary efficacy endpoint is 6-month target lesion primary patency and the primary safety endpoint is freedom from localized or systemic serious adverse events through 30 days. Secondary endpoints of interest include technical and clinical success rates and circuit access patency at 3 and 6 months. Follow-up will occur for 2 years for those patients whose AVFs remain patent. Pharmacokinetic and histological animal safety studies performed with the Selution™ coating formulation showed prolonged arterial tissue retention of sirolimus with therapeutic levels up to 60 days and non-toxic and rapidly declining blood levels. Histological results in animal models demonstrated safety, freedom from intraluminal thrombus, reduction in restenosis by sirolimus elution compared to CBA, and no evidence of embolic phenomena indicative of adverse particulate effects. DISCUSSION: Long release sirolimus coated balloons may serve as a promising novel alternative therapy to paclitaxel-based technology for treating conduit stenosis secondary to neointimal hyperplasia. Pre-clinical pharmacokinetic and histological animal data are encouraging and provide suggestion of safety and efficacy in this setting. This single-center trial will provide a first step toward demonstration of efficacy and safety of this device for treatment of stenotic fistulas.

Use of the helical SUPERA™ stent and Passeo-18 Lux™ drug-coated balloon to treat recurrent cephalic arch stenosis for dysfunctional brachiocephalic fistulas: 1 year results of the Arch V SUPERA-LUX study.

BACKGROUND: Aim of Arch V SUPERA-LUX was to evaluate the safety and efficacy of the combination therapy of SUPERA™ (Abbott Vascular, Santa Clara, CA, USA) helical stent implantation and Passeo-18 Lux™ (Biotronik Asia Pacific Pte Ltd, Singapore) drug coated balloon (DCB) elution to treat recurrent cephalic arch stenosis (CAS) in the setting of AV access dysfunction. METHODS: Investigator-initiated, single-center, single-arm prospective pilot study of 20 end-stage renal failure Asian patients with a dysfunctional brachiocephalic fistula. All had symptomatic recurrent CAS within 6 months of prior intervention. The lesion was pre-dilated with a standard high-pressure balloon (Biotronik Passeo-35 HP balloon). The DCB (Passeo-18 Lux™) is subsequently inflated and the SUPERA™ stent deployed to sit 2 mm distal to the cephalic arch and covering the CAS but within the DCB zone. All patients were prescribed dual antiplatelet therapy for 3 months and followed up with Duplex ultrasound at 6- and 12-months. RESULTS: There were 9 (45%) males and mean age was 67 ± 11.0 years. Mean time from prior procedure was 113 ± 68 days and main indication for reintervention was high venous pressure (9/20, 45%). Technical success was 100% and there were no peri-procedural complications related to either stent or DCB deployment. Target lesion primary patency at 6- and 12-months was 10/18 (55%) and 5/16 (31%), respectively. Mean time to target lesion re-intervention was 170 ± 82 days. Circuit access patency was 8/18 (44%) and 2/16 (13%) at 6- and 12-months respectively and mortality was 3/20 (15%) attributed to the patients' underlying co-morbidities. CONCLUSION: Dual prong strategy of using SUPERA™ stenting and Passeo-18 Lux™ drug elution for recurrent CAS, although safe, was no more efficacious than conventional balloon angioplasty or stenting alone. Development of an intense inflammatory reaction within the stent led to reinterventions of a number of cases with suboptimal results.

Understanding the use of evidence-based medical therapy in patients with peripheral artery disease: A qualitative study using the Tailored Implementation for Chronic Diseases Framework.

Introduction: The global burden of peripheral artery disease (PAD) has been increasing. Guidelines for PAD recommend evidence-based medical therapy (EBMT) to reduce the risks of cardiovascular events and death but the implementation of this is highly variable. This study aimed to understand the current practices regarding EBMT prescription in PAD patients and the key barriers and facilitators for implementing PAD guidelines. Method: A qualitative study was conducted in the largest tertiary hospital in Singapore from December 2021 to March 2023. The participants included healthcare professionals and in-patient pharmacists involved in the care of PAD patients, as well as patients with PAD who had undergone a lower limb angioplasty revascularisation procedure. Data were collected through in-depth, individual semi-structured interviews conducted face-to-face or remotely by a trained research assistant. Interviews were audio-recorded, transcribed and systematically coded using data management software NVivo 12.0. The Tailored Implementation for Chronic Diseases (TICD) framework was used to guide the interviews and analysis. Results: Twelve healthcare professionals (4 junior consultants, 7 senior consultants, and 1 senior in-patient pharmacist) and 4 patients were recruited. Nine themes in 7 domains emerged. Only a small proportion of doctors were aware of the relevant guidelines, and the generalisability of guidelines to patients with complicated conditions was the doctors' main concern. Other barriers included cost, frequent referrals, lack of interprofessional collaboration, not being the patients' long-term care providers, short consultation time and patients' limited medication knowledge. Conclusion: Findings from this study may inform strategies for improving healthcare professionals' adherence to guidelines and patients' medication adherence.

Study protocol for a Prospective, Randomized controlled trial of stEnt graft and Drug-coated bAlloon Treatment for cephalic arch stenOsis in dysfunctional arteRio-venous fistulas (PREDATOR).

BACKGROUND: Treatment of cephalic arch stenosis (CAS) is associated with high risk of failure and complications. Although stent-graft (SG) placement has improved patency rates, stent edge restenosis has been raised as a potential limiting factor for SG usage in CAS. This study aims to evaluate the safety and efficacy of combining stent graft placement with paclitaxel-coated balloon (PCB) angioplasty versus PCB alone in the treatment of CAS. METHODS: This is an investigator-initiated, prospective, international, multicenter, open-label, randomized control clinical trial that plans to recruit 80 patients, who require fistuloplasty from dysfunctional arteriovenous fistula (AVF) from CAS. Eligible participants are randomly assigned to receive treatment with SG and PCB or PCB alone in a 1:1 ratio post-angioplasty (n = 40 in each arm). Randomization is stratified by de novo or recurrent lesion, and the participants are followed up for 1 year. The primary endpoints of the study are target lesion primary patency (TLPP) and access circuit primary patency (ACPP) rates at 6-months. The secondary endpoints are TLPP and ACPP at 3- and 12-month; target lesion and access circuit assisted primary and secondary patency rates at 3, 6, and 12-months and the total number of interventions; complication rate; and cost-effectiveness. DISCUSSION: This study will evaluate the clinical efficacy and safety of combination SG and PCB implantation compared to PCB alone in the treatment of CAS for hemodialysis patients.

Pilot single-arm study to investigate the efficacy and safety of endovenous Microwave ablations for treatment of varicose veins in Singapore - one year results of the MAESTRO registry.

OBJECTIVES: Aim was to report a prospective two-centre Singaporean experience using Endovenous Microwave Ablation (EMA) to treat symptomatic primary great saphenous vein reflux. We evaluated 1-year safety, efficacy and patient satisfaction. METHODS: 50 patients (63 limbs; 29 females; mean age 58.0 ± 12.1 years) were included. Patients were reviewed at 2-weeks, 3-, 6- and 12-months and underwent Duplex ultrasound assessment. Three quality of life (QoL) questionnaires were completed. RESULTS: The truncal closure rates at 2-weeks, 3-, 6- and 12-months were 63/63 (100%), 59/59 (100%), 58/58 (100%) and 59/60 (98.3%), respectively. There was 100% technical success and no serious adverse events. There were sustained improvement of QoL questionnaire scores from 2 weeks to 12 months. CONCLUSION: EMA is a safe and efficacious venous ablative technology at 12 months and is associated with a high rate of target vein occlusion and sustained QoL improvement.

Parents' priorities for decision-making of pediatric epilepsy treatments and perceived needs for decision support in multi-ethnic Asian clinical setting: A qualitative analysis.

OBJECTIVE: To identify parents' priorities when making a decision on genetic testing and antiseizure drug (ASD) options for pediatric epilepsy and their support needs for informed decision-making in multi-ethnic Asian clinical settings. METHODS: Qualitative in-depth interviews, using a semi-structured interview guide, were conducted with purposively selected parents of pediatric patients with newly diagnosed epilepsy or known diagnosis of epilepsy (n = 26). Interviews were audio recorded and transcribed verbatim. Thematic analysis was undertaken to generate themes. RESULTS: Parents' narratives showed difficulty assimilating information, while knowledge deficit and emotional vulnerability led parents' desire to defer a decision for testing and ASDs to mitigate decisional burden. Priorities for decisions were primarily based on intuitive ideas of the treatment's risks and benefits, yet very few could elaborate on tradeoffs between risks and efficacy. Priorities outside the purview of the healthcare team, such as children's emotional wellbeing and family burden of ASD administration, were also considered important. Authority-of-medical-professional heuristic facilitated the ASD decision for parents who preferred shared rather than sole responsibility for a decision. Importantly, parents' support needs for informed decision-making were very much related to the availability of support mechanisms in post-treatment decisions owing to perceived uncertainty of the chosen ASD. CONCLUSIONS: Findings suggest that multiple priorities influenced ASD decision process. To address support needs of parents for informed decision-making, more consideration should be given to post-treatment decision support through the provision of educational opportunities, building peer support networks, and developing a novel communication channel between healthcare providers and parents.

One year clinical outcomes of Rutherford 6 chronic limb threatening ischemia patients undergoing lower limb endovascular revascularisation from Singapore.

BACKGROUND: Percutaneous transluminal angioplasty (PTA) is widely used as a first-line revascularisation option in patients with chronic limb threatening ischemia (CLTI). This study aimed to evaluate the short-term endovascular revascularisation treatment outcomes of a cohort of Rutherford 6 (R6) CLTI patients, from a multi-ethnic Asian population in Singapore. Patients with R6 CLTI who underwent endovascular revascularisation from June 2019 to February 2020 at Singapore General Hospital, a tertiary vascular centre in Singapore, were included and followed up for one year. Primary outcome measures included number and type of reinterventions required, 3-, 6- and 12-month mortality, 6- and 12-month amputation free survival (AFS), wound healing success and changes in Rutherford staging after 3, 6 and 12 months. RESULTS: Two hundred fifty-five procedures were performed on 86 patients, of whom 78 (90.7%) were diabetics, 54 (62.8%) had coronary artery disease (CAD) and 54 (62.8%) had chronic kidney disease (CKD). 42 patients (48.8%) required reintervention within 6 months. Multivariate analysis revealed that the presence of CAD was a significant independent predictor for reintervention. Mortality was 15.1%, 20.9% and 33.7% at 3, 6 and 12 months respectively. AFS was 64.0% and 49.4% at 6 and 12 months. Inability to ambulate, congestive heart failure (CHF), dysrhythmia and CKD were significant independent predictors of lower 12-month AFS. CONCLUSIONS: PTA for R6 CLTI patients was associated with relatively high mortality and reintervention rates at one year. CAD was an independent predictor of reintervention. More research is required to help risk stratify which CLTI patients would benefit from an endovascular-first approach versus conservative treatment or an immediate major lower extremity amputation policy.

Implementation of prediction models in the emergency department from an implementation science perspective-Determinants, outcomes and real-world impact: A scoping review protocol.

The number of prediction models developed for use in emergency departments (EDs) have been increasing in recent years to complement traditional triage systems. However, most of these models have only reached the development or validation phase, and few have been implemented in clinical practice. There is a gap in knowledge on the real-world performance of prediction models in the ED and how they can be implemented successfully into routine practice. Existing reviews of prediction models in the ED have also mainly focused on model development and validation. The aim of this scoping review is to summarize the current landscape and understanding of implementation of predictions models in the ED. This scoping review follows the Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) checklist. We will include studies that report implementation outcomes and/or contextual determinants according to the RE-AIM/PRISM framework for prediction models used in EDs. We will include outcomes or contextual determinants studied at any point of time in the implementation process except for effectiveness, where only post-implementation results will be included. Conference abstracts, theses and dissertations, letters to editors, commentaries, non-research documents and non-English full-text articles will be excluded. Four databases (MEDLINE (through PubMed), Embase, Scopus and CINAHL) will be searched from their inception using a combination of search terms related to the population, intervention and outcomes. Two reviewers will independently screen articles for inclusion and any discrepancy resolved with a third reviewer. Results from included studies will be summarized narratively according to the RE-AIM/PRISM outcomes and domains. Where appropriate, a simple descriptive summary of quantitative outcomes may be performed.

Midterm outcomes (2 years) using the Venovo™ and Sinus Obliquus™ venous stents in the treatment of non-thrombotic and post-thrombotic iliac vein lesions - Results from a multi-centre Asian cohort.

INTRODUCTION: Medium-term outcome data are lacking for dedicated venous stents especially from the Asian population. OBJECTIVES: Aim was to determine the 2-year patency and symptomatic relief gained from using the BD Venovo™ and Optimed Sinus Obliquus™venous stents for ilio-femoral obstruction (IFO). METHODS: 60 patients (71 limbs; 39 females; mean age of 66.4 ± 11.9 years) were included in this prospective dual centre Asian cohort. Clinical improvement was determined by change in the CEAP, rVCSS and pain scores. Stent patency and stenosis were measured using area reduction on CTV and diameter reduction on Duplex ultrasound. RESULTS: At 2 years, 65.7% showed ≥1 CEAP score improvement from baseline and rVCSS and pain scores remained low and sustained. 87.1% venous leg ulcers remained healed. Freedom from target lesion revascularisation was 94.3% and overall stent patency was 87.1%. There were no stent fractures or migration reported. CONCLUSION: Dedicated venous stents for IFO were associated with sustained clinical improvement and a high freedom from reintervention at 2 years in Asian patients.

Effect of fertility health awareness strategies on fertility knowledge and childbearing in young married couples (FertStart): study protocol for an effectiveness-implementation hybrid type I multicentre three-arm parallel group open-label randomised clinical trial.

INTRODUCTION: Birth rates have been declining in many advanced societies including Singapore. We designed two interventions with vastly different resource requirements, which include fertility education, personalised fertility information and a behavioural change component targeting modifiable psychological constructs to modify fertility awareness and childbearing intentions. We aim to evaluate the effect of these two interventions on knowledge, attitudes and practice around childbearing compared with a control group among young married couples in Singapore and understand the implementation factors in the setting of an effectiveness-implementation hybrid type 1 three-arm randomised trial. METHODS AND ANALYSIS: We will randomise 1200 young married couples to no intervention (control), Fertility Health Screening group (FHS) or Fertility Awareness Tools (FAT) in a 7:5:5 ratio. Couples in FHS will undergo an anti-Mullerian hormone test and semen analysis, a doctor's consultation to explain the results and standardised reproductive counselling by a trained nurse. Couples in FAT will watch a standardised video, complete an adapted fertility status awareness (FertiSTAT) tool and receive an educational brochure. The attitudes, fertility knowledge and efforts to achieve pregnancy of all couples will be assessed at baseline and 6 months post-randomisation. Birth statistics will be tracked using administrative records at 2 and 3 years. The primary outcome is the change in the woman's self-reported intended age at first birth between baseline and 6 months post-randomisation. In addition, implementation outcomes and cost-effectiveness of the two interventions will be assessed. ETHICS AND DISSEMINATION: This study has been reviewed and approved by the Centralized Institutional Review Board of SingHealth (2019/2095). Study results will be reported to the study funder and there are plans to disseminate them in scientific conferences and publications, where authorship will be determined by the International Committee of Medical Journal Editors guidelines. TRIAL REGISTRATION NUMBER: NCT04647136; ClinicalTrails.gov Identifier.

Two-year clinical outcomes following lower limb endovascular revascularisation for chronic limb-threatening ischaemia at a tertiary Asian vascular centre in Singapore.

INTRODUCTION: Percutaneous transluminal angioplasty (PTA) is commonly used to treat patients with chronic limb-threatening ischaemia (CLTI). This study aimed to examine the mortality and functional outcomes of patients with CLTI who predominantly had diabetes mellitus in a multi-ethnic Asian population in Singapore. METHODS: Patients with CLTI who underwent PTA between January 2015 and March 2017 at the Vascular Unit at Singapore General Hospital, Singapore, were studied. Primary outcome measures were 30-day unplanned readmission, two-year major lower extremity amputation (LEA), mortality rates, and ambulation status at one, six and 12 months. RESULTS: A total of 221 procedures were performed on 207 patients, of whom 184 (88.9%) were diabetics. The one-, six- and 12-month mortality rate was 7.7%, 16.4% and 21.7%, respectively. The two-year LEA rate was 30.0%. At six and 12 months, only 96 (46.4%) and 93 (44.9%) patients were ambulant, respectively. Multivariate analysis revealed that preoperative ambulatory status, haemoglobin, Wound Ischaemia and foot Infection (WIfI) score, and end-stage renal failure (ESRF) were independent predictors of one-year ambulatory status. Predictors of mortality at one, six and 12 months were ESRF, preoperative albumin level, impaired functional status and employment status. CONCLUSION: PTA for CLTI was associated with low one-year mortality and two-year LEA rates but did not significantly improve ambulation status. ESRF and hypoalbuminaemia were independent predictors of mortality. ESRF/CKD and WIfI score were independent predictors of loss of ambulation at six months and one year. We need better risk stratification for patients with CLTI to decide between initial revascularisation and an immediate LEA policy.

Implementation science: A critical but undervalued part of the healthcare innovation ecosystem.

Healthcare systems face many competing demands and insufficient resources. Service innovations to improve efficiency are important to address this challenge. Innovations can range from new pharmaceuticals, alternate models of care, novel devices, and the use other technologies. Suboptimal implementation can mean lost benefits. This review article aims to highlight the role of implementation science, summarize how settings have leveraged this methodology to promote translation of innovation into practice, and describe our own experience of embedding implementation science into an academic medical center in Singapore. Implementation science offers a range of methods to promote systematic uptake of research findings about innovations and is gaining recognition worldwide as an important discipline for health services researchers. Health systems around the world have tried to promote implementation research in their settings by establishing (1) dedicated centers/programs, (2) offering funding, and (3) building knowledge and capacity among staff. Implementation science is a critical piece in the translational pathway of "evidence to innovation." The three efforts we describe should be strengthened to integrate implementation science into the innovation ecosystem around the world.

An Observational Clinical Trial Examining the Effect of Topical Oxygen Therapy (Natrox™) on the Rates of Healing of Chronic DiAbetic Foot Ulcers (OTONAL Trial).

Natrox™ topical oxygen therapy (TOT) (Inotec AMD Ltd, Cambridgeshire, UK) employs a small battery-powered "oxygen generator" to concentrate atmospheric oxygen and feeds pure, moist, oxygen through a fine, soft tube to a dressing-like "oxygen distribution system", which is placed over the wound and is held in place by a conventional dressing. The aim was to determine the effectiveness of Natrox™ for non-healing diabetic foot ulcers (DFU) over a 3-month period.Longitudinal, single-arm, open prospective registry study using 12 weeks of TOT using a 4 week run-in period. 20 patients recruited to OTONAL had chronic DFU greater than 3 months duration or minor amputation sites with less than 50% healing in 4 weeks.There were 13 (65%) males and the mean age was 65.7 (±11.6) years. The mean glycated haemoglobin (HbA1c) was 6.9 (±1.3) mmol mol-1 and mean wound duration before TOT was 114 (±79.1) days. 18/20 (90.0%) patients had concomitant lower limb revascularization angioplasty for chronic limb threatening ischaemia. The mean size of the foot ulcer at baseline was 11.3 ± 14.8 cm2 and mean transcutaneous oxygen measurement value was 34.1 (±19.6) mm Hg. Wound closure of >75% was observed in 14/20 (70.0%) patients. There was a 91.3% (±14.9%) wound area reduction by 3 months (P = .001) and mean time for 100% closure was 77.6 ± 32.5 days. Mean pain scores reduced from 2.4 (±1.8) at baseline to .5 (±1.0) at 3 months (P = .008). All patients were very satisfied using the ambulatory device. Use of TOT in chronic diabetic foot wounds stimulates a healing state, underpinning the concept that oxygen plays a central role in wound healing. Our results are more compelling if you consider they started with relatively large-sized DFUs and majority of patients were frail with underlying peripheral artery disease. (NCT03863054).