Predicting the outcome of conservative (non-surgical) voice therapy for adults with laryngeal pathologies associated with hyperfunctional voice use

Health Services Research Fund & Health Care and Promotion Fund: Research Dissemination Reports (Series 8)published_or_final_versio

Impact of prematurity on long-stay paediatric intensive care unit admissions in England 2008-2018

BACKGROUND: Survival following extreme preterm birth has improved, potentially increasing the number of children with ongoing morbidity requiring intensive care in childhood. Previous single-centre studies have suggested that long-stay admissions in paediatric intensive care units (PICUs) are increasing. We aimed to examine trends in long-stay admissions (≥28 days) to PICUs in England, outcomes for this group (including mortality and PICU readmission), and to determine the contribution of preterm-born children to the long-stay population, in children aged <2 years. METHODS: Data was obtained from the Paediatric Intensive Care Audit Network (PICANet) for all children <2 years admitted to National Health Service PICUs from 1/1/2008 to 31/12/2018 in England. We performed descriptive analysis of child characteristics and PICU outcomes. RESULTS: There were 99,057 admissions from 67,615 children. 2,693 children (4.0%) had 3,127 long-stays. Between 2008 and 2018 the annual number of long-stay admissions increased from 225 (2.7%) to 355 (4.0%), and the proportion of bed days in PICUs occupied by long-stay admissions increased from 24.2% to 33.2%. Of children with long-stays, 33.5% were born preterm, 53.5% were born at term, and 13.1% had missing data for gestational age. A considerable proportion of long-stay children required PICU readmission before two years of age (76.3% for preterm-born children). Observed mortality during any admission was also disproportionately greater for long-stay children (26.5% for term-born, 24.8% for preterm-born) than the overall rate (6.3%). CONCLUSIONS: Long-stays accounted for an increasing proportion of PICU activity in England between 2008 and 2018. Children born preterm were over-represented in the long-stay population compared to the national preterm birth rate (8%). These results have significant implications for future research into paediatric morbidity, and for planning future PICU service provision

Quantitative systems pharmacology analysis of drug combination and scaling to humans: the interaction between noradrenaline and vasopressin in vasoconstriction

Background and PurposeDevelopment of combination therapies has received significant interest in recent years. Previously, a two‐receptor one‐transducer (2R‐1T) model was proposed to characterize drug interactions with two receptors that lead to the same phenotypic response through a common transducer pathway. We applied, for the first time, the 2R‐1T model to characterize the interaction of noradrenaline and arginine‐vasopressin on vasoconstriction and performed inter‐species scaling to humans using this mechanism‐based model. Experimental ApproachContractile data were obtained from in vitro rat small mesenteric arteries after exposure to single or combined challenges of noradrenaline and arginine‐vasopressin with or without pretreatment with the irreversible α‐adrenoceptor antagonist, phenoxybenzamine. Data were analysed using the 2R‐1T model to characterize the observed exposure–response relationships and drug–drug interaction. The model was then scaled to humans by accounting for differences in receptor density. Key ResultsWith receptor affinities set to published values, the 2R‐1T model satisfactorily characterized the interaction between noradrenaline and arginine‐vasopressin in rat small mesenteric arteries (relative standard error ≤20%), as well as the effect of phenoxybenzamine. Furthermore, after scaling the model to human vascular tissue, the model also adequately predicted the interaction between both agents on human renal arteries. Conclusions and ImplicationsThe 2R‐1T model can be of relevance to quantitatively characterize the interaction between two drugs that interact via different receptors and a common transducer pathway. Its mechanistic properties are valuable for scaling the model across species. This approach is therefore of significant value to rationally optimize novel combination treatments. Pharmacolog

Characterizing the kinetics of presepsin and associated inflammatory biomarkers in human endotoxemia

In this study, we describe the kinetics of a new potential inflammatory biomarker, presepsin, together with a panel of well-established biomarkers in a human endotoxemia study. We evaluated biomarker correlations and identified combinations that could hold valuable insights regarding the state of infection.Pharmacolog

Community health center efficiency: The role of grant revenue in health center efficiency

Abstract: Objective: To test the relationship between external environments, organizational characteristics, and technical efficiency in federally qualified health centers (FQHCs). We tested the relationship between grant revenue and technical efficiency in FQHCs. Principal Findings: Increased grant revenues did not increase the probability that a health center would be on the efficiency frontier. However, increased grant revenues had a negative association with technical efficiency for health centers that were not fully efficient. Data Conclusion: If all health centers were operating efficiently, anywhere from 39 to 45 million patient encounters could have been delivered instead of the actual total of 29 million in 2007. Policy makers should consider tying grant revenues to performance indicators, and future work is needed to understand the mechanisms through which diseconomies of scale are present in FQHCs

Le Web du Goupil.

National audienc

Cloud cover amplifies the sleep-suppressing effect of artificial light at night in geese

In modern society the night sky is lit up not only by the moon but also by artificial light devices. Both of these light sources can have a major impact on wildlife physiology and behaviour. For example, a number of bird species were found to sleep several hours less under full moon compared to new moon and a similar sleep-suppressing effect has been reported for artificial light at night (ALAN). Cloud cover at night can modulate the light levels perceived by wildlife, yet, in opposite directions for ALAN and moon. While clouds will block moon light, it may reflect and amplify ALAN levels and increases the night glow in urbanized areas. As a consequence, cloud cover may also modulate the sleep-suppressing effects of moon and ALAN in different directions. In this study we therefore measured sleep in barnacle geese (Branta leucopsis) under semi-natural conditions in relation to moon phase, ALAN and cloud cover. Our analysis shows that, during new moon nights stronger cloud cover was indeed associated with increased ALAN levels at our study site. In contrast, light levels during full moon nights were fairly constant, presumably because of moonlight on clear nights or because of reflected artificial light on cloudy nights. Importantly, cloud cover caused an estimated 24.8% reduction in the amount of night-time NREM sleep from nights with medium to full cloud cover, particularly during new moon when sleep was unaffected by moon light. In conclusion, our findings suggest that cloud cover can, in a rather dramatic way, amplify the immediate effects of ALAN on wildlife. Sleep appears to be highly sensitive to ALAN and may therefore be a good indicator of its biological effects.ISSN:0269-7491ISSN:1878-2450ISSN:1873-642

Intracranial bleeding due to vitamin K deficiency: advantages of using a pediatric intensive care registry

Item does not contain fulltextAIM: To determine the incidence of late intracranial vitamin K deficiency bleeding (VKDB) in The Netherlands using the Dutch Pediatric Intensive Care Evaluation (PICE) registry. METHODS: The PICE registry was used to identify all infants who were admitted to a Dutch pediatric intensive care unit (PICU) with intracranial bleeding between 1 January 2004 and 31 December 2007. Cases of confirmed late intracranial VKDB were used to calculate the incidence for each year. To estimate the completeness of ascertainment of the PICE registry, data from 2005 were compared with general surveillance data from that year. RESULTS: In the 4-year study period, 16/64 (25%) of the infants admitted with intracranial bleeding had late intracranial VKDB, resulting in an overall incidence of 2.1/100,000 live births (95% confidence interval 1.2-3.5). The single-year incidence varied markedly between 0.5 and 3.3 per 100,000 live births. All five ascertained cases in 2005 were identified using the PICE registry, while general surveillance identified only three. CONCLUSIONS: The PICE registry allows ongoing monitoring of the incidence of late intracranial VKDB and appears to be associated with a higher rate of completeness than general surveillance. We propose the use of pediatric intensive care registries to assess the efficacy of national vitamin K prophylactic regimens