5,544 research outputs found
The PREVENT Study: Preventing hospital admissions attributable to gout
BackgroundGout is the most common form of inflammatory arthritis, affecting 1 in 40 people in the UK. Despite highly effective treatments, hospital admissions for gout flares have doubled in England over the last 20 years. Many of these admissions may have been prevented if optimal gout management had been delivered to patients.Objectives1. Describe the epidemiology of gout management in primary and secondary care in the UK.2. Develop an intervention package for implementation during hospitalisations for gout flares, with the aim of improving care and reducing hospitalisations.3. Implement and evaluate this intervention in people hospitalised for gout.MethodsI used population-level health datasets (CPRD, OpenSAFELY, NHS Digital Hospital Episode Statistics) to evaluate outcomes for people with incident gout diagnoses over a 20-year period. I used multivariable regression and survival modelling to analyse factors associated with outcomes, including: i) initiation of urate-lowering therapies (ULT); ii) attainment of serum urate targets; and iii) hospitalisations for gout flares.With extensive stakeholder input, I developed an evidence-based intervention package to optimise hospital gout care. This incorporated the findings of a systematic literature review and process mapping of the admitted patient journey in a cohort of hospitalised gout patients. My intervention consisted of a care pathway, based upon British (BSR), European (EULAR) and American (ACR) gout management guidelines, which encouraged ULT initiation prior to discharge, followed by a nurse-led, post-discharge review to facilitate handover to primary care. I implemented this intervention in patients hospitalised for gout flares at Kingâs College Hospital over a 12-month period, and evaluated outcomes including ULT initiation, urate target attainment and re-admission rates.ResultsIn the UK, between 2004 and 2020, I showed that only 29% of patients with gout were initiated on ULT within 12 months of diagnosis, while only 36% attained urate targets. No significant improvements in these outcomes were observed after publication of updated BSR and EULAR gout management guidelines. Comorbidities, including chronic kidney disease, heart failure and obesity, associated with increased odds of ULT initiation but decreased odds of attaining urate targets. For patients who were diagnosed with gout during the COVID-19 pandemic, I showed that ULT initiation improved modestly, relative to before the pandemic, while urate target attainment trends were similar. Underlying these trends was a 31% decrease in incident gout diagnoses in England during the first year of the pandemic.Using linked primary and secondary care data, I showed that the risk of hospitalisations for gout flares is greatest within the first 6 months after diagnosis. ULT initiation is associated with more hospitalisations for flares within the first 6 months of diagnosis, but a reduced risk of hospitalisations beyond 12 months; particularly when urate targets are attained.After process mapping the admitted patient journey and systematically appraising the evidence base, I developed and implemented a multi-faceted intervention at Kingâs College Hospital, with the aim of improving hospital gout care. Following implementation of this intervention, the proportion of hospitalised gout patients who initiated ULT increased from 49% to 92%; more patients achieved serum urate targets; and there were 38% fewer repeat hospitalisations for gout flares.ConclusionsAt a population level, ULT initiation and urate target attainment remain sub-optimal for people with gout in the UK, despite updated management guidelines. Initiation of ULT is associated with long-term reductions in hospitalisations for flares; however, only a minority of patients hospitalised for gout flares are initiated on ULT. After designing and implementing a strategy to optimise hospital gout care, over 90% of patients were initiated on ULT, urate target attainment improved, and repeat hospitalisations decreased. My findings suggest that improved primary-secondary care integration is essential if we are to reverse the epidemic of gout hospitalisations
Recommended from our members
Loss of Emerin Alters Myogenic Signaling and miRNA Expression in Mouse Myogenic Progenitors
Emerin is an integral membrane protein of the inner nuclear membrane. Mutations in emerin cause X-linked Emery-Dreifuss muscular dystrophy (EDMD), a disease characterized by skeletal muscle wasting and dilated cardiomyopathy. Current evidence suggests the muscle wasting phenotype of EDMD is caused by defective myogenic progenitor cell differentiation and impaired muscle regeneration. We obtained genome-wide expression data for both mRNA and micro-RNA (miRNA) in wildtype and emerin-null mouse myogenic progenitor cells. We report here that emerin-null myogenic progenitors exhibit differential expression of multiple signaling pathway components required for normal muscle development and regeneration. Components of the Wnt, IGF-1, TGF-β, and Notch signaling pathways are misexpressed in emerin-null myogenic progenitors at both the mRNA and protein levels. We also report significant perturbations in the expression and activation of p38/Mapk14 in emerin-null myogenic progenitors, showing that perturbed expression of Wnt, IGF-1, TGF-β, and Notch signaling components disrupts normal downstream myogenic signaling in these cells. Collectively, these data support the hypothesis that emerin is essential for proper myogenic signaling in myogenic progenitors, which is necessary for myogenic differentiation and muscle regeneration.</p
Recommended from our members
Association of Mitochondrial DNA Polymerase Îł Gene <i>POLG1</i> Polymorphisms with Parkinsonism in Chinese Populations
Background: Mitochondrial DNA polymerase gamma (POLG1) mutations were associated with levodopa-responsive Parkinsonism. POLG1 gene contains a number of common nonsynonymous SNPs and intronic regulatory SNPs which may have functional consequences. It is of great interest to discover polymorphisms variants associated with Parkinson's disease (PD), both in isolation and in combination with specific SNPs.Materials and Methods: We conducted a case-control study and genotyped twenty SNPs and poly-Q polymorphisms of POLG1 gene including in 344 Chinese sporadic PD patients and 154 healthy controls. All the polymorphisms of POLG1 we found in this study were sequenced by PCR products with dye terminator methods using an ABI-3100 sequencer. Hardy-Weinberg equilibrium and linkage disequilibrium (LD) for association between twenty POLG1 SNPs and PD were calculated using the program Haploview.Principal Results: We provided evidence for strong association of four intronic SNPs of the POLG1 gene (new report: c.2070-12T>A and rs2307439: c.2070-64G>A in intron 11, Pâ=â0.00011, ORâ=â1.727; rs2302084: c.3105-11T>C and rs2246900: c.3105-36A>G in intron 19, Pâ=â0.00031, ORâ=â1.648) with PD. However, we did not identify any significant association between ten exonic SNPs of POLG1 and PD. Linkage disequilibrium analysis indicated that c.2070-12T>A and c.2070-64G>A could be parsed into one block as Haplotype 1 as well as c.3105-11T>C and c.3105-36A>G in Haplotype 2. In addition, case and control study on association of POLG1 CAG repeat (poly-Q) alleles with PD showed a significant association (Pâ=â0.03, ORâ=â2.16) of the non-10/11Q variants with PD. Although intronic SNPs associated with PD didn't influence POLG1 mRNA alternative splicing, there was a strong association of c.2070-12T>A and c.2070-64G>A with decreased POLG1 mRNA level and protein levels.Conclusions: Our findings indicate that POLG1 may play a role in the pathogenesis of PD in Chinese populations.</p
Recommended from our members
Phylogenetic Analysis of Pelecaniformes (Aves) Based on Osteological Data: Implications for Waterbird Phylogeny and Fossil Calibration Studies
Background: Debate regarding the monophyly and relationships of the avian order Pelecaniformes represents a classic example of discord between morphological and molecular estimates of phylogeny. This lack of consensus hampers interpretation of the group's fossil record, which has major implications for understanding patterns of character evolution (e.g., the evolution of wing-propelled diving) and temporal diversification (e.g., the origins of modern families). Relationships of the Pelecaniformes were inferred through parsimony analyses of an osteological dataset encompassing 59 taxa and 464 characters. The relationships of the Plotopteridae, an extinct family of wing-propelled divers, and several other fossil pelecaniforms (Limnofregata, Prophaethon, Lithoptila, ?Borvocarbo stoeffelensis) were also assessed. The antiquity of these taxa and their purported status as stem members of extant families makes them valuable for studies of higher-level avian diversification.Methodology/Principal Findings: Pelecaniform monophyly is not recovered, with Phaethontidae recovered as distantly related to all other pelecaniforms, which are supported as a monophyletic Steganopodes. Some anatomical partitions of the dataset possess different phylogenetic signals, and partitioned analyses reveal that these discrepancies are localized outside of Steganopodes, and primarily due to a few labile taxa. The Plotopteridae are recovered as the sister taxon to Phalacrocoracoidea, and the relationships of other fossil pelecaniforms representing key calibration points are well supported, including Limnofregata (sister taxon to Fregatidae), Prophaethon and Lithoptila (successive sister taxa to Phaethontidae), and ?Borvocarbo stoeffelensis (sister taxon to Phalacrocoracidae). These relationships are invariant when âbackboneâ constraints based on recent avian phylogenies are imposed.Conclusions/Significance: Relationships of extant pelecaniforms inferred from morphology are more congruent with molecular phylogenies than previously assumed, though notable conflicts remain. The phylogenetic position of the Plotopteridae implies that wing-propelled diving evolved independently in plotopterids and penguins, representing a remarkable case of convergent evolution. Despite robust support for the placement of fossil taxa representing key calibration points, the successive outgroup relationships of several âstem fossil + crown familyâ clades are variable and poorly supported across recent studies of avian phylogeny. Thus, the impact these fossils have on inferred patterns of temporal diversification depends heavily on the resolution of deep nodes in avian phylogeny.</p
Optimising physiotherapy for people with lateral elbow tendinopathy - Results of a mixed-methods pilot and feasibility randomised controlled trial (OPTimisE)
The OPTimisE intervention was developed to address uncertainty regarding the most effective physiotherapy treatment strategy for people with Lateral Elbow Tendinopathy (LET). To assess the feasibility of conducting a fully-powered randomised controlled trial (RCT) evaluating whether the OPTimisE intervention is superior to usual physiotherapy treatment for adults with LET. A mixed-methods multi-centred, parallel pilot and feasibility RCT, conducted in three outpatient physiotherapy departments in the UK. Patients were independently randomised 1:1 in mixed blocks, stratified by site, to the OPTimisE intervention or usual care. Outcomes were assessed using pre-defined feasibility progression criteria. 50 patients were randomised (22 Female, 28 Male), mean age 48 years (range 27-75). Consent rate was 71% (50/70), fidelity to intervention 89% (16/18), attendance rate in the OPTimisE group 82% (55/67) vs 85% (56/66) in usual care, outcome measure completion 81% (39/48) at six-month follow-up. There were no related adverse events. Patients and physiotherapists reported that the OPTimisE intervention was acceptable but suggested improvements to the trial design. 49 patients were recruited from physiotherapy referrals vs one from primary care records. Outcome measure return rates were higher when completed online (74%) compared to postal questionnaire (50%). Exploratory analysis showed improvements in both groups over time. It is methodologically feasible to conduct a fully powered RCT comparing the clinical and cost-effectiveness of the OPTimisE intervention versus usual physiotherapy treatment. Considering the similar improvements observed in both groups, careful consideration is needed regarding the priority research question to be addressed in future research. [Abstract copyright: Copyright Š 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.
Combined Nutrition and Exercise Interventions in Community Groups
Diet and physical activity are two key modifiable lifestyle factors that influence health across the lifespan (prevention and management of chronic diseases and reduction of the risk of premature death through several biological mechanisms). Community-based interventions contribute to public health, as they have the potential to reach high population-level impact, through the focus on groups that share a common culture or identity in their natural living environment. While the health benefits of a balanced diet and regular physical activity are commonly studied separately, interventions that combine these two lifestyle factors have the potential to induce greater benefits in community groups rather than strategies focusing only on one or the other. Thus, this Special Issue entitled âCombined Nutrition and Exercise Interventions in Community Groupsâ is comprised of manuscripts that highlight this combined approach (balanced diet and regular physical activity) in community settings. The contributors to this Special Issue are well-recognized professionals in complementary fields such as education, public health, nutrition, and exercise. This Special Issue highlights the latest research regarding combined nutrition and exercise interventions among different community groups and includes research articles developed through five continents (Africa, Asia, America, Europe and Oceania), as well as reviews and systematic reviews
Acute adaptation of central and peripheral motor unit features to exerciseâinduced fatigue differs with concentric and eccentric loading
New Findings: What is the central question of this study? Conflicting evidence exists on motor unit (MU) firing rate in response to exerciseâinduced fatigue, possibly due to the contraction modality used: Do MU properties adapt similarly following concentric and eccentric loading? What is the main finding and its importance? MU firing rate increased following eccentric loading only despite a decline in absolute force. Force steadiness deteriorated following both loading methods. Central and peripheral MU features are altered in a contraction typeâdependant manner, which is an important consideration for training interventions. Abstract: Force output of muscle is partly mediated by the adjustment of motor unit (MU) firing rate (FR). Disparities in MU features in response to fatigue may be influenced by contraction type, as concentric (CON) and eccentric (ECC) contractions demand variable amounts of neural input, which alters the response to fatigue. This study aimed to determine the effects of fatigue following CON and ECC loading on MU features of the vastus lateralis (VL). Highâdensity surface (HDâsEMG) and intramuscular (iEMG) electromyography were used to record MU potentials (MUPs) from bilateral VLs of 12 young volunteers (six females) during sustained isometric contractions at 25% and 40% of the maximum voluntary contraction (MVC), before and after completing CON and ECC weighted stepping exercise. Multiâlevel mixed effects linear regression models were performed with significance assumed as P 0.1) but neuromuscular junction transmission instability increased in both legs (P < 0.04), and markers of fibre membrane excitability increased following CON only (P = 0.018). These data demonstrate that central and peripheral MU features are altered following exerciseâinduced fatigue and differ according to exercise modality. This is important when considering interventional strategies targeting MU function
Scientific opinion on the tolerable upper intake level for vitamin B6
Following a request from the European Commission, the EFSA Panel on Nutrition, Novel Foods and Food Allergens (NDA) was asked to deliver a scientific opinion on the tolerable upper intake level (UL) for vitamin B6. Systematic reviews of the literature were conducted by a contractor. The relationship between excess vitamin B6 intakes and the development of peripheral neuropathy is well established and is the critical effect on which the UL is based. A lowest-observed-effect-level (LOAEL) could not be established based on human data. A reference point (RP) of 50 mg/day is identified by the Panel from a caseâcontrol study, supported by data from case reports and vigilance data. An uncertainty factor (UF) of 4 is applied to the RP to account for the inverse relationship between dose and time to onset of symptoms and the limited data available. The latter covers uncertainties as to the level of intake that would represent a LOAEL. This leads to a UL of 12.5 mg/day. From a subchronic study in Beagle dogs, a LOAEL of 50 mg/kg body weight (bw) per day can be identified. Using an UF of 300, and a default bw of 70 kg, a UL of 11.7 mg/day can be calculated. From the midpoint of the range of these two ULs and rounding down, a UL of 12 mg/day is established by the Panel for vitamin B6 for adults (including pregnant and lactating women). ULs for infants and children are derived from the UL for adults using allometric scaling: 2.2â2.5 mg/day (4â11 months), 3.2â4.5 mg/day (1â6 years), 6.1â10.7 mg/day (7â17 years). Based on available intake data, EU populations are unlikely to exceed ULs, except for regular users of food supplements containing high doses of vitamin B6
- âŚ