Understanding Causes of Inferior Outcomes in Adolescents and Young Adults With Cancer.

Individuals diagnosed with cancer as adolescents and young adults (AYAs; ages 15-39 years) face unique vulnerabilities. Compared with individuals diagnosed when younger (≤14 years) or older (≥40 years), AYAs have not seen the same improvement in survival. Furthermore, they sit at a complex moment of social, emotional, and cognitive development, and have a unique interface with the healthcare system. With these observations, NCI prioritized addressing the unique vulnerabilities among AYAs with cancer, and NCCN developed guidelines regarding optimal AYA cancer care. Improvements in certain locales have been seen in the wake of this focus on AYAs, suggesting that continuing to consider AYA outcomes in the context of their specific needs is critical as we strive toward additional improvements. However, it is key to consider the drivers of these outcomes to continue this trajectory. This review presents a holistic conceptual model that includes factors that influence outcomes among AYAs with cancer, including domains in these levels that influence both clinical outcomes (such as relapse and survival) and health-related quality of life (HRQoL). These include domains at the patient level, such as social constructs (race/ethnicity, socioeconomic status), behavior (adherence, risk-taking), biologic characteristics (cancer biology, host genetics), medical treatment (treatment regimen, risk-based survivorship care), and treatment-related toxicities. The model also includes domains at the system level, which include treatment location (NCI designation, facility model, AYA program presence), clinical trial enrollment, transdisciplinary communication, fertility preservation, and psychosocial support. Recognizing these multiple factors at the level of the individual and the healthcare system influence AYA outcomes (from HRQoL to survival), it is key not only to consider patient-level interventions and development of novel cancer agents but also to develop systems-level interventions that can be executed in parallel. In this way, the impact can be expanded to a vast number of AYAs.

Teletriage-How Remote Advice Provides Better Care.

There are veterinary deserts across the country where access to veterinary care is limited. Teletriage allows animal owners in these areas to get expert advice about the time frame for care through convenient, commonly used methods of communication. Teletriage also creates financial benefits for traditional veterinary clinics by increasing scheduling efficiencies. Lastly, teletriage can creates employment opportunities for veterinary nurses without the burden of relocation.

Participation in Cancer Pharmacogenomic Studies: A Study of 8456 Patients Registered to Clinical Trials in the Cancer and Leukemia Group B (Alliance).

BACKGROUND: Clinically annotated specimens from cancer clinical trial participants offer an opportunity for discovery and validation of pharmacogenomic findings. The purpose of this observational study is to better understand patient/institution factors that may contribute to participation in the pharmacogenomic component of prospective cancer clinical trials. METHODS: Patient demographic information (age, sex, self-reported race) and institutional characteristics (CALGB/CTSU site, "diversity," and accrual) were evaluated for 8456 patients enrolled in seven CALGB phase III studies with a pharmacogenomic component. All statistical tests were two-sided. RESULTS: The majority of patients (81%) consented to participate in the pharmacogenomic component. However, in a multivariable analysis, site (CALGB vs CTSU) and "institutional diversity" (percent minority cancer patients on national trials) were statistically significantly associated with participation. For both whites and nonwhites, patients from CALGB sites were more likely to participate compared with patients from CTSU sites (whites: odds ratio [OR] = 2.26, 95% confidence interval [CI] = 1.68 to 3.04, P < .001; nonwhites: OR = 1.79, 95% CI = 1.52 to 2.11, P < .001). However, as "institutional diversity" increased, the likelihood of participation in the pharmacogenomics component decreased for both white (OR = 0.94, 95% CI = 0.91 to 0.97, P < .001) and nonwhite patients (OR = 0.90, 95% CI = 0.81 to 1.00, P = .05). CONCLUSIONS: Most clinical trial cancer patients across geographical, racial, and practice settings are willing to participate in pharmacogenomic studies. However, to promote equitable benefit to the larger cancer community, optimization of both patient and institutional participation are needed. Institutional factors may be even more compelling than patient demographics. Prospective studies are needed to identify and address barriers/incentives to participation in pharmacogenomic research at the patient, clinician, and institutional levels.

Human monoclonal antibodies directed against toxins A and B prevent Clostridium difficile-induced mortality in hamsters.

Clostridium difficile is the leading cause of nosocomial antibiotic-associated diarrhea, and recent outbreaks of strains with increased virulence underscore the importance of identifying novel approaches to treat and prevent relapse of Clostridium difficile-associated diarrhea (CDAD). CDAD pathology is induced by two exotoxins, toxin A and toxin B, which have been shown to be cytotoxic and, in the case of toxin A, enterotoxic. In this report we describe fully human monoclonal antibodies (HuMAbs) that neutralize these toxins and prevent disease in hamsters. Transgenic mice carrying human immunoglobulin genes were used to isolate HuMAbs that neutralize the cytotoxic effects of either toxin A or toxin B in cell-based in vitro neutralization assays. Three anti-toxin A HuMAbs (3H2, CDA1, and 1B11) could all inhibit the enterotoxicity of toxin A in mouse intestinal loops and the in vivo toxicity in a systemic mouse model. Four anti-toxin B HuMAbs (MDX-1388, 103-174, 1G10, and 2A11) could neutralize cytotoxicity in vitro, although systemic toxicity in the mouse could not be neutralized. Anti-toxin A HuMAb CDA1 and anti-toxin B HuMAb MDX-1388 were tested in the well-established hamster model of C. difficile disease. CDA1 alone resulted in a statistically significant reduction of mortality in hamsters; however, the combination treatment offered enhanced protection. Compared to controls, combination therapy reduced mortality from 100% to 45% (P<0.0001) in the primary disease hamster model and from 78% to 32% (P<0.0001) in the less stringent relapse model.