A RAND/UCLA-Modified VAS Study on Telemedicine, Telehealth, and Virtual Care in Daily Clinical Practice of Vascular Medicine.

Background: Telemedicine is increasingly used in several fields of healthcare, including vascular medicine. This study aimed to investigate the views of experts and propose clinical practice recommendations on the possible applications of telemedicine in vascular medicine. Methods: A clinical guidance group proposed a set of 67 clinical practice recommendations based on the synthesis of current evidence and expert opinion. The Telemedicine Vascular Medicine Working Group included 32 experts from Europe evaluating the appropriateness of each clinical practice recommendation based on published RAND/UCLA methodology in two rounds. Results: In the first round, 60.9% of clinical practice recommendations were rated as appropriate, 35.9% as uncertain, and 3.1% as inappropriate. The strongest agreement (a median value of 10) was reached on statements regarding the usefulness of telemedicine during the 2019 coronavirus disease (COVID-19) pandemic, its usefulness for geographical areas that are difficult to access, and the superiority of video calls compared to phone calls only. The lowest degree of agreement (a median value of 2) was reported on statements regarding the utility of telemedicine being limited to the COVID-19 pandemic and regarding the applicability of teleconsultation in the diagnosis and management of abdominal aortic aneurysm. In the second round, 11 statements were re-evaluated to reduce variability. Conclusions: This study highlights the levels of agreement and the points that raise concern on the use of telemedicine in vascular medicine. It emphasizes the need for further clarification on various issues, including infrastructure, logistics, and legislation.

Comparing frailty prevalence between countries: validation of the Global Burden of Disease study Frailty Index (GBD-FI) in the survey of health, ageing and retirement in Europe.

BACKGROUND: Accurate comparable prevalence proportions are required to better understand the epidemiology of frailty. Estimates in many countries are missing or incomparable. The Global Burden of Disease Frailty Index (GBD-FI) applies the deficit accumulation model to generate frailty scores from items available in the Global Burden of Disease study. OBJECTIVE: To externally validate the GBD-FI. METHODS: Data were obtained from the Survey of Health Ageing and Retirement in Europe (SHARE). A 20-item modified GBD-FI was compared with established frailty measures: a 70-item frailty index (FI-70), the Clinical Frailty Scale (CFS), Frailty Phenotype (FP) and SHARE-FI. Area under receiver operating characteristic curves (AUC) were fitted to examine diagnostic accuracy for frailty and predictive validity for 2-year mortality. RESULTS: In total, 31,624 participants aged ≥50 years from 15 countries were included. Frailty prevalence was 22% using the GBD-FI (ranging from 8% in Switzerland to 41% in Poland). The GBD-FI had good to excellent diagnostic accuracy for frailty, irrespective of approach; the AUC ranged from 0.86 (95% confidence interval: 0.85-0.87) measuring frailty using the CFS to 0.94 (0.93-0.94) with the FI-70. The GBD-FI had similar accuracy for 2-year mortality (AUC 0.71, 0.69-0.74) compared with the CFS (0.73; P = 0.186), FP (0.73; P = 0.392) and SHARE-FI (0.70; P = 0.255) but lower than the FI-70 (0.76; P < 0.001). CONCLUSION: The GBD-FI demonstrated concurrent and predictive validity, suggesting it is a valid measure of frailty. It has the potential to be an efficient, replicable and consistent approach to comparing frailty between countries and regions across time using GBD data.

Early Metformin in Gestational Diabetes: A Randomized Clinical Trial.

Importance: Gestational diabetes is a common complication of pregnancy and the optimal management is uncertain. Objective: To test whether early initiation of metformin reduces insulin initiation or improves fasting hyperglycemia at gestation weeks 32 or 38. Design, Setting, and Participants: Double-blind, placebo-controlled trial conducted in 2 centers in Ireland (one tertiary hospital and one smaller regional hospital). Participants were enrolled from June 2017 through September 2022 and followed up until 12 weeks' postpartum. Participants comprised 510 individuals (535 pregnancies) diagnosed with gestational diabetes based on World Health Organization 2013 criteria. Interventions: Randomized 1:1 to either placebo or metformin (maximum dose, 2500 mg) in addition to usual care. Main Outcomes And Measures: The primary outcome was a composite of insulin initiation or a fasting glucose level of 5.1 mmol/L or greater at gestation weeks 32 or 38. Results: Among 510 participants (mean age, 34.3 years), 535 pregnancies were randomized. The primary composite outcome was not significantly different between groups and occurred in 150 pregnancies (56.8%) in the metformin group and 167 pregnancies (63.7%) in the placebo group (between-group difference, -6.9% [95% CI, -15.1% to 1.4%]; relative risk, 0.89 [95% CI, 0.78-1.02]; P = .13). Of 6 prespecified secondary maternal outcomes, 3 favored the metformin group, including time to insulin initiation, self-reported capillary glycemic control, and gestational weight gain. Secondary neonatal outcomes differed by group, with smaller neonates (lower mean birth weights, a lower proportion weighing >4 kg, a lower proportion in the >90% percentile, and smaller crown-heel length) in the metformin group without differences in neonatal intensive care needs, respiratory distress requiring respiratory support, jaundice requiring phototherapy, major congenital anomalies, neonatal hypoglycemia, or proportion with 5-minute Apgar scores less than 7. Conclusion and relevance: Early treatment with metformin was not superior to placebo for the composite primary outcome. Prespecified secondary outcome data support further investigation of metformin in larger clinical trials. Trial Registration: ClinicalTrials.gov Identifier: NCT02980276; EudraCT: 2016-001644-19.

No More Venous Ulcers-What More Can We Do?

Venous leg ulcers (VLUs) are the most severe complication caused by the progression of chronic venous insufficiency. They account for approximately 70-90% of all chronic leg ulcers (CLUs). A total of 1% of the Western population will suffer at some time in their lives from a VLU. Furthermore, most CLUs are VLUs, defined as chronic leg wounds that show no tendency to heal after three months of appropriate treatment or are still not fully healed at 12 months. The essential feature of VLUs is their recurrence. VLUs also significantly impact quality of life and could cause social isolation and depression. They also have a significant avoidable economic burden. It is estimated that the treatment of venous ulceration accounts for around 3% of the total expenditure on healthcare. A VLU-free world is a highly desirable aim but could be challenging to achieve with the current knowledge of the pathophysiology and diagnostic and therapeutical protocols. To decrease the incidence of VLUs, the long-term goal must be to identify high-risk patients at an early stage of chronic venous disease and initiate appropriate preventive measures. This review discusses the epidemiology, socioeconomic burden, pathophysiology, diagnosis, modes of conservative and invasive treatment, and prevention of VLUs.

Statistical techniques used in analysing simultaneous continuous glucose monitoring and ambulatory electrocardiography in patients with diabetes: A systematic review.

OBJECTIVES: There has been a steady increase in the number of studies of the complex relationship between glucose and electrical cardiac activity which use simultaneous continuous glucose monitors (CGM) and continuous electrocardiogram (ECG). However, data collected on the same individual tend to be similar (yielding correlated or dependent data) and require analyses that take into account that correlation. Many opt for simplified techniques such as calculating one measure from the data collected and analyse one observation per subject. These simplified methods may yield inconsistent and biased results in some instances. In this systematic review, we aim to examine the adequacy of the statistical analyses performed in such studies and make recommendations for future studies. RESEARCH QUESTIONS: What are the objectives of studies collecting simultaneous CGM and ECG data? Do methods used in analysing CGM and continuous ECG data fully optimise the data collected? DESIGN: Systematic review. DATA SOURCES: PubMed and Web of Science. METHODS: A comprehensive search of the PubMed and Web of Science databases to June 2022 was performed. Studies utilising CGM and continuous ECG simultaneously in people with diabetes were included. We extracted information about study objectives, technologies used to collect data and statistical analysis methods used for analysis. Reporting was done following PRISMA guidelines. RESULTS: Out of 118 publications screened, a total of 31 studies met the inclusion criteria. There was a diverse array of study objectives, with only two studies exploring the same exposure-outcome relationship, allowing only qualitative analysis. Only seven studies (23%) incorporated methods which fully utilised the study data using methods that yield the correct power and minimize type I error rate. The rest (77%) used analyses that summarise the data first before analysis and/or totally ignored data dependency. Of those who applied more advanced methods, one study performed both simple and correct analyses and found that ignoring data structure resulted in no association whilst controlling for repeated measures yielded a significant relationship. CONCLUSION: Most studies underutilised statistical methods suitable for analysis of dynamic continuous data, potentially attenuating their statistical power and overall conclusions. We recommend that aggregated data be used only as exploratory analysis, while primary analysis should use methods applied to the raw data such as mixed models or functional data analyses. These methods are widely available in many free, open source software applications.

Efficacy and Safety of Direct Oral Anticoagulants (DOACs) Versus Warfarin in Atrial Fibrillation Patients with Prior Stroke: a Systematic Review and Meta-analysis.

BACKGROUND: The purpose of this meta-analysis was to compare efficacy and safety of direct oral anticoagulants (DOACs) to warfarin for secondary stroke prevention among adult patients with atrial fibrillation and prior stroke. METHODS: Major repositories were screened for randomized controlled trials (RCTs), RCT subgroups, and observational studies (OBSs, divided in claims and non-claims). Occurrences of ischemic stroke or transient ischemic attack, systemic embolism, all-cause mortality, intracranial hemorrhage (ICH), and major bleeding were outcomes of interest. Hazard ratios (HRs) and their confidence intervals (95%CIs) were pooled using random-effects models for each study design. Claims studies were analyzed separately from non-claims, while RCT subgroups were grouped with OBSs (non-claims) as the randomization was broken. RESULTS: Of 8647 articles, 20 were included (one RCT, six RCT subgroups, nine claims, and four non-claims). Comparing DOACs to warfarin, pooled HRs (95%CI) were consistently in favor of DOACs although some did not reach statistical significance: for ischemic stroke, 0.84 (0.66-1.07) in claims; 0.90 (0.77-1.06) in non-claims and RCT subgroups; for systemic embolism, 0.77 (0.62-0.96) in claims; 0.86 (0.77-0.96) in non-claims and RCT subgroups; for all-cause mortality, 0.57 (0.33-0.99) in claims; 0.87 (0.79-0.96) in non-claims and RCT subgroups; for ICH, 0.72 (0.39-1.33) in claims; 0.51 (0.38-0.67) in non-claims and RCT subgroups; and for major bleeding, 0.86 (0.71-1.03) in claims; 0.90 (0.76-1.08) for non-claims and RCT subgroups. CONCLUSION: DOACs were associated with better efficacy and safety profiles than warfarin in atrial fibrillation patients with prior stroke, more specifically a lower risk of systemic embolism, all-cause mortality, and ICH.

Transcranial Doppler and computed tomography angiography for detecting cerebral vasospasm post-aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm is a life-threatening complication following aneurysmal subarachnoid hemorrhage (aSAH). While digital subtraction angiography (DSA) is the current gold standard for detection, the diagnostic performance of computed tomography angiography (CTA) and transcranial Doppler (TCD) remains controversial. We aimed to summarize the available evidence and provide recommendations for their use based on GRADE criteria. A literature search was conducted for studies comparing CTA or TCD to DSA for adults ≥ 18 years with aSAH for radiographic vasospasm detection. The DerSimonian-Laird random-effects model was used to pool sensitivity and specificity and their 95% confidence intervals (CI) and derive positive and negative pooled likelihood ratios (LR + /LR -). Out of 2070 studies, seven studies (1646 arterial segments) met inclusion criteria and were meta-analyzed. Compared to the gold standard (DSA), CTA had a pooled sensitivity of 82% (95%CI, 68-91%) and a specificity of 97% (95%CI, 93-98%), while TCD had lower sensitivity 38% (95%CI, 19-62%) and specificity of 91% (95%CI, 87-94%). Only the LR + for CTA (27.3) reached clinical significance to rule in diagnosis. LR - for CTA (0.19) and TCD (0.68) approached clinical significance (< 0.1) to rule out diagnosis. CTA showed higher LR + and lower LR - than TCD for diagnosing radiographic vasospasm, thereby achieving a strong recommendation for its use in ruling in or out vasospasm, based on the high quality of evidence. TCDs had very low LR + and a reasonably low LR - , thereby achieving a weak recommendation against its use in ruling in vasospasm and weak recommendation for its use in ruling out vasospasm.

Methodological considerations in injury burden of disease studies across Europe: a systematic literature review.

BACKGROUND: Calculating the disease burden due to injury is complex, as it requires many methodological choices. Until now, an overview of the methodological design choices that have been made in burden of disease (BoD) studies in injury populations is not available. The aim of this systematic literature review was to identify existing injury BoD studies undertaken across Europe and to comprehensively review the methodological design choices and assumption parameters that have been made to calculate years of life lost (YLL) and years lived with disability (YLD) in these studies. METHODS: We searched EMBASE, MEDLINE, Cochrane Central, Google Scholar, and Web of Science, and the grey literature supplemented by handsearching, for BoD studies. We included injury BoD studies that quantified the BoD expressed in YLL, YLD, and disability-adjusted life years (DALY) in countries within the European Region between early-1990 and mid-2021. RESULTS: We retrieved 2,914 results of which 48 performed an injury-specific BoD assessment. Single-country independent and Global Burden of Disease (GBD)-linked injury BoD studies were performed in 11 European countries. Approximately 79% of injury BoD studies reported the BoD by external cause-of-injury. Most independent studies used the incidence-based approach to calculate YLDs. About half of the injury disease burden studies applied disability weights (DWs) developed by the GBD study. Almost all independent injury studies have determined YLL using national life tables. CONCLUSIONS: Considerable methodological variation across independent injury BoD assessments was observed; differences were mainly apparent in the design choices and assumption parameters towards injury YLD calculations, implementation of DWs, and the choice of life table for YLL calculations. Development and use of guidelines for performing and reporting of injury BoD studies is crucial to enhance transparency and comparability of injury BoD estimates across Europe and beyond.

Marrow changes and reduced proliferative capacity of mesenchymal stromal cells from patients with "no-option" critical limb ischemia; observations on feasibility of the autologous approach from a clinical trial.

BACKGROUND AIMS: Approximately 1 in 3 patients with critical limb ischemia (CLI) are not suitable for surgical or endovascular revascularization. Those "no-option" patients are at high risk of amputation and death. Autologous bone marrow mesenchymal stromal cells (MSCs) may provide a limb salvage option. In this study, bone marrow characteristics and expansion potentials of CLI-derived MSCs produced during a phase 1b clinical trial were compared with young healthy donor MSCs to determine the feasibility of an autologous approach. Cells were produced under Good Manufacturing Practice conditions and underwent appropriate release testing. METHODS: Five bone marrow aspirates derived from patients with CLI were compared with six young healthy donor marrows in terms of number of colony-forming units-fibroblast (CFUF) and mononuclear cells. The mean population doubling times and final cell yields were used to evaluate expansion potential. The effect of increasing the volume of marrow on the CFUF count and final cell yield was evaluated by comparing 5 CLI-derived MSCs batches produced from a targeted 30 mL of marrow aspirate to five batches produced from a targeted 100 mL of marrow. RESULTS: CLI-derived marrow aspirate showed significantly lower numbers of mononuclear cells with no difference in the number of CFUFs when compared with healthy donors' marrow aspirate. CLI-derived MSCs showed a significantly longer population doubling time and reduced final cell yield compared with young healthy donors' MSCs. The poor growth kinetics of CLI MSCs were not mitigated by increasing the bone marrow aspirate from 30 to 100 mL. CONCLUSIONS: In addition to the previously reported karyotype abnormalities in MSCs isolated from patients with CLI, but not in cells from healthy donors, the feasibility of autologous transplantation of bone marrow MSCs for patients with no-option CLI is further limited by the increased expansion time and the reduced cell yield.

Thromboembolic Disease in Patients With Cancer and COVID-19: Risk Factors, Prevention and Practical Thromboprophylaxis Recommendations-State-of-the-Art.

Cancer and COVID-19 are both well-established risk factors predisposing to thrombosis. Both disease entities are correlated with increased incidence of venous thrombotic events through multifaceted pathogenic mechanisms involving the interaction of cancer cells or SARS-CoV2 on the one hand and the coagulation system and endothelial cells on the other hand. Thromboprophylaxis is recommended for hospitalized patients with active cancer and high-risk outpatients with cancer receiving anticancer treatment. Universal thromboprophylaxis with a high prophylactic dose of low molecular weight heparins (LMWH) or therapeutic dose in select patients, is currentlyindicated for hospitalized patients with COVID-19. Also, prophylactic anticoagulation is recommended for outpatients with COVID-19 at high risk for thrombosis or disease worsening. However, whether there is an additive risk of thrombosis when a patient with cancer is infected with SARS-CoV2 remains unclear In the current review, we summarize and critically discuss the literature regarding the epidemiology of thrombotic events in patients with cancer and concomitant COVID-19, the thrombotic risk assessment, and the recommendations on thromboprophylaxis for this subgroup of patients. Current data do not support an additive thrombotic risk for patients with cancer and COVID-19. Of note, patients with cancer have less access to intensive care unit care, a setting associated with high thrombotic risk. Based on current evidence, patients with cancer and COVID-19 should be assessed with well-established risk assessment models for medically ill patients and receive thromboprophylaxis, preferentially with LMWH, according to existing recommendations. Prospective trials on well-characterized populations do not exist.

Retrospective national cohort study of pregnancy outcomes for women with type 1 and type 2 diabetes mellitus in Republic of Ireland.

AIM: Report the outcomes of pregnant women with type 1 and type 2 diabetes and to identify modifiable and non-modifiable factors associated with poor outcomes. METHODS: Retrospective analysis of pregnancy preparedness, pregnancy care and outcomes in the Republic of Ireland from 2015 to 2020 and subsequent multivariate analysis. RESULTS: In total 1104 pregnancies were included. Less than one third attended pre-pregnancy care (PPC), mean first trimester haemoglobin A1c was 7.2 ± 3.6% (55.5 ± 15.7 mmol/mol) and 52% received pre-conceptual folic acid. Poor preparation translated into poorer pregnancy outcomes. Livebirth rates (80%) were comparable to the background population however stillbirth rates were 8.7/1000 (four times the national rate). Congenital anomalies occurred in 42.5/1000 births (1.5 times the background rate). More than half of infants were large for gestational age and 47% were admitted to critical care. Multivariate analyses showed strong associations between non-attendance at PPC, poor glycaemic control and critical care admission (adjusted odds ratio of 1.68 (1.48-1.96) and 1.61 (1.43-1.86), p < 0.05 respectively) for women with type 1 diabetes. Smoking and teratogenic medications were also associated with critical care admission and hypertensive disorders of pregnancy. CONCLUSION: Pregnancy outcomes in women with diabetes are suboptimal. Significant effort is needed to optimize the modifiable factors identified in this study.

An International Delphi Consensus on Diagnostic Criteria for Buerger's Disease.

BACKGROUND: Buerger's disease (BD) remains a debilitating condition. Despite multiple published diagnostic criteria for BD, none is universally accepted as a gold standard. METHODS: We conducted a 2-round modified Delphi consensus study to establish a consensus on the diagnostic. The questionnaire included statements from several commonly used diagnostic criteria for BD. Qualitative and quantitative analysis methods were performed. An agreement level of 70% was applied. RESULTS: Twenty nine experts from 18 countries participated in this study. Overall, 75 statements were circulated in Round 1. Of these, 28% of statements were accepted. Following comments, 21 statements were recirculated in Round 2 and 90% were accepted. Although more than 90% of the experts did not agree that the diagnosis of BD can be based only on clinical manifestation, none of the nonclinical manifestations of BD were agreed as a part of the diagnostic criteria. There was an agreement that a history of tobacco consumption in any form, not necessarily confined to the current use, should be a part of the diagnostic criteria of BD. The history of thrombophlebitis migrans, even if not present at presentation, was accepted as a clue for BD diagnosis. It was also agreed that discoloration of the toes or fingers could be included in the diagnostic criteria of BD. Experts agreed that histology results could differentiate BD from atherosclerosis obliterans and other types of vasculitis. The presence of corkscrew collaterals on imaging and burning pain reached the agreement at the first round but not at the second. There was no consensus regarding age cut-off, the requirement of normal lipid profile, and normal blood glucose for BD diagnosis. CONCLUSIONS: The present study demonstrated discrepancies in the various published diagnostic criteria for BD and their selective utilization in routine clinical practice worldwide. We propose that all published diagnostic criteria for BD be re-evaluated for harmonization and universal use.

The Role of MicroRNAs in Endothelial Cell Senescence.

Cellular senescence is a complex, dynamic process consisting of the irreversible arrest of growth and gradual deterioration of cellular function. Endothelial senescence affects the cell's ability to repair itself, which is essential for maintaining vascular integrity and leads to the development of endothelial dysfunction, which has an important role in the pathogenesis of cardiovascular diseases. Senescent endothelial cells develop a particular, senescence-associated secretory phenotype (SASP) that detrimentally affects both surrounding and distant endothelial cells, thereby facilitating the ageing process and development of age-related disorders. Recent studies highlight the role of endothelial senescence and its dysfunction in the pathophysiology of several age-related diseases. MicroRNAs are small noncoding RNAs that have an important role in the regulation of gene expression at the posttranscriptional level. Recently, it has been discovered that miRNAs could importantly contribute to endothelial cell senescence. Overall, the research focus has been shifting to new potential mechanisms and targets to understand and prevent the structural and functional changes in ageing senescent endothelial cells in order to prevent the development and limit the progression of the wide spectrum of age-related diseases. The aim of this review is to provide some insight into the most important pathways involved in the modulation of endothelial senescence and to reveal the specific roles of several miRNAs involved in this complex process. Better understanding of miRNA's role in endothelial senescence could lead to new approaches for prevention and possibly also for the treatment of endothelial cells ageing and associated age-related diseases.

The Diagnostic Accuracy and Clinimetric Properties of Screening Instruments to Identify Frail Older Adults Attending Emergency Departments: A Protocol for a Mixed Methods Systematic Review and Meta-Analysis.

BACKGROUND: Prompt and efficient identification and stratification of patients who are frail is important, as this cohort are at high risk of adverse healthcare outcomes. Numerous frailty screening tools have been developed to support their identification across different settings, yet relatively few have emerged for use in emergency departments (EDs). This protocol provides details for a systematic review aiming to synthesize the accumulated evidence regarding the diagnostic accuracy and clinimetric properties of frailty screening instruments to identify frail older adults in EDs. METHODS: Six electronic databases will be searched from January 2000 to March 2021. Eligible studies will include adults aged ≥60 years screened in EDs with any available screening instrument to identify frailty (even if not originally designed for this purpose). Studies, including case-control, longitudinal, and cohort studies, will be included, where instruments are compared to a reference standard to explore diagnostic accuracy. Predictive accuracy for a selection of outcomes, including mortality, institutionalization, and readmission, will be assessed. Clinical and methodological heterogeneity will be examined, and a random effects meta-analysis performed if appropriate. CONCLUSION: Understanding whether frailty screening on presentation to EDs is accurate in identifying frailty, and predicting these outcomes is important for decision-making and targeting appropriate management.

Early identification of frailty: Developing an international delphi consensus on pre-frailty.

BACKGROUND: Frailty is associated with a prodromal stage called pre-frailty, a potentially reversible and highly prevalent intermediate state before frailty becomes established. Despite being widely-used in the literature and increasingly in clinical practice, it is poorly understood. OBJECTIVE: To establish consensus on the construct and approaches to diagnose and manage pre-frailty. METHODS: We conducted a modified (electronic, two-round) Delphi consensus study. The questionnaire included statements concerning the concept, aspects and causes, types, mechanism, assessment, consequences, prevention and management of pre-frailty. Qualitative and quantitative analysis methods were employed. An agreement level of 70% was applied. RESULTS: Twenty-three experts with different backgrounds from 12 countries participated. In total, 70 statements were circulated in Round 1. Of these, 52.8% were accepted. Following comments, 51 statements were re-circulated in Round 2 and 92.1% were accepted. It was agreed that physical and non-physical factors including psychological and social capacity are involved in the development of pre-frailty, potentially adversely affecting health and health-related quality of life. Experts considered pre-frailty to be an age-associated multi-factorial, multi-dimensional, and non-linear process that does not inevitably lead to frailty. It can be reversed or attenuated by targeted interventions. Brief, feasible, and validated tools and multidimensional assessment are recommended to identify pre-frailty. CONCLUSIONS: Consensus suggests that pre-frailty lies along the frailty continuum. It is a multidimensional risk-state associated with one or more of physical impairment, cognitive decline, nutritional deficiencies and socioeconomic disadvantages, predisposing to the development of frailty. More research is needed to agree an operational definition and optimal management strategies.

Milestones in thromboangiitis obliterans: a position paper of the VAS-European independent foundation in angiology/vascular medicine.

Even today thromboangiitis obliterans has disease features that remain misunderstood or underappreciated. The epidemiology, etiology and pathophysiology of the disease are still unclear. Biomarkers and disease activity markers are lacking, thus clinical assessment is difficult. We are still struggling to establish unique diagnostic, staging and treatment criteria. This is an academic-collaborative effort to describe the pathophysiology, the clinical manifestations, the diagnostic approach, and the challenges of management of patients with TAO. A systematic search for relevant studies dating from 1900 to the end of 2020 was performed on the PubMed, SCOPUS, and Science Direct databases. Given the intriguing nature of presentation of TAO, its management, to some extent is not only different in different regions of the world but also varies within the same region. Following this project, we discovered ambiguity, overlap and lack of clear-cut criteria for management of TAO. An international group of experts however came to one conclusion. They all agree that management of TAO needs a call for action for a renewed global look with multi-center studies, to update the geographical distribution of the disease and to establish a unique set of diagnostic criteria and a consensus-based guideline for best treatment based on current evidence.

Modelling the relationship between continuously measured glucose and electrocardiographic data in adults with type 1 diabetes mellitus.

INTRODUCTION: Type 1 diabetes mellitus (T1DM) is associated with earlier onset of cardiovascular disease. Recent evidence has found hyperglycaemia appears to play a greater role in this association among T1DM compared to T2DM. This study investigates the relationship between glucose and QTc (a key cardiovascular measure) using data from continuous electrocardiogram (ECG) and glucose monitors. METHODS: Seventeen adults with T1DM were recruited at a clinical facility in Ireland. A continuous glucose monitoring system was fitted to each participant that measured glucose every 5 min for 7 days. The participants simultaneously wore a vest with sensors to measure 12-lead ECG data every 10 min for 7 days. Area under the glucose curve (AUC), proportion of time spent in hypoglycaemia and hyperglycaemia, and mean daily absolute deviation of glucose were calculated. Mixed effects ANOVA and functional regression models were fitted to the data to investigate the aggregate and time-dependent association between glucose and QTc. RESULTS: All participants were male with an average age of 52.5 (SD 3.8) years. Those with neuropathy had a significantly higher mean QTc compared to their counterparts. Mean QTc was significantly longer during hyperglycaemia. There was a significant positive association between QTc and time spent in hyperglycaemia. A negative association was found between QTc and time spent in hypoglycaemia. A functional model suggested a positive relationship between glucose and QTc at several times during the 7-day follow-up. CONCLUSION: This study used sensor technology to investigate, with high granularity, the temporal relationship between glucose and ECG data over one week. QTc was found to be longer on average during hyperglycaemia.

Thromboembolism, Bleeding, and Mortality Incidence of Direct Oral Anticoagulants Versus Warfarin Postbariatric Surgery.

BACKGROUND: There is no randomized controlled trial comparing direct oral anticoagulants (DOACs) and warfarin following bariatric surgery to date. The mortality, thromboembolism, and bleeding risk of DOACs in comparison with warfarin following bariatric surgery remains unclear. We aimed to provide a clinical comparison between DOACs and warfarin for these 3 prespecified outcomes. METHODS: A systematic literature search was performed on November 10, 2019, using PubMed, Embase, clinicaltrial.gov, and Cochrane databases. Studies with adult patients who were on either warfarin or DOACs following bariatric surgery and reported the incidence of thromboembolism, bleeding, or mortality were included. Pooled incidence for these prespecified outcomes and its 95% confidence interval (CI) were calculated for each drug separately using the random-effects model, along with a nonadjusted P value comparing the 2 subgroups. RESULTS: A total of 11 studies (805 patients) were included. Comparing DOACs to warfarin, the following pooled incidences were observed for mortality (DOACs: 3.0%; 95% CI 0.4%-18.6% versus warfarin: 1.5%; 95% CI 0.8%-2.9%; P value comparing the 2 subgroups = .38), thromboembolism (DOACs: 4.9%; 95% CI 1%-21.1% versus warfarin: 1.5%; 95% CI 0.8%-2.9%; P value = .18), and bleeding (DOACs: 3.9%; 95% CI 0.7%-18.2% versus warfarin: 11.3%; 95% CI 5.7%-21.4%; P value = .23). CONCLUSION: The results of our meta-analysis remain hypothesis-generating, providing rationale for future randomized controlled trial design or well-designed comparative observational studies. Currently, it does not support the change in the current recommendation from warfarin to DOACs following bariatric surgery.