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1.  Antibodies in the Diagnosis of Coeliac Disease: A Biopsy-Controlled, International, Multicentre Study of 376 Children with Coeliac Disease and 695 Controls 
PLoS ONE  2014;9(5):e97853.
Diagnosis of coeliac disease (CD) relies on a combination of clinical, genetic, serological and duodenal morphological findings. The ESPGHAN suggested that biopsy may not be necessary in all cases. New guidelines include omission of biopsy if the concentration of CD-specific antibodies exceeds 10 times the upper limit of normal (10 ULN) and other criteria are met. We analysed the 10 ULN criterion and investigated multiple antibody-assays. Serum was collected from 1071 children with duodenal biopsy (376 CD patients, 695 disease-controls). IgA-antibodies to tissue transglutaminase (IgA-aTTG), IgG-antibodies to deamidated gliadin peptides (IgG-aDGL) and IgA-endomysium antibodies (IgA-EMA) were measured centrally. We considered 3 outcomes for antibody test procedures utilizing IgA-aTTG and/or IgG-aDGL: positive (≥10 ULN, recommend gluten-free diet), negative (<1 ULN, no gluten-free diet) or unclear (perform biopsy). Positive (PPV) and negative (NPV) predictive values were based on clear test results. We required that they and their lower confidence bounds (LCB) be simultaneously very high (LCB >90% and PPV/NPV >95%). These stringent conditions were met for appropriate antibody-procedures over a prevalence range of 9–57%. By combining IgG-aDGL with IgA-aTTG, one could do without assaying total IgA. The PPV of IgG-aDGL was estimated to be extremely high, although more studies are necessary to narrow down the LCB. The proportion of patients requiring a biopsy was <11%. The procedures were either equivalent or even better in children <2 years compared to older children. All 310 of the IgA-aTTG positive children were also IgA-EMA positive. Antibody-assays could render biopsies unnecessary in most children, if experienced paediatric gastroenterologists evaluate the case. This suggestion only applies to the kits used here and should be verified for other available assays. Confirming IgA-aTTG positivity (≥10 ULN) by EMA-testing is unnecessary if performed on the same blood sample. Prospective studies are needed.
PMCID: PMC4022637  PMID: 24830313
2.  The Impact of ACGME Work-Hour Reforms on the Operative Experience of Fellows in Surgical Subspecialty Programs 
In July 2003, the Accreditation Council for Graduate Medical Education (ACGME) introduced a set of regulations that mandated a reduction in the number of hours that medical residents can work. These requirements have generated controversy among medical educators, with some expressing concern that reducing resident hours may limit clinical exposure and competency, particularly in surgical specialties.
This study examines the impact of duty hour restrictions on resident operative experience in residents in 2 surgical subspecialties since the implementation of the ACGME duty hour limits.
We examined operative log data for vascular surgery and pediatric surgery, using the academic year immediately preceding the duty hour restrictions, 2002 to 2003, as a baseline for comparison to subsequent academic years through 2006 to 2007 for vascular surgery and 2007 to 2008 for pediatric surgery.
Graduating fellows in pediatric surgery showed no change in their total operative volume following duty hour restrictions. The pediatric-defined category of neonate procedures showed an increase following duty hour restrictions. Graduating fellows in vascular surgery showed an increase in total major procedures as surgeon. The vascular-defined categories of endovascular-diagnostic, endovascular-therapeutic, and endovascular-graft procedures also increased.
The reduction of duty hours has not resulted in a decrease in operative volume as some have predicted. Operative volume in pediatric surgery remained mainly unchanged, whereas operative volume in vascular surgery increased. We explore possible explanations for the observed findings.
PMCID: PMC3186271  PMID: 22379533
3.  307 Asthma Prevalence and Body Mass Index in Children 
Overweight seems to be a growing problem associated with diseases which are increase during the last decades. As an example both the BMI (Body Mass Index) and the asthma prevalence are increasing. The question is whether a link exists between these changes or whether the increase is independent of each other.
In the frame of a longitudinal repeated cross-sectional epidemiological study 4925 children in total have been medical checked up. A questionnaire was filled out by the parents. Among other things data were gathered concerning anamnesis, physical measurements, and physician diagnosed diseases, like asthma. Describing the overweight in children's age until 15 years the BMI was divided in percentiles <10%, 10 to 25%, 25 to 75%, 75 to 90%, >90% respectively >97%. The full data set was available for 3946 children (80.1% of all participants).
Descriptive: The lifetime prevalence of asthma was 7.1% (age group until 15 years). The BMI was for the overweight group of 6/8/15 year old kids; 18.1/20.1/24.5 kg/m2 and in the adiposity group 20.2/22.4/27.7 kg/m2 respectively. Frequent air way infections and parental predisposition enhance the risk for asthma (4.1 vs 10.9%); boys are more affected than girls (8.1 vs 6.1%). Starting with the 10%-BMI-percentile the asthma prevalence increases using the above mentioned intervals from 3.6% up to 8.3% for children with overweight (>90%-BMI-percentile). Analytical: The logistic regression adjusted for relevant confounders (gender, smoking and passive smoking, parental predisposition, pets (like cats), duration of breastfeeding, socioeconomic status) confirms the descriptive results. The BMI dependent adjusted Odds Ratio (aOR) (range) for asthma was 1.6 (95% CI, 1.0-2.7; P = 0.048).
The results clearly show that within the group of higher BMI more asthma will detected. Contrary to other studies this study may not confirm that the dependence on asthma from the BMI is bimodal since no higher asthma prevalence was observed in the lower and lowest BMI classes. Up to now this pilot study does not answer the question about the underlying processes.
PMCID: PMC3512670
4.  337 Allergic Disorders Prevented by Helicobacter Pylori Colonization 
The World Allergy Organization Journal  2012;5(Suppl 2):S125-S126.
Previous studies suggest that an association exists between microbiological colonization and allergic disorders. The derived hygiene hypothesis postulates that the increase in atopic diseases may in part be due to diminished exposure to microorganisms. The study should contribute to clear up whether the association exists focused on chronic microbial colonization/infection and which type of infection does render the expected protection.
As part of a 3 times repeated cross-sectional epidemiological study 4925 children in total have been medical checked up. Gastrointestinal and respiratory types of infection where considered: (1) gastrointestinal colonization (Helicobacter pylori detection using in vivo [13C] urea breath test) and (2) respiratory infections (physician-diagnosed lower (bronchitis) and upper (common cold) respiratory tract infections). Physician diagnosed allergic asthma, atopic eczema, rhinitis allergica and allergic symptoms were selected as allergic target variables.
Descriptive: Whereas respiratory infections lead to higher prevalence of the allergic disorders (not infected/infected: asthma 3/10%, eczema 10/24%, hay fever 6/12%) Helicobacter pylori colonization protects against allergies (not infected/infected: asthma 6/3%, eczema 16/7%, hay fever 8/7%). Analytical: The descriptive results could be confirmed using a logistic regression adjusted for relevant confounders (gender, smoking and passive smoking, parental predisposition, pets (like cats), number of older siblings, duration of breastfeeding, socioeconomic status) except and not significant for rhinitis allergica. Related to asthma/eczema/hay fever the adjusted odds ratios (aOR) for Helicobacter pylori colonization were 0.58 (P = 0.05)/0.48 (P < 0.01)/1.07 (P = 0.75). Contrary respiratory tract infection shows an amplifying effect on asthma/eczema/hay fever of aOR 3.75 (P < 0.01)/1.96 (P < 0.01)/2.07 (P < 0.01).
Helicobacter pylori colonization seems to protect against allergic disorders in comparison with the effect of respiratory tract infections. The hygiene hypothesis may be better explained when this kind of gastrointestinal and respiratory tract infections are subtly differentiated.
PMCID: PMC3512867
5.  Tracking Residents Through Multiple Residency Programs: A Different Approach for Measuring Residents' Rates of Continuing Graduate Medical Education in ACGME-Accredited Programs 
Increased focus on the number and type of physicians delivering health care in the United States necessitates a better understanding of changes in graduate medical education (GME). Data collected by the Accreditation Council for Graduate Medical Education (ACGME) allow longitudinal tracking of residents, revealing the number and type of residents who continue GME following completion of an initial residency. We examined trends in the percent of graduates pursuing additional clinical education following graduation from ACGME-accredited pipeline specialty programs (specialties leading to initial board certification).
Using data collected annually by the ACGME, we tracked residents graduating from ACGME-accredited pipeline specialty programs between academic year (AY) 2002–2003 and AY 2006–2007 and those pursuing additional ACGME-accredited training within 2 years. We examined changes in the number of graduates and the percent of graduates continuing GME by specialty, by type of medical school, and overall.
The number of pipeline specialty graduates increased by 1171 (5.3%) between AY 2002–2003 and AY 2006–2007. During the same period, the number of graduates pursuing additional GME increased by 1059 (16.7%). The overall rate of continuing GME increased each year, from 28.5% (6331/22229) in AY 2002–2003 to 31.6% (7390/23400) in AY 2006–2007. Rates differed by specialty and for US medical school graduates (26.4% [3896/14752] in AY 2002–2003 to 31.6% [4718/14941] in AY 2006–2007) versus international medical graduates (35.2% [2118/6023] to 33.8% [2246/6647]).
The number of graduates and the rate of continuing GME increased from AY 2002–2003 to AY 2006–2007. Our findings show a recent increase in the rate of continued training for US medical school graduates compared to international medical graduates. Our results differ from previously reported rates of subspecialization in the literature. Tracking individual residents through residency and fellowship programs provides a better understanding of residents' pathways to practice.
PMCID: PMC3010950  PMID: 22132288
6.  Helicobacter pylori colonisation and eczema 
The hygiene hypothesis postulates that the increase in atopic diseases may in part be due to diminished exposure to microorganisms. But it is unknown which type of infection does render protection. An epidemiological study was conducted in Leipzig, Germany, and its rural county, involving 3347 school starters. Two types of infection were considered: (1) gastrointestinal colonisation (Helicobacter pylori detection using in vivo [13C] urea breath test) and (2) respiratory infections (physician‐diagnosed lower (bronchitis) and upper (common cold) respiratory infections). H pylori colonisation was selected because it is very common and plays an important role in gastrointestinal disorders. Atopic eczema was selected as the (allergic) target variable because of its high frequency in the age of the study participants. The results, adjusted for relevant confounders, showed a significant inverse association between H pylori infection and eczema (adjusted odds ratio (aOR) = 0.31, p = 0.006) in children not predisposed to atopy. In contrast, bronchitis increased the risk of eczema (aOR = 1.98, p<0.001). Bacterial digestive tract colonisation (infection) seems to protect against eczema in comparison with the effect of respiratory tract infections. The hygiene hypothesis may be better explained when gastrointestinal and respiratory infections are subtly differentiated.
PMCID: PMC2465748  PMID: 17568058
7.  A Critical Role of Platelet Adhesion in the Initiation of Atherosclerotic Lesion Formation 
The contribution of platelets to the process of atherosclerosis remains unclear. Here, we show in vivo that platelets adhere to the vascular endothelium of the carotid artery in ApoE−/− mice before the development of manifest atherosclerotic lesions. Platelet–endothelial cell interaction involved both platelet glycoprotein (GP)Ibα and GPIIb-IIIa. Platelet adhesion to the endothelium coincides with inflammatory gene expression and preceded atherosclerotic plaque invasion by leukocytes. Prolonged blockade of platelet adhesion in ApoE−/− mice profoundly reduced leukocyte accumulation in the arterial intima and attenuated atherosclerotic lesion formation in the carotid artery bifurcation, the aortic sinus, and the coronary arteries. These findings establish the platelet as a major player in initiation of the atherogenetic process.
PMCID: PMC2194025  PMID: 12370251
platelets; endothelium; atherosclerosis; integrin; glycoprotein Ib

Results 1-7 (7)