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.
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.
Abstract
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.
Objective: Patients with sickle cell disease require lifelong comprehensive care, necessitating patient compliance with primary care appointments, specialty clinical visits, medications, ...transfusions, and regular health maintenance. As patients transition from pediatric care to adult care, they are at risk for lapses in care that can result in serious complications, making the period of transition a medically vulnerable time. The goal of this study was to use formative interviews to identify targets for a mentoring intervention to improve transition outcomes. Methods: Ten young adults preparing to transition and 10 young adults within 10 years of their transition (ages 18-30 years) completed a semistructured interview. Interviews were analyzed using template thematic analysis, with the Social-Ecological Model of Adolescent and Young Adult Readiness to Transition (SMART) framework as the a priori thematic framework. Results: Themes were consistent with the SMART framework components. Young adults identified self-advocacy, provider communication, and disease knowledge as important targets for intervention. Participants were receptive to having a medical student as a mentor and also viewed it as an opportunity to educate health professionals. Conclusions: The SMART framework and patient interviews were useful in designing a transition mentor program to meet the needs of patients with sickle cell disease. Future research will evaluate the feasibility of this program.
Implications for Impact Statement
This study describes the development of a transition mentor program for young adults with sickle cell disease informed by a formative needs assessment and the Social-Ecological Model of Adolescent and Young Adult Readiness to Transition framework. These methods are generalizable to future transition intervention development in pediatric psychology.
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