Understanding and assessing the impact of treatment in diabetes: the Treatment-Related Impact Measures for Diabetes and Devices (TRIM-Diabetes and TRIM-Diabetes Device)

<p>Abstract</p> <p>Purpose</p> <p>Diabetes is a debilitating illness requiring lifelong management. Treatments can be varied in terms of mode of administration as well as type of agent. Unfortunately, most patient reported outcome measures currently available to assess the impact of treatment are specific to diabetes type, treatment modality or delivery systems and are designed to be either a HRQoL or treatment satisfaction measure. To address these gaps, the Treatment Related Impact Measure-Diabetes and Device measures were developed. This paper presents the item development and validation of the TRIM Diabetes/Device.</p> <p>Methods</p> <p>Patient interviews were conducted to collect the patient perspective and ensure high content validity. Interviews were hand coded and qualitatively analyzed to identify common themes. A conceptual model of the impact of diabetes medication was developed and preliminary items for the TRIM-Diabetes/Device were generated and cognitively debriefed. Validation data was collected via an on-line survey and analyzed according to an a priori statistical analysis plan to validate the overall score as well as each domain. Item level criteria were used to reduce the preliminary item pool. Next, factor analysis to identify structural domains was performed. Reliability and validity testing was then performed.</p> <p>Results</p> <p>One hundred and five patients were interviewed in focus groups, individual interviews and for cognitive debriefing. Five hundred seven patients participated in the validation study. Factor analysis identified seven domains: Treatment Burden, Daily Life; Diabetes Management; Psychological Health; Compliance and Device Function and Bother. Internal consistency reliability coefficients of the TRIM-Diabetes/Device ranged from 0.80 and 0.94. Test-retest reliability of the TRIM-Diabetes/Device ranged from 0.71 to 0.89. All convergent and known groups validity hypotheses were met for the TRIM-Diabetes/Device total scores and sub-scales.</p> <p>Conclusion</p> <p>Validation is an ongoing and iterative process. These findings are the first step in that process and have shown that both the TRIM-Diabetes and the TRIM-Diabetes Device have acceptable psychometric properties. Future research is needed to continue the validation process and examine responsiveness and the validity of the TRIM-Diabetes/Device in a clinical trial population.</p

Health-related quality of life of children with attention-deficit/hyperactivity disorder versus children with diabetes and healthy controls

The impact of attention-deficit/hyperactivity disorder (ADHD) on health-related quality of life (HRQoL) is reported to be similar to that of other mental health and physical disorders. In this cross-sectional study, we hypothesized that children with ADHD and children with type 1 diabetes mellitus (T1DM) would have significantly worse HRQoL compared with healthy children, and that better clinical status in ADHD and T1DM would be associated with better HRQoL. Children were recruited from three outpatient services in Scotland. Responses to two frequently used validated HRQoL instruments, the Paediatric Quality of Life Inventory (PedsQL) and Child Health and Illness Profile-child edition (CHIP-CE), were obtained from parents/carers and children (6–16 years) with/without ADHD or T1DM. Child and parent/carer-completed HRQoL measurements were evaluated for 213 children with ADHD, 58 children with T1DM and 117 healthy children (control group). Significantly lower self and parent/carer ratings were observed across most PedsQL (P < 0.001) and CHIP-CE (P < 0.05) domains (indicating reduced HRQoL) for the ADHD group compared with the T1DM and control groups. Parent/carer and child ratings were significantly correlated for both measures of HRQoL (PedsQL total score: P < 0.001; CHIP-CE all domains: P < 0.001), but only with low-to-moderate strength. Correlation between ADHD severity and HRQoL was significant with both PedsQL and CHIP-CE for all parent/carer (P < 0.01) and most child (P < 0.05) ratings; more ADHD symptoms were associated with poorer HRQoL. These data demonstrate that ADHD has a significant impact on HRQoL (as observed in both parent/carer and child ratings), which seems to be greater than that for children with T1DM

Some recommendations for developing multidimensional computerized adaptive tests for patient-reported outcomes

PURPOSE: Multidimensional item response theory and computerized adaptive testing (CAT) are increasingly used in mental health, quality of life (QoL), and patient-reported outcome measurement. Although multidimensional assessment techniques hold promises, they are more challenging in their application than unidimensional ones. The authors comment on minimal standards when developing multidimensional CATs. METHODS: Prompted by pioneering papers published in QLR, the authors reflect on existing guidance and discussions from different psychometric communities, including guidelines developed for unidimensional CATs in the PROMIS project. RESULTS: The commentary focuses on two key topics: (1) the design, evaluation, and calibration of multidimensional item banks and (2) how to study the efficiency and precision of a multidimensional item bank. The authors suggest that the development of a carefully designed and calibrated item bank encompasses a construction phase and a psychometric phase. With respect to efficiency and precision, item banks should be large enough to provide adequate precision over the full range of the latent constructs. Therefore CAT performance should be studied as a function of the latent constructs and with reference to relevant benchmarks. Solutions are also suggested for simulation studies using real data, which often result in too optimistic evaluations of an item bank's efficiency and precision. DISCUSSION: Multidimensional CAT applications are promising but complex statistical assessment tools which necessitate detailed theoretical frameworks and methodological scrutiny when testing their appropriateness for practical applications. The authors advise researchers to evaluate item banks with a broad set of methods, describe their choices in detail, and substantiate their approach for validation

Study protocol: EXERcise and Cognition In Sedentary adults with Early-ONset dementia (EXERCISE-ON)

<p>Abstract</p> <p>Background</p> <p>Although the development of early-onset dementia is a radical and invalidating experience for both patient and family there are hardly any non-pharmacological studies that focus on this group of patients. One type of a non-pharmacological intervention that appears to have a beneficial effect on cognition in older persons without dementia and older persons at risk for dementia is exercise. In view of their younger age early-onset dementia patients may be well able to participate in an exercise program. The main aim of the EXERCISE-ON study is to assess whether exercise slows down the progressive course of the symptoms of dementia.</p> <p>Methods/Design</p> <p>One hundred and fifty patients with early-onset dementia are recruited. After completion of the baseline measurements, participants living within a 50 kilometre radius to one of the rehabilitation centres are randomly assigned to either an <it>aerobic exercise program in a rehabilitation centre</it> or a <it>flexibility and relaxation program in a rehabilitation centre</it>. Both programs are applied three times a week during 3 months. Participants living outside the 50 kilometre radius are included in a feasibility study where participants join in a <it>daily physical activity program set at home making use of pedometers</it>. Measurements take place at baseline (entry of the study), after three months (end of the exercise program) and after six months (follow-up). Primary outcomes are cognitive functioning; psychomotor speed and executive functioning; (instrumental) activities of daily living, and quality of life. Secondary outcomes include physical, neuropsychological, and rest-activity rhythm measures.</p> <p>Discussion</p> <p>The EXERCISE-ON study is the first study to offer exercise programs to patients with early-onset dementia. We expect this study to supply evidence regarding the effects of exercise on the symptoms of early-onset dementia, influencing quality of life.</p> <p>Trial registration</p> <p>The present study is registered within The Netherlands National Trial Register (ref: NTR2124)</p

The Belle II physics book

The Belle II detector will provide a major step forward in precision heavy flavor physics, quarkonium and exotic states, searches for dark sectors, and many other areas. The sensitivity to a large number of key observables can be improved by about an order of magnitude compared to the current measurements, and up to two orders in very clean search measurements. This increase in statistical precision arises not only due to the increased luminosity, but also from improved detector efficiency and precision for many channels. Many of the most interesting observables tend to have very small theoretical uncertainties that will therefore not limit the physics reach. This book has presented many new ideas for measurements, both to elucidate the nature of current anomalies seen in flavor, and to search for new phenomena in a plethora of observables that will become accessible with the Belle II dataset. The simulation used for the studiesinthis book was state ofthe artat the time, though weare learning a lot more about the experiment during the commissioning period. The detector is in operation, and working spectacularly well

Averages of b-hadron, c-hadron, and tau-lepton properties as of 2018 Heavy Flavor Averaging Group (HFLAV)

This paper reports world averages of measurements of b-hadron, c-hadron, and τ -lepton properties obtained by the Heavy Flavour Averaging Group using results available through September 2018. In rare cases, significant results obtained several months later are also used. For the averaging, common input parameters used in the various analyses are adjusted (rescaled) to common values, and known correlations are taken into account. The averages include branching fractions, lifetimes, neutral meson mixing parameters, C P violation parameters, parameters of semileptonic decays, and Cabibbo–Kobayashi–Maskawa matrix elements

De Novo Truncating Mutations in WASF1 Cause Intellectual Disability with Seizures.

Next-generation sequencing has been invaluable in the elucidation of the genetic etiology of many subtypes of intellectual disability in recent years. Here, using exome sequencing and whole-genome sequencing, we identified three de novo truncating mutations in WAS protein family member 1 (WASF1) in five unrelated individuals with moderate to profound intellectual disability with autistic features and seizures. WASF1, also known as WAVE1, is part of the WAVE complex and acts as a mediator between Rac-GTPase and actin to induce actin polymerization. The three mutations connected by Matchmaker Exchange were c.1516C>T (p.Arg506Ter), which occurs in three unrelated individuals, c.1558C>T (p.Gln520Ter), and c.1482delinsGCCAGG (p.Ile494MetfsTer23). All three variants are predicted to partially or fully disrupt the C-terminal actin-binding WCA domain. Functional studies using fibroblast cells from two affected individuals with the c.1516C>T mutation showed a truncated WASF1 and a defect in actin remodeling. This study provides evidence that de novo heterozygous mutations in WASF1 cause a rare form of intellectual disability

QCD and strongly coupled gauge theories : challenges and perspectives

We highlight the progress, current status, and open challenges of QCD-driven physics, in theory and in experiment. We discuss how the strong interaction is intimately connected to a broad sweep of physical problems, in settings ranging from astrophysics and cosmology to strongly coupled, complex systems in particle and condensed-matter physics, as well as to searches for physics beyond the Standard Model. We also discuss how success in describing the strong interaction impacts other fields, and, in turn, how such subjects can impact studies of the strong interaction. In the course of the work we offer a perspective on the many research streams which flow into and out of QCD, as well as a vision for future developments.Peer reviewe