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BACKGROUND: Overweight/obesity and iron deficiency are highly prevalent in women of reproductive age (WRA), impacting on women's health. Obesity is a risk factor for nutritional deficiencies but its association with iron deficiency is unclear. OBJECTIVE: To determine the association between adiposity and markers of iron status and iron deficiency prevalence in WRA. METHODS: This cross-sectional study analyzed the National Diet and Nutrition Survey (NDNS, 2008-2019) data, focusing on women aged 18-49y with BMI ≥18.5 kg/m2. Prevalence of anemia, Iron Deficiency Anemia (IDA), and Iron Deficiency (ID) were analyzed. Ferritin was adjusted for C-reactive protein. Iron status was assessed across high and low BMI, waist circumference (WC), waist-to-height (WHtR), and waist-to-hip ratio (WHR). Chi2, linear and logistic regression were performed adjusting for covariates. RESULTS: Among 1,098 WRA, 496 normal weight and 602 overweight/obesity, prevalence rates were: anemia 9.2% and IDA 6.8%. Anemia was more prevalent in those with higher WHtR and WHR (11.9% vs 5.9% and 16.7% vs 6.5%, both p<0.001). WRA with increased WC, WHtR, and WHR had higher IDA prevalence than those with lower adiposity. (8.5% vs 4.3%, p=0.005; 9.4% vs 3.3%, p<0.001; 12.1% vs 4.9%, p<0.001). ID prevalence was 49.7% (ferritin cut-off 30 µg/L) and 19.6% (ferritin cut-off 15 µg/L), showing similar rates across adiposity groups. ID prevalence defined by soluble transferrin receptor (sTfR) was higher in women with increased WHR (p=0.001). Higher WHR predicted ID categorized by sTfR (aOR 2.104, p=0.004), and WHtR and WHR predicted anemia and IDA (anemia: WHtR aOR 2.006 p=0.036; WHR aOR 4.489 p<0.001; IDA: WHtR: aOR 2.942, p=0.012; WHR aOR 4.142, p<0.001). CONCLUSIONS: At least one in five WRA in the UK are iron deficient, highlighting the need to revise current policies. Greater central adiposity was strongly associated with impaired iron status and the development of anemia, IDA, and ID.

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AIMS: Dynamic alterations in cardiac DNA methylation have been implicated in the development of heart failure (HF) with evidence of ischaemic heart disease (IHD); however, there is limited research into cell specific, DNA methylation sensitive genes that are affected by dysregulated DNA methylation patterns. In this study, we aimed to identify DNA methylation sensitive genes in the ischaemic heart and elucidate their role in cardiac fibrosis. METHODS: A multi-omics integrative analysis was carried out on RNA sequencing and methylation sequencing on HF with IHD (n = 9) versus non-failing (n = 9) left ventricular tissue, which identified Integrin beta-like 1 (ITGBL1) as a gene of interest. Expression of Itgbl1 was assessed in three animal models of HF; an ischaemia-reperfusion pig model, a myocardial infarction mouse model and an angiotensin-II infused mouse model. Single nuclei RNA sequencing was carried out on heart tissue from angiotensin-II infused mice to establish the expression profile of Itgbl1 across cardiac cell populations. Subsequent in vitro analyses were conducted to elucidate a role for ITGBL1 in human cardiac fibroblasts. DNA pyrosequencing was applied to assess ITGBL1 CpG methylation status in genomic DNA from human cardiac tissue and stimulated cardiac fibroblasts. RESULTS: ITGBL1 was >2-fold up-regulated (FDR adj P = 0.03) and >10-fold hypomethylated (FDR adj P = 0.01) in human HF with IHD left ventricular tissue compared with non-failing controls. Expression of Itgbl1 was up-regulated in three isolated animal models of HF and showed conserved correlation between increased Itgbl1 and diastolic dysfunction. Single nuclei RNA sequencing highlighted that Itgbl1 is primarily expressed in cardiac fibroblasts, while functional studies elucidated a role for ITGBL1 in cardiac fibroblast migration, evident in 50% reduced 24 h fibroblast wound closure occurring subsequent to siRNA-targeted ITGBL1 knockdown. Lastly, evidence provided from DNA pyrosequencing supports the theory that differential expression of ITGBL1 is caused by DNA hypomethylation. CONCLUSIONS: ITGBL1 is a gene that is mainly expressed in fibroblasts, plays an important role in cardiac fibroblast migration, and whose expression is significantly increased in the failing heart. The mechanism by which increased ITGBL1 occurs is through DNA hypomethylation.

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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.

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Hypertrophic cardiomyopathy (HCM) is a disease, which is difficult to diagnose at an early stage and for which there is a pressing need for more effective treatment options. The purpose of this study was to compare the molecular profile of HCM to that of ischaemic cardiomyopathy (ISCM) and dilated cardiomyopathy (DCM) for identification of protein and pathway targets that could support the development of better diagnostic and treatment options for HCM. A high-throughput mass spectrometry workflow was applied to achieve deep quantitative coverage of left ventricular tissue from HCM, DCM, ISCM and non-heart-failure control patients. HCM had a diverse proteomic profile compared to that of DCM and ISCM. Differentially expressed proteins unique to HCM were identified based on an observed fold change of ≥1.5 or ≤0.67 and q-value ≤ 0.05. Candidate proteins of interest were found to be significantly associated with clinical features of HCM. The significant association between these proteins and HCM was validated in an independent dataset. This represents one of the largest and deepest proteomic datasets for myocardial tissue reported to date. The dataset highlights the diverse proteomic profile of HCM, relative to other cardiomyopathies, and reveals disease-relevant pathways and promising biomarker candidates that are uniquely associated with HCM.

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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.

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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.

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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.

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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.

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Rationale: Obstructive sleep apnea (OSA) is an independent risk factor for cardiovascular (CV) morbidity and mortality, but the benefit of continuous positive airway pressure (CPAP) is uncertain. However, most randomized controlled trials have focused on the role of CPAP in secondary prevention, although there is growing evidence of a potential benefit on early CV disease. Weight loss in combination with CPAP may be superior but is difficult to achieve and maintain with conventional measures alone. Objectives: The aim of this study was to gain insights into the effect of CPAP on early atherosclerotic processes and to compare it with a glucagon-like peptide (GLP)-1-mediated weight loss regimen in patients with OSA. Methods: We performed a randomized proof-of-concept study comparing CPAP, a GLP1-mediated weight-loss regimen (liraglutide [Lir]), and both in combination for 24 weeks in 30 consecutive patients with OSA (apnea-hypopnea index >15 events/h; body mass index 30-40 kg/m2; and no history of diabetes, heart failure, or unstable CV disease). In addition to extensive evaluation for CV risk factors and endothelial function at baseline and end of study, subjects underwent 18F-fluoro-2-deoxy-D-glucose positron emission tomography-computed tomography (18F-FDG PET-CT) for the measurement of aortic wall inflammation (target-to-background ratio) and coronary computed tomography angiography for semiautomated coronary plaque analysis. Results: Baseline characteristics were similar between groups. CPAP alone and in combination resulted in greater reduction in apnea-hypopnea index than Lir alone (mean difference, -45 and -43 events/h, respectively, vs. -12 events/h; P < 0.05). Both Lir and combination treatment led to significant weight loss, but only CPAP alone resulted in significant decrease in vascular inflammation (aortic wall target-to-background ratio from 2.03 ± 0.34 to 1.84 ± 0.43; P = 0.010), associated with an improvement in endothelial function and a decrease in C-reactive protein. Low-attenuation coronary artery plaque volume as a marker of unstable plaque also decreased with CPAP (from 571 ± 490 to 334 ± 185 mm3) and with combination therapy (from 401 ± 145 to 278 ± 126 mm3) but not with Lir. Conclusions: These data suggest that CPAP therapy, but not GLP1-mediated weight loss, improves vascular inflammation and reduces unstable plaque volume in patients with OSA. Further large randomized controlled studies are warranted to assess the benefit of CPAP therapy in modifying early CV disease. Clinical trial registered with www.clinicaltrials.gov (NCT04186494).

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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.

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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.

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BACKGROUND: The heart failure (HF) virtual consultation (VC) is an eHealth tool for delivery of peer-to-peer specialist advice to general practitioners (GPs) to discuss HF diagnosis/management. We aim to investigate the impact of the VC service on onward referral rate and quality of assessment by GPs, as well as assess VC patient characteristics; Clinical Frailty Score (CSF), age and morbidity. METHODS: This prospective observational study collected VC data on: demographics, comorbidity, frailty, referral indication, the impact of VC on clinical care and the GP response to the question 'what would you have done without the VC service'. We compared patient characteristics to a control population of patients attending the HF unit (HFU) (n=118). REULTS: Between 2015 and 2021, 1681 VC cases were discussed. The majority of cases were discussed from remote areas (75%). Rediscussion cases increased from 0% to 34%. VC patients were older (76.2 (±11.3) vs 73.1 (±12.5) years, p<0.05), more frail (CSF=3.8 (±1.7) vs 3 (±1.6), p<0.01) and multimorbid (number of comorbidities=7.1 (±3.4) vs 3.8 (±1.9), p<0.001) compared with patients attending the HFU. Without the VC, 93% of cases would have been referred to face-to-face hospital services. Instead, VC resulted in only 9% of cases being referred to hospital services. The remainder of cases were managed by the VC service, in a shared GP-specialist approach. GP use of natriuretic peptide (NP) increased from 0% in 2015-2016 to 63% in 2021 and use of TTE increased from 0% in 2015-2016 to 69% by 2021. CONCLUSIONS: The VC service provides a platform for case discussion in particular for older, frailer patients and reduces onward hospital referrals. This may facilitate early diagnosis and management of suspected HF in the current era of long outpatient waiting times. The quality of community HF assessment improved as indicated by increased use of NP/TTE by GPs.

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Importance: Pre-heart failure with preserved ejection fraction (pre-HFpEF) is common and has no specific therapy aside from cardiovascular risk factor management. Objective: To investigate the hypothesis that sacubitril/valsartan vs valsartan would reduce left atrial volume index using volumetric cardiac magnetic resonance imaging in patients with pre-HFpEF. Design, Setting, and Participants: The Personalized Prospective Comparison of ARNI [angiotensin receptor/neprilysin inhibitor] With ARB [angiotensin-receptor blocker] in Patients With Natriuretic Peptide Elevation (PARABLE) trial was a prospective, double-blind, double-dummy, randomized clinical trial carried out over 18 months between April 2015 and June 2021. The study was conducted at a single outpatient cardiology center in Dublin, Ireland. Of 1460 patients in the STOP-HF program or outpatient cardiology clinics, 461 met initial criteria and were approached for inclusion. Of these, 323 were screened and 250 asymptomatic patients 40 years and older with hypertension or diabetes, elevated B-type natriuretic peptide (BNP) greater than 20 pg/mL or N-terminal pro-b-type natriuretic peptide greater than 100 pg/mL, left atrial volume index greater than 28 mL/m2, and preserved ejection fraction greater than 50% were included. Interventions: Patients were randomized to angiotensin receptor neprilysin inhibitor sacubitril/valsartan titrated to 200 mg twice daily or matching angiotensin receptor blocker valsartan titrated to 160 mg twice daily. Main Outcomes and Measures: Maximal left atrial volume index and left ventricular end diastolic volume index, ambulatory pulse pressure, N-terminal pro-BNP, and adverse cardiovascular events. Results: Among the 250 participants in this study, the median (IQR) age was 72.0 (68.0-77.0) years; 154 participants (61.6%) were men and 96 (38.4%) were women. Most (n = 245 [98.0%]) had hypertension and 60 (24.0%) had type 2 diabetes. Maximal left atrial volume index was increased in patients assigned to receive sacubitril/valsartan (6.9 mL/m2; 95% CI, 0.0 to 13.7) vs valsartan (0.7 mL/m2; 95% CI, -6.3 to 7.7; P < .001) despite reduced markers of filling pressure in both groups. Changes in pulse pressure and N-terminal pro-BNP were lower in the sacubitril/valsartan group (-4.2 mm Hg; 95% CI, -7.2 to -1.21 and -17.7%; 95% CI, -36.9 to 7.4, respectively; P < .001) than the valsartan group (-1.2 mm Hg; 95% CI, -4.1 to 1.7 and 9.4%; 95% CI, -15.6 to 4.9, respectively; P < .001). Major adverse cardiovascular events occurred in 6 patients (4.9%) assigned to sacubitril/valsartan and 17 (13.3%) assigned to receive valsartan (adjusted hazard ratio, 0.38; 95% CI, 0.17 to 0.89; adjusted P = .04). Conclusions and Relevance: In this trial of patients with pre-HFpEF, sacubitril/valsartan treatment was associated with a greater increase in left atrial volume index and improved markers of cardiovascular risk compared to valsartan. More work is needed to understand the observed increased cardiac volumes and long-term effects of sacubitril/valsartan in patients with pre-HFpEF. Trial Registration: ClinicalTrials.gov Identifier: NCT04687111.

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Heart failure (HF) is the leading cause of hospitalisations worldwide, with only 35% of patients surviving the first 5 years after diagnosis. The pathogenesis of HF with preserved ejection fraction (HFpEF) is still unclear, impeding the implementation of effective treatments. FK506-binding protein like (FKBPL) and its therapeutic peptide mimetic, AD-01, are critical mediators of angiogenesis and inflammation. Thus, in this study, we investigated-for the first time-FKBPL's role in the pathogenesis and as a biomarker of HFpEF. In vitro models of cardiac hypertrophy following exposure to a hypertensive stimulus, angiotensin-II (Ang-II, 100 nM), and/or AD-01 (100 nM), for 24 and 48 h were employed as well as human plasma samples from people with different forms of HFpEF and controls. Whilst the FKBPL peptide mimetic, AD-01, induced cardiomyocyte hypertrophy in a similar manner to Ang-II (p < 0.0001), when AD-01 and Ang-II were combined together, this process was abrogated (p < 0.01-0.0001). This mechanism appears to involve a negative feedback loop related to FKBPL (p < 0.05). In human plasma samples, FKBPL concentration was increased in HFpEF compared to controls (p < 0.01); however, similar to NT-proBNP and Gal-3, it was unable to stratify between different forms of HFpEF: acute HFpEF, chronic HFpEF and hypertrophic cardiomyopathy (HCM). FKBPL may be explored for its biomarker and therapeutic target potential in HFpEF.

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INTRODUCTION: Across all WHO regions, Africa has the highest prevalence of hypertension with 46% of the population >25 years estimated to be hypertensive. Blood pressure (BP) control is poor, with <40% of hypertensives diagnosed, <30% of those diagnosed receiving medical treatment, and <20% with adequate control. We report an intervention to improve BP control in a cohort of hypertensive patients attending a single hospital in Mzuzu Malawi, by introducing a limited protocol of four antihypertensive medications taken once-daily. METHODS: A drug protocol based on international guidelines, drug availability in Malawi, cost and clinical effectiveness was developed and implemented. Patients were transitioned to the new protocol as they attended for clinic visits. Records of 109 patients completing at least three visits were assessed for BP control. RESULTS: Two-thirds of patients (n=73) were female and average age at enrolment was 61.6 ± 12.8 years. Median [interquartile range] systolic BP (SBP) was 152 [136;167] mm Hg at baseline and reduced over the follow-up period to 148 [135; 157, p<0.001 vs baseline]. Median diastolic BP (DBP) reduced from 90.0 [82.0; 100] mm Hg to 83.0 [77.0; 91.0], p<0.001 vs baseline. Patients with highest baseline blood pressures benefited most and there were no associations noted between BP responses and either age or gender. DISCUSSION: We conclude that a limited evidence based once-daily drug regimen can improve blood pressure control by comparison with standard management. Cost effectiveness of this approach will also be reported.

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Background: As pharmacogenomic services begin to emerge in primary care, the insight of the public is crucial for its integration into clinical practice. Objectives: To establish perceptions of pharmacogenomics (awareness, understanding, openness to availability, perceived benefits and concerns, willingness to pay, and service setting) and investigate if they differ between those with and without chronic disease(s). Methods: An anonymous, online questionnaire generated using Qualtrics® and circulated via social media and posters placed in eight participating community pharmacies was conducted with Irish adults. The questions were designed to consider existing literature on patient perceptions of pharmacogenomics. Descriptive statistics were used to summarize questionnaire responses. Chi-square test was used to compare categorical variables, while independent sample t-test and one-way ANOVA were used to compare the mean values of two (with and without chronic disease) and three groups (multimorbidity (two or more chronic conditions) and polypharmacy (prescribed four or more regular medicines) (MMPP), a single chronic disease, and those without existing medical conditions) respectively Logistic regression was used to evaluate age and gender adjusted associations of chronic disease(s) with responses. A p-value <0.05 was considered statistically significant. Results: A total of 421 responses were received, 30% (n = 120) of whom reported having a chronic disease. Overall, respondents reported low awareness (44%, n = 166) and poor knowledge (55%, n = 212) of pharmacogenomics. After explaining pharmacogenomics to respondents, patients with chronic disease(s) were 2.17 times more likely (p < 0.001) to want pharmacogenomic services availability than those without existing conditions, adjusted for age and gender (driven by preferences of those with MMPP than those with single chronic disease). Respondents demonstrated a high level of interest and noted both the potential benefits and downsides of pharmacogenomic testing. Willingness-to-pay was not associated with having a chronic disease and respondents were more positive about primary care (community pharmacy or general practice) rather than hospital-based pharmacogenomics implementation. Conclusion: The Irish public in general and those with chronic disease in particular are strongly supportive of pharmacogenomic testing, highlighting an unmet need for its incorporation in medicines optimization. These data underline the need for more research on the implementation of community-based pharmacogenomics services for MMPP patients and ubiquitous pharmacogenomics education programs.

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BACKGROUND: Myocardial fibrosis leads to diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM). OBJECTIVES: To evaluate a manual method of measuring mitral annular relaxation velocity (termed cardiac MRI e') as a measure of diastolic dysfunction on routine cardiac MRI and its relationship with myocardial late-gadolinium enhancement (LGE) and feature tracking measures of diastolic dysfunction in patients with HCM. METHODS: CMR e', feature tracking measures of diastolic function, left atrial, left ventricular (LV) parameters and LGE were retrospectively measured in 75 patients with HCM (mean age, 54.7 years ± 15.3, 54 men). Multivariate regression and partial Spearman correlations were performed. RESULTS: Cardiac MRI e' measures correlated with LGE (r = 0.49, P < 0.001) and multiple feature tracking measures of diastolic function, adjusted for patient demographics, left atrial and left ventricular parameters. Cardiac MRI e' measures were independently predictive of LGE ≥ 10% (mean total cardiac MRI e': LGE < 10% vs LGE ≥ 10% was 3.5 cm/s vs. 1.7 cm/s, P < 0.001). Superior CMR e' had an AUC of 0.79 [95%CI 0.66-0.92, P < 0.0001]) in predicting patients with LGE ≥ 10% and a cutoff of 1.7 cm/s resulted in a sensitivity and specificity of 81.0% and 78.0% respectively. CONCLUSION: Cardiac MRI e' is a manual measure of LV diastolic dysfunction acquired on routine cardiac MRI without specialized software and is an independent predictor of LGE ≥ 10% and diastolic dysfunction in HCM.

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Conventional medicines optimisation interventions in people with multimorbidity and polypharmacy are complex and yet limited; a more holistic and integrated approach to healthcare delivery is required. Pharmacogenetics has potential as a component of medicines optimisation. Studies involving multi-medicine pharmacogenetics in adults with multimorbidity or polypharmacy, reporting on outcomes derived from relevant core outcome sets, were included in this systematic review. Narrative synthesis was undertaken to summarise the data; meta-analysis was inappropriate due to study heterogeneity. Fifteen studies of diverse design and variable quality were included. A small, randomised study involving pharmacist-led medicines optimisation, including pharmacogenetics, suggests this approach could have significant benefits for patients and health systems. However, due to study design heterogeneity and the quality of the included studies, it is difficult to draw generalisable conclusions. Further pragmatic, robust pharmacogenetics studies in diverse, real-world patient populations, are required to establish the benefit of multi-medicine pharmacogenetic screening on patient outcomes.

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