Asymptomatic Clostridium difficile colonization in two Australian tertiary hospitals, 2012-2014: prospective, repeated cross-sectional study.

OBJECTIVES: To investigate the prevalence and risk factors for asymptomatic toxigenic (TCD) and nontoxigenic Clostridium difficile (NTCD) colonization in a broad cross section of the general hospital population over a 3-year period. METHODS: Patients without diarrhoea admitted to two Australian tertiary hospitals were randomly selected through six repeated cross-sectional surveys conducted between 2012 and 2014. Stool specimens were cultured under anaerobic conditions, and C. difficile isolates were tested for the presence of toxin genes and ribotyped. Patients were then grouped into noncolonized, TCD colonized or NTCD colonized for identifying risk factors using multinomial logistic regression models. RESULTS: A total of 1380 asymptomatic patients were enrolled; 76 patients (5.5%) were TCD colonized and 28 (2.0%) were NTCD colonized. There was a decreasing annual trend in TCD colonization, and asymptomatic colonization was more prevalent during the summer than winter months. TCD colonization was associated with gastro-oesophageal reflux disease (relative risk ratio (RRR) = 2.20; 95% confidence interval (CI) 1.17-4.14), higher number of admissions in the previous year (RRR = 1.24; 95% CI 1.10-1.39) and antimicrobial exposure during the current admission (RRR = 2.78; 95% CI 1.23-6.28). NTCD colonization was associated with chronic obstructive pulmonary disease (RRR = 3.88; 95% CI 1.66-9.07) and chronic kidney failure (RRR = 5.78; 95% CI 2.29-14.59). Forty-eight different ribotypes were identified, with 014/020 (n = 23), 018 (n = 10) and 056 (n = 6) being the most commonly isolated. CONCLUSIONS: Risk factors differ between patients with asymptomatic colonization by toxigenic and nontoxigenic strains. Given that morbidity is largely driven by toxigenic strains, this novel finding has important implications for disease control and prevention

"Me's me and you's you": Exploring patients' perspectives of single patient (n-of-1) trials in the UK

BACKGROUND: The n-of-1 trial offers a more methodologically sound approach to determining optimum treatment for an individual patient than "trials of therapy" routinely conducted in clinical practice. However, such methodology is rarely used in the UK. This pilot study explores the acceptability of n-of-1 trials to patients in the UK. METHODS: Patients with osteoarthritis of the knee were recruited to their own 12-week n-of-1 trial comparing either two knee supports or an NSAID with simple analgesic. Patients were interviewed at the start and completion of their trial to explore reasons for participation, understanding of the trial design and experiences of participation. Daily diaries were completed to inform future treatment. RESULTS: Nine patients participated (5 supports, 4 drugs). Patients were keen to participate, believing that the trial may lead to personal gains such as improved symptom control and quality of life. However, recruitment to the pharmacological comparison was more difficult since this could also entail risk. All patients were eager to complete the trial, even when difficulties were encountered. Completing the daily diary provided some patients with greater insight into their condition, which allowed them to improve their self-management. The n-of-1 trial design was viewed as a 'logical' design offering an efficient method of reaching a personalised treatment decision tailored to suit individual needs and preferences. CONCLUSION: This pilot study suggests that patients perceive the n-of-1 trial as an acceptable approach to the individualisation of treatment. In addition, further benefits over and above any gained from the interventions can be derived from involvement in such a study

SHV Lactamase Engineering Database: a reconciliation tool for SHV β-lactamases in public databases

<p>Abstract</p> <p>Background</p> <p>SHV β-lactamases confer resistance to a broad range of antibiotics by accumulating mutations. The number of SHV variants is steadily increasing. 117 SHV variants have been assigned in the SHV mutation table (<url>http://www.lahey.org/Studies/</url>). Besides, information about SHV β-lactamases can be found in the rapidly growing NCBI protein database. The SHV β-Lactamase Engineering Database (SHVED) has been developed to collect the SHV β-lactamase sequences from the NCBI protein database and the SHV mutation table. It serves as a tool for the detection and reconciliation of inconsistencies, and for the identification of new SHV variants and amino acid substitutions.</p> <p>Description</p> <p>The SHVED contains 200 protein entries with distinct sequences and 20 crystal structures. 83 protein sequences are included in the both the SHV mutation table and the NCBI protein database, while 35 and 82 protein sequences are only in the SHV mutation table and the NCBI protein database, respectively. Of these 82 sequences, 41 originate from microbial sources, and 22 of them are full-length sequences that harbour a mutation profile which has not been classified yet in the SHV mutation table. 27 protein entries from the NCBI protein database were found to have an inconsistency in SHV name identification. These inconsistencies were reconciled using information from the SHV mutation table and stored in the SHVED.</p> <p>The SHVED is accessible at <url>http://www.LacED.uni-stuttgart.de/classA/SHVED/</url>. It provides sequences, structures, and a multisequence alignment of SHV β-lactamases with the corrected annotation. Amino acid substitutions at each position are also provided. The SHVED is updated monthly and supplies all data for download.</p> <p>Conclusions</p> <p>The SHV β-Lactamase Engineering Database (SHVED) contains information about SHV variants with reconciled annotation. It serves as a tool for detection of inconsistencies in the NCBI protein database, helps to identify new mutations resulting in new SHV variants, and thus supports the investigation of sequence-function relationships of SHV β-lactamases.</p

Biochemical mutagens affect the preservation of fungi and biodiversity estimations

Many fungi have significant industrial applications or biosafety concerns and maintaining the original characteristics is essential. The preserved fungi have to represent the situation in nature for posterity, biodiversity estimations, and taxonomic research. However, spontaneous fungal mutations and secondary metabolites affecting producing fungi are well known. There is increasing interest in the preservation of microbes in Biological Resource Centers (BRC) to ensure that the organisms remain viable and stable genetically. It would be anathema if they contacted mutagens routinely. However, for the purpose of this discussion, there are three potential sources of biochemical mutagens when obtaining individual fungi from the environment: (a) mixtures of microorganisms are plated routinely onto growth media containing mutagenic antibiotics to control overgrowth by contaminants, (b) the microbial mixtures may contain microorganisms capable of producing mutagenic secondary metabolites, and (c) target fungi for isolation may produce “self” mutagens in pure culture. The probability that these compounds could interact with fungi undermines confidence in the preservation process and the potential effects of these biochemical mutagens are considered for the first time on strains held in BRC in this review

Clinical characteristics of bloodstream infections due to ampicillin-sulbactam-resistant, non-extended-spectrum-β-lactamase-producing Escherichia coli and the role of TEM-1 hyperproduction

Ampicillin-sulbactam is commonly used as an empirical therapy for invasive infections where Escherichia coli is a potential pathogen. We evaluated the clinical and microbiologic characteristics of bloodstream infection due to E. coli, with focus on cases that were nonsusceptible to ampicillin-sulbactam and not producing extended-spectrum beta-lactamase (ESBL). Of a total of 357 unique bacteremic cases identified between 2005 and 2008, 111 (31.1%) were intermediate or resistant to ampicillin-sulbactam by disk testing. In multivariate analysis, a history of liver disease, organ transplant, peptic ulcer disease, and prior use of ampicillin-sulbactam were independent risk factors for bloodstream infection with ampicillin-sulbactam-nonsusceptible E. coli. Among cases that received ampicillin-sulbactam as an empirical therapy, an early clinical response was observed in 65% (22/34) of susceptible cases but in only 20% (1/5) of nonsusceptible cases. Among 50 ampicillin-sulbactam-resistant isolates examined, there was no clonal relatedness and no evidence of production of inhibitor-resistant TEM (IRT). Instead, the resistance was attributed to hyperproduction of TEM-1 beta-lactamase in the majority of isolates. However, promoter sequences of bla(TEM-1) did not predict resistance to ampicillin-sulbactam. While the plasmid copy number did not differ between representative resistant and susceptible isolates, the relative expression of bla(TEM-1) was significantly higher in two of three resistant isolates than in three susceptible isolates. These results suggest high-level bla(TEM-1) expression as the predominant cause of ampicillin-sulbactam resistance and also the presence of yet-unidentified factors promoting overexpression of bla(TEM-1) in these isolates

Outcome related to impact on daily living: preliminary validation of the ORIDL instrument

<p>Abstract</p> <p>Background</p> <p>The challenge of finding practical, patient-rated outcome measures is a key issue in the evaluation of health care systems and interventions. The ORIDL (Outcome in Relation to Impact on Daily Living) instrument (formerly referred to as the Glasgow Homoeopathic Hospital Outcomes Scale or GHHOS) has been developed to measure patient's views of the outcome of their care by asking about change, and relating this to impact on daily life. The aim of the present paper is to describe the background and potential uses of the ORIDL, and to report on its preliminary validation in a series of three studies in secondary and primary care.</p> <p>Methods</p> <p>In the first study, 105 patients attending the Glasgow Homoeopathic Hospital (GHH) were followed-up at 12 months and changes in health status were measured by the EuroQol (EQOL) and the ORIDL. In the second study, 187 new patients at the GHH were followed-up at 3, 12, and 33 months, using the ORIDL, the Short Form 12 (SF-12), and the Measure Yourself Medical Outcome Profile (MYMOP). In study three, 323 patients in primary care were followed for 1 month post-consultation using the ORIDL and MYMOP. In all 3 studies the Patient Enablement Instrument (PEI) was also used as an outcome measure.</p> <p>Results</p> <p>Study 1 showed substantial improvements in main complaint and well-being over 12 months using the ORIDL, with two-thirds of patients reporting improvements in daily living. These improvements were not significantly correlated with changes in serial measures of the EQOL between baseline and 12 months, but were correlated with the EQOL transitions measure. Study 2 showed step-wise improvements in ORIDL scores between 3 and 33 months, which were only weakly associated with similar changes in SF-12 scores. However, MYMOP change scores correlated well with ORIDL scores at all time points. Study 3 showed similar high correlations between ORIDL scores and MYMOP scores. In all 3 studies, ORIDL scores were also significantly correlated with PEI-outcome scores.</p> <p>Conclusion</p> <p>There is significant agreement between patient outcomes assessed by the ORIDL and the EQOL transition scale, the MYMOP, and the PEI-outcome instrument, suggesting that the ORIDL may be a valid and sensitive tool for measuring change in relation to impact on life.</p

Loss and dispersion of superficial white matter in Alzheimer's disease: a diffusion MRI study

Pathological cerebral white matter changes in Alzheimer’s disease have been shown using diffusion tensor imaging. Superficial white matter changes are relatively understudied despite their importance in cortico-cortical connections. Measuring superficial white matter degeneration using diffusion tensor imaging is challenging due to its complex organizational structure and proximity to the cortex. To overcome this, we investigated diffusion MRI changes in young-onset Alzheimer’s disease using standard diffusion tensor imaging and Neurite Orientation Dispersion and Density Imaging to distinguish between disease-related changes that are degenerative (e.g. loss of myelinated fibres) and organizational (e.g. increased fibre dispersion). Twenty-nine young-onset Alzheimer’s disease patients and 22 healthy controls had both single-shell and multi-shell diffusion MRI. We calculated fractional anisotropy, mean diffusivity, neurite density index, orientation dispersion index and tissue fraction (1-free water fraction). Diffusion metrics were sampled in 15 a priori regions of interest at four points along the cortical profile: cortical grey matter, grey/white boundary, superficial white matter (1 mm below grey/white boundary) and superficial/deeper white matter (2 mm below grey/white boundary). To estimate cross-sectional group differences, we used average marginal effects from linear mixed effect models of participants’ diffusion metrics along the cortical profile. The superficial white matter of young-onset Alzheimer’s disease individuals had lower neurite density index compared to controls in five regions (superior and inferior parietal, precuneus, entorhinal and parahippocampus) (all P < 0.05), and higher orientation dispersion index in three regions (fusiform, entorhinal and parahippocampus) (all P < 0.05). Young-onset Alzheimer’s disease individuals had lower fractional anisotropy in the entorhinal and parahippocampus regions (both P < 0.05) and higher fractional anisotropy within the postcentral region (P < 0.05). Mean diffusivity was higher in the young-onset Alzheimer’s disease group in the parahippocampal region (P < 0.05) and lower in the postcentral, precentral and superior temporal regions (all P < 0.05). In the overlying grey matter, disease-related changes were largely consistent with superficial white matter findings when using neurite density index and fractional anisotropy, but appeared at odds with orientation dispersion and mean diffusivity. Tissue fraction was significantly lower across all grey matter regions in young-onset Alzheimer’s disease individuals (all P < 0.001) but group differences reduced in magnitude and coverage when moving towards the superficial white matter. These results show that microstructural changes occur within superficial white matter and along the cortical profile in individuals with young-onset Alzheimer’s disease. Lower neurite density and higher orientation dispersion suggests underlying fibres undergo neurodegeneration and organizational changes, two effects previously indiscernible using standard diffusion tensor metrics in superficial white matter