Lene Theil Skovgaard

Good Clinical Research Practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents

Based on an international consensus conference held in Copenhagen in the autumn of 1994, a set of guidelines for Good Clinical Research Practice (GCRP) in pharmacodynamic studies of neuromuscular blocking agents are presented. The guidelines are intended to be a help for people working in this research field, and it is hoped that the guidelines will assist researchers, editors, and drug companies to enhance the quality of their pharmacodynamic studies of neuromuscular blocking agents.

Teenage girls and elderly women living in northern Europe have low winter vitamin D status

Objective:To determine the vitamin D status (serum 25-hydroxyvitamin D; S-25OHD) in adolescent girls and elderly community-dwelling women living in four countries of northern Europe and to explain differences in S-25OHD concentrations between and within the countries.Design:A cross-sectional observational study conducted in a standardised way during February–March. S-25OHD was analysed by high-performance liquid chromatography. Vitamin D and calcium intake was calculated using a standardised food composition database.Setting:Denmark, Finland, Ireland, and Poland.Subjects:A total of 199 girls (mean (s.d.) age 12.6 (0.5) y) and 221 women (mean (s.d.) age 71.8 (1.4) y).Results:The median (inter quartiles) concentration of S-25OHD was 29.4 (20.3, 38.3) nmol/l for the girls and 40.7 (28.0, 54.2) nmol/l for the women. S-25OHD below 25 nmol/l was found in 37% of the girls and 17% of the women, and S-25OHD below 50 nmol/l was found in 92% of the girls and 37% of the women. Positive significant determinants for S-25OHD in girls were use of vitamin D supplements, and in women sun habits, dietary vitamin D intake, use of vitamin D and calcium supplements. Body mass index and smoking were negative determinants in women. For women predictors could explain the differences between countries (Pcountry=0.09, R2=0.39), but for girls the difference remained significant even after including predictors (Pcountry=0.03, R2=0.15).Conclusion:Vitamin D status is low in northern Europe during winter. More than one-third of the adolescent girls have vitamin D status below 25 nmol/l and almost all are below 50 nmol/l. Two-thirds of the elderly community-dwelling women have vitamin D status below 50 nmol/l. Use of vitamin D supplements is a significant positive determinant for S-25OHD for both girls and women (P=0.001).Sponsorship:The European Fifth Framework Programme (Contract No. QLK1-CT-2000-00623).

Validation of the danish birth registration

We assessed validity and reliability of data on four serious pregnancy complications and gestational age in two national registers, the Medical Birth Register (MBR) and the National Register of Hospital Discharges (NRHD). From a cohort of all women in Denmark who gave birth to their first and second singleton infant in 1982-1987, a review was made of a selected sample of 1662 medical records. Regarding registration of pregnancy complications, there was good agreement (kappa above 0.6) between medical records and the registers, and between the registers. However, there was a tendency toward understatement evidenced by low sensitivity of three of four pregnancy complications. The level of agreement (43%) for length of gestation was disappointing. The number of systematic and nonsystematic errors indicate that there was about 52% more singleton preterm deliveries in Denmark in 1982 than previously reported (6.9% instead of 4.5%). It is concluded that the validity of the Danish birth registers should be improved by explicit definitions, increased use of raw data, and data collection by motivated professionals at birth.

Persistent High Incidence of Tuberculosis in Immigrants in a Low-Incidence Country

Immigration from areas of high incidence is thought to have fueled the resurgence of tuberculosis (TB) in areas of low incidence. To reduce the risk of disease in low-incidence areas, the main countermeasure has been the screening of immigrants on arrival. This measure is based on the assumption of a prompt decline in the incidence of TB in immigrants during their first few years of residence in a country with low overall incidence. We have documented that this assumption is not true for 619 Somali immigrants reported in Denmark as having TB. The annual incidence of TB declined only gradually during the first 7 years of residence, from an initial 2,000 per 100,000 to 700 per 100,000. The decline was described by an exponential function with a half-time of 5.7 (95% confidence interval 4.0 to 9.7) years. This finding seriously challenges the adequacy of the customary practice of screening solely on arrival.

Serum levels of YKL-40 and PIIINP as prognostic markers in patients with alcoholic liver disease

BACKGROUND/AIMS YKL-40 (growth factor) and PIIINP (N-terminal propeptide of Type III procollagen) are potential markers of liver fibrosis. The aim was to evaluate the prognostic value of serum YKL-40 and PIIINP levels in patients with alcoholic liver disease. METHODS Three hundred and seventy patients with alcoholic liver disease were studied in a trial of malotilate with a median follow-up period of 470 days; 75 patients died; 336 patients had a liver biopsy on entry. Serum levels of YKL-40 and PIIINP were determined by radioimmunoassay (RIA). RESULTS Serum YKL-40 and PIIINP were elevated in the patients compared to controls. Patients with steatosis or no fibrosis had the lowest serum levels of YKL-40 and PIIINP, whereas patients with alcoholic hepatitis and/or cirrhosis had the highest levels. Serum YKL-40 was associated with the presence of fibrosis, and serum PIIINP was also associated with the different grades of fibrosis. Patients with elevated serum YKL-40 or PIIINP had shorter survival than patients with normal serum levels of YKL-40 (P<0.0001) or PIIINP (P=0.044). High degree of fibrosis predicted shorter survival (P=0.004). CONCLUSIONS Serum levels of YKL-40 and PIIINP are elevated in alcoholic patients, related to the presence of liver fibrosis and may provide prognostic information.

Progress of emphysema in severe α1,-Antitrypsin Deficiency as Assessed by Annual CT

Purpose: To assess serial CT as a measure of the progress of emphysema in patients with severe α1,-antitrpsin deficiency (phenotype PiZ). Material and Methods: In a randomized placebo-controlled study of α1,-antitrypsin augmentation therapy, 22 patients with moderate emphysema were followed for 2–4 years with an annual lung CT. The images were analysed by means of semiautomatic lung detection, and the degree of emphysema was quantitated by the density-mask and the percentile methods. The influence of lung volume was standardised by a regression model. Results: A highly significant decline in Hounsfield units (HU) was found in low-density areas, corresponding to a mean (SE) annual loss of lung tissue of 2.1 (0.4) g/l lung volume. Analysis of a single slice at 5 cm below the level of the carina gave comparable results: 2.4 (0.4) g/l. Conclusion: Serial CT is a sensitive measure of the progress of emphysema in patients with severe α1-antitrypsin deficiency.

Lung function in patients with primary ciliary dyskinesia: a cross-sectional and 3-decade longitudinal study.

RATIONALE Early diagnosis and treatment is considered important to prevent lung damage in primary ciliary dyskinesia (PCD). OBJECTIVES Few studies have addressed long-term evolution of lung function after PCD diagnosis. We investigated whether long-term lung function was dependent on age or level of lung function at PCD diagnosis. METHODS An observational, single-center, cross-sectional, and three-decade longitudinal study of FEV(1) and FVC related to age at diagnosis until current age was performed. Linear regression was used to describe the relation between first measured lung function values and age at diagnosis across the cohort. Courses of lung function after diagnosis and the according slopes were used to group patients into increasing, stable, or decreasing courses. Additionally, slopes from courses of 10 years of follow-up were related to age at diagnosis and initial level of lung function, respectively, using linear regression. MEASUREMENTS AND MAIN RESULTS Seventy-four children and adults with PCD were observed for median 9.5 (range, 1.5-30.2) years during which 2,937 lung function measurements were performed. First measured FEV(1) was less than 80% of predicted in one-third of preschool-diagnosed children. During observation, 34% of patients lost more than 10 percentage points, 57% were stable, and 10% improved more than 10 percentage points in FEV(1). Courses of lung function after diagnosis were related to neither age at diagnosis nor initial level. CONCLUSIONS Our study strongly suggests that PCD is a disease of serious threat to lung function already at preschool age, and with a high degree of variation in courses of lung function after diagnosis that was not linked to either age or level of lung function at diagnosis. Early diagnosis did not protect against decline in lung function.

Prevalence and bother of nocturia, and causes of sleep interruption in a Danish population of men and women aged 60–80 years

To study the prevalence and bother of nocturia, and sleep interruptions in an unselected population of Danish men and women aged 60–80 years.

Half-life of plasma cholinesterase

The half–life of plasma cholinesterase (acylcholine acylhydrolase EC 3.1.1.8) was determined in three patients homozygous for the atypical gene for plasma cholinesterase by measuring the rate of disappearance of enzyme activity following intravenous injection of concentrated human cholinesterase. Half–life values of 10.9, 11.1, and 11.3 days were estimated. The distribution volume was estimated to be 18.0, 18.2, and 13.8% of body weight, respectively.

Postoperative muscle paralysis after rocuronium: less residual block when acceleromyography is used

Background: Residual muscle paralysis after anesthesia is common after pancuronium, but less common following the intermediate‐acting drugs vecuronium and atracurium. Therefore, many anesthetists do not monitor neuromuscular function when using an intermediate‐acting agent. The purpose of this prospective, randomised and double‐blind study was to establish the incidence and degree of postoperative residual block following the use of rocuronium in patients not monitored with a nerve stimulator, and to compare it with results obtained in patients monitored using acceleromyography (AMG).