Análisis coste-efectividad del implante percutáneo de válvula aórtica SAPIEN 3 en pacientes con estenosis aórtica grave sintomática / Cost-effectiveness analysis of the SAPIEN 3 transcatheter aortic valve implant in patients with symptomatic severe aortic stenosis

Introducción y objetivos: El implante percutáneo de la válvula aórtica se ha consolidado como tratamiento de la estenosis aórtica grave inoperable o de alto riesgo quirúrgico. Recientemente las indicaciones se han ampliado a riesgo intermedio y bajo. Nuestro objetivo es evaluar la eficiencia de SAPIEN 3 frente al tratamiento médico conservador (TMC) o el reemplazo quirúrgico de válvula aórtica (RVA) en pacientes sintomáticos inoperables con riesgo alto e intermedio.´Métodos: Análisis de coste-efectividad de SAPIEN 3 frente a RVA/TMC mediante un modelo de Markov (ciclos mensuales) adaptado con 8 estados definidos por la New York Hearth Association y resultados a 15 años, incluidos las complicaciones mayores y el tratamiento tras el alta hospitalaria, desde la perspectiva del Sistema Nacional de Salud. Los parámetros de efectividad se basan en los estudios PARTNER. Se incluyeron costes sanitarios (en euros de 2019) derivados del procedimiento, hospitalización, complicaciones clínicas y seguimiento. Se aplicó una tasa de descuento anual del 3% en costes y beneficios. El análisis de sensibilidad fue determinístico y probabilístico (Monte Carlo). Resultados: En comparación con el RVA (riesgo alto e intermedio) y el TMC (inoperables), el SAPIEN 3 implicó mejores resultados en las 3 poblaciones y menor estancia. Las tasas de coste-utilidad incremental fueron 5.471 (riesgo alto), 8.119 (riesgo intermedio) y 9.948 (inoperables) euros/años de vida ajustados por calidad ganados. En el análisis probabilístico, el SAPIEN 3 resultó coste-efectivo por encima del 75% de las simulaciones en los 3 perfiles. Conclusiones: En nuestro medio, el SAPIEN 3 permite un tratamiento eficiente de la estenosis aórtica grave tanto en pacientes inoperables como en riesgo alto e intermedio (AU)

Introduction and objectives: Transcatheter aortic valve implant has become a widely accepted treatment for inoperable patients with aortic stenosis and patients at high surgical risk. Its indications have recently been expanded to include patients at intermediate and low surgical risk. Our aim was to evaluate the efficiency of SAPIEN 3 vs conservative medical treatment (CMT) or surgical aortic valve replacement (SAVR) in symptomatic inoperable patients at high or intermediate risk. Methods: We conducted a cost-effectiveness analysis of SAPIEN 3 vs SAVR/CMT, using a Markov model (monthly cycles) with 8 states defined by the New York Heart Association and a time horizon of 15 years, including major complications and management after hospital discharge, from the perspective of the National Health System. Effectiveness parameters were based on the PARTNER trials. Costs related to the procedure, hospitalization, complications, and follow-up were included (euros in 2019). An annual discount rate of 3% was applied to both costs and benefits. Deterministic and probabilistic sensitivity analyses (Monte Carlo) were performed. Results: Compared with SAVR (high and intermediate risk) and CMT (inoperable), SAPIEN 3 showed better clinical results in the 3 populations and lower hospital stay. Incremental cost-utility ratios (€/quality-adjusted life years gained) were 5471 (high risk), 8119 (intermediate risk) and 9948 (inoperable), respectively. In the probabilistic analysis, SAPIEN 3 was cost-effective in more than 75% of the simulations in the 3 profiles. Conclusions: In our health system, SAPIEN 3 facilitates efficient management of severe aortic stenosis in inoperable and high- and intermediate-risk patients (AU)

NEEM: UNUSUALLY VERSATILE PLANT GENUS AZADIRACHTA WITH MANY USEFUL AND SO FAR INSUFFICIENTLY EXPLOITED PROPERTIES FOR AGRICULTURE, MEDICINE, AND INDUSTRY.

Neem plants (Rutales: Meliaceae) are well known for their multitude of human benefits in various fields. Specifically well investigated are the Indian neem tree Azadirachta indica A. Juss., the Thai neem A. siamensis Val., the originally Malaysian/Philippinean neem A. excelsa (Jack) and, as a close relative, the Persian lilac, Melia azedarach. The major and most active natural products are azadirachtin, salannin, nimbin and marrangin from Azadirachta species, and azadirachtin analogues like meliantriol from Melia species. Neem fruits, leaves, bark, and roots have specific virtues. They have been traditionally exploited for a considerable part of human history and are documented in Sanskrit texts. Due to human activity in trade and travel both at land and sea, the plant species has been distributed around the globe and is cultivated in many tropical, and subtropical regions. A multitude of natural products of neem have been isolated, chemically characterized or identified, and investigated for their properties in the management of insects, Acarina, Crustacea, nematodes, bacteria, fungi, viruses and soil fertility (for reviews see Kraus, 2002; Schmutterer, 2002A; Rembold, 2002; Koul, 2004; Schmutterer and Huber, 2005; Kleeberg and Strang, 2009; Hummel et al., 2008, 2011, 2012). Neem products are virtually nontoxic, compatible with beneficial insects, pollinators and bees. They are environmentally benign, sustainable, renewable, and of a price affordable for developed countries. In conclusion, neem is a prime example of a natural resource with many beneficial applications in agriculture, human and veterinary medicine. So far, its use is practically free of resistance problems which are frustratingly prevalent in many areas of synthetic insecticide and drug development. Investigating more neem applications will increase future human welfare and health while being of general ecological benefit to the planet.

EXPLOITING CHEMICAL ECOLOGY FOR LIVELIHOOD IMPROVEMENT OF SMALL HOLDER FARMERS IN KENYA.

"Push-Pull" is an inexpensive and eminently practical strategy designed for developing countries in order to exploit sound principles of chemical ecology for agricultural pest management. This strategy is specifically suitable for small holder farmers. Their experience can easily be integrated into existing farming practices in their immediate environment. "Push-pull" within one and a half decades became widely established and meanwhile is greatly beneficial to practitioners in East Africa, mainly Kenya. The classical push-pull approach used for applied plant-insect management was pioneered by Khan and Pickett (2000) and subsequent papers of Pickett (2003) and Khan et al. (2006, 2008). Relevant plant species explored so far were maize or sorghum intercropped with other East African plants (Desmodium spp. resp. Melinis minutiflora) possessing natural chemicals repellent resp. attractive for stem borer moths Chilo partellus (Lepidoptera), whereby Desmodium spp. was grown inside the maize rows while M. minutiflora surrounded it. Both simultaneous actions combined resulted in a significant decrease of stem borers in the area to be protected. A benefit to cost ratio of 2.5 was realized. Within a period of 15 years the number of subscribing farmers substantially increased from a few dozen to more than 80,000 in 2014. Two experiments along the paths of chemical ecology were undertaken between Sept 2012 and Feb 2013: One was designed to investigate if the legume D. intortum known to produce repellent volatiles against stem borer moths induces defence in Zea mays varieties. We looked at two open-pollinated farmers' varieties and two commercial hybrid varieties suspecting the farmers' varieties to be responsive rather than the hybrids. However, no defence induction was detected in this study so far. This could be explained by an insufficient production of defence inducing volatiles in leaves of D. intortum whereas flowers might produce a sufficient response. More detailed study is needed. A second approach made use of species-specific insect monitoring traps baited with highly specific female sex pheromones for attracting and monitoring destructive insect pests. The female sex pheromone (8-methyl-decane-2-ol propanoate) of Diabrotica virgifera virgifera (Coleoptera: Chrysomelidae) (Western Corn Rootworm) is readily available as bait in the "Metcalf sticky cup trap" for trapping males, an extraordinarily sensitive technique for monitoring the presence or absence of male beetles in a given area. Li et al. (2006) had argued for the likelihood of easy immigration of this cosmopolitan maize pest into East Africa. Our results, however, so far indicate the absence of a local population in the area of Mbita, while not excluding its presence at Nairobi or Mombasa. Both investigations contribute to different aspects of Kenyan economic development and may be seen as two independent but complementary contributions towards livelihood improvement of small holder farmers in Kenya.

Diabrotica virgifera virgifera on South-Northern expansion drive?

As Wudtke and colleagues predicted and Hummel and colleagues later confirmed, the Western corn rootworm Diabrotica v. virgifera LeConte (Coleoptera: Chrysomelidae) (WCR) had shown the ability to expand northward from South and Eastern into Central Europe. Decades earlier WCR had done the same in North America. Yet, European entomologists erroneously assumed they would be somehow magically protected from such aggressive moves of WCR. Meanwhile we know better: Southern Germany is infested, and also many East European countries are victims of these Northern and also Eastern advances. In Germany, neither speed nor extent of such advances is well defined. Jumping advances similar to earlier spreading episodes may be the rule, but they are not well predictable. In this report, we argue for a persistent northbound trend of WCR.

New dispenser types for integrated pest management of agriculturally significant insect pests: an algorithm with specialized searching capacity in electronic data bases.

Pheromone effects discovered some 130 years, but scientifically defined just half a century ago, are a great bonus for basic and applied biology. Specifically, pest management efforts have been advanced in many insect orders, either for purposes or monitoring, mass trapping, or for mating disruption. Finding and applying a new search algorithm, nearly 20,000 entries in the pheromone literature have been counted, a number much higher than originally anticipated. This compilation contains identified and thus synthesizable structures for all major orders of insects. Among them are hundreds of agriculturally significant insect pests whose aggregated damages and costly control measures range in the multibillions of dollars annually. Unfortunately, and despite a lot of effort within the international entomological scene, the number of efficient and cheap engineering solutions for dispensing pheromones under variable field conditions is uncomfortably lagging behind. Some innovative approaches are cited from the relevant literature in an attempt to rectify this situation. Recently, specifically designed electrospun organic nanofibers offer a lot of promise. With their use, the mating communication of vineyard insects like Lobesia botrana (Lep.: Tortricidae) can be disrupted for periods of seven weeks.

Sex pheromone monitoring as a versatile tool for determining presence and abundance of Cydia pomonella (Lep.: Tortricidae) in German apple orchards.

Cydia pomonella (Lep.: Tortricidae), the codling moth, is an apple, pear, quince and walnut pest with considerable impact on horticultural production systems in many parts of the world. In commercial apple production, it is responsible for a yearly damage level of 40 billion dollars. In response to the need of tight codling moth control there are several options for intervention by pest managers in commercially operated orchards. Spray and count methods have been used for decades with success, but at considerable external costs for the integrity of ecological cycles. Also, problems with pesticide residues and with resistant strains are an issue of concern. For environmental reasons, toxicological means are discounted here. Instead, flight curves based on sex pheromone trapping and monitoring are preferred means towards determining the optimal timing of interventions by biotechnical and biological control methods. Finally, ecological reasons are discussed for vastly different population levels of C. pomonella developing in closely neighboring field sections which operated under different environmental management.

Organic nanofibers containing insect pheromone disruptants: a novel technical approach to controlled release dispensers with potential for process mechanization.

Beginning fifty years ago, the search for suitable dispensers containing insect pheromones grew with the availability of these synthetic biotechnical tools. Many economic entomologists and application engineers dearly wish they had the "smart, intelligent and ideal dispenser". More or less suitable approximations are available commercially, but none so far meets all demands. Under economic strictures, novel inexpensive systems would be advantageous with release characteristics tailored to the specific life histories of pest insects, the plants considered and the numerous requirements of growers alike. Simultaneously, their field distribution should be mechanizable and be accomplished by one (or very few) application runs. The dispensers should be biodegradable, biocompatible, sustainably applicable, and they should be based on renewable resources. This report presents first results of a novel organic, electrospun nanofiber dispenser with dimensions in the upper nanometer range. Its load of pheromone can be adjusted to be sufficient for 7 weeks of constant disruptive action in vineyards and can be directed against the European Grape Vine Moth Lobesia botrana (Lepidoptera: Tortricidae) which here serves as a readily available model. Mating disruption in L. botrana and the related Eupoecilia ambiguella is a well studied and developed engineering process. Equally, nanofiber production by electrospinning (for a comprehensive review see Greiner and Wendorff, 2007A, B) is well known and already has numerous applications in filtration technology, air conditioning, and medical wound dressing. Our goal was to bring together and successfully mate these (partly incompatible) technologies via technical tricks of a proprietary nature. Even though the lifetime and effectiveness of currently available nanofibers still must be doubled, the rather complicated system of their production and analysis is known well enough to identify the parameters that need future adjustment. Another challenge is the mechanical distribution of the fibers in the vineyards by suitable machinery. Also, in this respect, certain technical leads are available for future development.

Organic electrospun nanofibers as vehicles toward intelligent pheromone dispensers: characterization by laboratory investigations.

Organic nanofibers have a history of technical application in various independent fields, including medical technology, filtration technology, and applications of pharmaceuticals via inhalation into the lungs. Very recently, in a joint effort with polymer chemists, agricultural applications have been added to this list of priorities. The aim is finding novel approaches to insect control. Pheromones, dispensed in a quantifiable way, are being used here in disrupting the mating communication between male and female pest insects, e.g. the European grapevine moth Lobesia botrana (Lepidoptera: Tortricidae), where current dispenser technology does not fully meet the high expectations of growers and environmentalists with respect to longevity of constant release, self decomposition, mechanical distribution, renewability as well as sustainability of resources. The methodology of electrospinning is exhaustively covered by Greiner and Wendorff (2007), with technical details reported by Hellmann et al. (2009), Hein et al. (2011), and Hummel et al. (2010). Wind tunnel studies were run within a tunnel with adjustable laminar flow and 0.5 m/sec air velocity. Mass losses of the electrospun fiber bundles were determined with a sensitive analytical balance 2-3 times per week and recorded as time vs. mass change. CLSA experiments were performed with a self developed glass apparatus (Lindner, 2010) based on various suggestions of previous authors. Microgram quantities of volatile pheromone (E,Z)-7,9-Dodecadienylacetate were absorbed on a filter of rigorously purified charcoal and desorbed by repeated micro extraction with a suitable solvent mixture. Aliquots of the solution were subjected to temperature programmed capillary GLC. Retention times were used for identification, whereas the area covered by the pheromone peak originating from a FID detector signal was integrated and compared with a carefully calibrated standard peak. Since these signals were usually in the low nanogram range, several replications were averaged for statistical improvement. - Thermogravimetric analysis between ambient temperature and 500 degrees C provided a series of degradation curves where the diagram contained information on the evaporation of pheromone alone, polymer fiber alone and pheromone included in the fiber.- Microscopic investigations resulted in pictures of nanofibers from which the overall morphology and the fiber dimensions could be quantified. Organic nanofibers loaded with the grapevine moth pheromone have been well characterized by 5 different lab methods, followed by field bioassays reported elsewhere in these communications volumes (HUMMEL et al., 2011). This comprehensive analytical approach to fiber characterization is new and will be further refined. The federal agency JKI Berlin subjected the pheromone loaded organic fibers to various independent toxicological and ecotoxicological tests and found no adverse side effects.

The western corn rootworm (Diabrotica virgifera virgifera) and its first appearance in Germany 2007.

Diabrotica v. virgifera (WCR) is one of the most successful invasive insect species and owes this success to its close association with mankind, to worldwide trade and commerce connections, and to widely practiced, monoculturally oriented production patterns which are characteristic for contemporary agriculture in several parts of the world. Without a drastic change in attitudes and approaches of a globalizing agriculture, WCR will in the foreseeable future have invaded all maize growing areas. WCR is continuing its spreading within Europe with its first documented appearance in Germany 2007, where two major and three minor sites of invasion are identified. Unfortunately, WCR already has secondary hosts and, through accelerated microevolution, soon may acquire more of them. The beetle may be seen as a clever follower in the footsteps of Homo sapiens and may thrive on worldwide ecological imbalances. Without major new paradigms in control and management approaches, WCR will be one of the big winners of globalization and mercilessly occupy the niches opening up. Some biotechnical and cultural alternatives are discussed which, in combination with biocontrol, may assist in evironmentally compatible management of WCR.