The Avatar Acceptability Study: Survivor, Parent and Community Willingness to Use Patient-Derived Xenografts to Personalize Cancer Care.

BACKGROUND: Using patient-derived xenografts (PDXs) to assess chemosensitivity to anti-cancer agents in real-time may improve cancer care by enabling individualized clinical decision-making. However, it is unknown whether this new approach will be met with acceptance by patients, family and community. METHODS: We used a cross-sectional structured survey to investigate PDX acceptability with 1550 individuals across Australia and New Zealand (648 survivors of adult and childhood cancer, versus 650 community comparisons; and 48 parents of childhood cancer survivors versus 204 community parents). We identified factors influencing willingness-to-use PDXs, willingness-to-pay, maximum acceptable wait-time, and maximum acceptable number of mice used per patient. FINDINGS: PDXs were highly acceptable: >80% of those affected by cancer felt the potential advantages of PDXs outweighed the disadvantages (community participants: 68%). Survivors' and survivors' parents' most highly endorsed advantage was 'increased chance of survival'. 'Harm to animals' was the least endorsed disadvantage for all groups. Cancer survivors were more willing to use PDXs than community comparisons [p < ·001]. Survivors and survivors' parents were willing to pay more [p < ·001; p = ∙004 respectively], wait longer for results [p = ·03; p = ∙01], and use more mice [p = ·01; p < ∙001] than community comparisons. Male survivors found PDXs more acceptable [p = ·01] and were willing to pay more [p < ·001] than female survivors. Survivors with higher incomes found PDXs more acceptable [p = ·002] and were willing to pay more [p < ·001] than survivors with lower incomes. Mothers found PDXs more acceptable [p = ·04] but were less willing to wait [p = ·02] than fathers. INTERPRETATION: We found significant attitudinal support for PDX-guided cancer care. Willingness-to-pay and maximum acceptable number of mice align well with likely future usage. Maximum acceptable wait-times were lower than is currently achievable, highlighting an important area for future patient education until technology has caught up.

Parents' attitudes toward genetic testing of children for health conditions: A systematic review.

This review assessed parents' attitudes toward childhood genetic testing for health conditions, with a focus on perceived advantages and disadvantages. We also evaluated the factors that influence parents' attitudes toward childhood genetic testing. We searched Medline, Medline In-Process, EMBASE, PsycINFO, Social Work Abstracts and CINAHL. We screened 945 abstracts and identified 21 studies representing the views of 3934 parents. Parents reported largely positive attitudes toward childhood genetic testing across different genetic tests with varying medical utility. Parents perceived a range of advantages and disadvantages of childhood genetic testing. Childhood genetic testing was viewed by most as beneficial. Parents' education level, genetic status, sex and sociodemographic status were associated with reported attitudes. This yielded some conflicting findings, indicating the need for further research. Genetic counseling remains essential to support this population in making well-informed decisions. Targeted interventions tailored to specific families with different sociodemographic characteristics may be useful. Further research on the long-term impact of childhood genetic testing on families is warranted.

Latent Inhibition Reduces Nocebo Nausea, Even Without Deception.

BACKGROUND: Nocebo nausea is a debilitating and prevalent side effect that can develop after conditioning occurs between cues present in the treatment context and the experience of nausea. Interventions that retard conditioning may therefore be able to reduce nocebo nausea. PURPOSE: To test whether 'latent inhibition', where pre-exposing cues in the absence of an outcome retards subsequent learning about those cues, could reduce nocebo nausea in healthy adults. METHODS: We examined this possibility using a Galvanic Vestibular Stimulation (GVS) model of nausea in healthy participants, with pre-exposure to the treatment cues achieved using a placebo version of GVS. RESULTS: In Experiment 1 we found clear evidence of conditioned nocebo nausea that was eradicated by latent inhibition following pre-exposure to placebo stimulation. Experiment 2 tested whether deception, which may be unethical in clinical settings, was necessary to produce latent inhibition by including an open pre-exposure group informed they were pre-exposed to placebo stimulation. Experiment 2 replicated the latent inhibition effect on nocebo nausea following deceptive pre-exposure from Experiment 1 and found that open pre-exposure was just as effective for reducing nocebo nausea. In both experiments, there was an interesting discrepancy found in expectancy ratings whereby expectations appeared to drive the development of conditioned nocebo nausea, but were not responsible for its suppression through latent inhibition. CONCLUSIONS: These findings have significant clinical implications. Applying open pre-exposure in clinical settings may effectively and ethically reduce the development of nocebo effects for nausea and other conditions via latent inhibition.

When knowledge of a heritable gene mutation comes out of the blue: treatment-focused genetic testing in women newly diagnosed with breast cancer.

Selection of women for treatment-focused genetic testing (TFGT) following a new diagnosis of breast cancer is changing. Increasingly a patient's age and tumour characteristics rather than only their family history are driving access to TFGT, but little is known about the impact of receiving carrier-positive results in individuals with no family history of cancer. This study assesses the role of knowledge of a family history of cancer on psychosocial adjustment to TFGT in both women with and without mutation carrier-positive results. In-depth semistructured interviews were conducted with 20 women who had undergone TFGT, and who had been purposively sampled to represent women both family history and carrier status, and subjected to a rigorous qualitative analysis. It was found that mutation carriers without a family history reported difficulties in making surgical decisions quickly, while in carriers with a family history, a decision regarding surgery, electing for bilateral mastectomy (BM), had often already been made before receipt of their result. Long-term adjustment to a mutation-positive result was hindered by a sense of isolation not only by those without a family history but also those with a family history who lacked an affected relative with whom they could identify. Women with a family history who had no mutation identified and who had not elected BM reported a lack of closure following TFGT. These findings indicate support deficits hindering adjustment to positive TFGT results for women with and without a family history, particularly in regard to immediate decision-making about risk-reducing surgery.

Galvanic Vestibular Stimulation: a new model of placebo-induced nausea.

OBJECTIVE: Traditional rotation-based models of placebo nausea are limited because they do not have vehicle settings and are tied to their context. The present study introduces a new model for examining placebo-induced nausea in the laboratory that overcomes these limitations, namely, Galvanic Vestibular Stimulation (GVS). GVS stimulates the vestibular system to cause nausea through sensory mismatch with visual cues and importantly has a non-nauseating placebo setting. Using this, we tested whether conditioning could elicit placebo nausea when participants were later exposed to placebo stimulation as well as whether this placebo nausea was generalised across contexts--something that is extremely difficult to test with rotation-based models of placebo nausea. METHODS: Thirty healthy undergraduate students were randomised to receive either placebo GVS (controls) or active GVS during training (Context-Consistent and Context-Change). On test, all groups received placebo GVS. The controls and Context-Consistent groups were tested in the same context as training, whereas the Context-Change group was tested in a new context. RESULTS: Participants conditioned with nausea during training had significantly higher nausea symptom ratings after placebo stimulation on test than those given no conditioning. This placebo-induced nausea also generalised to a novel test context with no differences observed between the Context-Change and Context-Consistent groups. CONCLUSION: GVS provides a new model of placebo-induced nausea that overcomes limitations to traditional rotation-based paradigms. Future studies should use this device to explore the effect of instructions and conditioning on the development of placebo nausea and to assess the efficacy of conditioning-based interventions for clinical use.