Phase I and pharmacokinetic study of veliparib,a PARP inhibitor,and pegylated liposomal doxorubicin (PLD) in recurrent gynecologic cancer and triple negative breast cancer with long-term follow-up

Poly(ADP-ribosyl) polymerases (PARPs) are nuclear enzymes with roles in DNA damage recognition and repair. PARP1 inhibition enhances the effects of DNA-damaging agents like doxorubicin. We sought to determine the recommended phase two dose (RP2D) of veliparib with pegylated liposomal doxorubicin (PLD) in breast and recurrent gynecologic cancer patients. Veliparib and PLD were administered in a standard phase 1, 3 + 3 dose-escalation design starting at 50 mg veliparib BID on days 1–14 with PLD 40 mg/mg2 on day 1 of a 28-day cycle. Dose escalation proceeded in two strata: A (prior PLD exposure) and B (no prior PLD exposure). Patients underwent limited pharmacokinetic (PK) sampling; an expansion PK cohort was added. 44 patients with recurrent ovarian or triple negative breast cancer were enrolled. Median age 56 years; 23 patients BRCA mutation carriers; median prior regimens four. Patients received a median of four cycles of veliparib/PLD. Grade 3/4 toxicities were observed in 10% of patients. Antitumor activity was observed in both sporadic and BRCA-deficient cancers. Two BRCA mutation carriers had complete responses. Two BRCA patients developed oral squamous cell cancers after completing this regimen. PLD exposure was observed to be higher when veliparib doses were > 200 mg BID. The RP2D is 200 mg veliparib BID on days 1–14 with 40 mg/m2 PLD on day 1 of a 28-day cycle. Anti-tumor activity was seen in both strata. However, given development of long-term squamous cell cancers and the PK interaction observed, efforts should focus on other targeted combinations to improve efficacy.     

Ostriches and Obligations: Ethical Challenges Facing Research on Usual Care

In recent years, a robust body of scholarship has emerged that examines ethical challenges facing the learning health organization model. In “Bystander Ethics and Good Samaritanism,” James Sabin and colleagues make a valuable addition to this scholarship, identifying and exploring the important question of what researchers' obligations are to patients receiving “usual care” if “that care is seen as suboptimal.” The central issue that Sabin et al. faced was whether it would be acceptable for researchers to identify patients with untreated atrial fibrillation but then assign them to a control group that would not receive education about the importance of oral anticoagulation. The authors present this challenge as an issue of “bystander ethics.” To avoid being “bystanders” to identified instances of suboptimal care, the research team decided to instead identify a “delayed intervention” group for which they would not determine the members' anticoagulation status, thereby preventing them from knowing that specific patients met the criteria for oral anticoagulants but were not using them. This “workaround” approach strikes me as disingenuous.     

Impact of training level on postplacental levonorgestrel 52 mg intrauterine device expulsion

Objective

To determine the association between provider training level and postplacental intrauterine device (IUD) outcomes following insertion instruction by email only.

Confidentiality Discussions and Private Time With a Health-Care Provider for Youth,United States, 2016

Purpose

The objective of the study was to define factors associated with adolescent and young adult (AYA) experiences with private time and having discussed confidentiality and the impact of these experiences on improving delivery of clinical preventive services.

HPV Vaccine recommendations: does a health care provider’s gender and ethnicity matter to Unvaccinated Latina college women?

Objectives: There are disparities in the uptake of HPV vaccine among racial/ethnic minority women. The strongest predictor of HPV vaccine uptake among adult women is health care provider (HCP) recommendation; however, it is unclear how issues relating to race/ethnicity may mitigate these recommendations. Research shows that racial/ethnic and gender concordance between a patient and HCP can improve patient satisfaction, access and quality of care. If concordance contributes to improved patient-provider interactions, then it may be a factor in patient decisions regarding HPV vaccination. The objectives of this study were to (1) explore gender and ethnicity HCP preference regarding HPV vaccination among unvaccinated; and (2) understand factors associated with those preferences.

Design: Unvaccinated Latina college students (n?=?187) completed a survey that assessed HCP preferences, medical mistrust, cultural assimilation and HPV vaccine recommendation. Logistic regression models evaluated associations between above variables with HPV knowledge and preference for a female and/or Latina HCP.

Results: Most respondents had health insurance (71%), a regular HCP (64%), were US-born (67%), with foreign-born parents (74%). Thirty-four percent and 18% agreed that they would be more likely to get the HPV vaccine if the recommending HCP was female and Latino, respectively. Latina women reporting higher medical mistrust preferred a HPV vaccine recommendation from a Latino/a provider.

Conclusions: Latinas’ preferences regarding gender and ethnicity of their HCPs may affect patient-provider interactions. Increasing diversity and cultural awareness among HCPs, and providing linguistically and culturally-appropriate information may decrease patient-provider mistrust, increase uptake of the HPV vaccine, and decrease persistent cervical cancer disparities.