Alcohol consumption and heart failure: a dose-response meta-analysis.

OBJECTIVES: This is a protocol for a Cochrane Review (prototype). The objectives are as follows: Main objective To assess the effects of alcohol consumption on the progression to symptomatic (stage C) heart failure in people at risk for heart failure (stage A) or in people with pre-heart failure (stage B). Secondary objectives To assess the effects of alcohol consumption on progression of left ventricular dysfunction in people with stage A or stage B heart failure. We will assess the effect of alcohol consumption on the development of heart failure with reduced ejection fraction, mildly reduced ejection fraction, and preserved ejection fraction. We also aim to evaluate the effects of alcohol consumption on the development of symptomatic (stage C) heart failure over the short, medium and long term.

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.

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.

Alcohol Consumption and Progression of Heart Failure in Those at Risk for or With Pre-heart Failure.

BACKGROUND: This study aimed to understand the dose-response relationship between alcohol consumption, progression of left ventricular dysfunction (LVD) and/or symptomatic heart failure (HF) in an older European population at risk for HF (stage A) or with pre-HF (stage B). METHODS: This longitudinal, observational, secondary analysis of the STOP-HF (St Vincent's Screening TO-Prevent Heart Failure) trial follow-up study excluded former alcohol drinkers and included patients with documented alcohol intake and echocardiography at baseline and follow-up ≥ 18 months. It evaluated the relationship between alcohol intake and progression of LVD/symptomatic (stage C) HF in those at risk for or with pre-HF. RESULTS: Of 744 patients (mean age 66.5 [SD 9.8] years), 395 (53.1%) were female, and 260 (34.9%) had pre-HF at baseline. Overall, 201 (27.0%) patients reported no alcohol usage, 356 (47.8%) reported ≤70 g/week (low) alcohol intake, and 187 (25.1%) reported > 70g/week (moderate-high). Over a median follow-up of 5.44 (IQR 4.33;6.73) years, 84 (11.3%) patients experienced progression of LVD/symptomatic HF. Alcohol usage of > 70g/week was associated with an adjusted 4.9-fold (95% CI 1.7-15.1; P < 0.01) increased risk of HF progression among those with pre-HF at baseline. The adverse relationship remained significant when adjusting for age, sex, diabetes, hypertension, body mass index, as well as further models with baseline liver function and alcohol dehydrogenase 1B gene variant rs1229984 status. The association remained when excluding those with high (> 140 g) weekly alcohol intake. In patients at risk for HF, there was no association of alcohol usage with progression of LVD/symptomatic HF. No protective associations of low alcohol usage (≤70 g/week) on progression of HF were found. CONCLUSION: Moderate to high alcohol (> 70 g/week) usage appears to be associated with progression of LVD/symptomatic HF in those with pre-HF, and we did not observe protective benefits of low alcohol usage.

A pilot study of the quality of care of atrial fibrillation in Irish general practice.

BACKGROUND: Worldwide, atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in adults and poses a significant burden to patients, physicians, and healthcare systems. We developed a quality of care score based on the Atrial Fibrillation Better Care pathway recommended by the European Society of Cardiology and the European Heart Rhythm Association guidelines. This is a 14-point score that we have termed the MAGIC score(Management of Atrial Fibrillation in Integrated Care and General Practice). OBJECTIVE: The objective of this pilot study was to develop and test a quality of care score for patients with permanent AF in general practice. METHODS: An observational cross-sectional pilot study was undertaken. Proportionate sampling was used across 11 practices from the Ireland East practice-based research network. The GPs completed a report form on each patient by undertaking a retrospective chart review. Eleven practices participated with a total of 1855 patients with AF. We received data on 153 patients. RESULTS: The main findings were that no patient met all 14 guideline based recommendations. The mean MAGIC score was 11.3. Points were most commonly deducted because the creatinine clearance and HAS-BLED score were not recorded, and the patient was not on the correct dose of oral anti-coagulation. CONCLUSION: This study demonstrates the feasibility of using a quality of care score to measure the quality of AF management in general practice. This scoring system, which is based on internationally recognized quality of care markers, highlights key areas that can be targeted with quality improvement intervention.

Atrial fibrillation (AF) is the most common arrhythmia in the world. An arrhythmia is when your heart beats in a disorganized way with no pattern. AF is a serious health problem because this rhythm can lead to other heart problems, stroke, and even death. Even though it is common, we know that people with AF do not always receive the correct treatment and monitoring. Treatment aims to control the heart rate, rhythm and minimize blood clot formation. Treating patients according to recommended guidelines will improve their medical care and outcomes. We created a 14-point quality-of-care score based on international clinical practice guidelines. This project was done to check if this score was practical to use and if it showed any patterns in the quality of care being delivered. Eleven GP practices from the Southeast of Ireland participated and gave us information on 153 patients with AF. We assigned each chart a quality-of-care score based on the tool we developed. No chart scored 14 points (full marks). The most common reasons for points being deducted were not recording kidney function, bleeding risk, and the patients being on the wrong dose of medication. With this information, we can now move forward and try to improve care for these patients by targeting the highlighted deficits.

Management of iron deficiency in women of childbearing age with oral iron intolerance: a prospective, randomised, controlled trial of three doses of an iron-whey-protein formulation : Prospective RandomisEd study of women of Childbearing age with gastroInteStinal Intolerance to Oral iroN (PRECISION).

BACKGROUND: Nutritional deficit and oral iron gastrointestinal intolerance may be a common cause of iron deficiency, which can be managed by pharmacists. AIM: To understand the prevalence of iron deficiency in women of childbearing age with a self-reported history of intolerance to oral iron and the tolerability of three doses of an iron-whey-protein formulation in the care of these women. METHOD: Ferritin and haemoglobin levels were documented in women of childbearing age with oral iron gastrointestinal intolerance. In those with iron deficiency (ferritin < 30 µg/L), adherence, gastrointestinal tolerability, ferritin, transferrin saturation and haemoglobin levels were compared between their prior oral iron product and iron-whey-protein microspheres randomised to three doses (14 mg daily, 25 mg daily and 50 mg daily) for 12 weeks. RESULTS: Most screened women had low iron stores (128 (62.7%); ferritin < 30 µg/L), 65 (31.9%) had moderate to severe iron deficiency (ferritin < 12 µg/L) and 33 (16.2%) had iron deficiency anaemia (ferritin < 30 µg/L, haemoglobin < 12 g/dL). Amongst the 59 women who participated in the prospective clinical study of iron-whey-protein microspheres over 12 weeks, 48 (81.4%) were classified as adherent/persistent and fewer instances of gastrointestinal intolerance were reported (0.59 ± 0.91) when compared to 12 (20.3%) and (4.0 ± 2.2) respectively while taking the prior oral iron (Fisher's Exact and T-test respectively, both p < 0.001). There was no difference in adherence or tolerability of different iron-whey-protein formulation doses. Ferritin, haemoglobin and energy levels increased significantly over 12 weeks. CONCLUSION: Undiagnosed iron deficiency is common in women of childbearing age with a history of intolerance to oral iron and iron-whey-protein microspheres can improve adherence, GI tolerability, iron stores, haemoglobin and energy levels in these women. CLINICAL TRIAL REGISTRATION: Clinicaltrials.gov identifier (registration includes full trial protocol): NCT04778072.

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.