Coherent diffractive imaging of proteins and viral capsids: simulating MS SPIDOC.

MS SPIDOC is a novel sample delivery system designed for single (isolated) particle imaging at X-ray Free-Electron Lasers that is adaptable towards most large-scale facility beamlines. Biological samples can range from small proteins to MDa particles. Following nano-electrospray ionization, ionic samples can be m/z-filtered and structurally separated before being oriented at the interaction zone. Here, we present the simulation package developed alongside this prototype. The first part describes how the front-to-end ion trajectory simulations have been conducted. Highlighted is a quadrant lens; a simple but efficient device that steers the ion beam within the vicinity of the strong DC orientation field in the interaction zone to ensure spatial overlap with the X-rays. The second part focuses on protein orientation and discusses its potential with respect to diffractive imaging methods. Last, coherent diffractive imaging of prototypical T = 1 and T = 3 norovirus capsids is shown. We use realistic experimental parameters from the SPB/SFX instrument at the European XFEL to demonstrate that low-resolution diffractive imaging data (q < 0.3 nm-1) can be collected with only a few X-ray pulses. Such low-resolution data are sufficient to distinguish between both symmetries of the capsids, allowing to probe low abundant species in a beam if MS SPIDOC is used as sample delivery.

Estimating the economic consequences of an increased medication adherence due to a potential improvement in the inhaler technique with Spiromax® compared with Turbuhaler® in patients with moderate-to-severe chronic obstructive pulmonary disease in Spain.

OBJECTIVE: The objective of this study was to estimate the economic impact of the introduction of DuoResp® Spiromax®, budesonide/formoterol fixed-dose combination (FDC), focusing on an increase in medication adherence due to an enhancement of the inhalation technique for the treatment of COPD patients in Spain and 5 regions including Andalusia, Catalonia, Galicia, Madrid, and Valencia. METHODS: A 4-year budget impact model was developed for the time period of 2015-2018. This study aimed at evaluating the budget impact associated with the introduction of DuoResp Spiromax in comparison with Symbicort® Turbuhaler® and Rilast® Turbuhaler. National and regional data on COPD prevalence were obtained from the literature. Input data on health care resource utilization were obtained by clinical consultation. Resource included primary care visits, specialist visits, hospitalization, and emergency room visits as well as the length of hospital stay. Based on both pharmacological and health care resource costs, overall annual treatment cost per patient was estimated in EUR 2015. RESULTS: It was calculated that 130,777 adults were treated with budesonide/formoterol FDC delivered by a dry powder inhaler, Turbuhaler, in Spain in 2015. However, the target population decreases over the next 4 years. This pattern was observed in 4 regions, but for Andalusia, the treated population increased slightly. The overall budget savings in Spain with the market share of DuoResp Spiromax were estimated to be €6.01 million for the time period of 2015-2018. Region-specific data resulted in savings of €902,133 in Andalusia, €740,520 in Catalonia, €464,281 in Galicia, €748,996 in Madrid, and €495,812 in Valencia for the time period of 2015-2018. CONCLUSION: The introduction of budesonide/formoterol FDC delivered by Spiromax for COPD treatment is likely to contribute in a reduction of health care costs for Spain and in 5 Spanish regions. This model forecasts that Spain and these 5 Spanish regions were likely to have savings, which might be due to fewer days of hospitalization, avoided emergency room, and primary care visits.

A budget impact analysis of Spiromax(®) compared with Turbuhaler(®) for the treatment of moderate to severe asthma: a potential improvement in the inhalation technique to strengthen medication adherence could represent savings for the Spanish Healthcare System and five Spanish regions.

OBJECTIVE: To assess the economic impact of the introduction of DuoResp(®) Spiromax(®) by focusing on a potential improvement in the inhalation technique to strengthen medication adherence for the treatment of moderate to severe asthmatics in Spain and five Spanish regions including Andalusia, Catalonia, Galicia, Madrid, and Valencia. METHODS: A 4-year budget impact model was developed for the period 2015-2018 from the Spanish Healthcare System perspective. Budesonide-formoterol fixed-dose combination delivered by Turbuhaler(®) was considered to be the most appropriate comparator for assessing the budget impact with the introduction of DuoResp(®) Spiromax(®). National and regional data on asthma prevalence were obtained from the literature. Input parameters on health care resources were obtained by consulting experts from different Spanish hospitals. Resources used included medical visits, emergency room visits, and hospitalizations. The average numbers of primary care and specialist visits per year were also gathered. Based on health care resource use per patient, the total treatment cost per patient was estimated. RESULTS: The population with moderate to severe asthma treated with budesonide-formoterol fixed-dose combinations delivered by Turbuhaler(®) in 2015 was estimated to be 166,985 in Spain. Region-specific prevalence data resulted in 25,081, 12,392, 16,097, 17,829, and 15,148 patients in Andalusia, Catalonia, Galicia, Madrid, and Valencia, respectively. Based on the forecast uptake of DuoResp(®) Spiromax(®), the total budget savings in Spain were expected to be €1.509 million over the next 4 years. Region-specific rates imply that the total savings were expected to be €229,706 in Andalusia, €90,145 in Catalonia, €188,327 in Galicia, €122,669 in Madrid, and €165,796 in Valencia over 2015-2018. CONCLUSION: The introduction of DuoResp(®) Spiromax(®), which represents a potential improvement in the inhalation technique to strengthen medication adherence for the treatment of moderate to severe asthma, could represent savings for the Spanish National Health Society and five Spanish regions.