Neurobehavioral consequences of chronic intrauterine opioid exposure in infants and preschool children: a systematic review and meta-analysis

<b>Background</b><p></p> It is assumed within the accumulated literature that children born of pregnant opioid dependent mothers have impaired neurobehavioral function as a consequence of chronic intrauterine opioid use.<p></p> <b>Methods</b><p></p> Quantitative and systematic review of the literature on the consequences of chronic maternal opioid use during pregnancy on neurobehavioral function of children was conducted using the Meta-analysis of Observational Studies in Epidemiology (MOOSE) and the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. We searched Cinahl, EMBASE, PsychINFO and MEDLINE between the periods of January 1995 to January 2012.<p></p> <b>Results</b><p></p> There were only 5 studies out of the 200 identified that quantitatively reported on neurobehavioral function of children after maternal opioid use during pregnancy. All 5 were case control studies with the number of exposed subjects within the studies ranging from 33–143 and 45–85 for the controls. This meta-analysis showed no significant impairments, at a non-conservative significance level of p < 0.05, for cognitive, psychomotor or observed behavioural outcomes for chronic intra-uterine exposed infants and pre-school children compared to non-exposed infants and children. However, all domains suggested a trend to poor outcomes in infants/children of opioid using mothers. The magnitude of all possible effects was small according to Cohen’s benchmark criteria.<p></p> <b>Conclusions</b><p></p> Chronic intra-uterine opioid exposed infants and pre-school children experienced no significant impairment in neurobehavioral outcomes when compared to non-exposed peers, although in all domains there was a trend to poorer outcomes. The findings of this review are limited by the small number of studies analysed, the heterogenous populations and small numbers within the individual studies. Longitudinal studies are needed to determine if any neuropsychological impairments appear after the age of 5 years and to help investigate further the role of environmental risk factors on the effect of ‘core’ phenotypes

Framework and indicator testing protocol for developing and piloting quality indicators for the UK quality and outcomes framework

Contains fulltext : 96936.pdf (publisher's version ) (Open Access)BACKGROUND: Quality measures should be subjected to a testing protocol before being used in practice using key attributes such as acceptability, feasibility and reliability, as well as identifying issues derived from actual implementation and unintended consequences. We describe the methodologies and results of an indicator testing protocol (ITP) using data from proposed quality indicators for the United Kingdom Quality and Outcomes Framework (QOF). METHODS: The indicator testing protocol involved a multi-step and methodological process: 1) The RAND/UCLA Appropriateness Method, to test clarity and necessity, 2) data extraction from patients' medical records, to test technical feasibility and reliability, 3) diaries, to test workload, 4) cost-effectiveness modelling, and 5) semi-structured interviews, to test acceptability, implementation issues and unintended consequences. Testing was conducted in a sample of representative family practices in England. These methods were combined into an overall recommendation for each tested indicator. RESULTS: Using an indicator testing protocol as part of piloting was seen as a valuable way of testing potential indicators in 'real world' settings. Pilot 1 (October 2009-March 2010) involved thirteen indicators across six clinical domains and twelve indicators passed the indicator testing protocol. However, the indicator testing protocol identified a number of implementation issues and unintended consequences that can be rectified or removed prior to national roll out. A palliative care indicator is used as an exemplar of the value of piloting using a multiple attribute indicator testing protocol - while technically feasible and reliable, it was unacceptable to practice staff and raised concerns about potentially causing actual patient harm. CONCLUSIONS: This indicator testing protocol is one example of a protocol that may be useful in assessing potential quality indicators when adapted to specific country health care settings and may be of use to policy-makers and researchers worldwide to test the likely effect of implementing indicators prior to roll out. It builds on and codifies existing literature and other testing protocols to create a field testing methodology that can be used to produce country specific quality indicators for pay-for-performance or quality improvement schemes

Eta Carinae and the Luminous Blue Variables

We evaluate the place of Eta Carinae amongst the class of luminous blue variables (LBVs) and show that the LBV phenomenon is not restricted to extremely luminous objects like Eta Car, but extends luminosities as low as log(L/Lsun) = 5.4 - corresponding to initial masses ~25 Msun, and final masses as low as ~10-15 Msun. We present a census of S Doradus variability, and discuss basic LBV properties, their mass-loss behaviour, and whether at maximum light they form pseudo-photospheres. We argue that those objects that exhibit giant Eta Car-type eruptions are most likely related to the more common type of S Doradus variability. Alternative atmospheric models as well as sub-photospheric models for the instability are presented, but the true nature of the LBV phenomenon remains as yet elusive. We end with a discussion on the evolutionary status of LBVs - highlighting recent indications that some LBVs may be in a direct pre-supernova state, in contradiction to the standard paradigm for massive star evolution.Comment: 27 pages, 6 figures, Review Chapter in "Eta Carinae and the supernova imposters" (eds R. Humphreys and K. Davidson) new version submitted to Springe

Development of paediatric quality of inpatient care indicators for low-income countries - A Delphi study

BACKGROUND: Indicators of quality of care for children in hospitals in low-income countries have been proposed, but information on their perceived validity and acceptability is lacking. METHODS: Potential indicators representing structural and process aspects of care for six common conditions were selected from existing, largely qualitative WHO assessment tools and guidelines. We employed the Delphi technique, which combines expert opinion and existing scientific information, to assess their perceived validity and acceptability. Panels of experts, one representing an international panel and one a national (Kenyan) panel, were asked to rate the indicators over 3 rounds and 2 rounds respectively according to a variety of attributes. RESULTS: Based on a pre-specified consensus criteria most of the indicators presented to the experts were accepted: 112/137(82%) and 94/133(71%) for the international and local panels respectively. For the other indicators there was no consensus; none were rejected. Most indicators were rated highly on link to outcomes, reliability, relevance, actionability and priority but rated more poorly on feasibility of data collection under routine conditions. There was moderate to substantial agreement between the two panels of experts. CONCLUSIONS: This Delphi study provided evidence for the perceived usefulness of most of a set of measures of quality of hospital care for children proposed for use in low-income countries. However, both international and local experts expressed concerns that data for many process-based indicators may not currently be available. The feasibility of widespread quality assessment and responsiveness of indicators to intervention should be examined as part of continued efforts to improve approaches to informative hospital quality assessment

Synthetic microparticles conjugated with VEGF165 improve the survival of endothelial progenitor cells via microRNA-17 inhibition

Several cell-based therapies are under pre-clinical and clinical evaluation for the treatment of ischemic diseases. Poor survival and vascular engraftment rates of transplanted cells force them to work mainly via time-limited paracrine actions. Although several approaches, including the use of soluble vascular endothelial growth factor (sVEGF)-VEGF165, have been developed in the last 10 years to enhance cell survival, they showed limited efficacy. Here, we report a pro-survival approach based on VEGF-immobilized microparticles (VEGF-MPs). VEGF-MPs prolong VEGFR-2 and Akt phosphorylation in cord blood-derived late outgrowth endothelial progenitor cells (OEPCs). In vivo, OEPC aggregates containing VEGF-MPs show higher survival than those treated with sVEGF. Additionally, VEGF-MPs decrease miR-17 expression in OEPCs, thus increasing the expression of its target genes CDKN1A and ZNF652. The therapeutic effect of OEPCs is improved in vivo by inhibiting miR-17. Overall, our data show an experimental approach to improve therapeutic efficacy of proangiogenic cells for the treatment of ischemic diseases.Soluble vascular endothelial growth factor (VEGF) enhances vascular engraftment of transplanted cells but the efficacy is low. Here, the authors show that VEGF-immobilized microparticles prolong survival of endothelial progenitors in vitro and in vivo by downregulating miR17 and upregulating CDKN1A and ZNF652

Pdl1 Is a Putative Lipase that Enhances Photorhabdus Toxin Complex Secretion

The Toxin Complex (TC) is a large multi-subunit toxin first characterized in the insect pathogens Photorhabdus and Xenorhabdus, but now seen in a range of pathogens, including those of humans. These complexes comprise three protein subunits, A, B and C which in the Xenorhabdus toxin are found in a 4∶1∶1 stoichiometry. Some TCs have been demonstrated to exhibit oral toxicity to insects and have the potential to be developed as a pest control technology. The lack of recognisable signal sequences in the three large component proteins hinders an understanding of their mode of secretion. Nevertheless, we have shown the Photorhabdus luminescens (Pl) Tcd complex has been shown to associate with the bacteria's surface, although some strains can also release it into the surrounding milieu. The large number of tc gene homologues in Pl make study of the export process difficult and as such we have developed and validated a heterologous Escherichia coli expression model to study the release of these important toxins. In addition to this model, we have used comparative genomics between a strain that releases high levels of Tcd into the supernatant and one that retains the toxin on its surface, to identify a protein responsible for enhancing secretion and release of these toxins. This protein is a putative lipase (Pdl1) which is regulated by a small tightly linked antagonist protein (Orf53). The identification of homologues of these in other bacteria, linked to other virulence factor operons, such as type VI secretion systems, suggests that these genes represent a general and widespread mechanism for enhancing toxin release in Gram negative pathogens

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015

SummaryBackground The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defined criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specific DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI). Findings Between 1990 and 2015, global exposure to unsafe sanitation, household air pollution, childhood underweight, childhood stunting, and smoking each decreased by more than 25%. Global exposure for several occupational risks, high body-mass index (BMI), and drug use increased by more than 25% over the same period. All risks jointly evaluated in 2015 accounted for 57·8% (95% CI 56·6–58·8) of global deaths and 41·2% (39·8–42·8) of DALYs. In 2015, the ten largest contributors to global DALYs among Level 3 risks were high systolic blood pressure (211·8 million [192·7 million to 231·1 million] global DALYs), smoking (148·6 million [134·2 million to 163·1 million]), high fasting plasma glucose (143·1 million [125·1 million to 163·5 million]), high BMI (120·1 million [83·8 million to 158·4 million]), childhood undernutrition (113·3 million [103·9 million to 123·4 million]), ambient particulate matter (103·1 million [90·8 million to 115·1 million]), high total cholesterol (88·7 million [74·6 million to 105·7 million]), household air pollution (85·6 million [66·7 million to 106·1 million]), alcohol use (85·0 million [77·2 million to 93·0 million]), and diets high in sodium (83·0 million [49·3 million to 127·5 million]). From 1990 to 2015, attributable DALYs declined for micronutrient deficiencies, childhood undernutrition, unsafe sanitation and water, and household air pollution; reductions in risk-deleted DALY rates rather than reductions in exposure drove these declines. Rising exposure contributed to notable increases in attributable DALYs from high BMI, high fasting plasma glucose, occupational carcinogens, and drug use. Environmental risks and childhood undernutrition declined steadily with SDI; low physical activity, high BMI, and high fasting plasma glucose increased with SDI. In 119 countries, metabolic risks, such as high BMI and fasting plasma glucose, contributed the most attributable DALYs in 2015. Regionally, smoking still ranked among the leading five risk factors for attributable DALYs in 109 countries; childhood underweight and unsafe sex remained primary drivers of early death and disability in much of sub-Saharan Africa. Interpretation Declines in some key environmental risks have contributed to declines in critical infectious diseases. Some risks appear to be invariant to SDI. Increasing risks, including high BMI, high fasting plasma glucose, drug use, and some occupational exposures, contribute to rising burden from some conditions, but also provide opportunities for intervention. Some highly preventable risks, such as smoking, remain major causes of attributable DALYs, even as exposure is declining. Public policy makers need to pay attention to the risks that are increasingly major contributors to global burden. Funding Bill & Melinda Gates Foundation

Cross-Sectional Study into the Costs and Impact on Family Functioning of 4-Year-Old Children with Aggressive Behavior

Early-onset aggressive behavior is known for its negative developmental consequences, and the associated high costs for families, the health care system and wider society. Although the origins of aggressive behavior are to be found in early childhood, the costs incurred by aggressive behavior of young children have not been studied extensively. The present study aimed to investigate whether preschool children with a high level of aggressive behavior already differ in the generated amount of costs and impact on family functioning from children with lower levels of aggressive behavior. A population-based sample of 317 preschool children was divided into four groups with different levels of aggression (moderate, borderline, clinical). Parents filled out questionnaires to assess service use (lifetime and past 3 months) and impact on family functioning. Over the past 3 months as well as over the first 4 years of life, children with a clinical level of aggression were more costly than children with a low level of aggression (mean total costs over the past 3 months: low = €167,05 versus clinical € = 1034,83 and mean lifetime costs: low € = 817,37 versus clinical € = 1433,04), due to higher costs of services used by the child. In addition, families of children with a borderline or clinical level of aggressive behavior reported more impairment in their daily functioning than families of children with lower levels of aggression. The findings demonstrate that a high level of aggressive behavior results in high costs and impaired family functioning in the preschool years already

Conducting Online Expert panels: a feasibility and experimental replicability study

<p>Abstract</p> <p>Background</p> <p>This paper has two goals. First, we explore the feasibility of conducting online expert panels to facilitate consensus finding among a large number of geographically distributed stakeholders. Second, we test the replicability of panel findings across four panels of different size.</p> <p>Method</p> <p>We engaged 119 panelists in an iterative process to identify definitional features of Continuous Quality Improvement (CQI). We conducted four parallel online panels of different size through three one-week phases by using the RAND's ExpertLens process. In Phase I, participants rated potentially definitional CQI features. In Phase II, they discussed rating results online, using asynchronous, anonymous discussion boards. In Phase III, panelists re-rated Phase I features and reported on their experiences as participants.</p> <p>Results</p> <p>66% of invited experts participated in all three phases. 62% of Phase I participants contributed to Phase II discussions and 87% of them completed Phase III. Panel disagreement, measured by the mean absolute deviation from the median (MAD-M), decreased after group feedback and discussion in 36 out of 43 judgments about CQI features. Agreement between the four panels after Phase III was fair (four-way kappa = 0.36); they agreed on the status of five out of eleven CQI features. Results of the post-completion survey suggest that participants were generally satisfied with the online process. Compared to participants in smaller panels, those in larger panels were more likely to agree that they had debated each others' view points.</p> <p>Conclusion</p> <p>It is feasible to conduct online expert panels intended to facilitate consensus finding among geographically distributed participants. The online approach may be practical for engaging large and diverse groups of stakeholders around a range of health services research topics and can help conduct multiple parallel panels to test for the reproducibility of panel conclusions.</p