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Biomedical subjects

K M Knudsen

Publications and source records attributed to K M Knudsen.

12 recordsLinked to original sources
PubMed2000

Bioequivalence between ready-to-use recombinant human growth hormone (rhGH) in liquid formulation and rhGH for reconstitution.

The bioequivalence of recombinant human growth hormone (rhGH) for reconstitution, at either 24 IU or 8 mg, and three strengths of liquid formulation of rhGH (5, 10 or 15 mg per 1.5 ml, hGH) was tested in two randomized, single-blind, four-period, crossover studies in healthy subjects. The study drugs were administered by subcutaneous injection at a dose of 2.5 mg rhGH/m(2)body surface area or as a fixed dose of 5 mg rhGH. Endogenous hGH release was suppressed by a continuous somatostatin infusion. The 90% confidence intervals for the estimated mean ratios of AUC(0-24 h)and C(max)(analysis of variance) between all products were within 80-125% in both studies. Also, no significant differences (P> 0.05; Wilcoxon signed rank test) were found between t(max)for the liquid formulations of rhGH. These data demonstrate that there is bioequivalence between rhGH for reconstitution and the liquid formulations of rhGH.

Adult↗
PubMed1997

Estimation of variance in Cox's regression model with shared gamma frailties.

The Cox regression model with a shared frailty factor allows for unobserved heterogeneity or for statistical dependence between the observed survival times. Estimation in this model when the frailties are assumed to follow a gamma distribution is reviewed, and we address the problem of obtaining variance estimates for regression coefficients, frailty parameter, and cumulative baseline hazards using the observed nonparametric information matrix. A number of examples are given comparing this approach with fully parametric inference in models with piecewise constant baseline hazards.

Adult↗
PubMed1996

[A non-specific, beneficial effect of measles vaccination. Analysis of mortality studies from developing countries].

The study examined whether the reduction in mortality after standard titre measles immunization in developing countries can be explained by the prevention of acute measles and its long-term consequences. All studies comparing mortality of unimmunised children and children immunised with standard titre measles vaccine in developing countries were included; ten cohort and two case-control studies from Bangladesh, Benin, Burundi, Guinea-Bissau, Haiti, Senegal, and Zaire. We examined the protective efficacy of standard titre measles immunization against all cause mortality. Furthermore, by restricting the analysis to children who had not developed measles, we examined how much of the difference in mortality between immunised and unimmunised children could be explained by prevention of measles disease. In the ten cohort studies, protective efficacy against death after measles immunization was found to be in the range of 30-86%. Efficacy was highest in the studies with short follow-up and where children were immunised in infancy (range: 44-100%). Vaccine efficacy against death was much greater than the proportion of deaths attributed to acute measles disease. In four studies from Guinea-Bissau, Senegal and Burundi, vaccine efficacy against death remained almost unchanged when measles cases were excluded from the analysis. Hence, the reduction in mortality among immunized children cannot be explained by the prevention of acute and long-term consequences of measles. In contrast to the effect of measles vaccine, studies from Guinea-Bissau, Senegal and Benin suggest that diphtheria-tetanus-pertussis and polio vaccinations are not associated with reduction in mortality. These observations suggest that standard titre measles vaccine may confer a beneficial effect which is unrelated to the specific protection against measles disease.

Cohort Studies↗
PubMed1996

Child mortality following standard, medium or high titre measles immunization in West Africa.

BACKGROUND: The World Health Organization (WHO) recommended the use of high titre measles vaccine in 1989. Subsequent long term follow-up of several trials yielded results suggesting higher mortality among children inoculated with medium and high titre vaccines compared to standard titre vaccines, although none of the individual trials found significant differences in mortality. METHODS: Long term survival after standard, medium and high titre measles vaccines has been investigated in a combined analysis of all West African trials with mortality data. In trials from Guinea-Bissau, The Gambia and Senegal, children received medium or high titre vaccines from 4 months of age and were compared to control groups recruited at the same time later receiving standard titre vaccine from 9 months of age. All children were followed up to at least 3 years old. RESULTS: Combining trials of high titre vaccines showed higher mortality among the high titre group compared to the standard group: mortality ratio (MR) = 1.33 (95% CI : 1.02-1. 73). Mortality among recipients of medium titre vaccines was not different from that in the standard vaccine group, MR = 1.11 (95% CI: 0.54-2.27). In a combined analysis by sex, the adjusted mortality ratios comparing high titre vaccine with standard vaccine were 1.86 (95% CI : 1.28-2.70) for females and 0.91 (95% CI : 0.61-1.35) for males. The trials were not designed to study long term mortality. Adjustments for several possible sources of bias did not alter the results. CONCLUSIONS: The combined analysis showed a decreased survival related to high titre measles vaccine compared with standard titre vaccines, though solely among females. As a result of these studies from West Africa and a study from Haiti, WHO has recommended that high titre measles vaccine no longer be used.

Age Distribution↗
PubMed1993

[How much is lung function affected by smoking and occupation? Dichotomy of continuous variables can change the results].

Data from a cross-sectional study of 1045 men comprising a random population sample (768 men) and a sample of cement workers (277 men) were analyzed in order to examine the effects of smoking and occupation on forced expiratory volume in one second (FEV1). The continuous FEV1 variable and five dichotomous FEV1 variables based on % of predicted were analyzed. Differences between the "relative importance" of smoking and occupation were found to depend on the choice of the FEV1 variable. The effects of occupation compared with the effects of smoking varied considerably with different FEV1 variables, continuous or dichotomized at different cut-off levels. We conclude that comparison of surveys utilizing different FEV1 variables must be made with caution.

Adult↗
PubMed1991

Are respiratory symptoms and chronic airflow limitation really associated with an increased risk of respiratory cancer?

The relationship between respiratory symptoms, chronic airflow limitation and respiratory cancer was examined in a random population sample of 876 middle-aged men. All men were examined in 1974 with interview and lung function tests. Information on respiratory cancer from 1974 to June 1985 was obtained from the Danish Cancer Register. Using a multivariate Cox regression model including age as the underlying time scale and controlling for pack-years of cigarettes, cough and breathlessness were found to be significantly related to cancer--relative risks (RRs) 2.5 (95% confidence interval (CI): 1.3-5.0) and 2.2 (95% CI: 1.0-4.9), respectively. Phlegm, chronic phlegm, and chronic bronchitis were not related to respiratory cancer after controlling for age and smoking. Forced expiratory volume in one second (FEV1) was related to respiratory cancer, RR = 2.1 (95% CI: 1.3-3.4) per litre under the expected FEV1 given height. Thus, our study demonstrates some relationship between respiratory symptoms and FEV1 and respiratory cancer; however, the study at the same time questions the previously demonstrated relationship between phlegm and respiratory cancer.

Aged↗
PubMed1991

Exposure to cement dust at a Portland cement factory and the risk of cancer.

The relation between exposure to cement dust and cancer was examined in a population of 546 cement workers and a reference population of 858 randomly sampled men of similar age and area of residence. In 1974 all men gave lifelong occupational and smoking histories; information on incidence of cancer in the period 1974-85 was obtained from the Danish Cancer Registry. No increased risk of overall cancer was found among cement workers. Among men with more than 20 years exposure to cement dust, 14 cases of respiratory cancer were observed (observed/expected (O/E) 1.52, 95% confidence interval (95% CI) 0.90-2.57) when compared with all Danish men. Men with 1-20 years exposure had O/E 1.14 (95% CI 0.59-2.19) based on nine cases of cancer. After excluding all men with documented exposure to asbestos during employment in an asbestos cement factory no increased risk of overall cancer or respiratory cancer was found among cement workers compared with white collar workers from the local reference population, using a Cox regression model controlling for age and smoking habits. Relative risks were 0.5 (95% CI 0.1-1.5) and 1.0 (95% CI 0.4-2.6) for men with 1-20 and more than 20 years of exposure to cement dust respectively compared with white collar workers.

Aged↗
PubMed1990

Predictive value of the single-breath nitrogen test for hospitalization due to respiratory disease.

The relationship between indices of the single-breath nitrogen test (SBNT) measured in 1974 and hospitalization in the 9 year period 1977-1986 was examined in a random population sample of 876 men aged 46-69 years. Men who could not perform acceptable SBNT tracings had an increased risk of hospitalization due to respiratory disease in general. When age and smoking habits were controlled for, slope of phase III was significantly related to hospitalization due to respiratory disease in general and chronic obstructive pulmonary disease (COPD), whereas closing volume and closing capacity were marginally related to hospitalization due to respiratory disease in general but not to hospitalization due to COPD. The relationship between slope of phase III and hospitalization due to COPD remained significant after the forced expiratory volume in 1 sec (FEV1) was controlled for: odds ratio 1.4 per % N2/L (95% confidence interval 1.1-1.7). The effect of the slope of phase III was considered to be clinically insignificant, and we conclude that in a random population sample indices from only 1 SBNT do not provide prognostic information concerning hospitalization in addition to that provided by FEV1.

Aged↗
PubMed1990

The effect of smoking and occupation on changes in respiratory symptoms in middle-aged Danish men.

A group of 1404 middle-aged men from Aalborg who were examined in 1974 with interview and lung function tests were re-examined in 1985 using a postal questionnaire. Of the 1404 men, 1045 could be classified into well-defined occupational categories using information up to 1974. Of these men, 791 were alive at the time of the questionnaire survey. Questions on lung symptoms, occupation and smoking habits since the 1974 study were included in the follow-up survey; the response rate was 88%. Age and main occupation until 1974 were significantly related to the development of severe breathlessness from 1974 to 1985. After controlling for age, both cement workers and blue collar workers were considerably more likely to develop severe breathlessness than white collar workers: odds ratios (ORs) 2.51 (95% confidence interval 1.04-6.7) and 2.35 (1.02-5.42), respectively. Although weakened, these relationships remained after further controlling for forced expiratory volume in one second (FEV1) in 1974. Present smoking habit was an important determinant for the presence of cough, both in men with and without cough in 1974, yielding ORs of approximately 3 when comparing with lifetime nonsmokers. Cement workers tended to have cough in 1985 more frequently than white collar workers, OR = 2.09 (0.89-4.89) for men without cough in 1974 and OR = 2.60 (1.04-6.51) for men with cough in 1974.

Air Pollutants, Occupational↗
PubMed1989

The value of mucus hypersecretion as a predictor of mortality and hospitalization. An 11-year register based follow-up study of a random population sample of 876 men.

The value of mucus hypersecretion as a predictor of mortality and hospitalization was studied in a random population sample of 876 men, aged 46-69 years. The cohort was examined in 1974 with the British Medical Research Council questionnaire and lung function tests. A total of 219 men had died between 1974 and 1985. Twenty-seven men died from lung cancer and 14 died from other respiratory diseases. Mucus hypersection was not found to be significantly related to overall mortality after controlling for age, smoking and FEV1. Similarly, mucus hypersection was not a predictor of lung cancer mortality after controlling for age and smoking habits. The predictive value concerning death due to respiratory disease could not be examined because of the limited number of deaths in the cohort from these diseases. Mucus hypersecretion was not significantly related to hospitalization in general. Mucus hypersecretion had a significant predictive value concerning hospitalization due to respiratory disease in general, but the value was insignificant after controlling for FEV1. In contrast to this, mucus hypersecretion was a significant predictor of hospitalization due to COPD, even after controlling for FEV1. We conclude that the predictive value of mucus hypersecretion concerning mortality is of no value. Concerning morbidity, our results show that, although secondary to airflow obstruction, mucus hypersecretion must be viewed as an indicator of severity of COPD.

Aged↗
PubMed1988

Should we continue using questionnaires on breathlessness in epidemiologic surveys?

The construct validity and ability to predict mortality on the basis of 4 British Medical Research Council (BMRC) questions on breathlessness were examined and compared to that of spirometric measurements, in particular FEV1, in a cohort of 1,045 men. Of these, 1,030 answered questions on breathlessness and 994 performed acceptable spirometry. Using 2 levels of dyspnea, white collar workers had significantly fewer symptoms of breathlessness than both cement workers and other blue collar workers, and this effect was present even after controlling for FEV1 as well as other spirometric measurements. We found an effect of age on dyspnea but not of smoking category. Furthermore, questions on breathlessness showed a dependence on extreme overweight. In a 10-yr follow-up, 219 men had died. Dyspnea Grade 3 or worse according to Fletcher's breathlessness score was a good predictor of overall mortality, yielding a mortality ratio of 1.57 for given occupation, smoking category, years with central heating, and overweight status, after controlling for FEV1. We conclude that in a standardized setting, questions on breathlessness provide a sensitive and objective tool. They contain information additional to that provided by FEV1 and other spirometric measurements.

Aged↗