Biomedical subjects

M G Russel

Publications and source records attributed to M G Russel.

At least 19 recordsLinked to original sources

PubMed2005

Phenotype at diagnosis predicts recurrence rates in Crohn's disease.

BACKGROUND: In Crohn's disease (CD), studies associating phenotype at diagnosis and subsequent disease activity are important for patient counselling and health care planning. AIMS: To calculate disease recurrence rates and to correlate these with phenotypic traits at diagnosis. METHODS: A prospectively assembled uniformly diagnosed European population based inception cohort of CD patients was classified according to the Vienna classification for disease phenotype at diagnosis. Surgical and non-surgical recurrence rates throughout a 10 year follow up period were calculated. Multivariate analysis was performed to classify risk factors present at diagnosis for recurrent disease. RESULTS: A total of 358 were classified for phenotype at diagnosis, of whom 262 (73.2%) had a first recurrence and 113 patients (31.6%) a first surgical recurrence during the first 10 years after diagnosis. Patients with upper gastrointestinal disease at diagnosis had an excess risk of recurrence (hazard ratio 1.54 (95% confidence interval (CI) 1.13-2.10)) whereas age >/=40 years at diagnosis was protective (hazard ratio 0.82 (95% CI 0.70-0.97)). Colonic disease was a protective characteristic for resective surgery (hazard ratio 0.38 (95% CI 0.21-0.69)). More frequent resective surgical recurrences were reported from Copenhagen (hazard ratio 3.23 (95% CI 1.32-7.89)). CONCLUSIONS: A mild course of disease in terms of disease recurrence was observed in this European cohort. Phenotype at diagnosis had predictive value for disease recurrence with upper gastrointestinal disease being the most important positive predictor. A phenotypic North-South gradient in CD may be present, illustrated by higher surgery risks in some of the Northern European centres.

Adult↗

PubMed2005

Crohn's disease: increased mortality 10 years after diagnosis in a Europe-wide population based cohort.

BACKGROUND: No previous correlation between phenotype at diagnosis of Crohn's disease (CD) and mortality has been performed. We assessed the predictive value of phenotype at diagnosis on overall and disease related mortality in a European cohort of CD patients. METHODS: Overall and disease related mortality were recorded 10 years after diagnosis in a prospectively assembled, uniformly diagnosed European population based inception cohort of 380 CD patients diagnosed between 1991 and 1993. Standardised mortality ratios (SMRs) were calculated for geographic and phenotypic subgroups at diagnosis. RESULTS: Thirty seven deaths were observed in the entire cohort whereas 21.5 deaths were expected (SMR 1.85 (95% CI 1.30-2.55)). Mortality risk was significantly increased in both females (SMR 1.93 (95% CI 1.10-3.14)) and males (SMR 1.79 (95% CI 1.11-2.73)). Patients from northern European centres had a significant overall increased mortality risk (SMR 2.04 (95% CI 1.32-3.01)) whereas a tendency towards increased overall mortality risk was also observed in the south (SMR 1.55 (95% CI 0.80-2.70)). Mortality risk was increased in patients with colonic disease location and with inflammatory disease behaviour at diagnosis. Mortality risk was also increased in the age group above 40 years at diagnosis for both total and CD related causes. Excess mortality was mainly due to gastrointestinal causes that were related to CD. CONCLUSIONS: This European multinational population based study revealed an increased overall mortality risk in CD patients 10 years after diagnosis, and age above 40 years at diagnosis was found to be the sole factor associated with increased mortality risk.

Adolescent↗

PubMed2003

[Calprotectin: a fecal marker for diagnosis and follow-up in patients with chronic inflammatory bowel disease].

Chronic inflammatory bowel disease (IBD) is characterised clinically by periods of well being interspersed by exacerbations of disease activity. Differentiation between IBD and less severe disorders such as irritable bowel syndrome requires invasive and expensive diagnostic procedures. Diagnostic differentiation between active disease, symptoms due to residual constriction of the fibrotic lumen and functional symptoms is a well-known problem. There are not yet any laboratory parameters with sufficient discrimination in terms of sensitivity and specificity. Colonoscopy and histopathological examination remain the gold standards: in Crohn's disease this may be complex due to the variable localisation of the inflammatory process. Abdominal scintigraphic procedures, although informative, are complex and expensive. The recent assessment of faecal calprotectin, a calcium- and zinc-binding anti-inflammatory protein found in neutrophilic granulocytes and monocytes, offers an attractive alternative as an index of intestinal inflammation. We measured this stable marker in random stool samples from 187 patients including healthy volunteers, patients with endoscopically classified active IBD or IBD in remission, and patients with other gastrointestinal disorders. Disease activity was monitored by clinical symptoms, blood tests and endoscopy. Our results confirm previous literature findings that faecal calprotectin is a promising and useful non-invasive tool in the screening of patients presenting with abdominal pain and diarrhoea. Moreover, calprotectin seems helpful in differentiating between active and non-active IBD and possibly also in the monitoring of disease activity.

Biomarkers↗

PubMed2001

[Epidemiological developments and insights in chronic inflammatory bowel diseases].

In the Western world, a sharp increase in the incidence of both Crohn's disease and ulcerative colitis was observed during the sixties and seventies, after which it reached a plateau at around 7 and 12 new cases per 100,000 inhabitants per year, respectively. Both chronic inflammatory bowel diseases usually commence between 15 and 30 years of age. Most patients have a normal life expectancy. A multifactorial model has been proposed to explain the pathogenesis, in which there seems to be an interaction between genetic predisposition, environmental factors and an altered immune response (occurring either after or because of the disease). Smoking is a clear risk factor in the development of Crohn's disease and it also negatively influences the clinical outcome. On the other hand, stopping smoking is a risk factor in the development of ulcerative colitis.

Adolescent↗

PubMed2001

Musculoskeletal manifestations in a population-based cohort of inflammatory bowel disease patients.

BACKGROUND: Musculoskeletal disorders are the most common extra-intestinal manifestation of inflammatory bowel disease (IBD). Wide ranges of prevalence have been reported depending on the criteria used to define spondylarthropathy and on the selection of patients. We aimed to evaluate the prevalence and clinical spectrum of musculoskeletal manifestations in an inception cohort of European IBD patients. METHODS: From 1 October 1991 to 30 September 1993, 202 IBD patients were diagnosed in three centres of two countries (Italy and The Netherlands) by means of a population-based inception cohort study. Of this group of patients, 160 (79%) were interviewed and examined by a rheumatologist and a gastroenterologist in the period June-September 1996. A total of 139/160 patients had an antero-posterior radiograph of the pelvis, and in 140/160 HLA-B27 was determined. RESULTS: 53 (33.1%) of the 160 patients had experienced at least one musculoskeletal manifestation, 29 (18.1%) satisfied the European Spondylarthropathy Study Group (ESSG) criteria for spondylarthropathy and 5 (3.1%) satisfied the modified New York criteria for ankylosing spondylitis. However, 23 (14.4%) patients developed one or more spondylarthropathy-related manifestations without fulfilling any of the classification criteria. In patients satisfying ESSG criteria a significantly higher frequency of women (P = 0.03), of ocular and liver involvement (P = 0.01 and P = 0.03, respectively), and use of immunosuppressive drugs (P = 0.02) was observed. CONCLUSION: Our study shows a high prevalence of musculoskeletal manifestations in an inception cohort of IBD patients. The clinical spectrum is broader than that defined by spondylarthropathy criteria.

Adult↗

PubMed2001

Muscoloskeletal manifestations in inflammatory bowel disease.

Muscoloskeletal manifestations are the most common extraintestinal complications of inflammatory bowel disease. Wide ranges in prevalence have been reported, depending on the criteria used to define spondylarthropathy. In 1991, the European Spondylarthropathy Study Group developed classification criteria that included previously neglected cases of undifferentiated spondylarthropathies, which had been ignored in most of the oldest epidemiological studies on inflammatory bowel disease. The spectrum of muscoloskeletal manifestations in inflammatory bowel disease patients includes all of the clinical features of spondylarthropathies: peripheral arthritis, inflammatory spinal pain, dactylitis, enthesitis (Achilles tendinitis and plantar fasciitis), buttock pain and anterior chest wall pain. Radiological evidence of sacroiliitis is common but not obligatory. The articular manifestations begin either concomitantly or subsequent to the bowel disease; however, the onset of spinal disease often precedes the diagnosis of inflammatory bowel disease. The prevalence of the different muscoloskeletal manifestations is similar in ulcerative colitis and Crohn's disease. Symptoms usually disappear after proctocolectomy. The pathogenetic mechanisms that produce the muscoloskeletal manifestations in inflammatory bowel disease are unclear. Several arguments favour an important role of the intestinal mucosa in the development of spondylarthropathy. The natural history is characterized by periods of flares and remission; therefore, the efficacy of treatment is difficult to establish. Most patients respond to rest, physical therapy and nonsteroidal anti-inflammatory drugs, but these drugs may activate bowel disease. Sulphasalazine may be recommended in some patients. There is no indication for the systemic use of steroids.

Humans↗

PubMed2000

Bone mineral density in patients with recently diagnosed inflammatory bowel disease.

BACKGROUND & AIMS: A high prevalence of osteoporosis is reported in inflammatory bowel disease (IBD), and its pathogenesis is not completely resolved. We investigated whether bone mineral density (BMD) in patients with IBD at diagnosis is lower than in population controls, and whether BMD differs between patients with Crohn's disease and those with ulcerative colitis. METHODS: In 68 patients and 68 age- and gender-matched population controls, BMD of total body, spine, and hip was assessed using dual-energy x-ray absorptiometry within 6 months after establishing the diagnosis. Determinants for low BMD were assessed. RESULTS: There were no significant differences in BMD (g/cm(2)) between patients and controls, and no significant differences in BMD between patients with either Crohn's disease or ulcerative colitis. Multivariate regression analysis showed that duration of complaints longer than 6 months before diagnosis (P = 0.041), age (P = 0.019), and body mass index less than 20 kg/m(2) (P = 0.006) significantly correlated with low BMD. CONCLUSIONS: BMD in patients with recently diagnosed IBD was not significantly decreased compared with population controls. Subsequent development of osteoporosis in patients with IBD seems to be a phenomenon related to the disease process and/or the treatment modalities of IBD.

Absorptiometry, Photon↗

PubMed2000

Disease outcome in inflammatory bowel disease: mortality, morbidity and therapeutic management of a 796-person inception cohort in the European Collaborative Study on Inflammatory Bowel Disease (EC-IBD).

BACKGROUND: The course of inflammatory bowel diseases (IBD) has mainly been studied using different methods in single patient cohorts. The aim of the present study was to assess clinical aspects of disease outcome in a population-based cohort of IBD patients over a 4-year period in multiple centres across Europe. METHODS: A total of 796 patients with IBD diagnosed in 10 centres between October 1991 and October 1993, registered at the EC IBD study centre (98% of the original cohort), participated in the study. Investigators filled out a standard follow-up form containing questions on the method of follow-up, vital status of the patient, change in diagnosis, extraintestinal manifestations, medical and surgical treatment, and physician's global assessment of disease activity. RESULTS: Complete relief of the complaints was reported in 255 (48%) patients with ulcerative colitis (UC), 9 (50%) with indeterminate colitis (IC), but only in 87 (35%) of patients with Crohn disease (CD). Improvement was reported in 195 (37%) patients with UC, 113 (45%) with CD and 6 (33%) with IC. During the 4-year follow-up period, 23 patients died (14 UC, 8 CD. and 1 IC). The mean age at death was 69.3 years (s, 14.9 years). The deaths of three patients were recorded as directly due to IBD. CONCLUSIONS: With the present approach to therapeutic management the short-term outcome of patients with IBD seems to be favourable in 10 medical centres in the north and south of Europe. However, more detailed studies including both objective and subjective measures are necessary.

Adult↗

PubMed2000

Nutritional supplementation with N-3 fatty acids and antioxidants in patients with Crohn's disease in remission: effects on antioxidant status and fatty acid profile.

In patients with Crohn's disease (CD), malnutrition is frequently observed and is generally accepted to be an important issue. The aim of this study was to investigate the effects of 3 months of supplementation with a liquid formula containing either antioxidants (AO) or n-3 fatty acids plus AO on the antioxidant status and fatty acid profile of plasma phospholipids and adipose tissue, respectively, in patients with long-standing CD currently in remission. In a randomized, double-blind placebo-controlled study, CD patients received either placebo, AO, or n-3 fatty acids plus AO for 3 months in addition to their regular diet. In all, 25/37 CD patients completed the study. AO status was assessed by blood biochemical parameters. A statistical per-protocol analysis was performed. Serum concentrations of selenium, vitamin C, and vitamin E, the activity of superoxide dismutase and total antioxidant status were significantly (p < 0.05) increased after AO supplementation. Furthermore, compared with controls, serum concentrations of beta-carotene, selenium, and vitamin C and the activity of glutathione peroxidase (GPx) were significantly (p < 0.05) lower before supplementation; however, after AO supplementation these levels were not significantly different from controls (except for GPx). N-3 fatty acids plus AO supplementation significantly (p < 0.05) decreased the proportion of arachidonic acid, and increased the proportion of eicosapentanoic acid and docosahexanoic acid in both plasma phospholipids and adipose tissue. Supplementation with antioxidants improved antioxidant status in patients with CD in remission. In addition, supplementation with n-3 fatty acids plus antioxidants significantly changed the eicosanoid precursor profile, which may lead to the production of eicosanoids with attenuated proinflammatory activity. This study indicates that an immunomodulating formula containing n-3 fatty acids and/or AO may have the potential to play a role in the treatment of CD.

Adult↗

PubMed2000

Diet as a risk factor for the development of ulcerative colitis.

OBJECTIVE: Dietary factors have been considered as a possible risk factor for ulcerative colitis (UC). However, available data are inconsistent. The aim of the present study was to evaluate the etiological role of dietary factors in the development of UC. METHODS: Recently diagnosed (<6 Months) UC patients (n = 43) and age- and gender-matched population controls (n = 43) were studied in a case-control design. The crosscheck dietary history method was used to assess dietary intake of 5 yr before the study. Adipose tissue fatty acid composition was used as a biomarker of long-term fat intake. Conditional logistic regression-derived odds ratios (OR), and 95% confidence intervals (CI) were used for statistical analysis. Dietary intake ORs were adjusted for energy intake. RESULTS: High intakes of monounsaturated fat (OR: 33.9 [95% CI 2.6-443.1]), polyunsaturated fat (OR: 5.1 [95% CI 1.0-26.7]), and vitamin B6 (OR: 6.9 [95% CI 1.6-30.7]) were associated with an increased risk to develop UC. No other significant associations were found with UC risk. CONCLUSIONS: High intakes of mono- and polyunsaturated fat and vitamin B6 may enhance the risk of developing UC. Whether this observation is a true risk factor in the development of UC or rather a reflection of a certain dietary lifestyle needs to be investigated.

Adult↗

PubMed2000

Osteopenia and osteoporosis in Crohn's disease: prevalence in a Dutch population-based cohort.

Reduced bone mineral density (BMD) has been reported in 3-77% of patients with inflammatory bowel disease (IBD). The majority of these studies are cross-sectional and from tertiary referral centres. The aim of our study was to estimate the prevalence of metabolic bone disease and of symptomatic fractures in a population of patients with Crohn's disease (CD) living in a well-defined geographic area. Patients with CD living in three adjacent municipalities within the IBD South-Limburg study area were investigated. BMD was measured by dual X-ray absorptiometry (DXA) of the femoral neck, lumbar spine and total body. The population comprised of 181 CD patients, 23 of whom were excluded. One-hundred-and-nineteen (75%) of the 158 eligible patients (37 males, 82 females with a mean age of 42 years (17-78)) were investigated. Osteopenia of lumbar spine and/or femoral neck was found in 45% of patients. Osteoporosis was found in another 13% of patients. Mean BMD (T-score) of femoral neck was significantly lower than of lumbar spine (P < 0.001). Male CD patients and patients aged under 18 at diagnosis are more at risk of having a low bone mass at the lumbar spine (P < 0.001) and total body (P = 0.018). The prevalence of osteoporosis in postmenopausal CD patients (29%) was significantly higher than in premenopausal patients (3%) (odds ratio: 12). Twenty-nine of 119 (24%) patients had a history of symptomatic fractures. Osteopenia and osteoporosis are frequent in CD and should have the full attention of the treating physician.

Absorptiometry, Photon↗

PubMed1998

High incidence of inflammatory bowel disease in The Netherlands: results of a prospective study. The South Limburg IBD Study Group.

PURPOSE: To gain recent epidemiologic information about inflammatory bowel disease in The Netherlands, a prospective study over four years (1991-1995) was performed. METHODS: The incidence of inflammatory bowel disease and its subgroups was examined using standardized reports of newly diagnosed patients. A separate study compared the Inflammatory Bowel Disease Registration and computerized diagnostic files of a subgroup of general practitioners with the aim of estimating completeness of case ascertainment. RESULTS: The following mean incidence rates (per 100,000 inhabitants and year) were found: 6.9 (95 percent confidence interval, 5.9-7.9) for Crohn's disease, 10 (95 percent confidence interval, 8.7-11.2) for ulcerative colitis (23 percent of these with ulcerative proctitis), and 1.1 (95 percent confidence interval, 0.7-1.5) for indeterminate colitis. In the age category 20 to 29 years, the incidence rate of Crohn's disease with small-bowel involvement was higher in females than in males. In extended ulcerative colitis, a male preponderance was observed in the older age groups. Estimated case ascertainment was 78 percent. CONCLUSIONS: Compared with recent studies in neighboring countries, the observed age and gender standardized incidence rates are high in the south of The Netherlands. Completeness of case ascertainment might have contributed to this observation; however, case ascertainment was low in ulcerative proctitis. In the study area, differences in age and gender standardized incidence rates and in disease localizations could be compatible with an influence of environmental risk factors.

Adolescent↗

PubMed1998

Modern life' in the epidemiology of inflammatory bowel disease: a case-control study with special emphasis on nutritional factors.

OBJECTIVE: The rising incidence of inflammatory bowel disease (IBD) since the Second World War coincides with profound changes of the dietary pattern. The aim of the study was to investigate the possible pathogenic role of some characteristic 'modern life' dietary factors in IBD. DESIGN: Case-control, studying risk factors in recently diagnosed cases, 290 with Crohn's disease and 398 with ulcerative colitis, compared with 616 population controls. Smoking, age, gender and education were taken into account by using logistic regression analysis. SETTING: Hospital cases and population controls. INTERVENTIONS: Questionnaires. MAIN OUTCOME MEASURES: Logistic regression-derived odds ratios. RESULTS: A positive association with cola drinks [OR: 2.2 (95% CI 1.5-3.1)], chewing gum [OR: 1.5 (95% CI: 1.1-2.1)] and chocolate consumption [OR: 2.5 (95% CI: 1.8-3.5)] and a negative association with citrus fruit consumption [OR: 0.5 (95% CI 0.3-0.7)] and the development of Crohn's disease were found. Consumption of cola drinks [OR: 1.6 (95% CI 1.1-2.3)] and chocolate consumption [OR: 2.5 (95% CI 1.8-3.5)] were positively associated with developing ulcerative colitis. There was a negative association between the intake of citrus fruits [OR: 0.5 (95% CI 0.4-0.8)] and 'having a stuffed pet' for a period longer than 5 years [OR: 0.6 (95% CI 0.4-0.9)] and developing the disorder. No association with the frequency of tooth brushing and developing IBD was found. CONCLUSION: All the nutritional items mentioned may be true risk factors or they just might be the expression of a modern life-style also involving other risk factors for the development of IBD which at the present are still unknown.

Adult↗

PubMed1998

Is appendectomy a causative factor in ulcerative colitis?

There are strong indicators that the aetiology of inflammatory bowel disease should be regarded as multifactorial, involving an interaction between genetic and environmental factors which give rise to an inadequate immunological response. During the past decade at least seven case-control studies have shown an inverse association between appendectomy and ulcerative colitis. Conclusions have been that either ulcerative colitis protects against appendicitis, or appendectomy protects against ulcerative colitis. The immunological function of the appendix is not well known, but experimental studies suggest that the appendix is possibly an important site for priming of the cells involved in the development of inflammatory bowel disease. Experimental and prospective cohort studies are needed to provide more insight in a possible relation between ulcerative colitis and the appendix.

Appendectomy↗

PubMed1998

Inflammatory bowel disease: is there any relation between smoking status and disease presentation? European Collaborative IBD Study Group.

Smoking is associated with Crohn's disease and nonsmoking with ulcerative colitis. The aim of this study was to compare the clinical features at diagnosis and during the first year of follow-up in smokers and nonsmokers with inflammatory bowel disease (IBD). In 19 centers across Europe, a prospective study was performed of 457 newly diagnosed patients with Crohn's disease and 930 with ulcerative colitis. The characteristics of the disease were recorded by the treating physician by using a standard protocol at the time of diagnosis. Treatment characteristics were assessed after 1 year of follow-up. Weight loss occurred significantly more often in smoking patients with Crohn's disease, as well as in smokers with ulcerative colitis (p < 0.02), and diarrhea was more frequent in smoking patients with Crohn's disease compared with non-smoking individuals (p < 0.01). Patients with Crohn's disease who smoke were less likely to have colonic involvement (p < 0.01) and were more often prescribed immunosuppressive medication (p < 0.02). The study suggests that (a) smoking protects the colon from inflammation and (b) is associated with more active disease in Crohn's disease. The association between weight loss and smoking in both diseases is probably due to a general effect of smoking. The reported relation between smoking and the course of Crohn's disease is a strong argument for encouraging patients to give up smoking.

Adolescent↗

PubMed1997

Appendectomy and the risk of developing ulcerative colitis or Crohn's disease: results of a large case-control study. South Limburg Inflammatory Bowel Disease Study Group.

BACKGROUND & AIMS: Appendectomy has been pointed out as a protective factor for ulcerative colitis (UC). The aim of this study was to elucidate the role of appendectomy in inflammatory bowel disease (IBD). METHODS: Prevalent as well as incident cases with IBD were studied separately using a pairwise age- and sex-matched case-control study design. RESULTS: In 232 prevalent UC cases, the risk of developing UC was significantly lower after previous appendectomy (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.15-0.80); subgroup analysis found a protective effect only in pancolitis (OR, 0.2; 95% CI, 0.02-0.7). In 208 patients with Crohn's disease (CD), the OR was not significantly increased but a positive association with appendectomy was observed in ileocecal disease. A significant larger proportion of appendectomies was performed close to the time of diagnosis. Smoking was not a confounding factor. No statistically significant associations were observed in incident IBD patients. Prevalent and incident patients taken together resulted in ORs of 0.44 (95% CI, 0.24-0.78) in UC and 1.65 (95% CI, 0.96-2.91) in CD. CONCLUSIONS: An overall protective role of appendectomy for UC was observed. The observations in CD suggest that appendectomy in some cases was a result of still undiagnosed CD.

Adolescent↗

PubMed1997

Validation of the Dutch translation of the Inflammatory Bowel Disease Questionnaire (IBDQ): a health-related quality of life questionnaire in inflammatory bowel disease.

Health-related quality of life assessment can benefit several groups involved with health care. The aim of our study was to assess construct validity, reliability, discriminant ability and sensitivity to change of the Dutch translation of the Inflammatory Bowel Disease Questionnaire (IBDQ), a disease-specific quality-of-life questionnaire. A group of 120 IBD patients completed the IBDQ and two Visual Analogue Scales concerning general well-being and bowel function twice. Fifty-two patients also completed the Short-Form 36 twice. Disease activity was assessed once. Correlations between the IBDQ scores and the global assessments were reasonably high and the IBDQ was shown to be discriminative. High intraclass correlation coefficients between both measurements of the IBDQ were observed in patients who reported no change in bowel complaints. In contrast, significant differences were found between both moments in patients who reported change. The Dutch IBDQ proved to be valid, discriminative and reliable.

Adolescent↗

PubMed1997

Familial aggregation of inflammatory bowel disease: a population-based study in South Limburg, The Netherlands. The South Limburg IBD Study Group.

BACKGROUND: The aim of our study was to investigate the prevalence of Crohn's disease (CD) and ulcerative colitis (UC) in first-degree relatives of IBD patients living in a well-defined area. METHODS: IBD patients known at the IBD Registration South Limburg as well as population controls were asked about the occurrence of IBD in their first-degree relatives. RESULTS: IBD was reported and confirmed in 16 (out of 1554) relatives by 11 (out of 245) patients. Prevalence of IBD was highest for siblings (1.5%) and children (1.3%), while only 0.2% of the parents were affected with IBD. Among relatives of the control subjects, IBD was observed in 0.8% (versus 4.5% in IBD patients), resulting in an odds ratio of 5.7 (95% CI: 2.0-16.7). CONCLUSIONS: The observed risk of IBD for first-degree relatives of IBD patients was higher than in controls. However, the risk in our population is lower than has been reported by other centres, possibly because of the population-based character of our study.

Adolescent↗