Modelling PK/QT relationships from Phase I dose‐escalation trials for drug combinations and developing quantitative risk assessments of clinically relevant QT prolongations

In current industry practice, it is difficult to assess QT effects at potential therapeutic doses based on Phase I dose‐escalation trials in oncology due to data scarcity, particularly in combinations trials. In this paper, we propose to use dose‐concentration and concentration‐QT models jointly to model the exposures and effects of multiple drugs in combination. The fitted models then can be used to make early predictions for QT prolongation to aid choosing recommended dose combinations for further investigation. The models consider potential correlation between concentrations of test drugs and potential drug–drug interactions at PK and QT levels. In addition, this approach allows for the assessment of the probability of QT prolongation exceeding given thresholds of clinical significance. The performance of this approach was examined via simulation under practical scenarios for dose‐escalation trials for a combination of two drugs. The simulation results show that invaluable information of QT effects at therapeutic dose combinations can be gained by the proposed approaches. Early detection of dose combinations with substantial QT prolongation is evaluated effectively through the CIs of the predicted peak QT prolongation at each dose combination. Furthermore, the probability of QT prolongation exceeding a certain threshold is also computed to support early detection of safety signals while accounting for uncertainty associated with data from Phase I studies. While the prediction of QT effects is sensitive to the dose escalation process, the sensitivity and limited sample size should be considered when providing support to the decision‐making process for further developing certain dose combinations. Copyright © 2016 John Wiley & Sons, Ltd.     

Applying the use of activity in the assessment of malingering: A case illustration

The assessment of malingering has predominantly been considered within the domains of neuropsychologists and psychiatrists, who use consistency of performance criteria similar to those used in functional capacity evaluations (FCE). The use of activity has traditionally been used in occupational therapy as an assessment and treatment modality with goals not always considered obvious and which could easily be used for diversional reasons. The appropriate use of activity adds an additional dimension to a layered approach of using multiple data sources and methods as recommended by FCE practitioners and neuropsychologists alike. The case illustration aims to explain the above using a layered model.     

The effect of a novel ADL-based training program on performance of activities of daily living and physical fitness

The purpose of this study was to determine the degree to which a novel training program based on activities of daily living (ADL) would affect performance of ADLs, as well as the fitness of older adults. Fourteen individuals (mean age 82 years) took part in a 10-week control period followed by a 10-week ADL-based training program. Pre- and posttests included the Physical Performance Test (PPT), the Physical Functional Performance-10 (PFP-10), and the Senior Fitness Test (SFT). After the training period, improvements ranging from 7% to 33% (p<.05) were seen on the PPT and PFP-10 and on three items of the SFT. After conversion to standard scores, the magnitude of change in the PPT and the PFP10 was significantly greater (p<.05) than the magnitude of change in the SFT. These data support the idea that this novel ADL-based training program was able to facilitate improved performance of ADLs, as well as select measures of fitness among older adults.     

Complexities in attracting and retaining direct support professionals

Recruiting and retaining direct support professionals (DSPs) remains essential to the full inclusion for persons with disabilities. Using a mixed-evaluation model, we measured DSPs' views versus those of their supervisors. DSPs expressed lower perceptions concerning their supervisors, satisfaction with their work situation, and environmental and safety factors. Focus groups provided insights into resolving issues related to compensation, work environment, and recruiting and retaining future DSPs. Motivating factors included wanting to be part of a helping community where all are valued. To improve their performance, DSPs stated their desire to understand the roles of managers and of the consumer. DSPs indicated that having career paths that provided advancement opportunities and direct contact with persons with disabilities were primary motivators.     

Older women's fears of violence: the need for interventions that enable active ageing

Women's fear of violence can impact negatively on their active participation in life. An ageing survey conducted with 2,620 Australian respondents aged 50 to 90 years examined aspects of work, learning, social, spiritual and emotional status, health, vision, home, life events, demographics, and asked an open-ended question about what being actively engaged in life meant. Ordinal regression was carried out on two dependent variables: wanting and needing to learn to discourage violence. Analyses found that as women's age increased, those on lower incomes were more likely than others to say they needed to learn how to discourage violence against them. This paper investigates the variables associated with the findings-transport, finances, news media, home safety, and reduced social interactions. Results highlight the importance of understanding women's fear in the context of personal and social issues, and the need to provide learning opportunities to improve safety and social engagement.     

Everything for the Children: Orphans Growing Up in Informal Adoptive Families in China

Most orphaned children in China are cared for by their extended families or become state wards under the guardianship of child welfare institutions. Some exceptions are children who are found and cared for by families in the community, without a formalized adoption or foster relationship. In some locations, institutions now accept guardianship for these children and support the informal adoptive family to continue to care for them. This article examines the outcomes for these children as they became young adults by comparing these 12 children raised within the system as they approach or have approached young adulthood (now aged 16–40 years-old). Some of the participants were either informally adopted or lived in institutional care. The results of this study found that the family environment was more conducive to the young people’s wellbeing as they approached or entered adulthood. The participants raised in informal care appeared to be treated similar to the biological children in these families. When the institution formalized the state guardianship responsibility, it also meant the families had state resources for support to protect the children’s rights to economic security, education, health care, and social participation. This practice by the institution supported the addition of informal adoption, as one step closer to permanency than foster care. Future implications include considering this option to help promote the family system assisting these children, families, and the state.     

Asking about the future: methodological insights from energy biographies

Temporality is fundamental to qualitative longitudinal (QLL) research, inherent in the design of returning to participants over time, often to explore moments of change. Previous research has indicated that talking about the future can be difficult, yet there has been insufficient discussion of methodological developments to address these challenges. This paper presents insights from the Energy Biographies project, which has taken a QLL and multimodal approach to investigating how everyday energy use can be understood in relation to biographical pasts and imagined futures. In particular, we detail innovative techniques developed within the project (e.g. SMS photograph activities) to elicit data on anticipated futures, in ways that engender thinking about participants’ own biographical futures and wider societal changes. We conclude by considering some of the significant benefits and challenges such techniques present. These methodological insights have a wider relevance beyond the substantive topic for those interested in eliciting data about futures in qualitative research.