Heart of England: HEFT Repository
Not a member yet
5360 research outputs found
Sort by
Targeted communication reduces the inappropriate use of Early Warning Scores in patients with treatment limitations.
No full textAcute intermittent hypoxia drives hepatic lipogenesis in humans and rodents.
No full textBackground and aims
Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver condition. It is tightly associated with an adverse metabolic phenotype (including obesity and type 2 diabetes) as well as with obstructive sleep apnoea (OSA) of which intermittent hypoxia is a critical component. Hepatic (DNL) is a significant contributor to hepatic lipid content and the pathogenesis of NAFLD and has been proposed as a key pathway to target in the development of pharmacotherapies to treat NAFLD. Our aim is to use experimental models to investigate the impact of hypoxia on hepatic lipid metabolism independent of obesity and metabolic disease.
Methods
Human and rodent studies incorporating stable isotopes and hyperinsulinaemic euglycaemic clamp studies were performed to assess the regulation of DNL and broader metabolic phenotype by intermittent hypoxia. Cell-based studies, including pharmacological and genetic manipulation of hypoxia-inducible factors (HIF), were used to examine the underlying mechanisms.
Results
Hepatic DNL increased in response to acute intermittent hypoxia in humans, without alteration in glucose production or disposal. These observations were endorsed in a prolonged model of intermittent hypoxia in rodents using stable isotopic assessment of lipid metabolism. Changes in DNL were paralleled by increases in hepatic gene expression of acetyl CoA carboxylase 1 and fatty acid synthase. In human hepatoma cell lines, hypoxia increased both DNL and fatty acid uptake through HIF-1α and -2α dependent mechanisms.
Conclusions
These studies provide robust evidence linking intermittent hypoxia and the regulation of DNL in both acute and sustained models of intermittent hypoxia, providing an important mechanistic link between hypoxia and NAFLD
A population-based study of 92 clinically recognized risk factors for heart failure: co-occurrence, prognosis and preventive potential.
No full textAIMS
Primary prevention strategies for heart failure (HF) have had limited success, possibly due to a wide range of underlying risk factors (RFs). Systematic evaluations of the prognostic burden and preventive potential across this wide range of risk factors are lacking. We aimed at estimating evidence, prevalence and co-occurrence for primary prevention and impact on prognosis of RFs for incident HF.
METHODS AND RESULTS
We systematically reviewed trials and observational evidence of primary HF prevention across 92 putative aetiologic RFs for HF identified from US and European clinical practice guidelines. We identified 170 885 individuals aged ≥30 years with incident HF from 1997 to 2017, using linked primary and secondary care UK electronic health records (EHR) and rule-based phenotypes (ICD-10, Read Version 2, OPCS-4 procedure and medication codes) for each of 92 RFs. Only 10/92 factors had high quality observational evidence for association with incident HF; 7 had effective randomized controlled trial (RCT)-based interventions for HF prevention (RCT-HF), and 6 for cardiovascular disease prevention, but not HF (RCT-CVD), and the remainder had no RCT-based preventive interventions (RCT-0). We were able to map 91/92 risk factors to EHR using 5961 terms, and 88/91 factors were represented by at least one patient. In the 5 years prior to HF diagnosis, 44.3% had ≥4 RFs. By RCT evidence, the most common RCT-HF RFs were hypertension (48.5%), stable angina (34.9%), unstable angina (16.8%), myocardial infarction (15.8%), and diabetes (15.1%); RCT-CVD RFs were smoking (46.4%) and obesity (29.9%); and RCT-0 RFs were atrial arrhythmias (17.2%), cancer (16.5%), heavy alcohol intake (14.9%). Mortality at 1 year varied across all 91 factors (lowest: pregnancy-related hormonal disorder 4.2%; highest: phaeochromocytoma 73.7%). Among new HF cases, 28.5% had no RCT-HF RFs and 38.6% had no RCT-CVD RFs. 15.6% had either no RF or only RCT-0 RFs.
CONCLUSION
One in six individuals with HF have no recorded RFs or RFs without trials. We provide a systematic map of primary preventive opportunities across a wide range of RFs for HF, demonstrating a high burden of co-occurrence and the need for trials tackling multiple RFs
Comparing medication adherence in patients receiving bisphosphonates for preventing fragility fractures: a comprehensive systematic review and network meta-analysis.
No full textBACKGROUND
Bisphosphonates are effective in preventing fragility fractures; however, high rates of adherence are needed to preserve clinical benefits.
OBJECTIVE
To investigate persistence and compliance to oral and intravenous bisphosphonates (alendronate, ibandronate, risedronate, and zoledronate).
METHODS
Searches of 12 databases, unpublished sources, and trial registries were conducted, covering the period from 2000 to April 2021. Screening, data extraction, and risk of bias assessment (Cochrane Collaboration risk-of-bias tool 1.0 & ROBINS-I) were independently undertaken by two study authors. Randomised controlled trials (RCTs) and observational studies that used prescription claim databases or hospital medical records to examine patients' adherence were included. Network meta-analyses (NMA) embedded within a Bayesian framework were conducted, investigating users' likelihood in discontinuing bisphosphonate treatment. Where meta-analysis was not possible, data were synthesised using the vote-counting synthesis method.
RESULTS
Fifty-nine RCTs and 43 observational studies were identified, resulting in a total population of 2,656,659 participants. Data from 59 RCTs and 24 observational studies were used to populate NMAs. Zoledronate users were the least likely to discontinue their treatment HR = 0.73 (95%CrI: 0.61, 0.88). Higher rates of compliance were observed in those receiving intravenous treatments. The paucity of data and the heterogeneity in the reported medication possession ratio thresholds precluded a NMA of compliance data.
CONCLUSIONS
Users of intravenously administered bisphosphonates were found to be the most adherent to treatment among bisphosphonates' users. Patterns of adherence will permit the more precise estimation of clinical and cost-effectiveness of bisphosphonates.
TRIAL REGISTRATION
PROSPERO 2020 CRD42020177166
Correction: Rate of pancreatic cancer following a negative endoscopic ultrasound and associated factors.
No full textFemoral neck system reduces surgical time and complications in adults with femoral neck fractures: A systematic review and meta-analysis.
No full textPurpose
Femoral neck fractures (FNF) in adults are conventionally managed with surgical options. This paper is aimed to assess the safety, and functional outcomes of the novel Femoral neck system (FNS) for FNF treatment in adult population.
Methods
An organized quest of four literature databases (PubMed, Scopus, Web of Science, and Cochrane Library) was performed on March 1, 2022 using the term "femoral neck system". Fixed or random-effect meta-analysis was used to analyse the outcome measures after selecting relevant studies and assessing their quality. Heterogeneity was considered when calculating pooled effect sizes and 95% confidence ranges.
Results
On comparing FNS with cannulated cancellous screws (CCS) or other methods, in a total of 762 patients (351 FNS and 411 CCS) in the 11 comparative studies considered for meta-analysis, blood loss was pointedly higher overall in the FNS group, mean difference 115.77 ml; 95% CI 3.11 ml, 28.42 ml; test of overall effect: z = 1.68, p = 0.09); with considerable heterogeneity. However, in the FNS group the operative time was substantially lower (Mean difference -7.91 min; 95% CI -15.01, -0.80; test of overall effect: z = 2.18, p = 0.03, with marked heterogeneity). Moreover, complications such as infections, non-union, osteonecrosis, implant cut-out were significantly lower in the FNS group with a Mantel Haenszel Odds ratio of 0.20 (95% CI 0.12, 0.34: Z = 6.01, p < 0.0001).
Conclusion
Keeping in mind the heterogenicity of the studies, -management of adult patients with FNF with FNS can provide results comparable to traditional fixation methods with significantly lower rate of complications
Combined Perioperative Lapatinib and Trastuzumab in Early HER2-Positive Breast Cancer Identifies Early Responders: Randomized UK EPHOS-B Trial Long-Term Results.
No full textBACKGROUND
EPHOS-B aimed to determine whether perioperative anti-HER2 therapy inhibited proliferation and/or increased apoptosis in HER2-positive breast cancer.
PATIENTS AND METHODS
This randomized phase II, two-part, multicenter trial included newly diagnosed women with HER2-positive invasive breast cancer due to undergo surgery. Patients were randomized to: part 1 (1:2:2), no treatment (control), trastuzumab or lapatinib; part 2 (1:1:2) control, trastuzumab, or lapatinib and trastuzumab combination. Treatment was given for 11 days presurgery. Coprimary endpoints were change in Ki67 and apoptosis between baseline and surgery tumor samples (biologic response: ≥30% change). Central pathology review scored residual cancer burden (RCB). Relapse-free survival (RFS) explored long-term effects.
RESULTS
Between November 2010 and September 2015, 257 patients were randomized (part 1: control 22, trastuzumab 57, lapatinib 51; part 2: control 29, trastuzumab 32, combination 66). Ki67 response was evaluable for 223 patients: in part 1 Ki67 response occurred in 29/44 (66%) lapatinib versus 18/49 (37%) trastuzumab ( = 0.007) and 1/22 (5%) control ( < 0.0001); in part 2 in 36/49 (74%) combination versus 14/31 (45%) trastuzumab ( = 0.02) and 2/28 (7%) control ( < 0.0001). No significant increase in apoptosis after 11 days was seen in treatment groups. Six patients achieved complete pathologic response (pCR, RCB0) and 13 RCB1, all but two in the combination group. After 6 years median follow-up, 28 (11%) had recurrence and 19 (7%) died. No recurrences or deaths were observed among patients who achieved a pCR. Ki67% falls ≥50% associated with fewer recurrences ( = 0.002).
CONCLUSIONS
Early response after short duration anti-HER2 dual therapy identifies cancers dependent on the HER2 pathway providing a strategy for exploring risk-adapted individualized treatment de-escalation
Myocardial Fibrosis Predicts Ventricular Arrhythmias and Sudden Death After Cardiac Electronic Device Implantation.
No full textBACKGROUND
Increasing evidence supports a link between myocardial fibrosis (MF) and ventricular arrhythmias.
OBJECTIVES
The purpose of this study was to determine whether presence of myocardial fibrosis on visual assessment (MF) and gray zone fibrosis (GZF) mass predicts sudden cardiac death (SCD) and ventricular fibrillation/sustained ventricular tachycardia after cardiac implantable electronic device (CIED) implantation.
METHODS
In this prospective study, total fibrosis and GZF mass, quantified using cardiovascular magnetic resonance, was assessed in relation to the primary endpoint of SCD and the secondary, arrhythmic endpoint of SCD or ventricular arrhythmias after CIED implantation.
RESULTS
Among 700 patients (age 68.0 ± 12.0 years), 27 (3.85%) experienced a SCD and 121 (17.3%) met the arrhythmic endpoint over median 6.93 years (IQR: 5.82-9.32 years). MF predicted SCD (HR: 26.3; 95% CI: 3.7-3,337; negative predictive value: 100%). In competing risk analyses, MF also predicted the arrhythmic endpoint (subdistribution HR: 19.9; 95% CI: 6.4-61.9; negative predictive value: 98.6%). Compared with no MF, a GZF mass measured with the 5SD method (GZF) >17 g was associated with highest risk of SCD (HR: 44.6; 95% CI: 6.12-5,685) and the arrhythmic endpoint (subdistribution HR: 30.3; 95% CI: 9.6-95.8). Adding GZF mass to MF led to reclassification of 39% for SCD and 50.2% for the arrhythmic endpoint. In contrast, LVEF did not predict either endpoint.
CONCLUSIONS
In CIED recipients, MF excluded patients at risk of SCD and virtually excluded ventricular arrhythmias. Quantified GZF mass added predictive value in relation to SCD and the arrhythmic endpoint
The Barriers and Facilitators to the Use of Lifestyle Apps: A Systematic Review of Qualitative Studies.
No full textBACKGROUND
Mobile-health applications are revolutionising the way healthcare is being delivered. However, current research focusses on apps aimed at monitoring of conditions rather than the prevention of disease. Healthcare apps that prevent disease can be classified as lifestyle apps (LAs) and encompass mindfulness, exercise, and diet apps. In order for widespread implementation of these apps, perspectives of the user must be taken into consideration. Therefore, this systematic literature review identifies the barriers and facilitators to the use of LAs from a user's perspective.
OBJECTIVE
To both identify the facilitators to the use of LAs from a user perspective as well as identify the barriers to the use of LAs from a user perspective.
METHODS
A systematic literature review was conducted following PRISMA guidelines. Qualitative articles focussed on a healthy non-diseased population were obtained. Two independent researchers coded the articles, and themes were identified.
RESULTS
Our results found that there were five barriers and five facilitators to app use. The facilitators included (1) motivational aspects to the user, (2) effective marketing and communication, (3) user-centred design and content, (4) humanising technology, and (5) accessibility. The five barriers identified were (1) a non-conducive, (2) poor marketing and branding, (3) controlling and invasive, (4) disengaging content, and (5) inaccessibility.
CONCLUSIONS
By overcoming the barriers of LAs and encouraging the facilitators found, users are more likely to engage with this method of health promotion. Future research must be conducted on the barriers and facilitators to development and distribution of apps in order for LAs to be implemented in widespread healthcare practice
