Developmentally appropriate care for adolescents and young adults with cancer: how well is Australia doing?

PURPOSE: Developmentally appropriate care underpins quality cancer treatment. This study aimed to describe how well Australian cancer services deliver patient-focussed, developmentally appropriate care to adolescents and young adults (AYAs) with cancer. METHODS: In a national, cross sectional study, 196 AYAs with cancer aged between 15 and 25 years at diagnosis reported their general experiences of the cancer care team (Cancer Needs Questionnaire), access to age-appropriate treatment environments (Cancer Needs Questionnaire) and frequency of psychosocial assessment (Adolescent Friendly Hospital Survey). RESULTS: Very positive responses were reported around engagement and communication with staff who were reported as approachable, friendly and trustworthy; 11 of the 14 items were positively rated by over 90% of respondents. In contrast, over 70% of AYAs expressed unmet need around their physical and social environments, whether in relation to the opportunity to be nursed in wards designed for AYAs, spend time with other young people with cancer, or talk to young people their own age; less than a third reported their needs had been met on the majority of these items. The frequency that specific psychosocial assessment domains were discussed was highly variable; responses suggested that AYAs were less commonly questioned about overtly sensitive topics. AYAs who experienced private consultations with health care providers (41%) were significantly more likely to experience thorough psychosocial assessment. CONCLUSION: Australian cancer services are generally communicating well with AYAs. There is room for improvement around more developmentally specific aspects of healthcare quality, such as psychosocial assessment, and around treatment environments that promote greater social interaction between AYAs.

Gender differences in doxorubicin pharmacology for subjects with chemosensitive cancers of young adulthood.

PURPOSE: For many cancers, adolescents and young adults (AYA) have worse outcomes than for children and adults. Many factors may contribute to the AYA survival gap, including differences in biology, therapeutic intent, and adherence to therapy. It has been observed that male AYAs have poorer outcomes than females. The purpose of this work was to test the proposition that gender-related pharmacologic factors may account for a component of the AYA survival gap. PATIENTS AND METHODS: A prospective, multi-institutional pharmacologic study of 79 patients in total with chemosensitive cancers (Ewing sarcoma, osteosarcoma and Hodgkin lymphoma) was conducted, with conventional doxorubicin treatment. Pharmacokinetic data of 13 children, 40 AYAs and 13 adults were valid for analysis. Population pharmacokinetics models were developed for doxorubicin and its metabolite doxorubicinol based on the data created in this study. Consequently, model-based analysis was conducted to investigate the relevant topics. RESULTS: The clearance of doxorubicinol (normalized to body surface area), the main active metabolite of doxorubicin, appears faster in male AYAs than female (p = 0.04, 95% CI 0.1-3.9 L/h). The exposure of doxorubicinol (normalized to dose) is lower in male AYA than female (p = 0.03, 95% CI - 0.005 to - 0.0002 h/L). These might be correlated to the observed difference on nadir neutrophil count between male AYA and female (p = 0.027, 95% CI 0.09-1.4). CONCLUSION: Gender-related differences in doxorubicin pharmacology may account for worse outcomes for male AYAs with chemosensitive cancers compared to females. These findings may reduce the AYA survival gap compared to other age groups.

Clinical management of Australian adolescents and young adults with acute lymphoblastic and myeloid leukemias: A national population-based study.

BACKGROUND: While several studies have examined the treatment of adolescents and young adults (AYAs) with acute lymphoblastic leukemia (ALL), studies of acute myeloid leukemia (AML) are rare. Using national data for Australia, we describe (i) the number and type of treatment centers caring for AYAs, (ii) induction/first-line treatments, and (iii) survival outcomes. PROCEDURE: National population-based study assessing treatment of 15- to 24-year-olds diagnosed with ALL or AML between 2007 and 2012. Treatment details were abstracted from hospital medical records. Treatment centers were classified as pediatric or adult (adult AYA-focused or other adult; and by AYA volume [high/low]). Cox proportional hazard regression analyses examined associations between treatment and overall, event-free, and relapse-free survival outcomes. RESULTS: Forty-seven hospitals delivered induction therapy to 351 patients (181 ALL and 170 AML), with 74 (21%) treated at pediatric centers; 70% of hospitals treated less than two AYA leukemia patients per year. Regardless of treatment center, 82% of ALL patients were on pediatric protocols. For AML, pediatric protocols were not used in adult centers, with adult centers using a non-COG 7+3-type induction protocol (51%, where COG is Cooperative Oncology Group) or an ICE-type protocol (39%, where ICE is idarubicin, cytarabine, etoposide). Exploratory analyses suggested that for both ALL and AML, AYAs selected for adult protocols have worse overall, event-free, and relapse-free survival outcomes. CONCLUSIONS: Pediatric protocols were commonly used for ALL patients regardless of where they are treated, indicating rapid assimilation of recent evidence by Australian hematologists. For AML, pediatric protocols were only used at pediatric centers. Further investigation is warranted to determine the optimal treatment approach for AYA AML patients.

Factors influencing the documentation of fertility-related discussions for adolescents and young adults with cancer.

PURPOSE: A cancer diagnosis and treatment may have significant implications for a young patient's future fertility. Documentation of fertility-related discussions and actions is crucial to providing the best follow-up care, which may occur for many years post-treatment. This study examined the rate of medical record documentation of fertility-related discussions and fertility preservation (FP) procedures for adolescents and young adults (AYAs) with cancer in Australia. METHODS: A retrospective review of medical records for 941 patients in all six Australian states. Patients were identified through population-based cancer registries (four states) and hospital admission lists (two states). Trained data collectors extracted information from medical records using a comprehensive data collection survey. Records were reviewed for AYA patients (aged 15-24 years at diagnosis), diagnosed with acute myeloid leukaemia, acute lymphoblastic leukaemia, central nervous system (CNS) tumours, soft tissue sarcomas (STS), primary bone cancer or Ewing's family tumours between 2007 and 2012. RESULTS: 47.2% of patients had a documented fertility discussion and 35.9% had a documented FP procedure. Fertility-related documentation was less likely for female patients, those with a CNS or STS diagnosis and those receiving high-risk treatments. In multivariable models, adult hospitals with an AYA focus were more likely to document fertility discussions (odds ratio[OR] = 1.60; 95%CI = 1.08-2.37) and FP procedures (OR = 1.74; 95%CI = 1.17-2.57) than adult hospitals with no AYA services. CONCLUSIONS: These data provide the first national, population-based estimates of fertility documentation for AYA cancer patients in Australia. Documentation of fertility-related discussions was poor, with higher rates observed in hospitals with greater experience of treating AYA patients.

Inconsistencies and time delays in site-specific research approvals hinder collaborative clinical research in Australia.

BACKGROUND/AIM: The aim of this study was to describe the time and documentation needed to gain ethics and governance approvals in Australian states with and without a centralised ethical review system. METHODS: This is a prospective descriptive study undertaken between February 2012 and March 2015. Paediatric and adult hospitals (n = 67) in Australian states were approached to allow the review of their medical records. Participants included 15- to 24-year-olds diagnosed with cancer between 2008 and 2012. The main outcomes measures were time (weeks) to approval for ethics and governance and the number and type of documents submitted. RESULTS: Centralised ethics approval processes were used in five states, with approval taking between 2 and 18 weeks. One state did not use a centralised process, with ethics approval taking a median of 4.5 weeks (range: 0-15) per site. In four states using a centralised ethics process, 33 governance applications were submitted, with 20 requiring a site clinician listed as an investigator. Governance applications required the submission of 11 documents on average, including a Site-Specific Assessment form. Thirty-two governance applications required original signatures from a median of 3.5 (range: 1-10) non-research persons, which took a median of 5 weeks (range: 0-15) to obtain. Governance approval took a median of 6 weeks (range: 1-45). Twelve research study agreements were needed, each taking a median of 7.5 weeks (range: 1-20) to finalise. CONCLUSION: The benefits of centralised ethics review systems have not been realised due to duplicative, inflexible governance processes. A system that allowed the recognition of prior ethical approval and low-risk applications was more efficient than a central ethics and site-specific governance process.

A prospective cohort of American Indian and Alaska Native people: study design, methods, and implementation.

In 2001, the National Cancer Institute funded three centers to test the feasibility of establishing a cohort of American Indian and Alaska Native people. Participating tribal organizations named the study EARTH (Education and Research Towards Health). This paper describes the study methods. A computerized data collection and tracking system was developed using audio computer-assisted survey methodology with touch screens. Data were collected on diet, physical activity, lifestyle and cultural practices, medical and reproductive history, and family history of heart disease, diabetes, and cancer. In addition, a small panel of medical measurements was obtained, including height, weight, waist and hip circumferences, blood pressure, and a lipid panel plus glucose. At the completion of the enrollment visit, data were used to provide immediate health feedback to study participants. During the initial funding period, the authors anticipate enrolling 16,000 American Indian and Alaska Native participants. The age distribution of the study population was similar to that reported in the 2000 US Census for the relevant populations. A component critical to the success of the EARTH Study has been the partnerships with tribal members. The study has focused on involvement of American Indian and Alaska Native communities in development and implementation and on provision of feedback to participants and communities.

Osteosarcoma associated with absent thumbs: a report of two cases.

An 8-year-old Hispanic boy with a hypoplastic left thumb, absent right thumb, and short stature experienced right leg pain and limp. A right tibial lesion was imaged and found to be osteosarcoma on biopsy. A 6-year-old Hispanic girl with congenitally absent thumbs experienced a pathologic fracture of her left femur after a minor sports injury. The radiologic abnormality seen was diagnosed as osteosarcoma on biopsy. Both patients continue to do well after intensive preoperative and postoperative high-dose chemotherapy and definitive reconstructive limb surgery. Osteosarcoma has been linked to several congenital syndromes in which absent thumbs are a feature. These two patients with absent thumbs and no definable syndrome experiencing osteosarcoma suggest that congenitally absent thumbs might be a risk factor for osteosarcoma in the absence of a syndrome.

Relationship between USDA and Japanese beef grades.

Angus steers (n = 78) were feedlot-finished to approximately 703 kg live weight. The finished steers were slaughtered at a commercial packing plant, chilled, and evaluated for USDA and Japanese yield and quality-grade characteristics. The resulting carcasses were excessively heavy and fat for the domestic (US) beef industry. Over 70% of the carcasses were US Yield Grade 5, and almost 40% were Japanese Yield Score 'C'. Although excessively fat externally, fewer than 50% of the carcasses qualified for US Prime, and none of the carcasses qualified for Japanese Meat Quality Score 5. Moderate to high correlations were observed between US twelfth-rib carcass traits and Japanese sixth-rib traits; however, multiple-regression equations based on USDA carcass characteristics explained only 46 and 25% of the observed variation in Japanese marbling score and estimated percentage wholesale-cut yield, respectively.

Decision-making in clinical practice: how do expert nurses, midwives and health visitors make decisions?

Decision-making is an essential and integral aspect of clinical practice. Preparation for clinical decision-making is haphazard and unplanned, in part because the process of making clinical decisions is not fully understood. This is one study of how expert nurses, midwives and health visitors make clinical decisions. The project involved a literature review and a series of workshops with expert practitioners to uncover the decision-making process in clinical practice. The study found that decision-making is an essential attribute of the expert practitioner, must be based on sound knowledge, may involve risk-taking and can only flourish in a supportive environment. Most importantly, clinical decision-making must take place within the context of a philosophy of care. Without such a philosophy, decisions will be arbitrary, uninformed and probably unsafe.

Effects of sire and dam on late-pregnancy conceptus and hormone traits in beef cattle.

Forty-six primiparous F1 heifers produced from mating Brahman (B), Charolais (C), Jersey (J), Longhorn (L), or Shorthorn (S) sires to crossbred cows were bred by AI to one of two Angus sires selected to produce high (H) or moderate (M) fetal growth. Dams were slaughtered at an average of 231 d of gestation. Daily blood samples were obtained from the dam on d 228 to 231 to determine serum estradiol, progesterone, and testosterone concentrations. Pelvic height was greatest (P < .05) in B, C, and L and pelvic width was greatest (P < .05) in S, C, and J dams, but pelvic areas did not differ (P > .10). Dams with greater hip height had larger pelvic areas (r = .45; P < .01). Intact fetuses from C and S dams were heaviest (P < .05), those from S dams had the greatest (P < .05) head width, and heart girth was greatest (P < .05) in fetuses from L dams. Fetuses from H sires were greater in weight (P < .01), body length (P < .01), and cannon circumference (P < .01). Dam differences were found in fetal heart weight (P < .01), trimmed placental membrane weight (P < .01), and average placentome weight (P < .05). Weights of eviscerated fetuses were greatest from C dams (P < .05). Placentome number was lowest (P < .05) in J dams, but J dams had the highest (P < .05) average placentome weight. Interactions between fetal genotype and breed of maternal environment were found for weight of eviscerated fetus (P < .05), body length, and heart weight (P < .01) and resulted from both magnitude and direction of change in the sire effect. The H sire increase in fetal weight was greatest in J dams, whereas B dams allowed expression of the fetal growth potential but at a lower level. Fetal trait interactions were also found for breed x sex and sex x sire (P < .05 to P < .01) and were due to the magnitude of differences expressed between the M and H sires. Serum testosterone concentrations were highest (P < .05) in B and L dams, dams gestating fetuses sired by the H sire (P = .08), and those with male fetuses (P < .01). We interpret these results to indicate that some maternal environments can suppress fetal growth, whereas others seem to complement the growth and allow maximum expression of the fetal genetic growth potential.(ABSTRACT TRUNCATED AT 400 WORDS)

Feedlot performance and carcass evaluation of heifers fed finishing diets as weanling calves or as yearlings.

Twenty commercial Herefored, Angus and Hereford × Angus, weanling and yearling heifers from the same herd were compared for feedlot performance and certain carcass characteristics. Yearlings tended to gain weight more rapidly than did weanlings. Since the cattle were group-fed, no analyses of feed efficiency could be performed. Yearlings appeared, however, to require less feed per unit of gain. The cattle were slaughtered when live weight approached 443 kg. Weanlings were fatter; had more kidney, pelvic and heart fat; merited higher (less desirable) USDA yield grades; had more desirable USDA quality grades and higher dressing percentage (P<0·05) than did yearlings. Ribeye area was not different between treatments. Yearlings yielded a higher percentage of closely trimmed retail lean cuts than did weanlings (P < 0·05). Sensory panel scores were higher (more desirable) for weanlings than for yearlings for both ribeye and inside round steaks (P < 0·05), while no differences were identified for flavor, juiciness or overall palatability of steaks. Warner-Bratzler shear force data generally supported taste panel evaluations for tenderness. These data suggest that carcass composition is impacted by the way cattle are managed and refute the idea that cattle have the same body composition at a given weight regardless of age at slaughter or nutrient density of the diet during finishing.

Embryonal carcinoma cell growth and differentiation. Production of and response to molecules with transforming growth factor activity.

Transforming growth factors are known to induce anchorage-independent growth of non-transformed cells, and are released by a variety of cells, including MSV-transformed cells. This study demonstrates that the differentiated cells derived from F9 and PC-13 embryonal carcinoma cells, but not the parental cells themselves, respond by increased growth to several factors released by MSV-transformed cells, including partially purified sarcoma growth factor. The chemical properties of the growth-promoting activity are shown to match the chemical properties of the transforming growth factors released by MSV-transformed cells. Furthermore, F9 and PC-13 embryonal carcinoma cells, which do not respond to factors released by MSV-transformed cells, are shown to release factors with transforming growth factor activity. Based on the close relationship between mouse embryonal carcinoma cells and cells of early mouse embryos, it is suggested that molecules with transforming growth factor activity may play a role during the early stages of mammalian development.