Management and grading of EGFR inhibitor-induced cutaneous toxicity.

Cutaneous toxicities associated with EGFR inhibitors (EGFRIs) have a significant impact on patient treatment continuation, quality of life and healthcare resource utilization. This paper reviews the current prophylaxis and management of EGFRI-induced cutaneous toxicities in patients with colorectal cancer, and combines these findings with the authors' clinical expertise to define a novel algorithm for healthcare professionals managing patients receiving EGFRIs. This tool includes a grading system based on the location, severity and psychological impact, and provides a standard prescription pack, advice on prophylaxis/self-management of cutaneous symptoms for patients initiating EGFRIs, and essential guidance on subsequent review and treatment escalation. It aims to optimize treatment of metastatic colorectal cancer by minimizing cutaneous toxicities to maintain dose intensity and efficacy of EGFRI-based chemotherapy.

Intersectoral collaboration to implement school-based health programmes: Australian perspectives.

Understanding the processes and the factors influencing intersectoral collaboration is vital for the ongoing success of programmes that rely on effective partnerships between sectors, such as the school-based immunization programme, the school dental health programme and health promotion interventions delivered in school settings. We studied school-based health programmes delivered by partnerships between health, education and the local government sectors. We used purposive sampling to identify 19 people working in school-based health programmes and interviewed them about the barriers and enablers of successful collaboration. Data were analysed thematically. We found that collaboration between complex systems was a skilled endeavour which relied on a strong foundation of communication and interpersonal professional relationships. Understanding the core business, operational context and intersectoral point-of-view of collaborative partners was important both for establishing good intersectoral programmes and sustaining them as contexts and personnel changed. Aligning divergent sectoral agendas early in the collaborative process was essential for ensuring that all partners could meet their core business needs while also delivering the programme outcomes.

A qualitative study of work-life balance amongst specialist orthodontists in the United Kingdom.

OBJECTIVE: To identify factors affecting work-life balance amongst male and female orthodontists in the UK. DESIGN: A qualitative interview-based study with a cross-sectional design. SUBJECTS: Specialist orthodontists working in specialist practice and the hospital service in the UK were selected by purposive sampling. METHODS: In-depth semi-structured interviews were conducted with 18 orthodontic specialists. Interview transcripts were analyzed using Framework Analysis. RESULTS: Four main themes pertaining to work-life balance in orthodontics were identified: work factors affecting work-life balance, life factors affecting work-life balance, perception and effects of work-life balance and suggestions for managing work-life balance within the profession. CONCLUSIONS: There was substantial variation in the work-life balance of the orthodontists interviewed in this study; however the majority reported high levels of career satisfaction despite difficulties maintaining a good work-life balance. Whilst there were some clear distinctions in the factors affecting work-life balance between the hospital environment and specialist practice (including additional professional commitments and teaching/training-related issues), there were also a number of similarities. These included, the lack of flexibility in the working day, managing patient expectations, taking time off work at short notice and the ability to work part-time.

Evaluation of the orthodontic component of the hypodontia care pathway.

INTRODUCTION: This study evaluated patients' experiences of the Hypodontia Care Pathway at a large teaching hospital at key stages: specifically patient expectations/experience following the diagnosis of hypodontia and then patient satisfaction with the orthodontic care received and the outcome at the end of active orthodontic treatment. METHODOLOGY: In-depth, semi-structured interviews were conducted with 20 hypodontia patients following completion of orthodontic treatment but prior to any planned prosthodontic treatment commencing. Interviews were analysed qualitatively, using a framework approach. RESULTS: The framework analysis identified four main themes: perceptions of treatment, impact of the original malocclusion and the treatment process, the care team and communication. The themes were then further divided into subthemes. DISCUSSION: There was a large amount of positive feedback and the importance of the patient-clinician relationship was evident throughout. Where issues of concern were identified, these related mainly to communication and areas were identified where change could take place in the future. CONCLUSIONS: Positive feedback was received and the importance of patient-clinician rapport was highlighted in all interviews. The main areas that could be enhanced related to the importance of ensuring optimum communication, particularly with a cohort of patients who are often undergoing complex multidisciplinary treatment. Recommendations for the service have been made.

Ethical Challenges in School-Based Immunization Programs for Adolescents: A Qualitative Study.

OBJECTIVES: We investigated ethical issues in school-based immunization programs for adolescents and how they are addressed. METHODS: We used qualitative methods and an ethnographic approach to observe 9 secondary schools on immunization days in South Australia in 2011; concurrently, we conducted 9 focus groups with female secondary school students, 6 semistructured interviews with parents, and 10 interviews with nurses and teachers. We explored ethical challenges from the perspective of these groups. RESULTS: We identified ethical challenges for the delivery of adolescent immunization in a school-based setting in 3 main areas: informed consent, restrictions on privacy, and harm to students in the form of fear and anxiety. CONCLUSIONS: We found areas in which the design and delivery of school-based immunization programs can be improved. Information about immunization should be provided in ways that are appropriate to young people and their parents, and privacy protections should be enhanced when possible. Involving young people in the design and delivery of programs would assist with making these improvements.

HPV.edu study protocol: a cluster randomised controlled evaluation of education, decisional support and logistical strategies in school-based human papillomavirus (HPV) vaccination of adolescents.

BACKGROUND: The National Human Papillomavirus (HPV) Vaccination Program in Australia commenced in 2007 for females and in 2013 for males, using the quadrivalent HPV vaccine (HPV 6,11,16,18). Thus far, we have demonstrated very substantial reductions in genital warts and in the prevalence of HPV among young Australian women, providing early evidence for the success of this public health initiative. Australia has a long history of school-based vaccination programs for adolescents, with comparatively high coverage. However, it is not clear what factors promote success in a school vaccination program. The HPV.edu study aims to examine: 1) student knowledge about HPV vaccination; 2) psycho-social outcomes and 3) vaccination uptake. METHODS/DESIGN: HPV.edu is a cluster randomised trial of a complex intervention in schools aiming to recruit 40 schools with year-8 enrolments above 100 students (approximately 4400 students). The schools will be stratified by Government, Catholic, and Independent sectors and geographical location, with up to 20 schools recruited in each of two states, Western Australia (WA) and South Australia (SA), and randomly allocated to intervention or control (usual practice). Intervention schools will receive the complex intervention which includes an adolescent intervention (education and distraction); a decisional support tool for parents and adolescents and logistical strategies (consent form returns strategies, in-school mop-up vaccination and vaccination-day guidelines). Careful process evaluation including an embedded qualitative evaluation will be undertaken to explore in depth possible mechanisms for any observed effect of the intervention on primary and secondary outcomes. DISCUSSION: This study is the first to evaluate the relative effectiveness of various strategies to promote best practice in school-based vaccination against HPV. The study aims to improve vaccination-related psychosocial outcomes, including adolescent knowledge and attitudes, decision-making involvement, self-efficacy, and to reduce fear and anxiety. The study also aims to improve school vaccination program logistics including reduction in time spent vaccinating adolescents and increased number of consent forms returned (regardless of decision). Less anxiety in adolescents will likely promote more efficient vaccination, which will be more acceptable to teachers, nurses and parents. Through these interventions, it is hoped that vaccination uptake will be increased. TRIAL REGISTRATION: Australian and New Zealand Clinical Trials Registry, ACTRN12614000404628 , 14.04.2014.

Understanding the school community's response to school closures during the H1N1 2009 influenza pandemic.

BACKGROUND: During the 2009 H1N1 influenza pandemic, Australian public health officials closed schools as a strategy to mitigate the spread of the infection. This article examines school communities' understanding of, and participation in, school closures and the beliefs and values which underpinned school responses to the closures. METHODS: We interviewed four school principals, 25 staff, 14 parents and 13 students in five schools in one Australian city which were either fully or partially closed during the 2009 H1N1 pandemic. RESULTS: Drawing on Thompson et al's ethical framework for pandemic planning, we show that considerable variation existed between and within schools in their attention to ethical processes and values. In all schools, health officials and school leaders were strongly committed to providing high quality care for members of the school community. There was variation in the extent to which information was shared openly and transparently, the degree to which school community members considered themselves participants in decision-making, and the responsiveness of decision-makers to the changing situation. Reservations were expressed about the need for closures and quarantine and there was a lack of understanding of the rationale for the closures. All schools displayed a strong duty of care toward those in need, although school communities had a broader view of care than that of the public health officials. Similarly, there was a clear understanding of and commitment to protect the public from harm and to demonstrate responsible stewardship. CONCLUSIONS: We conclude that school closures during an influenza pandemic represent both a challenge for public health officials and a litmus test for the level of trust in public officials, government and the school as institution. In our study, trust was the foundation upon which effective responses to the school closure were built. Trust relations within the school were the basis on which different values and beliefs were used to develop and justify the practices and strategies in response to the pandemic.

COVID-19 vaccine hesitancy and health literacy in US Southern states.

OBJECTIVES: COVID-19 vaccination in the United States has stalled, with some of the lowest rates in the South. Vaccine hesitancy is a primary contributor and may be influenced by health literacy (HL). This study assessed the association between HL and COVID-19 vaccine hesitancy in a population residing in 14 Southern states. STUDY DESIGN: Cross-sectional study using a web-based survey conducted between February and June 2021. METHODS: The outcome was vaccine hesitancy, and the main independent variable was HL, assessed as an index score. Descriptive statistical tests were performed, and multivariable logistic regression analysis was conducted, controlling for sociodemographic and other variables. RESULTS: Of the total analytic sample (n = 221), the overall rate of vaccine hesitancy was 23.5%. Vaccine hesitancy was more prevalent in those with low/moderate HL (33.3%) vs those with high HL (22.7%). The association between HL and vaccine hesitancy, however, was not significant. Personal perception of COVID-19 threat was significantly associated with lower odds of vaccine hesitancy compared with those without perception of threat (adjusted odds ratio, 0.15; 95% CI, 0.03-0.73; P = .0189). The association between race/ethnicity and vaccine hesitancy was not statistically significant (P = .1571). CONCLUSIONS: HL was not a significant indicator of vaccine hesitancy in the study population, suggesting that general low rates of vaccination in the Southern region may not be due to knowledge about COVID-19. This indicates a critical need for place-based or contextual research on why vaccine hesitancy in the region transcends most sociodemographic differences.

Modification to Systemic Anticancer Therapy at the Start of the COVID-19 Pandemic and its Overall Impact on Survival Outcomes in Patients with Colorectal Cancer.

BACKGROUND: Since the beginning of the COVID-19 pandemic, multiple changes to the provision of cancer care has been introduced to maximize patient safety and protect staff. We aimed to identify factors influencing clinicians' decision on treatment modification during the initial phase of the pandemic, and to assess its impact on outcomes in patients with colorectal cancer. PATIENTS AND METHODS: Electronic records of patients seen in a large United Kingdom tertiary cancer center was reviewed. The frequency and type of changes to systemic anticancer therapy , as well as the factors predicting clinicians' decision were assessed. RESULTS: A total of 418 patients; mean age 63 ± 12 years and 57% male were included. More than half of the patients had modification to their treatment; with treatment delay (21%) or cancellation (10%), being the most common. Majority of patients on neoadjuvant treatment (97%) proceeded with treatment, with some form of treatment modification in 20%. Half of patients on adjuvant treatment had their treatment plan modified. Overall, a change in treatment was more likely in older patients (OR 1.028 [95% CI 1.010-1.047]; P = .002), and in patients who had already received higher number of cycles of systemic anticancer therapy (OR 1.040 [95% CI 1.016-1.065]; P = .001). A change in treatment was less likely further out of the first national lockdown (OR 0.837 [95% CI 0.758-0.925]; P < .001). Patients on third-line treatment were most likely to have alterations to their treatment plan (69%, n=33/48). CONCLUSION: During the first wave of COVID-19 in the United Kingdom, clinicians adapted clinical practice in accordance to local and national guidance, especially amongst older patients and those on third-line treatment. Further real-world data are needed to document the important impact of changes to treatment on outcomes in patients with cancer.

Parecoxib for opioid-induced hyperalgesia.

This paper describes the case report of a patient admitted to hospital with severe and complex pain and subacute bowel obstruction, who failed to respond to multiple analgesic regimens including ketamine burst and opioid rotation, and was subsequently successfully managed with a parecoxib infusion.

A supervised exercise intervention during cancer treatment for adolescents and young adults-FiGHTING F!T: study protocol of a randomised controlled trial.

BACKGROUND: High-quality evidence supports the integration of exercise to mitigate treatment-related side effects in a wide range of paediatric and adult cancer cohorts. However, the implementation of exercise in adolescent and young adult (AYA) cancer patients is yet to be explored in depth. FiGHTINGF!T is a randomised controlled cross over trial designed to determine if a supervised, structured, and progressive exercise programme can reduce the decline in physical fitness (V02peak) associated with cancer treatment in AYAs from diagnosis. METHODS/DESIGN: A total of 40 AYAs recently diagnosed and due to commence systemic treatment (± 2 weeks) for a primary haematological malignancy or solid tumour will be recruited and randomised to either an immediate exercise intervention or usual care (delayed exercise) for 10 weeks. This randomised controlled crossover trial will see both groups engage in a supervised exercise intervention from either diagnosis (baseline assessment) for 10 weeks (0-10 weeks) or following an interim assessment to 20 weeks (10-20 weeks). The bi-weekly tailored exercise programme will combine aerobic and resistance exercises and be supervised by an Accredited Exercise Physiologist. Participants will complete a range of assessments at 0, 10, and 20 weeks including cardiopulmonary exercise tests, 1 repetition maximum strength measures, physical functioning, and self-reported quality of life measurements. Patient-reported treatment-related toxicities will be recorded on a weekly basis. DISCUSSION: The FiGHTINGF!T trial will provide insight into the potential benefits of a supervised exercise programme in AYAs undergoing cancer treatment. This trial will contribute to the evidence supporting the necessary integration of exercise during cancer treatment, specifically in the under-reported AYA cohort. TRIAL REGISTRATION: This trial was registered retrospectively with the Australia New Zealand Clinical Trial registry ( ACTRN12620000663954 ). Registered on 10 June 2020.

An alternative retainer design for cleft patients: the "aesthetic" retainer.

The objective of this report is to describe an original retainer design for retention following orthodontic treatment in cleft lip and palate patients in order to improve the aesthetics of anterior maxillary dentoalveolar cleft defects. The technique incorporates features of both traditional and modern retainer design. The advantages of the technique and fabrication process are described.

Do we know what patients want? The doctor-patient communication gap in functional gastrointestinal disorders.

BACKGROUND & AIMS: Understanding patients' expectations at initial consultation for functional gastrointestinal disorders (FGIDs) might influence future health care utilization. Ideally, patients and doctors would have a common understanding of the issues involved. We sought to investigate this with matched questionnaires. METHODS: Patients' needs/expectations/understanding were compared with gastroenterologists' and general practitioners' awareness of these. Patients were followed up to investigate satisfaction with and outcomes of specialist consultation. RESULTS: Specialists underestimated the number and severity of patients' symptoms (in 43% and 41%, respectively), and patients and specialists had quite discordant views on what treatment would best suit their symptoms. Strikingly, only 1 of 13 patients available for follow-up agreed with or accepted the functional diagnosis, despite all being diagnosed by a specialist as having an FGID. CONCLUSIONS: In FGIDs there is a communication gap between patients and gastroenterologists. Importantly, at follow-up, patients do not acknowledge their FGID diagnosis. This communication gap and lack of acceptance of a functional diagnosis are likely to influence future management and health care utilization.

Mental, emotional, and social problems among school children with asthma.

OBJECTIVES: To use representative population chronic disease and risk factor data to investigate the relationship between asthma and social factors in school-age children. METHODS: Representative cross-sectional data for children 5 to 15 years of age were collected from 2002 to June 2007 (n = 4,611) in the South Australian Monitoring and Surveillance System (SAMSS) using Computer-Assisted Telephone Interviews (CATI). Univariate and multivariate analyses were conducted to investigate the variables that were associated with asthma among children. RESULTS: The overall prevalence of self-reported asthma among children 5 to 15 years of age was 18.6% (95% CI = 17.5-19.8). Children with asthma were more likely to have been treated for a mental health problem, have been unhappy at school, have been absent from school in the last month, have fair or poor overall health and well-being, have ongoing pain or chronic illness, and less likely to have a group of friends to play with. Asthma was also more prevalent among males and less likely to occur in children from households where the gross annual income was greater than $AU80,000. CONCLUSIONS: Children with asthma were more likely to be treated for a mental health problem and demonstrate more negative social outcomes as well as poorer overall health and well-being. Asthma management plans need to be sensitive to these psychosocial factors for adequate care of these vulnerable young patients.

Evaluation of the Litron In Vitro MicroFlow Kit for the flow cytometric enumeration of micronuclei (MN) in mammalian cells.

We have evaluated the performance of the prototype In Vitro MicroFlow Kit (Litron Laboratories), which offers a flow cytometric method for scoring micronuclei (MN). This method uses sequential staining to differentiate MN from chromatin fragments derived from apoptotic or necrotic cells. Data were generated using the genotoxins methylmethane sulphonate (MMS), dimethylbenzanthracene (DMBA) and vinblastine, and the non-genotoxins dexamethasone and staurosporine, which are known to induce apoptosis in vitro. The results obtained with these agents were compared with conventional microscopy. For short-duration exposures (3-4h) both manual and flow methodologies demonstrated good concordance, with concentration-related increases in the percentage of MN for MMS, DMBA and vinblastine. Statistically significant increases were observed at > or = 20 and 40 microg/mL, for manual and flow analysis, respectively, for MMS; at 0.5 and 0.75 microg/mL for DMBA; and at 0.035 and 0.04 microg/mL, respectively, for vinblastine. Dexamethasone showed clear negative responses by manual and flow cytometric analysis, with comparable results for both methodologies (all <1.7-fold compared with concurrent vehicle controls). Data for staurosporine, however, were less consistent showing significantly higher flow cytometric MN frequencies compared with those seen after manual analysis. Continuous (24 h) treatments were also conducted with MMS, vinblastine, dexamethasone and staurosporine. There was good concordance between the methodologies for MMS, staurosporine and vinblastine. However, dexamethasone generated discordant results, i.e. microscopic analysis was clearly negative at all doses tested, whereas flow cytometry produced significant increases in MN frequency (up to 8.1-fold at 100 microg/mL compared with the concurrent vehicle control). The inconsistencies observed between flow cytometry and standard microscopy, and the differences in assay sensitivity, particularly for apoptosis-inducing compounds, suggest that the prototype In Vitro MicroFlow Kit requires further refinement. Studies to investigate new parameters to address these issues are now under way and will be reported separately.

Interlaboratory evaluation of a flow cytometric, high content in vitro micronucleus assay.

An international, multi-lab trial was conducted to evaluate a flow cytometry-based method for scoring micronuclei in mouse lymphoma L5178Y cells [S.L. Avlasevich, S.M. Bryce, S.E. Cairns, S.D. Dertinger, In vitro micronucleus scoring by flow cytometry: differential staining of micronuclei versus apoptotic and necrotic chromatin enhances assay reliability, Environ. Mol. Mutagen. 47 (2006) 56-66]. A reference laboratory investigated the potential of six chemicals to induce micronuclei -- the genotoxicants mitomycin C (MMC), etoposide (ETOPO), and vinblastine (VB), and the non-genotoxicants sucrose (SUC), staurosporine (STS), and dexamethasone (DEX). The latter two non-genotoxicants were selected as extreme challenges to the assay because of their potent apoptogenic activity. Three collaborating laboratories were supplied with prototype In Vitro MicroFlow kits, and each was assigned one genotoxicant and one non-genotoxicant. Cells were treated continuously for 24h over a range of concentrations up to 5 mg/ml, or overtly cytotoxic concentrations. Micronuclei were scored via standard microscopy and flow cytometry. In addition to enumerating micronucleus frequencies, a cytotoxicity measurement that is simultaneously acquired with the flow cytometric micronucleus scoring procedure was evaluated (Flow-NBR). With this method, latex particles served as counting beads, and facilitated relative survival measurements that exclude the presence of dead/dying cells. For comparison purposes, additional cytotoxicity endpoints were measured, including several that are based on cell number, and others that reflect compromised membrane integrity, including dye permeability and/or phospholipid distribution. Key findings for this set of compounds include the following: (1) significant discrepancies in top concentration selection were found when cytotoxicity measurements were based on different methods, with the Flow-NBR approach tending to be the most sensitive, (2) both microscopy- and flow cytometry-based scoring methods detected concentration-dependent micronucleus formation for the three genotoxic agents studied, with good agreement between the reference laboratory and the collaborating laboratories, and (3) whereas flow cytometric analyses showed no significant increases for the non-genotoxicants when top concentration selection was based on Flow-NBR, significantly elevated micronucleus frequencies were observed for concentrations that were chosen based on less-sensitive cytotoxicity assays. Collectively, these results indicate that rapid assessment of genotoxicity can be accomplished with a relatively simple flow cytometric technique, and that the scoring system is transferable across laboratories. Furthermore, a concurrent assessment of cytotoxicity, Flow-NBR, may help reduce the occurrence of irrelevant positive results, as it may represent a more appropriate means for choosing top concentration levels. Finally, the data presented herein reinforce concerns about the manner in which cytotoxicity limits are described in guidance documents, since these recommendations tend to cite fixed cut-off values without reference to methodology.

Patterns in Clinical Trial Enrollment and Supportive Care Services Provision Among Adolescents and Young Adults Diagnosed with Having Cancer During the Period 2000-2004 in Western Australia.

PURPOSE: Support services provision and clinical trial enrollment were examined for a cohort of adolescent and young adults (AYAs) diagnosed with having cancer and treated at adult hospitals in Western Australia (WA). METHODS: The sample was 383 AYAs aged 15-24 years diagnosed from 2000 to 2004, with follow-up until 2007. Sociodemographic, clinical trial participation, and health service data were obtained from Statewide administrative health data collections and patient medical records at hospitals in WA. Separate multivariate logistic regression models were used to identify which sociodemographic and treatment setting variables predicted whether a patient had formal contact with a mental health professional, social worker, or occupational therapist. Due to the small number of clinical trial enrollments in the sample (n = 5), modeling was not used to explore group differences in this outcome. RESULTS: Mental health professional, social worker, and occupational therapist consultations were received only by patients who attended a metropolitan hospital. Compared with patients treated at only tertiary centers, those treated at only nontertiary centers had lower odds of consulting with a mental health professional (OR = 0.12, 95% CI 0.03, 0.58) or occupational therapist (OR = 0.02, 95% CI 0.001, 0.23). Less than 2% of the cohort enrolled in a clinical trial. CONCLUSION: Access to clinical trials and support services by AYAs diagnosed with having cancer in WA was generally low, particularly outside the metropolitan area. Variations in accessibility across different treatment settings in WA warrant efforts for greater awareness of AYA needs and increased communication and collaboration between specialists and centers involved in the care of AYAs with cancer.

Understanding motivators and barriers of hospital-based obstetric and pediatric health care worker influenza vaccination programs in Australia.

Understanding motivators and barriers of health care worker (HCW) vaccination programs is important for determining strategies to improve uptake. The aim of this study was to explore key drivers and HCW decision making related to recommended vaccines and seasonal influenza vaccination programs. We used a qualitative approach with semi-structured one-to-one interviews with 22 HCWs working at a tertiary pediatric and obstetric hospital in South Australia. A thematic analysis and coding were used to examine data. Key motivators that emerged included: sense of responsibility, convenience and ease of access, rotating trolleys, the influenza vaccine being free, basic knowledge about influenza and influenza vaccination, peer pressure, personal values and family culture, as well as the culture of support for the program. Personal decisions were the major barrier to HCWs receiving the influenza vaccine which were predominantly self-protection related or due to previous experience or fear of adverse reactions. Other barriers that emerged were misconceptions about the influenza vaccine, needle phobia and privacy concerns. This study identified both attitudinal and structural barriers that could be addressed to improve uptake of the seasonal influenza vaccine.

Prioritizing government funding of adolescent vaccinations: recommendations from young people on a citizens' jury.

OBJECTIVE: Adolescents' views, and preferences are often over-looked when public health policies that affect them are designed and implemented. The purpose of this study was to describe young people's views and preferences for determining government funding priorities for adolescent immunization programs. METHODS: In 2015 we conducted a youth jury in metropolitan Adelaide, South Australia to deliberate on the question "What criteria should we use to decide which vaccines for young people in Australia should receive public funding?" Fifteen youth aged 15-19 years participated in the jury. Jury members were recruited from the general community through a market research company using a stratified sampling technique. RESULTS: The jury's key priorities for determining publically funded vaccines were: Disease severity - whether the vaccine preventable disease (VPD) was life threatening and impacted on quality of life. Transmissibility - VPDs with high/fast transmission and high prevalence. Demonstration of cost-effectiveness, taking into account purchase price, program administration, economic and societal gain. The jury's recommendations for vaccine funding policy were strongly underpinned by the belief that it was critical to ensure that funding was targeted to not only population groups who would be medically at risk from vaccine preventable diseases, but also to socially and economically disadvantaged population groups. A novel recommendation proposed by the jury was that there should be a process for establishing criteria to remove vaccines from publically funded programs as a complement to the process for adding new vaccines. CONCLUSIONS: Young people have valuable contributions to make in priority setting for health programs and their views should be incorporated into the framing of health policies that directly affect them.

In Vivo Pig-a gene mutation assay: Guidance for 3Rs-friendly implementation.

The rodent Pig-a assay is an in vivo method for the detection of gene mutation, where lack of glycosylphosphatidylinositol-anchored proteins on the surface of circulating red blood cells (RBCs) serves as a reporter for Pig-a gene mutation. In the case of rats, the frequency of mutant phenotype RBCs is measured via fluorescent anti-CD59 antibodies and flow cytometry. The Pig-a assay meets the growing expectations for novel approaches in animal experimentation not only focusing on the scientific value of the assay but also on animal welfare aspects (3Rs principles), for example, amenable to integration into pivotal rodent 28-day general toxicology studies. However, as recommended in the Organisation for Economic Co-operation and Development Test Guidelines for genotoxicity testing, laboratories are expected to demonstrate their proficiency. While this has historically involved the extensive use of animals, here we describe an alternative approach based on a series of blood dilutions covering a range of mutant frequencies. The experiments described herein utilized either non-fluorescent anti-CD59 antibodies to provide elevated numbers of mutant-like cells, or a low volume blood sample from a single N-ethyl-N-nitrosourea treated animal. Results from these so-called reconstruction experiments from four independent laboratories showed good overall precision (correlation coefficients: 0.9979-0.9999) and accuracy (estimated slope: 0.71-1.09) of mutant cell scoring, which was further confirmed by Bland-Altman analysis. These data strongly support the use of reconstruction experiments for training purposes and demonstrating laboratory proficiency with very few animals, an ideal situation given the typically conflicting goals of demonstrating laboratory proficiency and reducing the use of animals. Environ. Mol. Mutagen. 57:678-686, 2016. © 2016 Wiley Periodicals, Inc.