Evaluation of the Statistical Detection of Change Algorithm for Screening Patients with MS with New Lesion Activity on Longitudinal Brain MRI.

BACKGROUND AND PURPOSE: Identification of new MS lesions on longitudinal MR imaging by human readers is time-consuming and prone to error. Our objective was to evaluate the improvement in the performance of subject-level detection by readers when assisted by the automated statistical detection of change algorithm. MATERIALS AND METHODS: A total of 200 patients with MS with a mean interscan interval of 13.2 (SD, 2.4) months were included. Statistical detection of change was applied to the baseline and follow-up FLAIR images to detect potential new lesions for confirmation by readers (Reader + statistical detection of change method). This method was compared with readers operating in the clinical workflow (Reader method) for a subject-level detection of new lesions. RESULTS: Reader + statistical detection of change found 30 subjects (15.0%) with at least 1 new lesion, while Reader detected 16 subjects (8.0%). As a subject-level screening tool, statistical detection of change achieved a perfect sensitivity of 1.00 (95% CI, 0.88-1.00) and a moderate specificity of 0.67 (95% CI, 0.59-0.74). The agreement on a subject level was 0.91 (95% CI, 0.87-0.95) between Reader + statistical detection of change and Reader, and 0.72 (95% CI, 0.66-0.78) between Reader + statistical detection of change and statistical detection of change. CONCLUSIONS: The statistical detection of change algorithm can serve as a time-saving screening tool to assist human readers in verifying 3D FLAIR images of patients with MS with suspected new lesions. Our promising results warrant further evaluation of statistical detection of change in prospective multireader clinical studies.

A comparison of undergraduate teaching of psychiatry across medical schools in the Republic of Ireland.

OBJECTIVES: To examine the delivery and assessment of psychiatry at undergraduate level in the six medical schools in the Republic of Ireland offering a medical degree programme. METHODS: A narrative description of the delivery and assessment of psychiatry at undergraduate level by collaborative senior faculty members from all six universities in Ireland. RESULTS: Psychiatry is integrated to varying degrees across all medical schools. Clinical experience in general adult psychiatry and sub-specialities is provided by each medical school; however, the duration of clinical attachment varies, and the provision of some sub-specialities (i.e. forensic psychiatry) is dependent on locally available resources. Five medical schools provide 'live' large group teaching sessions (lectures), and all medical schools provide an array of small group teaching sessions. Continuous assessment encompasses 10-35% of the total assessment marks, depending on the medical school. Only one medical school does not provide a clinical examination in the form of an Objective Structured Clinical Examination with viva examinations occurring at three medical schools. CONCLUSIONS: Many similarities exist in relation to the delivery of psychiatry at undergraduate level in Ireland. Significant variability exists in relation to assessment with differences in continuous assessment, written and clinical exams and the use of vivas noted. The use of e-learning platforms has increased significantly in recent years, with their role envisaged to include cross-disciplinary teaching sessions and analysis of examinations and individual components within examinations which will help refine future examinations and enable greater sharing of resources between medical schools.

National Guidelines on the Provision of Outpatient Parenteral Antimicrobial Therapy (OPAT).

Aim Outpatient parenteral antimicrobial therapy (OPAT) is an option in patients who require parenteral antimicrobial administration and are clinically well enough for hospital discharge. This is an update of the Irish National OPAT guidelines which were last reviewed in 2011. Methods The guideline was devised through a collaborative process with the national OPAT Working Group and a review of the literature. It is intended for clinicians who prescribe any intravenous (IV) antimicrobials outside of the inpatient setting in the Republic of Ireland. Results Patient care while on OPAT should be provided by a designated OPAT service, with clear managerial and clinical governance lines of responsibility. It should be conducted using a team approach with a clinical lead on each site either as an infection specialist, or a general medical physician with infection specialist input and an OPAT nurse. An antimicrobial pharmacist is also desirable. Several factors must be considered when assessing patient's suitability for OPAT including exclusion criteria, infection-specific factors, and patient specific factors such as physical, social and logistic criteria. Conclusion This updated guideline advocates a more individualised OPAT approach, with the recognition that specific antimicrobials and/or specific delivery models may be more appropriate for certain patient groups. Full guidelines are available through www.opat.ie.

To MSNAP or not to MSNAP? Testing a small regional memory clinic against the UK Memory Service National Accreditation Program (MSNAP).

AimTo investigate whether a small regional memory clinic would benefit from engaging with a structured external audit process such as the Royal College of Psychiatrists' Memory Service National Accreditation Program (MSNAP). BACKGROUND: The Psychiatry of Old Age service in Navan operates a public cognitive clinic. Despite the publication of the 2014 National Dementia Strategy, there are currently no national standards for memory clinics in Ireland. It may be beneficial to link in with an external quality control system as part of routine clinical governance. METHODS: Published data from the MSNAP group was reviewed and a set of audit materials extrapolated to replicate the MSNAP self-review process. The audit cycle involved (1) retrospective case review, (2) institution of a range of interventions and (3) a prospective audit, which included service user feedback. RESULTS: Overall the results demonstrated a high standard of service, especially in the areas of accessibility, assessment and communication of diagnosis. The clinic performed well against MSNAP key performance indicators. Patient and carer satisfaction with the service was very high. Clinic policies needed further development, particularly in the areas of referral, consent and data protection. CONCLUSIONS: The process was useful, providing clear pointers for action. It highlighted the need to formalise organisational and practice policies, patient support and education, audit and outreach. Although accreditation is a laborious process requiring financial investment, it provides a strong scaffold to maintain and improve standards and is likely to be a valuable learning experience, where national guidelines are lacking.

An in vitro biofilm model of Staphylococcus aureus infection of bone.

Chronic osteomyelitis is difficult to treat, with biofilm growth and the diffusion barrier to antibiotics presented by bone contributory factors. The aim of this study was to develop and evaluate an in vitro model of osteomyelitis. A bioluminescent strain of Staphylococcus aureus was grown in bone blocks made from bovine femur. Light output was insufficient for detection of bacterial cells within bone by 24 h and viable counting of crushed bone blocks was used to determine bacterial survival. Challenge of 72 h biofilms with gentamicin and daptomycin for 24 h demonstrated that only concentrations of 10 times the clinical peak serum target levels (100 mg l-1 gentamicin and 1000 mg l-1 daptomycin) resulted in significant reductions in cell viability compared to controls. Once daily dosing over 7 days resulted in ≥3 log reductions in cell numbers by 48 h. Thereafter no significant reduction was achieved, although emergence of resistance was suppressed. Determination of antibiotic concentration in bone blocks over 7 days indicated that neither agent was able to consistently reach levels in bone of >10% of the original dose. The model was, therefore, able to demonstrate the challenges posed by biofilm growth on and within bone. SIGNIFICANCE AND IMPACT OF THE STUDY: The majority of studies of antibiotic efficacy in the treatment of chronic osteomyelitis are carried out in animals. We developed an in vitro model of Staphylococcus aureus infection of bone to evaluate the ability of antibiotics to eradicate mature biofilms on surfaces analogous to necrotic bone. The results demonstrated the difficulties which occur in osteomyelitis treatment, with only very high concentrations of antibiotic able to penetrate the bone sufficiently to reduce bacterial survival whilst still failing to eradicate biofilms. This model could be of use in initial screening of novel compounds intended for use in the treatment of osteomyelitis.

Levels of Mycoplasma genitalium Antimicrobial Resistance Differ by Both Region and Gender in the State of Queensland, Australia: Implications for Treatment Guidelines.

Mycoplasma genitalium is frequently associated with urogenital and rectal infections, with the number of cases of macrolide-resistant and quinolone-resistant M. genitalium infection continuing to increase. In this study, we examined the levels of resistance to these two common antibiotic treatments in geographically distinct locations in Queensland, Australia. Samples were screened for macrolide resistance-associated mutations using a commercially available kit (ResistancePlus MG; SpeeDx), and quinolone resistance-associated mutations were identified by PCR and DNA sequencing. Comparisons between antibiotic resistance mutations and location/gender were performed. The levels of M. genitalium macrolide resistance were high across both locations (62%). Quinolone resistance mutations were found in ∼10% of all samples, with a number of samples harboring mutations conferring resistance to both macrolides and quinolones. Quinolone resistance was higher in southeast Queensland than in north Queensland, and this was consistent in both males and females (P = 0.007). The M. genitalium isolates in rectal swab samples from males harbored high levels of macrolide (75.9%) and quinolone (19%) resistance, with 15.5% harboring resistance to both classes of antibiotics. Overall, the lowest observed level of resistance was to quinolones in females from north Queensland (1.6%). These data highlight the high levels of antibiotic resistance in M. genitalium isolates within Queensland and the challenges faced by sexually transmitted infection clinicians in managing these infections. The data do, however, show that the levels of antibiotic resistance may differ between populations within the same state, which has implications for clinical management and treatment guidelines. These findings also support the need for ongoing antibiotic resistance surveillance and tailored treatment.

Food for thought. Malnutrition risk associated with increased risk of healthcare-associated infection.

BACKGROUND: Infection and malnutrition are interconnected. UK and Irish guidelines recommend the Malnutrition Universal Screening Tool (MUST) for nutritional risk screening. Patients with a MUST score of ≥2 are considered at high risk of malnutrition and referral for nutritional assessment is recommended. AIM: To explore the association between healthcare-associated infection (HCAI) and the MUST score categories of patients. METHODS: This was a cross-sectional study in May 2017 on ten representative wards in our institution. Patient demographics, MUST score, presence of medical devices, HCAI and antimicrobial use were collected. FINDINGS: Of 240 patients, the HCAI prevalence was 10.4% (N = 25) and 26% (N = 63) were at high risk of malnutrition (MUST score ≥2). Patients with HCAI were more likely to have had surgery (odds ratio (OR): 5.5; confidence interval (CI): 2.1-14.3; P < 0.001), a central vascular catheter (OR: 10.0; CI: 3.6-27.2; P < 0.001), or a urinary catheter in situ (OR: 7.5; CI: 2.8-20.0; P < 0.001), and to have a high risk of malnutrition (OR: 4.3; CI: 1.7-11.2; P < 0.001). A higher MUST score remained a significant predictor of a patient having HCAI on multivariate regression analysis (CI: 0.2-0.6; P < 0.001). CONCLUSION: Patients at risk of malnutrition when assessed with the MUST were more likely to have HCAI. However, prospective studies are required to investigate the temporal association between MUST and HCAI and which interventions best address malnutrition risk and HCAI reduction in different settings.

The effect of breastmilk and saliva combinations on the in vitro growth of oral pathogenic and commensal microorganisms.

Neonates are exposed to microbes in utero and at birth, thereby establishing their microbiota (healthy microbial colonisers). Previously, we reported significant differences in the neonatal oral microbiota of breast-fed and formula-fed babies after first discovering a primal metabolic mechanism that occurs when breastmilk (containing the enzyme xanthine oxidase) and neonatal saliva (containing highly elevated concentrations of the substrates for xanthine oxidase: xanthine and hypoxanthine). The interaction of neonatal saliva and breast milk releases antibacterial compounds including hydrogen peroxide, and regulates the growth of bacteria. Using a novel in vitro experimental approach, the current study compared the effects of this unique metabolic pathway on a range of bacterial species and determined the period of time that microbial growth was affected. We demonstrated that microbial growth was inhibited predominately, immediately and for up to 24 hr following breastmilk and saliva mixing; however, some microorganisms were able to recover and continue to grow following exposure to these micromolar amounts of hydrogen peroxide. Interestingly, growth inhibition was independent of whether the organisms possessed a catalase enzyme. This study further confirms that this is one mechanism that contributes to the significant differences in the neonatal oral microbiota of breast-fed and formula-fed babies.

Deep sequencing of the 16S ribosomal RNA of the neonatal oral microbiome: a comparison of breast-fed and formula-fed infants.

In utero and upon delivery, neonates are exposed to a wide array of microorganisms from various sources, including maternal bacteria. Prior studies have proposed that the mode of feeding shapes the gut microbiota and, subsequently the child's health. However, the effect of the mode of feeding and its influence on the development of the neonatal oral microbiota in early infancy has not yet been reported. The aim of this study was to compare the oral microbiota of healthy infants that were exclusively breast-fed or formula-fed using 16S-rRNA gene sequencing. We demonstrated that the oral bacterial communities were dominated by the phylum Firmicutes, in both groups. There was a higher prevalence of the phylum Bacteroidetes in the mouths of formula-fed infants than in breast-fed infants (p = 0.01), but in contrast Actinobacteria were more prevalent in breast-fed babies; Proteobacteria was more prevalent in saliva of breast-fed babies than in formula-fed neonates (p = 0.04). We also found evidence suggesting that the oral microbiota composition changed over time, particularly Streptococcus species, which had an increasing trend between 4-8 weeks in both groups. This study findings confirmed that the mode of feeding influences the development of oral microbiota, and this may have implications for long-term human health.

Outcomes of intravenous tissue plasminogen activator for acute ischaemic stroke in HIV-infected adults.

BACKGROUND AND PURPOSE: To our knowledge there are no studies reporting the use and short-term outcomes of intravenous tissue plasminogen activator (IV-TPA) for the treatment of acute ischaemic stroke (AIS) in people living with HIV. METHODS: The US Nationwide Inpatient Sample (NIS) (2006-2010) was searched for HIV-infected AIS patients treated with IV-TPA. RESULTS: In the NIS, 2.2% (62/2877) of HIV-infected AIS cases were thrombolyzed with IV-TPA (median age 52 years, range 27-78, 32% female, 22% Caucasian) vs. 2.1% (19 335/937 896) of HIV-uninfected cases (median age 72 years, range 17-102 years, 50% female, 74% Caucasian; P = 0.77). There were more deaths in HIV-infected versus uninfected patients with stroke (220/2877, 7.6% vs. 49 089/937 547, 5.2%, P < 0.001) but no difference in the proportion of deaths amongst IV-TPA-treated patients. The age- and sex-adjusted odds ratio for death following IV-TPA administration in HIV-infected versus uninfected patients was 2.26 (95% CI 1.12, 4.58), but the interaction on mortality between HIV and IV-TPA use was not statistically significant, indicating no difference in risk of in-hospital death by HIV serostatus with IV-TPA use. A higher number of HIV-infected patients remained in hospital versus died or were discharged at both 10 and 30 days (P < 0.01 at 10 and 30 days). No difference in the proportion of intracerebral hemorrhage in the two groups was found (P = 0.362). CONCLUSIONS: The in-hospital mortality is higher amongst HIV-infected AIS patients than HIV-uninfected patients. However, the risk of death amongst HIV-infected patients treated with IV-TPA is similar to HIV-uninfected groups.

Automatic lesion incidence estimation and detection in multiple sclerosis using multisequence longitudinal MRI.

BACKGROUND AND PURPOSE: Detecting incidence and enlargement of lesions is essential in monitoring the progression of MS. In clinical trials, lesion load is observed by manually segmenting and comparing serial MR images, which is time consuming, costly, and prone to inter- and intraobserver variability. Subtracting images from consecutive time points nulls stable lesions, leaving only new lesion activity. We propose SuBLIME, an automated method for segmenting incident lesion voxels. MATERIALS AND METHODS: We used logistic regression models incorporating multiple MR imaging sequences and subtraction images from consecutive longitudinal studies to estimate voxel-level probabilities of lesion incidence. We used T1-weighted, T2-weighted, FLAIR, and PD volumes from a total of 110 MR imaging studies from 10 subjects. RESULTS: To assess the performance of the model, we assigned 5 subjects to a training set and the remaining 5 to a validation set. With SuBLIME, lesion incidence is detected and delineated in the validation set with an AUC of 99% (95% CI [97%, 100%]) at the voxel level. CONCLUSIONS: This fully automated and computationally fast method allows sensitive and specific detection of lesion incidence that can be applied to large collections of images. Using the explicit form of the statistical model, SuBLIME can easily be adapted to cases when more or fewer imaging sequences are available.

Analyses of teicoplanin concentrations from 1994 to 2006 from a UK assay service.

Objectives An analysis of the trough serum concentrations sent to the UK Antimicrobial Reference Laboratory for teicoplanin therapeutic drug monitoring (TDM). Methods All trough concentrations over a 13 year period were analysed and the percentages were calculated for the following: <10 mg/L (a sub-optimal concentration for all); ≥10-<20 mg/L (the target used for ordinary Gram-positive infections); ≥20-<60 mg/L (the target for all severe staphylococcal infections including endocarditis); and ≥60 mg/L (the concentration associated with toxicity). Results The percentage of patients with concentrations of <10 mg/L decreased each year to 13% in 2006. Almost 40% of the samples each year were in the ≥10-<20 mg/L range. In 1996, the percentage of samples in the ≥20-<60 mg/L range reached a study high of ∼70%. That percentage then fell to 30% and increased slowly to 50% at the end of the study. Fewer than 5% of the samples were ≥60 mg/L. Conclusions Our study shows that there is a need to increase the initial dose or extend the number of days that the loading dose is used in a significant number of patients. With such a wide optimal range and a low potential for toxicity, it is unclear why optimal therapy is not achieved in a higher percentage of patients.

Caring for nursing home patients--a primary care perspective.

Older people in nursing homes constitute a vulnerable population with complex medical and mental health issues. They are predicted to make up an increasing proportion of our communities. In Ireland the majority of long term residents are in private-sector nursing homes. Their medical care needs are the responsibility of general practitioners (GPs). This study aims to identify current practice and major challenges facing GPs and highlight their contractual, educational and specialist support needs to care for this vulnerable group of patients. Survey of 476 general practitioners in the greater Dublin city area; 186 (39%) replied. 54% of respondents believed nursing home patients (NHP's) required more contact time than other practice patients. 62% regularly reviewed repeat prescriptions. Only 60% felt they had adequate geriatric medical training to look after this population. 37% had witnessed substandard care in nursing homes and of these 26% did not report it. 53% of those that did report it did so to the management of the nursing home only.

A clinical and genetic study of the Say/Barber/Biesecker/Young-Simpson type of Ohdo syndrome.

We report a series of eight patients with the Say/Barber/Biesecker/Young-Simpson (SBBYS) type of Ohdo syndrome, which is the largest cohort described to date. We expand on the type, frequency and severity of the clinical characteristics in this condition; comment on the natural history of Ohdo syndrome and further refine previously published diagnostic criteria. Cytogenetic investigations and microarray CGH analysis undertaken in this cohort of patients failed to identify a chromosomal aetiology. It remains possible that this rare condition is heterogeneous and therefore caution must be undertaken during counselling until the underlying genetic mechanism(s) is (are) identified.

Quantum dots light up pathology.

Quantum dots (QDs) are novel nanocrystal fluorophores with extremely high fluorescence efficiency and minimal photobleaching. They also possess a constant excitation wavelength together with sharp and symmetrical tunable emission spectra. These unique optical properties make them near-perfect fluorescent markers and there has recently been rapid development of their use for bioimaging. QDs can be conjugated to a wide range of biological targets, including proteins, antibodies, and nucleic acid probes, rendering them of particular interest to pathology researchers. They have been used in multiplex immunohistochemistry and in situ hybridization, which when combined with multispectral imaging, has enabled quantitative measurement of gene expression in situ. QDs have also been used for live in vivo animal imaging and are now being applied to an ever-increasing range of biological problems. These are detailed in this review, which also acts to outline the important advances that have been made in their range of applications. The relative novelty of QDs can present problems in their practical use and guidelines for their application are given.