Simulation or cohort models? Continuous time simulation and discretized Markov models to estimate cost-effectiveness

The choice of model design for decision analytic models in cost-effectiveness analysis has been the subject of discussion. The current work addresses this issue by noting that, when time is to be explicitly modelled, we need to represent phenomena occurring in continuous time. Multistate models evaluated in continuous time might be used but closed form solutions of expected time in each state may not exist or may be difficult to obtain. Two approximations can then be used for costeffectiveness estimation: (1) simulation models, where continuous time estimates are obtained through Monte Carlo simulation, and (2) discretized models. This work draws recommendations on their use by showing that, when these alternative models can be applied, it is preferable to implement a cohort discretized model than a simulation model. Whilst the bias from the first can be minimized by reducing the cycle length, the second is inherently stochastic. Even though specialized literature advocates this framework, the current practice in economic evaluation is to define clinically meaningful cycle lengths for discretized models, disregarding potential biases.

Recent advances regarding the phytochemical and therapeutic benefits of diospyros kaki fruit

Lately, several studies have demonstrated the health benefits associated with natural compounds consumption. Fruit phenolics, lycopene and ascorbic acid, have strong antioxidant, anti-inflammatory, antimugenic and anticarcinogenic activities. In the present study parameters related to fruit quality and climacteric conditions, such as color, moisture, pH, water activity, total phenolic compounds, ascorbic acid and lycopene content were analyzed. Diospyros kaki cv. chocolate fruits were extracted with different solvents, such as methanol, ethanol and water. Total polyphenolics of each extract determined by Folin-Ciocalteu method were found to be higher in methanolic extract and lower in ethanol considering Diospyros fruits with peel. Significant variations were found in the levels of these parameters according to different geographic regions. Results support the importance of Diospyros kaki cv. chocolate fruits, Portuguese cultivar, as a functional food with high antioxidant potential that may have beneficial effects against oxidative human damage.info:eu-repo/semantics/publishedVersio

Cost effectiveness analysis of larval therapy for leg ulcers

Objective: To assess the cost effectiveness of larval therapy compared with hydrogel in the management of leg ulcers. Design: Cost effectiveness and cost utility analyses carried out alongside a pragmatic multicentre, randomised, open trial with equal randomisation. Population: Intention to treat population comprising 267 patients with a venous or mixed venous and arterial ulcers with at least 25% coverage of slough or necrotic tissue. Interventions: Patients were randomly allocated to debridement with bagged larvae, loose larvae, or hydrogel. Main outcome measure: The time horizon was 12 months and costs were estimated from the UK National Health Service perspective. Cost effectiveness outcomes are expressed in terms of incremental costs per ulcer-free day (cost effectiveness analysis) and incremental costs per quality adjusted life years (cost utility analysis). Results: The larvae arms were pooled for the main analysis. Treatment with larval therapy cost, on average, 96.70 pound ((sic)109.61; $140.57) more per participant per year (95% confidence interval -491.9 pound to 685.8) pound than treatment with hydrogel. Participants treated with larval therapy healed, on average, 2.42 days before those in the hydrogel arm (95% confidence interval -0.95 to 31. 91 days) and had a slightly better health related quality of life, as the annual difference in QALYs was 0.011 (95% confidence interval -0.067 to 0.071). However, none of these differences was statistically significant. The incremental cost effectiveness ratio for the base case analysis was estimated at 8826 pound per QALY gained and 40 pound per ulcer-free day. Considerable uncertainty surrounds the outcome estimates. Conclusions: Debridement of sloughy or necrotic leg ulcers with larval therapy is likely to produce similar health benefits and have similar costs to treatment with hydrogel. Trial registration: Current Controlled Trials ISRCTN55114812 and National Research Register N0484123692

Larval therapy for leg ulcers (VenUS II) : randomised controlled trial

Objective To compare the clinical effectiveness of larval therapy with a standard debridement technique (hydrogel) for sloughy or necrotic leg ulcers. Design Pragmatic, three armed randomised controlled trial. Setting Community nurse led services, hospital wards, and hospital outpatient leg ulcer clinics in urban and rural settings, United Kingdom. Participants 267 patients with at least one venous or mixed venous and arterial ulcer with at least 25% coverage of slough or necrotic tissue, and an ankle brachial pressure index of 0.6 or more. Interventions Loose larvae, bagged larvae, and hydrogel. Main outcome measures The primary outcome was time to healing of the largest eligible ulcer. Secondary outcomes were time to debridement, health related quality of life (SF-12), bacterial load, presence of meticillin resistant Staphylococcus aureus, adverse events, and ulcer related pain (visual analogue scale, from 0 mm for no pain to 150 mm for worst pain imaginable). Results Time to healing was not significantly different between the loose or bagged larvae group and the hydrogel group (hazard ratio for healing using larvae v hydrogel 1.13, 95% confidence interval 0.76 to 1.68; P=0.54). Larval therapy significantly reduced the time to debridement (2.31, 1.65 to 3.2; P<0.001). Health related quality of life and change in bacterial load over time were not significantly different between the groups. 6.7% of participants had MRSA at baseline. No difference was found between larval therapy and hydrogel in their ability to eradicate MRSA by the end of the debridement phase (75% (9/12) v 50% (3/6); P=0.34), although this comparison was underpowered. Mean ulcer related pain scores were higher in either larvae group compared with hydrogel (mean difference in pain score: loose larvae v hydrogel 46.74 (95% confidence interval 32.44 to 61.04), P<0.001; bagged larvae v hydrogel 38.58 (23.46 to 53.70), P<0.001). Conclusions Larval therapy did not improve the rate of healing of sloughy or necrotic leg ulcers or reduce bacterial load compared with hydrogel but did significantly reduce the time to debridement and increase ulcer pain. Trial registration Current Controlled Trials ISRCTN55114812 and National Research Register N0484123692

Angolan cymbopogon citratus used for therapeutic benefits: nutritional composition and influence of solvents in phytochemicals content and antioxidant activity of leaf extracts

Folk medicine is a relevant and effective part of indigenous healthcare systems which are, in practice, totally dependent on traditional healers. An outstanding coincidence between indigenous medicinal plant uses and scientifically proved pharmacological properties of several phytochemicals has been observed along the years. This work focused on the leaves of a medicinal plant traditionally used for therapeutic benefits (Angolan Cymbopogon citratus), in order to evaluate their nutritional value. The bioactive phytochemical composition and antioxidant activity of leaf extracts prepared with different solvents (water, methanol and ethanol) were also evaluated. The plant leaves contained ~60% of carbohydrates, protein (~20%), fat (~5%), ash (~4%) and moisture (~9%). The phytochemicals screening revealed the presence of tannins, flavonoids, and terpenoids in all extracts. Methanolic extracts also contained alkaloids and steroids. Several methods were used to evaluate total antioxidant capacity of the different extracts (DPPH; NO; and H2O2 scavenging assays, reducing power, and FRAP). Ethanolic extracts presented a significantly higher antioxidant activity (p < 0.05) except for FRAP, in which the best results were achieved by the aqueous extracts. Methanolic extracts showed the lowest radical scavenging activities for both DPPH; and NO; radicals

Phytochemical characterization and radical scavenging activity of aqueous extracts of medicinal plants from Portugal

Aims: The aim of this study was to evaluate the total phenolic and flavonoid contents of four medicinal plants from Portugal usually consumed as tea infusion, Melissa officinalis (Lamiaceae) – lemon balm, Matricaria chamomilla (Asteraceae) – chamomile, Olea europaea (Oleaceae) – olive leaves, and Aloysia triphylla (Verbenaceae) – lemon verbena. Place and Duration of Study: Air-dried leaves of four of the most consumed medicinal plants from Portugal were analyzed in the Department of Pharmacognosy (UFP) and Laboratory of Bromatology (FFUP) and, Department of Pharmacy, and Chemical Laboratory, Health Technology Research Center (CITS) between June 2010 and September 2011. Methodology: Qualitative phytochemical analysis was done for several phytoconstituents (alkaloids, steroids, terpenoids, flavonoids, and tannins). Total phenolic, flavonoid, and tannin contents were quantified by UV-Vis spectrophotometry. It was also analyzed the possible correlation between antioxidant activity (in vitro) and the synergistic effect between different phytochemicals, using the free radical 2,2’-diphenyl-1-picrylhydrazyl (DPPH•). Results: Steroids, terpenoids, flavonoids and tannin, were present in Melissa officinalis and Matricaria chamomilla. In Olea europaea leaves, all the chemical constituents were present except alkaloids, and terpenoids. Aloysia triphylla showed the presence of all the constituents. Total phenol contents ranged from 12.91mg.100g-1 to 87.25 mg.100g-1 and flavonoid contents ranged from 25.17mg.100g-1 to 57.28mg.100g-1. The screening of the leaf of the four selected medicinal plants indicates that the presence of high phenolic content may be due to the presence of tannins and flavonoids which are known to possess antioxidant activities. A slight correlation has been observed between total phenolics and antioxidant activity. Conclusion: Our findings provided evidence that aqueous extracts of these tested plants from Portugal contain medicinally important bioactive compounds. Results showed that plants from Portugal usually used as tea infusions are a good source of phytochemical compounds presenting antioxidant activity, so their consumption must be incremented in younger generations which usually consume other less beneficial drinks.info:eu-repo/semantics/publishedVersio

Classifying information-sharing methods

BACKGROUND: Sparse relative effectiveness evidence is a frequent problem in Health Technology Assessment (HTA). Where evidence directly pertaining to the decision problem is sparse, it may be feasible to expand the evidence-base to include studies that relate to the decision problem only indirectly: for instance, when there is no evidence on a comparator, evidence on other treatments of the same molecular class could be used; similarly, a decision on children may borrow-strength from evidence on adults. Usually, in HTA, such indirect evidence is either included by ignoring any differences ('lumping') or not included at all ('splitting'). However, a range of more sophisticated methods exists, primarily in the biostatistics literature. The objective of this study is to identify and classify the breadth of the available information-sharing methods. METHODS: Forwards and backwards citation-mining techniques were used on a set of seminal papers on the topic of information-sharing. Papers were included if they specified (network) meta-analytic methods for combining information from distinct populations, interventions, outcomes or study-designs. RESULTS: Overall, 89 papers were included. A plethora of evidence synthesis methods have been used for information-sharing. Most papers (n=79) described methods that shared information on relative treatment effects. Amongst these, there was a strong emphasis on methods for information-sharing across multiple outcomes (n=42) and treatments (n=25), with fewer papers focusing on study-designs (n=23) or populations (n=8). We categorise and discuss the methods under four 'core' relationships of information-sharing: functional, exchangeability-based, prior-based and multivariate relationships, and explain the assumptions made within each of these core approaches. CONCLUSIONS: This study highlights the range of information-sharing methods available. These methods often impose more moderate assumptions than lumping or splitting. Hence, the degree of information-sharing that they impose could potentially be considered more appropriate. Our identification of four 'core' methods of information-sharing allows for an improved understanding of the assumptions underpinning the different methods. Further research is required to understand how the methods differ in terms of the strength of sharing they impose and the implications of this for health care decisions

Experiences of structured elicitation for model based cost-effectiveness analyses

BACKGROUND: Empirical evidence supporting the cost-effectiveness estimates of particular health care technologies may be limited, or it may even be missing entirely. In these situations, additional information, often in the form of expert judgments, is needed to reach a decision. There are formal methods to quantify experts' beliefs, termed as structured expert elicitation (SEE), but only limited research is available in support of methodological choices. Perhaps as a consequence, the use of SEE in the context of cost-effectiveness modelling is limited. OBJECTIVES: This article reviews applications of SEE in cost-effectiveness modelling with the aim of summarizing the basis for methodological choices made in each application and recording the difficulties and challenges reported by the authors in the design, conduct, and analyses. METHODS: The methods used in each application were extracted along with the criteria used to support methodological and practical choices and any issues or challenges discussed in the text. Issues and challenges were extracted using an open field, and then categorised and grouped for reporting. RESULTS: The review demonstrates considerable heterogeneity in methods used, and authors acknowledge great methodological uncertainty in justifying their choices. Specificities of the context area emerging as potentially important in determining further methodological research in elicitation are between- expert variation and its interpretation, the fact that substantive experts in the area may not be trained in quantitative subjects, that judgments are often needed on various parameter types, the need for some form of assessment of validity, and the need for more integration with behavioural research to devise relevant debiasing strategies. CONCLUSIONS: This review of experiences of SEE highlights a number of specificities/constraints that can shape the development of guidance and target future research efforts in this area

Bayesian econometric modelling of observational data for cost-effectiveness analysis : establishing the value of Negative Pressure Wound Therapy in the healing of open surgical wounds

Background/Introduction In the absence of evidence from randomised controlled trials on the relative effectiveness of treatments, cost-effectiveness analyses increasingly use observational data instead. Treatment assignment is not, however, randomised, and naïve estimates of treatment effect may be biased. To deal with this bias, one may need to adjust for observed and unobserved confounders. In this work we aim to explore and discuss the challenges of these adjustment strategies using a case study of negative pressure wound therapy (NPWT) versus standard dressings for the treatment of open surgical wounds. Methods Time to wound healing, was estimated using Bayesian inference methods: i) OLS models, ii) OLS model adjusting for potential observed confounders and iii) two-stage instrumental variable (IV) models. A panel data regression approach was used to model health-related quality of life weights and costs. Cost-effectiveness estimates were obtained for selected models. Results The case study was a longitudinal cohort study of 393 participants followed up by on average 500 days. In all the modelling approaches we implemented, the treatment NPWT was estimated to offer less benefit at higher costs than competing interventions. Conclusions This study shows how to use observational data to assess cost-effectiveness by adjusting for both observable and unobservable confounders. Within the case study, we could not demonstrate that existing uncontrolled confounding affects the effectiveness of NPWT. There was no evidence that NPWT was effective or cost-effective compared to standard dressings for the treatment of SWHSI