Ulcerative colitis in the county of Uppsala 1945-2007: incidence and clinical characteristics.

OBJECTIVE: The incidence of ulcerative colitis has increased in many parts of the world during the second part of the twentieth century. In the county of Uppsala in the middle part of Sweden, the epidemiology of ulcerative colitis has been studied during two different time periods, 1945-1964 and 1965-1983. These figures have now been compared to the present day situation, 2005-2007. METHOD: The incidence figures in the two first studies were the results of retrospective studies but the figures from 2005 to 2007 were generated prospectively. The clinical characteristics during 1945-1964 were described according to the Montreal classification and a comparison between the first and third study periods could therefore be done. RESULTS: During the study period, the population of the county increased from 146000 to 323270 inhabitants. The crude incidence of ulcerative colitis increased from 2 to 19.2 new cases per 100000 inhabitants/year. The age distribution was remarkably stable when the first 20 years was compared with the last 3 years (mean age 36 vs. 38.1 and range 2-84 vs. 3-84) except for those below 11 years of age. CONCLUSION: Between 1945 and 2007 the incidence of UC in the County of Uppsala increased from 2 to 19.2 new cases/100000. The increase affected all age groups except those below 11 years of age.

Declining incidence of meningococcal disease in Denmark, confirmed by a capture-recapture analysis for 1994 and 2002.

Denmark has in the past 10 years experienced a decrease in the number of notified cases of meningococcal disease. In 1994 the completeness of the Notification System for Meningococcal Disease (NSMD) was estimated as 96% (95% CI 93-98). To answer the question whether the observed decrease reflects a real decrease in the incidence; we estimated the completeness of the notification system in 2002. We estimated the completeness of registration by a capture-recapture analysis. As the first data source, we used the national NSMD, which is an integrated surveillance system between the Department of Epidemiology and the Neisseria Reference Laboratory. The second independent source was the National Patient Registry (NPR). In 2002, the completeness of the NSMD was estimated as 96% (95% CI 95-98) and for the NPR as 84% (95% CI 82-85). The 'real' incidence rate was 1.9/100 000 population, which compared to 4.4/100 000 population in 1994. We concluded that the observed decrease in incidence rate is real. The NSMD in Denmark functions well and captures almost all cases of meningococcal disease. The complete registration which includes a unique personal identification number serves as an outstanding source for nationwide registry linkage studies.

Using sentinel surveillance to monitor effectiveness of influenza vaccine is feasible: a pilot study in Denmark.

The influenza vaccine for the season 2003/04 did not contain the circulating A(H3N2)/Fujian virus strain. Vaccine effectiveness (VE) estimates were needed but unavailable. We explored whether or not laboratory based influenza surveillance can be used to estimate VE. We carried out a case-control study nested within Danish sentinel surveillance. A case was defined as a person aged 25 or above with A(H3N2)/Fujian/411/02 influenza. Four controls per case, matched on age groups and time, were selected from clients of sentinel practitioners (SP) who reported cases. SPs collected the following data in structured one-page questionnaires: vaccination status, chronic illness and previous pneumococcal vaccination. We sent postal survey questionnaires to participating SPs to assess acceptability and simplicity of data collection. Twenty four cases were identified. Data from 19 case-control sets were analysed. One control was excluded because information on vaccination status was missing. Two of the 19 cases and 11 of 75 controls had been vaccinated against influenza. The VE adjusted for chronic illness was 33% (95% CI 0%-88%) and 37% (95% CI 0%-89%) when excluding 5 controls with influenza-like illness. Twenty two SPs returned survey questionnaires. Fifteen of 17 SPs reported that it was easy to find controls. SPs collected data through interviews and clinical notes, spending 1 to 5 minutes per case and 5 to 15 minutes for all four controls. Nineteen of 22 SPs considered the amount of time they spent on the study to be acceptable, 17 said that they would like to participate again, and none ruled out further participation. Monitoring VE within sentinel surveillance systems is feasible. The small numbers in our study limit interpretation of VE. Expansion to a European multicountry study could overcome this limitation and provide VE estimates earlier in the season, for different age groups and emerging virus strains, including new and pandemic subtypes.

Food does not affect the pharmacokinetics of tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist.

Tesaglitazar is a dual peroxisome proliferator-activated receptor (PPAR) alpha/gamma agonist in development to treat lipid and glucose abnormalities associated with type 2 diabetes. This study evaluated the effects of food on tesaglitazar pharmacokinetics. In an open, randomized, 2-way crossover study, 20 healthy men received tesaglitazar 1 mg during fasting and after a high-fat, high-calorie breakfast. Blood samples were taken to assess pharmacokinetic variables. Systemic exposure to tesaglitazar was unaffected by food intake. Estimated ratios were 0.99 (90% confidence interval [CI], 0.94-1.04) for fed/fasted area under plasma concentration-time curve and 0.82 (90% CI, 0.78-0.86) for fed/fasted maximum plasma concentration (C(max)). Mean C(max) was approximately 18% lower (0.41 [95% CI, 0.38-0.43] versus 0.50 [95% CI, 0.47-0.53] mumol/L), and median time to C(max) was increased (2.00 vs 0.75 h) in fed versus fasted state. The median difference of t(max) was 1.25 h (P = .0001, signed-rank test). Tesaglitazar was well tolerated. Tesaglitazar pharmacokinetics is unaffected by food intake, allowing once-daily administration of tesaglitazar with or without food in clinical practice.

Effectiveness of different policies in preventing meningococcal disease clusters following a single case in day-care and pre-school settings in Europe.

National policies for chemoprophylaxis after single cases of meningococcal disease in day-care or nursery settings vary across Europe. We carried out a multi-national retrospective study to compare the effectiveness of different policies. Countries were divided into those recommending chemoprophylaxis only to close contacts (policy A, close) and those recommending chemoprophylaxis for all children in the same nursery (policy B, mass). Country-specific relative risk (RR) of a cluster was defined as the ratio of the number of clusters observed to the number of clusters expected by chance. In total, 37 clusters were identified between 1 January 1993 and 31 December 2002. After adjusting for marked heterogeneity in RR by country, the ratio of RR between countries suggested possible benefit from mass prophylaxis (RR ratio 3.8, 95% CI 0.7-22.0), although the difference was not statistically significant (P=0.22). The costs of this approach and the low risk of clustering need to be taken into account when deciding national policy.

Using sentinel surveillance to monitor effectiveness of influenza vaccine is feasible: A pilot study in Denmark.

The influenza vaccine for the season 2003/04 did not contain the circulating A(H3N2)/Fujian virus strain. Vaccine effectiveness (VE) estimates were needed but unavailable. We explored whether or not laboratory based influenza surveillance can be used to estimate VE. We carried out a case-control study nested within Danish sentinel surveillance. A case was defined as a person aged 25 or above with A(H3N2)/Fujian/411/02 influenza. Four controls per case, matched on age groups and time, were selected from clients of sentinel practitioners (SP) who reported cases. SPs collected the following data in structured one-page questionnaires: vaccination status, chronic illness and previous pneumococcal vaccination. We sent postal survey questionnaires to participating SPs to assess acceptability and simplicity of data collection. Twenty four cases were identified. Data from 19 case-control sets were analysed. One control was excluded because information on vaccination status was missing. Two of the 19 cases and 11 of 75 controls had been vaccinated against influenza. The VE adjusted for chronic illness was 33% (95% CI 0%-88%) and 37% (95% CI 0%-89%) when excluding 5 controls with influenza-like illness. Twenty two SPs returned survey questionnaires. Fifteen of 17 SPs reported that it was easy to find controls. SPs collected data through interviews and clinical notes, spending 1 to 5 minutes per case and 5 to 15 minutes for all four controls. Nineteen of 22 SPs considered the amount of time they spent on the study to be acceptable, 17 said that they would like to participate again, and none ruled out further participation. Le contrôle de l'EV au sein des systèmes de surveillance sentinelle est faisable. Les nombres restreints de notre étude limitent l'interprétation de l'EV. Une étude étendue à l'échelle européenne, comprenant plusieurs pays, pourrait surmonter cette limitation et offrir des évaluations de l'efficacité vaccinale plus tôt dans la saison, pour différents groupes d'âge et pour des souches virales émergentes, incluant les sous-types nouveaux et pandémiques. Monitoring VE within sentinel surveillance systems is feasible. The small numbers in our study limit interpretation of VE. Expansion to a European multicountry study could overcome this limitation and provide VE estimates earlier in the season, for different age groups and emerging virus strains, including new and pandemic subtypes.

Ascertainment of meningococcal disease in Europe.

Meningococcal disease surveillance in most countries is based upon a combination of statutory notification systems and laboratory reporting, both of which are recognised to underestimate the true burden of disease. The incidence of meningococcal disease varies throughout Europe, and although there are many reasons for this, it is important to quantify the degree of under-ascertainment in order to validate international comparisons. Here, we review the literature on the ascertainment of meningococcal disease in Europe and the available methods for estimating the degree of under-reporting. We found that the sensitivity of surveillance varies between countries and over time, with estimates ranging from 40% to 96%. We identified five methods suitable for conducting ascertainment studies, from simple comparative studies to more complicated capture-recapture and regression analyses. Studies of ascertainment may be used to identify weaknesses and biases in surveillance data, and facilitate the improvement of these systems. These findings are relevant to the surveillance of other infectious diseases, particularly those with lower mortality and a lower public profile than meningococcal disease, for which ascertainment may be worse.

Ascertainment of meningococcal disease in Europe.

Meningococcal disease surveillance in most countries is based upon a combination of statutory notification systems and laboratory reporting, both of which are recognised to underestimate the true burden of disease. The incidence of meningococcal disease varies throughout Europe, and although there are many reasons for this, it is important to quantify the degree of under-ascertainment in order to validate international comparisons. Here, we review the literature on the ascertainment of meningococcal disease in Europe and the available methods for estimating the degree of under-reporting. We found that the sensitivity of surveillance varies between countries and over time, with estimates ranging from 40% to 96%. We identified five methods suitable for conducting ascertainment studies, from simple comparative studies to more complicated capture-recapture and regression analyses. Studies of ascertainment may be used to identify weaknesses and biases in surveillance data, and facilitate the improvement of these systems. These findings are relevant to the surveillance of other infectious diseases, particularly those with lower mortality and a lower public profile than meningococcal disease, for which ascertainment may be worse.

Very-low-birth-weight children at school age: academic achievement, behavior and self-esteem and relation to risk factors.

OBJECTIVE: To investigate school performance, behavior and self-esteem of children with very low birth weight (VLBW). METHODS: All children with birth weight below 1501 g (VLBW) and normal birth weight controls, born in the south-east region of Sweden during a 15-month period in 1987-88, were enrolled in a prospective follow-up study. At the age of 9 years, 81% and 82%, respectively, were re-examined regarding growth, neurofunctional classification, academic achievement tests, need for special education and behavioral problems. At 12 years, 89% and 76%, respectively, were re-examined regarding growth, neurofunctional classification, visual acuity and self-esteem. RESULTS: VLBW children were shorter and lighter, and differed from the controls with regard to neurological functional classification. They produced poorer results in most academic achievement tests. When the comparison was restricted to children with normal intelligence, almost all the differences in other academic achievements disappeared. VLBW children had more reading difficulties but were less often than expected defined as dyslexics compared to control children. We did not find any major disparity in visual acuity and self-esteem between the groups. Low Apgar scores, intracranial hemorrhage and the need for mechanical ventilation neonatally were associated with poorer results in most outcome measures. Neurofunctional assessments in early childhood were associated with most outcome measures. The mother's education was related to delayed reading skills and need for special education. CONCLUSIONS: Although VLBW children performed less well in most academic achievement tests and on some behavioral subscales, those who had a normal intellectual capacity did not differ in any important aspects from the controls.

Short-term functional outcome of hospitalised first-ever strokes in Finnmark, Norway in 1998-1999. Results from the Finnmark Stroke Register.

Data on the functional outcome, prevalence of risk factors and comorbidity of stroke were collected in the population-based Finnmark Stroke Register in northern Norway. Findings for hospitalised first-ever strokes (n = 125) during the first registration year (1998-1999) are presented here. The median age of the patients was 70 years for men and 79 years for women. Cerebral infarctions comprised 81.6% of the strokes. Patients were severely handicapped: at discharge from hospital about 46% of those 75 years or older and about 21% of those younger than 75 years had severe disability by Rankin Scale. Women were more impaired than men. After hospitalisation, 45% of those 75 years or older and 21% of those younger than 75 years were sent to nursing home. The prevalence of risk factors and comorbidity was high: 29% of men (52% of women) had high blood pressure, 22% of men (25% of women) had atrial fibrillation, 22% of both men and women had diabetes, and 50% of men and 33% of women were current smokers. In conclusion, stroke victims in Finnmark were left with severe disability and need intensive rehabilitation. The prevalence of treatable risk factors was high; thus, primary and secondary prevention is the key to reduce the individual and social burden of stroke.

The prevalence of depression in relation to cerebral atrophy and cognitive performance in 70- and 74-year-old women in Gothenburg. The Women's Health Study.

BACKGROUND: Hospital-based studies report that depression in the elderly is associated with brain atrophy. This notion could not be confirmed in a population study on 85-year-olds. We aimed to assess depression in relation to brain atrophy and cognition in 70- and 74-year-old women. METHODS; A representative sample of 70- and 74-year-old women (N = 501) was examined with a psychiatric examination including the Mini-Mental State Examination (MMSE), measuring global cognitive function, and computerized tomography (CT) of the brain (N = 268). Depression was diagnosed according to DSM-III-R. Previous depression was diagnosed by history and by information from previous examinations in this 24-year longitudinal study. RESULTS: The prevalence of depression was 11.6%, including 8.4% with major depression (MDD). Among those who were currently mentally healthy, 43.0% had a history of previous depression. Women with current MDD had lower scores on the MMSE than the mentally healthy women. This association was only found in women with a lower level of education. Current depressives, previous depressives and mentally healthy women without a history of depression did not differ on CT with regard to brain atrophy or white matter lesions. The association between MDD and lower cognitive performance was independent of the association of cognitive performance with structural brain changes on CT. CONCLUSIONS: Brain atrophy on CT is not associated with depression in the general population, despite the fact that individuals with depression have a worse cognitive performance. The finding that cognitive performance was not decreased in individuals with previous depression suggests that cognitive dysfunction is a state phenomenon in depression.

[School maladjustment common among children with very low birth weight Special attention and support are required during school start]. / Skolsvårigheter vanliga hos barn med mycket låg födelsevikt. Extra uppmärksamhet och stöd behövs vid skolstart.

Children of very low birth weight (VLBW), defined as less than 1500 g, and normal birth weight controls (NBW) were enrolled in a long-term follow-up study. Five of 86 surviving VLBW children had a neurological handicap. Seventy VLBW children and 72 NBW children were re-examined at the age of nine, which entailed a neurological examination, a non-verbal intelligence test and a test for reading ability, mathematical skills and vocabulary. Their behavior was rated regarding hyperactivity, social behavior and fine and motor skills. The two groups differed with regard to the neurological examination and the tests, with poorer results shown for the low birth weight group. The VLBW children were also more hyperactive and scored lower on fine motor skills. Considering only those who scored normally as regards non-verbal intelligence (54% of VLBW children and 88% of controls), practically all differences disappeared.

Prevention of secondary cases of meningococcal disease in Denmark.

Close contacts of cases of meningococcal disease are at increased risk of disease themselves. We identified household-like contacts of index cases, to investigate whether relevant target groups are informed, receive and follow recommended chemoprophylaxis and vaccination, and to ascertain the time delay for implementation of these measures. A telephone interview of 172 households of index cases and a questionnaire survey among 634 parents of contacts of cases in institutions were carried out. Results were compared with reports from Medical Officers of Health. In 21% of the cases, Medical Officers reported fewer household-like contacts than were identified in this study. Written information was effective. However, 59% of households, and 36% of parents of contacts in institutions felt a lack of information about how the disease is acquired, the risk and signs of illness. For household-like contacts the coverage rate for chemoprophylaxis with an appropriate drug was 90% and for vaccination 59%. No secondary cases occurred among those treated with chemoprophylaxis, but among those not treated, there were two secondary cases. The study design provided a useful audit methodology to evaluate the completeness of implementation and the success of prophylactic measures for meningococcal disease.

Visual implicit memory deficit and developmental surface dyslexia: a case of early occipital damage.

This study reports the case of EBON, a fifteen-year-old right-handed female Swedish student, who suffered an early medial/dorsal occipital brain lesion and showed a clearly defined pattern of developmental surface dyslexia. EBON and 17 controls were examined with within and cross-modality (visual and auditory) word stem completion tasks together with tasks requiring free-recall and recognition for visually and auditory presented words. Compared to age-matched controls, EBON was found to show a significant deficit of visual priming following visual presentation, and a deficit approaching significance following auditory presentation. Explicit memory and visual and spatial abilities were not significantly different from controls. Therefore, EBON represents the first childhood case establishing the role of occipital regions in visual priming, as well as illustrating a profile of surface reading difficulty as a developmental consequence of this locus of lesion.

Fentanyl and midazolam anaesthesia for coronary bypass surgery: a clinical study of bispectral electroencephalogram analysis, drug concentrations and recall.

Bispectral index (BIS) was assessed as a monitor of depth of anaesthesia during fentanyl and midazolam anaesthesia for coronary bypass surgery. In 10 patients given morphine premedication, anaesthesia was induced with a combination of midazolam and fentanyl and thereafter maintained with a continuous infusion of a mixture of midazolam and fentanyl 5 and 50 micrograms kg-1 h-1, respectively. BIS was recorded continuously but not shown to the attending anaesthetist. Plasma concentrations of midazolam and fentanyl were measured five times during the procedure. An auditory stimulus was given during bypass. All patients were interviewed twice after operation for explicit and implicit recall. No patient had any anaesthetic complications. BIS decreased during anaesthesia, but varied considerably during surgery (range 36-91) with eight patients having values > 60. Midazolam and fentanyl drug concentrations did not correlate with BIS. No patient reported explicit or implicit recall. During clinically adequate anaesthesia with midazolam and fentanyl BIS varies considerably. The most likely reason is that BIS is not an accurate measure of the depth of anaesthesia when using this combination of agents.

Family caregiving in dementia--an analysis of the caregiver's burden and the "breaking-point" when home care becomes inadequate.

The burden of caregivers of patients suffering from of Alzheimer type dementia (DAT) and vascular dementia (VD) was analysed at the critical time, the "breaking-point", when home care becomes insufficient and/or inadequate and the caregiver burden has probably reached its upper limit. Primary family caregivers of 39 DAT and 40 VD patients who were being considered for relocation into group-living units were studied. Total caregiving burden and different aspects of the burden: general strain, isolation, disappointment, and emotional involvement, were correlated with the patients' diagnoses, abilities, and symptoms. Closer kinship to the patient imposed a heavier burden. The caregiver's gender, social class, and previous institutionalization of the patient did not influence the caregiver burden. There was no significant correlation between the patients' ADL ability or cognition and the burden. A higher level of disappointment was found among the VD carers. Different symptomatology in patients of the two diagnostic groups was related to special aspects of the burden. Multiple regression analysis showed that the amount of caregiving time each week and impaired sense of own identity, misidentifications, clinical fluctuations, and nocturnal deterioration in the patients predicted the breaking-point.

Rodent nerve-muscle cell culture system for studies of neuromuscular junction development: refinements and applications.

Understanding of vertebrate neuromuscular junction (NMJ) development has been advanced by experimentation with cultures of dissociated embryonic nerve and skeletal muscle cells, particularly those derived from Xenopus and chick embryos. We previously developed a rodent (rat) nerve-muscle coculture system that is characterized by extensive induction of acetylcholine receptor (AChR) aggregation at sites of axonal contact with myotubes (Dutton et al., 1995). In this article, we report modifications of this culture system and examples of its application to the study of NMJ development: (1) We describe improved methods for the enrichment of myoblasts to give higher yields of myotubes with equal or greater purity. (2) We demonstrate lipophilic dye labeling of axons in cocultures by injection of dye into neuron aggregates and show the feasibility of studying the growth of living axons on myotubes during synapse formation. (3) We describe the preparation of a better-defined coculture system containing myotubes with purified rat motoneurons and characterize the system with respect to axon-induced AChR aggregation. (4) We demonstrate dependence of the pattern of axon-induced AChR aggregation on muscle cell species, by the use of chick-rat chimeric co-cultures. (5) We provide evidence for the role of alternatively-spliced agrin isoforms in synapse formation by using single cell RT-PCR with neurons collected from co-cultures after observation of axon-induced AChR aggregation. Microsc. Res. Tech. 49:26-37, 2000. Published 2000 Wiley-Liss, Inc.

Converging evidence for the role of occipital regions in orthographic processing: a case of developmental surface dyslexia.

Recently, there have been several reports focusing on the neural basis for word recognition. Two different views have emerged: one emphasizing the role of the left angular gyrus in recognizing printed words, and the second view suggesting that visual word processing activates the left extrastriate cortex. This paper describes the case of EBON, a 14-year-old girl with an extensive early (most likely congenital) brain lesion in the left occipital lobe. She demonstrates a clear pattern of developmental surface dyslexia in that she is more successful at reading and spelling regular words than irregular words and makes frequent regularization errors. Thus, EBON is the first case reported with the potential to establish converging evidence for the role of extrastriate regions in the left hemisphere in the acquisition of orthographic representations.