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.

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.

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.

Prescription patterns of outpatients and the potential of multiplexed pharmacogenomic testing.

BACKGROUND: Pre-emptive pharmacogenomic (PGx) testing is potentially an efficient approach to improve drug safety and efficacy but the target population to test is unclear. OBJECTIVES: We aim to describe the prescription pattern of PGx drugs among adult medical outpatients. METHODS: We estimated the 5-year cumulative incidence (CI) for receiving three groups of PGx drugs using competing risks analysis: (i) all PGx drugs, (ii) PGx drugs with guidelines and (iii) PGx drugs with serious clinical effects. Comparisons of CIs were also done by patient characteristics using Gray's test. RESULTS: The 5-year CIs of receiving any new PGx drug, PGx drug with guidelines and serious clinical effects were 42.6%, 37.3% and 13.7%, respectively. The 5-year CI of receiving any new PGx drug was higher for patients >40 years old (43.6% vs ≤40 years old 36.0%, P < 2.2 × 10-22 ), Malays and Indians (50.3% and 49.8% vs Chinese 31.1%, P < 2.2 × 10-22 ), those who attended one of the following four specialties at the index visit compared to other specialties (infectious diseases [46.2% vs 42.6%, P = 2.9 × 10-4 ], psychiatry [48.3% vs 42.3%, P = 7.4 × 10-13 ], renal [49.8% vs 40.9%, P < 2.2 × 10-22 ], and rheumatology and immunology [54.8% vs 41.7%, P < 2.2 × 10-22 ]) and those prescribed ≥5 drugs at index visit (51.7% vs 0-4 drugs 41.7%, P < 2.2 × 10-22 ). CONCLUSIONS: Medical outpatients have a substantial probability of benefiting from pre-emptive PGx testing and this is higher in certain subgroups of patients.

World's First Experience Treating TASC II C and D Tibial Occlusive Disease Using the Selution SLR Sirolimus-Eluting Balloon: Six-Month Results From the PRESTIGE Study.

PURPOSE: The performance of sirolimus-coated devices has not been studied in patients with chronic limb-threatening ischemia patients. PRESTIGE aims to investigate the 6-month efficacy and safety profile of the Selution Sustained Limus Release (SLR) sirolimus-eluting balloon for treatment of TASC II C and D tibial occlusive lesions in patients with CLTI. MATERIALS AND METHODS: PRESTIGE is a pilot prospective, nonrandomized, single-arm, multi-investigator, single-center clinical study. Endpoints were adverse event-free survival at 1 month, technical success rate, primary tibial patency at 6 months, limb salvage success, target lesion revascularization (TLR), and amputation free survival (AFS). RESULTS: A total of 25 patients were included. There were 17 (68.0%) males; mean age, 63.7±9.73 years. CLTI severity was based on the Rutherford scale (R5=25/25; 100.0%). Significant comorbidities included diabetes mellitus (n=22; 88.0%) and end-stage renal failure (n=11; 44.0%). A total of 33 atherosclerotic lesions were treated (TASC II D=15 (45.5%)). Mean lesion length treated was 191±111 mm. Technical success was 100%. Primary tibial patency at 6 months was 22/27 (81.5%) and freedom from clinically driven TLR was 25/30 (83.3%). AFS was 21/25 (84.0%; 3 deaths and 1 major lower extremity amputation). Mean Rutherford score improved from 5.00 at baseline to 1.14±2.10 (p<0.05) at 6 months. There was a wound healing rate of 13/22 (59.1%) and 17/21 (81.0%) at 3 and 6 months respectively. CONCLUSIONS: Selution SLR drug-eluting balloon is a safe and efficacious modality in treating complex tibial arterial occlusive lesions in what is an otherwise frail cohort of CLTI patients, with a high prevalence of diabetes and end-stage renal failure. Technical and clinical success rates are high and 6-month target lesion patency and AFS are more than satisfactory.

Single Asian Center Experience Using the Flixene™ Early Cannulation Graft for Hemodialysis Access Creation.

BACKGROUND: The aim of this study was to review the efficacy of the Flixene™ (Atrium™, Hudson, NH, USA) hemodialysis arterio-venous graft (AVG) in a multiethnic Asian cohort of patients with end-stage renal failure (ESRF). Primary outcome was graft primary patency rate and secondary end points included graft usability, time to cannulation, reinterventions required for access salvage, complications, and patient mortality. METHODS: Single-center, single-arm, multi-investigator nonrandomized retrospective study. Patients with ESRF who underwent Flixene™ graft implantation over a two-year period (January 2017 - December 2018) were included to allow at least one-year follow-up. Demographics, procedural and follow-up data were collected from the hospital electronic medical records. RESULTS: About 48 patients (49 AVG) were included. There were 24 (50%) men; mean age 63.7 (IQR 58.2-71.3) years. Technical success rate was 45/49 (91.8%); 4/49 (8.2%) AVG created did not reach cannulation. 11/49 (22.4%) and 28/49 (57.1%) achieved cannulation within 1 and 2 weeks, respectively. 6- and 12- month primary patencies were 33.5% and 19.6%, respectively. Primary-assisted patency rates were 46.6% and 29.6% at the same time intervals. Secondary patency rate was 77.6% and 63.9% at 6 and 12 months, respectively. There were 6 (12.2%) graft infections requiring explant and one-year mortality was 14%. CONCLUSIONS: Our experience with the Flixene™ early cannulation graft is comparable with other AVGs in terms of patency and infection rates. However, early cannulation rates are lower than in other case series.

Utility of a novel high pressure non-compliant balloon for tibial atherosclerotic lesions in Asian patients with chronic limb threatening ischaemia.

Background: The aim was to evaluate the safety and efficacy of a high pressure, non-compliant balloon in the treatment of infrapopliteal occlusive disease in Asian patients with chronic limb threatening ischaemia (CLTI) from Singapore. Patients and methods: Prospective, multi-centre, single arm, non-randomized study. Immediate technical success, 6-month primary vessel patency (determined by Duplex ultrasonography), limb salvage, one-year clinically driven target lesion re-intervention (TLR) and amputation free survival (AFS) were the efficacy endpoints of interest. Results: 86 patients (63% males, mean age 68.9 ± 9.9 years) were enrolled over a 15-month period. Diabetes mellitus (DM) and end-stage renal failure (ESRF) were present in 94% and 38% of patients respectively. All had some degree of tissue loss at baseline (Rutherford scale 5 and 6 = 91% and 9% respectively). Of the 86 legs, 72% had 3 crural vessel disease and 84% had moderate/severe vessel wall calcification. 90% had > = 1 TASC D tibial lesion. Acute technical success was 89%. One month mortality was 3.5% and one-year freedom from TLR was 91%. 6-month tibial patency was 73%. 54/66 (82%) patients had at least one target treated tibial artery open at 6 months. A lower baseline toe pressure (OR 1.03, 95%CI 1.00-1.05) and elastic recoil post angioplasty (OR 0.20, 95%CI 0.05-0.79) were associated with a worse 6 month tibial patency. One-year AFS was 67%. 47/66 (71%) patients had a clinical improvement of at least one Rutherford class at 6 months and 52/59 (88%) experienced complete wound healing at 12 months. Conclusions: Use of a high pressure non-compliant balloon is safe and efficacious in treating highly complex infra-popliteal atherosclerotic lesions in an otherwise challenging population of CLTI patients with a high incidence of DM and ESRF. It is associated with highly satisfactory acute technical success, 6-month target lesion patency and one-year limb salvage.

Heal or no heel: Outcomes of ischaemic heel ulcers following lower limb revascularization from a multi-ethnic Asian Cohort in Singapore.

Ischaemic diabetic heel ulcers are difficult to treat and prognosis is often guarded. The aim was to document our outcome of treating heel ulcers following revascularization in a predominantly diabetic Asian cohort presenting with chronic limb threatening ischaemia from Singapore. Retrospective cohort study (n = 66, 66 limbs) over a 5-year period. Data were collected from hospital electronic health records. Outcomes included time to healing, amputation free survival (AFS), and mortality. Minimum follow-up period was 6 months. Multivariate regression analysis was performed to look for factors associated with poor outcome. Mean age was 67.4 ± 8.8 years. 62/66 (93.9%) were diabetics. Mean wound size at presentation was 3.6 ± 2.3 cm. Mean Wound, Ischaemia, Foot Infection (WIFI) score was 5 ± 1.6. 12/66 (18%) patients had a patent posterior tibial artery pre-operatively. Straight line flow was restored in only 31/66 (46.9) patients but 47/66 (71.2%) had successful limb salvage. Median time to wound healing was 90.0 (IQR 60-180) days. A median of 1 (IQR 0-2) wound debridement was required. Patients who underwent negative pressure dressing (23/66; 34.8%) required a median of 26 (IQR 13-33) cycles to achieve healing. Amputation free survival (AFS) was 72% and 68% at 6- and 12-months, respectively. Mortality rate was 16.7% and 19.7% at 6- and 12-months, respectively. Low albumin level and initial Rutherford class were independent predictors of worse 6-month AFS. Outcomes of heel ulcers post revascularisation may not be as poor as previously described. Persistent attention to wound care with multidisciplinary effort is needed for optimal healing.

Economic burden of adverse drug reactions and potential for pharmacogenomic testing in Singaporean adults.

Adverse drug reactions (ADRs) contribute to hospitalization but data on its economic burden is scant. Pre-emptive pharmacogenetic (PGx) testing can potentially reduce ADRs and its associated costs. The objectives of this study were to quantify the economic burden of ADRs and to estimate the breakeven cost of pre-emptive PGx testing in Singapore. We collected itemized costs for 1000 random non-elective hospitalizations of adults admitted to a tertiary-care general hospital in Singapore. The presence of ADRs at admission and their clinical characteristics were reported previously. The economic burden of ADRs was assessed from two perspectives: (1) Total cost and (2) incremental costs. The breakeven cost of PGx testing was estimated by dividing avoidable hospitalization costs for ADRs due to selected drugs by the number of patients taking those drugs. The total cost of 81 admissions caused by ADRs was US$570,404. Costs were significantly higher for bleeding/elevated international normalized ratio (US$9906 vs. US$2251, p = 6.58 × 10-3) compared to other ADRs, and for drugs acting on the blood coagulation system (US$9884 vs. US$2229, p = 4.41 × 10-3) compared to other drug classes. There were higher incremental laboratory costs due to ADRs causing or being present at admission. The estimated breakeven cost of a pre-emptive PGx test for patients taking warfarin, clopidogrel, chemotherapeutic and neuropsychiatric drugs was US$114 per patient. These results suggest that future studies designed to directly measure the clinical and cost impact of a pre-emptive genotyping program will help inform clinical practice and health policy decisions.

Genetic diversity of variants involved in drug response and metabolism in Sri Lankan populations: implications for clinical implementation of pharmacogenomics.

BACKGROUND: Interpopulation differences in drug responses are well documented, and in some cases they correspond to differences in the frequency of associated genetic markers. Understanding the diversity of genetic markers associated with drug response across different global populations is essential to infer population rates of drug response or risk for adverse drug reactions, and to guide implementation of pharmacogenomic testing. Sri Lanka is a culturally and linguistically diverse nation, but little is known about the population genetics of the major Sri Lankan ethnic groups. The objective of this study was to investigate the diversity of pharmacogenomic variants in the major Sri Lankan ethnic groups. METHODS: We examined the allelic diversity of more than 7000 variants in genes involved in drug biotransformation and response in the three major ethnic populations of Sri Lanka (Sinhalese, Sri Lankan Tamils, and Moors), and compared them with other South Asian, South East Asian, and European populations using Wright's Fixation Index, principal component analysis, and STRUCTURE analysis. RESULTS: We observed overall high levels of similarity within the Sri Lankan populations (median FST=0.0034), and between Sri Lankan and other South Asian populations (median FST=0.0064). Notably, we observed substantial differentiation between Sri Lankan and European populations for important pharmacogenomic variants related to warfarin (VKORC1 rs9923231) and clopidogrel (CYP2C19 rs4986893) response. CONCLUSION: These data expand our understanding of the population structure of Sri Lanka, provide a resource for pharmacogenomic research, and have implications for the clinical use of genetic testing of pharmacogenomic variants in these populations.

Prevalence and characteristics of adverse drug reactions at admission to hospital: a prospective observational study.

AIMS: Adverse drug reactions (ADRs) contribute to poorer patient outcomes and additional burden to the healthcare system. However, data on the true burden, relevant types and drugs causing ADRs are lacking. The aim of this study was to determine the prevalence of ADR-related hospitalization in the general adult population in Singapore and to investigate their characteristics. METHODS: We prospectively recruited 1000 adult patients with unplanned admission to a large tertiary-care hospital. Two independent reviewers evaluated all suspected ADRs for causality, type, severity and avoidability. The prevalence of ADR-related hospitalization was calculated based on 'definite' and 'probable' ADRs. Logistic regression was used to evaluate predictors for having an ADR at admission. RESULTS: The prevalence of all ADRs at admission was 12.4% (95% CI: 10.5-14.6%) and ADRs causing admission was 8.1% (95% CI: 6.5-10.0%). The most common ADRs were gastrointestinal-related. The most common drug category causing ADRs were cardiovascular drugs. Patients with ADRs had a longer length of stay than those who did not (median 4 vs. 3 days, P = 1.70 × 10-3 ). About 30% of ADRs at admission were caused by at least one drug with a clinical annotation in the Pharmacogenomics KnowledgeBase (PharmGKB), suggesting that some of these ADRs may have been predicted by pharmacogenetic testing. CONCLUSIONS: We have quantified the burden and characteristics of clinically impactful ADRs in the Singaporean general adult population. Our results will provide vital information for efforts in reducing ADRs through targeted vigilance, patient education and pharmacogenomics in Singapore.

Attitudes on warfarin pharmacogenetic testing in Chinese patients and public.

INTRODUCTION: Genetic factors affecting warfarin maintenance dose have been well established, but patient acceptance is a necessary consideration for the successful clinical implementation of warfarin pharmacogenetic testing (WPGT). In this study, we aimed to determine the attitudes toward WPGT among Singaporean Chinese. METHODS: A total of 194 warfarin patients and 187 members of the public completed a structured survey on paper and the Internet, respectively. Attitudes were expressed as willingness to undergo WPGT (single item with 5-point response) and expectations and concerns about WPGT (two multi-item scales). Relationships between attitudes and socio-demographic and clinical variables were explored using Fisher's exact test, Student's t-test, one-way analysis of variance or Pearson's correlation. RESULTS: Majority of respondents were willing to or neutral about undergoing WPGT. Both patients and public had relatively high expectations (mean [SD]: 3.77 [0.63], and 3.97 [0.55], respectively) and moderately high concerns (mean [SD]: 3.30 [0.69] and 3.33 [0.68], respectively) about WPGT. Willingness to undergo WPGT was associated with gender, educational status, length of warfarin treatment, and number of chronic diseases among warfarin patients, and with history of adverse drug reactions and number of chronic diseases among the public. Higher expectation of WPGT was associated with higher willingness (p < .001 in both populations), while higher concern was associated with lower willingness to undergo WPGT among the public (p = .004) but not among patients (p = .072). CONCLUSION: Patient acceptance is not a major barrier to clinical implementation of WPGT but patient education is necessary and the ethical, social, and legal issues should be addressed.

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.

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.

Singapore Pharmacogenomics Portal: a web resource for evaluating human genetic variations of genes responsible for drug responses.

The Singapore Pharmacogenomics Portal is the first genomics web platform that links public resources from PharmGKB and DrugBank with population genetics data from the International HapMap Project and the Singapore Genome Variation Project. The web portal provides the opportunity to survey genetic differences across populations for all autosomal genes in the genome, and serves as an integrated platform for linking these data with drugs and genetic variants that affect drug responses, adverse reactions, and dosage requirements. We envisage that the information provided by the portal will be useful to drug regulators and clinical researchers when evaluating the transferability of results from clinical trials conducted in one population to other populations for which no direct clinical testing has been conducted. The utility of this resource may extend to other countries in the region that also have significant populations of Chinese, Malay, or Indian ancestry.

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.

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.

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.

Therapeutic effects of acupuncture for neurogenic dysphagia--a randomized controlled trial.

OBJECTIVE: To evaluate the therapeutic effects and long-term efficacy of acupuncture for neurogenic dysphagia. METHODS: Subjects with neurogenic dysphagia undergoing routine swallowing management were randomized to receive either 20 sessions of true acupuncture (experimental group) or sham acupuncture (control group 1) for approximately one and a half months. A third group (control group 2) comprised of non-randomized subjects with neurogenic dysphagia who received routine care were recruited from separate wards. The outcomes were assessed by the Royal Brisbane Hospital Outcome Measure for Swallowing (RBHOMS), as well as by the consistencies of ingested food and fluid. RESULTS: A total of 87 subjects (experimental group, n = 20; control group 1, n = 19; control group 2, n = 48) were recruited into the trial. The average RBHOMS score showed a greater improvement in the experimental group and in control group 1 than in control group 2. The average levels of food and fluid consistencies displayed greater improvement in the experimental group than in the two control groups. CONCLUSIONS: This study demonstrates that acupuncture may have therapeutic effects and long-term efficacy for neurogenic dysphagia. However, due to an insufficient sample size and the lack of follow-up for control group 2, multi-centre trials employing a larger sample size may be required to draw concrete conclusions.

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.