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Determinants of sugar‐sweetened beverage consumption in young children: a systematic review
SummarySugar‐sweetened beverage (SSB) consumption is associated with adverse health outcomes. Improved understanding of the determinants will inform effective interventions to reduce SSB consumption. A total of 46,876 papers were identified through searching eight electronic databases. Evidence from intervention (n = 13), prospective (n = 6) and cross‐sectional (n = 25) studies on correlates/determinants of SSB consumption was quality assessed and synthesized. Twelve correlates/determinants were associated with higher SSB consumption (child's preference for SSBs, TV viewing/screen time and snack consumption; parents' lower socioeconomic status, lower age, SSB consumption, formula milk feeding, early introduction of solids, using food as rewards, parental‐perceived barriers, attending out‐of‐home care and living near a fast food/convenience store). Five correlates/determinants were associated with lower SSB consumption (parental positive modelling, parents' married/co‐habiting, school nutrition policy, staff skills and supermarket nearby). There was equivocal evidence for child's age and knowledge, parental knowledge, skills, rules/restrictions and home SSB availability. Eight intervention studies targeted multi‐level (child, parents, childcare/preschool setting) determinants; four were effective. Four intervention studies targeted parental determinants; two were effective. One (effective) intervention targeted the preschool environment. There is consistent evidence to support potentially modifiable correlates/determinants of SSB consumption in young children acting at parental (modelling), child (TV viewing) and environmental (school policy) levels.
Protocol for systematic review of evidence on the determinants and influence of early glycaemic control in childhood-onset type 1 diabetes.
BACKGROUND: Landmark studies in adult-onset type 1 diabetes (T1D) populations indicate that improved glycaemic control through use of intensive insulin therapy is strongly associated with reduced risk for the development of diabetes-related complications and mortality in later years. However, it is unclear whether these associations can be extrapolated to childhood-onset T1D, given the influence of other important biological and psychosocial determinants of glycaemic control, particularly during adolescence. The aims of the review are (1) to investigate the impact of early glycaemic control (within the first 2 years after diagnosis) on subsequent glycaemic trends and risk of complications during the life course of childhood-onset T1D and (2) to identify the predictors of early glycaemic control in children and young people (0-25 years). METHODS: The methods used in this study are systematic identification, review and mapping of quantitative (intervention and observational) and qualitative literature; assessing the effect and predictors of early glycaemic control in T1D (diagnosed ≤18 years) on risk or prevalence of later complications. An iterated search strategy, with no language or period restrictions, was applied to identify studies from six electronic databases. This will be supplemented by hand-searching (reference lists and contacting authors of studies meeting the inclusion criteria). Studies assessing glycaemic control within the first 2 years of diagnosis in children (at baseline) will be quality-assessed against predefined criteria and mapped descriptively to future health outcomes. Extracted data will be analysed and synthesised using narrative and forest plots or harvest plots for quantitative evidence and thematic analyses for qualitative studies. To get a deeper understanding of the predictors of early glycaemic control in reducing complications in childhood and adult life, we will integrate qualitative and quantitative evidence using mixed methods or parallel synthesis approach. DISCUSSION: These linked reviews will be the first to systematically investigate the effects of early glycaemic control and integrate both the quantitative and qualitative evidence on predictors of early glycaemic control in childhood-onset T1D in reducing future diabetes complications. This will help identify and map current research and inform development of effective future interventions. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015024546.
Factors influencing obesogenic dietary intake in young children (0–6 years): systematic review of qualitative evidence
BackgroundObesogenic dietary intake is prevalent in young children and is associated with obesity and other adverse health outcomes in childhood and later in life.ObjectiveTo describe the barriers to and facilitators of obesogenic dietary intake in early childhood, in order to inform interventions and public health policies to prevent obesity.DesignSystematic review of qualitative literature on factors influencing obesogenic diets in children aged 0–6 years.Data sourcesMEDLINE, EMBASE, CINAHL, PsycINFO, Web of Knowledge, British Nursing Index, ASSIA and Sociological Abstracts.Review methodsQualitative studies meeting the inclusion criteria were synthesised. Data were analysed by creating a thematic framework, underpinned by the socioecological model, which included familiarisation of data across the studies, indexing, charting, mapping and interpretation.Results20 studies from the USA (10), Europe (6) and Australia (4) included the views of 1067 participants (901 parents/caregivers, 37 children, 87 teachers, 15 dieticians and 27 nursery staff). Study designs included focus groups (n=16), individual interviews (n=6) and ethnography (n=1) with some studies using more than one design. Despite wide differences in the study context and focus, several consistent themes emerged. Parental factors increasing young children's obesogenic diets were: negative parent/family/peer modelling, lack of knowledge, time constraints, using food as reward, affordability and concerns about child's health. Child preferences also increased intake. Environmental factors increasing intake include: availability, advertising, societal, cultural and preschool/childcare influences.ConclusionsFuture intervention strategies should aim to promote modelling of positive behaviours, create home and preschool environments that promote healthy diets, and simultaneously target factors at the family and preschool/childcare levels.Trial registration numberThis review is one of a series of systematic reviews on the determinants of obesogenic behaviours in young children, registered with the International Prospective Register for Systematic Reviews (PROSPERO), CRD42012002881.
Refining reporting guidelines using behaviour change theory
The lasting legacy of most medical research is the written account. When writing up their work, researchers often omit information that readers — including clinicians, reviewers, patients, and other researchers — need to fully understand, appraise, replicate, or apply the research. Reporting guidelines try to solve this problem. They are community-created recommendations of information to include when writing up research so that everybody can use it. The first reporting guideline was created almost 30 years ago, and many more have been created since. Most leading medical journals ask authors to adhere to reporting guidelines, yet adherence remains low in almost all medical fields. When authors do not adhere to reporting guidelines their work is less transparent, less valuable, contributes less to patient outcomes and has potential to inadvertently harm by distorting the evidence base. The aim of my thesis is to understand why authors do not adhere to reporting = guidelines when writing up medical research, and to address these reasons with the intention of increasing adherence in the future. I began my thesis with this clear aim but without a route to get there. My first step was a qualitative synthesis (chapter 3) of research exploring authors experiences of reporting guidelines, and I discovered authors’ adherence to reporting guidelines is influenced by features of the guidelines themselves, but also the system that surrounds them including the websites that disseminate them and the people and policies of the broader scholarly ecosystem. I probed this system further with a review of quantitative surveys and an evaluation of a key dissemination website (chapters 4 & 5). Given the complexity of the system and the complexity of the behaviour in question, I realised I would need a framework to help me make sense of them. I decided to use the Behaviour Change Wheel (chapter 6), a well established and evidenced framework for designing and defining complex behaviour change interventions. I led workshops and focus groups (chapters 7 & 8) to guide stakeholders through frameworks’ steps and, ultimately, ended up identifying 32 influences that needed to change, and 128 ideas of how to change them. These ideas were applicable to guideline developers, the EQUATOR Network, journals, publishers, funders, ethics committees, and institutions. I decided that redesigning reporting guidelines and EQUATOR’s website would be an effective, affordable, acceptable, and equitable way to realise many of the generated ideas. I defined 63 intervention components and managed to incorporate 46 into a prototype website that included a redesigned reporting guideline (the Standards for Reporting Qualitative Research) and the EQUATOR Network’s home page (chapter 9). I then explored authors experiences of using this prototype through in-depth interviews, observation, think aloud, and writing appraisals (chapter 10) and I identified 53 possible areas for improvement. My key outputs include a design blueprint for user-friendly reporting guideline resources, and an online platform for creating and hosting resources following this blueprint. This platform will benefit guideline developers who typically lack the money, time, and skills to create user friendly resources. A future feasibility study and parallel process evaluation will explore the acceptability and usability of this platform amongst authors submitting to journals, in preparation for a future evaluation to determine whether my redesign leads to more authors adhering to reporting guidelines successfully.
TGF-β is elevated in hyperuricemic individuals and mediates urate-induced hyperinflammatory phenotype in human mononuclear cells.
BACKGROUND: Soluble urate leads to a pro-inflammatory phenotype in human monocytes characterized by increased production of IL-1β and downregulation of IL-1 receptor antagonist, the mechanism of which remains to be fully elucidated. Previous transcriptomic data identified differential expression of genes in the transforming growth factor (TGF)-β pathway in monocytes exposed to urate in vitro. In this study, we explore the role of TGF-β in urate-induced hyperinflammation in peripheral blood mononuclear cells (PBMCs). METHODS: TGF-β mRNA in unstimulated PBMCs and protein levels in plasma were measured in individuals with normouricemia, hyperuricemia and gout. For in vitro validation, PBMCs of healthy volunteers were isolated and treated with a dose ranging concentration of urate for assessment of mRNA and pSMAD2. Urate and TGF-β priming experiments were performed with three inhibitors of TGF-β signalling: SB-505124, 5Z-7-oxozeaenol and a blocking antibody against TGF-β receptor II. RESULTS: TGF-β mRNA levels were elevated in gout patients compared to healthy controls. TGF-β-LAP levels in serum were significantly higher in individuals with hyperuricemia compared to controls. In both cases, TGF-β correlated positively to serum urate levels. In vitro, urate exposure of PBMCs did not directly induce TGF-β but did enhance SMAD2 phosphorylation. The urate-induced pro-inflammatory phenotype of monocytes was partly reversed by blocking TGF-β. CONCLUSIONS: TGF-β is elevated in individuals with hyperuricemia and correlated to serum urate concentrations. In addition, the urate-induced pro-inflammatory phenotype in human monocytes is mediated by TGF-β signalling. Future studies are warranted to explore the intracellular pathways involved and to assess the clinical significance of urate-TGF-β relation.
Early radiological outcomes of a fully porous bridging collar in lower-limb endoprosthetic reconstructions: a case-matched retrospective series to assess osseointegration.
BACKGROUND: Limb-salvage surgery involving the utilization of endoprosthetic replacements is commonly employed following segmental bone resection for primary and secondary bone tumors. This study aimed to evaluate whether a fully porous bridging collar promotes early osseous integration in endoprosthetic replacements. METHODS: We undertook a retrospective review of all lower-limb endoprostheses utilizing a fully porous endosteal bridging collar design. We matched this cohort with a conventional extra-osteal non-porous fully hydroxyapatite-coated grooved collar cohort according to surgical indication, implant type, resection length, age, and follow-up time. At 6, 12, and 24 months post-implantation, radiographs were assessed for the number of cortices with or without osseointegration on orthogonal radiographs. Each radiograph was scored on a scale of -4 to + 4 for the number of cortices bridging the ongrowth between the bone and the collar of the prosthesis. Implant survival was estimated using the Kaplan-Meier method, and the mean number of osseointegrated cortices at each time point between the collar designs was compared using a paired t-test. RESULTS: Ninety patients were retrospectively identified and analyzed. After exclusion, 40 patients with porous bridging collars matched with 40 patients with conventional extra-osteal non-porous collars were included in the study (n = 80). The mean age was 63.4 years (range 16-91 years); there were 37 males and 43 females. The groups showed no difference in implant survival (P = 0.54). The mean number of cortices with radiographic ongrowth for the porous bridging collar and non-porous collar groups was 2.1 and 0.3, respectively, at 6-month (P
Surgical factors that contribute to tibial periprosthetic fracture after cementless Oxford Unicompartmental Knee Replacement: a finite element analysis.
BACKGROUND: Tibial periprosthetic fracture (TPF) is a severe complication of cementless Oxford Unicompartmental Knee Replacement (OUKR) with patient risk factors including small tibial size and tibia vara with an overhanging medial tibial condyle. Surgical factors also influence fracture but remain poorly defined. This finite element (FE) analysis study identified surgical risk factors for TPF after OUKR and determined the optimal tibial component positioning to minimise fracture risk. METHODS: Knees in two very high-risk, small, bilateral OUKR patients who had a TPF in one knee and a good result in the other were studied with FE analysis. Each patient's unfractured tibia was used as a comparator to study surgical factors. The tibial geometries were segmented from the pre-operative CT scans and FE models were built with the tibial components implanted in their post-operative positions. The resections in the fractured and unfractured tibias were compared regarding their mediolateral position, distal-proximal position, internal-external rotation and varus-valgus orientation. Models of the TPF tibial resections in the contralateral sides were also built in both patients. The risk of TPF was assessed by examining the magnitude and location of the highest maximum principal stress. RESULTS: In both patients, large differences were found in the position and orientation of the tibial components in the fractured and unfractured tibias with the components in the fractured tibias placed more medially and distally. Suboptimal saw cuts resulted in poor positioning of the tibial components and created very high local stresses in the bone, particularly anteriorly (157 MPa and 702 MPa in the fractured side vs. 49 MPa and 63 MPa in the unfractured side in patient 1 and 2 respectively), causing fractures. CONCLUSION: In small patients with marked tibia vara the surgery is unforgiving. To avoid fracture, the horizontal cut should be conservative, aiming for a 3 bearing, the vertical cut should abut the apex of the medial tibial spine, and extreme internal or external rotation should be avoided. The component should be aligned with the posterior cortex and should not overhang anteriorly. In addition, contrary to current recommendations, the tibial component should be placed in varus (about 5°).
Effect of genetically predicted sclerostin on cardiovascular biomarkers, risk factors, and disease outcomes.
Sclerostin inhibitors protect against osteoporotic fractures, but their cardiovascular safety remains unclear. We conducted a cis-Mendelian randomisation analysis to estimate the causal effect of sclerostin levels on cardiovascular risk factors. We meta-analysed three GWAS of sclerostin levels including 49,568 Europeans and selected 2 SNPs to be used as instruments. We included heel bone mineral density and hip fracture risk as positive control outcomes. Public GWAS and UK Biobank patient-level data were used for the study outcomes, which include cardiovascular events, risk factors, and biomarkers. Lower sclerostin levels were associated with higher bone mineral density and 85% reduction in hip fracture risk. However, genetically predicted lower sclerostin levels led to 25-85% excess coronary artery disease risk, 40% to 60% increased risk of type 2 diabetes, and worse cardiovascular biomarkers values, including higher triglycerides, and decreased HDL cholesterol levels. Results also suggest a potential (but borderline) association with increased risk of myocardial infarction. Our study provides genetic evidence of a causal relationship between reduced levels of sclerostin and improved bone health and fracture protection, but increased risk of cardiovascular events and risk factors.
Incidence, prevalence, and survival of prostate cancer in the UK
Importance Incidence, prevalence, and survival are pertinent measures to inform the management and provision of prostate cancer care. Objective To calculate the incidence, prevalence, and survival rates for prostate cancer in the UK from 2000 to 2021. Design, Setting, and Participants This population-based cohort study uses routinely collected primary care data from the UK. Male patients aged 18 years or older with at least 1 year of history registered in Clinical Practice Research Datalink (CPRD) GOLD or Aurum were included. Data were analyzed from January 2023 to March 2024. Main Outcomes and Measures Prostate cancer incidence rates (IR), period prevalence (PP), and 1-, 5-, and 10-year survival after diagnosis between 2000 and 2021, stratified by age and calendar years. Results This study included 64 925 and 133 200 patients with prostate cancer in CPRD GOLD and Aurum, respectively, with a median age of 72 (65-78) years. The overall IR of prostate cancer was 151.7 (95% CI, 150.6 to 152.9) per 100 000 person-years in GOLD to 153.1 (95% CI, 152.3 to 153.9) per 100 000 person-years for Aurum and increased with age. The incidence of prostate cancer increased from 109 per 100 000 person-years in 2000 to 159 per 100 000 person-years in 2021. Peaks of incidence occurred in 2004 and 2018, before a decline in 2020. PP increased 3.5 times over the study period for both databases, from 0.4% in 2000 to 1.4% in 2021. IR and PP were highest in those aged 80 to 89 years. Median (95% CI) survival was similar in both databases (GOLD: 10.9 [95% CI, 10.7-11.1] years and Aurum: 11.1 [95% CI, 11.0-11.2] years). Survival at 1, 5, and 10 years after diagnosis were 93.4% (95% CI, 93.2%-93.6%), 71.8% (95% CI, 71.4%-72.2%), 53.2% (95% CI, 52.6%-53.7%) in GOLD and 93.9% (95% CI, 93.7%-94.0%), 72.7% (95% CI, 72.5%-73.0%), 53.7% (95% CI, 53.3%-54.1%) in AURUM, respectively. Survival increased over time: 1-year survival was 94.8% (95% CI, 94.5%-95.2%) in those diagnosed between 2015 to 2019 compared with 90.8% (95% CI, 90.2%-91.3%) from 2000 to 2004; 5-year survival improved from 65.3% (95% CI, 64.4%-66.3%) from 2000 to 2004 to 75.3% (95% CI, 74.4%-76.3%) in 2015 to 2019. Conclusions and Relevance In this population-based cohort study, incidence and prevalence increased with older age, with high survival rates reflecting a high burden of disease, particularly in the management of cancer survivorship in an aging population. Health care systems should consider this when managing the increasing numbers of people with prevalent prostate cancer.
WERF Endometriosis Phenome and Biobanking Harmonisation Project for Experimental Models in Endometriosis Research (EPHect-EM-Organoids): endometrial organoids as an emerging technology for endometriosis research
The aetiology of endometriosis remains poorly understood. In vitro model systems provide the opportunity to identify the mechanisms driving disease pathogenesis using human cells. Three-dimensional models, particularly organoid systems, have revolutionized how we study epithelial biology and are powerful tools for modelling endometriosis. As an emerging model system, it is important to define protocols and identify the remaining challenges surrounding endometrial organoid culture to increase reproducibility and scientific rigour in endometriosis research. The World Endometriosis Research Foundation (WERF) established an international working group comprised of experts using in vitro approaches for the study of endometriosis. This working group harmonized protocols and documentation of existing and emerging organoid systems to maximize comparison and replication across the field and guide specific research hypotheses testing. This evaluation of organoid protocols, limitations, challenges, and alternative approaches assessed both published and grey literature papers across several disciplines pertinent to endometriosis research. Recommendations for protocol and documentation harmonization are presented, and we created the first-ever decision tree diagram to guide and facilitate the selection of existing models best suited for specific areas of endometriosis research. Rigorous and systematic assessment of emerging organoid systems, recognizing the inferential strengths and limitations of these approaches, is vital for endometriosis research. This comprehensive review of the benefits, limitations, and utilization of organoid models, as well as the consequent integration of protocols and documentation, will contribute to the scientific knowledge base by maximizing the reproducibility, comparability, and interpretation of research studies in endometriosis. Additionally, these newly developed protocols and documentation should serve as a resource for, and facilitate collaboration between, endometriosis investigators using organoids in their research methods.