Kreesten Meldgaard Madsen

Validity of Childhood Autism in the Danish Psychiatric Central Register: Findings from a Cohort Sample Born 1990–1999

The purpose of this study was to assess the validity of the diagnosis of childhood autism in the Danish Psychiatric Central Register (DPCR) by reviewing medical records from 499 of 504 total children with childhood autism born 1990–1999. Based on review of abstracted behaviors recorded in case records from child psychiatric hospitals, case status determination was performed using a standardized coding scheme. In 499 children diagnosed with childhood autism in the DPCR, the diagnosis could be confirmed in 469 children (94%). Of the 30 non-confirmed cases, five were classified by the reviewers as non-autistic cases and the remaining 25 cases were either classified with another ASD diagnosis or the specific diagnosis was not possible to determine.

Risk and Patterns of Bacteraemia After Splenectomy: a Population-Based Study

During a period in which vaccination of splenectomized patients has been recommended, we analysed the patterns of severe post-splenectomy infections (i.e. bacteraemia or meningitis) in a defined population-based cohort. A total of 561 patients undergoing splenectomy were identified during 1984-93 in a Danish county, and the 538 eligible patients were followed for 1731 person-years. After splenectomy, 38 patients contracted a bacteraemia, of which 45% occurred within 30 d (i.e. during the postoperative period). No cases of meningitis were found. Among splenectomized patients the incidence rate of bacteraemia was 2.3 per 100 person-years at risk. Beyond the postoperative period we found an 8-fold increased risk of bacteraemia. Enterobacteria were the predominant cause (45%), and only 1 case due to Streptococcus pneumoniae was recorded. 89 (17%) died during the postoperative period, and the overall mortality rate was 18.4 per 100 person-years at risk. In all, 60% of the patients had been given a pneumococcal vaccination, and a Cox proportional hazard regression model showed that vaccination significantly reduced the risk of bacteraemia of any cause beyond the postoperative period. We conclude that splenectomy increases the risk of severe infections, and that vaccinated patients carry a lower risk of infection than non-vaccinated ones.During a period in which vaccination of splenectomized patients has been recommended, we analysed the patterns of severe post-splenectomy infections (i.e. bacteraemia or meningitis) in a defined population-based cohort. A total of 561 patients undergoing splenectomy were identified during 1984-93 in a Danish county, and the 538 eligible patients were followed for 1731 person-years. After splenectomy, 38 patients contracted a bacteraemia, of which 45% occurred within 30 d (i.e. during the postoperative period). No cases of meningitis were found. Among splenectomized patients the incidence rate of bacteraemia was 2.3 per 100 person-years at risk. Beyond the postoperative period we found an 8-fold increased risk of bacteraemia. Enterobacteria were the predominant cause (45%), and only 1 case due to Streptococcus pneumoniae was recorded. 89 (17%) died during the postoperative period, and the overall mortality rate was 18.4 per 100 person-years at risk. In all, 60% of the patients had been given a pneumococcal vaccination, and a Cox proportional hazard regression model showed that vaccination significantly reduced the risk of bacteraemia of any cause beyond the postoperative period. We conclude that splenectomy increases the risk of severe infections, and that vaccinated patients carry a lower risk of infection than non-vaccinated ones.

Paternal age and preterm birth.

Background: There is growing evidence that advanced paternal age can be a reproductive hazard. Methods: We studied couples and their first children using nationwide registers in Denmark between 1980 and 1996. We restricted the analysis to mothers age 20–29 years. We estimated odds ratios (ORs) of preterm (<37 weeks gestation) and very preterm birth (<32 weeks) as a function of paternal age using logistic regression to adjust for potential confounding variables. Results: The risk of preterm birth increased with paternal age, almost entirely resulting from an association for very preterm birth. Compared with fathers age 20–24 years, ORs for very preterm birth were 1.3 (age 25–29), 1.4 (age 35–39), 1.7 (age 40–44), 1.6 (age 45–49), and 2.1 (age 50+) (test for trend: P = 0.01). Conclusions: Risk of very preterm birth increases among older fathers, perhaps as a result of a paternal placental effect.

Secular trends in incidence and mortality of bacteraemia in a Danish county 1981–1994

We estimated the incidence and mortality of bacteraemia in the County of North Jutland and examined factors that could explain the changes observed. A population‐based survey of bacteraemia was conducted in the Danish County of North Jutland during 1981–1994. Data were retrieved from a regional bacteraemia register. The mortality was determined through linkage to the Danish Civil Registration System. A total of 7198 bacteraemias were detected, and the annual incidence increased from 76 per 100,000 person‐years in 1981 to 153 in 1994. One major determining factor was a change in blood culture system with a higher volume of blood per sample, but annual numbers of blood cultures also increased. The 30‐day mortality rate increased from 17 to 40 per 100,000 person‐years during the study period, whereas the case‐fatality rate remained constant (23.6%; 95% confidence intervals 22.6%‐24.6%). The number of bacteraemias increased significantly. This observation could be explained only partly by changes in demography, in blood culture system, and in diagnostic activity. The case fatality rate remained constant despite the fact that more people were diagnosed with bacteraemia; this indicates that, with recent blood culture practice, more clinically significant bacteraemias are diagnosed.

Can hospital discharge diagnosis be used for surveillance of bacteremia? A data quality study of a Danish hospital discharge registry.

OBJECTIVE To assess the data quality of septicemia and sepsis registration in a hospital discharge registry in the County of Northern Jutland, Denmark. DESIGN Comparison of data from the discharge registry of an 880-bed, public, urban hospital in the County of Northern Jutland with data from a computerized bacteremia database at the regional department of clinical microbiology. SETTING Urban hospital with approximately 45,000 admissions per year. PATIENTS The study included 406 episodes of bacteremia in the bacteremia database and 83 discharges with the diagnosis of septicemia registered in the hospital discharge registry between January 1, 1994, and December 31, 1994. INTERVENTIONS None. RESULTS Eighteen episodes were registered in both the hospital discharge registry and the bacteremia database. Using the bacteremia database as reference standard, the sensitivity for the diagnosis of septicemia in the hospital discharge registry was 4.4% (18/406; 95% confidence intervals [CI95, 2.4%-6.4%]). By review of hospital records, we estimated the positive predictive value of septicemia registration in the hospital discharge registry as 21.7% (18/83; CI95, 12.8%-30.5%). No blood culture had been obtained in 44.4% (36/81; CI95, 33.6%-55.3%) of the cases with a discharge diagnosis of septicemia. In 33.3% (27/81; CI95, 23.1%-43.6%), the discharge diagnosis of septicemia was given, although blood cultures were negative. CONCLUSIONS The hospital discharge registry revealed numerous misclassifications, and the system was found not suited for surveillance of, or research in, bacteremia at present.

Continued increase in prevalence of obesity in Danish young men

BACKGROUND: Previous studies of Danish young men showed a steep increase of obesity since the birth years of the early 1940s with a levelling off in the 1950s. OBJECTIVE: To study the current prevalence of obesity and its recent changes in Danish young men. DESIGN: Cross‐sectional study based on weight and height measured at the military board for the birth cohorts 1955, 1965 and 1973–75. SUBJECTS: We obtained information from the old paper files comprising the two cohorts of men born in 1955 (6549 adults) and 1965 (6404 adults) and prospectively examined 4300 from the birth cohorts 1973–75 in a conscription district in Denmark during the period 1 August 1993 to 31 July 1994. RESULTS: The prevalence of obesity (defined as body mass index (BMI)≥30 kg/m2) was 1.5% in 1955, 2.1% in 1965 and 4.6% in 1973–75 birth cohorts. The median BMI has increased during the period from 21.7–22.8 kg/m2. CONCLUSION: Obesity is relatively common and has increased among Danish young men.

Febrile seizures and risk of schizophrenia

BACKGROUND Febrile seizure is a benign condition for most children, but experiments in animals and neuroimaging studies in humans suggest that some febrile seizures may damage the hippocampus, a brain area of possible importance in schizophrenia. METHODS A population-based cohort of all children born in Denmark between January 1977 and December 1986 was followed until December 2001 by using data from nationwide registries. RESULTS We followed 558,958 persons including 16,429 with a history of febrile seizures for 2.8 million person-years and identified 952 persons who were diagnosed with schizophrenia. A history of febrile seizures was associated with a 44% increased risk of schizophrenia [relative risk (RR)=1.44; 95% confidence interval (CI), 1.07-1.95] after adjusting for confounding factors. The association between febrile seizures and schizophrenia remained virtually unchanged when restricting the analyses to people with no history of epilepsy. A history of both febrile seizures and epilepsy was associated with a 204% increased risk of schizophrenia (RR=3.04; 95% CI, 1.36-6.79) as compared with people with no such history. CONCLUSIONS We found a slightly increased risk of schizophrenia among persons with a history of febrile seizures. The association may be due to a damaging effect of prolonged febrile seizures on the developing brain, shared etiological factors, or confounding by unmeasured factors.

MMR vaccination and autism : what is the evidence for a causal association?

It has been suggested that vaccination with the measles-mumps-rubella (MMR) vaccine causes autism. The wide-scale use of the MMR vaccine has been reported to coincide with the apparent increase in the incidence of autism. Case reports have described children who developed signs of both developmental regression and gastrointestinal symptoms shortly after MMR vaccination.A review of the literature revealed no convincing scientific evidence to support a causal relationship between the use of MMR vaccines and autism. No primate models exist to support the hypothesis. The biological plausibility remains questionable and there is a sound body of epidemiological evidence to refute the hypothesis. The hypothesis has been subjected to critical evaluation in many different ways, using techniques from molecular biology to population-based epidemiology, and with a vast number of independent researchers involved, none of which has been able to corroborate the hypothesis.

The risk of bacteremia in patients with monoclonal gammopathy of undetermined significance

Abstract: We estimated the risk of bacteremia in patients with monoclonal gammopathy of undetermined significance (MGUS) compared with the general population; 1237 cases of MGUS were identified by linking information on detected monoclonal components in the North Jutland County with the Danish Cancer Registry. We evaluated the risk of bacteremia in the MGUS cohort during the 13‐yr period from 1981 to 1993 by linkage to the Bacteremia Registry in the County. Follow‐up for the occurrence of bacteremia started 30 d after detection of the M‐component and continued until malignant transformation, death or until 31 December 1993, whichever came first. The expected numbers of bacteremia was based upon county, age, sex and period‐specific incidence rates. The median follow‐up period was 3.8 yr. Forty episodes of bacteremia occurred during 5500 person‐years versus 18 expected. The crude standardized incidence ratio of bacteremia was 2.2 (95% confidence interval, 1.6–3.0). There was no distinct pattern of bacterial etiology in the MGUS cohort. Although we found an association between MGUS and risk of bacteremia, the overall risk is small and this finding hardly affects the clinical handling of MGUS patients.

Fetal Growth and Blood Pressure in a Danish Population Aged 31-51 Years

During the past decade, studies have shown an inverse association between birth weight and blood pressure and risk of coronary heart disease in adult life. From old public archives we were able to trace the birth records of 545 out of 905 persons (60.2%) aged 31-51 years who participated in the Ebeltoft Health Promotion Project in Denmark. We examined the associations between birth weight, length at birth, Ponderal Index and systolic and diastolic blood pressure. No associations were found for women. For men, the mean systolic blood pressure fell from 131.1 mmHg with a birth weight of less than 3300 g to 129.6 mmHg with a birth weight of more than 4000 g, and for diastolic blood pressure 81.6 mmHg to 80.3 mmHg, respectively. For men, the mean systolic blood pressure fell from 135.7 mm Hg with a birth length of 30-51 cm to 131.6 with a birth length of 55-62 cm, and for diastolic blood pressure 83.0 mmHg to 78.8 mmHg, respectively. The associations may reflect organ programming in fetal life.During the past decade, studies have shown an inverse association between birth weight and blood pressure and risk of coronary heart disease in adult life. From old public archives we were able to trace the birth records of 545 out of 905 persons (60.2%) aged 31-51 years who participated in the Ebeltoft Health Promotion Project in Denmark. We examined the associations between birth weight, length at birth, Ponderal Index and systolic and diastolic blood pressure. No associations were found for women. For men, the mean systolic blood pressure fell from 131.1 mmHg with a birth weight of less than 3300 g to 129.6 mmHg with a birth weight of more than 4000 g, and for diastolic blood pressure 81.6 mmHg to 80.3 mmHg, respectively. For men, the mean systolic blood pressure fell from 135.7 mm Hg with a birth length of 30-51 cm to 131.6 with a birth length of 55-62 cm, and for diastolic blood pressure 83.0 mmHg to 78.8 mmHg, respectively. The associations may reflect organ programming in fetal life.