Comparison of Cox and Gray's survival models in severe sepsis

BACKGROUND: Although survival is traditionally modeled using Cox proportional hazards modeling, this approach may be inappropriate in sepsis, in which the proportional hazards assumption does not hold. Newer, more flexible models, such as Gray's model, may be more appropriate. OBJECTIVES: To construct and compare Gray's model and two different Cox models in a large sepsis cohort. To determine whether hazards for death after sepsis were nonproportional. To explore how well the different survival modeling approaches describe these data. DESIGN: Analysis of combined data from the treatment and placebo arms of a large, negative, sepsis trial. SETTING: Intensive care units at 136 U.S. medical centers. SUBJECTS: A total of 1090 adults aged 18 yrs or older with signs and symptoms of severe sepsis and documented or probable Gram-negative infection. MEASUREMENTS: We considered 27 potential baseline risk factors and modeled survival over the 28 days after the onset of sepsis. We tested proportionality in single-variable Cox analysis using Schoenfeld residuals and log-log plots. We constructed a traditional multivariable Cox model, a multivariable Cox model with time-varying covariates, and a multivariable Gray's model. RESULTS: In single-variable analyses, 20 of the 27 potential factors were significantly associated with mortality, and 10 of 20 had nonproportional hazards. In multivariate analysis, all three models retained a very similar set of significant covariates (two models retained the identical set of nine variables, and the third differed only in that it retained the same nine plus a tenth variable). Four of the nine common covariates had nonproportional hazards. Of the three models, Gray's model best captured these changing hazard ratios over time. CONCLUSION: We confirm that many of the important predictors of mortality in severe sepsis are nonproportional and find that Gray's model seems best suited for modeling survival in this condition.     

Attitudes of medical students in Belgrade, Yugoslavia, toward preventive medicine and epidemiology

Medical students in Belgrade were interviewed regarding their opinions about the teaching of preventive medicine, with particular emphasis on epidemiology, at the beginning and at the end of the course. Results indicated that the course provoked no interest whatsoever in the disciplines of preventive medicine. A part of social factors influencing the motivation of students, the didactic approach to teaching and the strict division between preventive and clinical medicine were implicated as the main reasons for this lack of enthusiasm. The absence in this country of clear and generally accepted ideas regarding what a graduate student should know in order to meet optimally the health needs of the community has been assessed as the factor which obscures definition of the aims of teaching and, accordingly, the creation of purposeful syllabuses.     

Association of moderate alpha-1 antitrypsin deficiency with lung cancer in the Serbian population

BACKGROUND: Alpha-1 antitrypsin (AAT) is an important serine protease inhibitor in human plasma. Its major physiological role is to inhibit neutrophil elastase (NE) in the lower respiratory tract and protect lung tissue from destruction. Recent studies indicated an etiological role of NE in lung cancer development. The aim of this study was to investigate the association of alpha-1 antitrypsin deficiency (AATD) with lung cancer in patients with four different histological types of cancer: squamous cell carcinoma, adenocarcinomas, large cell carcinoma and small cell carcinoma. METHODS: Phenotyping was carried out by isoelectric focusing (pH 4.2-4.9). We compared the frequency of AATD phenotypes in 186 lung cancer patients with the value obtained in our previous study in a healthy Serbian population (3.7%) using the Fisher exact test. RESULTS: Allele frequencies in patients were Pi *M 0.9677, Pi *Z 0.0215, Pi *S 0.0081 and Pi *other rare 0.0027. Eleven of the 186 lung cancer patients (5.9%) were AATD heterozygotes with moderate deficiencies (PiMZ and PiMS). When this value was compared with AATD heterozygote frequency obtained in the healthy individuals (3.7%), the difference was close to the level of significance (p = 0.055). However, individuals with AATD phenotypes had a higher risk of developing squamous cell lung cancer then those with non-deficient AAT variants (OR = 4.51, 95% CI = 1.66-12.29). CONCLUSIONS: Our findings provide evidence of an association between AAT phenotypes with moderate deficiency and squamous cell lung cancer.     

The connection between HLA microsatellites and HLA-B*27 gene in patients with psoriatic arthritis in Croatian population

The polymorphism at HLA microsatellites (D6S248, D6S2674, D6S2811 and D6S273) among patients with psoriatic arthritis (PsA) (N = 22) and healthy control subjects (K; N = 94), as well as haplotypic associations between tested loci were analysed in this study. All subjects were previously typed for HLA-A and -B by PCR-SSP method and were HLA-B*27 positive. HLA microsatellites were analysed using PCR-STR method and electrophoresis in an ALFexpress sequencer. The results demonstrated statistically significant P value for following alleles: D6S273-3 (PsA-21.1% vs. K-4.9%; P = 0.0013) and D6S273-4 (PsA-15.8% vs. K-32.1%; P = 0.0180). Analysis of haplotypic associations showed the only statistically significant difference for combination HLA-B*27/D6S273-4 (PsA-10.5% vs. K-40.2%; P = 0.0164). The results presented in this study lead to the assumption that some other gene/s involved in ethiology of PsA are located in the proximity of D6S273 microsatellite, but in order to reach a final conclusion, an increase in the number of patients is necessary.     

Two cases of probable endogenous extensive cutaneous larva migrans in Serbia

Cutaneous larva migrans (CLM) is a skin infestation clinically characterized by erythematous serpiginous lesions caused by nematode larvae, usually of animal hookworms. It is most commonly seen in tropical and subtropical geographic areas. It is occasionally seen in Europe and other temperate climates, most often in patients that have previously traveled to tropical areas. We present two male patients that did not travel abroad with clinical features of extensive CLM located on the trunk acquired in an unusual way. CLM is not characteristic of Serbia, which is located in southeast Europe Unusually hot and sunny weather with heavy rainfall and high humidity during the summers of 2005 and 2006 were favorable conditions for the development of parasites in the soil and infestation with large numbers of larvae. To the best of our knowledge, this is the first report of extensive CLM in Serbia.