Manipulation of drugs to achieve the required dose is intrinsic to paediatric practice but is not supported by guidelines or evidence

Background: A lack of age-appropriate formulations can make it difficult to administer medicines to children. A manipulation of the dosage form may be required to achieve the required dose. This study aimed to describe medicines that are manipulated to achieve the required dose in paediatric practice.Method: A structured, undisguised observational study and postal survey. The observational study investigated drug manipulations occurring in clinical practice across three sites. The questionnaire, administered to a sample of paediatric nurses throughout the UK, surveyed manipulations conducted and nurses' experiences and views.Results: The observational study identified 310 manipulations, of which 62% involved tablets, 21% were intravenous drugs and 10% were sachets. Of the 54 observed manipulations 40 involved tablets with 65% of the tablets being cut and 30% dispersed to obtain a smaller dose. 188 manipulations were reported by questionnaire respondents, of these 46% involved tablets, 12% were intravenous drugs, and 12% were nebuliser solutions. Manipulations were predominantly, but not exclusively, identified in specialist clinical areas with more highly dependent patients. Questionnaire respondents were concerned about the accuracy of the dose achieved following manipulations and the lack of practice guidance.Conclusion: Manipulations to achieve the required dose occur throughout paediatric in-patient settings. The impact of manipulations on the efficacy of the drugs, the accuracy of the dose and any adverse effects on patients is not known. There is a need to develop evidence-based guidance for manipulations of medicines in children

Congenital anomalies in low- and middle-income countries: the unborn child of global surgery.

Surgically correctable congenital anomalies cause a substantial burden of global morbidity and mortality. These anomalies disproportionately affect children in low- and middle-income countries (LMICs) due to sociocultural, economic, and structural factors that limit the accessibility and quality of pediatric surgery. While data from LMICs are sparse, available evidence suggests that the true human and financial cost of congenital anomalies is grossly underestimated and that pediatric surgery is a cost-effective intervention with the potential to avert significant premature mortality and lifelong disability

Identifying Factors to Improve Oral Cancer Screening Uptake: A Qualitative Study

Aims: To engage with high risk groups to identify knowledge and awareness of oral cancer signs and symptoms and the factors likely to contribute to improved screening uptake. Methods: Focus group discussions were undertaken with 18 males; 40+ years of age; smokers and/or drinkers (15+ cigarettes per day and/or 15+ units of alcohol per week), irregular dental attenders living in economically deprived areas of Teesside. Results: There was a striking reported lack of knowledge and awareness of oral cancer and its signs and symptoms among the participants. When oral/mouth cancer leaflets produced by Cancer Research UK were presented to the participants, they claimed that they would seek help on noticing such a condition. There was a preference to seek help from their general practitioner rather than their dentist due to perceptions that a dentist is ‘inaccessible ’ on a physical and psychological level, costly, a ‘tooth specialist ’ not a ‘mouth specialist’, and also not able to prescribe medication and make referrals to specialists. Interestingly, none of the 18 participants who were offered a free oral cancer examination at a dental practice took up this offer. Conclusions: The uptake of oral cancer screening may be improved by increasing knowledge of the existence and signs and symptoms of oral cancer. Other factors that may increase uptake are increased awareness of the role of dentists in diagnosing oral cancer, promotion of oral cancer screening by health professionals during routine health checks, and the use of a ‘‘health’ ’ screening setting as opposed to a ‘‘dental’ ’ setting for such checks

Bmi-1 dependence distinguishes neural stem cell self-renewal from progenitor proliferation

Stem cells persist throughout life by self-renewing in numerous tissues including the central(1) and peripheral(2) nervous systems. This raises the issue of whether there is a conserved mechanism to effect self-renewing divisions. Deficiency in the polycomb family transcriptional repressor Bmi-1 leads to progressive postnatal growth retardation and neurological defects(3). Here we show that Bmi-1 is required for the self-renewal of stem cells in the peripheral and central nervous systems but not for their survival or differentiation. The reduced self-renewal of Bmi-1-deficient neural stem cells leads to their postnatal depletion. In the absence of Bmi-1, the cyclin-dependent kinase inhibitor gene p16(Ink4a) is upregulated in neural stem cells, reducing the rate of proliferation. p16(Ink4a) deficiency partially reverses the self-renewal defect in Bmi-1(-/-) neural stem cells. This conserved requirement for Bmi-1 to promote self-renewal and to repress p16(Ink4a) expression suggests that a common mechanism regulates the self-renewal and postnatal persistence of diverse types of stem cell. Restricted neural progenitors from the gut and forebrain proliferate normally in the absence of Bmi-1. Thus, Bmi-1 dependence distinguishes stem cell self-renewal from restricted progenitor proliferation in these tissues.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62726/1/nature02060.pd

Detection of involved margins in breast specimens with X-ray phase-contrast computed tomography.

Margins of wide local excisions in breast conserving surgery are tested through histology, which can delay results by days and lead to second operations. Detection of margin involvement intraoperatively would allow the removal of additional tissue during the same intervention. X-ray phase contrast imaging (XPCI) provides soft tissue sensitivity superior to conventional X-rays: we propose its use to detect margin involvement intraoperatively. We have developed a system that can perform phase-based computed tomography (CT) scans in minutes, used it to image 101 specimens approximately half of which contained neoplastic lesions, and compared results against those of a commercial system. Histological analysis was carried out on all specimens and used as the gold standard. XPCI-CT showed higher sensitivity (83%, 95% CI 69-92%) than conventional specimen imaging (32%, 95% CI 20-49%) for detection of lesions at margin, and comparable specificity (83%, 95% CI 70-92% vs 86%, 95% CI 73-93%). Within the limits of this study, in particular that specimens obtained from surplus tissue typically contain small lesions which makes detection more difficult for both methods, we believe it likely that the observed increase in sensitivity will lead to a comparable reduction in the number of re-operations

Detection of involved margins in breast specimens with x-ray phase-contrast computed tomography

Margins of wide local excisions in breast conserving surgery are tested through histology, which can delay results by days and lead to second operations. Detection of margin involvement intraoperatively would allow the removal of additional tissue during the same intervention. X-ray phase contrast imaging (XPCI) provides soft tissue sensitivity superior to conventional X-rays: we propose its use to detect margin involvement intraoperatively. We have developed a system that can perform phase-based computed tomography (CT) scans in minutes, used it to image 101 specimens approximately half of which contained neoplastic lesions, and compared results against those of a commercial system. Histological analysis was carried out on all specimens and used as the gold standard. XPCI-CT showed higher sensitivity (83%, 95% CI 69–92%) than conventional specimen imaging (32%, 95% CI 20–49%) for detection of lesions at margin, and comparable specificity (83%, 95% CI 70–92% vs 86%, 95% CI 73–93%). Within the limits of this study, in particular that specimens obtained from surplus tissue typically contain small lesions which makes detection more difficult for both methods, we believe it likely that the observed increase in sensitivity will lead to a comparable reduction in the number of re-operations

Volumetric high-resolution X-ray phase-contrast virtual histology of breast specimens with a compact laboratory system

The assessment of margin involvement is a fundamental task in breast conserving surgery to prevent recurrences and reoperations. It is usually performed through histology, which makes the process time consuming and can prevent the complete volumetric analysis of large specimens. X-ray phase contrast tomography combines high resolution, sufficient penetration depth and high soft tissue contrast, and can therefore provide a potential solution to this problem. In this work, we used a high-resolution implementation of the edge illumination X-ray phase contrast tomography based on "pixel-skipping" X-ray masks and sample dithering, to provide high definition virtual slices of breast specimens. The scanner was originally designed for intra-operative applications in which short scanning times were prioritised over spatial resolution; however, thanks to the versatility of edge illumination, high-resolution capabilities can be obtained with the same system simply by swapping x-ray masks without this imposing a reduction in the available field of view. This makes possible an improved visibility of fine tissue strands, enabling a direct comparison of selected CT slices with histology, and providing a tool to identify suspect features in large specimens before slicing. Combined with our previous results on fast specimen scanning, this works paves the way for the design of a multi-resolution EI scanner providing intra-operative capabilities as well as serving as a digital pathology system

Automated and unsupervised detection of malarial parasites in microscopic images

<p>Abstract</p> <p>Background</p> <p>Malaria is a serious infectious disease. According to the World Health Organization, it is responsible for nearly one million deaths each year. There are various techniques to diagnose malaria of which manual microscopy is considered to be the gold standard. However due to the number of steps required in manual assessment, this diagnostic method is time consuming (leading to late diagnosis) and prone to human error (leading to erroneous diagnosis), even in experienced hands. The focus of this study is to develop a robust, unsupervised and sensitive malaria screening technique with low material cost and one that has an advantage over other techniques in that it minimizes human reliance and is, therefore, more consistent in applying diagnostic criteria.</p> <p>Method</p> <p>A method based on digital image processing of Giemsa-stained thin smear image is developed to facilitate the diagnostic process. The diagnosis procedure is divided into two parts; enumeration and identification. The image-based method presented here is designed to automate the process of enumeration and identification; with the main advantage being its ability to carry out the diagnosis in an unsupervised manner and yet have high sensitivity and thus reducing cases of false negatives.</p> <p>Results</p> <p>The image based method is tested over more than 500 images from two independent laboratories. The aim is to distinguish between positive and negative cases of malaria using thin smear blood slide images. Due to the unsupervised nature of method it requires minimal human intervention thus speeding up the whole process of diagnosis. Overall sensitivity to capture cases of malaria is 100% and specificity ranges from 50-88% for all species of malaria parasites.</p> <p>Conclusion</p> <p>Image based screening method will speed up the whole process of diagnosis and is more advantageous over laboratory procedures that are prone to errors and where pathological expertise is minimal. Further this method provides a consistent and robust way of generating the parasite clearance curves.</p

Clinical course, therapeutic responses and outcomes in relapsing MOG antibody-associated demyelination.

Abstract OBJECTIVE: We characterised the clinical course, treatment and outcomes in 59 patients with relapsing myelin oligodendrocyte glycoprotein (MOG) antibody-associated demyelination. METHODS: We evaluated clinical phenotypes, annualised relapse rates (ARR) prior and on immunotherapy and Expanded Disability Status Scale (EDSS), in 218 demyelinating episodes from 33 paediatric and 26 adult patients. RESULTS: The most common initial presentation in the cohort was optic neuritis (ON) in 54% (bilateral (BON) 32%, unilateral (UON) 22%), followed by acute disseminated encephalomyelitis (ADEM) (20%), which occurred exclusively in children. ON was the dominant phenotype (UON 35%, BON 19%) of all clinical episodes. 109/226 (48%) MRIs had no brain lesions. Patients were steroid responsive, but 70% of episodes treated with oral prednisone relapsed, particularly at doses <10\u2009mg daily or within 2 months of cessation. Immunotherapy, including maintenance prednisone (P=0.0004), intravenous immunoglobulin, rituximab and mycophenolate, all reduced median ARRs on-treatment. Treatment failure rates were lower in patients on maintenance steroids (5%) compared with non-steroidal maintenance immunotherapy (38%) (P=0.016). 58% of patients experienced residual disability (average follow-up 61 months, visual loss in 24%). Patients with ON were less likely to have sustained disability defined by a final EDSS of 652 (OR 0.15, P=0.032), while those who had any myelitis were more likely to have sustained residual deficits (OR 3.56, P=0.077). CONCLUSION: Relapsing MOG antibody-associated demyelination is strongly associated with ON across all age groups and ADEM in children. Patients are highly responsive to steroids, but vulnerable to relapse on steroid reduction and cessation