935 research outputs found
Cost-minimisation analysis of a treat-and-extend regimen with anti-VEGFs in patients with neovascular age-related macular degeneration
PURPOSE: Although intraocular anti-vascular endothelial growth factors (anti-VEGFs) are effective as treatment of neovascular age-related macular degeneration (nAMD), the (economic) burden on the healthcare system is considerable. A treat-and-extend (T&E) regimen is associated with a lower number of injections without compromising the effectiveness and can therefore help optimise nAMD treatment. This study investigates the per-patient costs associated with nAMD treatment, when using aflibercept, bevacizumab, or ranibizumab with a T&E regimen. METHODS: In this cost-minimisation model, the per-patient costs in the Netherlands were modelled using a healthcare payersâ perspective over a 3-year time horizon with the assumption that efficacy of treatments is similar. Additionally, the break-even price of the different anti-VEGFs was calculated relative to the cheapest option and injection frequency. RESULTS: The injection frequency varied from 14.2 for aflibercept to 27.4 for bevacizumab in 3 years. Nonetheless, bevacizumab remains the cheapest treatment option (âŹ14,215), followed by aflibercept (âŹ18,202) and ranibizumab (âŹ31,048). The medication covers the majority of the per-patient costs for aflibercept and ranibizumab, while administration covers the majority of the per-patient costs for bevacizumab. The break-even prices of aflibercept and ranibizumab are respectively âŹ507 and âŹ60.58 per injection. Brolucizumab was included in the scenario analysis and was more expensive than aflibercept (âŹ20,446). Brolucizumab should reduce to 13.8 injections over 3 years to be as costly as aflibercept. CONCLUSION: Bevacizumab is the cheapest anti-VEGF treatment. The list prices of all anti-VEGFs should reduce to be as costly as bevacizumab. Aflibercept is the second-choice treatment and so far brolucizumab is not
Advancing participatory backcasting for climate change adaptation planning using 10 cases from 3 continents
In the face of climate change, a major challenge is to inform and guide long-term climate change adaptation planning under deep uncertainty, while aiming at transformative change. Normative futures studies approaches, such as participatory backcasting, visioning and transition management, are increasingly applied, but their potential for climate change adaptation research and practice remains undervalued. This paper aims to advance the potential of backcasting in climate adaptation, by comparing various climate change adaptation studies that have used backcasting or visioning approaches. A framework has been further developed and applied to evaluate 10 cases in Africa, Europe and North America, using four dimensions: (i) inputs and settings; (ii) process and methods (iii) results, and (iv), impact. Our evaluation provides key insights into the use and further development of backcasting for climate adaptation. Key elements to add are advanced system modeling, robust elements, pathway switching and hybrid pathways, enhancing participation of marginal groups, and contributing to impact by facilitating the utilization of results and knowledge in practice and decision making
Identifying Sources of Error in Surveys of Devils Hole Pupfish (Cyprinodon diabolis)
We assessed four potential sources of error in estimating size of the population of Devils Hole pupfish (Cyprinodon diabolis): net, time of day, diver, and order of diver. Experimental dives (3/day) were conducted during 4 days in July 2009. Effects of the four sources of error on estimates from dive surveys were analyzed using a split-split plot ANOVA. Diver and order of diver had no significant influence on estimates, whereas the effect of presence or absence of a net was significant. Effects of time of day and presence or absence of a net showed a significant interaction with depth of water. Results indicated that pupfish may move upward during the dive, and as a result, the standard methods of dive surveys may underestimate abundance
Peanut ball for decreasing length of labor: A systematic review and meta-analysis of randomized controlled trials
INTRODUCTION:
Prolonged length of labor is associated with increased maternal and neonatal complications. Therefore, great attention has been given to interventions aimed at reducing the length of labor. One such intervention is the peanut ball, a large elongated exercise ball placed between a woman's legs during labor.
OBJECTIVE:
The aim of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to assess the effect of the use of peanut ball in reducing length of labor.
STUDY DESIGN:
Data sources: MEDLINE, EMBASE, Web of Sciences, Scopus, ClinicalTrial.gov, OVID and Cochrane Library were searched from inception until January 2019.
SELECTION CRITERIA:
Selection criteria included RCTs of laboring women with singleton gestations in cephalic presentation at term (â„37weeks) who were randomized to either use of peanut ball or control group (no peanut ball).
DATA COLLECTION AND ANALYSIS:
Four trials with 648 nulliparous and multiparous women in spontaneous or induced labor were identified and included. 330 women were randomized to the intervention (peanut ball between the knees during labor) and 318 women to the control. Summary measures were reported as mean difference (MD) with 95% of confidence interval (CI) using the random effects model of DerSimonian and Laird. The primary outcome was total length of labor. PROSPERO Registration Number: CRD42018082438 RESULTS: Total length of labor was 79min shorter in the peanut ball group, but this was not significant (MD -79.1 min, 95% CI -204.9, 46.7). Peanut ball use showed trends toward higher incidence of spontaneous vaginal deliveries (RR 1.1, 95% CI 1.0, 1.2) and lower incidence of cesarean deliveries (RR 0.8, 95% CI 0.6, 1.0).
CONCLUSIONS:
Peanut ball use was not associated with a significant decrease in total length of labor. Since there were trends toward reductions in length of labor, an increased incidence in spontaneous vaginal deliveries, and lower incidence of cesarean deliveries, more research is needed
Loss of Potential Aquatic-Terrestrial Subsidies Along the Missouri River Floodplain
The floodplains of large rivers have been heavily modified due to riparian development and channel modifications, both of which can eliminate shallow off-channel habitats. The importance of these habitats for aquatic organisms like fishes is well studied. However, loss of off-channel habitat also eliminates habitats for the production of emerging aquatic insects, which subsidize riparian consumers in terrestrial food webs. We used field collections of insect emergence, historical mapping, and statistical modeling to estimate the loss of insect emergence due to channel modifications along eight segments of the Missouri River (USA), encompassing 1566 river km, between 1890 and 2012. We estimate annual production of emerging aquatic insects declined by a median of 36,000 kgC (95% CrI: 3000 to 450,000) between 1890 and 2012 (a 34% loss), due to the loss of surface area in backwaters and related off-channel habitats. Under a conservative assumption that riparian birds obtain 24% of their annual energy budget from adult aquatic insects, this amount of insect loss would be enough to subsidize approximately 790,000 riparan woodland birds during the breeding and nesting period (May to August; 95% CrI: 57,000 to 10,000,000). Most of the loss is concentrated in the lower reaches of the Missouri River, which historically had a wide floodplain, a meandering channel, and a high density of off-channel habitats, but which were substantially reduced due to channelization and bank stabilization. Our results indicate that the loss of off-channel habitats in large river floodplains has the potential to substantially affect energy availability for riparian insectivores, further demonstrating the importance of maintaining and restoring these habitats for linked aquatic-terrestrial ecosystems
Perinatal death by bile acid levels in intrahepatic cholestasis of pregnancy: a systematic review
Background: Intrahepatic cholestasis of pregnancy (ICP) is characterized by the elevation of total bile acids (TBAs). The primary concern in women with ICP is the increased risk of stillbirth. ICP is generally considered as âmildâ when TBA levels range from 10 to 39 ”mol/L and âsevereâ with levels greater than 40 ”mol/L, although levels of TBA â„100 ”mol/L have been also considered as a further threshold of severity. Objective: To quantify the association between different severities of ICP (TBA 10â39, 40â99, and â„100 ”mol/L) and perinatal death. Data sources: Medline, Embase, Scopus, Web of Sciences, and ClinicalTrial.gov were searched from the inception of each database to February 2019. Methods of study selection: Randomized, cohort, case-control, or case series studies reporting maternal and perinatal outcomes on women with ICP by the three prespecified TBA levels (10â39, 40â99, and â„100 ”mol/L) were included. We excluded multiple gestations and trials which included an intervention. The analysis was performed with Pearson chi-square and Fisherâs exact test as appropriate. Continuous outcomes were compared using metaregression with inverse variance weighting using reported sample sizes and standard deviations. Pairwise comparisons used a Bonferroni correction to control for multiple testing. Tabulation, integration, and results: Six articles including 1280 singleton pregnancies affected by ICP were included in the systematic review. Out of the 1280 singleton pregnancies affected by ICP included, 118 had ICP with TBA â„100 ”mol/L. Perinatal death was more common in women with TBA â„100 ”mol/L (0.4% for TBA 10-39 ÎŒmol/L versus 0.3% for TBA 40-99 ÎŒmol/L versus 6.8% for TBA â„ 100 ÎŒmol/L, p <.0001). Of the 8 perinatal deaths in the TBA â„100 ”mol/L group, 3 occurred â„34 weeks. TBA â„100 ”mol/L increased the risk of spontaneous preterm birth (PTB) (5.4% versus 8.6% versus 18.2% respectively, p <.0001) and iatrogenic PTB (10.8% versus 21.6% versus 35.8% respectively, p<.0001) as well as meconium-stained amniotic fluid (9.0% versus 18.4% versus 31.6% respectively, p <.0001). Conclusions: Maternal TBA â„100 ”mol/L is associated with a 6.8% incidence of perinatal death, most of which (5.9% overall) are stillbirths, while TBA <100 ”mol/L are associated with an incidence of perinatal death of 0.3%. It may be reasonable to consider late preterm delivery (at about 35â36 weeks) in women with TBA â„100 ”mol/L
Prioritization of fish communities with a view to conservation and restoration on a large scale European basin, the Loire (France)
The hierarchical organization of important sites for the conservation or the
restoration of fish communities is a great challenge for managers, especially because of
financial or time constraints. In this perspective, we developed a methodology, which is
easy to implement in different locations. Based on the fish assemblage characteristics of
the Loire basin (France), we created a synthetic conservation value index including the
rarity, the conservation status and the species origin. The relationship between this new
synthetic index and the Fish-Based Index allowed us to establish a classification protocol
of the sites along the Loire including fish assemblages to be restored or conserved. Sites
presenting disturbed fish assemblages, a low rarity index, few threatened species, and a
high proportion of non-native species were considered as important for the restoration of
fish biodiversity. These sites were found mainly in areas where the assemblages are
typical of the bream zone, e.g. with a higher number of eurytopic and limnophilic
species. On the contrary, important sites for conservation were defined as having an
important conservation potential (high RI, a lot of threatened species, and few nonnatives
fish species) and an undisturbed fish assemblage similar to the expected community
if habitats are undisturbed. Important sites for conservation were found in the
Loire basinâs medium reaches which host assemblages typical for the grayling and the
barbell zones, e.g. with a higher number of rheophilic species. The synthetic conservation value index could be adapted and completed with other criteria according to
management priorities and capacities
Crater formation by fast ions: comparison of experiment with Molecular Dynamics simulations
An incident fast ion in the electronic stopping regime produces a track of
excitations which can lead to particle ejection and cratering. Molecular
Dynamics simulations of the evolution of the deposited energy were used to
study the resulting crater morphology as a function of the excitation density
in a cylindrical track for large angle of incidence with respect to the surface
normal. Surprisingly, the overall behavior is shown to be similar to that seen
in the experimental data for crater formation in polymers. However, the
simulations give greater insight into the cratering process. The threshold for
crater formation occurs when the excitation density approaches the cohesive
energy density, and a crater rim is formed at about six times that energy
density. The crater length scales roughly as the square root of the electronic
stopping power, and the crater width and depth seem to saturate for the largest
energy densities considered here. The number of ejected particles, the
sputtering yield, is shown to be much smaller than simple estimates based on
crater size unless the full crater morphology is considered. Therefore, crater
size can not easily be used to estimate the sputtering yield.Comment: LaTeX, 7 pages, 5 EPS figures. For related figures/movies, see:
http://dirac.ms.virginia.edu/~emb3t/craters/craters.html New version uploaded
5/16/01, with minor text changes + new figure
GMOs: Non-Health Issues
The controversy over genetically modified [GM] organisms is often framed in terms of possible hazards for human health. Articles in a previous volume of this *Encyclopedia* give a general overview of GM crops [@Mulvaney2014] and specifically examine human health [@Nordgard2014] and labeling [@Bruton2014] issues surrounding GM organisms. This article explores several other aspects of the controversy: environmental concerns, political and legal disputes, and the aim of "feeding the world" and promoting food security. Rather than discussing abstract, hypothetical GM organisms, this article explores the consequences of the GM organisms that have actually been deployed in the particular contexts that they have been deployed, on the belief that there is little point in discussing GM organisms in an idealized or context-independent way
Discovery of a small molecule probe that post-translationally stabilizes the survival motor neuron protein for the treatment of spinal muscular atrophy.
Spinal muscular atrophy (SMA) is the leading genetic cause of infant death. We previously developed a high-throughput assay that employs an SMN2-luciferase reporter allowing identification of compounds that act transcriptionally, enhance exon recognition, or stabilize the SMN protein. We describe optimization and characterization of an analog suitable for in vivo testing. Initially, we identified analog 4m that had good in vitro properties but low plasma and brain exposure in a mouse PK experiment due to short plasma stability; this was overcome by reversing the amide bond and changing the heterocycle. Thiazole 27 showed excellent in vitro properties and a promising mouse PK profile, making it suitable for in vivo testing. This series post-translationally stabilizes the SMN protein, unrelated to global proteasome or autophagy inhibition, revealing a novel therapeutic mechanism that should complement other modalities for treatment of SMA
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