Pain in Intellectually Disabled Children: Towards Evidence-Based Pharmacotherapy?

This critical opinion article deals with the challenges of finding the most effective pharmacotherapeutic options for the management of pain in intellectually disabled children and provides recommendations for clinical practice and research. Intellectual disability can be caused by a wide variety of underlying diseases and may be associated with congenital anomalies such as cardiac defects, small-bowel obstructions or limb abnormalities as well as with comorbidities such as scoliosis, gastro-esophageal reflux disease, spasticity, and epilepsy. These conditions themselves or any necessary surgical interventions are sources of pain. Epilepsy often requires chronic pharmacological treatment with antiepileptic drugs. These antiepileptic drugs can potentially cause drug–drug interactions with analgesic drugs. It is unfortunate that children with intellectual disabilities often cannot communicate pain to caregivers. Although these children are at high risk of experiencing pain, researchers nevertheless often have to exclude them from trials on pain management because of ethical considerations. We therefore make a plea for prescribers, researchers, patient organizations, pharmaceutical companies, and policy makers to study evidence-based, safe and effective pharmacotherapy in these children through properly designed studies. In the meantime, parents and clinicians must resort to validated pain assessment tools such as the revised FLACC scale

Parameterization of oceanic whitecap fraction based on satellite observations

In this study, the utility of satellite-based white-cap fraction (W) data for the prediction of sea spray aerosol (SSA) emission rates is explored. More specifically, the study aims at evaluating how an account for natural variability of whitecaps in the W parameterization would affect SSA mass flux predictions when using a sea spray source function (SSSF) based on the discrete whitecap method. The starting point is a data set containing W data for 2006 together with matching wind speed U-10 and sea surface temperature (SST) T. Whitecap fraction W was estimated from observations of the ocean surface brightness temperature T-B by satellite-borne radiometers at two frequencies (10 and 37 GHz). A global-scale assessment of the data set yielded approximately quadratic correlation between W and U-10. A new global W(U-10) parameterization was developed and used to evaluate an intrinsic correlation between W and U-10 that could have been introduced while estimating W from T B. A regional-scale analysis over different seasons indicated significant differences of the coefficients of regional W(U-10) relationships. The effect of SST on W is explicitly accounted for in a new W(U-10, T) parameterization. The analysis of W values obtained with the new W(U-10) and W(U-10, T) parameterizations indicates that the influence of secondary factors on W is for the largest part embedded in the exponent of the wind speed dependence. In addition, the W(U-10, T) parameterization is able to partially model the spread (or variability) of the satellite-based W data. The satellite-based parameterization W(U-10, T) was applied in an SSSF to estimate the global SSA emission rate. The thus obtained SSA production rate for 2006 of 4.4 x 10(12) kg year(-1) is within previously reported estimates, however with distinctly different spatial distribution.Peer reviewe

Usability and usefulness of a mobile health app for pregnancy-related work advice : mixed-methods approach

Acknowledgments The authors would like to thank all the pregnant participants who participated in the TA sessions and the employees of the obstetric care facilities. This pilot study received funding from ZonMw, the Netherlands Organization for Health Research and Development. This project is part of the Pregnancy and Birth Program.Peer reviewedPublisher PD

Anaesthesia and postoperative analgesia in surgical neonates with or without Downs syndrome: Is it really different?

BackgroundReports conflict on optimal postoperative analgesic treatment in children with intellectual disability. We retrospectively compared postoperative analgesics consumption between neonates with and without Downs syndrome in relation to anaesthesia requirements and pain scores. MethodsWe analysed hypnotic and analgesic drug administration, pain scores [COMFORT-Behaviour (COMFORT-B) scale], and duration of mechanical ventilation during the first 48 h after surgical repair of congenital duodenal obstruction in neonates, between 1999 and 2011. Data of 15 children with Downs syndrome were compared with data of 30 children without Downs syndrome. ResultsGeneral anaesthesia requirements did not differ. The median (inter-quartile range) maintenance dose of morphine during the first 24 h after operation was 9.5 (7.810.1) g kg -1 h -1 in the Downs syndrome group vs 7.7 (5.010.0) g kg -1 h -1 in the control group (P0.46). Morphine doses at postoperative day 2 and COMFORT-B scores at day 1 did not significantly differ between the two groups. COMFORT-B scores at day two were lower in children with Downs syndrome (P0.04). The duration of postoperative mechanical ventilation did not statistically differ between the two groups (P0.89). ConclusionsIn this study, neonates with and without Downs syndrome received adequate postoperative analgesia, as judged from comparable analgesic consumption and pain scores. We recommend prospective studies in children of different age groups with Downs syndrome and in other groups of intellectually disabled children to provide further investigation of the hypothesis that intellectual disability predisposes to different analgesic requirements

Aortic atherosclerosis at middle age predicts cerebral white matter lesions in the elderly

BACKGROUND AND PURPOSE: MRI scans of the brains of elderly people frequently show white matter lesions. Clinically, these lesions are associated with cognitive impairment and dementia. A relation between atherosclerosis and white matter lesions was found in some small cross-sectional studies. However, atherosclerosis is a gradual process that starts early in life. We investigated the longitudinal association between aortic atherosclerosis assessed during midlife and late life and cerebral white matter lesions. METHODS: We randomly sampled subjects between 60 and 90 years old from 2 population-based follow-up studies in which subjects had their baseline examinations in 1975 to 1978 (midlife) and in 1990 to 1993 (late life). In 1995 to 1996, subjects underwent 1.5-T MRI scanning; white matter lesions were rated in the deep subcortical and periventricular regions separately. Aortic atherosclerosis was assessed on abdominal radiographs that were obtained from 276 subjects in midlife and 531

Interactions between five candidate genes and antihypertensive drug therapy on blood pressure

Despite the availability of effective antihypertensive drugs, there is a large variation in response to these drugs. This study investigates whether polymorphisms in the angi

How open science can support the 3Rs and improve animal research

Open science in its broadest sense can make better science and provide benefits to researchers. When applied to animal experimentation, it can prevent unnecessary use of animals, because knowledge and experiences about past animal experimentation are shared openly to be consulted and used by other researchers. By extension, open science can accelerate the much anticipated transition towards animal-free innovations or New Approach Methodologies (NAMs). The purpose of this paper is to bring together and further share the preparations and findings of a symposium held at Utrecht University on aspects of open science that researchers doing animal experiments can and should take into account to improve their research and benefit themselves. The paper offers a one-figure guideline for that purpose

The Rotterdam Scan Study: design and update up to 2012

Neuroimaging plays an important role in etiologic research on neurological diseases in the elderly. The Rotterdam Scan Study was initiated as part of the ongoing Rotterdam Study with the aim to unravel causes of neurological disease by performing neuroimaging in a population-based longitudinal setting. In 1995 and 1999 random subsets of the Rotterdam Study underwent neuroimaging, whereas from 2005 onwards MRI has been implemented into the core protocol of the Rotterdam Study. In this paper, we discuss the background and rationale of the Rotterdam Scan Study. We also describe the imaging protocol and post-processing techniques, and highlight the main findings to date. Finally, we make recommendations for future research, which will also be the main focus of investigation in the Rotterdam Scan Study

Biallelic loss-of-function variants in PLD1 cause congenital right-sided cardiac valve defects and neonatal cardiomyopathy

Congenital heart disease is the most common type of birth defect, accounting for one-third of all congenital anomalies. Using whole-exome sequencing of 2718 patients with congenital heart disease and a search in GeneMatcher, we identified 30 patients from 21 unrelated families of different ancestries with biallelic phospholipase D1 (PLD1) variants who presented predominantly with congenital cardiac valve defects. We also associated recessive PLD1 variants with isolated neonatal cardiomyopathy. Furthermore, we established that p.I668F is a founder variant among Ashkenazi Jews (allele frequency of ~2%) and describe the phenotypic spectrum of PLD1-associated congenital heart defects. PLD1 missense variants were overrepresented in regions of the protein critical for catalytic activity, and, correspondingly, we observed a strong reduction in enzymatic activity for most of the mutant proteins in an enzymatic assay. Finally, we demonstrate that PLD1 inhibition decreased endothelial-mesenchymal transition, an established pivotal early step in valvulogenesis. In conclusion, our study provides a more detailed understanding of disease mechanisms and phenotypic expression associated with PLD1 loss of function

Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration: A united approach

Item does not contain fulltextCerebral small vessel disease (SVD) is a common accompaniment of ageing. Features seen on neuroimaging include recent small subcortical infarcts, lacunes, white matter hyperintensities, perivascular spaces, microbleeds, and brain atrophy. SVD can present as a stroke or cognitive decline, or can have few or no symptoms. SVD frequently coexists with neurodegenerative disease, and can exacerbate cognitive deficits, physical disabilities, and other symptoms of neurodegeneration. Terminology and definitions for imaging the features of SVD vary widely, which is also true for protocols for image acquisition and image analysis. This lack of consistency hampers progress in identifying the contribution of SVD to the pathophysiology and clinical features of common neurodegenerative diseases. We are an international working group from the Centres of Excellence in Neurodegeneration. We completed a structured process to develop definitions and imaging standards for markers and consequences of SVD. We aimed to achieve the following: first, to provide a common advisory about terms and definitions for features visible on MRI; second, to suggest minimum standards for image acquisition and analysis; third, to agree on standards for scientific reporting of changes related to SVD on neuroimaging; and fourth, to review emerging imaging methods for detection and quantification of preclinical manifestations of SVD. Our findings and recommendations apply to research studies, and can be used in the clinical setting to standardise image interpretation, acquisition, and reporting. This Position Paper summarises the main outcomes of this international effort to provide the STandards for ReportIng Vascular changes on nEuroimaging (STRIVE)