Biomedical subjects

Franz Koenig

Publications and source records attributed to Franz Koenig.

9 recordsLinked to original sources

PubMed2006

The reassessment of trial perspectives from interim data--a critical view.

If an interim analysis is performed during a trial it is tempting to determine the conditional power to reach a rejection in the trial given the observed results in the interim analysis. Since the true effect size is unknown the conditional power may be calculated by using the effect size, which the study has been powered for in the planning phase or by using an interim estimate of the true size (or a combination of both). In either case the conditional power is a random variable and its density is investigated depending on the analysis time and the true effect size. Under the null hypothesis, in early interim analyses after a small proportion of sample units, the conditional power typically will be close to the overall power when the effect size from the planning stage is used for calculation. In this case the majority of observations must still be made and the small first-stage sample in general will be dominated by the hypothetical second-stage chance based on the wrong parameter value. It is shown that the conditional power in moderately underpowered studies can have a distribution symmetric around 0.5. When using the interim estimate for calculating the conditional power the density in general will be u-shaped. The impact of using conditional power to reassess the sample size using flexible two-stage combination tests is shown for a specific example in terms of overall power and average sample size as compared to the corresponding group sequential design. For small true effect sizes mid-trial sample size recalculation based on an interim estimate may lead to an overly large price to be paid in average sample size in relation to the gain in overall power. Finally, the problem is discussed in terms of estimating the true conditional power.

Clinical Trials as Topic↗

PubMed2005

Testing and estimation in flexible group sequential designs with adaptive treatment selection.

Integrating selection and confirmation phases into a single trial can expedite the development of new treatments and allows to use all accumulated data in the decision process. In this paper we review adaptive treatment selection based on combination tests and propose overall adjusted p-values and simultaneous confidence intervals. Also point estimation in adaptive trials is considered. The methodology is illustrated in a detailed example based on an actual planned study.

Austria↗

PubMed2005

Geriatric polytrauma.

BACKGROUND: compared to a younger population, the treatment of geriatric trauma victims is known to be associated with a higher mortality and morbidity. The objectives of this study are to assess the clinical course and outcome of multitrauma patients aged 65 years and over. In addition, a direct comparison between the geriatric trauma patients and the younger collective is performed. METHOD: our study includes all multitrauma patients treated between 1992 and 2001 at a major urban trauma center. The major issues of this analysis are: injury severity, injury pattern, preclinical hemodynamics and intubation rate, operative treatment, ventilation time, outcome as well as incidence of multiorgan failure (MOF) and adult respiratory distress syndrome (ARDS). Out of these results, adults over 65 years of age (group B, n = 45) are compared to the younger group, ranging from 16 to 64 years of age (group A, n = 369). RESULTS: The preclinical intubation rate was comparable in both groups (A: 73.2%, B: 68.9%). Significantly more cases of group B were primarily shocked (A: 29.0%, B: 48.9%). The mean ISS was comparable in both groups (A: 34.0; B: 32.1). The younger group showed a significantly higher incidence of spine injuries (A: 21.1%; B: 6.7%). The number of emergency procedures (A: 24.2%; B: 24.4%) and operations during the first 24 hours (A: 70.2%; B: 60.0%) was comparable in both groups. The older group showed a lower number of reconstructive operations (A: 57.6%; B: 35.6%). Geriatric trauma patients had a longer ventilation time compared to their younger counterparts (A: 13.0 days, B: 20.0 days). During ICU-therapy, the ARDS rate was comparable (A: 16.0%, B: 15.6%). In contrast, the incidence of MOF was significantly higher in group B (A: 7.1%; B: 17.8%). The older group showed a significantly higher mortality rate (A: 26.8%; B: 53.3%) as well as early mortality during the first 24 hours after admission (A: 16.3%, B: 31.11%). CONCLUSION: Despite similarity in injury severity and a comparable injury pattern, elderly multitrauma patients initially presented a higher rate of hemodynamic instability, had to be ventilated longer and had a higher mortality.

Adolescent↗

PubMed2005

IFN-gamma-enhanced allergen penetration across respiratory epithelium augments allergic inflammation.

BACKGROUND: Respiratory allergen contact is the critical event in the elicitation and boosting of allergen-specific immune responses, as well as in the induction of immediate and late inflammatory reactions. OBJECTIVE: We sought to investigate the influence of various factors of allergic inflammation on the integrity and barrier function of respiratory epithelium for allergens. METHODS: We cultured the human bronchial epithelial cell line 16HBE14o- in a transwell culture system as a surrogate of intact respiratory epithelium and used purified iodine 125-labeled recombinant major birch pollen allergen (rBet v 1) to study the extent, kinetics, and factors influencing transepithelial allergen penetration. RESULTS: Culture supernatants from activated allergen-specific T H 1 clones decreased transepithelial resistance. A screening of various factors (histamine, IFN-gamma, IL-1beta, IL-2, IL-3, IL-4, IL-5, IL-8, IL-12, and TNF-alpha) identified IFN-gamma as a potent factor capable of reducing epithelial barrier properties and enhancing transepithelial allergen penetration. Increased submucosal allergen concentrations caused by IFN-gamma-mediated reduction of epithelial barrier function provoked a more than 7-fold augmentation of histamine release from sensitized basophils. CONCLUSION: These results demonstrate that the T H 1 cell-derived cytokine IFN-gamma facilitates allergen penetration through the respiratory epithelium and thereby can aggravate allergic inflammation.

Allergens↗

PubMed2004

Do monthly or seasonal variations exist in suicides in a high-risk setting?

An unequal distribution of suicides over months and seasons has been a consistent finding in epidemiological surveys on suicide. Jails and prisons are a high-risk setting for suicide all over the world. The high prevalence of both outward and self-directed violence in prison populations indicates dysfunctional central serotonin (5-HT) neurotransmission and, therefore, could account for an unequal distribution of suicides over months and seasons due to underlying bioclimatic factors. Within a total survey of suicides in the Austrian penitentiary system, the weekly, monthly and seasonal distribution of custodial suicides between 1947 and 1999 was studied. After an explorative comparison of suicide distribution over weekdays, months and seasons of the year by chi2-tests, a harmonic Poisson regression model was performed to detect seasonality of suicides. No unequal distribution of suicides was evident over the 53-year period. A limitation of this study was its sample size of 412, a low number compared with population-based samples, where a spring suicide peak was consistently found. An explanation for lacking seasonality could be that bioclimatic factors are less relevant in urban, industrialized areas, where jails and prisons usually are located. One of the core characteristics of penal institutions is the limited possibility for communication and social interaction. This social isolation is independent of seasonal changes. If the individual's possibilities for social interactions are limited, the influence of seasonal changes in social activities may be less relevant. This could explain the absence of seasonal changes in custodial suicide incidence.

Austria↗

PubMed2004

Suicide in custody: case-control study.

BACKGROUND: Few risk factors and indicators of vulnerability for suicide in custody are known so far. AIMS: A case-control study was conducted to investigate the relevance of criminal history, psychiatric morbidity and social integration to suicide in prison. METHOD: For every suicide that occurred in an Austrian correctional institution between 1975 and 1999, two controls matched for correctional institution, gender, nationality, age, custodial status and time of admission were selected. Psychiatric characteristics, previous suicidal behaviour, criminal history and indicators of social integration were compared. RESULTS: Of 250 recorded suicides, 220 personal files were available and matched to 440 controls. The most important predictors for suicide in custody were a history of suicidality (status following attempted suicide and suicide threat), psychiatric diagnosis, psychotropic medication, a highly violent index offence and single- cell accommodation. CONCLUSIONS: A significant finding is the importance of suicidal behaviour as an indicator of risk of suicide in correctional institutions, which until now has been a matter of debate. This study demonstrates the need for staff to take suicidal behaviour as seriously in custodial settings as in any other circumstances.

Adolescent↗

PubMed2003

Effects of a femoral shaft fracture on multiply injured patients with a head injury.

To study the effects of a femoral shaft fracture and its early stabilization on the morbidity, mortality, and outcome of patients with multiple injuries and a concomitant head injury, we analyzed the clinical course of patients using a prospectively gathered database. A series of 42 patients with multiple injuries, including head injuries and femoral fractures, formed the study group. A series of 133 patients with multiple injuries and head injuries but without femoral fractures formed the control group. The parameters examined included injury severity, injury pattern, hemodynamics at admission, mortality, duration of ventilation, length of intensive care unit (ICU) stay, and outcome. There were no significant differences regarding the demographics, injury severity score (ISS), injury pattern except the extremity Abbreviated Injury Scale (AIS) between the study and control groups. No significant differences were found in terms of mortality, duration of ventilation/ICU stay, and outcome. Injury severity (ISS), severity of the head injury (AIS), and hemodynamics at admission were shown to have a significant effect on the examined parameters. The present study suggests that a femoral fracture and its early stabilization in a multitrauma patient with a concomitant head injury do not adversely affect mortality and outcome and supports aggressive surgical management for these patients.

Adolescent↗

PubMed2003

Fixation of femoral fractures in multiple-injury patients with combined chest and head injuries.

BACKGROUND: The purpose of the present paper was to study the effects of a femoral shaft fracture and its early stabilization on the morbidity, mortality, and outcome of multiple-injury patients with combined blunt head and chest trauma. The clinical course of patients was analysed using a prospectively gathered data base. METHODS: Out of 352 multitrauma patients, from September 1992 to June 2000, we identified 28 patients with combined blunt chest and head trauma (abbreviated injury scale >/= 2) and a femoral fracture as the study group. A total of 120 patients with combined chest and head trauma but without femoral fracture formed the control group. Parameters examined included injury severity, injury pattern, haemodynamics at admission, mortality, duration of ventilation, length of stay in intensive care unit, and outcome. RESULTS: There were no significant differences regarding the demographics and injury severity (injury severity score) between the two groups. No significant differences were found in terms of mortality, duration of ventilation\intensive care unit stay and outcome. Injury severity (P < 0.0001), age (P = 0.0153), and haemodynamics at admission (P = 0.0036) were shown to have a significant effect on mortality and outcome. Injury severity (P < 0.0001) and age (P = 0.017) had a significant effect on the duration of ventilation\intensive care unit stay. CONCLUSIONS: The present study suggests that a femoral shaft fracture and its early stabilization in a multitrauma patient with combined chest and head injury do not adversely affect mortality and outcome and supports aggressive surgical management for these patients.

Adolescent↗

PubMed2003

Survival in patients undergoing transjugular intrahepatic portosystemic shunt: ePTFE-covered stentgrafts versus bare stents.

In patients with liver cirrhosis, implantation of a transjugular intrahepatic shunt (TIPS) leads to reduction of portal pressure, but not of mortality compared with other therapies. The high stenosis rates of conventional bare stents causes high reintervention rates and costs and may be correlated with poor survival. ePTFE-covered stentgrafts provide much improved patency rates, but their impact on survival is unclear. All suitable patients receiving either bare TIPS (419/466) or undergoing implantation of ePTFE endoprostheses (89/100) in several centers in Austria up to 2002 were included in this retrospective analysis. Both patient groups were compared regarding survival with Kaplan-Meier and Cox regression analysis. Unmatched and 1:1-matched survival analyses were performed. Patients undergoing ePTFE stentgraft implantation had significantly higher survival rates in all analyses. The 3-month, 1-year, and 2-year survival rates were 93%, 88%, and 76% for the ePTFE-group and 83%, 73%, and 62% for conventional TIPS patients, respectively. The matched survival analyses validated these findings. The model of the stent, patient age, and Child-Pugh Class (CPC) were independent predictors of survival. In conclusion, patients undergoing ePTFE-endoprosthesis implantation had higher survival rates within 2 years after TIPS-implantation. This may be the result of improved patency rates after correct placement (up to the inferior caval vein [ICV]) of the ePTFE stentgraft. These data should be validated in a prospective series.

Adult↗