A phase II trial of nivolumab followed by ipilimumab and nivolumab in advanced non-clear-cell renal cell carcinoma.

OBJECTIVE: To evaluate the efficacy of sequential treatment with ipilimumab and nivolumab following progression on nivolumab monotherapy in individuals with advanced, non-clear-cell renal cell carcinoma (nccRCC). MATERIALS AND METHODS: UNISoN (ANZUP1602; NCT03177239) was an open-label, single-arm, phase 2 clinical trial that recruited adults with immunotherapy-naïve, advanced nccRCC. Participants received nivolumab 240 mg i.v. two-weekly for up to 12 months (Part 1), followed by sequential addition of ipilimumab 1 mg/kg three-weekly for four doses to nivolumab if disease progression occurred during treatment (Part 2). The primary endpoint was objective tumour response rate (OTRR) and secondary endpoints included duration of response (DOR), progression-free (PFS) and overall survival (OS), and toxicity (treatment-related adverse events). RESULTS: A total of 83 participants were eligible for Part 1, including people with papillary (37/83, 45%), chromophobe (15/83, 18%) and other nccRCC subtypes (31/83, 37%); 41 participants enrolled in Part 2. The median (range) follow-up was 22 (16-30) months. In Part 1, the OTRR was 16.9% (95% confidence interval [CI] 9.5-26.7), the median DOR was 20.7 months (95% CI 3.7-not reached) and the median PFS was 4.0 months (95% CI 3.6-7.4). Treatment-related adverse events were reported in 71% of participants; 19% were grade 3 or 4. For participants who enrolled in Part 2, the OTRR was 10%; the median DOR was 13.5 months (95% CI 4.8-19.7) and the median PFS 2.6 months (95% CI 2.2-3.8). Treatment-related adverse events occurred in 80% of these participants; 49% had grade 3, 4 or 5. The median OS was 24 months (95% CI 16-28) from time of enrolment in Part 1. CONCLUSIONS: Nivolumab monotherapy had a modest effect overall, with a few participants experiencing a long DOR. Sequential combination immunotherapy by addition of ipilimumab in the context of disease progression to nivolumab in nccRCC is not supported by this study, with only a minority of participants benefiting from this strategy.

Exploring the practicality and acceptability a brief exercise communication and clinician referral pathway in cancer care: a feasibility study.

BACKGROUND: The majority of cancer patients and cancer care clinicians-CCCs (e.g., oncologists) believe that exercise is an important adjunct therapy that should be embedded in standard practice. Yet, CCCs do not routinely discuss exercise with their patients, nor do they regularly refer them to exercise professionals (e.g., exercise physiologists-EPs). This study evaluated the feasibility and acceptability of an evidence-based approach to improving exercise communication between CCCs and their patients, including an exercise referral pathway. METHODS: Implementation and testing of the Exercise Communication and Referral Pathway (ECRP) occurred in Sydney, Australia. The ECRP included a brief oncology-initiated communication exchange with patients, CCC exercise referral to an EP, followed by EP-initiated telephone consultation with patients concerning tailored exercise advice. Participant perceptions concerning the feasibility and applicability of the ECPR were evaluated. Semi-structured interviews were conducted with CCCs (n = 3), cancer patients (n = 21), and an EP (n = 1). Inductive thematic analysis was undertaken. RESULTS: Analysis generated three themes: (1) Navigating the role of CCCs in the ECRP, suggesting that oncology-initiated communication is a cue to action, however there was a lack of role clarity regarding exercise referral; (2) Implementing Patient-Orientated Care within a Standardised Pathway, highlighting the need for tailored information and advice for patients that reflects individual disease, socio-cultural, and environmental factors, and; (3) Taking Steps Towards Action, revealing the need for structural (e.g., EP initiated contact with patients) and policy changes (i.e., changes to Medicare, direct oncologist referral) to engage patients and better integrate exercise as part of standard care. CONCLUSIONS: Findings provide important insights into improving oncology-patient exercise communication and developing an exercise referral pathway to increase engagement and patient reach. However, individual (e.g., experience, knowledge) and contextual factors (e.g., time, resources) need consideration when implementing an ECRP. TRIAL REGISTRATION: This trial was prospectively registered with the Australian New Zealand Clinical (#ACTRN12620000358943) on March 13, 2020.

Teacher Physical Education Practices and Student Outcomes in a Sample of Middle Schools Participating in the Presidential Youth Fitness Program.

Obesity and lack of physical activity among children and adolescents are public health problems in the United States. This Presidential Youth Fitness Program (PYFP) evaluation measured program implementation in 13 middle schools and its effect on physical education practices, student fitness knowledge, and student physical activity and fitness levels. PYFP, a free program with the potential to positively affect student health and fitness outcomes, was designed to improve fitness education practices that are easily integrated into existing physical education programs. We used a 2-group (13 PYFP and 13 comparison schools) quasi-experimental design to collect FitnessGram assessments, accelerometry data, and surveys of students, physical education teachers, and administrators. Although the program was positively associated with student cardiovascular endurance and physical activity gains during the semester, schools underused professional development courses and fitness recognition resources.

Overweight and obesity among low-income women in rural West Virginia and urban Los Angeles County.

We described the prevalence of overweight and obesity among low-income women in rural West Virginia (WV) and urban Los Angeles County (LA County). Both communities participated in the national Communities Putting Prevention to Work program during 2010-2012. In each community, we completed health assessments on adult women recruited from public-sector clinics serving low-income populations. All participants answered survey questions regarding socio-demographics and diets. In both jurisdictions, we assessed obesity using objectively measured height and weight (calculated BMI). As part of each community case study, we performed multivariable regression analyses to describe the relationships between overweight and obesity and selected covariates (e.g., dietary behaviors). Overweight and obesity were prevalent among low-income women from WV (73%, combined) and LA County (67%, combined). In both communities, race and ethnicity appeared to predict the two conditions; however, the associations were not robust. In LA County, for example, African American and Hispanic women were 1.4 times (95% CI=1.12, 1.81) more likely than white women to be overweight and obese. Collectively, these subpopulation health data served as an important guide for further planning of obesity prevention efforts in both communities. These efforts became a part of the subsequent Community Transformation Grants portfolio.

Children's understandings and motivations surrounding novelty sweets: a qualitative study.

BACKGROUND: Novelty sweets resemble or can be used as toys, are brightly coloured, with striking imagery, and sold at pocket money prices. They encourage regular consumption as packaging can be resealed, leading to prolonged exposure of these high-sugar and low pH products to the oral tissues, risk factors for dental caries and erosion, respectively. AIM: To determine how children conceptualise novelty sweets and their motivations for buying and consuming them. DESIGN: Focus groups conducted using a brief schedule of open-ended questions, supported by novelty sweets used as prompts in the latter stages. Participants were school children (aged 9-10) from purposively selected state primary schools in Cardiff, UK. RESULTS: Key findings related to the routine nature of sweet eating; familiarity with and availability of novelty sweets; parental awareness and control; lack of awareness of health consequences; and the overall appeal of novelty sweets. CONCLUSIONS: Parents reported vagueness regarding consumption habits and permissiveness about any limits they set may have diluted the concept of treats. Flexible permissiveness to sweet buying applied to sweets of all kinds. Parents' reported lack of familiarity with novelty sweets combined with their low cost, easy availability, high sugar content, and acidity give cause for concern.

Assessing moderate to vigorous physical activity in rural West Virginia elementary school physical education classes.

BACKGROUND: Physical education (PE) provides a natural opportunity for students to be physically active during the school day; however, the amount and intensity of this activity varies. The Centers for Disease Control and Prevention recommends that students engage in MVPA for at least 50% of their PE class period. The purpose of the present study was to quantify the amount of MVPA that occurs during elementary school PE. METHODS: Accelerometer data were collected from 203 students (100 2nd grade; 103 5th grade) in 10 West Virginia elementary schools. At each school, PE teachers identified three 2nd grade classes and three 5th grade classes in which to collect the physical activity data. For each selected class, the teachers identified the first 4 students on their alphabetic roll to wear the accelerometers. PE teachers recorded the date and time of the class and the gender of the students wearing the accelerometers. RESULTS: Using 5-second epochs and Puyau's cut-offs, results indicated that, on average, students engaged in MVPA for 27% of their PE class. No significant differences were observed in MVPA between 2nd and 5th grade students or between males and females. Male and female students spent equal amounts of PE class in MVPA. CONCLUSION: Findings support policy to increase the required minimum amount of MVPA during each PE class.

Systemic treatment of advanced and metastatic urothelial cancer: The landscape in Australia.

The 5-year survival rate of metastatic urothelial carcinoma (mUC) is estimated to be as low as 5%. Currently, systemic platinum-based chemotherapy followed by avelumab maintenance therapy is the only first-line treatment for mUC that has an overall survival benefit. Cisplatin-based chemotherapy (usually in combination with gemcitabine) is the preferred treatment but carboplatin is substituted where contraindications to cisplatin exist. Treatment with immune checkpoint inhibitors, antibody-drug conjugates, and kinase inhibitors has not yet demonstrated superiority to chemotherapy as first-line therapy and remains investigational in this setting. A recent media release indicates that chemotherapy plus nivolumab gives an OS advantage as first-line treatment but results of this study have not yet been made public. Pembrolizumab remains an option in those having primary progression on first-line chemotherapy or within 12 months of neoadjuvant chemotherapy. The antibody-drug conjugate, enfortumab vedotin has TGA approval for patients whose cancer has progressed following chemotherapy and immunotherapy and has just received a positive Pharmaceutical Benefits Scheme recommendation. The use of molecular screens for somatic genetic mutations, gene amplifications, and protein expression is expanding as drugs that target such abnormalities show promise. However, despite these advances, a substantial proportion of patients with mUC have significant barriers to receiving any treatment, including advancing age, frailty, and comorbidities, and less toxic, effective therapies are needed.

Exploring the relationship between parental concern and the management of childhood obesity.

Parental concern about child weight has been identified as a factor in parental monitoring and regulation of child diet. However, little is known about factors that influence parental concern or about how concern may influence parent management of child physical activity. The objectives of the current study were to identify the factors associated with parental concern about child weight and determine if parental concern is associated with specific actions to improve diet and increase physical activity. A stratified random sample of 1,500 parents of children in kindergarten, 2nd, 4th, 5th, 7th, and 9th grade were interviewed. Interviews addressed: (a) child and parent physical activity, (b) child and family nutrition, (c) child and parent BMI weight category, (d) interactions with health care providers, (e) parent obesity knowledge, (f) school assessment of BMI, and (g) parent perception of and concern about child weight. Child gender, weight status, and parent perception of child weight were significant predictors of parental concern. Parents were significantly more likely to report concern if their child was female, they believed their child to be overweight/obese, or their child was overweight/obese as indicated by BMI percentile. Concerned parents were significantly more likely to limit child screen time, take steps to improve child diet, and increase child physical activity than were parents who reported no concern. Treatment and prevention efforts should emphasize parental concern and awareness about child weight by providing accurate feedback on child weight status and education regarding the health risks associated with childhood overweight and obesity. Schools can play an important role in this process through the incorporation of BMI screenings.

Identifying the people and factors that influence children's intentions to make lifestyle changes.

Childhood obesity and health behavior programs are increasingly a focus within literature and individual provider practices. This study was designed to inform "best practices" for establishing effective programs in the medical setting by identifying persons and factors that influence children's willingness to be active, eat healthy, and lose weight when medically appropriate. A total of 342 child and parent dyads living in a rural setting participated in this study. Child and parent report of theory of planned behavior constructs and child intentions to lose weight, eat healthier, and increase own exercise was established as the study outcomes. Parent and child perceptions and child characteristics (e.g., weight status) were associated with children's intentions to lose weight and obtain more exercise whereas only child perceptions were associated with children's intentions to eat healthier. Incorporating children as young as 10 years of age in conversations and planning for diet and physical activity lifestyle changes is essential for the success of the treatment option.

Development of Condom-Use Self-Efficacy over 36 months among Early Adolescents: A Mediation Analysis.

This research evaluates condom-use self-efficacy and its increase throughout adolescence. Documentation of the development of condom-use self-efficacy would be important for prevention efforts given the influence of self-efficacy on actual condom-usage. This study assesses a hypothesized mediation mechanism of the development of self-efficacy using a mediation analysis approach. The participants, 497 grade-6 Bahamian students, were randomly assigned to the control condition in a 3-year longitudinal HIV prevention program trial. Condom-use self-efficacy consistently increased and condom-use self-efficacy assessed at earlier periods was positively associated with its values at subsequent periods. Additionally, self-efficacy assessed between two time points one year apart or longer (e.g., 6 months between baseline and 12 months) significantly mediated the impact of its levels at the previous assessment on the level at the subsequent assessment. To sustain program effect, HIV prevention programs should strive to enhance self-efficacy and provide reinforcing "boosters" no later than 12 months post-intervention.

Angiogenesis Inhibitors and Immunomodulation in Renal Cell Cancers: The Past, Present, and Future.

Angiogenesis inhibitors have been adopted into the standard armamentarium of therapies for advanced-stage renal cell carcinomas (RCC), but more recently, combination regimens with immune checkpoint inhibitors have demonstrated better outcomes. Despite this, the majority of affected patients still eventually experience progressive disease due to therapeutic resistance mechanisms, and there remains a need to develop novel therapeutic strategies. This article will review the synergistic mechanisms behind angiogenesis and immunomodulation in the tumor microenvironment and discuss the pre-clinical and clinical evidence for both clear-cell and non-clear-cell RCC, exploring opportunities for future growth in this exciting area of drug development.

Cancer survivors' exercise beliefs, knowledge, and behaviors: An Australian National Survey.

AIMS: This study aimed to (1) explore the perceptions of people living with cancer about exercise in general and exercise as an adjunct form of cancer care, (2) explore their perceptions regarding exercise counselling needs and preferences, and (3) investigate how these perceptions of exercise as an adjunct form of cancer care shape survivors exercise levels postcancer diagnosis. METHODS: A cross-sectional design and online survey were used to recruit cancer survivors via cancer-related networks throughout Australia. Two factor analyses were conducted to examine the structure and reduce the number of variables pertaining to exercise during and after the cancer treatment. Extracted components were used in one-way analysis of variance to compare differences in physical activity levels postcancer diagnosis. RESULTS: Participants (N = 288) had very positive perceptions of exercise, yet only 50% of participants would prefer to receive exercise counselling. Those who were more active postcancer diagnosis had higher exercise beliefs than those who were similarly active (p = 0.04, r = 0.27) and less active (p = 0.03, r = 0.24) postdiagnosis. Those who were less active also had lower exercise knowledge than those who were similarly active (p = 0.01, r = 0.31) and more active (p = 0.03, r = 0.26). Safety beliefs did not significantly differ between cancer survivors' activity levels (p = 0.16) CONCLUSION: This survey highlights the potential benefits of a concentrated effort in connecting survivors to relevant services and resources, and utilizing cancer clinicians to communicate with survivors about the role of exercise in cancer care.

Bridging the gap between attitudes and action: A qualitative exploration of clinician and exercise professional's perceptions to increase opportunities for exercise counselling and referral in cancer care.

OBJECTIVE: This study aimed to 1) understand factors impacting the implementation of exercise communication and referral, and 2) explore integrated clinical approaches to exercise communication and referral in cancer care. METHODS: Seven focus groups (N = 53) were conducted with clinicians and exercise professionals throughout Sydney, Australia. A sub-sample of participants (n = 9) attended a half-day workshop to identifying best practice approaches for moving forward. Data were analysed using thematic content analysis. RESULTS: Two themes emerged: 1) Factors impacting the knowledge-to-action gap, inclusive of limited exercise specific knowledge and training opportunities, funding structure, and current referral process, and 2) Recommendations for a consistent and efficient way forward, detailing the need for oncologist-initiated communication, distribution of cancer-exercise resources, and access to exercise professionals with cancer expertise. CONCLUSIONS: This study identified factors (e.g., cancer-exercise specific training, integration of exercise physiologists) influencing exercise counselling and referral. A potential implementation-referral approach accounting for these factors and how to incorporate exercise into a standard model of cancer care, is described. Future testing is required to determine feasibility and practicality of these approaches. PRACTICAL IMPLICATIONS: A pragmatic model is provided to guide implementation-referral, inclusive of oncologist-initiated communication exchange, relevant resources, and access to exercise professionals with cancer expertise.

Immune checkpoint inhibitor-induced myocarditis, myositis, myasthenia gravis and transaminitis: a case series and review.

Immune checkpoint inhibitors have been incorporated into the treatment of various malignancies. An increasing body of literature is reporting rare but potentially fatal adverse events associated with these agents. In this case series, the authors report the clinical features and outcomes of seven patients who received immune checkpoint inhibitors for different solid organ malignancies and developed a tetrad of immune-related myocarditis, myositis, myasthenia gravis and transaminitis. Herein the authors review the literature and describe the current diagnostic and management approach for this overlapping syndrome. The authors' series highlights the importance of a high index of clinical suspicion, prompt comprehensive investigations, early multidisciplinary team involvement and initiation of immunosuppressive therapy when immune-related adverse events are suspected.

Cancer immunotherapy is used in the treatment of different cancer types. Immunotherapy activates the immune system to detect and attack cancer cells, but side effects may arise from the immune system inadvertently attacking normal tissues and organs. The increased use of immunotherapy has led to an increase in the reporting of rare but potentially life-threatening treatment-related side effects. In this case series, the authors report the clinical features and outcomes of seven patients who developed inflammation of the heart, muscles, nerve and muscle junctions and liver following treatment with immunotherapy. The authors review the scientific literature and discuss the current understanding of and management approach to this rare syndrome. The authors' report highlights the importance of a high degree of clinical suspicion, prompt comprehensive testing to confirm diagnosis, early involvement of experts from different specialties and early initiation of treatment in the management of this unique syndrome.

Developing culturally tailored health belief-based intervention materials to improve child and parent participation in a cardiovascular screening program.

The Coronary Artery Risk Detection in Appalachian Communities Project was developed to reduce children's future cardiovascular risk by implementing a school-based screening program statewide. Despite the elimination of environmental barriers related to screening cost and accessibility, only half of eligible children participate in the program each year. The authors used the theory of planned behavior to identify health beliefs associated with screening participation. This article describes the process used to identify community health beliefs and the development of theoretically based materials to increase participation. Focus groups and individual interviews were conducted to identify core health beliefs held by parents, community leaders, and children (Phase I). Data obtained were used to expand and revise a Health Beliefs Questionnaire, which was distributed to larger samples (Phase II). This information was used to design recruitment materials that emphasized the benefits of screening while directly addressing potential belief-based barriers to screening participation (Phase III).

Modeling early sexual initiation among young adolescents using quantum and continuous behavior change methods: implications for HIV prevention.

Behavioral research and prevention intervention science efforts have largely been based on hypotheses of linear or rational behavior change. Additional advances in the field may result from the integration of quantum behavior change and catastrophe models. Longitudinal data from a randomized trial for 1241 pre-adolescents 9-12 years old who self-described as virgin were analyzed. Data for 469 virgins in the control group were included for linear and cusp catastrophe models to describe sexual initiation; data for the rest in the intervention group were added for program effect assessment. Self-reported likelihood to have sex was positively associated with actual initiation of sex (OR = 1.72, 95% CI: 1.43-2.06, R² = 0.13). Receipt of a behavioral prevention intervention based on a cognitive model prevented 15.6% (33.0% vs. 48.6%, OR = 0.52, 95% CI: 0.24-1.11) of the participants from initiating sex among only those who reported 'very likely to have sex.' The beta coefficients for the cubic term of the usp assessing three bifurcating variables (planning to have sex, intrinsic rewards from sex and self-efficacy for abstinence) were 0.0726, 0.1116 and 0.1069 respectively; R² varied from 0.49 to 0.54 (p < 0.001 for all). Although an intervention based on a model of continuous behavior change did produce a modest impact on sexual initiation, quantum change has contributed more than continuous change in describing sexual initiation among young adolescents, suggesting the need for quantum change and chaotic models to advance behavioral prevention of HIV/AIDS.

Treatment selection for first-line metastatic renal cell carcinoma in Australia: Impact of new therapy options.

Vascular endothelial growth factor receptor tyrosine kinase inhibitors have provided an effective standard of care for the treatment of metastatic clear cell renal cell carcinoma (mRCC). Survival is prolonged with emergence of modern immuno-oncology combination regimens. Prognostic risk assessment is essential for choosing between these therapies to determine the most appropriate first line treatment option, with selection based on International Metastatic RCC Database Consortium Risk Category. We review the current subsidized first line treatments for mRCC in Australia and consider the evidence for treatment selection and sequencing.

Childhood Obesity Declines Project: Highlights of Community Strategies and Policies.

BACKGROUND: The social ecological model (SEM) is a framework for understanding the interactive effects of personal and environmental factors that determine behavior. The SEM has been used to examine childhood obesity interventions and identify factors at each level that impact behaviors. However, little is known about how those factors interact both within and across levels of the SEM. METHODS: The Childhood Obesity Declines (COBD) project was exploratory, attempting to capture retrospectively policies and programs that occurred in four communities that reported small declines in childhood obesity. It also examined contextual factors that may have influenced initiatives, programs, or policies. Data collection included policy and program assessments, key informant interviews, and document reviews. These data were aggregated by the COBD project team to form a site report for each community (available at www.nccor.org/projects/obesity-declines ). These reports were used to develop site summaries that illustrate how policies, programs, and activities worked to address childhood obesity in each study site. RESULTS/CONCLUSIONS: Site summaries for Anchorage, AK; Granville County, NC; Philadelphia, PA; and New York City, NY, describe those policies and programs implemented across the levels of the SEM to address childhood obesity and examine interactions both across and within levels of the model to better understand what factors appear important for implementation success.

Childhood Obesity Declines Project: A Different Methodology.

BACKGROUND: The evidence for and our understanding of community-level strategies such as policies, system, and environmental changes that support healthy eating and active living is growing. However, researchers and evaluation scientists alike are still not confident in what to recommend for preventing or sustaining declines in the prevalence of obesity. METHODS: The Systematic Screening and Assessment (SSA) methodology was adapted as a retrospective process to confirm obesity declines and to better understand what and how policies and programs or interventions may contribute as drivers. The Childhood Obesity Declines (COBD) project's adaptation of the SSA methodology consisted of the following components: (1) establishing and convening an external expert advisory panel; (2) identification and selection of sites reporting obesity declines; (3) confirmation and review of what strategies occurred and contextual factors were present during the period of the obesity decline; and (4) reporting the findings to sites and the field. RESULTS/DISCUSSION: The primary result of the COBD project is an in-depth examination of the question, "What happened and how did it happen in communities where the prevalence of obesity declined?" The primary aim of this article is to describe the project's methodology and present its limitations and strengths. CONCLUSIONS: Exploration of the natural experiments such that occurred in Anchorage, Granville County, New York City, and Philadelphia is the beginning of our understanding of the drivers and contextual factors that may affect childhood obesity. This retrospective examination allows us to: (1) describe targeted interventions; (2) examine the timeline and summarize intervention implementation; (3) document national, state, local, and institutional policies; and (4) examine the influence of the reach and potential multisector layering of interventions.

Childhood Obesity Declines Project: An Exploratory Study of Strategies Identified in Communities Reporting Declines.

BACKGROUND: Although childhood obesity rates have been high in the last few decades, recent national reports indicate a stabilization of rates among some subpopulations of children. This study examines the implementation of initiatives, policies, and programs (referred to as strategies) in four communities that experienced declines in childhood obesity between 2003 and 2012. METHODS AND RESULTS: The Childhood Obesity Decline project verified obesity declines and identified strategies that may have influenced and supported the decline in obesity. The project used an adaptation of the Systematic Screening and Assessment method to identify key informants in each site. Four settings were highlighted related to childhood: (1) communities, (2) schools, (3) early care and education, and (4) healthcare. The findings indicate that programs and policies were implemented across local settings (primarily in schools and early childhood settings) and at the state level, during a timeframe of supportive federal policies and initiatives. CONCLUSIONS: Multilevel approaches were aimed to improve the nutrition and physical activity environments where children spend most of their time. We hypothesized that other, more distal strategies amplified and reinforced the impact of the efforts that more directly targeted children. The simultaneous public health messaging and multilayered initiatives, supported by cross-sector partnerships and active, high-level champions, were identified as likely important contributors to success in attaining declines in rates of childhood obesity.