IMPORTANCE Observational studies demonstrate links between patient-centered communication, quality of life (QOL), and aggressive treatments in advanced cancer, yet few randomized clinical trials (RCTs) of communication interventions have been reported. OBJECTIVE To determine whether a combined intervention involving oncologists, patients with advanced cancer, and caregivers would promote patient-centered communication, and to estimate intervention effects on shared understanding, patient-physician relationships, QOL, and aggressive treatments in the last 30 days of life. DESIGN, SETTING, AND PARTICIPANTS Cluster RCT at community- and hospital-based cancer clinics in Western New York and Northern California; 38 medical oncologists (mean age 44.6 years; 11 (29%) female) and 265 community-dwelling adult patients with advanced nonhematologic cancer participated (mean age, 64.4 years, 146 [55.0%] female, 235 [89%] white; enrolled August 2012 to June 2014; followed for 3 years); 194 patients had participating caregivers. INTERVENTIONS Oncologists received individualized communication training using standardized patient instructors while patients received question prompt lists and individualized communication coaching to identify issues to address during an upcoming oncologist visit. Both interventions focused on engaging patients in consultations, responding to emotions, informing patients about prognosis and treatment choices, and balanced framing of information. Control participants received no training. MAIN OUTCOMES AND MEASURES The prespecified primary outcome was a composite measure of patient-centered communication coded from audio recordings of the first oncologist visit following patient coaching (intervention group) or enrollment (control). Secondary outcomes included the patient-physician relationship, shared understanding of prognosis, QOL, and aggressive treatments and hospice use in the last 30 days of life. RESULTS Data from 38 oncologists (19 randomized to intervention) and 265 patients (130 intervention) were analyzed. In fully adjusted models, the intervention resulted in clinically and statistically significant improvements in the primary physician-patient communication end point (adjusted intervention effect, 0.34; 95% CI, 0.06–0.62; P = .02). Differences in secondary outcomes were not statistically significant. CONCLUSIONS AND RELEVANCE A combined intervention that included oncologist communication training and coaching for patients with advanced cancer was effective in improving patient-centered communication but did not affect secondary outcomes. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01485627

The plant viruses alfalfa mosaic virus (AMV) and brome mosaic virus (BMV) each divide their genetic information among three RNAs while tobacco mosaic virus (TMV) contains a single genomic RNA. Amino acid sequence comparisons suggest that the single proteins encoded by AMV RNA 1 and BMV RNA 1 and by AMV RNA 2 and BMV RNA 2 are related to the NH2-terminal two-thirds and the COOH-terminal one-third, respectively, of the largest protein encoded by TMV. Separating these two domains in the TMV RNA sequence is an amber termination codon, whose partial suppression allows translation of the downstream domain. Many of the residues that the TMV read-through domain and the segmented plant viruses have in common are also conserved in a read-through domain found in the nonstructural polyprotein of the animal alphaviruses Sindbis and Middelburg. We suggest that, despite substantial differences in gene organization and expression, all of these viruses use related proteins for common functions in RNA replication. Reassortment of functional modules of coding and regulatory sequence from preexisting viral or cellular sources, perhaps via RNA recombination, may be an important mechanism in RNA virus evolution.Viruses with single-stranded RNA genomes that infect higher eukaryotic hosts form a diverse group displaying wide variation in genomic organization (reviewed in ref. 1). The genome of tobacco mosaic virus (TMV), for example, is a single RNA molecule of 6.4 kilobases (kb) (ref. 2; reviewed in ref. 3). It encodes at least four proteins in three open reading frames. That nearest the 5' end contains an in-phase amber termination codon that is partly suppressed during translation in vitro or in vivo to give two products, the larger (known from its molecular weight as p183) being a readthrough extension of the smaller (p126). The template for translation of both of these proteins is the genomic RNA, the two remaining genes being expressed via subgenomic RNAs.The genomes of alfalfa mosaic virus (AMV) and brome mosaic virus (BMV), in contrast, each consist of three RNA segments, termed RNAs 1, 2, and 3 in order of decreasing size (ref. 4-8; reviewed in ref. 9). The two larger RNAs of each virus are monocistronic. The smallest is dicistronic, with the 3' proximal gene in both cases encoding the coat protein that is translated from a subgenomic mRNA. Although both viruses require all three RNAs for infection, AMV, unlike BMV, also requires either coat protein or the subgenomic mRNA for coat. Conversely, all three BMV RNAs, unlike the AMV RNAs, are aminoacylatable with tyrosine. In this respect, the BMV RNAs resemble TMV RNA (which accepts either histidine or valine according to the strain). Each virus has a different morphology, TMV being rod-shaped, AMV bacilliform, and BMV icosahedral.All three viruses are thus clearly distinguished by conventional criteria. Nevertheless, we show in this paper that the amino acid sequences of the proteins encoded by AMV RNA 1 and BMV RNA 1 are strikingly similar both to each other and to that...

Genetic recombination of DNA is one of the fundamental mechanisms underlying the evolution of DNA-based organisms and results in their diversity and adaptability. The importance of the role of recombination is far less evident for the RNA-based genomes that occur in most plant viruses and in many animal viruses. RNA recombination has been shown to promote the evolutionary variation of picornaviruses, it is involved in the creation of defective interfering (DI) RNAs of positive- and negative-strand viruses and is implicated in the synthesis of the messenger RNAs of influenza virus and coronavirus. However, RNA recombination has not been found to date in viruses that infect plants. In fact, the lack of DI RNAs and the inability to demonstrate recombination in mixedly infected plants has been regarded as evidence that plants do not support recombination of viral RNAs. Here we provide the first molecular evidence for recombination of plant viral RNA. For brome mosaic virus (BMV), a plus-stranded, tripartite-genome virus of monocots, we show that a deletion in the 3' end region of a single BMV RNA genomic component can be repaired during the development of infection by recombination with the homologous region of either of the two remaining wild-type BMV RNA components. This result clearly shows that plant viruses have available powerful recombinatory mechanisms that previously were thought to exist only in animal hosts, thus they are able to adapt and diversify in a manner comparable to animal viruses. Moreover, our observation suggests an increased versatility of viruses for use as vectors in introducing new genes into plants.

BackgroundCommunication about prognosis and treatment choices is essential for informed decision making in advanced cancer. This article describes an investigation designed to facilitate communication and decision making among oncologists, patients with advanced cancer, and their caregivers.Methods/designThe Values and Options in Cancer Care (VOICE) Study is a National Cancer Institute sponsored randomized controlled trial conducted in the Rochester/Buffalo, NY and Sacramento, CA regions. A total of 40 oncologists, approximately 400 patients with advanced cancer, and their family/friend caregivers (one per patient, when available) are expected to enroll in the study. Drawing upon ecological theory, the intervention uses a two-pronged approach: oncologists complete a multifaceted tailored educational intervention involving standardized patient instructors (SPIs), and patients and caregivers complete a coaching intervention to facilitate prioritizing and discussing questions and concerns. Follow-up data will be collected approximately quarterly for up to three years.DiscussionThe intervention is hypothesized to enhance patient-centered communication, quality of care, and patient outcomes. Analyses will examine the effects of the intervention on key elements of physician-patient-caregiver communication (primary outcomes), the physician-patient relationship, shared understanding of prognosis, patient well-being, and health service utilization (secondary outcomes).Trial registrationClinical Trials Identifier: NCT01485627

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