Feasibility of Medical Student Mentors to Improve Transition in Sickle Cell Disease.

OBJECTIVE: Advances in medical care have resulted in nearly 95% of all children with sickle cell disease (SCD) living to adulthood. There is a lack of effective transition programming, contributing to high rates of mortality and morbidity among adolescents and young adults (AYAs) during the transition from pediatric to adult healthcare. This nonrandomized study evaluated the feasibility, acceptability, and preliminary outcomes of a novel medical student mentor intervention to improve transition outcomes for AYA with SCD. METHODS: Eligible participants were ages 18-25 years, either preparing for transition or had transferred to adult care within the past year. Twenty-four AYA with SCD (Mage = 20.3, SD = 2.6) enrolled in the program and were matched with a medical student mentor. Feasibility and acceptability of the intervention was assessed through enrollment rates, reasons for refusal, retention rates, engagement with the intervention, satisfaction, and reasons for drop-out. Dependent t-tests were used to evaluate the preliminary effects of the intervention on patient transition readiness, health-related quality of life, self-efficacy, SCD knowledge, medication adherence, and health literacy. RESULTS: Participants (N = 24) demonstrated adequate retention (75.0%), adherence to the intervention (M = 5.3 of 6 sessions), and satisfaction with the intervention components. Participants demonstrated significant improvements in transition readiness (p = .001), self-efficacy (p = .002), medication adherence (p = .02), and health literacy (p = .05). CONCLUSIONS: A medical student mentor intervention to facilitate transition from pediatric to adult care for AYA with SCD is both feasible and acceptable to patients and medical students. Preliminary results suggest benefits for patients, warranting a larger efficacy study.

Risk of venous thromboembolism and endocrine therapy in older women with breast cancer in the United States.

Our aim was to evaluate the risk of venous thromboembolism (VTE) with tamoxifen and aromatase inhibitor in older women with breast cancer in the United States. The SEER-Medicare-linked database (2007--2013) was used for women of at least 65 years of age diagnosed with breast cancer in the United States. Logistic regression was used to examine unadjusted and adjusted odds ratios (OR) with 95% confidence intervals (CIs) for the risk of VTE. There were 178 059 women aged at least 65 years with breast cancer in the United States. Twenty-two thousand and forty-two (12.4%) women received tamoxifen, 64 384 (36.2%) women received aromatase inhibitors and 17 419 (9.8%) women received chemotherapy. Adjusted OR = 1.18 (95% CI 1.05--1.32) for VTE with tamoxifen for 3 years or less compared with tamoxifen use more than 3 years and OR = 1.07 (95% CI 1.05--1.16) for VTE with aromatase inhibitors 4 years or less compared with aromatase inhibitors use for more than 4 years. White women had OR = 1.19 (95% CI 1.05--1.35) and black women had OR = 1.07 (95% CI 0.76--1.51) for VTE with 3 years or less tamoxifen use compared with longer use. White women had OR = 1.09 (95% CI 1.00--1.18) and black women had OR = 1.07 (95% CI 0.86--1.34) for VTE with 4 years or less aromatase inhibitors use compared with longer use. Chemotherapy was associated with an increased risk of VTE (OR = 1.77, 95% CI 1.69--1.86). Chemotherapy combined with tamoxifen had OR = 1.64 (95% CI 1.45--1.86) and chemotherapy combined with aromatase inhibitors had OR = 1.71 95% CI 1.59-1.84). The study may help to identify a treatment profile for VTE risk that may facilitate VTE prevention.

A phase I trial of MK-2206 and hydroxychloroquine in patients with advanced solid tumors.

PURPOSE: Given the evidence that coordinate inhibition of AKT induces autophagy, we studied the combination of the AKT inhibitor, MK-2206 with hydroxychloroquine (HCQ) in patients with advanced solid tumors. METHODS: Patients were treated with weekly MK-2206 (135 mg or 200 mg) plus HCQ (200 mg, 400 mg or 600 mg BID). RESULTS: Thirty-five patients were enrolled across 5 dose levels. Two DLTs of grade 3 maculo-papular rash were observed at dose level 2 (MK-2206 200 mg weekly plus HCQ at 400 mg BID) and 1 DLT of grade 3 fatigue at dose level 2B (MK-2206 135 mg weekly plus HCQ 600 mg BID). The maximum tolerated dose (MTD) was declared as dose level 2B. The most common adverse events attributed to MK-2206 were hyperglycemia (N = 18; 51%), fatigue (N = 17; 49%), maculo-papular rash (N = 16; 46%), diarrhea (N = 12; 34%), anorexia (N = 11; 31%), and nausea (N = 11; 31%). Patients experiencing adverse events attributed to HCQ were small in number (N = 13) and primarily included fatigue (N = 5; 14%) and maculo-papular rashes (N = 3; 9%). Statistically significant effects on the pharmacokinetic properties of MK-2206 were observed in combination with HCQ. In addition, the plasma concentrations of HCQ in the combination with MK-2206 were significantly higher than the plasma levels of HCQ as monotherapy in prior studies. The best overall response of stable disease was observed in 5/34 (15%) patients. CONCLUSION: The combination of MK-2206 and hydroxychloroquine was tolerable, but with substantial number of drug-related AEs and minimal evidence of antitumor activity.

Mild factor XIII deficiency and concurrent hypofibrinogenemia: effect of pregnancy.

Factor XIII (FXIII) deficiency is a rare bleeding disorder. Patients with mild congenital FXIII deficiency tend to be asymptomatic, but may demonstrate significant bleeding symptoms with surgery, trauma, and pregnancy. Postpartum hemorrhage has been described in mild FXIII deficiency. We present a case of mild FXIII deficiency and concurrent hypofibrinogenemia manifested by recurrent postpartum hemorrhage, menorrhagia, and miscarriage. Mutational analysis identified a previously unreported heterozygous mutation of the FXIIIA subunit (p.Trp315Arg). No mutation was noted in the fibrinogen gene. FXIII levels decreased approximately 50% from nonpregnant levels to their nadir during labor, whereas fibrinogen levels rose approximately 1.5-fold from decreased nonpregnant levels to their peak at the time of labor. This case illustrates the course of mild FXIII and fibrinogen deficiencies during pregnancy, labor, and postpartum, and raises possible management options for prevention of antepartum and postpartum hemorrhage in women with these deficiencies.