Reactive oxygen species (ROS) play a pivotal role in the orchestration of the normal wound-healing response. They act as secondary messengers to many immunocytes and non-lymphoid cells, which are involved in the repair process, and appear to be important in coordinating the recruitment of lymphoid cells to the wound site and effective tissue repair. ROS also possess the ability to regulate the formation of blood vessels (angiogenesis) at the wound site and the optimal perfusion of blood into the wound-healing area. ROS act in the host's defence through phagocytes that induce an ROS burst onto the pathogens present in wounds, leading to their destruction, and during this period, excess ROS leakage into the surrounding environment has further bacteriostatic effects. In light of these important roles of ROS in wound healing and the continued quest for therapeutic strategies to treat wounds in general and chronic wounds, such as diabetic foot ulcers, venous and arterial leg ulcers and pressure ulcers in particular, the manipulation of ROS represents a promising avenue for improving wound-healing responses when they are stalled. This article presents a review of the evidence supporting the critical role of ROS in wound healing and infection control at the wound site, and some of the new emerging concepts associated with ROS modulation and its potential in improving wound healing are discussed.
BackgroundAntimicrobial resistance continues to be a global issue in healthcare organisations. Honey has long been shown to possess wound healing and antimicrobial properties that are dependent on a number of physical and chemical properties of the honey. We tested the antimicrobial activity of a medicinal honey, Surgihoney® (SH) and two prototype modified honeys made by Apis mellifera (honeybee) against Staphylococcus aureus (NCIMB 9518). We also examined the modified honey prototypes for the ability to generate reactive oxygen species (ROS) by changing the level of production of hydrogen peroxide from the samples.MethodsSurgihoney® (SH) was compared with two modified honeys, Prototype 1 (PT1) and Prototype 2 (PT2) using a bioassay method against a standard strain of Staphylococcus aureus. Further work studied the rate of generation of ROS hydrogen peroxide from these preparations.ResultsSurgihoney® antimicrobial activity was shown to be largely due to ROS hydrogen peroxide production. By modification of Surgihoney®, two more potent honey prototypes were shown to generate between a two- and three-fold greater antibacterial activity and up to ten times greater ROS peroxide activity.ConclusionsSurgihoney® is a clinically available wound antiseptic dressing that shows good antimicrobial activity. Two further honey prototypes have been shown to have antimicrobial activity that is possible to be enhanced due to demonstrated increases in ROS peroxide activity.
Background: Health inequalities can be partially addressed through the range of treatments funded by health systems. Nevertheless, although health technology assessment agencies assess the overall balance of health benefits and costs, no quantitative assessment of health inequality impact is consistently undertaken.Objectives: To assess the inequality impact of technologies recommended under the NICE single technology appraisal process from 2012 to 2014 using an aggregate distributional cost-effectiveness framework.Methods: Data on health benefits, costs, and patient populations were extracted from the NICE website. Benefits for each technology were distributed to social groups using the observed socioeconomic distribution of hospital utilization for the targeted disease. Inequality measures and estimates of cost-effectiveness were compared using the health inequality impact plane and combined using social welfare indices.Results: Twenty-seven interventions were evaluated. Fourteen interventions were estimated to increase population health and reduce health inequality, 8 to reduce population health and increase health inequality, and 5 to increase health and increase health inequality. Among the latter 5, social welfare analysis, using inequality aversion parameters reflecting high concern for inequality, indicated that the health gain outweighs the negative health inequality impact. Conclusions:The methods proposed offer a way of estimating the health inequality impacts of new health technologies. The methods do not allow for differences in technology-specific utilization and health benefits, but require less resources and data than conducting full distributional cost-effectiveness analysis. They can provide useful quantitative information to help policy makers consider how far new technologies are likely to reduce or increase health inequalities.
Patients with atopic dermatitis (AD) who do not adequately respond to topical therapy and phototherapy often need systemic immunomodulatory treatment to control their symptoms. Conventional systemic agents, such as ciclosporin, azathioprine, and methotrexate, have been used for decades, but there are concerns about their safety profile. There are now many novel systemic agents emerging through clinical trials, which may have great potential in the treatment of AD. Despite this, there are very few data comparing the performance of these drugs against each other. The purpose of this article is to review the current systemic therapies in AD and present an indirect comparison of systemic AD treatments using effectiveness and safety data from published randomised controlled trials, highlighting important remaining gaps in knowledge. Although the latest developments in systemic AD treatments are exciting and dearly needed, further work is required before the promise of a therapeutic revolution becomes reality.
ObjectivesIn order to address the current deficiency of health utility evidence relevant for economic evaluations involving treatments for rheumatoid arthritis (RA) in the Chinese setting, this study aims to develop a mapping algorithm linking the Health Assessment Questionnaire (HAQ) and EQ-5D-5L in a Chinese population of patients with RA.MethodsAn estimation sample was obtained from a cross-sectional study that collected HAQ, the pain Visual Analogue Scale, and EQ-5D-5L in RA patients in two tertiary referral hospitals in China. Mapping algorithms were derived in this study using two alternative regression methods: the beta regression and a multivariate ordered probit regression. The internal validity of the mapping algorithms was assessed in each case by calculating predictive performance using a bootstrapping procedure.ResultsOf the several algorithms developed using these data, predictive performance was shown to be better when VAS pain was included as a predictor and when the multivariate ordered probit regression method was used, rather than the beta regression method. The algorithms developed were shown to be comparable, in terms of predictive performance, to existing mapping studies despite the small sample size of the estimation data.ConclusionIt is hoped that the availability of these algorithms will facilitate the development of cost-effectiveness studies evaluating RA treatments in the Chinese health care setting.Electronic supplementary materialThe online version of this article (10.1007/s11136-018-1925-1) contains supplementary material, which is available to authorized users.
Background. The English National Health Service publishes hospital performance indicators based on average postoperative EQ-5D index scores after hip replacement surgery to inform prospective patients’ choices of hospital. Unidimensional index scores are derived from multidimensional health-related quality-of-life data using preference weights estimated from a sample of the UK general population. This raises normative concerns if general population preferences differ from those of the patients who are to be informed. This study explores how the source of valuation affects hospital performance estimates. Methods. Four different value sets reflecting source of valuation (general population v. patients), valuation technique (visual analog scale [VAS] v. time tradeoff [TTO]), and experience with health states (currently experienced vs. experimentally estimated) were used to derive and compare performance estimates for 243 hospitals. Two value sets were newly estimated from EQ-5D-3L data on 122,921 hip replacement patients and 3381 members of the UK general public. Changes in hospital ranking (nationally) and performance outlier status (nationally; among patients’ 5 closest hospitals) were compared across valuations. Results. National rankings were stable under different valuations (rank correlations >0.92). Twenty-three (9.5%) hospitals changed outlier status when using patient VAS valuations instead of general population TTO valuations, the current approach. Outlier status also changed substantially at the local level. This was explained mostly by the valuation technique, not the source of valuations or experience with the health states. Limitations. No patient TTO valuations were available. The effect of value set characteristics could be established only through indirect comparisons. Conclusion. Different value sets may lead to prospective patients choosing different hospitals. Normative concerns about the use of general population valuations are not supported by empirical evidence based on VAS valuations.
Background: Several aspects of the opioid epidemic and of public health care organization in the United States (US) make the conduct of economic evaluation and the design of policies to respond to this crisis particularly challenging. Objectives: This commentary offers suggestions for how economic evaluation may address and overcome four key features of the opioid epidemic: 1) its magnitude and geographical distribution, 2) its intersection with multiple epidemics, 3) its rapidly changing dynamics, 4) its multi-sectoral causes and consequences. Results: We first offer pragmatic suggestions to address the difficulties in delivering a coordinated response given the fragmented nature of health care in the US. In view of the broad suite of responses required to address opioid use disorder and its associated comorbidities, we highlight the need for economic evaluations which consider interventions throughout the continuum of care (i.e. primary, secondary and tertiary levels of prevention). We examine how the use of predictive modelling alongside economic evaluation might be adopted to address the rapidly evolving situation affecting distinct populations and geographic areas and encourage investments in epidemic preparedness. Finally, we propose methods to capture the interdependence of various sectors of government affected by the opioid crisis in economic evaluations to ensure optimal levels of investment towards a comprehensive response. Conclusions: The opioid epidemic in the US represents an unprecedented public health challenge, but sound epidemiological modelling and economic analysis can help to guide use of limited resources committed to addressing it in ways that can have greatest impact in limiting its adverse consequences.
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