A vein bypass first versus a best endovascular treatment first revascularisation strategy for patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal revascularisation procedure to restore limb perfusion (BASIL-2): an open-label, randomised, multicentre, phase 3 trial.

BACKGROUND: Chronic limb-threatening ischaemia is the severest manifestation of peripheral arterial disease and presents with ischaemic pain at rest or tissue loss (ulceration, gangrene, or both), or both. We compared the effectiveness of a vein bypass first with a best endovascular treatment first revascularisation strategy in terms of preventing major amputation and death in patients with chronic limb threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. METHODS: Bypass versus Angioplasty for Severe Ischaemia of the Leg (BASIL)-2 was an open-label, pragmatic, multicentre, phase 3, randomised trial done at 41 vascular surgery units in the UK (n=39), Sweden (n=1), and Denmark (n=1). Eligible patients were those who presented to hospital-based vascular surgery units with chronic limb-threatening ischaemia due to atherosclerotic disease and who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion. Participants were randomly assigned (1:1) to receive either vein bypass (vein bypass group) or best endovascular treatment (best endovascular treatment group) as their first revascularisation procedure through a secure online randomisation system. Participants were excluded if they had ischaemic pain or tissue loss considered not to be primarily due to atherosclerotic peripheral artery disease. Most vein bypasses used the great saphenous vein and originated from the common or superficial femoral arteries. Most endovascular interventions comprised plain balloon angioplasty with selective use of plain or drug eluting stents. Participants were followed up for a minimum of 2 years. Data were collected locally at participating centres. In England, Wales, and Sweden, centralised databases were used to collect information on amputations and deaths. Data were analysed centrally at the Birmingham Clinical Trials Unit. The primary outcome was amputation-free survival defined as time to first major (above the ankle) amputation or death from any cause measured in the intention-to-treat population. Safety was assessed by monitoring serious adverse events up to 30-days after first revascularisation. The trial is registered with the ISRCTN registry, ISRCTN27728689. FINDINGS: Between July 22, 2014, and Nov 30, 2020, 345 participants (65 [19%] women and 280 [81%] men; median age 72·5 years [62·7-79·3]) with chronic limb-threatening ischaemia were enrolled in the trial and randomly assigned: 172 (50%) to the vein bypass group and 173 (50%) to the best endovascular treatment group. Major amputation or death occurred in 108 (63%) of 172 patients in the vein bypass group and 92 (53%) of 173 patients in the best endovascular treatment group (adjusted hazard ratio [HR] 1·35 [95% CI 1·02-1·80]; p=0·037). 91 (53%) of 172 patients in the vein bypass group and 77 (45%) of 173 patients in the best endovascular treatment group died (adjusted HR 1·37 [95% CI 1·00-1·87]). In both groups the most common causes of morbidity and death, including that occurring within 30 days of their first revascularisation, were cardiovascular (61 deaths in the vein bypass group and 49 in the best endovascular treatment group) and respiratory events (25 deaths in the vein bypass group and 23 in the best endovascular treatment group; number of cardiovascular and respiratory deaths were not mutually exclusive). INTERPRETATION: In the BASIL-2 trial, a best endovascular treatment first revascularisation strategy was associated with a better amputation-free survival, which was largely driven by fewer deaths in the best endovascular treatment group. These data suggest that more patients with chronic limb-threatening ischaemia who required an infra-popliteal, with or without an additional more proximal infra-inguinal, revascularisation procedure to restore limb perfusion should be considered for a best endovascular treatment first revascularisation strategy. FUNDING: UK National Institute of Health Research Health Technology Programme.

ELCA-Tripsy: Combination of Laser and Lithotripsy for Severely Calcified Lesions.

Rotational atherectomy (RA) and intravascular lithotripsy (IVL) are complementary calcium-debulking techniques. RA ablates intimal calcium and makes a channel that permits crossing of the Shockwave balloon, which cannot be easily delivered through severe lesions. Shockwave IVL completes lesion preparation, cracking deep calcium. When RA is discouraged, excimer-laser coronary angioplasty (ELCA) in combination with IVL (ELCA-Tripsy) may be useful, as ELCA facilitates Shockwave balloon delivery without impairment of recently implanted stents. To the best of our knowledge, this is the first description of this technique.

Immunomodulation of IL-33 and IL-37 with Vitamin D in the Neointima of Coronary Artery: A Comparative Study between Balloon Angioplasty and Stent in Hyperlipidemic Microswine.

Inflammation is a major contributor to the development and progression of atherosclerosis. Interleukin (IL)-33 and IL-37, members of the IL-1 family, modulate inflammation, with IL-33 having a pro-inflammatory effect and IL-37 having anti-inflammatory properties. IL-37 is constitutively expressed at low levels but upregulated in inflammatory contexts. The aim of this study was to evaluate the effect of vitamin D on the expression of IL-33, IL-37, macrophages, and caspase-1 in the neointimal tissue of coronary artery in Yucatan microswine with vitamin D deficient, sufficient, and supplemented status. The intimal injury was induced by balloon angioplasty and stenting in the coronary artery, and tissues were harvested after 6 months. The expression of various proteins of interest was evaluated by immunostaining. Increased expression of IL-33 and IL-37 in the neointimal tissue of the vitamin D deficient, as compared to the sufficient and supplemented microswine, as revealed by histological evaluation and semi-quantitative analysis, suggested the immunomodulatory effect of vitamin D on the expression of IL-33 and IL-37. The minimal expression or absence of IL-33 and IL-37 expression in stented arteries is suggestive of an attenuated inflammatory response in stented arteries, compared to balloon angioplasty. The decreased IL-33 expression in the sufficient and supplemented microswine could be a potential mechanism for controlling the inflammatory process and neointima formation leading to attenuated luminal narrowing of the coronary artery. Overall, these results support supplementation of vitamin D to attenuate inflammation, neointima formation, and restenosis.

The Effect of Foot Reflexology Applied Before Coronary Angiography and Percutaneous Transluminal Coronary Angioplasty on Anxiety, Stress, and Cortisol Levels of Individuals: A Randomized Controlled Trial.

BACKGROUND: Coronary angiography and percutaneous transluminal coronary angioplasty procedures cause anxiety and stress in individuals. OBJECTIVE: The aim of this study was to determine the effect of foot reflexology applied before coronary angiography and percutaneous transluminal coronary angioplasty on the anxiety, stress, and cortisol levels of individuals. METHODS: A simple randomized trial design was used. The patients who met the inclusion criteria were divided into 4 groups including experimental and control groups of coronary angiography patients (30 patients in each group) and percutaneous transluminal coronary angioplasty (26 patients in each group) by randomization method. Data were collected with the State-Trait Anxiety Inventory and Distress Thermometer 90 minutes before coronary angiography and percutaneous transluminal coronary angioplasty and the laboratory samples were taken. After these procedures, foot reflexology was applied to both feet of the patients in the experimental group for 30 minutes, and the control group received only standard care. The inventories were reapplied 30 minutes after the reflexology application and after coronary angiography and percutaneous transluminal coronary angioplasty. RESULTS: Whereas there was no statistically significant difference (P > .05) between the coronary angiography and percutaneous transluminal coronary angioplasty experimental and control groups in Anxiety Inventory and stress median scores before reflexology, a significant difference was found (P < .001) 30 minutes after reflexology application and after coronary angiography and percutaneous transluminal coronary angioplasty. After the reflexology, anxiety and stress scores were significantly lower in the experimental group compared with the control group (P < .001). Whereas there was a significant difference (P < .001) in the within-group cortisol values of both reflexology groups, no significant difference was found in the control groups (P > .05). CONCLUSIONS: The application of reflexology before coronary angiography and percutaneous transluminal coronary angioplasty reduces the levels of anxiety, stress, and cortisol without any side effects.

A randomized comparison of a novel iopromide-based paclitaxel-coated balloon Shenqi versus SeQuent Please for the treatment of in-stent restenosis.

BACKGROUND: Treatment of coronary in-stent restenosis (ISR) remains challenging in contemporary clinical applications. Drug-coated balloon (DCB) angioplasty offers an effective treatment for ISR. Shenqi is a novel iopromide-based paclitaxel-coated balloon and its clinical safety, effectiveness and angiographic efficacy in patients with ISR have not been investigated. METHODS: A total of 216 subjects with the first occurrence of ISR at 11 investigational sites in China were randomly allocated in a 1:1 fashion to treatment with DCB SeQuent Please or Shenqi. Clinical follow-up was planned at 1, 6, 9 and 12 months, and angiographic follow-up was planned at 9 months. The study was powered for the primary endpoint of 9-month in-segment late loss. RESULTS: At 9-month follow-up, the in-segment late loss was 0.29 ± 0.43 mm with Shenqi versus 0.30 ± 0.46 mm with SeQuent Please, and the one-sided 97.5% upper confidence limit of the difference was 0.14 mm, achieving noninferiority of Shenqi compared with SeQuent Please (P = 0.002). In total, 12 patients developed target lesion failure (TLF) in the Shenqi group compared with 16 patients in the SeQuent Please group (10.91% versus 15.09%; P = 0.42) within 1 year. TLF was mainly driven by target lesion revascularization (9.09%) followed by target vessel-related myocardial infarction (1.82%) and cardiovascular death (0.91%) in the Shenqi group. CONCLUSIONS: Shenqi DCB was noninferior to SeQuent Please DCB for the primary endpoint of 9-month in-segment late loss. Shenqi DCB may become an attractive alternative treatment for patients with coronary ISR, withholding the need for additional stent implantation.

Efficacy and safety of balloon-assisted microdissection with Sapphire® II 1.0-mm balloon in balloon-uncrossable chronic total occlusion lesions.

OBJECTIVE: Earlier studies have shown that the balloon-assisted microdissection (BAM) technique is feasible using a 1.2- to 1.5-mm small balloon in balloon-uncrossable chronic total occlusion (CTO) lesions. This study was performed to assess the efficacy and safety of the BAM technique with a Sapphire® II 1.0-mm balloon. METHODS: In this retrospective study, patients undergoing percutaneous coronary intervention for CTO were consecutively screened for balloon-uncrossable CTO lesions using BAM with the Sapphire® II 1.0-mm balloon. The patients' clinical and angiographic characteristics and procedural outcomes were collected for analyses. RESULTS: Twenty-four balloon-uncrossable CTO lesions were identified. Most of the CTO lesions were located in the right coronary artery, followed by the left anterior descending artery and left circumflex artery. The mean Japanese Multicenter CTO Registry (J-CTO) and Prospective Global Registry for the Study of Chronic Total Occlusion Intervention (PROGRESS CTO) scores were 1.96 and 1.38, respectively. The total technical success rates were 91.6% (22/24) and 75.00% (18/24) for the lesions that were successfully treated with BAM. No patients developed major complications with the exception of one patient who developed a femoral hematoma. CONCLUSION: BAM with the Sapphire® II 1.0-mm balloon may be an effective and safe technique for balloon-uncrossable CTO lesions.

[Partnership development between two hospitals: the integration process of Interventional Cardiology Units between the San Luigi Gonzaga University Hospital and the Local Health Unit Torino 3]. / Lo sviluppo di una partnership tra Aziende Sanitarie: l'integrazione dei laboratori di Emodinamica tra l'Azienda Ospedaliera Universitaria San Luigi Gonzaga di Orbassano e l'Azienda Sanitaria Locale Torino 3.

BACKGROUND: The healthcare sector is among the most complex ones where partnerships and interdependencies between different hospitals can achieve real technical and managerial operational models aimed at optimizing resources. However, the construction of this type of interdependence is not simple to implement, making it necessary to integrate at different organizational and professional levels. The aim of this work is to present the integration process and results achieved during the first 3 years of experience after a synergic integration of the interventional cath lab units of the San Luigi Gonzaga University Hospital, Orbassano and the Infermi Hospital Local Health Unit TO 3, Rivoli. METHODS: Starting from March 2016, data concerning number and type of procedures as well as the distribution of workloads of each operator in the two cath labs were recorded and monitored. Moreover, numbers of urgent procedures performed as well as the door-to-balloon time in case of primary angioplasty were recorded. RESULTS: Compared to the first 12 months of non-integrated activity, the number of procedures remained constant with an overall trend of activity increase (total procedures: +2.6% from 2016 to 2017; +8.7% from 2017 to 2018). No statistically significant differences were found in the average door-to-balloon time, either by stratifying by period (year 2015 vs 2016 vs 2017 vs 2017 vs 2018) or by single institution. All ST-elevation myocardial infarctions were treated at the arrival site, displacing the medical availability team. The mortality rate and the number of complications were not different compared to the trend recorded in previous years. The implementation of joint programs with an exchange of expertise between operators has allowed the rapid development of skills necessary for the execution of structural heart procedures not previously performed in one of the operating centers. CONCLUSIONS: The model of an integrated cath lab unit represents an example of a partnership between two hospitals, which allows a synergistic growth of professional skills, even facing daily logistical challenges. The integration has made it possible to expand the number and type of procedures performed as well to join the on-call equipe without impacting on the door-to-balloon time in case of primary coronary angioplasty.

Carbon monoxide poisoning can act as a stress test to reveal underlying coronary artery disease: case report.

Carbon monoxide (CO) poisoning presents with many different cardiac effects, but one important presentation is its effect as a CO stress test to reveal underlying coronary artery disease (CAD). There are a limited number of publications detailing this phenomenon, but after CO intoxication it is important to suspect CAD in association with mild troponin leak or non-ST segment elevation myocardial infarction (NSTEMI) shown on electrocardiogram (EKG). We recently treated three patients with CO poisoning who had underlying CAD. In the first case a man presented to the emergency department with CO toxicity and an ST segment elevation myocardial infarction (STEMI), resulting in emergent angioplasty and the discovery of severe CAD. The second case involved an individual who presented with CO poisoning with rising troponin levels. An angioplasty discovered a stable 90% occlusion. The third case was a patient with CO poisoning and transient inferior T wave inversion EKG with borderline troponin elevation. Angioplasty showed only 30% occlusion, so the patient's presentation was likely due to direct CO cardiac toxicity. These cases demonstrate the varied presentations that CO poisoning can have on patients with underlying heart disease.

Stent underexpansion due to heavy coronary calcification resistant to rotational atherectomy: A case for coronary lithoplasty?

Stent underexpansion is frequently observed in calcified coronary lesions and increases the risk of future adverse cardiac events. Current plaquemodification techniques might not be suitable when calcium deposition is circumferential and deep inside the vessel wall. We report a case during which coronary lithoplasty was used as an adjuvant therapy to improve severe stent underexpansion after failed atherectomy and high-pressure non-compliant balloon dilatations.

An Overview of the Cardiac Catheterization Lab.

The role of the cardiac catheterization lab technologist differs from other radiologic technologist roles. This article demystifies the cardiac catheterization lab by explaining commonly performed procedures. The anatomy and pathology that might require treatment in the catheterization lab also are discussed.

Modulation of Cathepsin L Expression in the Coronary Arteries of Atherosclerotic Swine.

INTRODUCTION: Neointimal hyperplasia (NIH) and restenosis after percutaneous transluminal coronary angioplasty (PTCA) and intravascular stenting remain a problem on a long-term basis by causing endothelial denudation and damage to the intima and media. Vascular sterile inflammation has been attributed to the formation of NIH. Cathepsin L (CTSL), a lysosome protease, is associated with diet-induced atherogenesis. Vitamin D regulates the actions and regulatory effects of proteases and protease inhibitors in different cell types. Objectives of this study are to evaluate the modulatory effect of vitamin D on CTSL activity in post-PTCA coronary arteries of atherosclerotic swine. METHODS: Yucatan microswine were fed with high-cholesterol atherosclerotic diets. The swine were stratified to receive three diets: (1) vitamin D-deficient diet, (2) vitamin D-sufficient diet, and (3) vitamin D-supplement diet. After 6 mo, PTCA was performed in the left circumflex coronary artery (LCx). After 1 y, angiography and optical coherence tomography imaging were performed, and swine was euthanized. Coronary arteries were embedded in paraffin. Tissue sections were stained with hematoxylin and eosin. Expression of Ki67 and CTSL were evaluated by immunofluorescence. RESULTS: Increased number of Ki67 + cells were observed in the postangioplasty LCx in vitamin D-deficient compared with vitamin D-sufficient or vitamin D-supplemented swine. Notably, the expression of CTSL was significantly increased in postangioplasty LCx of vitamin D-deficient swine compared with the vitamin D-sufficient or vitamin D-supplemented animal groups. CONCLUSIONS: Increased expression of CTSL correlates with the formation of NIH in the PTCA-injured coronary arteries. However, in the presence of sufficient or supplemented levels of vitamin D in the blood, CTSL expression was significantly reduced.

Low-Level Tragus Stimulation for the Treatment of Ischemia and Reperfusion Injury in Patients With ST-Segment Elevation Myocardial Infarction: A Proof-of-Concept Study.

OBJECTIVES: The aim of this study was to investigate whether low-level tragus stimulation (LL-TS) treatment could reduce myocardial ischemia-reperfusion injury in patients with ST-segment elevation myocardial infarction (STEMI). BACKGROUND: The authors' previous studies suggested that LL-TS could reduce the size of myocardial injury induced by ischemia. METHODS: Patients who presented with STEMI within 12 h of symptom onset, treated with primary percutaneous coronary intervention, were randomized to the LL-TS group (n = 47) or the control group (with sham stimulation [n = 48]). LL-TS, 50% lower than the electric current that slowed the sinus rate, was delivered to the right tragus once the patients arrived in the catheterization room and lasted for 2 h after balloon dilatation (reperfusion). All patients were followed for 7 days. The occurrence of reperfusion-related arrhythmia, blood levels of creatine kinase-MB, myoglobin, N-terminal pro-B-type natriuretic peptide and inflammatory markers, and echocardiographic characteristics were evaluated. RESULTS: The incidence of reperfusion-related ventricular arrhythmia during the first 24 h was significantly attenuated by LL-TS. In addition, the area under the curve for creatine kinase-MB and myoglobin over 72 h was smaller in the LL-TS group than the control group. Furthermore, blood levels of inflammatory markers were decreased by LL-TS. Cardiac function, as demonstrated by the level of N-terminal pro-B-type natriuretic peptide, the left ventricular ejection fraction, and the wall motion index, was markedly improved by LL-TS. CONCLUSIONS: LL-TS reduces myocardial ischemia-reperfusion injury in patients with STEMI. This proof-of-concept study raises the possibility that this noninvasive strategy may be used to treat patients with STEMI undergoing primary percutaneous coronary intervention.

[New oral anticoagulants in coronary artery disease]. / Les anticoagulants oraux directs dans la maladie coronaire.

Antiplatelet therapy is essential for the prevention of recurrent cardiovascular events in stable and unstable coronary artery disease. Oral anticoagulants have been rarely used for treatment of coronary artery disease. The new direct oral anticoagulants offer various molecules and dosages and may be used in coronary artery disease. Dedicated studies are currently being conducted to confirm the optimal doses and the ideal association of antithrombotic drugs in different settings of coronary artery disease.

Impact of around-the-clock in-house cardiology fellow coverage on door-to-balloon time in an academic medical center.

OBJECTIVES: To assess if a change in our cardiology fellowship program impacted our ST elevation myocardial infarction (STEMI) program. BACKGROUND: Fellows covering the cardiac care unit were spending excessive hours in the hospital while on call, resulting in increased duty hours violations. A night float fellow system was started on July 1, 2012, allowing the cardiac care unit fellow to sign out to a night float fellow at 5:30 pm. The night float fellow remained in-house until the morning. METHODS: We performed a retrospective study assessing symptom onset to arrival, arterial access to first device, and door-to-balloon (D2B) times, in consecutive STEMI patients presenting to our emergency department before and after initiation of the night float fellow system. RESULTS: From 2009 to 2013, 208 STEMI patients presented to our emergency department and underwent primary percutaneous coronary intervention. There was no difference in symptom onset to arrival (150±102 minutes vs 154±122 minutes, p=0.758), arterial access to first device (12±8 minutes vs 11±7 minutes, p=0.230), or D2B times (50±32 minutes vs 52±34 minutes, p=0.681) during regular working hours. However, there was a significant decrease in D2B times seen during off-hours (72±33 minutes vs 49±15 minutes, p=0.007). There was no difference in in-hospital mortality (11% vs 8%, p=0.484) or need for intra-aortic balloon pump placement (7% vs 8%, p=0.793). CONCLUSION: In academic medical centers, in-house cardiology fellow coverage during off-hours may expedite care of STEMI patients.

Timely Reperfusion in Stroke and Myocardial Infarction Is Not Correlated: An Opportunity for Better Coordination of Acute Care.

BACKGROUND: Timely reperfusion is critical in acute ischemic stroke (AIS) and ST-segment-elevation myocardial infarction (STEMI). The degree to which hospital performance is correlated on emergent STEMI and AIS care is unknown. Primary objective of this study was to determine whether there was a positive correlation between hospital performance on door-to-balloon (D2B) time for STEMI and door-to-needle (DTN) time for AIS, with and without controlling for patient and hospital differences. METHODS AND RESULTS: Prospective study of all hospitals in both Get With The Guidelines-Stroke and Get With The Guidelines-Coronary Artery Disease from 2006 to 2009 and treating ≥10 patients. We compared hospital-level DTN time and D2B time using Spearman rank correlation coefficients and hierarchical linear regression modeling. There were 43 hospitals with 1976 AIS and 59 823 STEMI patients. Hospitals' DTN times for AIS did not correlate with D2B times for STEMI (ρ=-0.09; P=0.55). There was no correlation between hospitals' proportion of eligible patients treated within target time windows for AIS and STEMI (median DTN time <60 minutes: 21% [interquartile range, 11-30]; median D2B time <90 minutes: 68% [interquartile range, 62-79]; ρ=-0.14; P=0.36). The lack of correlation between hospitals' DTN and D2B times persisted after risk adjustment. We also correlated hospitals' DTN time and D2B time data from 2013 to 2014 using Get With The Guidelines (DTN time) and Hospital Compare (D2B time). From 2013 to 2014, hospitals' DTN time performance in Get With The Guidelines was not correlated with D2B time performance in Hospital Compare (n=546 hospitals). CONCLUSIONS: We found no correlation between hospitals' observed or risk-adjusted DTN and D2B times. Opportunities exist to improve hospitals' performance of time-critical care processes for AIS and STEMI in a coordinated approach.

Vitamin C supplementation for the primary prevention of cardiovascular disease.

BACKGROUND: Vitamin C is an essential micronutrient and powerful antioxidant. Observational studies have shown an inverse relationship between vitamin C intake and major cardiovascular events and cardiovascular disease (CVD) risk factors. Results from clinical trials are less consistent. OBJECTIVES: To determine the effectiveness of vitamin C supplementation as a single supplement for the primary prevention of CVD. SEARCH METHODS: We searched the following electronic databases on 11 May 2016: the Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library; MEDLINE (Ovid); Embase Classic and Embase (Ovid); Web of Science Core Collection (Thomson Reuters); Database of Abstracts of Reviews of Effects (DARE); Health Technology Assessment Database and Health Economics Evaluations Database in the Cochrane Library. We searched trial registers on 13 April 2016 and reference lists of reviews for further studies. We applied no language restrictions. SELECTION CRITERIA: Randomised controlled trials of vitamin C supplementation as a single nutrient supplement lasting at least three months and involving healthy adults or adults at moderate and high risk of CVD were included. The comparison group was no intervention or placebo. The outcomes of interest were CVD clinical events and CVD risk factors. DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials for inclusion, abstracted the data and assessed the risk of bias. MAIN RESULTS: We included eight trials with 15,445 participants randomised. The largest trial with 14,641 participants provided data on our primary outcomes. Seven trials reported on CVD risk factors. Three of the eight trials were regarded at high risk of bias for either reporting or attrition bias, most of the 'Risk of bias' domains for the remaining trials were judged as unclear, with the exception of the largest trial where most domains were judged to be at low risk of bias.The composite endpoint, major CVD events was not different between the vitamin C and placebo group (hazard ratio (HR) 0.99, 95% confidence interval (CI) 0.89 to 1.10; 1 study; 14,641 participants; low-quality evidence) in the Physicians Health Study II over eight years of follow-up. Similar results were obtained for all-cause mortality HR 1.07, 95% CI 0.97 to 1.18; 1 study; 14,641 participants; very low-quality evidence, total myocardial infarction (MI) (fatal and non-fatal) HR 1.04 (95% CI 0.87 to 1.24); 1 study; 14,641 participants; low-quality evidence, total stroke (fatal and non-fatal) HR 0.89 (95% CI 0.74 to 1.07); 1 study; 14,641 participants; low-quality evidence, CVD mortality HR 1.02 (95% 0.85 to 1.22); 1 study; 14,641 participants; very low-quality evidence, self-reported coronary artery bypass grafting (CABG)/percutaneous transluminal coronary angioplasty (PTCA) HR 0.96 (95% CI 0.86 to 1.07); 1 study; 14,641 participants; low-quality evidence, self-reported angina HR 0.93 (95% CI 0.84 to 1.03); 1 study; 14,641 participants; low-quality evidence.The evidence for the majority of primary outcomes was downgraded (low quality) because of indirectness and imprecision. For all-cause mortality and CVD mortality, the evidence was very low because more factors affected the directness of the evidence and because of inconsistency.Four studies did not state sources of funding, two studies declared non-commercial funding and two studies declared both commercial and non-commercial funding. AUTHORS' CONCLUSIONS: Currently, there is no evidence to suggest that vitamin C supplementation reduces the risk of CVD in healthy participants and those at increased risk of CVD, but current evidence is limited to one trial of middle-aged and older male physicians from the USA. There is limited low- and very low-quality evidence currently on the effect of vitamin C supplementation and risk of CVD risk factors.

Evaluation of Geographic Indices Describing Health Care Utilization.

OBJECTIVES: The accurate measurement of geographic patterns of health care utilization is a prerequisite for the study of geographic variations in health care utilization. While several measures have been developed to measure how accurately geographic units reflect the health care utilization patterns of residents, they have been only applied to hospitalization and need further evaluation. This study aimed to evaluate geographic indices describing health care utilization. METHODS: We measured the utilization rate and four health care utilization indices (localization index, outflow index, inflow index, and net patient flow) for eight major procedures (coronary artery bypass graft surgery, percutaneous transluminal coronary angioplasty, surgery after hip fracture, knee replacement surgery, caesarean sections, hysterectomy, computed tomography scans, and magnetic resonance imaging scans) according to three levels of geographic units in Korea. Data were obtained from the National Health Insurance database in Korea. We evaluated the associations among the health care utilization indices and the utilization rates. RESULTS: In higher-level geographic units, the localization index tended to be high, while the inflow index and outflow index were lower. The indices showed different patterns depending on the procedure. A strong negative correlation between the localization index and the outflow index was observed for all procedures. Net patient flow showed a moderate positive correlation with the localization index and the inflow index. CONCLUSIONS: Health care utilization indices can be used as a proxy to describe the utilization pattern of a procedure in a geographic unit.