Australians with chronic lymphocytic leukaemia continue to have high rates of second primary malignancies in the modern era.

Population-based studies have demonstrated a high risk of second cancers, especially of the skin, among patients with chronic lymphocytic leukaemia (CLL). We describe age-standardised incidence ratios (SIRs) of second primary malignancies (SPM) in Australian patients with relapsed/refractory CLL treated with at least two lines of therapy, including ibrutinib. From December 2014 to November 2017, 156 patients were identified from 13 sites enrolled in the Australasian Lymphoma and Related Diseases Registry, and 111 had follow-up data on rates of SPM. At 38.4 months from ibrutinib therapy commencement, 25% experienced any SPM. SIR for melanoma and all cancers (excluding nonmelanomatous skin cancers) were 15.8 (95% confidence interval (CI): 7.0-35.3) and 4.6 (95% CI: 3.1-6.9) respectively. These data highlight the importance of primary preventive interventions and surveillance, particularly as survival from CLL continues to improve.

The Effects of Animations and Multimedia Messages on Public Engagement in Precision Medicine: Assessment of Moderation and Mediation.

Public participation in precision medicine (PM) research is essential to achieving effective health care but has been impeded by a lack of awareness and basic knowledge. There is a critical need for educational materials that can clearly explain PM to foster involvement. This randomized controlled trial with a posttest-only control group design aims to assess the effects of educational messages delivered through animations relative to live-action videos and leaflets on intentions of involvement in PM research. Knowledge as the moderator and four mediators (engagement, vividness, trustworthiness, and cognitive value) of the intended effects were also evaluated. A total of 326 U.S. adults were sampled from Amazon Mechanical Turk. Among participants with less knowledge about PM, animations produced stronger information-seeking intentions and willingness to participate than leaflets. The effects of three message modalities were not significantly different among average and highly knowledgeable participants. Engagement and vividness mediated the effects of animations relative to two other message modalities. Trustworthiness and cognitive value mediated the effects of animations relative to live-action videos. Overall, animations can be an effective communication strategy to motivate involvement in PM but its effectiveness could decline as knowledge increases. The explanations and implications of the findings were discussed.

The role of perceived expertise and trustworthiness in research study and clinical trial recruitment: Perspectives of clinical research coordinators and African American and Black Caribbean patients.

This study investigates the role of source credibility on minority participant recruitment, particularly African American and Black Caribbean patients. A total of nine focus groups (N = 48 participants) were conducted with both patient groups and clinical research coordinators (CRCs). Using the elaboration likelihood model as a guiding framework for analysis, this study found that the credibility of research coordinators (or other professionals who recruit for research studies and clinical trials) was instrumental in shaping attitudes of prospective participants. The perspectives of patients and CRCs aligned closely, with few exceptions. For both groups, professionalism and professional displays (clothing, institutional artifacts) enhanced perceived expertise, a core component of credibility. Trustworthiness, another important component of credibility, was fostered through homophily between recruiter and patient, expressions of goodwill and assuaging anxiety about CRCs' financial motivations for recruitment. Additionally, CRCs believed that credibility was supported when CRCs could emphasize transparency and truthfulness in communication. The importance of these findings for the development of empirically-based training programs to improve communication practices in recruitment contexts is discussed.

Reducing Health Disparities Among African American and Black Caribbean Patients by Improving the Communication Practices of Clinical Research Coordinators.

This manuscript focuses on the communication factors that affect the willingness of African Americans and Black Caribbean patients to participate in clinical trials and research studies. Low rates of research participation by members of communities of color have long been linked to health disparities. While there are many factors that contribute to low rates of accrual of African American and Black patients to clinical trials, a lack of attention to communication factors that enhance or inhibit the recruitment process is central to the problem. In this study, we describe results from the analysis of six focus groups (N = 31) consisting of African American (k = 3) and Black Caribbean (k = 3) participants. Our analyses focus on verbal and nonverbal communication behaviors and how they affect participants' willingness to participate in clinical trials. Specifically, when clinical research coordinators (CRCs) had a professional appearance, made the effort to explain a study in detail, made eye contact, took the time to listen and answer questions patiently, and gave the sense that the CRC was being truthful and transparent, patients felt respected and valued. Additionally, participants emphasized the importance of the process of developing and maintaining a trusting relationship between study participants and CRCs. The results of this study will be used to develop a clinical trial communication training program designed to enhance the communication skills of clinical research coordinators who discuss research participation with African American and Caribbean Black patients.

Assessing the role of interactivity: An evaluation of information aids to support the enrollment of precision medicine research programs.

OBJECTIVE: Recruiting diverse participants for precision medicine (PM) research programs should overcome low literacy and varied expectations. Information aids (IA) can address these barriers through patient-centered education. The purpose of this study was to evaluate the effectiveness of three information aids (IA) on participating in PM. METHODS: An experiment with 290 U.S. participants recruited from Mturk was conducted to compare the effects of three IAs on the outcomes related to participation. Three conditions included an interactive IA (i.e., providing PM-related information responding to each participant's questions), a static IA (i.e., providing uniform PM-related information), and a control condition (i.e., providing non-interactive information irrelevant to PM). RESULTS: Both interactive and non-interactive IAs increased attitudes and information-seeking intentions, but not knowledge or participation intention. Perceived control and responsiveness mediated the effects of interactive IA. CONCLUSION: Both interactive and static IAs supported enrollment efforts for PM through fostering attitudes and follow-up information-seeking. Increased perceived control and responsiveness are key to the effects of interactive IA. PRACTICE IMPLICATIONS: IAs provide effective education and enrollment support for PM. Interactive IA can respond to individuals' inquiries and control the learning process.

Centre-based comparison of double versus single prevention strategy on transfusion-transmitted cytomegalovirus in at-risk haemopoietic stem cell transplant patients and a state survey on cytomegalovirus-seronegative ordering practises.

BACKGROUND: Universal leucocyte depletion reduces the risk of transfusion-transmitted cytomegalovirus; however, many clinicians still prescribe cytomegalovirus seronegative units. AIM: Our retrospective study aims to confirm the low risk of transfusion-transmitted cytomegalovirus with leucocyte depletion alone and demonstrate the ongoing variability in cytomegalovirus seronegative transfusion prescribing. METHODS: Over a 9-year period (July 2009-July 2018), occurrences of transfusion transmitted cytomegalovirus in cytomegalovirus seronegative donor/recipient haemopoietic stem cell transplant pairs were compared at one allogeneic haemopoietic stem cell transplant centre providing cytomegalovirus seronegative blood products and leucocyte depletion (double prevention) versus another providing leucocyte depletion only (single prevention). Retrospective chart audit identified patient demographics, blood product exposure and cytomegalovirus infection by polymerase chain reaction. A separate audit examined cytomegalovirus seronegative blood product ordering in a broader range of hospital types. RESULTS: We identified 122 and 66 cytomegalovirus-negative donor/recipient haemopoietic stem cell transplant pairs using double and single transfusion prevention strategy respectively. Transfusion exposure to red cells and pooled platelets was similar, although more apheresis platelets were used in the double prevention group. The cytomegalovirus infection rate was 3 (2.4%) and zero in the double and single prevention groups respectively. Cytomegalovirus seronegative unit ordering was not limited to hospitals with obstetric or neonatal populations, suggesting ongoing reliance of cytomegalovirus seronegative units outside this population. CONCLUSIONS: The analysis suggests a double prevention strategy does not provide additional protection against transfusion-transmitted cytomegalovirus. There is ongoing variability in the acceptance of leucocyte depletion alone despite the low risk of cytomegalovirus infection.

Clinical characteristics of Australian treatment-naïve patients with classical Hodgkin lymphoma from the lymphoma and related diseases registry.

Comprehensive clinical characteristics of Australian patients with classical Hodgkin Lymphoma (cHL) have not previously been systematically collected and described. We report real-world data of 498 eligible patients from the first 5 years of the Lymphoma and Related Diseases Registry (LaRDR), including baseline characteristics, histologic subtype, and treatment patterns in first-line therapy. Patient demographics and distribution of histopathological subtypes of cHL are similar to reported international cohorts. Doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) was the most common therapy for both early and advanced-stage disease, and 48% of patients with the early-stage disease received radiotherapy. Treatment patterns are consistent with international guidelines. In comorbid patients ≥60 years of age with advanced-stage disease, there is greater variation in treatment. In patients with a recorded response, the objective response rate (ORR) was 96% in early-stage disease, and 88% in advanced-stage disease. Early progression-free survival data suggest Australian patients with cHL have good outcomes, similar to other international studies.

Integration of a Nationally Recognized Tobacco Treatment Specialist Certification into Health Sciences Curricula: A short report.

Tobacco use impacts every organ in the body. Dental professionals observe the detrimental oral and systemic consequences of tobacco use. Routine dental hygiene and dental appointments are an ideal opportunity for tobacco cessation discussions. Oral health care professionals can take the lead in assisting patients with evidence-based tobacco cessation strategies. Incorporation of tobacco cessation treatment within the curriculum of dental and dental hygiene programs will promote interprofessional tobacco cessation services. The purpose of this short report is to describe the process of introducing a Tobacco Treatment Specialist (TTS) program into the curricula of four health professional programs (dentistry, dental hygiene, pharmacy, and physician assistant) within a university health sciences center. Upon graduation, all involved students may qualify for TTS credentials. This report describes the importance of the interprofessional team, particularly dentists and dental hygienists, in the implementation of the first dental school-based certified tobacco treatment training program and incorporation of tobacco treatment content into interprofessional healthcare program curricula.

Lessons learned from the "Goodie Box": A message design study developed and evaluated in community settings for cervical cancer prevention.

Despite the availability of free pap testing services, Jamaican women have low human papillomavirus (HPV) screening rates; 16% of women in the Kingston Metropolitan Area have been screened within the prior 3 years. This paper discusses the testing of theory-based messages to increase HPV screening uptake in a low-resource setting, using HPV self-test kits designed for this intervention. A total of 163 Jamaican women, aged 30-65 years, who had not had a pap test in at least 3 years, from two low socioeconomic status communities in Kingston, were enrolled and assigned to one of two versions of an HPV self-test kit, either with or without culturally targeted fear appeal messages. The uptake of screening was high across conditions; 95.6% of participants used the HPV self-test and returned their kits. However, surprising variations were observed in self-test acceptability, explained by differing attitudes toward the message conditions. Based on the results, we recommend four key components to increase HPV screening in low-resource settings: 1) focus on perceived threat in message design, 2) avoid written materials due to literacy concerns, 3) use culturally appropriate interpersonal or community-based channels, and 4) consider alternative solutions (such as a self-test) available at no or low cost to address structural barriers.

Impact of Tumour Epstein-Barr Virus Status on Clinical Outcome in Patients with Classical Hodgkin Lymphoma (cHL): A Review of the Literature and Analysis of a Clinical Trial Cohort of Children with cHL.

In this study, we have re-evaluated how EBV status influences clinical outcome. To accomplish this, we performed a literature review of all studies that have reported the effect of EBV status on patient outcome and also explored the effect of EBV positivity on outcome in a clinical trial of children with cHL from the UK. Our literature review revealed that almost all studies of older adults/elderly patients have reported an adverse effect of an EBV-positive status on outcome. In younger adults with cHL, EBV-positive status was either associated with a moderate beneficial effect or no effect, and the results in children and adolescents were conflicting. Our own analysis of a series of 166 children with cHL revealed no difference in overall survival between EBV-positive and EBV-negative groups (p = 0.942, log rank test). However, EBV-positive subjects had significantly longer event-free survival (p = 0.0026). Positive latent membrane protein 1 (LMP1) status was associated with a significantly lower risk of treatment failure in a Cox regression model (HR = 0.21, p = 0.005). In models that controlled for age, gender, and stage, EBV status had a similar effect size and statistical significance. This study highlights the age-related impact of EBV status on outcome in cHL patients and suggests different pathogenic effects of EBV at different stages of life.

NeuroSAFE PROOF: study protocol for a single-blinded, IDEAL stage 3, multi-centre, randomised controlled trial of NeuroSAFE robotic-assisted radical prostatectomy versus standard robotic-assisted radical prostatectomy in men with localized prostate cancer.

BACKGROUND: Robotic radical prostatectomy (RARP) is a first-line curative treatment option for localized prostate cancer. Postoperative erectile dysfunction and urinary incontinence are common associated adverse side effects that can negatively impact patients' quality of life. Preserving the lateral neurovascular bundles (NS) during RARP improves functional outcomes. However, selecting men for NS may be difficult when there is concern about incurring in positive surgical margin (PSM) which in turn risks adverse oncological outcomes. The NeuroSAFE technique (intra-operative frozen section examination of the neurovascular structure adjacent prostate margin) can provide real-time pathological consult to promote optimal NS whilst avoiding PSM. METHODS: NeuroSAFE PROOF is a single-blinded, multi-centre, randomised controlled trial (RCT) in which men are randomly allocated 1:1 to either NeuroSAFE RARP or standard RARP. Men electing for RARP as primary treatment, who are continent and have good baseline erectile function (EF), defined by International Index of Erectile Function (IIEF-5) score > 21, are eligible. NS in the intervention arm is guided by the NeuroSAFE technique. NS in the standard arm is based on standard of care, i.e. a pre-operative image-based planning meeting, patient-specific clinical information, and digital rectal examination. The primary outcome is assessment of EF at 12 months. The primary endpoint is the proportion of men who achieve IIEF-5 score ≥ 21. A sample size of 404 was calculated to give a power of 90% to detect a difference of 14% between groups based on a feasibility study. Oncological outcomes are continuously monitored by an independent Data Monitoring Committee. Key secondary outcomes include urinary continence at 3 months assessed by the international consultation on incontinence questionnaire, rate of biochemical recurrence, EF recovery at 24 months, and difference in quality of life. DISCUSSION: NeuroSAFE PROOF is the first RCT of intra-operative frozen section during radical prostatectomy in the world. It is properly powered to evaluate a difference in the recovery of EF for men undergoing RARP assessed by patient-reported outcome measures. It will provide evidence to guide the use of the NeuroSAFE technique around the world. TRIAL REGISTRATION: NCT03317990 (23 October 2017). Regional Ethics Committee; reference 17/LO/1978.

Evaluation of a Tobacco Treatment Training Program.

There is a need for program evaluations associated with educating healthcare professionals about the treatment of patients who use tobacco. The purpose of this study was to evaluate a Tobacco Treatment Specialist Training program with a pre-test and post-test (provided six months after the program) to determine if participants-maintained knowledge and practices to help patients with tobacco cessation in a mixed-model analysis. A pre-test survey was administered to attendees of a three-day tobacco treatment training continuing education certification program. After 6 months, the attendees were provided a post-test survey with open-ended and Likert-style questions. There were 98 participants who completed the pre-test and 16 who completed the post-test. Responses to the knowledge, confidence, and skills post-test indicated that there was significant improvement and maintenance at the six-month post-test. For example, knowledge improved from a mean of 61.1% (SD: 25.6%) to a mean of 87.9% (SD: 14.4%); medians of 66.7% and 77.7%, respectively, p < 0.001. The in-depth, intensive, three-day TTS training program had a lasting impact. Providers reported greater commitment to helping their patients quit and maintain tobacco cessation habits.

A pilot clinical study to Evaluate Liraglutide-mediated Anti-platelet activity in patients with type-2 Diabetes (ELAID study).

BACKGROUND: Liraglutide is an effective treatment for the management of type 2 diabetes mellitus (T2DM). In addition to glycemic control and potential cardioprotective effects, recent studies suggest a possible role for liraglutide in the inhibition of platelet reactivity, further attenuating atherothrombotic risk in patients with T2DM. We evaluated the in-vivo antiplatelet effect of liraglutide in T2DM patients without macrovascular disease or concurrent anti-platelet therapy. METHODS: A double-blind, placebo-controlled pilot study of 16 T2DM patients, 51-69 y/o, (mean age 60.4 y/o, 63.0% male) randomised to receive liraglutide (1.8 mg/day) or placebo (saline) for 6 months was conducted. Platelet aggregation studies at baseline and after initiation of the study intervention: days 1, 7, and 14 and months 1, 3 and 6 were performed. RESULTS: Liraglutide (n = 7) and placebo (n = 9) treated patients demonstrated normal platelet aggregation responses although transient and significant attenuation in maximum slope of platelet aggregation in response to collagen (p ≤ 0.05), arachidonic acid (p ≤ 0.05) and ADP (p ≤ 0.02) was observed in liraglutide compared to placebo treated patients in the first week. CONCLUSIONS: In this pilot study of patients with T2DM liraglutide treatment was associated with a significant, early and transient decrease in maximum slope of platelet aggregation. The clinical significance of this effect is currently unknown and may warrant further investigation. CLINICAL TRIAL REGISTRATION NUMBER: UTN 1111-1181-9567.

Tailored Messages About Research Participation: Using an Interactive Information Aid to Improve Study Recruitment.

After a diagnosis of cancer (or other serious disease), patients may be asked to consider joining a clinical trial. Because most people are unfamiliar with the scientific concepts that are necessary to the provision of meaningful informed consent, patient education is necessary. Increasing knowledge alone is not sufficient; understanding how clinical trial participation aligns with personal circumstances and knowledge is central to the decision-making process. In this study, 302 cancer patients and survivors evaluated an interactive information aid (IA) designed to inform their decision to join a research study or clinical trial by providing tailored information to patients' responses to questions pertaining to seven key barriers or facilitators of clinical trial participation. The development of the IA was done with input from the authors' Clinical Translational Science Institute; linked components of the IA were vetted by members and leaders of the institution's NCI-designated comprehensive cancer center. Results of the study indicated that the information aid was successful in significantly reducing fears and increasing knowledge, attitudes, perceived behavioral control, and behavioral intentions about research participation relative to a control condition. Thus, an interactive information aid that provides information that is responsive to patients' values, knowledge, and personal circumstances can help patients to be better prepared to consider a decision about research participation.

Community-Based Participatory Research (CBPR) to Enhance Participation of Racial/Ethnic Minorities in Clinical Trials: A 10-Year Systematic Review.

There has not been a significant improvement in the rate of clinical trial accrual in more than 20 years. Worse, the challenge of inadequate representation among racial and ethnic minorities also persists, deepening disparities in health. Community-Based Participatory Research (CBPR) is a participatory communication method that centers on effective dialogue between researchers and community stakeholders with the goal of creating an equitable partnership for health and social change. The objective of the current study was to provide an update since a systematic review in 2012, on the current status of the empirical research, with a particular focus on the elements of CBPR methods used to improve the rate of accrual of members of racial and ethnic minority communities for clinical trials. Our systematic review found a large increase in the number of CBPR related studies and studies related to racial and ethnic representation in research. More than 85% of studies employing CBPR methods saw statistically positive outcomes. Specifically, the elements of CBPR that are associated with these positive outcomes include community partner participation in (1) a study advisory committee, (2) data collection, (3) the development of interventions, and (4) participant recruitment. However, the results of our study indicate that researchers need to be more transparent about the extent of community participation as well as more thoroughly and accurately describe the nature of the partnership with members of minority communities in order to build upon the scientific literature on community-engaged methods.

Measuring the processes of interdisciplinary team collaboration: Creating valid measures using a many-facet Rasch model approach.

Introduction: The science of team science (SciTS) is an emerging research area that studies the processes and outcomes of team-based research. A well-established conceptual framework and appropriate methodology for examining the effectiveness of team science are critically important for promoting and advancing collaborative and interdisciplinary research. Although many instruments have been developed and used in the SciTS field, psychometric evidence has not been routinely assessed or reported for these scales. In addition, commonly used psychometric methods were mainly limited to internal consistency and factor analysis. To fill the gaps, this study introduces a framework based on Rasch measurement theory for creating and evaluating measures for team sciences. Methods: We illustrate the application of Rasch measurement theory through the creation of valid measures to evaluate the processes of interdisciplinary scientific teams. Data were collected from 16 interdisciplinary teams through a university-wide initiative for promoting interdisciplinary team collaboration. Psychometric evidence based on a many-facet Rasch model was obtained for assessing the quality of the measures. Results: The interdisciplinary teams differed in their clarity measures. Significant differences were also found between gender groups, racial groups, and academic ranks. We reported the reliability of measures and identified items that do not fit the model and may present potential threat to validity and fairness of SciTS measures. Conclusion: This study shows the great potential of using Rasch measurement theory for developing and evaluating SciTS measures. Applying Rasch measurement theory produces objective measures that are comparable across individuals, interdisciplinary teams, institutions, time, and various demographic groups.

Developing and evaluating a team development intervention to support interdisciplinary teams.

INTRODUCTION: Incentivizing the development of interdisciplinary scientific teams to address significant societal challenges usually takes the form of pilot funding. However, while pilot funding is likely necessary, it is not sufficient for successful collaborations. Interdisciplinary collaborations are enhanced when team members acquire competencies that support team success. METHODS: We evaluated the impact of a multifaceted team development intervention that included an eight-session workshop spanning two half-days. The workshop employed multiple methods for team development, including lectures on empirically supported best practices, skills-based modules, role plays, hands-on planning sessions, and social interaction within and across teams. We evaluated the impact of the intervention by (1) asking participants to assess each of the workshop sessions and (2) by completing a pre/postquestionnaire that included variables such as readiness to collaborate, goal clarity, process clarity, role ambiguity, and behavioral trust. RESULTS: The content of the team development intervention was very well received, particularly the workshop session focused on psychological safety. Comparison of survey scores before and after the team development intervention indicated that scores on readiness to collaborate and behavioral trust were significantly higher among participants who attended the workshop. Goal clarity, process clarity, and role ambiguity did not differ among those who attended versus those who did not. CONCLUSIONS: Multicomponent team development interventions that focus on key competencies required for interdisciplinary teams can support attitudes and cognitions that the literature on the science of team science indicate are predictive of success. We offer recommendations for the design of future interventions.

Palliative Care in Rural Aboriginal Communities: Conversations Around Experiences and Needs.

The aim of this study was to investigate the experiences and needs of Aboriginal community members with regard to rural community-based palliative care. Conversations with Aboriginal Elders were conducted. (In this Aboriginal community, Elders was not confined to older age. It referred to community leaders and includes [younger] emerging leaders.) The results were analyzed using descriptive analysis. Our study showed that there was a general lack of understanding of palliative care as distinct from curative care and limited awareness of services available. There was a strong need for clear information and on-call and practical support. Some concerns were expressed regarding limited awareness among health care providers of specific cultural needs. However, the home-based nature of palliative care was not, in itself, perceived as a barrier, provided that appropriate respect was displayed. We concluded that the current lack of understanding and awareness of services still impedes access to, and utilization of, care. More attention is needed for specific cultural needs. Adoption of a cultural humility approach for the promotion and delivery of palliative care seems to best fit the expressed needs and experiences of the participants.

Self-regressing oral CD30-positive, EBV-negative, T-cell lymphoproliferative lesions. A poorly understood process highlighted by ominous clinicopathologic features and indolent behavior.

OBJECTIVE: Intraoral, primary, CD30-positive (CD30+) T-cell lymphoproliferative disorders (TLPDs) are uncommon, and their clinicopathologic presentation and management can vary and may be challenging. Herein, we present a retrospective study of 4 examples of self-regressing primary CD30+ TLPD affecting the gingiva. STUDY DESIGN: Archived files were retrospectively reviewed for oral CD30+ TLPDs featuring (1) proper immunohistochemical documentation, (2) Epstein-Barr virus negativity, (3) adequate follow-up information corroborating regression, and (4) no history of hematopoietic malignancy or related-mucocutaneous disease. RESULTS: Three women and 1 man (age range, 55-82 years; mean, 68.3 years) presented with rapidly growing gingival ulcers. Microscopic evaluation revealed diffuse infiltration by sheets of large, atypical cells admixed with lymphocytes and eosinophils, showing angiocentric distribution, focal neurotropism, and muscle infiltration. The lesional cells consistently stained for CD3 and CD30 and were variably immunoreactive against CD2, CD4, CD5, CD7, and CD8, but were negative for ALK1 and EBV-encoded small RNA. TCR-γ gene rearrangement studies revealed a monoclonal T-cell population in 1 case. All lesions showed complete regression 2 to 8 weeks postoperatively (mean follow-up, 4.5 weeks). CONCLUSIONS: Notwithstanding their alarming clinicopathologic appearance, there are CD30+ TLPDs confined to the oral cavity that have an indolent course. However, clinical staging is essential to exclude aggressive systemic malignancy.