Background and Aims: COVID-19 infection is associated with thrombosis, but the relationship with stroke is not fully understood.We report the incidence, characteristics of stroke, demographics, risk factors and outcomes in hospitalised COVID-19 patients. Methods: We conducted a multi-centre retrospective case-control study across five London hospitals. All PCR-positive COVID-19 cases were reviewed, and radiologically confirmed stroke patients identified, with incidence calculated from sites that recorded all COVID-19 patients. Two control groups, both age-and sex-matched, were used: COVID-19-positive without stroke;and COVID-19-negative with stroke. Pertinent clinical, biochemical and radiological data were collected from patient records. Multivariate analysis was performed to assess the covariate effect of markers of COVID-19 severity and traditional stroke risk factors. Results: Between 1st March and 31st May 2020, 35 patients had a confirmed diagnosis of COVID-19 up to two weeks before or after a radiologically confirmed stroke, with 14(41%) requiring intensive care unit (ITU) care and an inpatient mortality rate of 29%. The incidence of stroke was 1.7%. The median age was 66(±14.8) years, median NIHSS 10(±9) and 23(67.6%) of these strokes were ischaemic. Peak D-dimer during admission was associated with stroke (p=0.03), with no significant associations with any other biochemical or radiological marker on admission. Diabetes mellitus had a negative association with stroke (p=0.03). Cumulative hazard analysis using a composite outcome of ITU admission or death demonstrates concomitant COVID-19 and stroke conferring a greater hazard than stroke alone (p<0.01), but not COVID-19 alone (p=0.50). Conclusions: COVID-19 patients with stroke had poor outcomes. Peak D-dimer during admission was positively associated while diabetes was negatively associated with stroke.

Background Poorly performing diagnostic tests can impact patient safety. Clinical investigations must have good precision and diagnostic accuracy before widespread use in clinical practice. Transient elastography (TE) measures liver stiffness, a surrogate marker of liver fibrosis in adults and children. Studies to evaluate its repeatability and reproducibility (precision) in children are limited. Our aim was to determine (i) the normal range of TE measurements and (ii) the repeatability and reproducibility of TE in healthy children. Methods TE was performed in 257 healthy children, of whom 235 (91%, mean age 11.7 years, standard deviation (SD) 2.51, 107 were males (45.5%)) had two valid TE measurements performed, at least 24 h apart, by two operators under similar circumstances. High-quality TE images were obtained for each examination. Results The normal range of TE was 2.88–6.52 kPa. The mean difference between paired measurements was 0.044 (SD 0.4). The 95% limits of agreement ranged from −0.8 to +0.76 kPa for repeat measurements. There was a difference of >1 kPa between measurements in 61/235 (25.9%) children. The lack of precision was similar across all age groups. Conclusions This study demonstrates that TE does not have acceptable precision in healthy children, because random measurement variation results in the lack of agreement between paired measurements. Impact The precision and diagnostic accuracy of a new technology must be determined before it is deployed in children in order to ensure that appropriate clinical decisions are made, and healthcare resources are not wasted. TE is widely used to diagnose liver disease in children without adequate evaluation of the precision (repeatability) of TE either in healthy children or children with liver disease. This study demonstrates that TE does not have adequate precision in children. This study was performed in accordance with methods previously published for children. Refinements to the test protocol, such as duration of fasting or probe size, will have to be evaluated for their impact on precision and accuracy before the test is deployed in research studies or clinical practice.

Helicobacter pylori infection occurs within families but the transmission route is unknown. The use of stool specimens to genotype strains facilitates inclusion of complete families in transmission studies. Therefore, we aimed to use DNA from stools to analyze strain diversity in H. pylori infected families. We genotyped H. pylori strains using specific biprobe qPCR analysis of glmM, recA and hspA. Concentration of H. pylori organisms before DNA isolation enhanced subsequent DNA amplification. We isolated H. pylori DNA from 50 individuals in 13 families. Tm data for at least 2 of the 3 genes and sequencing of the glmM amplicon were analyzed. Similar strains were commonly found in both mothers and children and in siblings. However, 20/50 (40%) individuals had multiple strains and several individuals harbored strains not found in other family members, suggesting that even in developed countries sources of infection outside of the immediate family may exist. Whether infection occurs multiple times or one transmission event with several strains occurs is not known but future studies should aim to analyze strains from children much closer to infection onset. The presence of multiple stains in infected persons has implications for antibiotic sensitivity testing and treatment strategies.

Horizontal gene transfer (HGT) conferring resistance to many classes of antimicrobials has resulted in a worldwide epidemic of nosocomial and community infections caused by multidrug-resistant microorganisms, leading to suggestions of returning to the pre-antibiotic era. Whilst studies have focused on HGT in vivo, this work investigates whether the ability of antimicrobial resistant pathogens to persist in the environment, particularly on touch surfaces, may also play an important role. Escherichia coli clone ST131 and Klebsiella pneumoniae harbouring extended-spectrum--lactamase (ESBL) blaCTXM-15 and metallo--lactamase blaNDM-1, respectively, showed prolonged survival on stainless steel, with approximately 10e4 viable cells remaining from an inoculum of 10e7 CFU per cm2 after 1 month at 21°C. HGT of bla to an antibiotic-sensitive but azide-resistant recipient E. coli strain occurred on stainless steel dry touch surfaces and in suspension but not on dry copper. The conjugation frequency was approximately 10 to 50 times greater and occurred immediately, and resulting transconjugants were more stable with ESBL E. coli as the donor cell than with K. pneumoniae, but blaNDM-1 transfer increased with time. Rapid death, inhibition of respiration, and destruction of genomic and plasmid DNA of both pathogens occurred on copper alloys accompanied by a reduction in bla copy number. Naked E. coli DNA degraded on copper at 21°C and 37°C but slowly at 4°C, suggesting a direct role for the metal. Therefore, copper alloys could be useful in the prevention of infection spread and gene transfer in the healthcare and public transportation environments, particularly where cleaning and disinfection practice is not 24/7.

Objectives: Helicobacter pylori causes peptic ulcer disease and gastric cancer. Understanding the incidence of H. pylori could help guide research on potential infection prevention strategies. Previous studies indicate infection occurs in young children, but the risk of infection in older children and adolescents is unclear. Our hypothesis was that H. pylori infection is rare in adolescence or adulthood. Our aim was to determine the incidence of H. pylori over a prolonged follow-up in a cohort of 626 noninfected individuals. Methods: Participants, including index children, mothers, fathers and siblings, from a previous study (1997-2002) were traced, and 883 of 946 participated in this extended follow-up. We used the C-13 urea breath test (C-13-UBT) to determine the incidence of H. pylori among 626 family members not infected in 2002, including 75 younger siblings who were not born or too young for testing in 2002. Results: Eight (3.8%) of 210 index participants (mean +/- standard deviation age 17.92 +/- 0.77 years) became infected during 11.07 +/- 0.56 years of follow-up (incidence, 3.42 per 1000 person-years; 95% confidence interval (CI), 1.48-6.74). Only one (0.6%) of 165 older siblings became infected (incidence, 0.57 per 1000 person-years; 95% CI, 0.007-3.16) and one of 176 parents became infected (incidence, 0.63 per 1000 person-years; 95% CI, 0.01-3.5). Of 75 younger siblings (age 10.9 +/- 2.85 years) who were too young for testing or not yet born in 2002, nine (12%) became infected (incidence, 11.32 per 1000 person-years; 95% CI, 5.27-21.49). The highest incidence of H. pylori infection was in those born after 2005. Conclusions: The incidence of H. pylori was extremely low in older children and adults in developed countries. Spontaneous clearance of infection was uncommon in our study population. (C) 2017 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

Aim: Describe the outcomes of a cohort of older emergency department (ED) attendees and identify predictors of these outcomes.Design: retrospective cohort study.Methods: All patients aged 65 years or older attending an urban university hospital ED in January 2012 were included (N = 550). Outcomes were retrospectively followed for 12 months. Statistical analyses were based on multivariate binary logistic regression models and classification trees.Results: Of N = 550, 40.5% spent a parts per thousand currency sign6 h in the ED, but the proportion was 22.4% among those older than 81 years and not presenting with musculoskeletal problems/fractures. N = 349 (63.5%) were admitted from the ED. A significant multivariate predictor of in-hospital mortality was Charlson comorbidity index [CCI; odds ratio = 1.19, 95% confidence interval: 1.07, 1.34, P = 0.002]. Among patients who were discharged from ED without admission or after their first in-patient admission (N = 499), 232 (46.5%) re-attended ED within 1 year, with CCI being the best predictor of re-attendance (CCI a parts per thousand currency sign 4: 25.8%, CCI > 5: 60.4%). Among N = 499, 34 (6.8%) had died after 1 year of initial ED presentation. The subgroup (N = 114) with the highest mortality (17.5%) was composed by those aged > 77 years and brought in by ambulance on initial presentation.Conclusions: Advanced age and comorbidity are important drivers of outcomes among older ED attendees. There is a need to embed specialist geriatric services within frontline services to make them more gerontologically attuned. Our results predate the opening of an acute medical unit with specialist geriatric input.

For children with chronic abdominal pain, the early introduction of stress as a potential cause is likely to improve outcome. Parents underestimate their child's awareness of and capacity to worry about everyday events. Parents, children, and teachers need to be convinced that functional symptoms are a normal feature of life. The need for empathy and quality discussion between doctor, parents, and child concerning potential causes of stress is critical. All reinforcement should be removed including insistence on continued school attendance. Cognitive behavioural therapy appears to be helpful in resistant cases. Medication such as antidepressants should be avoided unless prescribed by a child psychiatrist.

There have been substantial developments in paediatrics in sub-speciality areas and in the mode of health care delivery. A model paediatric service needs to reflect these developments. The vast majority of admissions in the paediatric age group are acute with a good prognosis. On the other hand, paediatric sub-specialty care looks after conditions which are nearly always individuaiy rare. Thus there is a great need for centralisation of this kind of expertise at least in terms of initial diagnosis and management. Health Care delivery needs to be very flexible with an emphasis on reducing inpatient care as far as possible. The care needs to be child centred, and all the professional staff need to have expertise in children. Children's hospitals tailor their services to the special needs of children, but this is more difficult in a general hospital where the needs of children may not be well considered. Children are different physically and emotionally from adults and for most of their years are a dependent population requiring close contact with their family. The prevention of illness is an important component of paediatric care. Social factors have a major impact on child health and disease. The adult paradigm of hospital care does not usually suit the paediatric population. For all of the above reasons there is a well defined hierachy of care in paediatrics which combines and cooperates with community paediatrics and child psychiatry.

Background Cyclical vomiting syndrome (CVS) is a disorder that affects all ages and is characterized by episodes of severe nausea and vomiting with symptom-free intervals between episodes. The incidence in children is 3.15/100 000 children per year. Our objective was to evaluate the natural history of CVS and examine factors that predict symptom resolution. Methods Thirty newly diagnosed children (mean 9.15 years, SD 3.31 range 3.515.7) were enrolled. All children had a follow-up interview at 3 months, 27/30 at 6 months, and 22/30 at 9 months. Key Results Following diagnosis of CVS, only 5/22(22.7%) children had no further episodes of vomiting at 9 months, whereas 17/22 (77.3%) continued to vomit. In the year prior to diagnosis, 15/30 (50%) children were admitted to hospital. Of the 22 children with follow-up for 9 months, only one child required hospital admission. Children who continued to vomit had higher internalizing scores on CBCL compared with those who stopped vomiting (P = NS). The Pediatric Quality-of-Life Score suggested those who continued to vomit had a poorer quality of life at diagnosis compared with those who stopped vomiting (P < 0.05). Conclusions & Inferences Making a positive diagnosis of CVS and providing families with information is very important in the management of CVS. Although 75% of children reported regular episodes of vomiting 9 months after diagnosis, there was a significant reduction in the frequency and severity of symptoms in addition to a marked reduction in the use of medical services.

1. Sýkora J, Rowland M. Helicobacter pylori in Pediatrics. Helicobacter. 2011;16:59-64.2. Susser M, Stein Z. Civilisation and peptic ulcer. Lancet. 1962;1:115-9.3. Howson CP, Hiyama T, Wynder EL. The decline in gastric cancer: epidemiology of an unplanned triumph. Epidemiol Rev. 1986;8:1-27.4. Solnick JV, Chang K, Canfield DR, Parsonnet J. Natural acquisition of Helicobacter pylori infection in newborn rhesus macaques. J Clin Microbiol. 2003;41:5511-6.5. Solnick JV, Fong J, Hansen LM, Chang K, Canfield DR, Parsonnet J. Acquisition of Helicobacter pylori infection in rhesus macaques is most consistent with oral-oral transmission. J Clin Microbiol. 2006;44:3799-803.6. Escobar-Pardo ML, de Godoy AP, Machado RS, Rodrigues D, Fagundes Neto U, Kawakami E. Prevalence of Helicobacter pylori infection and intestinal parasitosis in children of the Xingu Indigenous Park. J Pediatr (Rio J). 2011;87:393-8.7. Rowland M, Daly L, Vaughan M, Higgins A, Bourke B, Drumm B. Age-specific incidence of Helicobacter pylori. Gastroenterology. 2006;130:65-72.8. Rowland M, Kumar D, Daly L, O’Connor P, Vaughan D, Drumm B. Low rates of Helicobacter pylori reinfection in children. Gastroenterology. 1999;117:336-41.9. Drumm B, Perez-Perez GI, Blaser MJ, Sherman PM. Intrafamilial clustering of Helicobacter pylori infection. N Engl J Med. 1990;322:359-63.10. Parsonnet J, Shmuely H, Haggerty T. Fecal and oral shedding of Helicobacter pylori from healthy infected adults. JAMA. 1999;282:2240-5.11. Perry S, de la Luz Sanchez M, Yang S, Haggerty TD, Hurst P, Perez-Perez G, Parsonnet J. Gastroenteritis and transmission of Helicobacter pylori infection in households. Emerg Infect Dis. 2006;12:1701-8.

BACKGROUND: At the time of diagnosis of Crohn’s disease there may be oral manifestations. The aim of this study was to describe the outcome for children with oral Crohn’s disease (OCD) at diagnosis, and to determine if there was a difference in the Paediatric Crohn’s Disease Activity Index (PCDAI) scores between those with and those without oral lesions at follow-up. METHODS: Thirty-one patients with OCD who had enrolled in two previous studies were invited to participate. Clinical and laboratory data were collected to calculate the PCDAI. Details of the management of Crohn’s disease were also recorded. RESULTS: Twenty-four of 31 patients participated (77%), of whom 17 were boys (M:F = 2.4:1). Mean age at follow-up was 15.7 years (SD 1.98, range 11.9–19.7 years). Mean duration of follow-up was 55 months (SD 22, range 20–97 months). Oral manifestations were present at follow-up in 7 (29%) of 24 patients. There were no differences between patients with and without OCD at follow-up with regard to medical treatments received or intestinal disease location. There was no difference in median PCDAI scores between those who had and those who had not oral lesions at follow-up. CONCLUSIONS: OCD resolved in the majority of children treated for intestinal Crohn’s disease. The occurrence of mouth lesions during follow-up of children who had oral manifestations at initial diagnosis was not a marker for Crohn’s disease activity elsewhere in the intestinal tract.

BACKGROUND & AIMS:Little is known about how bacteria establish chronic infections of mucosal surfaces. Helicobacter pylori (H. pylori), a chronic pathogen that lives in the gastric mucosa of humans, interacts with the trefoil factor family (TFF) protein TFF1, which is found in gastric mucus. We aimed to characterize the interaction of H. pylori with TFF1 and to assess the role of this interaction in mediating colonization.METHODS:Subcellular fractions of H. pylori were immobilized and then probed with TFF1, TFF2, or TFF3. The effect of glycosidases and preincubation with monosaccharides on the interaction and binding of TFF1 to a H. pylori adhesin was assessed. The interaction between H. pylori adhesin and TFF1 was characterized using surface plasmon resonance, flow cytometry, nondenaturing polyacrylamide gel electrophoresis, coimmunofluoresence, and incubation with tissue sections.RESULTS:The H. pylori core oligosaccharide portion (rough form) of lipopolysaccharide (RF-LPS) bound to TFF1 and to a lesser extent TFF3; this interaction was inhibited by incubation of RF-LPS with mannosidase, glucosidase, or mixed monosaccharides. TFF1 also bound to human serum albumin-conjugated mannose and glucose. The optimum pH for binding was 5.0-6.0 for TFF1 and 7.0 for TFF3. H. pylori bound TFF1 in gastric mucus ex vivo; binding of LPS-coated latex beads to human antral gastric tissue was inhibited by TFF1.CONCLUSIONS:TFF1 interacts specifically with H. pylori RF-LPS. The pH dependence of this interaction indicates that binding of H. pylori to TFF1 in the stomach could promote colonization of the mucus layer adjacent to the gastric epithelial surface.