What do patients want from a digital device that supports heart failure self-management?

OBJECTIVE: To assess patients' needs and the factors determining their acceptance of an e-Health intervention. METHODS: Purposive sample of patients with heart failure, attending an outpatient consultation were invited to complete a questionnaire designed to assess their needs and acceptance of an e-Health intervention. Data analysis was performed using Chi-square tests with post-hoc corrections. RESULTS: Response rate was 61 % (n = 101), with most patients (>70 %) indicating they could see themselves using an e-Health intervention to manage their heart failure. Participants with a healthy lifestyle (i.e., non-smoker and consumed alcohol < once/week) were more likely to have a positive attitude towards technology (p adj.=0.013). Those willing to use an e-Health intervention were convinced of its advantages by other patients with heart failure (p adj.=0.013). Advanced age, education level, employment or marital status did not influence patient attitudes toward health technology. CONCLUSIONS & PRACTICE IMPLICATIONS: Results indicate patients have a positive attitude towards the use of e-Health interventions to enable their self-management of heart failure. These findings will inform further development and delivery strategies of e-Health interventions.

Respiratory syncytial virus-associated pneumonia in primary care in Malawi.

OBJECTIVE: To identify the prevalence of respiratory syncytial virus (RSV) in a cohort of children under 5 years of age with World Health Organization (WHO)-defined pneumonia and the factors associated with developing severe RSV-associated community-acquired pneumonia (CAP) in primary care in a single centre in Northern Malawi. METHODS: The BIOmarkers TO diagnose PnEumonia (BIOTOPE) study was a prospective cohort study conducted from March to June 2016 that took place in a primary care centre in Northern Malawi. Data from this study was used to identify the characteristics of children under 5 years of age who presented with RSV and WHO-defined CAP. Means, standard deviations, medians and ranges were calculated for continuous variables. A univariate logistic regression was performed to examine the potential predictor variables. RESULTS: Four hundred and ninety-four infants presented with CAP and were eligible for inclusion in the study; RSV infection was detected in 205 (41.6%) of the infants. Eight factors were associated with increased risk for RSV CAP in the univariate model: age, born at term, presenting for care in June, crowded living environment, not being exclusively breastfed, not having received zinc or vitamin A supplementation in the last six months. Infants with RSV were more likely to have an oxygen saturation ≤92% compared to infants with other causes of pneumonia and more likely to have severe pneumonia as defined by the WHO. CONCLUSION: This study supports that RSV-associated CAP is linked to modifiable and non-modifiable risk factors; further research is indicated to determine which interventions would be most impactful. Developing and implementing an infant or maternal vaccine could be a cost-effective way to prevent RSV-associated CAP and mortality in developing nations. More research is needed to understand seasonal patterns of CAP and research over extended periods can offer valuable insights on host, environmental and pathogen-specific factors that contribute to RSV-associated CAP.

Feto-maternal indicators of cardiac dysfunction as a justification for the cardiac origins for pre-eclampsia.

While the pathophysiology of pre-eclampsia has been postulated as being secondary to placental dysfunction, a cardiac origin has more recently been proposed. Although an association between fetal congenital cardiovascular disease and pre-eclampsia has been demonstrated, no precise pathophysiologic mechanism for this association has been described. This review highlights the current biophysical (including echocardiography and Doppler indices) and biochemical (including proteomic, metabolomic and genetic/transcriptomic) markers of cardiac dysfunction that have been investigated in maternal and fetal cardiac disease and their overlap with predictors of pre-eclampsia.   Common pathways of inflammatory and anti-angiogenesis imbalance, endothelial damage, and oxidative stress have been demonstrated in both cardiovascular disease and pre-eclampsia and further investigation into these pathways could help to elucidate the common pathophysiologic mechanisms linking these disorders.

Impact of SGLT2 inhibition on markers of reverse cardiac remodelling in heart failure: Systematic review and meta-analysis.

INTRODUCTION: Several landmark randomized-controlled trials (RCTs) have demonstrated the efficacy of sodium-glucose co-transport 2 (SGLT2) inhibitors in reducing all-cause mortality, cardiovascular (CV) mortality and heart failure (HF) hospitalizations. Much interest surrounds their mechanism of action and whether they have direct effects on reverse cardiac remodelling. Therefore, we conducted a meta-analysis of placebo controlled RCTs evaluating the impact of SGLT2 inhibition on imaging derived markers of reverse cardiac remodelling in patients with HF. METHODS: We performed a systematic review and meta-analysis in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) Statement and Cochrane Collaboration. Data interrogation of each major database including PubMed, EMBASE, MEDLINE and Cochrane Library was performed. RCTs evaluating HF patients >18 years comparing SGLT2 inhibitor versus placebo-control were included. Outcome measures included left ventricular end-diastolic volume and volume index (LVEDV/LVEDVi), left ventricular end-systolic volume and volume index (LVSDV/LVSDVi), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMi), left atrial volume index (LAVi) and left ventricular global longitudinal strain (LV GLS). Studies with an HF with preserved ejection fraction population were excluded from analysis of parameters, which would be significantly affected by baseline LVEF, such as volumes and LVEF. The mean difference and standard error were extracted from each study and a random effects model used pool the mean difference and standard error across studies. A pre-specified sub-group analysis was performed to stratify results according to imaging modality used (cardiac magnetic resonance imaging and echocardiography). This study is registered on PROSPERO: CRD42023482722. RESULTS: Seven randomized, placebo-controlled trials in patients with HF comprising a total population of 657 patients were included. Overall LVEF of included studies ranged from 29 ± 8.0% to 55.5 ± 4.2%. In studies included in analysis of HFrEF parameters, baseline LVEF ranged from 29 ± 8% to 45.5 ± 12%. Pooled data demonstrated SGLT2 inhibition, compared with placebo control, resulted in significant improvements in mean difference of LVEDV [-11.62 ml (95% confidence interval, CI -17.90 to -5.25; z = 3.67, P = 0.0004)], LVEDVi [-6.08 ml (95% CI -9.96 to -2.20; z = 3.07; P = 0.002)], LVESV [-12.47 ml (95% CI -19.12 to -5.82; z = 3.68; P = 0.0002)], LVESVi [-6.02 ml (95% CI -10.34 to -1.70; z = 2.73; P = 0.006)], LVM [-9.77 g (95% CI -17.65 to -1.89; z = 2.43; P = 0.02)], LVMi (-3.52 g [95% CI -7.04 to 0.01; z = 1.96; P = 0.05)] and LVEF [+2.54 mL (95% CI 1.10 to 3.98; z = 3.62; P = 0.0005)]. No significant difference in GLS (n = 327) [+0.42% (95%CI -0.19 to 1.02; P = 0.18)] or LAVi [-3.25 ml (95% CI -8.20 to 1.69; z = 1.29; P = 0.20)] was noted. CONCLUSION: This meta-analysis provides additional data and insight into the effects of SGLT2 inhibition on reverse cardiac remodelling in patients with HF. Compared with placebo control, we found that treatment with a SGLT2 inhibitor produced significant improvements in several markers of reverse cardiac remodelling.

Single-Cell RNA Sequencing Reveals Cardiac Fibroblast-Specific Transcriptomic Changes in Dilated Cardiomyopathy.

Dilated cardiomyopathy (DCM) is the most common cause of heart failure, with a complex aetiology involving multiple cell types. We aimed to detect cell-specific transcriptomic alterations in DCM through analysis that leveraged recent advancements in single-cell analytical tools. Single-cell RNA sequencing (scRNA-seq) data from human DCM cardiac tissue were subjected to an updated bioinformatic workflow in which unsupervised clustering was paired with reference label transfer to more comprehensively annotate the dataset. Differential gene expression was detected primarily in the cardiac fibroblast population. Bulk RNA sequencing was performed on an independent cohort of human cardiac tissue and compared with scRNA-seq gene alterations to generate a stratified list of higher-confidence, fibroblast-specific expression candidates for further validation. Concordant gene dysregulation was confirmed in TGFß-induced fibroblasts. Functional assessment of gene candidates showed that AEBP1 may play a significant role in fibroblast activation. This unbiased approach enabled improved resolution of cardiac cell-type-specific transcriptomic alterations in DCM.

Impact of filgotinib on pain control in the phase 3 FINCH studies.

OBJECTIVE: This post hoc analysis of the FINCH 1-3 (NCT02889796, NCT02873936 and NCT02886728) studies assessed specific effects of filgotinib on pain control and their relationship with other aspects of efficacy in patients with rheumatoid arthritis (RA). METHODS: Assessments included: residual pain responses of ≤10 and ≤20 mm on a 100 mm visual analogue scale (VAS); the proportion of patients who achieved VAS pain responses in addition to remission or low disease activity by Disease Activity Score-28 with C-reactive protein (DAS28-CRP) or Clinical Disease Activity Index (CDAI) criteria. RESULTS: Across studies, filgotinib reduced pain from week 2, with responses sustained throughout the studies. In FINCH 1, at week 24, 35.8%, 25.0%, 24.6% and 11.6% of patients in the filgotinib 200 mg, filgotinib 100 mg, adalimumab and placebo arms (each plus methotrexate) achieved VAS pain ≤20 mm in addition to DAS28-CRP remission; 26.3%, 17.9%, 17.2% and 7.6% achieved VAS pain ≤10 mm in addition to DAS28-CRP remission. A similar pattern was seen for CDAI remission. Time during which VAS pain was ≤10 or ≤20 mm was longest with filgotinib 200 mg and comparable between adalimumab and filgotinib 100 mg. Similar findings were reported for filgotinib in FINCH 2 and 3. CONCLUSION: In all RA populations studied, pain improvements occurred from week 2 and were sustained over time. In FINCH 1, filgotinib 100 mg provided similar pain amelioration to adalimumab, whereas filgotinib 200 mg resulted in greater pain improvement and higher proportion of patients with residual pain ≤10 or ≤20 mm and meeting DAS28-CRP remission criteria.

Dose-dependent changes in cardiac function, strain and remodelling in a preclinical model of heart base irradiation.

BACKGROUND AND PURPOSE: Radiation induced cardiotoxicity (RICT) is as an important sequela of radiotherapy to the thorax for patients. In this study, we aim to investigate the dose and fractionation response of RICT. We propose global longitudinal strain (GLS) as an early indicator of RICT and investigate myocardial deformation following irradiation. METHODS: RICT was investigated in female C57BL/6J mice in which the base of the heart was irradiated under image-guidance using a small animal radiation research platform (SARRP). Mice were randomly assigned to a treatment group: single-fraction dose of 16 Gy or 20 Gy, 3 consecutive fractions of 8.66 Gy, or sham irradiation; biological effective doses (BED) used were 101.3 Gy, 153.3 Gy and 101.3 Gy respectively. Longitudinal transthoracic echocardiography (TTE) was performed from baseline up to 50 weeks post-irradiation to detect structural and functional effects. RESULTS: Irradiation of the heart base leads to BED-dependent changes in systolic and diastolic function 50 weeks post-irradiation. GLS showed significant decreases in a BED-dependent manner for all irradiated animals, as early as 10 weeks after irradiation. Early changes in GLS indicate late changes in cardiac function. BED-independent increases were observed in the left ventricle (LV) mass and volume and myocardial fibrosis. CONCLUSIONS: Functional features of RICT displayed a BED dependence in this study. GLS showed an early change at 10 weeks post-irradiation. Cardiac remodelling was observed as increases in mass and volume of the LV, further supporting our hypothesis that dose to the base of the heart drives the global heart toxicity.

SGLT2 Inhibition in Heart Failure: Clues to Cardiac Effects?

Following the publication of several landmark clinical trials such as dapagliflozin in patients with heart failure and reduced ejection fraction, dapagliflozin evaluation to improve the lives of patients with preserved ejection fraction heart failure, and empagliflozin outcome trial in patients with chronic heart failure with preserved ejection fraction, sodium-glucose cotransport 2 inhibitors have been rapidly incorporated as a guideline-directed therapy in the treatment of heart failure. Moreover, their benefits appear to extend across the spectrum of left ventricular dysfunction which in some respects, can be seen as the holy grail of heart failure pharmacotherapy. Despite its plethora of proven cardioprotective benefits, the mechanisms by which it exerts these effects remain poorly understood, however, it is clear that these extend beyond that of promotion of glycosuria and natriuresis. Several hypotheses have emerged over the years including modification of cardiovascular risk profile via weight reduction, improved glucose homeostasis, blood pressure control, and natriuretic effect; however, these mechanisms do not fully explain the potent effects of the drug demonstrated in large-scale randomized trials. Other mechanisms may be at play, specifically the down-regulation of inflammatory pathways, improved myocardial sodium homeostasis, modulation of profibrotic pathways, and activation of nutrient deprivation signaling pathways promoting autophagic flux. This review seeks to summarize the cardioprotective benefits demonstrated in major clinical trials and provide a succinct review of the current theories of mechanisms of action, based on the most recent evidence derived from both clinical and laboratory data.

Role of diagnostic tests for sepsis in children: a review.

Paediatric sepsis has a significant global impact and highly heterogeneous clinical presentation. The clinical pathway encompasses recognition, escalation and de-escalation. In each aspect, diagnostics have a fundamental influence over outcomes in children. Biomarkers can aid in creating a larger low-risk group of children from those in the clinical grey area who would otherwise receive antibiotics 'just in case'. Current biomarkers include C reactive protein and procalcitonin, which are limited in their clinical use to guide appropriate and rapid treatment. Biomarker discovery has focused on single biomarkers, which, so far, have not outperformed current biomarkers, as they fail to recognise the complexity of sepsis. The identification of multiple host biomarkers that may form a panel in a clinical test has the potential to recognise the complexity of sepsis and provide improved diagnostic performance. In this review, we discuss novel biomarkers and novel ways of using existing biomarkers in the assessment and management of sepsis along with the significant challenges in biomarker discovery at present. Validation of biomarkers is made less meaningful due to methodological heterogeneity, including variations in sepsis diagnosis, biomarker cut-off values and patient populations. Therefore, the utilisation of platform studies is necessary to improve the efficiency of biomarkers in clinical practice.

Non-specific effects of Pneumococcal and Haemophilus vaccines in children aged 5 years and under: a systematic review.

OBJECTIVE: To determine the evidence for non-specific effects of the Pneumococcal and Haemophilus influenza vaccine in children aged 5 years and under. DATA SOURCES: A key word literature search of MEDLINE, EMBASE, The Cochrane Central Register of Controlled Trials, the European Union Clinical Trials Register and ClinicalTrials.gov up to June 2023. STUDY ELIGIBILITY CRITERIA: Randomised controlled trials (RCTs), quasi-RCT or cohort studies. PARTICIPANTS: Children aged 5 or under. STUDY APPRAISAL AND SYNTHESIS METHODS: Studies were independently screened by two reviewers, with a third where disagreement arose. Risk of bias assessment was performed by one reviewer and confirmed by a second. Results were tabulated and a narrative description performed. RESULTS: Four articles were identified and included in this review. We found a reduction in hospitalisations from influenza A (44%), pulmonary tuberculosis (42%), metapneumovirus (45%), parainfluenza virus type 1-3 (44%), along with reductions in mortality associated with pneumococcal vaccine. No data on the Haemophilus vaccine was found. CONCLUSIONS AND IMPLICATIONS: In this systematic review, we demonstrate that there is a reduction in particular viral infections in children aged 5 years and under who received the 9-valent pneumococcal conjugate vaccine which differ from those for which the vaccine was designed to protect against. While limited studies have demonstrated a reduction in infections other than those which the vaccine was designed to protect against, substantial clinical trials are required to solidify these findings. PROSPERO REGISTRATION NUMBER: CRD42020146640.