Objectives: The steeling effect suggests that early-life adversity can have a beneficial impact later in life. However, little is known about its underlying mechanisms and long-term outcomes . The study aimed to examine the role of early-life adversity (ELA) on successful aging, and whether this relationship can be explained by mental and physical health.
Method: Socio-demographics, early-life adversity (ELA), individual quality of life (iQoL), and mental and physical health of 270 individuals (Mage = 66.82 years, 71.5% female) were assessed. Polynomial regressions and mediation analyses were conducted.
Results: Significant inverse U-shaped associations were found between ELA and iQoL (β = ?.59, p = .005) and between ELA and mental health (β = ?.64, p = .002), but not between ELA and physical health. Furthermore, mental health significantly mediated the relationship between ELA and iQoL (b = ?.84, BCa CI [?1.66, ?.27]).
Conclusion: Highest level of individual quality of life (i.e. successful aging) was related to a moderate amount of ELA. Additionally, mental health significantly mediated this relationship. These findings suggest that some amount of ELA could be beneficial for successful aging. Resource-focused interventions are needed to improve health and promote successful aging for an underdetected, at-risk subgroup with low early-life adversity. 相似文献
Fibroepithelial polyps (FEPs) are common, benign intraoral lesions that tend to develop slowly at predictable sites, often in response to local irritation or trauma. Historical precedent often results in referral to oral and maxillofacial surgery (OMFS) departments for biopsy, often irrespective of symptoms, and histological assessment. OMFS and pathology services are struggling to cope with an increasing workload that will potentially lead to widespread delays to diagnosis and treatment. Over the past 20 years, clinical pathways and guidance have been developed to ensure that healthcare interventions, such as the removal of third molars, tonsils, skin tags, and benign moles, are evidence-based, have a net patient benefit, and ensure the best use of finite NHS resources. However, no such guidance exists for intraoral lesions and we regard this as an oversight. We analysed the removal of 682 FEPs over a seven-year period and report sensitivities of 92.4% for a “confirmed clinical suspicion of an FEP” and 99.7% for a “confirmed clinical suspicion of a benign diagnosis”. The incidence of non-benign disease was 0.3%. Primary care dentists should be able to diagnose and monitor FEPs and refer only if symptoms are serious or in high-risk patients or sites. Adopting this practice across the UK could free up to 1825 four-hour OMFS clinics, 405 hours of consultant histopathologists’ time, and recurring savings to the NHS estimated to be in the region of £620 000/annum. We believe that the removal of FEPs should be reclassified as an “intervention not normally funded”, and the time and resources put to better use treating patients with lesions of questionable pathology. 相似文献
Tranexamic acid (TXA) is an antifibrinolytic drug that reduces surgical blood loss and death due to bleeding after trauma and post‐partum haemorrhage. One key issue for treatment success is early administration. While usually given intravenously, oral and intramuscular use would be useful in specific circumstances. Therefore, an understanding of TXA pharmacokinetics when given via different routes is valuable. The aim of this study was to perform an individual participant data meta‐analysis of pharmacokinetic studies with TXA given to healthy volunteers via different routes. We searched the following databases: PubMed, Web of Science, Wiley Online Library, Elsevier Science Direct and J‐STAGE. Individual subject data were extracted when available, otherwise arithmetic means were used. A population pharmacokinetic model was developed using nonlinear mixed effect modelling. Seven studies were included in the analysis with data from 10 patients for the IV route, six patients for the IM route and 114 patients for the oral route. The pharmacokinetics was ascribed to a two‐compartment model, and the main covariate was allometrically scaled bodyweight. Oral and IM bioavailabilities were 46 and 105%, respectively. For a 70 kg bodyweight, the population estimates were 7.6 L/h for clearance, 17.9 L for the volume of the central compartment, 2.5 L/h for the diffusional clearance and 16.6 L for the peripheral volume of distribution. Larger well‐designed studies are needed to describe the pharmacokinetics of TXA when given IM or as an oral solution before these can be recommended as alternatives to IV. 相似文献
ObjectivesWe applied principles for conducting economic evaluations of factorial trials to a trial-based economic evaluation of a cluster-randomized 2 × 2 × 2 factorial trial. We assessed the cost-effectiveness of atorvastatin, omega-3 fish oil, and an action-planning leaflet, alone and in combination, from a UK National Health Service perspective.MethodsThe Atorvastatin in Factorial With Omega EE90 Risk Reduction in Diabetes (AFORRD) Trial randomized 800 patients with type 2 diabetes to atorvastatin, omega-3, or their respective placebos and randomized general practices to receive a leaflet-based action-planning intervention designed to improve compliance or standard care. The trial was conducted at 59 UK general practices. Sixteen-week outcomes for each trial participant were extrapolated for 70 years using the United Kingdom Prospective Diabetes Study Outcomes Model v2.01. We analyzed the trial as a 2 × 2 factorial trial (ignoring interactions between action-planning leaflet and medication), as a 2 × 2 × 2 factorial trial (considering all interactions), and ignoring all interactions.ResultsWe observed several qualitative interactions for costs and quality-adjusted life-years (QALYs) that changed treatment rankings. However, different approaches to analyzing the factorial design did not change the conclusions. There was a ≥99% chance that atorvastatin is cost-effective and omega-3 is not, at a £20 000/QALY threshold.ConclusionsAtorvastatin monotherapy was the most cost-effective combination of the 3 trial interventions at a £20 000/QALY threshold. Omega-3 fish oil was not cost-effective, while there was insufficient evidence to draw firm conclusions about action planning. Recently-developed methods for analyzing factorial trials and combining parameter and sampling uncertainty were extended to estimate cost-effectiveness acceptability curves within a 2x2x2 factorial design with model-based extrapolation. 相似文献
Background Currently, there are a number of clinical trials, but no international collaboration for collating research on effectiveness of laparoscopic uterosacral nerve ablation (LUNA) for alleviating chronic pelvic pain. Objective Meta-analysis was used by collecting individual patient data (IPD) from the existing trials, to provide a comprehensive assessment of the effectiveness of LUNA that will be generalisable in various clinical contexts. Methods IPD will be sought and collected from all relevant (both already finished and continuing) randomised trials identified through previous systematic reviews. After obtaining raw data and cleaning the database, analysis will be of all patients ever randomised based on the intention-to-treat principle using endpoints measured at 12 months following randomisation. Proposal We will update searches, contact all authors, obtain data in whatever form it can be provided, build a single database, produce results for individual studies, have them verified by original authors, explore of any heterogeneity and reasons behind it and finally pool all raw data in to a meta-analysis using appropriate statistical methods. The project will test the effectiveness of LUNA for women with chronic pelvic pain. It will also motivate collaborating primary investigators to undertake new primary studies to corroborate or improve upon the conclusions derived from the retrospective analysis. 相似文献
Lipid peroxidation in the brain cortex, striatum, hippocampus, and hypothalamus of rats of the KLA and KHA lines which were distinguished by their strategies of adaptive behavior was investigated following emotional-painful stress. Significant long-term changes in lipid peroxidation were shown to occur in the brain. These had a phase character and depended on the behavioral characteristics of the animals. The investigated brain regions were characterized by different reactions of lipid peroxidation to the stress. The induced depressive-like states (on the 21st day after the stress) in rats of the KLA and KHA lines were distinguished by the largest changes in lipid peroxidation in the striatum and hypothalamus and in the striatum and hippocampus, respectively. One could conclude on the basis of these results that both identical and different mechanisms of formation and development of depression existed in the animals with different behavioral strategies. 相似文献