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Objectives: The study aimed to estimate the burden of metastatic breast cancer (mBC) in Spain over 5 years., Methods: An incidence-based cost-of-illness model was developed in which a cohort of patients with mBC was followed from the diagnosis of metastatic disease over 5 years or death. Resource use data were collected through a physician survey conducted with 10 clinical experts in Spain. The model distinguished patients according to HER2 and hormonal receptor (HR) status, and followed the patient cohort in monthly cycles., Results: The incident cohort was estimated to be 2,923 patients with mBC, consisting of 1,575 HER2-/HR+, 520 HER2+/HR+, 324 HER2+/HR-, and 503 triple negative patients. The estimated mean survival over the 5-year time period was 2.51 years, on average, with longer survival of 3.36 years for HER2+/HR+, 2.41 years for HER2-/HR+, 2.82 years for HER2+/HR- and shortest mean survival of 1.74 years for triple negative patients. The total costs were €469,92,731 for the overall population, €190,079,787 for the HER2-/HR+, €151,045,260 for the HER2+/HR+, €80,827,171 for the HER2+/HR- and €47,540,512 for the triple negative subgroups over 5 years. Per patient total costs were €160,642 on average, €120,664 for HER2-/HR+, €290,346 for HER2+/HR+, €249,152 for HER2+/HR-and €94,572 for triple negative patients over 5 years., Conclusions: The economic burden of mBC in Spain is significant, but differs by HER2 and HR status. HER2-/HR +patients account for the highest burden due to the prevalence of this category, but HER2+/HR +patients have the highest per patient costs., Competing Interests: Competing interests: None declared., (© European Association of Hospital Pharmacists 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Two diterpenoids were prepared from hexane anti-inflammatory extracts of the Spanish herb Sideritis javalambrensis: ent-13-epi-12 alpha-acetoxymanoyl oxide (= "manoyl oxide F1") and ent-8 alpha-hydroxy-labda-13(16), 14-diene (= "labdane F2"). They were evaluated for possible anti-inflammatory actions in vitro in the concentration range 10(-7)M to 10(-4)M, and were compared with aspirin, sodium salicylate, and indomethacin. Neither compound affected superoxide generation or scavenging and they did not inhibit non-enzymatic lipid peroxidation. Neither compound affected azurophil granular enzyme secretion from activated human and rat neutrophils. The diterpenoids were not toxic to the leukocytes or to washed human erythrocytes up to 3 x 10(-5)M but at 10(-4)M some leakage of LDH or haemolysis was observed. However, both F1 and F2 inhibited prostaglandin E2 generation in cultured mouse peritoneal macrophages stimulated by zymosan, ionophore A23187, melittin, and PMA. Labdane F2 was more potent (approximate IC50 = 3 microM in zymosan-activated macrophages). We conclude that these two natural products interact with the eicosanoid system, but do not interfere with the other tested leukocyte functions or with reactive oxygen species, and are essentially non-toxic at submaximal doses. This biochemical profile distinguishes these diterpenoids from the anti-inflammatory polyphenolics such as flavonoids obtained from the genus Sideritis, and suggests that medicinal decoctions of these plants are likely to owe any anti-inflammatory activity to more than one bioactive ingredient.