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Background Involving peer volunteers in intervention delivery can provide social support and improve adherence. Whilst such interventions have the potential to reduce physical activity (PA) intervention costs, little is known about the process of delivering them in practice. This qualitative study explored the facilitators and challenges of delivering a peer-support PA intervention for older adults, with a view to making recommendations for the delivery of future interventions. Methods Data were collected via (7) semi-structured interviews and a focus group with stakeholders involved in a peer-support PA intervention for older adults in a large city in the North-West of England. Participants included local authority staff ( n  = 3), peer volunteers ( n  = 2) and service users ( n  = 7). Audio data were transcribed verbatim and thematically coded to identify perceived facilitators and challenges. Results Facilitators to delivery included social interaction, community referral pathways, suitable facilities, peer volunteers and high-quality instructors. Challenges surrounded inconsistent practice, staff capacity, safety and accountability, and awareness raising. Conclusions Peer volunteers can provide an additional support mechanism alongside qualified instructors for increasing social interaction within PA interventions. For optimal intervention delivery, consideration needs to be given to equipment and space, safety and accountability and consistency of practice.

Background Telemonitoring for the remote patient self-management of chronic conditions can be a cost-effective method for delivering care in chronic disease; nonetheless, its implementation in clinical practice remains low. The aim of this meta-synthesis is to explore barriers and facilitators associated with the use of remote patient monitoring of chronic disease, drawing on qualitative research, and assessing participant interactions with this technology. Method A meta-synthesis of qualitative studies was performed. MEDLINE, SCOPUS and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from database date of inception to 5 February 2021. The Critical Appraisal Skills Programme (CASP) was used to critically appraise each study. Thematic synthesis was performed to identify user (patients, carers and healthcare professionals) perspectives and experiences of patient remote monitoring of chronic disease (Type 2 diabetes mellitus, chronic obstructive pulmonary disease, and cardiovascular disease). Results Searches returned 10,401 studies and following independent screening by two reviewers, nine studies were included in this meta-synthesis. Data were synthesised and categorised into four key themes: (1) Improved care ; (2) Communication ; (3) Technology feasibility & acceptability ; and (4) Intervention concerns . Most patients using patient remote devices felt motivated in managing their own lifestyles and felt reassured by the close monitoring and increased communication. Barriers identified involved generational differences and difficulties with the technology used. Conclusion Most studies showed a positive attitude to telemonitoring, with patients preferring the convenience of telemonitoring in comparison to attending regular clinics. Further research is required to assess the most effective technology for chronic disease management, how to maintain long-term patient adherence, and identify effective approaches to address generational variation in telemonitoring up-take.

Abstract Aims To consolidate evidence to determine (i) the association between cardiovascular risk factors and health outcomes with coronavirus 2019 (COVID-19); and (ii) the impact of COVID-19 on cardiovascular health. Methods and results An umbrella review of systematic reviews was conducted. Fourteen medical databases and pre-print servers were searched from 1 January 2020 to 5 November 2020. The review focused on reviews rated as moderate or high-quality using the AMSTAR 2 tool. Eighty-four reviews were identified; 31 reviews were assessed as moderate quality and one was high-quality. The following risk factors were associated with higher mortality and severe COVID-19: renal disease [odds ratio (OR) (95% confidence interval) for mortality 3.07 (2.43–3.88)], diabetes mellitus [OR 2.09 (1.80–2.42)], hypertension [OR 2.50 (2.02–3.11)], smoking history [risk ratio (RR) 1.26 (1.20–1.32)], cerebrovascular disease [RR 2.75 (1.54–4.89)], and cardiovascular disease [OR 2.65 (1.86–3.78)]. Liver disease was associated with higher odds of mortality [OR 2.81 (1.31–6.01)], but not severe COVID-19. Current smoking was associated with a higher risk of severe COVID-19 [RR 1.80 (1.14–2.85)], but not mortality. Obesity associated with higher odds of mortality [OR 2.18 (1.10–4.34)], but there was an absence of evidence for severe COVID-19. In patients hospitalized with COVID-19, the following incident cardiovascular complications were identified: acute heart failure (2%), myocardial infarction (4%), deep vein thrombosis (7%), myocardial injury (10%), angina (10%), arrhythmias (18%), pulmonary embolism (19%), and venous thromboembolism (25%). Conclusion Many of the risk factors identified as associated with adverse outcomes with COVID-19 are potentially modifiable. Primary and secondary prevention strategies that target cardiovascular risk factors may improve outcomes for people following COVID-19.

Telemedicine is an expanding and feasible approach to improve medical care for patients with long-term conditions. However, there is a poor understanding of patients' acceptability of this technology and their rate of uptake. The aim of this study was to systematically review the current evidence on telemonitoring in the management of patients with long-term conditions and evaluate the patients' uptake and acceptability of this technology. MEDLINE, Scopus, and CENTRAL (the Cochrane Central Register of Controlled Trials) were searched from the date of inception to February 5, 2021, with no language restrictions. Studies were eligible for inclusion if they reported any of the following outcomes: intervention uptake and adherence; study retention; patient acceptability, satisfaction, and experience using the intervention; changes in physiological values; all-cause and cardiovascular-related hospitalization; all-cause and disease-specific mortality; patient-reported outcome measures; and quality of life. In total, 2 reviewers independently assessed the articles for eligibility. A total of 96 studies were included, and 58 (60%) were pooled for the meta-analyses. Meta-analyses showed a reduction in mortality (risk ratio=0.71, 95% CI 0.56-0.89; P=.003; I =0%) and improvements in blood pressure (mean difference [MD]=-3.85 mm Hg, 95% CI -7.03 to -0.68; P=.02; I =100%) and glycated hemoglobin (MD=-0.33, 95% CI -0.57 to -0.09; P=.008; I =99%) but no significant improvements in quality of life (MD=1.45, 95% CI -0.10 to 3; P=.07; I =80%) and an increased risk of hospitalization (risk ratio=1.02, 95% CI 0.85-1.23; P=.81; I =79%) with telemonitoring compared with usual care. A total of 12% (12/96) of the studies reported adherence outcomes, and 9% (9/96) reported on satisfaction and acceptance outcomes; however, heterogeneity in the assessment methods meant that a meta-analysis could not be performed. Telemonitoring is a valid alternative to usual care, reducing mortality and improving self-management of the disease, with patients reporting good satisfaction and adherence. Further studies are required to address some potential concerns regarding higher hospitalization rates and a lack of positive impact on patients' quality of life. PROSPERO CRD42021236291; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=236291.

Previous studies have revealed the role of dysregulated urokinase plasminogen activator (encoded by ) expression and activity in several pathways associated with cancer progression. However, systematic investigation into the association of expression with factors that modulate PDAC (pancreatic ductal adenocarcinoma) progression is lacking, such as those affecting stromal (pancreatic stellate cell, PSC)-cancer cell interactions, tumour immunity, PDAC subtypes and clinical outcomes from potential inhibition. This study used an integrated bioinformatics approach to identify prognostic markers correlated with PLAU expression using different transcriptomics, proteomics, and clinical data sets. We then determined the association of dysregulated and correlated signatures with oncogenic pathways, metastatic phenotypes, stroma, immunosuppressive tumour microenvironment (TME) and clinical outcome. Finally, using an orthotopic model of pancreatic cancer, we confirmed the predicted effect of inhibiting PLAU on tumour growth and metastasis. Our analyses revealed that upregulation is not only associated with numerous other prognostic markers but also associated with the activation of various oncogenic signalling pathways, aggressive phenotypes relevant to PDAC growth and metastasis, such as proliferation, epithelial-mesenchymal transition (EMT), stemness, hypoxia, extracellular cell matrix (ECM) degradation, upregulation of stromal signatures, and immune suppression in the tumour microenvironment (TME). Moreover, the upregulation of was directly connected with signalling pathways known to mediate PSC-cancer cell interactions. Furthermore, upregulation was associated with the aggressive basal/squamous phenotype of PDAC and significantly reduced overall survival, indicating that this subset of patients may benefit from therapeutic interventions to inhibit activity. Our studies with a clinically relevant orthotopic pancreatic model showed that even short-term PLAU inhibition is sufficient to significantly halt tumour growth and, importantly, eliminate visible metastasis. Elevated correlates with increased aggressive phenotypes, stromal score, and immune suppression in PDAC. upregulation is also closely associated with the basal subtype type of PDAC; patients with this subtype are at high risk of mortality from the disease and may benefit from therapeutic targeting of .

Atrial fibrillation (AF) often remains undetected following stroke. Documenting AF is critical to initiate oral anticoagulation, which has proven benefit in reducing recurrent stroke and mortality in patients with AF. The accuracy and acceptability of using smart wearables to detect AF in patients following stroke is unknown. The aims of the Liverpool-Huawei Stroke Study are to determine the effectiveness, cost-effectiveness and patient and staff acceptability of using Huawei smart wearables to detect AF following ischemic stroke. The study plans to recruit 1,000 adults aged ≥18 years following ischemic stroke from participating hospitals over 12 months. All participants will be asked to wear a Huawei smart band for 4 weeks postdischarge. If participants do not have access to a compatible smartphone required for the study, they will be provided with a smartphone for the 4-week AF monitoring period. Participants with suspected AF detected by the smart wearables, without previous known AF, will be referred for further evaluation. To determine the effectiveness of the Huawei smart wearables to detect AF, the positive predictive value will be determined. Patient acceptability of using this technology will also be examined. Additional follow-up assessments will be conducted at 6 and 12 months, and clinical outcomes recorded in relation to prevalent and incident AF post-stroke. The study opened for recruitment on May 30, 2022, and is currently open at 4 participating hospitals; the first 106 participants have been recruited. One further hospital is preparing to open for recruitment. This prospective study will examine the effectiveness and acceptability of the use of smart wearables in patients following ischemic stroke. This could have important implications for detection of AF and therefore, earlier prophylaxis for recurrent stroke. The study is registered on https://www.isrctn.com/ (Identifier ISRCTN30693819).

Rationale & objective Glomerulonephritis (GN) is a leading cause of chronic kidney disease (CKD). Major adverse cardiovascular events (MACE) are prolific in CKD. The risk of MACE in GN cohorts is multifactorial. We investigated the prognostic significance of routine cardiac biomarkers, Troponin I and N-terminal pro-BNP (NT-proBNP) in predicting MACE within 5 years of GN diagnosis. Study Design Retrospective cohort study. Setting & participants Data were obtained from TriNetX, a global federated health research network of electronic health records (EHR). Exposure or predictor Biomarker thresholds: Troponin I: 18 ng/L, NT-proBNP: 400 pg/mL. Outcomes Primary outcome: Incidence of major adverse cardiovascular events (MACE). Secondary outcome: was the risk for each individual component of the composite outcome. Analytical Approach 1:1 propensity score matching using logistic regression. Cox proportional hazard models were used to assess the association of cardiac biomarkers with the primary and secondary outcomes, reported as Hazard Ratio (HR) and 95% confidence intervals (CI). Survival analysis was performed which estimates the probability of an outcome over a 5-year follow-up from the index event. Results Following PSM, 34,974 and 18,218 patients were analysed in the Troponin I and NTproBNP cohorts, respectively. In the Troponin I all cause GN cohort, 3,222 (9%) developed composite MACE outcome HR 1.79; (95% CI, 1.70, 1.88, p  < 0.0001). In the NTproBNP GN cohort, 1,686 (9%) developed composite MACE outcome HR 1.99; (95% CI, 1.86, 2.14, p  < 0.0001). Limitations The data are derived from EHR for administrative purposes; therefore, there is the potential for data errors or missing data. Conclusions In GN, routinely available cardiac biomarkers can predict incident MACE. The results suggest the clinical need for cardiovascular and mortality risk profiling in glomerular disease using a combination of clinical and laboratory variables.

IntroductionPeople with atrial fibrillation (AF) frequently have competing mechanisms for ischaemic stroke, including extracranial carotid atherosclerosis. The objective of this study was to determine associations between use of oral anticoagulants (OACs) plus antiplatelet agents (APA) after ischaemic stroke and outcomes for patients with AF and carotid artery disease.Patients and MethodsA retrospective cohort study was conducted. Participants receiving OACs with or without APA were propensity score–matched for age, sex, ethnicity, co-morbidities and presence of cardiac and vascular implants and grafts. Outcomes were 1-year mortality, recurrent stroke and major bleeding.ResultsOf 5708 patients, 24.1% (n=1628) received non-vitamin K antagonist OACs (NOACs) with no APA, 26.0% (n=1401) received NOACs plus APA, 20.7% (n=1243) received warfarin without APA and 29.2% (n=1436) received warfarin plus APA. There was no significant difference in risk of recurrent stroke between the groups. Compared to receiving NOACs without APA, receiving warfarin plus APA was associated with a higher risk of mortality (hazard ratio (HR) 1.51 (95% confidence interval (CI) 1.20, 1.89)) and major bleeding (HR 1.66 (95% CI 1.40, 1.96)). Receiving NOACs plus APA was also associated with a higher risk of major bleeding compared to NOACs without APA (HR 1.27 (95% CI 1.07, 1.51), respectively).ConclusionsThe results suggest for patients with AF and carotid artery disease after ischaemic stroke, receiving NOACs without APA is associated with a lower risk of major bleeding with no negative impact on recurrent stroke or mortality. Evidence from randomised trials is needed to confirm this finding.

The role of inflammation in predicting early cardiac complications among stroke patients is unclear. Electronic medical records from TriNetX, a global federated health research network, were used for this retrospective analysis. Patients with ischemic stroke and C-Reactive Protein (CRP) levels measured within 24 h post-stroke were categorized into three groups: (i) < 1 mg/L, (ii)1–3 mg/L and (iii) > 3 mg/L. The primary outcome was a composite outcome of cardiac complications (heart failure (HF), ischemic heart disease, atrial fibrillation (AF), ventricular arrhythmias and Takotsubo cardiomyopathy) or death at 30 days from the index event. Cox-regression analyses were used to produce hazard ratios (HRs) and 95% confidence intervals (CI) following 1:1 propensity score matching (PSM). Of the 104,741 patients enrolled, 51% were female and the mean age was 66 ± 16 years. After PSM, a new cardiac complication or death within 30 days occurred in 5624 (33.1%) patients with CRP > 3 mg/L, in 4243 (25.6%) patients with CRP 1–3 mg/L and in 3891 (23.5%) patients with CRP < 1 mg/L. Patients with CRP levels of 1–3 mg/L and > 3 mg/L had higher risk of the composite outcome (HR 1.10, 95%CI 1.05–1.52; HR 1.51, 95%CI 1.45–1.58), death (HR 1.43, 95%CI 1.24–1.64; HR 3.50, 95%CI 3.01–3.96), HF (HR 1.08, 95%CI 1.01–1.16; HR 1.51, 95%CI 1.41–1.61), AF (HR 1.10, 95% CI:1.02–1.18; HR 1.42, 95%CI 1.33–1.52) and ventricular arrhythmias (HR 1.25, 95%CI 1.02–1.52; HR 1.67, 95% CI 1.38–2.01) compared to those with CRP < 1 mg/L. Ischemic heart disease were more common among patients with CRP levels > 3 mg/L compared to those with CRP < 1 mg/L (HR:1.33, 95% CI:1.26–1.40), while no association with Takotsubo cardiomyopathy was found in all the analyses. CRP levels within the first 24 h of an ischemic stroke predict 30-day cardiac complications or death.

Pancreatic cancer is a highly aggressive malignancy that features high recurrence rates and the poorest prognosis of all solid cancers. The urokinase plasminogen activation system (uPAS) is strongly implicated in the pathophysiology and clinical outcomes of patients with pancreatic ductal adenocarcinoma (PDAC), which accounts for more than 90% of all pancreatic cancers. Overexpression of the urokinase-type plasminogen activator (uPA) or its cell surface receptor uPAR is a key step in the acquisition of a metastatic phenotype via multiple mechanisms, including the increased activation of cell surface localised plasminogen which generates the serine protease plasmin. This triggers multiple downstream processes that promote tumour cell migration and invasion. Increasing clinical evidence shows that the overexpression of uPA, uPAR, or of both is strongly associated with worse clinicopathological features and poor prognosis in PDAC patients. This review provides an overview of the current understanding of the uPAS in the pathogenesis and progression of pancreatic cancer, with a focus on PDAC, and summarises the substantial body of evidence that supports the role of uPAS components, including plasminogen receptors, in this disease. The review further outlines the clinical utility of uPAS components as prospective diagnostic and prognostic biomarkers for PDAC, as well as a rationale for the development of novel uPAS-targeted therapeutics.