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Advanced heart failure: parenteral diuretics for breathlessness and peripheral oedema - systematic review.
Hughes, A, Oluyase, AO, Below, N, Bajwah, S
BMJ supportive & palliative care. 2024;(1):1-13
Abstract
BACKGROUND Advanced heart failure patients suffer with breathlessness and peripheral oedema, which are frequently treated with parenteral diuretics despite limited evidence. AIM: To analyse the effectiveness of parenteral diuretics on breathlessness and peripheral oedema in advanced heart failure patients. METHODS We searched Embase, MEDLINE(R), PsycINFO, CINAHL and CENTRAL from their respective inceptions to 2021, and performed handsearching, citation searching and grey literature search; limited to English publications. Selection criteria included parenteral (intravenous/subcutaneous) diuretic administration in advanced heart failure patients (New York Heart Association class III-IV). Two authors independently assessed articles for inclusion; one author extracted data. Data were synthesised through narrative synthesis or meta-analysed as appropriate. RESULTS 4646 records were screened; 6 trials (384 participants) were included. All were randomised controlled trials (RCTs) comparing intravenous continuous furosemide infusion (CFI) versus intravenous bolus furosemide infusion (BFI). Improvement in breathlessness and peripheral oedema (two studies, n=161, OR 2.80, 95% CI 1.45 to 5.40; I2=0%), and increase in urine output (four studies, n=234, mean difference, MD 344.76, 95% CI 132.87 to 556.64; I2=44%), were statistically significant in favour of CFI. Significantly lower serum potassium was found in BFI compared with CFI (three studies, n=194, MD -0.20, 95% CI -0.38 to -0.01; I2=0%). There was no difference between CFI and BFI on reduction in weight, renal function or length of hospital stay. CONCLUSIONS CFI appears to improve congestion in advanced heart failure patients in the short term. Available data came from small trials. Larger, prospective RCTs are recommended to address the evidence gap.
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine.
Tobias, DK, Merino, J, Ahmad, A, Aiken, C, Benham, JL, Bodhini, D, Clark, AL, Colclough, K, Corcoy, R, Cromer, SJ, et al
Nature medicine. 2023;(10):2438-2457
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Abstract
Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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The effect of combined β-lactoglobulin supplementation and resistance exercise training prior to limb immobilisation on muscle protein synthesis rates in healthy young adults: study protocol for a randomised controlled trial.
Hughes, A, Francis, T, Marjoram, L, Rooney, JH, Ellison-Hughes, G, Pollock, R, Curtis, MJ, Cape, A, Larsen, M, Phillips, BE, et al
Trials. 2023;(1):401
Abstract
BACKGROUND The decline in skeletal muscle mass experienced following a short-term period (days to weeks) of muscle disuse is mediated by impaired rates of muscle protein synthesis (MPS). Previous RCTs of exercise or nutrition prehabilitation interventions designed to mitigate disuse-induced muscle atrophy have reported limited efficacy. Hence, the aim of this study is to investigate the impact of a complex prehabilitation intervention that combines β-lactoglobulin (a novel milk protein with a high leucine content) supplementation with resistance exercise training on disuse-induced changes in free-living integrated rates of MPS in healthy, young adults. METHODS/DESIGN To address this aim, we will recruit 24 healthy young (18-45 years) males and females to conduct a parallel, double-blind, 2-arm, randomised placebo-controlled trial. The intervention group will combine a 7-day structured resistance exercise training programme with thrice daily dietary supplementation with 23 g of β-lactoglobulin. The placebo group will combine the same training programme with an energy-matched carbohydrate (dextrose) control. The study protocol will last 16 days for each participant. Day 1 will be a familiarisation session and days 2-4 will be the baseline period. Days 5-11 represent the 'prehabilitation period' whereby participants will combine resistance training with their assigned dietary supplementation regimen. Days 12-16 represent the muscle disuse-induced 'immobilisation period' whereby participants will have a single leg immobilised in a brace and continue their assigned dietary supplementation regimen only (i.e. no resistance training). The primary endpoint of this study is the measurement of free-living integrated rates of MPS using deuterium oxide tracer methodology. Measurements of MPS will be calculated at baseline, over the 7-day prehabilitation period and over the 5-day immobilisation period separately. Secondary endpoints include measurements of muscle mass and strength that will be collected on days 4 (baseline), 11 (end of prehabilitation) and 16 (end of immobilisation). DISCUSSION This novel study will establish the impact of a bimodal prehabilitation strategy that combines ß-lactoglobulin supplementation and resistance exercise training in modulating MPS following a short-term period of muscle disuse. If successful, this complex intervention may be translated to clinical practice with application to patients scheduled to undergo, for example, hip or knee replacement surgery. TRIAL REGISTRATION NCT05496452. Registered on August 10, 2022. PROTOCOL VERSION 16-12-2022/1.
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Telehealth Diabetes Prevention Program for Adults With Prediabetes in an Academic Medical Center Setting: Protocol for a Hybrid Type III Trial.
Gamble, A, Khan, T, Hughes, A, Guo, Y, Vasaitis, S, Bidwell, J, Christman, B
JMIR research protocols. 2023;:e50183
Abstract
BACKGROUND Diabetes is a costly epidemic in the United States associated with both health and economic consequences. These consequences can be mitigated by participation in structured lifestyle change programs such as the National Diabetes Prevention Program (DPP) led by the Centers for Disease Control and Prevention. Mississippi consistently has among the highest rates of diabetes and prediabetes nationally. Implementing the National DPP through large health care systems can increase reach and accessibility for populations at the highest risk for diabetes. Translational research on the National DPP in Mississippi has not been studied. OBJECTIVE This study aims to evaluate the implementation and impact of the National DPP delivered using telehealth modalities at the University of Mississippi Medical Center in Jackson, Mississippi. METHODS An effectiveness-implementation hybrid type III research design is proposed. The study design is guided by the Reach, Effectiveness, Adoption, Implementation, and Maintenance framework and the Practical, Robust Implementation and Sustainability Model. Participants are being recruited via provider referral, and the DPP is being delivered by trained lifestyle coaches. Study participants include adult (≥18 years) patients eligible for the DPP with at least 1 encounter at 1 of 3 ambulatory clinic specialties (lifestyle medicine, family medicine, and internal medicine) between January 2019 and December 2023. The National DPP eligibility criteria include a BMI ≥25 kg/m2 and hemoglobin A1c between 5.7% and 6.4%. The University of Mississippi Medical Center criteria include Medicare or Medicaid beneficiaries. The University of Mississippi Medical Center's a priori implementation plan was developed using the Consolidated Framework for Implementation Research and includes 23 discrete strategies. The primary aim will use an embedded mixed method process analysis to identify and mitigate challenges to implementation. The secondary aim will use a nonrandomized quasi-experimental design to assess the comparative effectiveness of the DPP on health care expenditures. A propensity score matching method will be implemented to compare case subjects to control subjects. The primary outcomes include patient referrals, participant enrollment, retention, engagement, the incidence of diabetes, and health care resource use and costs. RESULTS At baseline, of the 26,151 patients across 3 ambulatory clinic specialties, 1010 (3.9%) had prediabetes and were eligible for the National DPP. Of the 1010 patients, more than half (n=562, 55.6%) were aged 65 years or older, 79.5% (n=803) were Medicare beneficiaries, 65.9% (n=666) were female, and 70.8% (n=715) were obese. CONCLUSIONS This is the first translational study of the National DPP in Mississippi. The findings will inform implementation strategies impacting the uptake and sustainability of the National DPP delivered in an academic medical setting using distance learning and telehealth modalities. TRIAL REGISTRATION ClinicalTrials.gov NCT04822480; https://clinicaltrials.gov/study/NCT03622580. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/50183.
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Within-sibship genome-wide association analyses decrease bias in estimates of direct genetic effects.
Howe, LJ, Nivard, MG, Morris, TT, Hansen, AF, Rasheed, H, Cho, Y, Chittoor, G, Ahlskog, R, Lind, PA, Palviainen, T, et al
Nature genetics. 2022;(5):581-592
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Estimates from genome-wide association studies (GWAS) of unrelated individuals capture effects of inherited variation (direct effects), demography (population stratification, assortative mating) and relatives (indirect genetic effects). Family-based GWAS designs can control for demographic and indirect genetic effects, but large-scale family datasets have been lacking. We combined data from 178,086 siblings from 19 cohorts to generate population (between-family) and within-sibship (within-family) GWAS estimates for 25 phenotypes. Within-sibship GWAS estimates were smaller than population estimates for height, educational attainment, age at first birth, number of children, cognitive ability, depressive symptoms and smoking. Some differences were observed in downstream SNP heritability, genetic correlations and Mendelian randomization analyses. For example, the within-sibship genetic correlation between educational attainment and body mass index attenuated towards zero. In contrast, analyses of most molecular phenotypes (for example, low-density lipoprotein-cholesterol) were generally consistent. We also found within-sibship evidence of polygenic adaptation on taller height. Here, we illustrate the importance of family-based GWAS data for phenotypes influenced by demographic and indirect genetic effects.
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Changes in the behavioural determinants of health during the COVID-19 pandemic: gender, socioeconomic and ethnic inequalities in five British cohort studies.
Bann, D, Villadsen, A, Maddock, J, Hughes, A, Ploubidis, GB, Silverwood, R, Patalay, P
Journal of epidemiology and community health. 2021;(12):1136-1142
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BACKGROUND The COVID-19 pandemic is expected to have far-reaching consequences on population health. We investigated whether these consequences included changes in health-impacting behaviours which are important drivers of health inequalities. METHODS Using data from five representative British cohorts (born 2000-2002, 1989-1990, 1970, 1958 and 1946), we investigated sleep, physical activity (exercise), diet and alcohol intake (N=14 297). We investigated change in each behaviour (pre/during the May 2020 lockdown), and differences by age/cohort, gender, ethnicity and socioeconomic position (childhood social class, education attainment and adult financial difficulties). Logistic regression models were used, accounting for study design and non-response weights, and meta-analysis used to pool and test cohort differences in association. RESULTS Change occurred in both directions-shifts from the middle part of the distribution to both declines and increases in sleep, exercise and alcohol use. Older cohorts were less likely to report changes in behaviours while the youngest reported more frequent increases in sleep, exercise, and fruit and vegetable intake, yet lower alcohol consumption. Widening inequalities in sleep during lockdown were more frequent among women, socioeconomically disadvantaged groups and ethnic minorities. For other outcomes, inequalities were largely unchanged, yet ethnic minorities were at higher risk of undertaking less exercise and consuming lower amounts of fruit and vegetables. CONCLUSIONS Our findings provide new evidence on the multiple changes to behavioural outcomes linked to lockdown, and the differential impacts across generation, gender, socioeconomic circumstances across life, and ethnicity. Lockdown appeared to widen some (but not all) forms of health inequality.
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Obesity in young children and its relationship with diagnosis of asthma, vitamin D deficiency, iron deficiency, specific allergies and flat-footedness: A systematic review and meta-analysis.
Malden, S, Gillespie, J, Hughes, A, Gibson, AM, Farooq, A, Martin, A, Summerbell, C, Reilly, JJ
Obesity reviews : an official journal of the International Association for the Study of Obesity. 2021;(3):e13129
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There is evidence that a number of medical conditions and co-morbidities are associated with obesity in young children. This review explored whether there is evidence of associations with other conditions or co-morbidities. Observational studies of young children (mean age < 10 years) were identified using electronic searches of five databases (MEDLINE, Embase, CINAHL, AMED and SPORTDiscus). Of 27 028 studies screened, 41 (comprising 44 comparisons) met the inclusion criteria. These studies provided data on five distinct diseases/conditions: asthma (n = 16), vitamin D deficiency (n = 10), iron deficiency (n = 10), allergies (n = 4) and flat-footedness (n = 4). Thirty-two studies were appropriate for meta-analysis using random-effects models, and revealed obesity was significantly associated with having asthma (OR 1.5, 95% CI 1.3-1.7), vitamin D deficiency (OR 1.9, 95% CI 1.4-2.5) and iron deficiency (OR 2.1, 95% CI 1.4-3.2). Heterogeneity (I2 ) ranged from 57% to 61%. Narrative synthesis was conducted for all studies. There was no evidence of a consistent association between obesity in young children and eczema, dermatitis or rhinitis due to the low number of studies. However, there was an association with flat-footedness. These results have implications for health policy and practice and families. Further research leading to a greater understanding of the associations identified in this review is suggested.
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Sinecatechins ointment as a potential novel treatment for usual type vulval intraepithelial neoplasia: a single-centre double-blind randomised control study.
Yap, J, Slade, D, Goddard, H, Dawson, C, Ganesan, R, Velangi, S, Sahu, B, Kaur, B, Hughes, A, Luesley, D
BJOG : an international journal of obstetrics and gynaecology. 2021;(6):1047-1055
Abstract
OBJECTIVE To compare the safety and efficacy of 10% sinecatechins (Veregen® ) ointment against placebo in the treatment of usual type vulvar intraepithelial neoplasia (uVIN). DESIGN A Phase II double-blind randomised control trial. SETTING A tertiary gynaecological oncology referral centre. POPULATION All women diagnosed with primary and recurrent uVIN. METHODS Eligible patients were randomised 1:1 to receive either sinecatechins or placebo ointment (applied three times daily for 16 weeks) and were followed up at 2, 4, 8, 16, 32 and 52 weeks. MAIN OUTCOME MEASURES The primary outcome measure, recorded at 16 and 32 weeks, was histological response (HR). Secondary outcome measures included clinical (CR) response, toxicity, quality of life and pain scores. RESULTS There was no observed difference in HR between the two arms. However, of the 26 patients who were randomised, all 13 patients who received sinecatechins showed either complete (n = 5) or partial (n = 8) CR, when best CR was evaluated. In placebo group, three patients had complete CR, two had partial CR, six had stable disease and two were lost to follow up. Patients in the sinecatechins group showed a statistically significant improvement in best observed CR as compared with the placebo group (P = 0.002). There was no difference in toxicity reported in either group. CONCLUSION Although we did not observe a difference in HR between the two treatment arms, we found that 10% sinecatechins application is safe and shows promise in inducing clinical resolution of uVIN lesions and symptom improvement, thus warranting further investigation in a larger multicentre study. TWEETABLE ABSTRACT A randomised control study indicating that sinecatechins ointment may be a novel treatment for uVIN.
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Assessing the acceptability of an adapted preschool obesity prevention programme: ToyBox-Scotland.
Malden, S, Reilly, JJ, Hughes, A, Bardid, F, Summerbell, C, De Craemer, M, Cardon, G, Androutsos, O, Manios, Y, Gibson, AM
Child: care, health and development. 2020;(2):213-222
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BACKGROUND Childhood obesity is a global public health issue. Interventions to prevent the onset of obesity in the early years are often implemented in preschool settings. The ToyBox intervention was delivered across Europe and targeted energy balance-related behaviours in preschools and children's homes through teacher-led activities and parental education materials and was adapted for use in Scotland. This study assessed the acceptability of the 18-week adapted intervention to both parents and teachers. METHODS Mixed methods were employed to collect both qualitative and quantitative data. Preschool staff and children's parents/caregivers completed post-intervention feedback surveys, from which acceptability scores were calculated and presented as proportions. Focus groups were conducted with preschool staff, whereas parents/caregivers participated in semi-structured interviews. A thematic analysis was applied to qualitative data following the development of a coding framework. Quantitative and qualitative data were analysed using SPSS and NVivo 10, respectively. RESULTS Preschool staff rated the intervention as highly acceptable based on post-intervention feedback surveys (80%; mean score 8.8/11). Lower acceptability scores were observed for parents/caregivers (49%; 3.9/8). Nine preschool practitioners participated in focus groups (n = 3). User-friendliness of the intervention materials, integration of the intervention with the curriculum, and flexibility of the intervention were identified as facilitators to delivery. Barriers to delivery were time, insufficient space, and conflicting policies within preschools with regard to changing classroom layouts. Parental interviews (n = 4) revealed a lack of time to be a major barrier, which prevented parents from participating in home-based activities. Parents perceived the materials to be simple to understand and visually appealing. CONCLUSIONS This study identified a number of barriers and facilitators to the delivery and evaluation of the ToyBox Scotland preschool obesity prevention programme, which should be considered before any further scale-up of the intervention.
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Using compositional principal component analysis to describe children's gut microbiota in relation to diet and body composition.
Leong, C, Haszard, JJ, Heath, AM, Tannock, GW, Lawley, B, Cameron, SL, Szymlek-Gay, EA, Gray, AR, Taylor, BJ, Galland, BC, et al
The American journal of clinical nutrition. 2020;(1):70-78
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BACKGROUND Gut microbiota data obtained by DNA sequencing are complex and compositional because of large numbers of detectable taxa, and because microbiota characteristics are described in relative terms. Nutrition researchers use principal component analysis (PCA) to derive dietary patterns from food data. Although compositional PCA methods are not commonly used to describe patterns from complex microbiota data, this approach would be useful for identifying gut microbiota patterns associated with diet and body composition. OBJECTIVES To use compositional PCA to describe the principal components (PCs) of gut microbiota in 5-y-old children and explore associations between microbiota components, diet, and BMI z-score. METHODS A fecal sample was provided by 319 children aged 5 y. Their primary caregiver completed a validated 123-item quantitative FFQ. Body composition was determined using DXA, and a BMI z-score was calculated. Compositional PCA identified characterizing taxa and weightings for calculation of gut microbiota PC scores at the genus level, and was examined in relation to diet and body size. RESULTS Three gut microbiota PCs were found. PC1 (negative loadings on uncultured Christensenellaceae and Ruminococcaceae) was related to lower BMI z-scores and longer duration of breastfeeding (per month) (β = -0.14; 95% CI: -0.26, -0.02; and β = 0.02; 95% CI: 0.003, 0.34, respectively). PC2 (positive loadings on Fusicatenibacter and Bifidobacterium; negative loadings on Bacteroides) was associated with a lower intake of nuts, seeds, and legumes (β = -0.05 per gram; 95% CI: -0.09, -0.01). When adjusted for fiber intake, PC2 was also associated with higher BMI z-scores (β = 0.12; 95% CI: 0.01, 0.24). PC3 (positive loadings on Faecalibacterium, Eubacterium, and Roseburia) was associated with higher intakes of fiber (β = 0.02 per gram; 95% CI: 0.003, 0.04) and total nonstarch polysaccharides (β = 0.02 per gram; 95% CI: 0.003, 0.04). CONCLUSIONS Our results suggest that specific gut microbiota components determined using compositional PCA are associated with diet and BMI z-score.This trial was registered at clinicaltrials.gov as NCT00892983.