Ocular drug delivery from contact lenses: mimetizing the hydrodynamic conditions of the eye

Poster presented at the 4th Congress on Innovation in Drug Delivery Site-Specific Drug Delivery (IDD2016). Antibes-Juan-les-Pins, France, 25-28 September 2016N/

Simulation of the hydrodynamic conditions of the eye to better reproduce the drug release from hydrogel contact lenses: experiments and modeling

The final publication is available at Springer via http://dx.doi.org/10.1007/s13346-016-0303-1Currently, most in vitro drug release studies for ophthalmic applications are carried out in static sink conditions. Although this procedure is simple and useful to make comparative studies, it does not describe adequately the drug release kinetics in the eye, considering the small tear volume and flow rates found in vivo. In this work, a microfluidic cell was designed and used to mimic the continuous, volumetric flow rate of tear fluid and its low volume. The suitable operation of the cell, in terms of uniformity and symmetry of flux, was proved using a numerical model based in the Navier-Stokes and continuity equations. The release profile of a model system (a hydroxyethyl methacrylate-based hydrogel (HEMA/PVP) for soft contact lenses (SCLs) loaded with diclofenac) obtained with the microfluidic cell was compared with that obtained in static conditions, showing that the kinetics of release in dynamic conditions is slower. The application of the numerical model demonstrated that the designed cell can be used to simulate the drug release in the whole range of the human eye tear film volume and allowed to estimate the drug concentration in the volume of liquid in direct contact with the hydrogel. The knowledge of this concentration, which is significantly different from that measured in the experimental tests during the first hours of release, is critical to predict the toxicity of the drug release system and its in vivo efficacy. In conclusion, the use of the microfluidic cell in conjunction with the numerical model shall be a valuable tool to design and optimize new therapeutic drug-loaded SCLs.info:eu-repo/semantics/publishedVersio

Cost-effectiveness of adjunct non-pharmacological interventions for osteoarthritis of the knee

BACKGROUND: There is limited information on the costs and benefits of alternative adjunct non-pharmacological treatments for knee osteoarthritis and little guidance on which should be prioritised for commissioning within the NHS. This study estimates the costs and benefits of acupuncture, braces, heat treatment, insoles, interferential therapy, laser/light therapy, manual therapy, neuromuscular electrical stimulation, pulsed electrical stimulation, pulsed electromagnetic fields, static magnets and transcutaneous electrical nerve Stimulation (TENS), based on all relevant data, to facilitate a more complete assessment of value. METHODS: Data from 88 randomised controlled trials including 7,507 patients were obtained from a systematic review. The studies reported a wide range of outcomes. These were converted into EQ-5D index values using prediction models, and synthesised using network meta-analysis. Analyses were conducted including firstly all trials and secondly only trials with low risk of selection bias. Resource use was estimated from trials, expert opinion and the literature. A decision analytic model synthesised all evidence to assess interventions over a typical treatment period (constant benefit over eight weeks or linear increase in effect over weeks zero to eight and dissipation over weeks eight to 16). RESULTS: When all trials are considered, TENS is cost-effective at thresholds of £20-30,000 per QALY with an incremental cost-effectiveness ratio of £2,690 per QALY vs. usual care. When trials with a low risk of selection bias are considered, acupuncture is cost-effective with an incremental cost-effectiveness ratio of £13,502 per QALY vs. TENS. The results of the analysis were sensitive to varying the intensity, with which interventions were delivered, and the magnitude and duration of intervention effects on EQ-5D. CONCLUSIONS: Using the £20,000 per QALY NICE threshold results in TENS being cost-effective if all trials are considered. If only higher quality trials are considered, acupuncture is cost-effective at this threshold, and thresholds down to £14,000 per QALY

A decision analytic model to investigate the cost-effectiveness of poisoning prevention practices in households with young children

Background: Systematic reviews and a network meta-analysis show home safety education with or without the provision of safety equipment is effective in promoting poison prevention behaviours in households with children. This paper compares the cost-effectiveness of home safety interventions to promote poison prevention practices. Methods: A probabilistic decision-analytic model simulates healthcare costs and benefits for a hypothetical cohort of under 5 year olds. The model compares the cost-effectiveness of home safety education, home safety inspections, provision of free or low cost safety equipment and fitting of equipment. Analyses are conducted from a UK National Health Service and Personal Social Services perspective and expressed in 2012 prices. Results: Education without safety inspection, provision or fitting of equipment was the most cost-effective strategy for promoting safe storage of medicines with an incremental cost-effectiveness ratio of £2888 (95 % credible interval (CrI) £1990–£5774) per poison case avoided or £41,330 (95%CrI £20,007–£91,534) per QALY gained compared with usual care. Compared to usual care, home safety interventions were not cost-effective in promoting safe storage of other household products. Conclusion: Education offers better value for money than more intensive but expensive strategies for preventing medicinal poisonings, but is only likely to be cost-effective at £30,000 per QALY gained for families in disadvantaged areas and for those with more than one child. There was considerable uncertainty in cost-effectiveness estimates due to paucity of evidence on model parameters. Policy makers should consider both costs and effectiveness of competing interventions to ensure efficient use of resources

Statistical analyses and quality of individual participant data network meta-analyses were suboptimal: a cross-sectional study

Background Network meta-analyses using individual participant data (IPD-NMAs) have been increasingly used to compare the effects of multiple interventions. Although there have been many studies on statistical methods for IPD-NMAs, it is unclear whether there are statistical defects in published IPD-NMAs and whether the reporting of statistical analyses has improved. This study aimed to investigate statistical methods used and assess the reporting and methodological quality of IPD-NMAs. Methods We searched four bibliographic databases to identify published IPD-NMAs. The methodological quality was assessed using AMSTAR-2 and reporting quality assessed based on PRISMA-IPD and PRISMA-NMA. We performed stratified analyses and correlation analyses to explore the factors that might affect quality. Results We identified 21 IPD-NMAs. Only 23.8% of the included IPD-NMAs reported statistical techniques used for missing participant data, 42.9% assessed the consistency, and none assessed the transitivity. None of the included IPD-NMAs reported sources of funding for trials included, only 9.5% stated pre-registration of protocols, and 28.6% assessed the risk of bias in individual studies. For reporting quality, compliance rates were lower than 50.0% for more than half of the items. Less than 15.0% of the IPD-NMAs reported data integrity, presented the network geometry, or clarified risk of bias across studies. IPD-NMAs with statistical or epidemiological authors often better assessed the inconsistency (P = 0.017). IPD-NMAs with a priori protocol were associated with higher reporting quality in terms of search (P = 0.046), data collection process (P = 0.031), and syntheses of results (P = 0.006). Conclusions The reporting of statistical methods and compliance rates of methodological and reporting items of IPD-NMAs were suboptimal. Authors of future IPD-NMAs should address the identified flaws and strictly adhere to methodological and reporting guidelines

Cost-effectiveness of interventions for increasing the possession of functioning smoke alarms in households with pre-school children: a modelling study

Background The UK has one of the highest rates for deaths from fire and flames in children aged 0-14 years compared to other high income countries. Evidence shows that smoke alarms can reduce the risk of fire-related injury but little exists on their cost-effectiveness. We aimed to compare the cost effectiveness of different interventions for the uptake of 'functioning' smoke alarms and consequently for the prevention of fire-related injuries in children in the UK. Methods We carried out a decision model-based probabilistic cost-effectiveness analysis. We used a hypothetical population of newborns and evaluated the impact of living in a household with or without a functioning smoke alarm during the first 5 years of their life on overall lifetime costs and quality of life from a public health perspective. We compared seven interventions, ranging from usual care to more complex interventions comprising of education, free/low cost equipment giveaway, equipment fitting and/or home safety inspection. Results Education and free/low cost equipment was the most cost-effective intervention with an estimated incremental cost-effectiveness ratio of [pound sign]34,200 per QALY gained compared to usual care. This was reduced to approximately £4,500 per QALY gained when 1.8 children under the age of 5 were assumed per household. Conclusions Assessing cost-effectiveness, as well as effectiveness, is important in a public sector system operating under a fixed budget restraint. As highlighted in this study, the more effective interventions (in this case the more complex interventions) may not necessarily be the ones considered the most cost-effective

Museum and herbarium collections for biodiversity research in Angola

The importance of museum and herbarium collections is especially great in biodiverse countries such as Angola, an importance as great as the challenges facing the effective and sustained management of such facilities. The interface that Angola represents between tropical humid climates and semi-desert and desert regions creates conditions for diverse habitats with many rare and endemic species. Museum and herbarium collections are essential foundations for scientific studies, providing references for identifying the components of this diversity, as well as serving as repositories of material for future study. In this review we summarise the history and current status of museum and herbarium collections in Angola and of information on the specimens from Angola in foreign collections. Finally, we provide examples of the uses of museum and herbarium collections, as well as a roadmap towards strengthening the role of collections in biodiversity knowledge generationinfo:eu-repo/semantics/publishedVersio