Understanding digital exclusion in older adults during the COVID-19 pandemic could help tailor responses to future outbreaks. This cohort study used data from older adults aged 60+ years in England ...who participated in wave nine (2018/2019) of the main English Longitudinal Study of Ageing (ELSA) survey, and/or wave one of the ELSA COVID-19 sub-study (June/July 2020). Using latent class analysis and latent transition analysis, we aimed to identify distinct subgroups of older adults characterised by different patterns of internet use pre- and intra-pandemic, explore the extent to which individuals remained in the same subgroup or transitioned to a different subgroup during the COVID-19 pandemic, and examine longitudinal associations of socio-economic factors (education, occupational class, and wealth) with latent class membership. Preliminary tests showed that the types of internet activities differed between men and women; therefore, subsequent analyses were stratified by biological sex. Three clusters (low, medium, and high) were identified in male participants at both timepoints. Among female participants, three clusters were distinguished pre-pandemic and two (low versus high) during the pandemic. The latent classes were characterised by participants' breadth of internet use. Higher education, occupational class, and wealth were associated with greater odds of membership in the medium and/or high classes, versus the low class, in men and women. A high degree of stability in latent class membership was observed over time. However, men experienced a stark decrease in online health information-seeking. Our results highlight that inequality regarding the range of functional and social opportunities provided by the internet prevailed during the pandemic. Policymakers should ensure that digital access and upskilling initiatives are equitable for all.
ObjectiveIron deficiency (ID) has an established impact on outcomes in patients with heart failure with reduced ejection fraction; however, there is a lack of conclusive evidence in patients with ...heart failure with preserved ejection fraction (HFpEF). We sought to clarify the prevalence and impact of ID in patients with HFpEF.MethodsA systematic search of Cohcrane, MEDLINE, EMBASE, Web of Science and CINAHL electronic databases was performed to identify relevant studies. Included studies defined HFpEF as heart failure with an ejection fraction ≥50%. We used a random-effects meta-analysis to determine the composite prevalence of ID in patients with HFpEF across the included studies. Other outcomes were assessed with qualitative analysis due to a paucity of studies with comparable outcome measures.ResultsThe prevalence of ID in the included studies was 59% (95% CI 52% to 65%). ID was associated with lower VO2 max in three of four studies reporting VO2 max as an outcome measure, lower functional status as determined by dyspnoea class or 6 min walk test in two of three studies, and worse health-related quality of life in both studies reporting on this outcome. Conversely, ID had no impact on death or hospitalisation in three of the four studies investigating this.ConclusionsID is highly prevalent in patients with HFpEF and is associated with worse exercise capacity and functional outcomes, but not hospitalisation or mortality. Our study establishes that ID may play an important a role in HFpEF.
Growth differentiation factor 15 (GDF15) is a divergent member of the transforming growth factor–β superfamily and has been identified in different contexts as a hypoxia-inducible gene product and as ...a molecule involved in hepcidin regulation. The biology of iron and oxygen is closely related, and known regulatory pathways involving hypoxia-inducible factor (HIF) and iron-regulatory proteins (IRPs) are responsive to both these stimuli. We therefore sought to characterize the regulation of GDF15 by iron and oxygen and to define the involvement or otherwise of HIF and IRP pathways. Here we show that GDF15 is strongly up-regulated by stimuli that deplete cells of iron and that this response is specifically antagonized by the reprovision of iron. GDF15 exhibits greater sensitivity to iron depletion than hypoxia, and responses to hypoxia and iron depletion are independent of HIF and IRP activation, suggesting a novel mechanism of regulation. We also report significant induction of serum GDF15 in iron-deficient subjects and after administration of an iron chelator to normal subjects. These findings indicate that GDF15 can be induced by pathophysiologic changes in iron availability, raising important questions about the mechanism of regulation and its role in iron homeostasis.
Aims
Implantable cardioverter defibrillator (ICD) therapy improves survival in patients at high sudden cardiac death (SCD) risk. However, some patient groups fulfilling indications for ICD therapy ...may not gain significant benefit: patients whose absolute risk of SCD is low and patients whose risk of death even with an ICD is high. The value of biomarkers in identifying patients' potential for survival benefit from ICD therapy is unknown. We performed a pilot study to investigate this.
Methods and results
Five established cardiovascular biomarkers were measured in patients with ICDs on the background of left ventricular dysfunction: N-terminal pro-brain natriuretic peptide NT-proBNP, soluble ST2 sST2, growth differentiation factor-15, C-reactive protein, and interleukin-6. The endpoints were all-cause mortality and survival with appropriate ICD therapy. One hundred and fifty-six patients were enrolled (age 69 years Q1-Q3 62-77, 85% male, 76% ischaemic aetiology). During a follow-up of 15 ± 3 months, 12 patients died and 43 survived with appropriate ICD therapy. In a Cox proportional hazards model, the strongest predictors of death were Log sST2 (P< 0.001), serum creatinine (P< 0.001), and Log NT-proBNP (P= 0.002). The strongest predictor of survival with appropriate ICD therapy was Log NT-proBNP (P= 0.01).
Conclusion
The biomarkers NT-proBNP and sST2 are promising biomarkers for identifying patients with little potential to gain significant survival benefit from ICD therapy. However, their incremental benefit, in addition to currently available clinical risk prediction models, remains unclear. These results demand a confirmatory prospective cohort study, designed and powered to derive and validate prediction algorithms incorporating these markers.
The ability to predict mode, as well as risk, of death in left ventricular systolic dysfunction (LVSD) is important, as the clinical and cost-effectiveness of implantable cardioverter defibrillators ...(ICD) therapy depends on its use in appropriately selected patient populations. The value of a proteomic approach in identifying prognostic biomarkers in LVSD is unknown. The aims of this pilot study were to use proteomic techniques to identify serum biomarkers associated with LVSD and to prospectively explore their association with prognosis.
Serum was analysed by surface-enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS) in patients with (n=78) and without (n=45) systolic heart failure (SHF). Spectra were compared to identify differentially expressed signal peaks as potential biomarker indicators. The ability of these peaks to predict all-cause mortality and survival with appropriate ICD therapy was then tested prospectively in patients with ICDs, on the background of LVSD (n=141).
For the identification stage spectra (2-200 kDa) from SHF and control patients were randomly separated into two equally sized discovery and validation sets. Six protein peaks were identified that were differentially expressed in SHF in both sets. In the prospective phase, during a mean follow-up of 15±3 months, 11 patients died and 39 survived with appropriate ICD therapy. Five out of the six proteomic biomarkers predicted all-cause mortality but none predicted appropriate ICD therapy.
These results provide proof-of-principle and are supportive of the SELDI proteomic approach as a high-throughput screening tool in identifying potentially prognostic protein peaks in patients with LVSD.
Introduction
The influence of the COVID-19 pandemic on physical activity behaviour in older adults is of particular concern. However, little is yet known about how pre-existing socioeconomic ...inequalities in older adults’ physical activity have been affected by the COVID-19 pandemic. The aim of this study was to explore socioeconomic disparities in physical activity levels and change over time among older adults in England, using data collected before and during the COVID-19 pandemic.
Methods
This longitudinal cohort study analysed data from 3720 older adults (aged 60+ years) who participated in wave 9 (2018/2019) of the main English Longitudinal Study of Ageing (ELSA) survey and wave 2 of the ELSA COVID-19 substudy (November/December 2020). Using multilevel ordinal logistic models, we investigated associations between socioeconomic variables (education, occupational class and wealth) and physical activity, adjusting for potential confounders. We also examined interactions between socioeconomic variables and time (prepandemic vs intrapandemic) to investigate changes in the magnitude of inequalities in physical activity across the two survey periods.
Results
The proportion of participants considered ‘inactive’ rose from 5.7% before the COVID-19 pandemic to 12.5% in November and December 2020. Higher education, occupational class and wealth were positively associated with physical activity before the lockdown. These socioeconomic disparities generally persisted during the COVID-19 pandemic. There was some evidence that differences in physical activity based on education and occupational class reduced during the COVID-19 pandemic, relative to prepandemic data. However, these associations were no longer statistically significant when the three socioeconomic variables and their interactions with time corrected for one another (p>0.05).
Conclusion
Our results suggest there was no additional influence of the COVID-19 pandemic on pre-existing socioeconomic inequalities in older adults’ physical activity levels.
Background: There is paucity of safe and effective analgesic drugs for osteoarthritis (OA). β-adrenoreceptor blockers have demonstrated anti-nociceptive effects in several painful conditions. We ...investigated whether β-blockers are associated with a reduced risk of total joint replacement (TJR) at the knee or the hip in people with incident knee or hip OA. Methods: This was a cohort study. We used data from the Clinical Practice Research Datalink. Participants aged 40 years or older with incident knee or hip OA, prescribed β-blockers following OA diagnosis (new-user design) and their age, sex, OA location and propensity score (PS) for β-blocker prescription matched controls were included in the study. Cox-proportional hazard ratios (HRs) and 95% confidence intervals (CI) were calculated. The analyses were adjusted for factors that influence health-seeking behaviour, progression of OA, and stratified according to β -blocker classification. Data analysis was conducted using STATA-MP v15. Results: Data for 6,970 PS-matched β -blocker exposed and unexposed participants were included. Any β -blocker prescription was not associated with knee or hip TJR (aHR 1.11; 95 % CI 0.98 – 1.25). However, prescription of lipophilic non-selective β-blockers with membrane stabilising effect associated with reduced risk of knee or hip TJR (aHR 0.69; 95 % CI 0.52 – 0.93). Of these, there was a protective effect for propranolol (aHR 0.71; 95 % CI 0.53 – 0.95), the commonest prescribed drug in this class. The number needed to treat (95%CI) with propranolol for two years, in order to prevent one TJR was 32 (23–52). Conclusions: The non-selective β-blocker propranolol reduces the risk of knee or hip TJR, consistent with its analgesic effects demonstrated in other conditions. A randomised controlled trial is required to further evaluate the analgesic potential of propranolol in OA.
This Review presents data describing the health burden of cardiovascular disease (CVD) within and across the WHO European Region. CVD remains the most common cause of death in the region. Deaths from ...CVD in those aged <70 years, commonly referred to as premature, are a particular concern, with >60 million potential years of life lost to CVD in Europe annually. Although more women than men die from CVD, age-standardized rates of both morbidity and death are higher in men, and these differences in rates are greatest in individuals aged <70 years. Large inequalities in all measures of morbidity, treatment and mortality can be found between countries across the continent and must be a focus for improving health. Large differences also exist in the data available between countries. The development and implementation of evidence-based preventive and treatment approaches must be supported in all countries by consistent surveillance and monitoring, such that we can quantify the health burden of CVD as well as target interventions and provide impetus for action across Europe.
Analyses of phylogenetic informativeness represent an important step in screening potential or existing datasets for their proclivity toward convergent or parallel evolution of molecular sites. ...However, while new theory has been developed from which to predict the utility of sequence data, adoption of these advances have been stymied by a lack of software enabling application of advances in theory, especially for large next-generation sequence data sets. Moreover, there are no theoretical barriers to application of the phylogenetic informativeness or the calculation of quartet internode resolution probabilities in a Bayesian setting that more robustly accounts for uncertainty, yet there is no software with which a computationally intensive Bayesian approach to experimental design could be implemented.
We introduce PhyInformR, an open source software package that performs rapid calculation of phylogenetic information content using the latest advances in phylogenetic informativeness based theory. These advances include modifications that incorporate uneven branch lengths and any model of nucleotide substitution to provide assessments of the phylogenetic utility of any given dataset or dataset partition. PhyInformR provides new tools for data visualization and routines optimized for rapid statistical calculations, including approaches making use of Bayesian posterior distributions and parallel processing. By implementing the computation on user hardware, PhyInformR increases the potential power users can apply toward screening datasets for phylogenetic/genomic information content by orders of magnitude.
PhyInformR provides a means to implement diverse substitution models and specify uneven branch lengths for phylogenetic informativeness or calculations providing quartet based probabilities of resolution, produce novel visualizations, and facilitate analyses of next-generation sequence datasets while incorporating phylogenetic uncertainty through the use parallel processing. As an open source program, PhyInformR is fully customizable and expandable, thereby allowing for advanced methodologies to be readily integrated into local bioinformatics pipelines. Software is available through CRAN and a package containing the software, a detailed manual, and additional sample data is also provided freely through github: https://github.com/carolinafishes/PhyInformR .
PDF
