Finn Rasmussen

Randomised controlled trial of two-component, three-component, and five-component acellular pertussis vaccines compared with whole-cell pertussis vaccine

Summary Background Trials in Italy and Sweden showed high efficacy for three-component and five-component pertussis vaccines, and poor efficacy for a whole-cell vaccine licensed in the USA and a two-component vaccine. We compared the efficacy of three acellular vaccines with a UK whole-cell vaccine. Methods We enrolled 82892 babies aged 2–3 months. Babies were vaccinated at age 3 months, 5 months, and 12 months, or age 2 months, 4 months, and 6 months. They were randomly assigned a two-component acellular diphtheria-tetanus-pertussis (DTP) vaccine (n=20697), a three-component acellular DTP vaccine (n=20728), a five-component acellular DTP vaccine (n=20747), or a UK whole-cell DTP vaccine (n=20720). We collected data for all reported cases of culture-confirmed pertussis during 3 years of follow-up. The treatment status of the two-component-vaccine group had to be made known midway through the trial for boosting because of poor efficacy. We included data for the two-component vaccine in the analysis of safety and immunogenicity, and data up its unmasking in secondary analyses of relative efficacy. Analyses were by intention to treat. Findings During follow-up from the third dose (mean 22 months), in the 3 months, 5 months, 12 months schedule, there were 15 cases of culture-confirmed pertussis with at least 21 days of paroxysmal cough in the whole-cell group, relative risk 1·00, compared with 13 in the five-component group (0·85 [95% Cl 0·41–1·79]), and 21 in the three-component group (1·38 [0·71–2·69]). For culture-confirmed pertussis, with or without cough, there were 19 cases in the whole-cell group (1·00), 27 in the five-component group (1·40 [0·78–2·52]), and 49 in the three-component group (2·55 [1·50–4·33]). In the intention-to-treat analyses, from the first dose in the 3 months, 5 months, 12 months schedule the whole-cell vaccine was significantly more protective than the three-component vaccine against typical pertussis. Between the second and the third doses, culture-confirmed pertussis with any cough and with at least 21 days of paroxysmal cough was significantly more frequent in the two-component group than in the three-component group, and in the three-component group than in the five-component and the whole-cell groups, respectively. The serological response of the acellular vaccines in the 2 months, 4 months, 6 months schedule were similar to those previously reported. The whole-cell vaccine was highly immunogenic for fimbriae, pertactin, and filamentous haemagglutinin, but had a low antipertussis toxin response. Hypotonic hyporesponsiveness occurred significantly more frequently in the whole-cell group (p Interpretations The efficacy of the UK whole-cell vaccine and the five-component and three-component vaccines was similar against culture-confirmed pertussis with at least 21 days of paroxysmal cough. The lower efficacy of the three-component vaccine against mild disease suggests that fimbriae have a role in protection against infection. The efficacy of acellular vaccines depends on the number of components, and different whole-cell vaccines have variable efficacies.

Paternal age and schizophrenia: a population based cohort study

Abstract Objective To investigate the association of paternal age at conception with the risk of offspring developing schizophrenia. Design A population based cohort study. Setting Sweden. Subjects 754 330 people born in Sweden between 1973 and 1980 and still alive and resident in Sweden at age 16 years. Main outcome measures Hospital admission with schizophrenia or non-schizophrenic, non-affective psychosis. Results After adjustment for birth related exposures, socioeconomic factors, family history of psychosis, and early parental death the overall hazard ratio for each 10 year increase in paternal age was 1.47 (95% confidence interval 1.23 to 1.76) for schizophrenia and 1.12 (0.98 to 1.29) for non-schizophrenic non-affective psychosis. This association between paternal age and schizophrenia was present in those with no family history of the disorder (hazard ratio for each 10 year increase in paternal age 1.60, 1.32 to 1.92), but not in those with a family history (0.91, 0.44 to 1.89) (P = 0.04 for interaction). Conclusions Advancing paternal age is an important independent risk factor for schizophrenia. The stronger association between paternal age and schizophrenia in people without a family history provides further evidence that accumulation of de novo mutations in paternal sperm contributes to the overall risk of schizophrenia.

Childhood Socioeconomic Position and Objectively Measured Physical Capability Levels in Adulthood: A Systematic Review and Meta-Analysis

Background Grip strength, walking speed, chair rising and standing balance time are objective measures of physical capability that characterise current health and predict survival in older populations. Socioeconomic position (SEP) in childhood may influence the peak level of physical capability achieved in early adulthood, thereby affecting levels in later adulthood. We have undertaken a systematic review with meta-analyses to test the hypothesis that adverse childhood SEP is associated with lower levels of objectively measured physical capability in adulthood. Methods and Findings Relevant studies published by May 2010 were identified through literature searches using EMBASE and MEDLINE. Unpublished results were obtained from study investigators. Results were provided by all study investigators in a standard format and pooled using random-effects meta-analyses. 19 studies were included in the review. Total sample sizes in meta-analyses ranged from N = 17,215 for chair rise time to N = 1,061,855 for grip strength. Although heterogeneity was detected, there was consistent evidence in age adjusted models that lower childhood SEP was associated with modest reductions in physical capability levels in adulthood: comparing the lowest with the highest childhood SEP there was a reduction in grip strength of 0.13 standard deviations (95% CI: 0.06, 0.21), a reduction in mean walking speed of 0.07 m/s (0.05, 0.10), an increase in mean chair rise time of 6% (4%, 8%) and an odds ratio of an inability to balance for 5s of 1.26 (1.02, 1.55). Adjustment for the potential mediating factors, adult SEP and body size attenuated associations greatly. However, despite this attenuation, for walking speed and chair rise time, there was still evidence of moderate associations. Conclusions Policies targeting socioeconomic inequalities in childhood may have additional benefits in promoting the maintenance of independence in later life.

Trends in overweight and obesity among 18-year-old males in Sweden between 1971 and 1995

The aims of the study are to analyse Swedish trends in overweight and obesity–as measured by body mass index (BMI)–between 1971 and 1995, and to examine socioeconomic and geographic differences between groups of individuals on the basis of information on 18‐y‐old military conscripts. The study population comprises all males born in 1953, 1958, 1963, 1968, and between 1973 and 1977, reported to be living in Sweden at 17 y of age according to nationwide population registers (RTPs). Utilizing the unique personal ID number, sociodemographic data in the RTPs and in Population and Housing censuses were linked to data on BMI in the national Military Service Conscription Registry for the years 1971 to 1995. These data were obtained from compulsory medical examinations held at military induction at 18 y of age. BMI data were available for 448 732 (89%) of a total of 503 689 subjects. Mean BMI increased by 6.6% over the study period–from 21.1 kg/m2 in 1971 to 22.4 kg/m2 in 1995. Unadjusted trend analyses showed a 2.4 times increase in the prevalence of overweight among 18‐y‐old males over the period–from 6.9% in 1971 to 16.3% in 1995. Over the same years, the prevalence of obesity increased 3.5 times– from 0.9% to 3.2%. After adjustment for muscle power, demographic factors, and living area, the prevalence of overweight was found to have increased 1.4 times, and obesity 1.7 times between 1971 and 1993. The prevalence of overweight was considerably higher among 18‐y‐old males from low‐educated families than among those from high‐educated families in both 1971 and 1995. The prevalence of overweight was also found to be higher in both 1971 and 1995 among young men from rural and/or sparsely populated areas than among those living in Swedens largest cities. Mean BMI, and the prevalence of overweight and obesity have increased among 18‐y‐old males in Sweden over the last 24 y. The increased risk of overweight among young men from low‐educated families and those from rural and/or sparsely populated areas detected in 1971 was still evident in 1995.

Muscular strength in male adolescents and premature death: cohort study of one million participants

Objectives To explore the extent to which muscular strength in adolescence is associated with all cause and cause specific premature mortality (<55 years). Design Prospective cohort study. Setting Sweden. Participants 1 142 599 Swedish male adolescents aged 16-19 years were followed over a period of 24 years. Main outcome measures Baseline examinations included knee extension, handgrip, and elbow flexion strength tests, as well as measures of diastolic and systolic blood pressure and body mass index. Cox regression was used to estimate hazard ratios for mortality according to muscular strength categories (tenths). Results During a median follow-up period of 24 years, 26 145 participants died. Suicide was a more frequent cause of death in young adulthood (22.3%) than was cardiovascular diseases (7.8%) or cancer (14.9%). High muscular strength in adolescence, as assessed by knee extension and handgrip tests, was associated with a 20-35% lower risk of premature mortality due to any cause or cardiovascular disease, independently of body mass index or blood pressure; no association was observed with mortality due to cancer. Stronger adolescents had a 20-30% lower risk of death from suicide and were 15-65% less likely to have any psychiatric diagnosis (such as schizophrenia and mood disorders). Adolescents in the lowest tenth of muscular strength showed by far the highest risk of mortality for different causes. All cause mortality rates (per 100 000 person years) ranged between 122.3 and 86.9 for the weakest and strongest adolescents; corresponding figures were 9.5 and 5.6 for mortality due to cardiovascular diseases and 24.6 and 16.9 for mortality due to suicide. Conclusions Low muscular strength in adolescents is an emerging risk factor for major causes of death in young adulthood, such as suicide and cardiovascular diseases. The effect size observed for all cause mortality was equivalent to that for well established risk factors such as elevated body mass index or blood pressure.

Low physical fitness in childhood is associated with the development of asthma in young adulthood: the Odense schoolchild study

Intense physical activity in children may either improve fitness and protect against asthma, or may trigger symptoms. The aim of this study was to determine whether physical fitness in childhood has an impact on the development of asthma. In this prospective, community-based study, 757 (84%) asymptomatic children with an average age at inclusion of 9.7 yrs were followed for 10.5 yrs. In both surveys a maximal progressive exercise test on a bicycle ergometer was used to measure physical fitness (maximal workload) and to induce airway narrowing. A methacholine provocation test was performed in the subjects at follow-up. During the 10-yr study period, 51 (6.7%) of the previously asymptomatic children developed asthma. These subjects had a lower mean physical fitness in 1985 than their peers: (3.63 versus 3.89 W x kg(-1); p=0.02) in boys and (3.17 versus 3.33 W x kg(-1); p=0.02) in girls. A weak correlation was found between physical fitness in childhood and airway responsiveness to methacholine at follow-up when adjusted for body mass index, age and sex (r=0.11; p<0.01). In a multiple regression analysis, physical fitness was inversely related to the development of physician diagnosed asthma, odds ratio=0.93 (0.87-0.99). Thus, the risk for the development of asthma during adolescence is reduced 7% by increasing the maximal workload 1 W x kg(-1). In conclusion, this study showed that physical fitness in childhood is weakly correlated with the development of asthma during adolescence and that high physical fitness seems to be associated with a reduced risk for the development of asthma.

Childhood overweight and obesity prevalences levelling off in Stockholm but socioeconomic differences persist

Background:Time trends in overweight, obesity and underweight among 10-year-old children were investigated between 1999 and 2003 with attention to gender and areas with different socioeconomic status (SES).Material:The study was performed in Stockholm County, where schools within eight different SES areas were randomly sampled. In selected schools, data on height and weight were abstracted from school health records of 2416 ten-year-old boys and girls examined by school nurses in 1999 and 2183 examined in 2003.Results:Among boys, the prevalence of overweight was 21.6% in 1999 and 20.5% in 2003 (difference −1.1% (95% confidence interval (CI), −4.6; 2.4)) and for obesity 3.2 and 3.8% (difference 0.6% (95% CI, −0.9; 2.2)). Among girls overweight decreased from 22.1 to 19.2% (difference −2.9% (95% CI, −6.3; 0.6)) and obesity from 4.4 to 2.8% (difference −1.6% (95% CI, −3.1; 0.0)). There was a marginally significant difference in obesity trends in girls versus boys (P=0.051). The prevalence of underweight decreased nonsignificantly both in boys and in girls. Strong gradients, with more obesity and overweight in socioeconomically disadvantaged areas, were observed in both genders in 2003. Differences between SES areas were also seen in 1999 but were more pronounced in 2003. Among boys divergent trends in obesity were observed between 1999 and 2003, with evidence for increases in less affluent areas only.Conclusion:This population-based study of 10-year-olds indicates that rates of obesity, overweight and underweight are stable in Stockholm County. However, obesity is more prevalent in relatively less advantaged SES.

The relation of weight, length and ponderal index at birth to body mass index and overweight among 18-year-old males in Sweden

The intrauterine environment seems to be important for the occurrence of cardiovascular and other chronic diseases in adulthood. The aim of the present study is to analyze the importance of birthweight, birthlength and Ponderal Index (PI) for Body Mass Index (BMI) and overweight at 18 years of age.In this cohort study, the nationwide Swedish Medical Birth Registry for the years 1973–1976 was linked with the national Military Service Conscription Registry for 1990–1996. Of 193,056 children born at term 1973–1976, 165,109 (85.5%) could be followed-up at 18 years of age. The children were divided into percentile groups according to birthweight and birthlength for each gestational week. They were also assigned to three different categories, according to birthweight and birthlength for each gestational week: infants with values ≤5th percentile, values >5th and ≤95th percentile, and values >95th percentile.Clear-cut associations were found between birthweight and BMI, and between PI at birth and BMI at 18 years of age. High birthweight and normal birthlength and also high birthweight and high birthlength for gestational age were found to be risk factors for overweight and severe overweight among young men in Sweden.

Nationwide cohort study of post-gastric bypass hypoglycaemia including 5,040 patients undergoing surgery for obesity in 1986–2006 in Sweden

Aims/hypothesisSymptomatic hypoglycaemia with related confusion, syncope, epilepsy or seizures is a newly recognised complication of gastric bypass surgery for obesity. The incidence of these conditions is not known. We therefore studied the incidence of post-gastric bypass hypoglycaemia and related symptoms in patients who have undergone gastric bypass and a reference cohort from the general population of Sweden.MethodsThis is a nationwide cohort study based on national registries with 5,040 persons who underwent gastric bypass, vertical banded gastroplasty or gastric banding for obesity in Sweden between 1 January 1986 and 31 December 2006 and a cohort of ten referents per patient matched for sex and age randomly sampled from the general population. The incidence rates of hospitalisation for hypoglycaemia, confusion, syncope, epilepsy or seizures before and after dates of surgery or inclusion in the reference cohort were studied.ResultsPreoperative incidences of hospitalisation for hypoglycaemia were similar in the surgical and referent cohorts. After gastric bypass surgery, the adjusted hazard ratios were significantly elevated for hypoglycaemia (2.7 [95% CI 1.2–6.3]), confusion (2.8 [1.3–6.0]), syncope (4.9 [3.4–7.0]), epilepsy (3.0 [2.1–4.3]) and seizures (7.3 [5.0–10.8]). The proportions of gastric bypass patients and reference participants affected by hypoglycaemia were very low (0.2% and 0.04%, respectively). There was no increased risk of hypoglycaemia after vertical banded gastroplasty or gastric banding compared with the referent population.Conclusions/interpretationObese persons who have undergone gastric bypass have an increased risk of hospitalisation for diagnoses associated with post-gastric bypass hypoglycaemia, although few patients are affected.

Trends in asthma, allergic rhinitis and eczema among Swedish conscripts from farming and non-farming environments. A nationwide study over three decades

Background Asthma and allergies are less common in children who have been raised in farming environments.