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Objective The aim was to characterise the short-term (up to 12 months) direct economic burden of new cardiovascular (CV) events among adults with type 2 diabetes (T2D) in Israel. Methods In this retrospective cohort study utilising the electronic health records of the Maccabi Healthcare Services, adults aged ≥ 21 years with T2D who experienced their first CV event (2013–2016) were identified via adjudicated enrolment in a CV registry. Wilcoxon rank-sum test estimated excess healthcare resource utilisation in three periods after the CV event: immediate (1 month; for all patients), acute (3 months; for survivors of 1 month of follow-up) and short-term (12 months; for survivors of 3 months of follow-up). Direct healthcare expenditure (2018 United States dollars [USD]) was estimated from unit costs from the State of Israel Ministry of Health price list. Results In total, 5133 adults experienced a qualifying CV event, with a mean (standard deviation [SD]) age of 67.4 (11.8) years, diabetes duration of 17.7 (11.1) years and glycated haemoglobin of 7.4% (1.6%); 38.0% were female. In USD per patient, mean (SD) immediate costs were $10,741 ($11,707) compared with $2820 ($5661) at baseline (cost ratio [CR] 3.81), acute costs were $14,586 ($15,410) compared with $5202 ($8971) at baseline (CR 2.80) and short-term costs were $23,847 ($25,227) compared with $11,123 ($15,990) at baseline (CR 2.14). A sensitivity analysis of survivors only was consistent with the main analysis. Conclusions Our results indicate that CV complications of T2D place a substantial excess economic burden on Israel’s healthcare system over the short term (up to 12 months). Supplementary Information The online version contains supplementary material available at 10.1007/s41669-021-00268-5.

Objectives To evaluate excess healthcare resource utilization (HRU) and costs among patients with both type 2 diabetes (T2D) and established cardiovascular disease (CVD) relative to those with T2D only, in Israel. Methods A retrospective, observational, cohort study of adult patients with T2D from the Maccabi Healthcare Services in Israel who enrolled in a cardiovascular registry between 2013 and 2016 (pre-index date period). Patients with established CVD between 2013 and 2016 were propensity matched 1:2 to control patients without established CVD. HRU and medical costs (2018 US Dollars [USD]) were extracted for a 2-year observation period (January 1, 2017, to December 31, 2018) and analyzed using generalized linear models. Results Overall, 4,582 patients with established CVD were matched 1:2 to 9151 controls (including 13 patients matched to a single control). HRU and costs were significantly higher in patients with established CVD versus controls across a wide range of resources. In total, annual costs per patient (USD) were 10 011.8 (95% confidence interval 9,502.2; 10 548) and 7206.8 (95% confidence interval 6631.8; 7831.7) in patients with established CVD and controls, respectively. Hospitalizations, primary care visits, and medications for any condition were the main cost drivers, with greater utilization and higher costs in the established CVD group versus controls (P Conclusions In a real-world setting, HRU and costs were significantly higher in patients with T2D and established CVD compared with controls across the vast majority of resource types. These up-to-date cost estimates of CVD improve our understanding of the financial implications of established CVD beyond the direct expenses.

Stable nano-sized vesicles with a monolayer encapsulating membrane were prepared from novel bolaamphiphiles with choline ester head groups. The head groups were covalently bound to the alkyl chain of the bolaamphiphiles either via the nitrogen atom of the choline moiety, or via the choline ester's methyl group. Both types of bolaamphiphiles competed with acetylthiocholine for binding to acetylcholine esterase (AChE), yet, only the choline ester head groups bound to the alkyl chain via the nitrogen atom of the choline moiety were hydrolyzed by the enzyme. Likewise, only vesicles composed of bolaamphiphiles with head groups that were hydrolyzed by AChE released their encapsulated material upon exposure to the enzyme. Injection of carboxyfluorescein (CF)-loaded vesicles with cleavable choline ester head groups into mice resulted in the accumulation of CF in tissues that express high AChE activity, including the brain. By comparison, when vesicles with choline ester head groups that are not hydrolyzed by AChE were injected into mice, there was no accumulation of CF in tissues that highly express the enzyme. These results imply that bolaamphiphilic vesicles with surface groups that are substrates to enzymes which are highly expressed in target organs may potentially be used as a drug delivery system with controlled site-directed drug release.