One to one specialling and sitters in acute care hospitals: a scoping review

Background One to one specialling is a type of care which is provided to ensure the safety of patients who may be suffering from cognitive impairment, exhibit challenging behaviour, or may be at risk of falls or of causing harm to themselves or others. Care such as this, often referred to as ‘specialling’ or ‘sitting’ is common practice in most hospitals around the world, but there is a lack of evidence regarding its cost effectiveness and the quality of care provided. Aim The aim of this scoping review was to explore the breadth and scope of literature on one to one specialling, sitters and similar types of care in acute secondary care settings, in order to identify the challenges and concerns relating to the quality of care (process and outcomes) and cost effectiveness emerging from the literature, and determine the implications of this for policy, practice and future research. Design This review was based on scoping review methodology following a five stage scoping review process. A keyword search was conducted in the following databases: MEDLINE, Scopus, CINAHL Plus, Web of Science, ProQuest Social Science, and ProQuest Nursing and Allied Health. The time limit placed on the search was January 2000 to April 2016. Inclusion and exclusion criteria were applied. The Mixed Methods Appraisal Tool was used to assess the quality of primary research articles. Findings Forty-four articles were included in the review. We found a lack of clarity in the terms used to describe one to one specialling and variability in what this type of care entails, who provides the care and the needs of patients requiring this type of care. High costs of specialling are often seen as a concern, but there was a lack of economic evaluations considering the full cost of specialling and balancing these against the benefits. Some of the articles proposed alternatives to one to one specialling or the use of sitters, but only some of these were evaluated. Conclusion There is wide variation in what specialling and one to one care entails, which can in turn lead to the provision of poor quality care. A reduction in this variation and improved quality care might be achieved through the development of guidelines, training and standardized decision-making tools. Further research on the impact of one to one specialling on patient outcomes and cost would be beneficial, as well as robust evaluations of the alternatives to specialling

Bedaquiline as Treatment for Disseminated Nontuberculous Mycobacteria Infection in 2 Patients Co-Infected with HIV.

Nontuberculous mycobacteria can cause disseminated infections in immunocompromised patients and are challenging to treat because of antimicrobial resistance and adverse effects of prolonged multidrug treatment. We report successful treatment with bedaquiline, a novel antimycobacterial drug, as part of combination therapy for 2 patients with disseminated nontuberculous mycobacteria co-infected with HIV

Antibiotic usage in chronic rhinosinusitis: analysis of national primary care electronic health records

Background : The aim of this study was to analyse rates of antibiotic usage in chronic rhinosinusitis (CRS) in primary care in England and Wales and to identify trends in the choice of antibiotics prescribed. Methods : We used linked data from primary care EHRs, with diagnoses coded using the Read terminology (Clinical Practice Research Datalink) from consenting general practices, with (2) hospital care administrative records (Hospital Episode Statistics, HES recorded using ICD-10). Results : From the total of 88,317 cases of CRS identified, 40,462 (46%) had an antibiotic prescription within 5 days of their first CRS diagnosis. Of patients receiving a first line antibiotic within 5 days of CRS diagnosis, over 80%, in each CRS group, received a subsequent prescription for an antibiotic. Within 5 years of diagnosis, 9% are estimated to have had 5 or more antibiotics within 5 days of a CRS-related consultation. With data spanning almost 20 years, it was possible to discern trends in antibiotics prescriptions, with a clear increasing trend towards macrolide and tetracycline prescribing evident. Conclusions : While antibiotics may have been prescribed for acute exacerbations, we have found high rates of repeated antibiotic prescription in some patients with CRS in primary care. There is a need for stronger evidence on the role of antibiotics in CRS management

Antibiotic usage in chronic rhinosinusitis: analysis of national primary care electronic health records

BACKGROUND: The aim of this study was to analyse rates of antibiotic usage in chronic rhinosinusitis (CRS) in primary care in England and Wales and to identify trends in the choice of antibiotics prescribed. METHODS: We used linked data from primary care EHRs, with diagnoses coded using the Read terminology (Clinical Practice Research Datalink) from consenting general practices, with (2) hospital care administrative records (Hospital Episode Statistics, HES recorded using ICD-10). RESULTS: From the total of 88,317 cases of CRS identified, 40,462 (46%) had an antibiotic prescription within 5 days of their first CRS diagnosis. Of patients receiving a first line antibiotic within 5 days of CRS diagnosis, over 80%, in each CRS group, received a subsequent prescription for an antibiotic. Within 5 years of diagnosis, 9% are estimated to have had 5 or more antibiotics within 5 days of a CRS-related consultation. With data spanning almost 20 years, it was possible to discern trends in antibiotics prescriptions, with a clear increasing trend towards macrolide and tetracycline prescribing evident. CONCLUSIONS: While antibiotics may have been prescribed for acute exacerbations, we have found high rates of repeated antibiotic prescription in some patients with CRS in primary care. There is a need for stronger evidence on the role of antibiotics in CRS management

Behavioral and molecular genetics of reading-related AM and FM detection thresholds

Auditory detection thresholds for certain frequencies of both amplitude modulated (AM) and frequency modulated (FM) dynamic auditory stimuli are associated with reading in typically developing and dyslexic readers. We present the first behavioral and molecular genetic characterization of these two auditory traits. Two extant extended family datasets were given reading tasks and psychoacoustic tasks to determine FM 2 Hz and AM 20 Hz sensitivity thresholds. Univariate heritabilities were significant for both AM (h2 = 0.20) and FM (h2 = 0.29). Bayesian posterior probability of linkage (PPL) analysis found loci for AM (12q, PPL = 81 %) and FM (10p, PPL = 32 %; 20q, PPL = 65 %). Bivariate heritability analyses revealed that FM is genetically correlated with reading, while AM was not. Bivariate PPL analysis indicates that FM loci (10p, 20q) are not also associated with reading

RNA Interference Is Responsible for Reduction of Transgene Expression after Sleeping Beauty Transposase Mediated Somatic Integration

Integrating non-viral vectors based on transposable elements are widely used for genetically engineering mammalian cells in functional genomics and therapeutic gene transfer. For the Sleeping Beauty (SB) transposase system it was demonstrated that convergent transcription driven by the SB transposase inverted repeats (IRs) in eukaryotic cells occurs after somatic integration. This could lead to formation of double-stranded RNAs potentially presenting targets for the RNA interference (RNAi) machinery and subsequently resulting into silencing of the transgene. Therefore, we aimed at investigating transgene expression upon transposition under RNA interference knockdown conditions. To establish RNAi knockdown cell lines we took advantage of the P19 protein, which is derived from the tomato bushy stunt virus. P19 binds and inhibits 21 nucleotides long, small-interfering RNAs and was shown to sufficiently suppress RNAi. We found that transgene expression upon SB mediated transposition was enhanced, resulting into a 3.2-fold increased amount of colony forming units (CFU) after transposition. In contrast, if the transgene cassette is insulated from the influence of chromosomal position effects by the chicken-derived cHS4 insulating sequences or when applying the Forg Prince transposon system, that displays only negligible transcriptional activity, similar numbers of CFUs were obtained. In summary, we provide evidence for the first time that after somatic integration transposon derived transgene expression is regulated by the endogenous RNAi machinery. In the future this finding will help to further improve the molecular design of the SB transposase vector system

The influence of the accessory genome on bacterial pathogen evolution

Bacterial pathogens exhibit significant variation in their genomic content of virulence factors. This reflects the abundance of strategies pathogens evolved to infect host organisms by suppressing host immunity. Molecular arms-races have been a strong driving force for the evolution of pathogenicity, with pathogens often encoding overlapping or redundant functions, such as type III protein secretion effectors and hosts encoding ever more sophisticated immune systems. The pathogens’ frequent exposure to other microbes, either in their host or in the environment, provides opportunities for the acquisition or interchange of mobile genetic elements. These DNA elements accessorise the core genome and can play major roles in shaping genome structure and altering the complement of virulence factors. Here, we review the different mobile genetic elements focusing on the more recent discoveries and highlighting their role in shaping bacterial pathogen evolution

Auditory training changes temporal lobe connectivity in Wernicke's aphasia: a randomised trial

Introduction Aphasia is one of the most disabling sequelae after stroke, occurring in 25%–40% of stroke survivors. However, there remains a lack of good evidence for the efficacy or mechanisms of speech comprehension rehabilitation. Trial Design This within-subjects trial tested two concurrent interventions in 20 patients with chronic aphasia with speech comprehension impairment following left hemisphere stroke: (1) phonological training using ‘Earobics’ software and (2) a pharmacological intervention using donepezil, an acetylcholinesterase inhibitor. Donepezil was tested in a double-blind, placebo-controlled, cross-over design using block randomisation with bias minimisation. Methods The primary outcome measure was speech comprehension score on the comprehensive aphasia test. Magnetoencephalography (MEG) with an established index of auditory perception, the mismatch negativity response, tested whether the therapies altered effective connectivity at the lower (primary) or higher (secondary) level of the auditory network. Results Phonological training improved speech comprehension abilities and was particularly effective for patients with severe deficits. No major adverse effects of donepezil were observed, but it had an unpredicted negative effect on speech comprehension. The MEG analysis demonstrated that phonological training increased synaptic gain in the left superior temporal gyrus (STG). Patients with more severe speech comprehension impairments also showed strengthening of bidirectional connections between the left and right STG. Conclusions Phonological training resulted in a small but significant improvement in speech comprehension, whereas donepezil had a negative effect. The connectivity results indicated that training reshaped higher order phonological representations in the left STG and (in more severe patients) induced stronger interhemispheric transfer of information between higher levels of auditory cortex

Modeling HIV/AIDS Drug Price Determinants in Brazil: Is Generic Competition a Myth?

Brazil became the first developing country to guarantee free and universal access to HIV/AIDS treatment, with antiretroviral drugs (ARVs) being delivered to nearly 190,000 patients. The analysis of ARV price evolution and market dynamics in Brazil can help anticipate issues soon to afflict other developing countries, as the 2010 revision of the World Health Organization guidelines shifts demand towards more expensive treatments, and, at the same time, current evolution of international legislation and trade agreements on intellectual property rights may reduce availability of generic drugs for HIV care.Our analyses are based on effective prices paid for ARV procurement in Brazil between 1996 and 2009. Data panel structure was exploited to gather ex-ante and ex-post information and address various sources of statistical bias. In-difference estimation offered in-depth information on ARV market characteristics which significantly influence prices. Although overall ARV prices follow a declining trend, changing characteristics in the generic segment help explain recent increase in generic ARV prices. Our results show that generic suppliers are more likely to respond to factors influencing demand size and market competition, while originator suppliers tend to set prices strategically to offset compulsory licensing threats and generic competition.In order to guarantee the long term sustainability of access to antiretroviral treatment, our findings highlight the importance of preserving and stimulating generic market dynamics to sustain developing countries' bargaining power in price negotiations undertaken with originator companies

The Use of a Stringent Selection System Allows the Identification of DNA Elements that Augment Gene Expression

The use of high stringency selection systems often results in the induction of very few recombinant mammalian cell lines, which limits the ability to isolate a cell line with favorable characteristics. The employment of for instance STAR elements in DNA constructs elevates the induced number of colonies and also the protein expression levels in these colonies. Here, we describe a method to systematically identify genomic DNA elements that are able to induce many stably transfected mammalian cell lines. We isolated genomic DNA fragments upstream from the human Rb1 and p73 gene loci and cloned them around an expression cassette that contains a very stringent selection marker. Due to the stringency of the selection marker, hardly any colony survives without flanking DNA elements. We tested fourteen ~3500 bp DNA stretches from the Rb1 and p73 loci. Only two ~3500 bp long DNA fragments, called Rb1E and Rb1F, induced many colonies in the context of the stringent selection system and these colonies displayed high protein expression levels. Functional analysis showed that the Rb1 DNA fragments contained no enhancer, promoter, or STAR activity. Our data show the potential of a methodology to identify novel gene expression augmenting DNA elements in an unbiased manner