Publications

BACKGROUND

Adequate antiretroviral exposure is crucial to virological suppression. We assessed the relationship between atazanavir hair levels with self-reported adherence, virological outcomes, and the effect of a home-based adherence intervention in HIV-infected adolescents failing second-line antiretroviral treatment in Zimbabwe.

METHODS

HIV-infected adolescents on atazanavir/ritonavir-based second-line treatment for ≥6 months with viral load (VL) >1000 copies/mL were randomized to either standard care (control) or standard care plus modified directly administered antiretroviral therapy (intervention). Questionnaires were administered; VL and hair samples were collected at baseline and after 90 days in each group. Viral suppression was defined as <1000 copies/mL after follow-up.

RESULTS

Fifty adolescents (10-18 years) were enrolled; 23 (46%) were randomized to intervention and 27 (54%) to control. Atazanavir hair concentration <2.35 ng/mg (lower interquartile range for those with virological suppression) defined a cutoff below which most participants experienced virological failure. Male sex (P = 0.03), virological suppression at follow-up (P = 0.013), greater reduction in VL (P = 0.006), and change in average self-reported adherence over the previous month (P = 0.031) were associated with adequate (>2.35 ng/mg) hair concentrations. Participants with virological failure were more likely to have suboptimal atazanavir hair concentrations (RR = 7.2, 95% CI: 1 to 51, P = 0.049). There were no differences in atazanavir hair concentration between the arms after follow-up.

CONCLUSIONS

A threshold of atazanavir concentrations in hair (2.35 ng/mg), above which virological suppression was likely, was defined for adolescents failing second-line atazanavir/ritonavir-based ART in Zimbabwe. Male sex and better self-reported adherence were associated with adequate atazanavir hair concentrations. Antiretroviral hair concentrations may serve as a useful clinical tool among adolescents.

Cancer disparities research is motivated by persistent inequities in cancer outcomes by race, ethnicity, social status, neighborhood location, and other subpopulation characteristics. These inequities have proven to be persistent and difficult to alter. Part of the reason for the frustration with slow progress is a lack of appreciation of the long-term nature of the undertaking. It is highly likely that the disparities observed in adulthood find their origins in young adulthood, if not earlier. A long-term perspective is needed, recognizing that successes may take many years to realize. This commentary presents the experience of the Center for Health And Risk in Minority youth and young adults project, which is a comprehensive center of excellence funded by the National Institute of Minority Health and Health Disparities for addressing disparities and chronic disease prevention in minority youth and young adults. The use of logic models is advanced for this kind of research because they can provide a theory of change and illustrate the course of knowledge translation over time. Logic models for cancer disparities research can place individual project activities in a realistic context that at one time indicates what is possible and reasonable to expect during the duration of a typical research project as well as the future steps that need to be taken on the way to an expected ultimate impact on cancer inequities.

BACKGROUND

Adipose fat transfer is increasingly used for contour corrections of the tumor bed after lumpectomy and breast reconstructions after mastectomy. The lipophilic nature of the fat tissue may render adipocytes an ideal vehicle with which to deliver a high boost of an antiestrogen to the tumor bed to serve as an adjunct systemic hormonal therapy. The authors therefore tested whether adipocytes could safely be loaded with an antiestrogen and allow for release at therapeutic concentrations to treat breast cancer.

METHODS

Adipose tissue was collected from patients undergoing autologous fat grafting. The influence of adipose tissue on tumorigenesis was determined both in vitro and in vivo using breast cancer cell lines. Ex vivo, adipose tissue was assessed for its ability to depot fulvestrant and inhibit the growth of breast cancer cell lines.

RESULTS

Adipose tissue harvested from patients did not promote breast cancer cell growth in vitro or in an in vivo mouse model. Adipose tissue was successfully loaded with fulvestrant and released at levels sufficient to inhibit estrogen receptor signaling and growth of breast cancer cells.

CONCLUSIONS

This work supports the hypothesis that adipose tissue used for autologous fat grafting can serve as a novel method for local drug delivery. As this technique is used to reconstruct a variety of postsurgical defects following cancer resection, this approach for local drug delivery may be an effective alternative in therapeutic settings beyond breast cancer.

Advance care planning (ACP) is increasingly implemented in oncology and beyond, but a definition of ACP and recommendations concerning its use are lacking. We used a formal Delphi consensus process to help develop a definition of ACP and provide recommendations for its application. Of the 109 experts (82 from Europe, 16 from North America, and 11 from Australia) who rated the ACP definitions and its 41 recommendations, agreement for each definition or recommendation was between 68-100%. ACP was defined as the ability to enable individuals to define goals and preferences for future medical treatment and care, to discuss these goals and preferences with family and health-care providers, and to record and review these preferences if appropriate. Recommendations included the adaptation of ACP based on the readiness of the individual; targeting ACP content as the individual's health condition worsens; and, using trained non-physician facilitators to support the ACP process. We present a list of outcome measures to enable the pooling and comparison of results of ACP studies. We believe that our recommendations can provide guidance for clinical practice, ACP policy, and research.

Importance

Poor communication by health care professionals contributes to physical and psychological suffering in patients living with serious illness. Patients may not fully understand their illness, prognosis, and treatment options or may not receive medical care consistent with their goals. Despite considerable research exploring the role of communication in this setting, many questions remain, and a clear agenda for communication research is lacking.

Observations

Through a consensus conference and subsequent activities, we reviewed the state of the science, identified key evidence gaps in understanding the impact of communication on patient outcomes, and created an agenda for future research. We considered 7 broad topics: shared decision making, advance care planning, communication training, measuring communication, communication about prognosis, emotion and serious illness communication, and cultural issues. We identified 5 areas in which further research could substantially move the field forward and help enhance patient care: measurement and methodology, including how to determine communication quality; mechanisms of communication, such as identifying the specific clinician behaviors that patients experience as both honest and compassionate, or the role of bias in the clinical encounter; alternative approaches to advance care planning that focus on the quality of serious illness communication and not simply completion of forms; teaching and disseminating communication skills; and approaches, such as economic incentives and other clinician motivators, to change communication behavior.

Conclusions

Our findings highlight the urgent need to improve quality of communication between health care professionals and patients living with serious illness through a broad range of research that covers communication skills, tools, patient education, and models of care.

Correctional health research requires important safeguards to ensure that research participation is ethically conducted. In addition to having disproportionately low educational attainment and low literacy, incarcerated people suffer from health-related conditions that can affect cognition (e.g., traumatic brain injury, substance use disorders, mental illness). Yet modified informed consent processes that assess participants' comprehension of the risks and benefits of participation are not required by relevant federal guidelines. A push to assess comprehension of informed consent documents is particularly timely given an increase in demand for correctional health research in the context of criminal justice reform. We argue that comprehension assessments can identify persons who should be excluded from research and help those who will ultimately participate in studies better understand the risks and benefits of their participation.

CONTEXT

Standardized outcomes that define successful advance care planning (ACP) are lacking.

OBJECTIVE

The objective of this study was to create an Organizing Framework of ACP outcome constructs and rate the importance of these outcomes.

METHODS

This study convened a Delphi panel consisting of 52 multidisciplinary, international ACP experts including clinicians, researchers, and policy leaders from four countries. We conducted literature reviews and solicited attendee input from five international ACP conferences to identify initial ACP outcome constructs. In five Delphi rounds, we asked panelists to rate patient-centered outcomes on a seven-point "not-at-all" to "extremely important" scale. We calculated means and analyzed panelists' input to finalize an Organizing Framework and outcome rankings.

RESULTS

Organizing Framework outcome domains included process (e.g., attitudes), actions (e.g., discussions), quality of care (e.g., satisfaction), and health care (e.g., utilization). The top five outcomes included 1) care consistent with goals, mean 6.71 (±SD 0.04); 2) surrogate designation, 6.55 (0.45); 3) surrogate documentation, 6.50 (0.11); 4) discussions with surrogates, 6.40 (0.19); and 5) documents and recorded wishes are accessible when needed 6.27 (0.11). Advance directive documentation was ranked 10th, 6.01 (0.21). Panelists raised caution about whether "care consistent with goals" can be reliably measured.

CONCLUSION

A large, multidisciplinary Delphi panel developed an Organizing Framework and rated the importance of ACP outcome constructs. Top rated outcomes should be used to evaluate the success of ACP initiatives. More research is needed to create reliable and valid measurement tools for the highest rated outcomes, particularly "care consistent with goals."

CONTEXT

The American Medical System is programmed to a default setting of aggressive care for the terminally ill. Institutional norms of decision making have been shown to promote high-intensity care, regardless of consistency with patient preferences. There are myriad factors at a system, clinician, surrogate, and patient level that drive the culture of overly aggressive treatments in American hospitals.

OBJECTIVE

The objective of this study was to understand physician perspective of the ways systems-level factors influence patient, physician, and surrogate perceptions and consequent behavior.

METHODS

Semi-structured in-depth qualitative interviews with 42 internal medicine physicians across three American academic medical centers were conducted. This qualitative study was exploratory in nature, intended to enhance conceptual understanding of underlying phenomena that drive physician attitudes and behavior.

RESULTS

The interviews revealed many factors that contributed to overly aggressive treatments at the end of life. Systemic factors, which describe underlying cultures (including institutional, professional, or community-based cultures), typical practices of care, or systemic defaults that drive patterns of care, manifested its influence both directly and through its impact on patient, surrogate, and physician behaviors and attitudes.

CONCLUSION

Institutional cultures, social norms, and systemic defaults influence both normative beliefs regarding standards of care and treatments plans that may not benefit seriously ill patients.

SETTING

Systematic screening for active pulmonary tuberculosis (PTB) is recommended for high-risk populations, including people living with the human immunodeficiency virus (PLHIV); however, currently recommended TB screening tools are inadequate for most high-burden settings.

OBJECTIVE

To determine whether C-reactive protein (CRP) possesses the necessary test characteristics to screen individuals for active PTB.

DESIGN

We performed a systematic review and meta-analysis of studies evaluating the diagnostic accuracy of CRP (10 mg/l cut-off point) for culture-positive PTB. Pooled diagnostic accuracy estimates were generated using random-effects meta-analysis for out-patients and in-patients, and for pre-specified subgroups based on HIV status and test indication.

RESULTS

We identified nine unique studies enrolling 1793 adults from out-patient (five studies, 1121 patients) and in-patient settings (five studies, 672 patients), 72% of whom had confirmed HIV infection. Among out-patients, CRP had high sensitivity (93%, 95%CI 88-98) and moderate specificity (60%, 95%CI 40-75) for active PTB. Specificity was lowest among in-patients (21%, 95%CI 6-52) and highest among out-patients undergoing TB screening (range 58-81%). There was no difference in summary estimates by HIV status.

CONCLUSION

CRP, which is available as a simple, inexpensive and point-of-care test, can be used to screen PLHIV presenting for routine HIV/AIDS (acquired immune-deficiency syndrome) care for active TB.