Introduction The prevalence of frailty at population level is unclear. We examined this in population-based studies, investigating sources of heterogeneity. Methods PubMed, Embase, CINAHL and Cochrane Library databases were searched for observational population-level studies published between 1 January 1998 and 1 April 2020, including individuals aged ≥50 years, identified using any frailty measure. Prevalence estimates were extracted independently, assessed for bias and analysed using a random-effects model. Results In total, 240 studies reporting 265 prevalence proportions from 62 countries and territories, representing 1,755,497 participants, were included. Pooled prevalence in studies using physical frailty measures was 12% (95% CI = 11–13%; n = 178), compared with 24% (95% CI = 22–26%; n = 71) for the deficit accumulation model (those using a frailty index, FI). For pre-frailty, this was 46% (95% CI = 45–48%; n = 147) and 49% (95% CI = 46–52%; n = 29), respectively. For physical frailty, the prevalence was higher among females, 15% (95% CI = 14–17%; n = 142), than males, 11% (95% CI = 10–12%; n = 144). For studies using a FI, the prevalence was also higher in females, 29% (95% CI = 24–35%; n = 34) versus 20% (95% CI = 16–24%; n = 34), for males. These values were similar for pre-frailty. Prevalence increased according to the minimum age at study inclusion. Analysing only data from nationally representative studies gave a frailty prevalence of 7% (95% CI = 5–9%; n = 46) for physical frailty and 24% (95% CI = 22–26%; n = 44) for FIs. Conclusions Population-level frailty prevalence varied by classification and sex. Data were heterogenous and limited, particularly from nationally representative studies making the interpretation of differences by geographic region challenging. Common methodological approaches to gathering data are required to improve the accuracy of population-level prevalence estimates. Protocol registration PROSPERO-CRD42018105431.

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The therapeutic potential of mesenchymal stem cell (MSC) transplantation for the treatment of ischemic conditions such as coronary artery disease, peripheral arterial disease, and stroke has been explored in animal models and early-phase clinical trials. A substantial database documents the safety profile of MSC administration to humans in a large number of disease states. The mechanism of the therapeutic effect of MSC transplantation in ischemic disease has been postulated to be due to paracrine, immunomodulatory, and differentiation effects. This review provides an overview of the potential role of MSC-based therapy for critical limb ischemia (CLI), the comparison of MSC cellular therapy with angiogenesis gene therapy in CLI, and the proposed mechanism of action of MSC therapy. Preclinical efficacy data in animal models of hindlimb ischemia, current early-phase human trial data, and considerations for future MSC-based therapy in CLI will also be discussed.

COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.

Increasing pressure on limited healthcare resources has necessitated the development of measures promoting early discharge and avoiding inappropriate hospital (re)admission. This systematic review examines the evidence for interventions in acute hospitals including (i) hospital-patient discharge to home, community services or other settings, (ii) hospital discharge to another care setting, and (iii) reduction or prevention of inappropriate hospital (re)admissions. Academic electronic databases were searched from 2005 to 2018. In total, ninety-four eligible papers were included. Interventions were categorized into: (1) pre-discharge exclusively delivered in the acute care hospital, (2) pre- and post-discharge delivered by acute care hospital, (3) post-discharge delivered at home and (4) delivered only in a post-acute facility. Mixed results were found regarding the effectiveness of many types of interventions. Interventions exclusively delivered in the acute hospital pre-discharge and those involving education were most common but their effectiveness was limited in avoiding (re)admission. Successful pre- and post-discharge interventions focused on multidisciplinary approaches. Post-discharge interventions exclusively delivered at home reduced hospital stay and contributed to patient satisfaction. Existing systematic reviews on tele-health and long-term care interventions suggest insufficient evidence for admission avoidance. The most effective interventions to avoid inappropriate re-admission to hospital and promote early discharge included integrated systems between hospital and the community care, multidisciplinary service provision, individualization of services, discharge planning initiated in hospital and specialist follow-up.

Endothelial progenitor cells (EPCs) may be defined as adherent cells derived from peripheral blood- or bone marrow-derived mononuclear cells demonstrating acLDL uptake and isolectin-binding capacity. The number of circulating EPCs inversely correlates with the number of cardiovascular risk factors and is reduced in cardiovascular disease. This measurement may therefore serves as a surrogate marker for cardiovascular disease risk. EPC numbers can be modified by various means. However, the effectiveness of risk-factor modification on EPC number and function is currently unknown. Furthermore, EPCs may be used as a potential therapy for a variety of vascular disease states including ischaemia, restenosis and pulmonary hypertension. This review provides an update on multiple factors that affect EPC number as well as highlighting the potential use of EPCs as a novel marker of vascular dysfunction. Furthermore, potential gene- and/or EPC-based approaches to a number of vascular disease states are explored.

Since the discovery of Endothelial Progenitor Cells (EPC) by Asahara and colleagues in 1997, an increasing number of preclinical studies have shown that EPC based therapy is feasible, safe, and efficacious in multiple disease states. Subsequently, this has led to several, mainly early phase, clinical trials demonstrating the feasibility and safety profile of EPC therapy, with the suggestion of efficacy in several conditions including ischemic heart disease, pulmonary arterial hypertension and decompensated liver cirrhosis. Despite the use of the common term “EPC,” the characteristics, manufacturing methods and subset of the cell type used in these studies often vary significantly, rendering clinical translation challenging. It has recently been acknowledged that the true EPC is the endothelial colony forming cells (ECFC). The objective of this review was to summarize and critically appraise the registered and published clinical studies using the term “EPC,” which encompasses a heterogeneous cell population, as a therapeutic agent. Furthermore, the preclinical data using ECFC from the PubMed and Web of Science databases were searched and analyzed. We noted that despite the promising effect of ECFC on vascular regeneration, no clinical study has stemmed from these preclinical studies. We showed that there is a lack of information registered on www.clinicaltrials.gov for EPC clinical trials, specifically on cell culture methods. We also highlighted the importance of a detailed definition of the cell type used in EPC clinical trials to facilitate comparisons between trials and better understanding of the potential clinical benefit of EPC based therapy. We concluded our review by discussing the potential and limitations of EPC based therapy in clinical settings.

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