Clinical Features and Long-Term Outcomes of a Pan-Canadian Cohort of Adolescents and Young Adults with Myeloproliferative Neoplasms: A Canadian MPN Group Study.

Myeloproliferative neoplasms (MPNs) are a group of chronic hematologic malignancies that lead to morbidity and early mortality due to thrombotic complications and progression to acute leukemia. Clinical and mutational risk factors have been demonstrated to predict outcomes in patients with MPNs and are used commonly to guide therapeutic decisions, including allogenic stem cell transplant, in myelofibrosis. Adolescents and young adults (AYA, age ≤45 years) comprise less than 10% of all MPN patients and have unique clinical and therapeutic considerations. The prevalence and clinical impact of somatic mutations implicated in myeloid disease has not been extensively examined in this population. We conducted a retrospective review of patients evaluated at eight Canadian centers for MPN patients diagnosed at ≤45 years of age. In total, 609 patients were included in the study, with median overall survival of 36.8 years. Diagnosis of prefibrotic or overt PMF is associated with the lowest OS and highest risk of AP/BP transformation. Thrombotic complications (24%), including splanchnic circulation thrombosis (9%), were frequent in the cohort. Mutations in addition to those in JAK2/MPL/CALR are uncommon in the initial disease phase in our AYA population (12%); but our data indicate they may be predictive of transformation to post-ET/PV myelofibrosis.

Can a kiss conquer all? The predictive utility of idealized first kiss beliefs on reports of romantic love among U.S. adults.

Research indicates that idealized romantic expectations and the extent to which they are met, are important predictors of relationship outcomes (e.g., love). However, no studies have investigated the impact of idealized beliefs associated with specific behaviors (e.g., kissing) on reports of romantic love. Thus, the two studies comprising this research assessed the association between idealized beliefs related to one's first romantic kiss with their current partner, unmet first kiss expectations, and reports of romantic love. Romantic attachment was also examined as a moderator. In Study One, the First Kiss Beliefs Scale was created and the results from 208 adults revealed that increased endorsement of idealized first kiss beliefs was associated with greater romantic love (r = 0.25). Romantic attachment also moderated this relationship, such that idealized first kiss beliefs significantly predicted love for those high in attachment anxiety and low in avoidance (ß = 0.68 and ß = 0.18, respectively). In Study Two, the First Kiss Beliefs Scale was modified to assess outcomes and expectations to capture unmet expectations. The results from 234 adults indicated that idealized first kiss beliefs predicted a greater proportion of the variance in romantic love (sr2 = 0.10) than did unmet expectations (sr2 = 0.07). A three-way interaction was also detected such that, among those low in attachment anxiety, the relationship between kissing beliefs and love was positive for those high in attachment avoidance and negative for those low. These results indicate that idealized first kiss expectations with one's current romantic partner are important predictors of love (beyond whether these expectations were met), particularly for those high in attachment insecurity. Implications are discussed for practitioners and those in the primary stages of romantic relationships.

The prevalence of relevant drug-drug interactions and associated clinical outcomes in patients with cancer-associated thrombosis on concurrent anticoagulation and anticancer or supportive care therapies.

BACKGROUND: A main concern in the management of patients with cancer-associated thrombosis (CAT) is drug-drug interactions (DDIs) between anticoagulants and anticancer therapies. Their clinical implications remain unclear. METHODS: To quantify the prevalence of DDIs and risks of recurrent venous thromboembolism (VTE) and bleeding events in patients with CAT on anticoagulation, we conducted a retrospective cohort study in patients with CAT on concurrent anticoagulants and anticancer and/or supportive care therapies. All patients were followed for 6 months from CAT diagnosis or until death (whichever occurred first). The primary outcome was the percentage of patients with anticoagulant DDIs classified as risk C, D, or X in Lexicomp® at any time during the 6 months. Secondary outcomes included recurrent VTE and clinically relevant bleeding events. We calculated the 6-month cumulative incidence of outcomes with 95 % confidence interval (CI) and compared those with and without DDIs, considering death as a competing risk. RESULTS: Among 267 patients included, 111 (41.6 %) had DDIs with anticoagulants at any time during the study. Those on DOACs at any time had more DDIs compared to LMWH (50.9 % vs 19.3 %, p < 0.0001). The 6-month incidence was 8.2 % (95 % CI 5.3-11.9) for recurrent VTE and 6.7 % (95 % CI 4.2-10.2) for clinically relevant bleeding, with no significant differences between groups with or without DDIs. CONCLUSIONS: There are high incidences of DDIs in patients with CAT on anticoagulants, more with DOACs. DDIs classified as risk C, D, or X by Lexicomp® were not associated with recurrent VTE or bleeding events in our cohort.

First inter-laboratory study of a Supercritical Fluid Chromatography method for the determination of pharmaceutical impurities.

Supercritical Fluid Chromatography (SFC) has known a strong regain of interest for the last 10 years, especially in the field of pharmaceutical analysis. Besides the development and validation of the SFC method in one individual laboratory, it is also important to demonstrate its applicability and transferability to various laboratories around the world. Therefore, an inter-laboratory study was conducted and published for the first time in SFC, to assess method reproducibility, and evaluate whether this chromatographic technique could become a reference method for quality control (QC) laboratories. This study involved 19 participating laboratories from 4 continents and 9 different countries. It included 5 academic groups, 3 demonstration laboratories at analytical instrument companies, 10 pharmaceutical companies and 1 food company. In the initial analysis of the study results, consistencies within- and between-laboratories were deeply examined. In the subsequent analysis, the method reproducibility was estimated taking into account variances in replicates, between-days and between-laboratories. The results obtained were compared with the literature values for liquid chromatography (LC) in the context of impurities determination. Repeatability and reproducibility variances were found to be similar or better than those described for LC methods, and highlighted the adequacy of the SFC method for QC analyses. The results demonstrated the excellent and robust quantitative performance of SFC. Consequently, this complementary technique is recognized on equal merit to other chromatographic techniques.