The potential of the Child Health Utility 9D Index as an outcome measure for child dental health

Background The Child Health Utility 9D (CHU9D) is a relatively new generic child health-related quality of life measure (HRQoL)—designed to be completed by children—which enables the calculation of utility values. The aim is to investigate the use of the CHU9D Index as an outcome measure for child dental health in New Zealand. Method A survey was conducted of children aged between 6 and 9 years attending for routine dental examinations in community clinics in Dunedin (New Zealand) in 2012. The CHU9D, a HRQoL, was used, along with the Child Perceptions Questionnaire (CPQ), a validated oral health-related quality of life (OHRQoL) measure. Socio-demographic characteristics (sex, age, ethnicity and household deprivation) were recorded. Dental therapists undertook routine clinical examinations, with charting recorded for each child for decayed, missing and filled deciduous teeth (dmft) at the d3 level. Results One hundred and forty 6-to-9-year-olds (50.7% female) took part in the study (93.3% participation rate). The mean d3mft was 2.4 (SD = 2.6; range 0 to 9). Both CHU9D and CPQ detected differences in the impact of dental caries, with scores in the expected direction: children who presented with caries had higher scores (indicating poorer OHRQoL) than those who were free of apparent caries. Children with no apparent caries had a higher mean CHU9D score than those with caries (indicating better HRQoL). The difference for the CPQ was statistically significant, but for CHU9D the difference was not significant. When the two indices were compared, there was a significant difference in mean CHU9D scores by the prevalence of CPQ and subscale impacts with children experiencing no impacts having mean CHU9D scores closer to 1.0 (representing perfect health). Conclusion The CHU9D may be useful in dental research. Further exploration in samples with different caries experience is required. The use of the CHU9D in child oral health studies will enable the calculation of quality-adjusted life years (QALYs) for use in economic evaluation

Assessment-schedule matching in unanchored indirect treatment comparisons of progression-free survival in cancer studies

Background The timing of efficacy-related clinical events recorded at scheduled study visits in clinical trials are interval censored, with the interval duration pre-determined by the study protocol. Events may happen any time during that interval but can only be detected during a planned or unplanned visit. Disease progression in oncology is a notable example where the time to an event is affected by the schedule of visits within a study. This can become a source of bias when studies with varying assessment schedules are used in unanchored comparisons using methods such as matching-adjusted indirect comparisons. Objective We illustrate assessment-time bias (ATB) in a simulation study based on data from a recent study in second-line treatment for locally advanced or metastatic urothelial carcinoma, and present a method to adjust for differences in assessment schedule when comparing progression-free survival (PFS) against a competing treatment. Methods A multi-state model for death and progression was used to generate simulated death and progression times, from which PFS times were derived. PFS data were also generated for a hypothetical comparator treatment by applying a constant hazard ratio (HR) to the baseline treatment. Simulated PFS times for the two treatments were then aligned to different assessment schedules so that progression events were only observed at set visit times, and the data were analysed to assess the bias and standard error of estimates of HRs between two treatments with and without assessment-schedule matching (ASM). Results ATB is highly affected by the rate of the event at the first assessment time; in our examples, the bias ranged from 3 to 11% as the event rate increased. The proposed method relies on individual-level data from a study and attempts to adjust the timing of progression events to the comparator’s schedule by shifting them forward or backward without altering the patients’ actual follow-up time. The method removed the bias almost completely in all scenarios without affecting the precision of estimates of comparative effectiveness. Conclusions Considering the increasing use of unanchored comparative analyses for novel cancer treatments based on single-arm studies, the proposed method offers a relatively simple means of improving the accuracy of relative benefits of treatments on progression times

Comparing plasma and faecal measures of steroid hormones in Adelie penguins Pygoscelis adeliae

Physiological measurements of both stress and sex hormones are often used to estimate the consequences of natural or human-induced change in ecological studies of various animals. Different methods of hormone measurement exist, potentially explaining variation in results across studies; methods should be cross-validated to ensure that they correlate. We directly compared faecal and plasma hormone measurements for the first time in a wild free-living species, the Adelie penguin (Pygoscelis adeliae). Blood and faecal samples were simultaneously collected from individual penguins for comparison and assayed for testosterone and corticosterone (or their metabolites). Sex differences and variability within each measure, and correlation of values across measures were compared. For both hormones, plasma samples showed greater variation than faecal samples. Males had higher mean corticosterone concentrations than females, but the difference was only statistically significant in faecal samples. Plasma testosterone, but not faecal testosterone, was significantly higher in males than females. Correlation between sample types was poor overall, and weaker in females than in males, perhaps because measures from plasma represent hormones that are both free and bound to globulins, whereas measures from faeces represent only the free portion. Faecal samples also represent a cumulative measure of hormones over time, as opposed to a plasma ‘snapshot’ concentration. Our data indicate that faecal sampling appears more suitable for assessing baseline hormone concentrations, whilst plasma sampling may best define immediate responses to environmental events. Consequently, future studies should ensure that they select the most appropriate matrix and method of hormone measurement to answer their research questions

Feasibility, reliability and validity of the health-related quality of life instrument Child Health Utility 9D (CHU9D) among school-aged children and adolescents in Sweden

Background This study was conducted in a general population of schoolchildren in Sweden, with the aim to assess the psychometric properties of a generic preference-based health related quality of life (HRQoL) instrument, the Swedish Child Health Utility 9D (CHU9D), among schoolchildren aged 7–15 years, and in subgroups aged 7–9, 10–12 and 13–15 years. Methods In total, 486 school aged children, aged 7–15 years, completed a questionnaire including the CHU9D, the Pediatric quality of life inventory 4.0 (PedsQL), KIDSCREEN-10, questions on general health, long-term illness, and sociodemographic characteristics. Psychometric testing was undertaken of feasibility, internal consistency reliability, test–retest reliability, construct validity, factorial validity, concurrent validity, convergent validity and divergent validity. Results The CHU9D evidenced very few missing values, minimal ceiling, and no floor effects. The instrument achieved satisfactory internal consistency (Cronbach’s Alfa > 0.7) and strong test–retest reliability (r > 0.6). Confirmatory factor analyses supported the proposed one-factor structure of the CHU9D. For child algorithm, RMSEA = 0.05, CFI = 0.95, TLI = 0.94, and SRMR = 0.04. For adult algorithm RMSEA = 0.04, CFI = 0.96, TLI = 0.95, and SRMR = 0.04. The CHU9D utility value correlated moderately or strongly with KIDSCREEN-10 and PedsQL total scores (r > 0.5–0.7). The CHU9D discriminated as anticipated on health and on three of five sociodemographic characteristics (sex, age, and custody arrangement, but not socioeconomic status and ethnic origin). Conclusions This study provides evidence that the Swedish CHU9D is a feasible, reliable and valid measure of preference-based HRQoL in children. The study furthermore suggests that the CHU9D is appropriate for use among children 7–15 years of age in the general population, as well as among subgroups aged 7– 9, 10–12 and 13–15 years

At the edge of intonation: the interplay of utterance-final F0 movements and voiceless fricative sounds

The paper is concerned with the 'edge of intonation' in a twofold sense. It focuses on utterance-final F0 movements and crosses the traditional segment-prosody divide by investigating the interplay of F0 and voiceless fricatives in speech production. An experiment was performed for German with four types of voiceless fricatives: /f/, /s/, /ʃ/ and /x/. They were elicited with scripted dialogues in the contexts of terminal falling statement and high rising question intonations. Acoustic analyses show that fricatives concluding the high rising question intonations had higher mean centres of gravity (CoGs), larger CoG ranges and higher noise energy levels than fricatives concluding the terminal falling statement intonations. The different spectral-energy patterns are suitable to induce percepts of a high 'aperiodic pitch' at the end of the questions and of a low 'aperiodic pitch' at the end of the statements. The results are discussed with regard to the possible existence of 'segmental intonation' and its implication for F0 truncation and the segment-prosody dichotomy, in which segments are the alleged troublemakers for the production and perception of intonation

Funding kidney research as a public health priority: challenges and opportunities

Medical societies have a social responsibility to disseminate knowledge and inform health authorities on threats to public health posed by various diseases. Advocacy for health protection programmes and for medical research funding is now embedded into the missions of most scientific societies. To promote kidney research funding in Europe, the European Renal Association - European Dialysis and Transplant Association (ERA-EDTA), rather than acting as an individual society advocating for the fight against kidney disease, has actively helped to create an alliance of national associations centred on kidney diseases, the European Kidney Health Alliance (EKHA), and joined the Biomedical Alliance (BMA). The ERA-EDTA is fully committed to supporting its working groups (WGs) and consortia of its members to allow them to produce valuable kidney research. The framing and formalization of projects, and the regulatory issues related to submission to the European Commission, are complex. To help WGs to gain expert advice from agencies with specific know-how, the ERA-EDTA has adopted a competitive approach. The best research projects proposed by WGs and consortia of other European investigators will receive seed funding to cover the costs of consultancy by expert agencies. Via its broader platforms, the EKHA and the BMA, the ERA-EDTA will strive towards broader recognition of kidney disease and related clusters of non-communicable diseases, by European and national agencies, as major threats to the qualities of life of their populations and their economies.Clinical epidemiolog

Liposomes in Biology and Medicine

Drug delivery systems (DDS) have become important tools for the specific delivery of a large number of drug molecules. Since their discovery in the 1960s liposomes were recognized as models to study biological membranes and as versatile DDS of both hydrophilic and lipophilic molecules. Liposomes--nanosized unilamellar phospholipid bilayer vesicles--undoubtedly represent the most extensively studied and advanced drug delivery vehicles. After a long period of research and development efforts, liposome-formulated drugs have now entered the clinics to treat cancer and systemic or local fungal infections, mainly because they are biologically inert and biocompatible and practically do not cause unwanted toxic or antigenic reactions. A novel, up-coming and promising therapy approach for the treatment of solid tumors is the depletion of macrophages, particularly tumor associated macrophages with bisphosphonate-containing liposomes. In the advent of the use of genetic material as therapeutic molecules the development of delivery systems to target such novel drug molecules to cells or to target organs becomes increasingly important. Liposomes, in particular lipid-DNA complexes termed lipoplexes, compete successfully with viral gene transfection systems in this field of application. Future DDS will mostly be based on protein, peptide and DNA therapeutics and their next generation analogs and derivatives. Due to their versatility and vast body of known properties liposome-based formulations will continue to occupy a leading role among the large selection of emerging DDS

Diving into the vertical dimension of elasmobranch movement ecology

Knowledge of the three-dimensional movement patterns of elasmobranchs is vital to understand their ecological roles and exposure to anthropogenic pressures. To date, comparative studies among species at global scales have mostly focused on horizontal movements. Our study addresses the knowledge gap of vertical movements by compiling the first global synthesis of vertical habitat use by elasmobranchs from data obtained by deployment of 989 biotelemetry tags on 38 elasmobranch species. Elasmobranchs displayed high intra- and interspecific variability in vertical movement patterns. Substantial vertical overlap was observed for many epipelagic elasmobranchs, indicating an increased likelihood to display spatial overlap, biologically interact, and share similar risk to anthropogenic threats that vary on a vertical gradient. We highlight the critical next steps toward incorporating vertical movement into global management and monitoring strategies for elasmobranchs, emphasizing the need to address geographic and taxonomic biases in deployments and to concurrently consider both horizontal and vertical movements