Oral estradiol/micronized progesterone may be associated with lower risk of venous thromboembolism compared with conjugated equine estrogens/medroxyprogesterone acetate in real-world practice.

OBJECTIVES: The Women's Health Initiative study reported an increased risk of venous thromboembolism among menopausal women treated with conjugated equine estrogens/medroxyprogesterone acetate (CEE/MPA) versus placebo. Newer hormone therapies may have a lower venous thromboembolism risk. The study compared the risk of venous thromboembolism between women treated with the combined oral product 17ß-estradiol/micronized progesterone (E2/P4) and those treated with oral CEE/MPA regimens. STUDY DESIGN: In a retrospective longitudinal study using real-world claims data from April 2019 to June 2021, women aged 40 years or more treated with oral E2/P4 or oral CEE/MPA who did not have a venous thromboembolism diagnosis before first dispensing claim of CEE/MPA or E2/P4 identified on or after May 1st 2019 (index date) were observed for 6 months or more after the index date. Oral E2/P4 and oral CEE/MPA had been prescribed by the treating physician in real-world practice and were observed through pharmacy dispensing records. MAIN OUTCOME MEASURES: Venous thromboembolism risk was compared between women receiving oral E2/P4 versus oral CEE/MPA. RESULTS: The study included 36,061 women treated with oral E2/P4 or oral CEE/MPA. In the analyses weighted by the inverse probability of treatment for control of potential confounding factors, the incidence of venous thromboembolism was significantly lower for oral E2/P4 compared with oral CEE/MPA (37/10,000 women-years for oral E2/P4 vs 53/10,000 women-years for oral CEE/MPA; incidence rate ratio 0.70, 95 % confidence interval: 0.53-0.92). CONCLUSIONS: Real-world evidence suggests that the risk of venous thromboembolism is significantly lower among women treated with oral E2/P4 compared with oral CEE/MPA.

Five-year direct costs of acute lymphoblastic leukemia pediatric patients undergoing allogeneic stem cell transplant.

AIM: To assess the 5-year healthcare resource utilization (HRU) and direct payer costs following allogeneic hematopoietic stem cell transplants (HSCTs) in acute lymphoblastic leukemia pediatric patients using data from two large US administrative databases. PATIENTS & METHODS: Among the 209 patients with acute lymphoblastic leukemia, HRU and costs were described over the up to 5 years after the HSCT. RESULTS: HRU and costs following the HSCTs were substantial. The highest average costs and most intensive HRU were observed within the first year following the HSCTs (49 outpatient visits; 29 laboratory service visits; 68 inpatient days), with a first year cost of US$683,099 and substantial costs over the following years. CONCLUSION: HRU and direct costs associated with allogeneic HSCTs are substantial.

Treatment patterns, resource use, and economic outcomes associated with atypical antipsychotic prescriptions in children and adolescents with attention-deficit hyperactivity disorder in quebec.

OBJECTIVE: To assess treatment patterns, health care resource utilization (HRU), and costs among previously stimulant-treated children and adolescents with attention-deficit hyperactivity disorder (ADHD) receiving atypical antipsychotic (AAP) prescriptions in Quebec. METHODS: Health care claims data extracted from Quebec's provincial health plan database between March 2007 and February 2012 were analyzed. Children and adolescents (6 to 17 years) with ADHD who were taking a stimulant and either switched to, or augmented with, an AAP (with the first AAP defined as the index AAP) without a documented diagnosis for which AAPs are Health Canada-approved were included. Discontinuation, augmentation, and switching of the index AAP during the 12-month, follow-up period were estimated using Kaplan-Meier survival analysis. HRU and costs for the 6 months before (baseline period) and after initiation of the index AAP were compared. RESULTS: A total of 453 children and adolescents with ADHD, mostly male (74.6%) and aged 6 to 12 years (73.7%), met the inclusion criteria. The 12-month discontinuation, augmentation, and switching rates were 45.5%, 68.2%, and 80.7%, respectively. Patients had, on average, more all-cause prescription fills (22.2, compared with 13.3) and incurred more all-cause pharmacy ($889, compared with $710), total medical ($1096, compared with $644), and total health care ($1985, compared with $1354) costs during the 6-month study period than during the 6-month baseline period (all P < 0.05). Similarly, ADHD-related total health care costs were higher during the study period ($1269, compared with $835; P < 0.05); all-cause and ADHD-related total health care costs increased by 46.6% and 52.0%, respectively. CONCLUSION: Use of an AAP among stimulant-treated children and adolescents with ADHD in Quebec was associated with high rates of therapy changes and increased HRU and costs.

High-affinity alphavbeta3 integrin targeted optical probe as a new imaging biomarker for early atherosclerosis: initial studies in Watanabe rabbits.

PURPOSE: A newly developed synthetic alpha v beta 3 integrin targeted optical probe (ITOP) has been demonstrated to target cancer cells, in vivo. Compared to the commercially available cyclic peptide c[RGDfv], this optical probe has at least 20 times better binding affinity for the alpha v beta 3 receptor. The present in vitro study was designed to investigate the possibility of detecting early atherosclerotic plaque by using this ITOP. PROCEDURES: Experiments were performed on five Watanabe heritable hyperlipidemic rabbits and two New Zealand White rabbits for control. Our ITOP was used for detecting the presence of alpha v beta 3 receptors in vitro. RESULTS: Segments of plaque accumulation from two distinct regions of ascending and descending aortas were labeled in Watanabe rabbits. The signal was found principally in the adventitia and proximal intima of the aortic vessel, corresponding directly to the expression of integrin alpha v beta 3 as determined by antibody assay. Moreover, there was a close association between the level of labeling with the alpha v beta 3 targeted probe and the thickness of the adventitia. CONCLUSIONS: This high-affinity ITOP identifies the site and extent of alpha v beta 3 expression and correlates with adventitial thickness. Recent evidence associates alpha v beta 3 expression with the inflammatory process in early vulnerable plaque, making this compound a promising potential biomarker for early atherosclerotic disease.

Leukocyte elastase inhibition therapy in cystic fibrosis: role of glycosylation on the distribution of alpha-1-proteinase inhibitor in blood versus lung.

Cystic fibrosis patients demonstrate an increased susceptibility to bacterial lung infections. Airway infiltration by neutrophils will then lead to an increase in human leukocyte elastase (HLE) within the extracellular compartment, thereby producing deleterious effects. Here, we investigated the properties and tissue distribution of an unglycosylated, recombinant form of the HLE inhibitor alpha-1-proteinase inhibitor (alpha(1)-antitrypsin rhalpha1PI) when it is administered to the airway surface. We produced rhalpha1PI using a bacterial expression system and found the purified protein to be indistinguishable from blood-purified, glycosylated alpha1PI at inhibiting elastase in vitro. In contrast to intravenous administration, direct delivery of either alpha1PI or rhalpha1PI to the airway surface of CD-1 mice by nasal instillation produced similar highly detectable levels of protein in bronchoalveolar lavage at all time points, suggesting that glycosylation of alpha1PI does not play the same critical role in determining protein stability at the respiratory surface as it does in the vascular compartment. Interestingly, this unglycosylated rhalpha1PI was also highly protective against elastase-mediated injury 24 h after rhalpha1PI instillation and was consistently found to be significantly more protective than glycosylated blood-derived alpha1PI. Thus, these results provide evidence that aerosol delivery of rhalpha1PI could be an effective strategy for controlling HLE-dependent pathophysiology associated with cystic fibrosis lung disease.