Late-onset bloodstream infection and perturbed maturation of the gastrointestinal microbiota in premature infants

Late-onset bloodstream infection (LO-BSI) is a common complication of prematurity, and lack of timely diagnosis and treatment can have life-threatening consequences. We sought to identify clinical characteristics and microbial signatures in the gastrointestinal microbiota preceding diagnosis of LO-BSI in premature infants.Daily faecal samples and clinical data were collected over two years from 369 premature neonates (<32 weeks gestation). We analysed samples from 22 neonates who developed LO-BSI and 44 matched control infants. Next-generation sequencing of 16S rRNA gene regions amplified by PCR from total faecal DNA was used to characterise the microbiota of faecal samples preceding diagnosis from infants with LO-BSI and controls. Culture of selected samples was undertaken, and bacterial isolates identified using MALDI-TOF. Antibiograms from bloodstream and faecal isolates were compared to explore strain similarity.From the week prior to diagnosis, infants with LO-BSI had higher proportions of faecal aerobes/facultative anaerobes compared to controls. Risk factors for LO-BSI were identified by multivariate analysis. Enterobacteriaceal sepsis was associated with antecedent multiple lines, low birth weight and a faecal microbiota with prominent Enterobacteriaceae. Staphylococcal sepsis was associated with Staphylococcus OTU faecal over-abundance, and the number of days prior to diagnosis of mechanical ventilation and of the presence of centrally-placed lines. In 12 cases, the antibiogram of the bloodstream isolate matched that of a component of the faecal microbiota in the sample collected closest to diagnosis.The gastrointestinal tract is an important reservoir for LO-BSI organisms, pathogens translocating across the epithelial barrier. LO-BSI is associated with an aberrant microbiota, with abundant staphylococci and Enterobacteriaceae and a failure to mature towards predominance of obligate anaerobes

The FDA guidance for industry on PROs: the point of view of a pharmaceutical company

The importance of the patients point of view on their health status is widely recognised. Patient-reported outcomes is a broad term encompassing a large variety of different health data reported by patients, as symptoms, functional status, Quality of Life and Health-Related Quality of Life. Measurements of Health-Related Quality of Life have been developed during many years of researches, and a lot of validated questionnaires exist. However, few attempts have been made to standardise the evaluation of instruments characteristics, no recommendations are made about interpretation on Health-Related Quality of Life results, especially regarding the clinical significance of a change leading a therapeutic approach. Moreover, the true value of Health-Related Quality of Life evaluations in clinical trials has not yet been completely defined. An important step towards a more structured and frequent use of Patient-Reported Outcomes in drug development is represented by the FDA Guidance, issued on February 2006. In our paper we aim to report some considerations on this Guidance. Our comments focus especially on the characteristics of instruments to use, the Minimal Important Difference, and the methods to calculate it. Furthermore, we present the advantages and opportunities of using the Patient-Reported Outcomes in drug development, as seen by a pharmaceutical company. The Patient-Reported Outcomes can provide additional data to make a drug more competitive than others of the same pharmacological class, and a well demonstrated positive impact on the patient' health status and daily life might allow a higher price and/or the inclusion in a reimbursement list. Applying extensively the FDA Guidance in the next trials could lead to a wider culture of subjective measurement, and to a greater consideration for the patient's opinions on his/her care. Moreover, prescribing doctors and payers could benefit from subjective information to better define the value of drugs

The association of cold weather and all-cause and cause-specific mortality in the island of Ireland between 1984 and 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. Methods A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and cold period (October-March), using distributed lag models. Model stratification by age and gender assessed for modification of the cold weather-mortality relationship. Results In the ROI, the impact of cold weather in winter persisted up to 35 days, with a cumulative mortality increase for all-causes of 6.4% (95%CI=4.8%-7.9%) in relation to every 1oC drop in daily maximum temperature, similar increases for cardiovascular disease (CVD) and stroke, and twice as much for respiratory causes. In NI, these associations were less pronounced for CVD causes, and overall extended up to 28 days. Effects of cold weather on mortality increased with age in both jurisdictions, and some suggestive gender differences were observed. Conclusions The study findings indicated strong cold weather-mortality associations in the island of Ireland; these effects were less persistent, and for CVD mortality, smaller in NI than in the ROI. Together with suggestive differences in associations by age and gender between the two Irish jurisdictions, the findings suggest potential contribution of underlying societal differences, and require further exploration. The evidence provided here will hope to contribute to the current efforts to modify fuel policy and reduce winter mortality in Ireland

Conditional Facilitation of an Aphid Vector, Acyrthosiphon pisum, by the Plant Pathogen, Pea Enation Mosaic Virus

Plant pathogens can induce symptoms that affect the performance of insect herbivores utilizing the same host plant. Previous studies examining the effects of infection of tic bean, Vicia faba L. (Fabales: Fabaceae), by pea enation mosaic virus (PEMV), an important disease of legume crops, indicated there were no changes in the growth and reproductive rate of its primary vector the pea aphid, Acyrthosiphon pisum (Harris) (Hemiptera: Aphididae). Here, we report the results of laboratory experiments investigating how A. pisum responded to PEMV infection of a different host plant, Pisum sativum L., at different stages of symptom development. Aphid growth rate was negatively related to the age of the host plant, but when they were introduced onto older plants with well-developed PEMV symptoms they exhibited a higher growth rate compared to those developing on uninfected plants of the same age. In choice tests using leaf discs A. pisum showed a strong preference for discs from PEMV-infected peas, probably in response to visual cues from the yellowed and mottled infected leaves. When adults were crowded onto leaves using clip-cages they produced more winged progeny on PEMV-infected plants. The results indicate that PEMV produces symptoms in the host plant that can enhance the performance of A. pisum as a vector, modify the production of winged progeny and affect their spatial distribution. The findings provide further evidence that some insect vector/plant pathogen interactions could be regarded as mutualistic rather than commensal when certain conditions regarding the age, stage of infection and species of host plant are met

Pediculosis and the Pediatrician

Head lice commonly evoke feelings of disgust, revulsion, anger, and shame among parents and patients. There should, however, be no great cause for such alarm if a physician suspects pediculosis capitis. The recent introduction of several new pediculicidal drugs now allows a choice among four distinct therapeutic agents, which should substantially improve control of isolated cases and epidemics. Physicians must be aware that consumer groups are pressing public health authorities and drug manufacturers to establish proper treatment standards and safety warnings for the use of these agents. In addition, some controversy surrounds the use of lindane in children. This paper reviews the epidemiology and clinical appearance of pediculosis capitis in children, with emphasis on these recent developments. Pubic lice ( Phthirus pubis ) and body lice ( Pedicutus humanus corporis ), both of which are much less common pediatric infestations, are mentioned only briefly.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72607/1/j.1525-1470.1984.tb00447.x.pd

Periodontal disease in a patient with Prader-Willi syndrome: a case report

<p>Abstract</p> <p>Introduction</p> <p>Prader-Willi syndrome is a complex genetic disease caused by lack of expression of paternally inherited genes on chromosome 15q11-q13. The prevalence of Prader-Willi syndrome is estimated to be one in 10,000 to 25,000. However, descriptions of the oral and dental phenotype are rare.</p> <p>Case presentation</p> <p>We describe the clinical presentation and periodontal findings in a 20-year-old Japanese man with previously diagnosed Prader-Willi syndrome. Clinical and radiographic findings confirmed the diagnosis of periodontitis. The most striking oral findings were anterior open bite, and crowding and attrition of the lower first molars. Periodontal treatment consisted of tooth-brushing instruction and scaling. Home care involved recommended use of adjunctive chlorhexidine gel for tooth brushing twice a week and chlorhexidine mouthwash twice daily. Gingival swelling improved, but further treatment will be required and our patient's oral hygiene remains poor. The present treatment of tooth-brushing instruction and scaling every three weeks therefore only represents a temporary solution.</p> <p>Conclusions</p> <p>Rather than being a direct result of genetic defects, periodontal diseases in Prader-Willi syndrome may largely result from a loss of cuspid guidance leading to traumatic occlusion, which in turn leads to the development of periodontal diseases and dental plaque because of poor oral hygiene. These could be avoided by early interventions to improve occlusion and regular follow-up to monitor oral hygiene. This report emphasizes the importance of long-term follow-up of oral health care by dental practitioners, especially pediatric dentists, to prevent periodontal disease and dental caries in patients with Prader-Willi syndrome, who appear to have problems maintaining their own oral health.</p

Limits on prediction in language comprehension: A multi-lab failure to replicate evidence for probabilistic pre-activation of phonology

In current theories of language comprehension, people routinely and implicitly predict upcoming words by pre-activating their meaning, morpho-syntactic features and even their specific phonological form. To date the strongest evidence for this latter form of linguistic prediction comes from a 2005 Nature Neuroscience landmark publication by DeLong, Urbach and Kutas, who observed a graded modulation of article- and noun-elicited electrical brain potentials (N400) by the pre-determined probability that people continue a sentence fragment with that word ('cloze'). In a direct replication study spanning 9 laboratories (N=334), we failed to replicate the crucial article-elicited N400 modulation by cloze, while we successfully replicated the commonly-reported noun-elicited N400 modulation. This pattern of failure and success was observed in a pre-registered replication analysis, a pre-registered single-trial analysis, and in exploratory Bayesian analyses. Our findings do not support a strong prediction view in which people routinely pre-activate the phonological form of upcoming words, and suggest a more limited role for prediction during language comprehension