Widespread implementation of EUCAST breakpoints for antibacterial susceptibility testing in Europe.

The European Committee on Antimicrobial Susceptibility Testing (EUCAST) was established to harmonise clinical antimicrobial breakpoints and to define breakpoints for new agents in Europe. Data from the European Antimicrobial Resistance Surveillance Network (EARS-Net) external quality assessment (EQA) exercises from 2009 to 2012, from the United Kingdom External Quality Assessment Scheme (UK NEQAS) from November 2009 to March 2013 and data collected by EUCAST through a questionnaire in the first quarter of 2013 were analysed to investigate implementation of EUCAST guidelines in Europe. A rapid change to use of EUCAST breakpoints was observed over time. Figures for implementation of EUCAST breakpoints at the end of the studied period were 61.2% from EARSNet data and 73.2% from UK NEQAS data. Responses to the EUCAST questionnaire indicated that EUCAST breakpoints were used by over 50% of laboratories in 18 countries, by 10 to 50% of laboratories in eight countries and by less than 10% in seven countries. The EUCAST disk diffusion method was used by more than 50% of laboratories in 12 countries, by 10 to 50% of laboratories in ten countries and by less than 10% in eleven countries. EUCAST guidelines implementation is essential to ensure consistent clinical reporting of antimicrobial susceptibility results and antimicrobial resistance surveillance.

Nutrient intake in adolescent girls and boys diagnosed with coeliac disease at an early age is mostly comparable to their non-coeliac contemporaries.

BACKGROUND: Food habits, nutrient needs and intakes differ between males and females, although few nutritional studies on patients with coeliac disease (CD) have reported results stratified by gender. OBJECTIVES: To compare energy and nutrient intakes among 13-year olds diagnosed with CD in early childhood with those of a non-coeliac (NC) age- and gender-matched control group, and also with estimated average requirements (EAR). METHODS: A case-control study was conducted in Sweden 2006-2007 within the coeliac screening study ETICS (Exploring The Iceberg of Coeliacs in Sweden). Dietary intake was assessed among 37 adolescents (23 girls) diagnosed with CD at median age 1.7 years (CD group) and 805 (430 girls) NC controls (NC group) using a food-frequency questionnaire covering 4 weeks. Reported energy intake was validated by comparison with the calculated physical activity level (PAL). RESULTS: Regardless of CD status, most adolescents reported an intake above EAR for most nutrients. However, both groups had a low intake of vitamin C, with 13% in the CD-group and 25% in the NC-group below EAR, and 21% of boys in the CD-group below EAR for thiamine. The intake of fatty acids was unbalanced, with a high intake of saturated and a low intake of unsaturated fats. Girls and boys in the CD-group had an overall lower nutrient density in reported food intake compared to girls and boys in the NC-group. CONCLUSIONS: Nutrient intake of adolescent girls and boys with CD was mostly comparable to intakes of NC controls. Dietitians should take the opportunity to reinforce a generally healthy diet when providing information about the gluten-free diet.

Birthweight discordant female twins and their offspring: is the intergenerational influence on birthweight due to genes or environment?

STUDY QUESTION: Does the intergenerational influence on birthweight and birth length remain within female dizygotic and monozygotic twin pairs? SUMMARY ANSWER: The intergenerational influence on birthweight and birth length remained within dizygotic but not within monozygotic twin pairs. WHAT IS KNOWN ALREADY: Low birthweight is associated with increased morbidity and mortality in both the short and long term; therefore it is important to understand determinants of fetal growth. There is a known intergenerational association between parents' and offspring's size at birth. STUDY DESIGN, SIZE, DURATION: This is a register-based cohort study with a nested within-twin-pair comparison. The study is retrospective, but based on prospectively collected information. The study population included 8685 monozygotic and like-sexed dizygotic female twins born in Sweden from 1926 to 1985, who had given birth to their first infant between 1973 and 2009. PARTICIPANTS/MATERIALS, SETTING, METHODS: This study is set in Sweden and used data from the Swedish Twin Register and the Swedish Medical Birth Register. We used generalized estimating equations to obtain regression coefficients with 95% confidence intervals (CI) for the outcomes: offspring birthweight and birth length. To control for genetic and shared environmental factors, we performed within-twin-pair analyses in 1479 dizygotic and 1526 monozygotic twin pairs. MAIN RESULTS AND THE ROLE OF CHANCE: In the cohort of both dizygotic and monozygotic twins, there was an association between mother's and offspring's size at birth. Within-dizygotic twin pairs, a 500-g increase from the twin pair's mean birthweight was associated with increased offspring birthweight [70 g (95% CI: 35-106)] and birth length [0.22 cm (95% CI: 0.07-0.38)]. The corresponding increase in birth length of 1 cm was estimated to increase offspring's birthweight by 26 g (95% CI: 12-40) and birth length by 0.11 cm (95% CI: 0.04-0.17). Within-monozygotic twin pairs there were no such associations. LIMITATIONS, REASONS FOR CAUTION: This study is limited to twins who themselves or whose co-twin voluntarily responded to questionnaires. WIDER IMPLICATIONS OF THE FINDINGS: The intergenerational influence on size at birth is suggested to be due to direct or indirect genetic factors.

Up-regulation of small intestinal interleukin-17 immunity in untreated coeliac disease but not in potential coeliac disease or in type 1 diabetes.

Up-regulation of interleukin (IL)-17 in small intestinal mucosa has been reported in coeliac disease (CD) and in peripheral blood in type 1 diabetes (T1D). We explored mucosal IL-17 immunity in different stages of CD, including transglutaminase antibody (TGA)-positive children with potential CD, children with untreated and gluten-free diet-treated CD and in children with T1D. Immunohistochemistry was used for identification of IL-17 and forkhead box protein 3 (FoxP3)-positive cells and quantitative polymerase chain reaction (qPCR) for IL-17, FoxP3, retinoic acid-related orphan receptor (ROR)c and interferon (IFN)-γ transcripts. IL-1ß, IL-6 and IL-17 were studied in supernatants from biopsy cultures. Expression of the apoptotic markers BAX and bcl-2 was evaluated in IL-17-stimulated CaCo-2 cells. The mucosal expression of IL-17 and FoxP3 transcripts were elevated in individuals with untreated CD when compared with the TGA-negative reference children, children with potential CD or gluten-free diet-treated children with CD (P < 0·005 for all IL-17 comparisons and P < 0·01 for all FoxP3 comparisons). The numbers of IL-17-positive cells were higher in lamina propria in children with CD than in children with T1D (P < 0·05). In biopsy specimens from patients with untreated CD, enhanced spontaneous secretion of IL-1ß, IL-6 and IL-17 was seen. Activation of anti-apoptotic bcl-2 in IL-17-treated CaCo-2 epithelial cells suggests that IL-17 might be involved in mucosal protection. Up-regulation of IL-17 could, however, serve as a biomarker for the development of villous atrophy and active CD.

Effect of the first wave of COVID-19 on Poison Control Centre activities in 21 European countries: an EAPCCT initiative.

BACKGROUND: Public health emergencies often affect Poison Control Centre (PCC) operations. We examined possible effects of the coronavirus disease 2019 (COVID-19) pandemic on call volume, call characteristics, and workload in European PCCs. METHOD: All 65 individual European PCCs were requested to supply data on the number of calls and call characteristics (caller, age groups, reason and specific exposures) from March to June in 2018, 2019, and 2020 (Part 1). Number of calls with specific characteristics was normalised to all calls. Calls (N) and call characteristics (%) were compared between 2020 and 2018/2019 (average), within PCCs/countries and grouped. Correlation between call volume and COVID-19 cases per PCC/country was examined. All PCCs received a survey on workload (Part 2). Parts 1 and 2 were independent. RESULTS: For Part 1, 36 PCCs (21 countries) supplied 26 datasheets. PCCs in the UK and in France merged data and supplied one datasheet each with national data. Summed data showed an increase of 4.5% in call volume from 228.794 in 2018/2019 (average) to 239.170 in 2020 (p < 0.001). Within PCCs/countries, calls significantly increased for 54% of PCCs/countries (N = 14/26) and decreased for 19% (N = 5/26), three of which (N = 3/5) only serve medical professionals. Correlation between call volume and COVID-19 cases was (non-significant) positive (Rho >0.7) in 5/26 PCCs/countries (19%), and negative in 6/26 (23%). Call characteristics (median proportion of grouped data in 2018/2019 vs. 2020) changed: fewer medical professionals called (40 vs. 34%, p < 0.001), calls on intentional exposures decreased (20 vs. 17%, p < 0.012), as did calls on patients between 13 and 17 years (5 vs. 4%, p < 0.05). Calls on specific exposures increased; disinfectants from 1.9 to 5.2%, and cleaning products from 4.4 to 5.7% (p < 0.001). For Part 2, 38 PCCs (24 countries) filled the survey on workload (number/length of shifts and time on PCC duties), which increased in 23/38 PCCs (61%), while 10/38 (26%) worked with fewer employees. CONCLUSIONS: Obtaining aggregated European PCC data proved challenging but showed an increase in overall call volume and workload during the first COVID-19 wave. Call characteristics changed including fewer calls from professionals and more calls on specific exposures. Within single PCCs/countries a variety of effects was observed.

Children with screening-detected coeliac disease show increased levels of nitric oxide products in urine.

AIM: Increased concentration of nitric oxide (NO) metabolites, nitrite and nitrate, in the urine is a strong indication of ongoing small intestinal inflammation, which is a hallmark of the enteropathy of coeliac disease (CD). It has previously been shown that children with symptomatic, untreated CD have increased levels of NO oxidation products in their urine. The aim of this study was to investigate whether screening-detected, asymptomatic coeliac children display the same urinary nitrite/nitrate pattern. METHODS: In a multicenter screening study, serum samples were collected from 7208 12-year-old children without previously diagnosed CD. Sera were analysed for anti-human tissue transglutaminase (tTG) of isotype IgA. Small bowel biopsy was performed in antibody-positive children, yielding 153 new cases of CD. In the screening-detected individuals, the sum of nitrite and nitrate concentrations in the urine was analysed and used as an indicator of NO production. For comparison, 73 children with untreated, symptomatic CD were studied. RESULTS: The nitrite/nitrate levels in children with screening-detected CD and those with untreated symptomatic CD did not differ significantly. Both groups had significantly increased urinary nitrite/nitrate concentrations compared to the children with normal small bowel biopsy (p < 0.001). CONCLUSION: Children with screening-detected CD have increased production of NO just as children with untreated symptomatic CD. High NO metabolite levels in the urine may indicate a pathogenetic feature of CD and be a marker of major clinical importance.

The influence of maternal smoking habits on the risk of subsequent stillbirth: is there a causal relation?

OBJECTIVE: Maternal smoking has previously been associated with risk of stillbirth. If women who quit smoking reduce their risk of stillbirth, the hypothesis of a causal association would be supported. DESIGN: Prospective cohort study. SETTING: Nationwide study in Sweden. POPULATION: All primiparous women who delivered their first and second consecutive single births between 1983 and 2001, giving a total number of 526,691 women. METHOD: A population-based Swedish study with data from the Medical Birth Registry, the Immigration Registry and the Education Registry. Logistic regression analyses were used to estimate odds ratios, using 95% confidence intervals. MAIN OUTCOME MEASURE: Stillbirth in the second pregnancy. RESULTS: Compared with nonsmokers in both pregnancies, women who smoked during the first pregnancy but not during the second do not have an increased risk of stillbirth (OR 1.02; 95% CI 0.79-1.30), while corresponding risk among women who smoked during both pregnancies was 1.35 (95% CI 1.15-1.58). CONCLUSION: The result supports that maternal smoking during pregnancy is causally associated with stillbirth risk. Smoking is a preventable cause of stillbirth, and smoking interventions is an important issue in antenatal care.

'Did you have flu last week?' A telephone survey to estimate a point prevalence of influenza in the Swedish population.

Sentinel surveillance usually underestimates the true burden of influenza in a population, as individuals must present to medical establishments to be included in the surveillance system. We carried out a telephone survey to estimate the national burden of influenza in the Swedish population for one week during the 2004/05 influenza season. Fixed-line telephone numbers were randomly sampled and households interviewed concerning influenza illness between 14-20 February 2005 (Week 7 of 2005). Questions regarding seasonal influenza vaccination status, symptoms and the impact of illness on daily life were also included. A self-defined influenza prevalence of 7.7% in week 7 of 2005 was estimated. On applying a case definition of 'cough and fever and muscle pain' for influenza like illness, the prevalence decreased to 3.6%. The survey provided insight into the burden of illness in the population further to that estimated through the sentinel surveillance system.

'Did you have flu last week?' A telephone survey to estimate a point prevalence of influenza in the Swedish population.

Sentinel surveillance usually underestimates the true burden of influenza in a population, as individuals must present to medical establishments to be included in the surveillance system. We carried out a telephone survey to estimate the national burden of influenza in the Swedish population for one week during the 2004/05 influenza season. Fixed-line telephone numbers were randomly sampled and households interviewed concerning influenza illness between 14-20 February 2005 (Week 7 of 2005). Questions regarding seasonal influenza vaccination status, symptoms and the impact of illness on daily life were also included. A self-defined influenza prevalence of 7.7% in week 7 of 2005 was estimated. On applying a case definition of 'cough and fever and muscle pain' for influenza like illness, the prevalence decreased to 3.6%. The survey provided insight into the burden of illness in the population further to that estimated through the sentinel surveillance system.

Pharmacokinetics of budesonide controlled ileal release capsules in children and adults with active Crohn's disease.

BACKGROUND: Systemic glucocorticosteroid therapy is effective in Crohn's disease, but is associated with side-effects. Budesonide has high topical anti-inflammatory activity, but considerably lower systemic activity than other oral glucocorticosteroids. AIM: To evaluate the systemic exposure to budesonide (controlled ileal release capsules) in children and adults with active Crohn's disease, and to assess the suppression of plasma cortisol. METHODS: In an open label study, patients (eight children and six adults) with active Crohn's disease received 9 mg budesonide (Entocort capsules) orally once daily for 7 days. Plasma concentrations were determined on the seventh day of administration, and pharmacokinetic parameters were calculated. For reference, 0.5 mg budesonide was given intravenously separately. Plasma cortisol levels were compared with the pre-treatment baseline values. RESULTS: Systemic exposure to budesonide (AUC0-24 h) after 1 week of oral administration was 41 +/- 21 nmol/L x h (mean +/- s.d.) in children and 35 +/- 20 nmol/L x h in adults. The estimated systemic availability in children was 9 +/- 5% and in adults 11 +/- 7%. The mean plasma cortisol (AUC0-24 h) decreased by 64 +/- 18% in children and by 50 +/- 27% in adults. CONCLUSIONS: The systemic exposure, systemic availability and cortisol suppression after oral administration of 9 mg budesonide were similar in children and adults with active Crohn's disease. Budesonide was well tolerated and no clinically important safety-related findings were identified.

Germline mutations in TGM2 do not contribute to coeliac disease susceptibility in the Swedish population.

OBJECTIVE: Coeliac disease (CD) shows a strong genetic predisposition involving HLA-DQ2 and non-HLA components. Tissue transglutaminase, encoded by TGM2, occupies a central role in the CD pathogenesis, necessary for the deamidation of specific glutamine residues of alpha-gliadin creating a T-cell epitope that binds with increased affinity to DQ2. To investigate whether germline mutations in TGM2 contribute to disease susceptibility we have carried out a comprehensive analysis of the gene in 52 patients with CD. DESIGN: Blood samples were collected from 52 children with biopsy proven CD attending one Swedish centre. DNA was extracted from lymphocytes and all exons and intron-exon boundaries of the TGM2 gene and the alternatively spliced form of the gene were screened for mutations. METHODS: Mutational analysis was undertaken by a combination of conformational specific gel electrophoresis and direct sequencing. RESULTS: Three novel polymorphisms were identified but no pathogenic mutations were detected. CONCLUSIONS: There is no evidence from this study that mutations in TGM2, which lead to an altered protein, contribute to CD susceptibility.

The effects of oats on the function of gut microflora in children with coeliac disease.

BACKGROUND: Faecal short chain fatty acids (SCFAs) are produced by the gut microflora. We have previously reported high faecal SCFA levels in children with coeliac disease (CD), indicating alteration in gut microfloral metabolism. Data accumulated over recent decades by us and others suggest that wheat-free oats can safely be included in a gluten-free diet (GFD). However, concerns have been raised with respect to the safety of oats in a subset of coeliacs. AIM: To describe faecal SCFA patterns in children with newly diagnosed CD treated for 1 year with a GFD with or without oats. METHODS: This report is part of a randomised, double-blind study on the effect of a GFD containing oats (GFD-oats) vs. a standard GFD (GFD-std). Faecal samples were received from 34 children in the GFD-oats group and 37 in the GFD-std group at initial diagnosis and/or after 1 year on a GFD. Faecal SCFAs were analysed. RESULTS: The GFD-std group had a significantly lower total faecal SCFA concentration at 12 months compared with 0 months (P < 0.05). In contrast, total SCFA in the GFD-oats group remained high after 1 year on the GFD. The children in the GFD-oats group had significantly higher acetic acid (P < 0.05), n-butyric acid (P < 0.05) and total SCFA concentration (P < 0.01) after 1-year diet treatment compared to the GFD-std group. CONCLUSIONS: Our results indicate that oats do affect the gut microflora function, and that some coeliac children receiving oats may develop gut mucosal inflammation, that may present a risk for future complications.

What happens to food choices when a gluten-free diet is required? A prospective longitudinal population-based study among Swedish adolescent with coeliac disease and their peers.

A dietary survey was performed during a large screening study in Sweden among 13-year-old adolescents. The aim was to study how the intake of food groups was affected by a screening-detected diagnosis of coeliac disease (CD) and its gluten-free (GF) treatment. Food intake was reported using a FFQ, and intake reported by the adolescents who were diagnosed with CD was compared with the intake of two same-aged referent groups: (i) adolescents diagnosed with CD prior to screening; and (ii) adolescents without CD. The food intake groups were measured at baseline before the screening-detected cases were aware of their CD, and 12-18 months later. The results showed that food intakes were affected by screen-detected CD and its dietary treatment. Many flour-based foods were reduced such as pizza, fish fingers and pastries. The results also indicated that bread intake was lower before the screened diagnosis compared with the other studied groups, but increased afterwards. Specially manufactured GF products (for example, pasta and bread) were frequently used in the screened CD group after changing to a GF diet. The present results suggest that changing to a GF diet reduces the intake of some popular foods, and the ingredients on the plate are altered, but this do not necessarily include a change of food groups. The availability of manufactured GF replacement products makes it possible for adolescents to keep many of their old food habits when diagnosed with CD in Sweden.

IgA endomysium antibodies--an early predictor for celiac disease in children without villous atrophy.

AIM: To evaluate possible differences between children with anti-endomysium antibodies (EMA) positivity and normal small bowel mucosa and children with positive EMA and an enteropathy diagnosed as celiac disease (CD). METHODS: Children with suspected CD and positive EMA (>or=1/10) undergoing small bowel biopsy during 1996 to 2002, were investigated (n=133). Data registered were: year and month of birth, timing of the first biopsy, sex, heredity for CD, dermatitis herpetiformis and diabetes mellitus and outcome of the anti-gliadin antibody test (AGA). The case group, with EMA positivity and normal histology (n=39; 59% female, mean age at the first biopsy 7.3 years, range 1.4-16), was compared with the disease control group, with positive EMA and a biopsy suggestive and further on diagnosed as CD (n=94; 56% female; mean age 7.6 years at the first biopsy, range 0.70-17). RESULTS: AGA positivity and heredity for CD were found to predict the outcome of a pathological jejunal mucosa. Nineteen of the 39 children in the case group were rebiopsied of whom 11 had developed an enteropathy during a follow-up period of 2-7 years (median 4.5 years). CONCLUSIONS: EMA positivity in the absence of small bowel enteropathy could be a very early predictor for later overt CD, and necessitates further follow-up, especially if the child is AGA positive and there is a family history of CD.

Gut microflora associated characteristics in children with celiac disease.

OBJECTIVES: The aim of the study was to investigate the metabolic function of intestinal microflora in children with celiac disease (CD) in order to find out if there is a deviant gut flora in CD patients compared to healthy controls. METHODS: The study group comprised children with CD, consecutively diagnosed according to current criteria given by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition. Thirty-six children were studied at presentation, i.e., on a normal gluten-containing diet, with clinical symptoms and signs indicative of CD, positive celiac serology markers, and a small bowel biopsy showing severe enteropathy. Forty-seven patients were studied when they had been on a gluten-free diet (GFD) for at least 3 months. For comparison, a group of 42 healthy controls (HC) were studied. The functional status of the intestinal microflora was evaluated by gas-liquid chromatography of short chain fatty acids (SCFAs) in fecal samples. RESULTS: There was a significant difference between untreated CD children and HC as well as between treated CD children and HC regarding acetic, i-butyric, i-valeric acid, and total SCFAs. The propionic and n-valeric acids differed significantly between CD children on GFD and HC. Moreover, there was a strong correlation between i-butyric and i-valeric acids in all study groups. CONCLUSIONS: This is the first study of the SCFA pattern in fecal samples from children with CD. The results indicate that there is a difference in the metabolic activity of intestinal microbial flora in children with CD compared to that in HC. The finding of a different pattern of some SCFAs in celiacs both at presentation and during treatment with GFD indicates that it is a genuine phenomenon of CD not affected by either the diet, the inflammation, or the autoimmune status of the patient.