Improving the measurement of QALYs in dementia: developing patient- and carer-reported health state classification systems using Rasch analysis

Objectives: Cost-utility analysis is increasingly used to inform resource allocation. This requires a means of valuing health states before and after intervention. Although generic measures are typically used to generate values, these do not perform well with people with dementia. We report the development of a health state classification system amenable to valuation for use in studies of dementia, derived from the DEMQOL system, a measure of health-related quality of life in dementia by patient self-report (DEMQOL) and carer proxy-report (DEMQOL-Proxy). Methods: Factor analysis was used to determine the dimensional structure of DEMQOL and DEMQOL-Proxy. Rasch analysis was subsequently used to investigate item performance across factors in terms of item-level ordering, functioning across subgroups, model fit and severity-range coverage. This enabled the selection of one item from each factor for the classification system. A sample of people with a diagnosis of mild/moderate dementia (n=644) and a sample of carers of those with mild/moderate dementia (n=683) were used. Results: Factor analysis found different 5-factor solutions for DEMQOL and DEMQOL-Proxy. Following item reduction and selection using Rasch analysis, a 5-dimension classification for DEMQOL and a 4-dimension classification for DEMQOL-Proxy were developed. Each item contained 4 health state levels. Conclusion: Combining Rasch and classical psychometric analysis is a valid method of selecting items for dementia health state classifications from both the patient and carer perspectives. The next stage is to obtain preference weights so that the measure can be used in the economic evaluation of treatment, care and support arrangements for dementia.quality adjusted life years; health related quality of life; Rasch analysis; preference-based measures of health; health states; dementia

The Analgesic Effect of Oxytocin in Humans: A Double-Blind, Placebo-Controlled Cross-Over Study Using Laser-Evoked Potentials

Oxytocin is a neuropeptide regulating social‐affiliative and reproductive behaviour in mammals. Despite robust preclinical evidence for the antinociceptive effects and mechanisms of action of exogenous oxytocin, human studies have produced mixed results regarding the analgesic role of oxytocin and are yet to show a specific modulation of neural processes involved in pain perception. In the present study, we investigated the analgesic effects of 40 IU of intranasal oxytocin in 13 healthy male volunteers using a double‐blind, placebo‐controlled, cross‐over design and brief radiant heat pulses generated by an infrared laser that selectively activate Aδ‐ and C‐fibre nerve endings in the epidermis, at the same time as recording the ensuing laser‐evoked potentials (LEPs). We predicted that oxytocin would reduce subjective pain ratings and attenuate the amplitude of the N1, N2 and P2 components. We observed that oxytocin attenuated perceived pain intensity and the local peak amplitude of the N1 and N2 (but not of P2) LEPs, and increased the latency of the N2 component. Importantly, for the first time, the present study reports an association between the analgesic effect of oxytocin (reduction in subjective pain ratings) and the oxytocin‐induced modulation of cortical activity after noxious stimulation (attenuation of the N2 LEP). These effects indicate that oxytocin modulates neural processes contributing to pain perception. The present study reports preliminary evidence that is consistent with electrophysiological studies in rodents showing that oxytocin specifically modulates Aδ/C‐fibre nociceptive afferent signalling at the spinal level and provides further specificity to evidence obtained in humans indicating that oxytocin may be modulating pain experience by modulating activity in the cortical areas involved in pain processing

Science and health for all children with cancer

Each year approximately 429,000 children and adolescents aged 0-19 years are expected to develop cancer. Five-year survival rates exceed 80% for the 45,000 children with cancer in highincome countries (HIC), but are less than 30% for the 384,000 children in low- and middle-income countries (LMIC). Improved survival rates in HIC have been achieved through multidisciplinary care and research, with treatment regimens utilizing mostly generic medicines and optimized risk stratification. Children’s outcomes in LMIC can be improved by adapting effective treatments to local resources and clinical needs, and addressing common problems such as delayed diagnosis and treatment abandonment. By supporting local leaders to increase service capacity and achieve measurable clinical improvements, collaborative partnerships can stimulate governmental and nongovernmental investments. These approaches should bring the new WHO childhood cancer survival target of 60% within reach of all by 2030

Pediatric cancer care in Africa: SIOP Global Mapping Program report on economic and population indicators

Introduction Inalignment with the World Health Organization (WHO) Global Initiative for Childhood Cancer (GICC), the International Society of Pediatric Oncology initiated a program to map global pediatric oncology services. As survival rates in Africa are low and data are scant, this continent was mapped first to identify areas with greatest need. Methods Beginning November 2018, an electronic survey was sent to all known stakeholders, followed by email communications and internet searches to verify data. Availability of pediatric oncologists, chemotherapy, surgical expertise, and radiotherapy was correlated with geographic region, World Bank income status, Universal Health Coverage, population < 15 and < 24 years, percentage of gross domestic product spent on healthcare, and Human Development Index (HDI). Results Responses were received from 48/54 African countries. All three treatment modalities were reportedly available in 9/48 countries, whereas seven countries reported no pediatric oncology services. Negative correlations were detected between provision of all three services and geographic region (P = 0.01), younger median population age (P = 0.002), low-income country status (P = 0.045), and lower HDI (P < 0.001). Conclusion This study provides a comprehensive overview of pediatric oncology care in Africa, emphasizing marked disparities between countries: some have highly specialized services, whereas others have no services. A long-term strategy to eliminate disparities in African pediatric cancer care should be aligned with the WHO GICC aims and facilitated by SIOP Africa. Meeting abstracts SIOP maps pediatric oncology services in Africa to address inequalities in childhood cancer services. Geel J, Ranasinghe N, Davidson A, Challinor J, Howard S, Wollaert S, Myezo K, Renner L, Hessissen L, Bouffet E. 51st Annual Congress of the International Society of Paediatric Oncology (SIOP), Lyon, France, October 2019. Pediatric Blood and Cancer Vol 66 S219-S219. Pediatric cancer care in Africa: SIOP Global Mapping Program report on economic and population indicators

A bird's eye view of discard reforms: bird-borne cameras reveal seabird/fishery interactions.

notes: PMCID: PMC3590202types: Journal Article; Research Support, Non-U.S. Gov'tCopyright: © 2013 Votier et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Commercial capture fisheries produce huge quantities of offal, as well as undersized and unwanted catch in the form of discards. Declines in global catches and legislation to ban discarding will significantly reduce discards, but this subsidy supports a large scavenger community. Understanding the potential impact of declining discards for scavengers should feature in an eco-system based approach to fisheries management, but requires greater knowledge of scavenger/fishery interactions. Here we use bird-borne cameras, in tandem with GPS loggers, to provide a unique view of seabird/fishery interactions. 20,643 digital images (one min(-1)) from ten bird-borne cameras deployed on central place northern gannets Morus bassanus revealed that all birds photographed fishing vessels. These were large (>15 m) boats, with no small-scale vessels. Virtually all vessels were trawlers, and gannets were almost always accompanied by other scavenging birds. All individuals exhibited an Area-Restricted Search (ARS) during foraging, but only 42% of ARS were associated with fishing vessels, indicating much 'natural' foraging. The proportion of ARS behaviours associated with fishing boats were higher for males (81%) than females (30%), although the reasons for this are currently unclear. Our study illustrates that fisheries form a very important component of the prey-landscape for foraging gannets and that a discard ban, such as that proposed under reforms of the EU Common Fisheries Policy, may have a significant impact on gannet behaviour, particularly males. However, a continued reliance on 'natural' foraging suggests the ability to switch away from scavenging, but only if there is sufficient food to meet their needs in the absence of a discard subsidy.EU INTERREG project CHARM-IIINatural Environment Research CouncilAssociation for the Study of Animal Behaviour research gran

Incidence and predictors of treatment-related mortality in paediatric acute leukaemia in El Salvador

Survival rates among children with leukaemia in low-income countries are lower than those in high-income countries. This has been attributed in part to higher treatment-related mortality (TRM). We examined the demographics, treatment, and outcomes of paediatric patients in El Salvador with acute lymphoblastic leukaemia (ALL) or acute myeloid leukaemia (AML) to determine the incidence, causes, and risk factors for TRM. Two trained data managers collected data prospectively; no patients were excluded. Biological, socioeconomic and nutritional predictors were examined. A total of 469 patients with ALL and 78 patients with AML were included. The 2-year cumulative incidence of TRM was significantly higher among children with AML (35.4±6.4%) than those with ALL (12.5±1.7%; P<0.0001). However, the proportion of deaths attributable to the toxicity of treatment did not differ significantly between AML (25/47, 53.2%) and ALL (55/107, 51.4%; P=0.98). Among children with ALL, low monthly income (P=0.04) and low parental education (P=0.02) significantly increased the risk of TRM. Among children with AML, biological, socioeconomic, and nutritional variables were not associated with TRM. In this low-income country, toxic death significantly contributes to mortality in both ALL and AML. A better understanding of the effect of socioeconomic status on TRM may suggest specific strategies for patients with ALL

The Relationship between Therapeutic Alliance and Service User Satisfaction in Mental Health Inpatient Wards and Crisis House Alternatives: A Cross-Sectional Study

Background Poor service user experiences are often reported on mental health inpatient wards. Crisis houses are an alternative, but evidence is limited. This paper investigates therapeutic alliances in acute wards and crisis houses, exploring how far stronger therapeutic alliance may underlie greater client satisfaction in crisis houses. Methods and Findings Mixed methods were used. In the quantitative component, 108 crisis house and 247 acute ward service users responded to measures of satisfaction, therapeutic relationships, informal peer support, recovery and negative events experienced during the admission. Linear regressions were conducted to estimate the association between service setting and measures, and to model the factors associated with satisfaction. Qualitative interviews exploring therapeutic alliances were conducted with service users and staff in each setting and analysed thematically. Results We found that therapeutic alliances, service user satisfaction and informal peer support were greater in crisis houses than on acute wards, whilst self-rated recovery and numbers of negative events were lower. Adjusted multivariable analyses suggest that therapeutic relationships, informal peer support and negative experiences related to staff may be important factors in accounting for greater satisfaction in crisis houses. Qualitative results suggest factors that influence therapeutic alliances include service user perceptions of basic human qualities such as kindness and empathy in staff and, at service level, the extent of loss of liberty and autonomy. Conclusions and Implications We found that service users experience better therapeutic relationships and higher satisfaction in crisis houses compared to acute wards, although we cannot exclude the possibility that differences in service user characteristics contribute to this. This finding provides some support for the expansion of crisis house provision. Further research is needed to investigate why acute ward service users experience a lack of compassion and humanity from ward staff and how this could be changed

Boosting Long-term Memory via Wakeful Rest: Intentional Rehearsal is not Necessary, Automatic Consolidation is Sufficient.

<div><p>People perform better on tests of delayed free recall if learning is followed immediately by a short wakeful rest than by a short period of sensory stimulation. Animal and human work suggests that wakeful resting provides optimal conditions for the consolidation of recently acquired memories. However, an alternative account cannot be ruled out, namely that wakeful resting provides optimal conditions for intentional rehearsal of recently acquired memories, thus driving superior memory. Here we utilised non-recallable words to examine whether wakeful rest boosts long-term memory, even when new memories could not be rehearsed intentionally during the wakeful rest delay. The probing of non-recallable words requires a recognition paradigm. Therefore, we first established, via Experiment 1, that the rest-induced boost in memory observed via free recall can be replicated in a recognition paradigm, using concrete nouns. In Experiment 2, participants heard 30 non-recallable non-words, presented as ‘foreign names in a bridge club abroad’ and then either rested wakefully or played a visual spot-the-difference game for 10 minutes. Retention was probed via recognition at two time points, 15 minutes and 7 days after presentation. As in Experiment 1, wakeful rest boosted recognition significantly, and this boost was maintained for at least 7 days. Our results indicate that the enhancement of memory via wakeful rest is <i>not</i> dependent upon intentional rehearsal of learned material during the rest period. We thus conclude that consolidation is <i>sufficient</i> for this rest-induced memory boost to emerge. We propose that wakeful resting allows for superior memory consolidation, resulting in stronger and/or more veridical representations of experienced events which can be detected via tests of free recall and recognition.</p></div

Blood pressure variability and cardiovascular risk in the PROspective study of pravastatin in the elderly at risk (PROSPER)

Variability in blood pressure predicts cardiovascular disease in young- and middle-aged subjects, but relevant data for older individuals are sparse. We analysed data from the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) study of 5804 participants aged 70–82 years with a history of, or risk factors for cardiovascular disease. Visit-to-visit variability in blood pressure (standard deviation) was determined using a minimum of five measurements over 1 year; an inception cohort of 4819 subjects had subsequent in-trial 3 years follow-up; longer-term follow-up (mean 7.1 years) was available for 1808 subjects. Higher systolic blood pressure variability independently predicted long-term follow-up vascular and total mortality (hazard ratio per 5 mmHg increase in standard deviation of systolic blood pressure = 1.2, 95% confidence interval 1.1–1.4; hazard ratio 1.1, 95% confidence interval 1.1–1.2, respectively). Variability in diastolic blood pressure associated with increased risk for coronary events (hazard ratio 1.5, 95% confidence interval 1.2–1.8 for each 5 mmHg increase), heart failure hospitalisation (hazard ratio 1.4, 95% confidence interval 1.1–1.8) and vascular (hazard ratio 1.4, 95% confidence interval 1.1–1.7) and total mortality (hazard ratio 1.3, 95% confidence interval 1.1–1.5), all in long-term follow-up. Pulse pressure variability was associated with increased stroke risk (hazard ratio 1.2, 95% confidence interval 1.0–1.4 for each 5 mmHg increase), vascular mortality (hazard ratio 1.2, 95% confidence interval 1.0–1.3) and total mortality (hazard ratio 1.1, 95% confidence interval 1.0–1.2), all in long-term follow-up. All associations were independent of respective mean blood pressure levels, age, gender, in-trial treatment group (pravastatin or placebo) and prior vascular disease and cardiovascular disease risk factors. Our observations suggest variability in diastolic blood pressure is more strongly associated with vascular or total mortality than is systolic pressure variability in older high-risk subjects