[Analysis of deaths during hospitalization and after discharge from hospital]. / Analyse af dødsfald under og efter hospitalsindlaeggelse.

INTRODUCTION: Analysis of deaths during and up to one month after discharge from hospital. MATERIALS AND METHODS: For 2006, all deaths during and up to one month after discharge were identified for patients admitted to hospital in Roskilde or Køge. Age, acute or planned hospitalisation, duration of in-hospital stay, department of discharge and main diagnose were registered. RESULTS: Out of 50,302 hospitalisations, 2.2% had a fatal outcome during hospitalisation, whereas 2.1% died within the following month. During hospitalisation, the proportion of deaths among patients with either planned or acute admission was 1.1% and 2.6%, respectively. For several diagnose groups the risk of death during the first month after discharge was higher than that of fatal outcome during hospitalisation. The diagnose groups most frequently related to fatal outcome were cancers, infectious diseases, cardiovascular diseases and respiratory diseases. Pneumonia was the most prevalent benign diagnosis for fatal cases during hospitalisation. Data are provided for mortality related to diagnose and age group. The incidence of fatal outcome increased with the length of in-patient stay. CONCLUSION: Analysis of fatality rates also during planned hospitalisations and within the first month after acute as well as planned hospitalisations should be in focus when planning quality improvement projects.

Body mass, fat-free body mass, and prognosis in patients with chronic obstructive pulmonary disease from a random population sample: findings from the Copenhagen City Heart Study.

RATIONALE: Low body mass index (BMI) is a marker of poor prognosis in chronic obstructive pulmonary disease (COPD). In the general population, the harmful effect of low BMI is due to the deleterious effects of a low fat-free mass index (FFMI; fat-free mass/weight(2)). OBJECTIVES: We explored distribution of low FFMI and its association with prognosis in a population-based cohort of patients with COPD. METHODS: We used data on 1,898 patients with COPD identified in a population-based epidemiologic study in Copenhagen. FFM was measured using bioelectrical impedance analysis. Patients were followed up for a mean of 7 yr and the association between BMI and FFMI and mortality was examined taking age, sex, smoking, and lung function into account. MAIN RESULTS: The mean FFMI was 16.0 kg/m(2) for women and 18.7 kg/m(2) for men. Among subjects with normal BMI, 26.1% had an FFMI lower than the lowest 10th percentile of the general population. BMI and FFMI were significant predictors of mortality, independent of relevant covariates. Being in the lowest 10th percentile of the general population for FFMI was associated with a hazard ratio of 1.5 (95% confidence interval, 1.2-1.8) for overall mortality and 2.4 (1.4-4.0) for COPD-related mortality. FFMI was also a predictor of overall mortality when analyses were restricted to subjects with normal BMI. CONCLUSIONS: FFMI provides information in addition to BMI and assessment of FFM should be considered in the routine assessment of COPD.

Variation of the McKusick-Kaufman gene and studies of relationships with common forms of obesity.

Obesity is a prominent feature of the Bardet-Biedl syndrome (BBS), one subset of which, BBS6, is due to mutations in the chaperonin-like gene termed the McKusick-Kaufman syndrome (MKKS) gene. We tested whether variation in MKKS contributes to common and probably polygenic forms of obesity by performing mutation analysis of the coding region in 60 Danish white men with juvenile-onset obesity. Five variants were identified, including two synonymous mutations (Pro(39)Pro and Ile(178)Ile) and three nonsynonymous variants (Ala(242)Ser, Arg(517)Cys, and Gly(532)Val). Furthermore, the rare Ala(242)Ser was identified in two families and showed partial cosegregation with obesity. The Pro(39)Pro, Ile(178)Ile, and Arg(517)Cys variants are in complete linkage disequilibrium and defined a prevalent haplotype. In a case-control study, the Arg(517)Cys polymorphism allele prevalence was 11.4% [95% confidence interval (CI), 9.7-13.0] among 744 men with juvenile-onset obesity and 9.3% (CI, 7.9-10.7) among 867 control subjects (P = 0.048). However, among middle-aged men the allelic prevalence was 9.7% (CI, 7.9-11.4) among 523 obese men and 12.2% (CI, 10.8-13.6) among 1051 lean men (P = 0.037). In conclusion, it is unlikely that MKKS variants play a major role in the pathogenesis of nonsyndromic obesity, although in rare cases the A242S allele may contribute to obesity.

Prevalence of mutations and functional analyses of melanocortin 4 receptor variants identified among 750 men with juvenile-onset obesity.

Mutations in the gene encoding the melanocortin 4 receptor (MC4R) are associated with the most common monogenic form of obesity. We examined 750 Danish men with juvenile-onset obesity (body mass index 33.3 +/- 2.4 kg/m(2)) and 706 control subjects (body mass index 21.4 +/- 2.1 kg/m(2)) for mutations in MC4R. A total of 14 different mutations were identified of which two, Ala219Val and Leu325Phe, were novel variants. The variant receptor, Leu325Phe, was unable to bind [Nle4,d-Phe7]-alphaMSH, whereas the Ala219Val variant showed a significantly impaired melanotan II induction of cAMP, compared with the wild-type receptor. The remaining 11 mutations have previously been reported, but selected MC4R variants were further characterized in vitro in the present study. A previously identified nonsense mutation, Tyr35stop, had a relatively high allele frequency (0.6%), suggesting a possible founder effect in the Danish population. This study shows a carrier frequency of 2.5% of pathogenic mutations in the MC4R gene in a population-based study of obese men. Thus, variation in this gene is the most common known specific genetic cause of obesity among Scandinavian men.

Mutation analysis of NR0B2 among 1545 Danish men identifies a novel c.278G>A (p.G93D) variant with reduced functional activity.

Variations of the small heterodimer partner (SHP, NR0B2) gene, an atypical nuclear receptor that inhibits transactivation by hepatocyte nuclear factor (HNF)-4alpha, are associated with obesity among Japanese. The purpose of the study was to evaluate the prevalence of SHP variants among obese Danish men. Using combined SSCP and heteroduplex analysis, we analyzed the entire coding region of SHP for variants in a cohort of 750 Danish men with early-onset obesity and genotyped a cohort of 795 nonobese control subjects using PCR-RFLP. Functional analyses of the identified coding region variants were performed in both MIN6-m9 and HepG2 cell lines. A total of five novel variants, including three missense variants (c.100C>G [p.R34G], c.278G>A [p.G93D], and c.415C>A [p.P139H]) and two silent variants (c.65C>T [p.Y22Y] and c.339G>A [p.P113P]) were identified. Moreover, the previously reported c.512G>C [p.G171A] polymorphism was identified. The 171A allele was not associated with obesity (p = 0.07). The 34G, 93D, and 139H-alleles were rare variants, which were found only among obese subjects. Among the four coding region variants, the 93D-allele showed a reduced in vitro inhibition of the HNF-4alpha transactivation of the HNF-1alpha promoter expression when expressed in MIN6-m9 and HepG2 cell lines (p<0.01). In contrast to reported findings among obese Japanese, functional variants are rare among Danish men. A functional 93D variant of SHP was identified in 1 out of 750 obese and in none of 795 nonobese control subjects. Further large-scale population studies are necessary to assess the clinical impact of this rare variant on obesity risk among European subjects.

Mutational analysis of the UCP2 core promoter and relationships of variants with obesity.

OBJECTIVE: To identify polymorphisms in the human uncoupling protein 2 gene (UCP2) promoter and to investigate whether these were associated with obesity or weight gain. RESEARCH METHODS AND PROCEDURES: The human UCP2 promoter was characterized by reporter gene analysis in cell lines derived from skeletal muscle, white adipose tissue, and embryonic tissue. We analyzed the core promoter for polymorphisms in 60 obese subjects. A prevalent polymorphism, the -866 G/A variant, was investigated for association with obesity in 749 men obese as young adults and 816 men of the same age representing the background population. Genotype-phenotype interaction studies were performed in two other population-based samples: one group of middle-aged-to-elderly Danish subjects (mean age, 53 years; range, 30 to 88 years) and one group of 60-year-old Danish subjects. RESULTS: The region up to -1202 bp relative to the UCP2 transcription initiation site gave rise to the highest promoter activity. Eight mutations in this region were identified comprising -866 G/A, -850 G/A, -337 G/C, -41 G/T, -28 insertion T, -5 insertion (cactgcgaagccc), +45 C/T, and +53 G/C, but none of these was associated with consistent alterations in BMI, body fat content, weight gain, or fasting levels of plasma glucose and serum insulin. DISCUSSION: Variation of the UCP2 promoter including the single common variant (-866 A/G) is not associated with obesity or obesity-related intermediary phenotypes in Danish subjects.

Are soft tissue composition of bone and non-bone pixels in spinal bone mineral measurements by DXA similar? Impact of weight loss.

Weight loss seems associated with a decrease in bone mineral density (BMD) as measured by absorptiometry, which may be the result of accuracy errors caused by differences in soft tissue between non-bone and bone pixels. The aim was to study the abdominal fat% and thickness in regions corresponding to non-bone, soft tissue-only and bone pixels for spinal BMD measurements by dual energy X-ray absorptiometry (DXA), and to calculate the theoretical errors in measurement of changes in BMD by DXA as a result of changes in soft tissue heterogeneity with weight loss. Abdominal computed tomography (CT) and DXA scans were performed in 34 obese subjects (42.1+/-10.1 years (mean +/- SD), wt: 102.1+/-12.8 kg and BMI: 36.6+/-3.8 kg m(-2)) before and after weight loss (11.3+/-6.9 kg after 1 year). There were some significant differences in fat% and thickness of soft tissue between abdominal regions corresponding to non-bone and bone pixels, respectively, for spinal BMD measurements by DXA, both before and after weight loss. With weight loss there were some changes in the soft tissue heterogeneity, which caused a minor theoretical error (apparent, but false decrease of 1-2%) of borderline significance for the anterior-posterior (AP) spinal BMD by DXA.