Northern European Centres Research Articles

Longitudinal Dietary Intake Data in Patients with Phenylketonuria from Europe: The Impact of Age and Phenylketonuria Severity.

In phenylketonuria (PKU), natural protein intake is thought to increase with age, particularly during childhood and adolescence. Longitudinal dietary intake data are scarce and lifelong phenylalanine tolerance remains unknown. Nine centres managing PKU in Europe and Turkey participated in a retrospective study. Data were collected from dietetic records between 2012 and 2018 on phenylalanine (Phe), natural protein, and protein substitute intake. A total of 1323 patients (age range: 1-57 y; 51% male) participated. Dietary intake data were available on 1163 (88%) patients. Patient numbers ranged from 59 to 320 in each centre. A total of 625 (47%) had classical PKU (cPKU), n = 357 (27%) had mild PKU (mPKU), n = 325 (25%) had hyperphenylalaninemia (HPA), and n = 16 (1%) were unknown. The mean percentage of blood Phe levels within target ranged from 65 ± 54% to 88 ± 49%. When intake was expressed as g/day, the mean Phe/natural protein and protein equivalent from protein substitute gradually increased during childhood, reaching a peak in adolescence, and then remained consistent during adulthood. When intake was expressed per kg body weight (g/kg/day), there was a decline in Phe/natural protein, protein equivalent from protein substitute, and total protein with increasing age. Overall, the mean daily intake (kg/day) was as follows: Phe, 904 mg ± 761 (22 ± 23 mg/kg/day), natural protein 19 g ± 16 (0.5 g/kg/day ± 0.5), protein equivalent from protein substitute 39 g ± 22 (1.1 g/kg/day ± 0.6), and total protein 59 g ± 21 (1.7 g/kg/day ± 0.6). Natural protein tolerance was similar between males and females. Patients with mPKU tolerated around 50% less Phe/natural protein than HPA, but 50% more than cPKU. Higher intakes of natural protein were observed in Southern Europe, with a higher prevalence of HPA and mPKU compared with patients from Northern European centres. Natural protein intake doubled with sapropterin usage. In sapropterin-responsive patients, 31% no longer used protein substitutes. Close monitoring and optimisation of protein intake prescriptions are needed, along with future guidelines specifically for different age groups and severities.

Platelet function testing: Current practice among clinical centres in Northern Europe.

IntroductionPlatelet function tests are used to screen and diagnose patients with possible inherited platelet function defects (IPFD). Some acquired platelet dysfunction may be caused by certain drugs or comorbidities, which need to be excluded before testing.AimsTo identify current practice among centres performing platelet function tests in Northern Europe.MethodsA total of 14 clinical centres from Sweden (six), Finland (two), Denmark (two), Norway (one), Estonia (two) and Iceland (one) completed the survey questionnaire, the population capture area of about 29.5 million.ResultsSix of the 14 (42.8%) centres providing platelet function assessment represent comprehensive treatment centres (EUHANET status). A Bleeding score (BS) or ISTH bleeding assessment tool (ISTH BAT score) is evaluated in 11/14 (78.6%) centres and family history in all. Five/14 centres (35.7%) use structured preanalytical patient instructions, and 10/14 (71.4%) recorded questionnaire on the preassessment of avoidance of any drugs or natural products affecting platelet functions. Preliminary investigations of screening tests of coagulation are performed in 10/14 (71.4%), while in 4/14 (28.6%), the diagnostic work‐up of IPFD and von Willebrand disease (VWD) is performed simultaneously. The work‐up of IPFD includes peripheral blood smear in 10/14 (71.4%), platelet aggregometry in all, flow cytometry in 10/14 (71.4%) and Platelet Function Analysis (PFA) in 3/11 (28.6%). Molecular genetic diagnosis is available in 7/14 (50%) centres.ConclusionsThe considerable variability in the current practice illustrates the need for harmonization between the Northern European centres according to the international registers (i.e. EUHASS) and IPFD guidelines (ISTH, EHA).

Early Secondary Alveolar Bone Grafting and Facial Growth of Patients with Complete Unilateral Cleft Lip and Palate.

To investigate the craniofacial growth outcomes of early secondary alveolar bone grafting(ABG) around 6 years of age. Retrospective cohort study. 1 North-American and 5 Northern-European cleft centers. 33 subjects with CUCLP consecutively treated with secondary ABG around 6 years of age were compared to 105 subjects from 4 centers treated with late secondary ABG and 19 subjects from 1 center with primary ABG. Preorthodontic standardized lateral cephalometric radiographs taken after 12 years of age were traced and analyzed according to the Eurocleft Study protocol. Fourteen angular and two proportional measurements were performed. Measurement means from the Study Center(SC) were compared to 5 Northern-European centers using analysis of variance and Welch's modified t-tests, and P < .05 was considered statistically significant. For the SC, the mean age ± SD at the time of bone graft was 5.85 ± 0.71 years and the mean age at the time of the lateral cephalogram was 13.4 ± 1.8 years. The sagittal maxillary prominence of the SC was favorably comparable to the 5 Northern-European centers. The mean SNA (78.1 ± 4.3) for the SC was significantly higher compared to 4 of the 5 Northern-European centers(all P < .05), and the mean ANB angle was comparable to 4 of the 5 centers. Similarly, the mean soft tissue ANB angle was not significantly different to the 5 centers. The soft tissue vertical proportions compared favorably to all 5 Northern-European centers(all P < .01). Craniofacial growth outcomes of early secondary ABG around 6 years compare favorably to the outcomes of late secondary ABG.

P629 Evolution of disease phenotype, time to biological therapy and medium-, long-term surgery rates in Crohn’s disease patients in Western Hungary – a population-based study between 2007–2018, data from the Veszprem county cohort

Abstract Background The number of prospective population-based studies evaluating the natural disease course and surgical outcomes of Crohn’s disease(CD) are still limited from Eastern Europe. The present study is a continuation of the Veszprem IBD population-based cohort with a follow-up of the incidence and disease course of IBD since 1977. Our aim was to evaluate disease course by examining progression in disease phenotype, time to biological therapy and surgery rates in a prospective population-based database from Veszprem Province, including incident CD patients diagnosed between January1,2007 and December31,2018. Methods Data of 421 incident CD patients were analyzed(male/female:237/184; median age at diagnosis:29 years(y)[IQR: 21–42]). Both in-hospital and outpatient records were collected and comprehensively reviewed at diagnosis and during clinical follow-up. The mean length of follow-up was 8.53y(SD: 3.3). Probability of medium-, long-term change in disease course and surgical outcomes were analyzed. Results Disease location was ileal(L1), colonic(L2) in and ileo-colonic(L3) in 29.7%/24.5%/45.8% of patients at diagnosis. At the end of follow-up(8.53y), disease location was 27.1%/22.8%/50.1%(L1/L2/L3). The proportion of patients with upper gastrointestinal manifestation remained stable(7.6% and 8.1%), while perianal disease increased from 13.5% to 19% by the end of follow-up. Disease behavior at diagnosis was luminal(B1) in 62.5% of the patients. The probability of disease behavior progression from luminal into stenosing or penetrating phenotype was 11.9%(SE:1.7) at 3 years, 13.2%(SE:1.7) at 5 years and 17.6%(SE:1.7) at 10 years.Figure 1. The Probability of receiving biological therapy after diagnosis was 20.9%(SE:2.0) at 5 years and 28.8%(SE:2.0) at 10 years in this cohort. Overall resective surgery rate was 29.5% in the total population, while perianal surgery rate was 31.3% in patients with perianal disease at the end of follow-up. The probability of resective surgery was 20.7%(SE:2.0) at 1 year, 26.1%(SE:2.2) at 5 years and 30.7%(SE:2.4) at 10 years.Figure 2. For the probability of first perianal surgery among patients with perianal disease see Figure 3. Conclusion The probability of progression in disease behavior was lower compared to data from previous decades and similar to results from recent pan-European population-based data.(Burisch 2018, JCC). One-year surgery rates after diagnosis were considerably higher compared to previous data from our cohort or compared to Western and Northern European centers.(Lakatos 2011, IBD). Medium-term(5y) surgery rates were similar(~20%) compared to recent Hungarian and European data, while long-term(10y) rates decreased compared to data from previous decades.(Lakatos 2011,IBD; Lakatos 2012,AJG).

Intensive therapies of delayed cerebral ischemia after subarachnoid hemorrhage: a propensity-matched comparison of different center-driven strategies.

Intensive therapies of delayed cerebral ischemia (DCI) following aneurysmal subarachnoid hemorrhage (aSAH) have still controversial and unproven benefit. We aimed to compare the overall efficacy of two different center-driven strategies for the treatment of DCI respectively with and without vasospasm angioplasty. Two hundred consecutive patients with aSAH were enrolled in each of two northern European centers. In an interventional center, vasospasm angioplasty was indicated as first line rather than rescue treatment of DCI using distal percutaneous balloon angioplasty technique combined with intravenous milrinone. In non-interventional center, induced hypertension was the only intensive therapy of DCI. Radiological DCI (new cerebral infarcts not visible on immediate post-treatment imaging), death at 1month, and favorable outcome at 6months (modified Rankin scale score ≤ 2) were retrospectively analyzed by independent observers and compared between two centers before and after propensity score (PS) matching for baseline characteristics. Baseline characteristics only differed between centers for age and rate of smokers and patients with chronic high blood pressure. In the interventional center, vasospasm angioplasty was performed in 38% of patients with median time from bleeding of 8days (Q1 = 6.5;Q3 = 10). There was no significant difference of incidence of radiological DCI (9% vs.14%, P = 0.11), death (8% vs. 9%, P = 0.4), and favorable outcome 74% vs. 72% (P = 0.4) between interventional and non-interventional centers before and after PS matching. Our results suggest either that there is no benefit, or might be minimal, of one between two different center-driven strategies for intensive treatment of DCI. Despite potential lack of power or unknown confounders in our study, these results question the use of such intensive therapies in daily practice without further optimization and validation.

Geographical differences in heart failure characteristics and treatment across Europe: results from the BIOSTAT-CHF study.

Geographical differences may impact the treatment of heart failure (HF) and the results of clinical trials. We have investigated the differences between geographical areas across Europe in the BIOSTAT-CHF program. Patients with worsening HF enrolled in BIOSTAT-CHF were subdivided, according to the European geographical areas, into those from Northern countries (The Netherlands, Norway, Sweden, UK), Central countries (Germany, Poland, Serbia, Slovenia), and Mediterranean countries (France, Greece, Italy). Patients were compared for baseline characteristics, treatment, and outcomes. The primary endpoint was a composite of all-cause mortality or HF hospitalization. Among 2516 patients enrolled in BIOSTAT-CHF, 814 (32.3%) were from Northern European centers, 816 (32.4%) from Central European centers, and 886 (35.2%) from Mediterranean centers. Patients from Northern European centers were older, had more severe signs and symptoms of HF, and with lower incidence of non-cardiac comorbidities such as chronic kidney dysfunction, diabetes and, hypertension, compared to those from the Central and Mediterranean centers. Patients receiving ≥ 50% of the target dose of both ACE-I/ARB after the up-titration phase were higher in the Northern European centers compared with the other regions (60% versus 58.7% in the Central European centers and 46.5% in the Mediterranean ones; p < 0.001). The primary endpoint occurred at a higher rate in the Northern centers (44.3% versus 37.4% in central centers and 39.6% in Mediterranean centers; p = 0.014), this difference became non-significant after the adjustment for important confounders. Importantly, treatment up-titration reduced the event rates regardless of the geographical region (p for interaction > 0.05). The BIOSTAT-CHF study showed significant differences in the clinical features, treatment and prognosis in European patients with HF. Patients from the Mediterranean centers less often had the HF treatments up-titrated; however, the treatment up-titration benefited patients irrespective of their geographical region and should be part of the "default" clinical practice.

Insomnia associated with traffic noise and proximity to traffic-a cross-sectional study of the Respiratory Health in Northern Europe III population.

Exposure to traffic noise increases the risk of sleeping disturbance, but little is known about the effect of traffic-related air pollution on insomnia symptoms. We aimed to investigate the separate associations of self-reported proximity to traffic and traffic noise with insomnia. This is a cross-sectional study of the population included in the Respiratory Health in Northern Europe study, consisting of randomly selected men and women born between 1945 and 1973, from 7 Northern European centers. Hearing traffic noise in the bedroom, bedroom window proximity to traffic, and insomnia symptoms were self-reported. Bedroom window proximity to traffic was used as a surrogate for exposure to traffic-related air pollution. The following insomnia symptoms were assessed: difficulty initiating sleep, difficulty maintaining sleep, and early morning awakening. A total of 12,963 individuals was included. Traffic noise was positively associated with all three insomnia symptoms: difficulty initiating sleep (odds ratio [OR] = 3.54; 95% confidence interval [CI]: 1.85, 6.76), difficulty maintaining sleep (OR = 2.95; 95% CI: 1.62, 5.37), and early morning awakening (OR = 3.25; 95% CI: 1.97, 5.37). Proximity to traffic without disturbing noise was associated with difficulty initiating sleep (OR = 1.62; 95% CI: 1.45, 1.82). This study adds further support to the identification of traffic noise as a risk factor for insomnia. Proximity to traffic without being exposed to noise was associated with an increased risk of difficulty initiating sleep. Our findings indicate that insomnia may be associated with both traffic noise and traffic-related air pollution.

The Association of Gum Bleeding with Respiratory Health in a Population Based Study from Northern Europe

BackgroundThere is little knowledge about how oral and respiratory health is interrelated even though the mucosa of the oral cavity and airways constitutes a continuum and the exposures to these are partly similar.AimsTo investigate whether gum bleeding is related to asthma, respiratory symptoms and self-reported COPD.MethodsA postal questionnaire including questions about respiratory and oral health was sent to general population samples in seven Northern European centres. In 13,409 responders, gum bleeding when brushing teeth was reported always/often by 4% and sometimes by 20%. Logistic regressions accounted for age, smoking, educational level, centre and gender. Effects of BMI, cardio-metabolic diseases, early life factors, gastro-oesophageal reflux, dental hygiene, nasal congestion, and asthma medication were addressed.ResultsGum bleeding always/often was significantly associated with ≥3 asthma symptoms (OR 2.58, 95% CI 2.10–3.18), asthma (1.62 [1.23–2.14]) and self-reported COPD (2.02 [1.28–3.18]). There was a dose-response relationship between respiratory outcomes and gum bleeding frequency (≥3 symptoms: gum bleeding sometimes 1.42 [1.25–1.60], often/always 2.58 [2.10–3.18]), and there was no heterogeneity between centres (pheterogeneity = 0.49). None of the investigated risk factors explained the associations. The observed associations were significantly stronger among current smokers (pinteraction = 0.004).ConclusionsA consistent link between gum bleeding and obstructive airways disease was observed, not explained by common risk factors or metabolic factors. We speculate that oral pathogens might have unfavourable impact on the airways, and that the direct continuity of the mucosa of the oral cavity and the airways reflects a pathway that might provide novel opportunities for interventions.

Dietary acrylamide intake of adults in the European Prospective Investigation into Cancer and Nutrition differs greatly according to geographical region

Methodological differences in assessing dietary acrylamide (AA) often hamper comparisons of intake across populations. Our aim was to describe the mean dietary AA intake in 27 centers of 10 European countries according to selected lifestyle characteristics and its contributing food sources in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. In this cross-sectional analysis, 36994 men and women, aged 35-74years completed a single, standardized 24-hour dietary recall using EPIC-Soft. Food consumption data were matched to a harmonized AA database. Intake was computed by gender and center, and across categories of habitual alcohol consumption, smoking status, physical activity, education, and body mass index (BMI). Adjustment was made for participants' age, height, weight, and energy intake using linear regression models. Adjusted mean AA intake across centers ranged from 13 to 47μg/day in men and from 12 to 39μg/day in women; intakes were higher in northern European centers. In most centers, intake in women was significantly higher among alcohol drinkers compared with abstainers. There were no associations between AA intake and physical activity, BMI, or education. At least 50% of AA intake across centers came from two food groups "bread, crisp bread, rusks" and "coffee." The third main contributing food group was "potatoes". Dietary AA intake differs greatly among European adults residing in different geographical regions. This observed heterogeneity in AA intake deserves consideration in the design and interpretation of population-based studies of dietary AA intake and health outcomes.

Low Colectomy Rates in Ulcerative Colitis in an Unselected European Cohort Followed for 10 Years

The colectomy rate in ulcerative colitis (UC) is related to morbidity and to treatment decisions made during disease course. The aims of this study were to determine the colectomy risk in UC in the first decade after diagnosis and to identify factors that may influence the choice of surgical treatment. In 1991-1993, 781 UC patients from 9 centers located in 7 countries in northern and southern Europe and in Israel were included in a prospective inception cohort study. After 10 years of follow-up, 617 patients had complete medical records, 73 had died, and 91 had been lost to follow-up. There were no significant differences in age, sex, or disease extent at diagnosis between patients followed for 10 years and those lost to follow-up. The 10-year cumulative risk of colectomy was 8.7%: 10.4% in the northern and 3.9% in the southern European centers (P < .001). Colectomy was more likely in extensive colitis than in proctitis, with an adjusted hazard ratio (HR) of 4.1 (95% CI: 2.0-8.4). Compared with the southern centers, the adjusted HR was 2.7 (95% CI: 1.3-5.6) for The Netherlands and Norway together and 8.2 (95% CI: 3.6-18.6) for Denmark. Age at diagnosis, sex, and smoking status at diagnosis had no statistically significant influence on colectomy rates. The colectomy rate was found to be lower than that in previous publications, but there was a difference between northern and southern Europe. Colectomy was associated with extensive colitis, but the geographic variations could not be explained.

Dietary intake of different types and characteristics of processed meat which might be associated with cancer risk – results from the 24-hour diet recalls in the European Prospective Investigation into Cancer and Nutrition (EPIC)

There is increasing evidence for a significant effect of processed meat (PM) intake on cancer risk. However, refined knowledge on how components of this heterogeneous food group are associated with cancer risk is still missing. Here, actual data on the intake of PM subcategories is given; within a food-based approach we considered preservation methods, cooking methods and nutrient content for stratification, in order to address most of the aetiologically relevant hypotheses. Standardised computerised 24-hour diet recall interviews were collected within the framework of the European Prospective Investigation into Cancer and Nutrition (EPIC), a prospective cohort study in 27 centres across 10 European countries. Subjects were 22,924 women and 13,031 men aged 35-74 years. Except for the so-called 'health-conscious' cohort in the UK, energy-adjusted total PM intake ranged between 11.1 and 47.9 g day(-1) in women and 18.8 and 88.5 g day(-1) in men. Ham, salami-type sausages and heated sausages contributed most to the overall PM intake. The intake of cured (addition of nitrate/nitrite) PM was highest in the German, Dutch and northern European EPIC centres, with up to 68.8 g day(-1) in men. The same was true for smoked PM (up to 51.8 g day(-1)). However, due to the different manufacturing practice, the highest average intake of NaNO2 through PM consumption was found for the Spanish centres (5.4 mg day(-1) in men) as compared with German and British centres. Spanish centres also showed the highest intake of NaCl-rich types of PM; most cholesterol- and iron-rich PM was consumed in central and northern European centres. Possibly hazardous cooking methods were more often used for PM preparation in central and northern European centres. We applied a food-based categorisation of PM that addresses aetiologically relevant mechanisms for cancer development and found distinct differences in dietary intake of these categories of PM across European cohorts. This predisposes EPIC to further investigate the role of PM in cancer aetiology.

Consumption of added fats and oils in the European Prospective Investigation into Cancer and Nutrition (EPIC) centres across 10 European countries as assessed by 24-hour dietary recalls.

To evaluate the consumption of added fats and oils across the European centres and countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC). 24-Hour dietary recalls were collected by means of standardised computer-guided interviews in 27 redefined EPIC centres across 10 European countries. From an initial number of 36 900 subjects, single dietary recalls from 22 924 women and 13 031 men in the age range of 35-74 years were included. Mean daily intake of added fats and oils varied between 16.2 g (Varese, Italy) and 41.1 g (Malmö, Sweden) in women and between 24.7 g (Ragusa, Italy) and 66.0 g (Potsdam, Germany) in men. Total mean lipid intake by consumption of added fats and oils, including those used for sauce preparation, ranged between 18.3 (Norway) and 37.2 g day-1 (Greece) in women and 28.4 (Heidelberg, Germany) and 51.2 g day-1 (Greece) in men. The Mediterranean EPIC centres with high olive oil consumption combined with low animal fat intake contrasted with the central and northern European centres where fewer vegetable oils, more animal fats and a high proportion of margarine were consumed. The consumption of added fats and oils of animal origin was highest in the German EPIC centres, followed by the French. The contribution of added fats and oils to total energy intake ranged from 8% in Norway to 22% in Greece. The results demonstrate a high variation in dietary intake of added fats and oils in EPIC, providing a good opportunity to elucidate the role of dietary fats in cancer aetiology.

Meat consumption in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts: results from 24-hour dietary recalls.

To evaluate meat intake patterns in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohorts. 24-Hour dietary recalls were assessed within the framework of a prospective cohort study in 27 centres across 10 European countries by means of standardised computer-assisted interviews. In total, 22 924 women and 13 031 men aged 35-74 years. Mean total meat intake was lowest in the 'health-conscious' cohort in the UK (15 and 21 g day-1 in women and men, respectively) and highest in the north of Spain, especially in San Sebastian (124 and 234 g day-1, respectively). In the southern Spanish centres and in Naples (Italy), meat consumption was distinctly lower than in the north of these countries. Central and northern European centres/countries showed rather similar meat consumption patterns, except for the British and French cohorts. Differences in the intake of meat sub-groups (e.g. red meat, processed meat) across EPIC were even higher than found for total meat intake. With a few exceptions, the Mediterranean EPIC centres revealed a higher proportion of beef/veal and poultry and less pork or processed meat than observed in central or northern European centres. The highest sausage consumption was observed for the German EPIC participants, followed by the Norwegians, Swedish, Danish and Dutch. The results demonstrate distinct differences in meat consumption patterns between EPIC centres across Europe. This is an important prerequisite for obtaining further insight into the relationship between meat intake and the development of chronic diseases.

Evaluation of dietary quality in relationship to nutritional and lifestyle factors in elderly people of the US Framingham Heart Study and the European SENECA study.

To evaluate dietary quality of European and American elderly subjects using different derivatives of dietary patterns (dietary scores and clusters) and to investigate the relationship of these approaches to nutritional and lifestyle factors. Data from the cross-sectional SENECA baseline study and Framingham Heart Study (original cohort and offspring) were used for data analysis. Food intake data were summarised into dietary clusters and into dietary scores (Healthy Diet Indicator and Mediterranean Diet Score). These measures of dietary quality were then tested for associations with lifestyle factors and measures of nutritional status. The study population, aged 70-77 y, consisted of 828 subjects from Framingham, MA (USA) and 1282 subjects from the following European centres: Hamme, Belgium; Roskilde, Denmark; Padua, Italy; Culemborg, The Netherlands; Vila Franca de Xira, Portugal; Betanzos, Spain; and Yverdon, Burgdorf and Bellinzona, Switzerland. Dietary intake varied widely across the European and American research centres. In general, Southern European centres and Framingham had higher mean diet scores, indicating a higher dietary quality, than Northern European centres (MD-scores: 4.2-4.4 vs 2.7-3.5). Cluster analysis identified the following five dietary patterns characterised by: (1) sugar and sugar products; (2) fish and grain; (3) meat, eggs and fat; (4) milk and fruit; and (5) alcohol intake. The meat, eggs and fat pattern had significantly lower average dietary quality, as measured with all three diet scores than all other groups except the alcohol group. The fish and grain group had significantly better Mediterranean diet scores than all other groups. Dietary scores and dietary clusters are complementary measures to classify dietary quality. The associations with nutritional and lifestyle factors indicate the adequate categorisation into dietary quality groups. European Union, US Department of Agriculture, Agriculture Research Service, under agreement (58-1950-9-001), Haak Bastiaanse-Kuneman Foundation.