Jochem König

Evaluation of health information systems—problems and challenges

OBJECTIVES Information technology (IT) is emerging in health care. A rigorous evaluation of this technology is recommended and of high importance for decision makers and users. However, many authors report problems during the evaluation of information technology in health care. In this paper, we discuss some of these problems, and propose possible solutions for these problems. METHODS Based on own experience and backed up by a literature review, some important problems during IT evaluation in health care together with their reasons, consequences and possible solutions are presented and structured. RESULTS AND CONCLUSIONS We define three main problem areas-the complexity of the evaluation object, the complexity of an evaluation project, and the motivation for evaluation. Many evaluation problems can be subsumed under those three problem areas. A broadly accepted framework for evaluation of IT in healthcare seems desirable to address those problems. Such a framework should help to formulate relevant questions, to find adequate methods and tools, and to apply them in a sensible way.

Epidemiology of invasive mycosis in ICU patients : a prospective multicenter study in 435 non-neutropenic patients

Objective: To determine the epidemiological and clinical significance of invasive fungal infections in non-neutropenic patients in intensive care who stay longer than 10 days on the intensive care unit (ICU). Design: Prospective epidemiological multicenter study over a period of 11 months, based on strict clinical, bacteriological, serological and histological criteria. Setting: Six surgical and two medical ICUs units in five university and two municipal hospitals. Patients: 435 non-neutropenic patients from medical and surgical ICUs with an ICU stay of more than 10 days. Measurements and main results: A new occurrence of invasive mycosis (3 sepsis/ 4 peritonitis/ 1 disseminated candidiasis), corresponding to the protocol conditions with onset after day 10 in the ICU, was detectable in 2.0 % (95 % confidence interval 0.85 to 3.8 %) of the 409 patients who could be assessed. Candida species were identified as an infection-relevant pathogen in all cases. The most important risk factor for the development of an invasive mycosis was the onset of peritonitis by the day 11 in the ICU (odds ratio 11.3; p = 0.003). A fungal colonization was detected in 64 % of patients (Candida species 56 %, Aspergillus 4 %, and other fungi). Six of 8 patients with an invasive mycosis died on the ICU; ICU mortality in patients with fungal colonization was 31 % and in noncolonized patients 26 %. Serological tests were not helpful clinically. The sensitivity was 88 % for the Candida HAT (haemagglutination test) (threshold titer > 1:160), 100 % for the Candida IFT (immunofluorescence test) (threshold titer > 1:80), and 50 % for the Candida Antigen Test (Candtec Ramco, threshold titer ≥ 1:8), and the specificity was 26, 6, and 73 %, respectively. The specificity for the Aspergillus HAT (threshold titer > 1:10) was 29 %. Conclusions: Invasive mycoses are rare in non-neutropenic ICU patients, even after a longer stay in the intensive care unit; fungal colonization, on the other hand, is frequently detectable. The mortality of invasive mycosis – even with systemic antimycotic therapy- was high; the mortality in patients with fungal colonization was not significantly increased compared to that in noncolonized patients. The serological test procedures, Candida HAT, Candida IFT, and the Candida Ramco Antigen Test, had a low specificity and were not helpful in diagnosing relevant invasive mycosis.

Vascular Effects of Diet Supplementation With Plant Sterols

OBJECTIVES The purpose of this study was to evaluate vascular effects of diet supplementation with plant sterol esters (PSE). BACKGROUND Plant sterol esters are used as food supplements to reduce cholesterol levels. Their effects on endothelial function, stroke, or atherogenesis are not known. METHODS In mice, plasma sterol concentrations were correlated with endothelial function, cerebral lesion size, and atherosclerosis. Plasma and tissue sterol concentrations were measured by gas-liquid chromatography-mass spectrometry in 82 consecutive patients with aortic stenosis. RESULTS Compared with those fed with normal chow (NC), wild-type mice fed with NC supplemented with 2% PSE showed increased plant sterol but equal cholesterol plasma concentrations. The PSE supplementation impaired endothelium-dependent vasorelaxation and increased cerebral lesion size after middle cerebral artery occlusion. To test the effects of cholesterol-lowering by PSE, apolipoprotein E (ApoE)-/- mice were randomized to Western-type diet (WTD) with the addition of PSE or ezetimibe (EZE). Compared with WTD, both interventions reduced plaque sizes; however, WTD + PSE showed larger plaques compared with WTD + EZE (20.4 +/- 2.1% vs. 10.0 +/- 1.5%). Plant sterol plasma concentration strongly correlated with increased atherosclerotic lesion formation (r = 0.50). Furthermore, we examined plasma and aortic valve concentrations of plant sterol in 82 consecutive patients with aortic stenosis. Patients eating PSE-supplemented margarine (n = 10) showed increased plasma concentrations and 5-fold higher sterol concentrations in aortic valve tissue. CONCLUSIONS Food supplementation with PSE impairs endothelial function, aggravates ischemic brain injury, effects atherogenesis in mice, and leads to increased tissue sterol concentrations in humans. Therefore, prospective studies are warranted that evaluate not only effects on cholesterol reduction, but also on clinical endpoints.

T grafts with the right internal thoracic artery to left internal thoracic artery versus the left internal thoracic artery and radial artery: Flow dynamics in the internal thoracic artery main stem

OBJECTIVE Complete arterial coronary artery bypass grafting with 2 grafts can be achieved even in triple vessel disease by use of a T configuration. There is still uncertainty whether the coronary flow reserve in the main stem of the left internal thoracic artery is sufficient to supply more than 1 anastomosed coronary vessel. METHODS Between March 1996 and February 1999, 251 patients with multivessel coronary artery disease underwent complete arterial revascularization with T grafts, using either the left internal thoracic artery with the free right internal thoracic artery graft (n = 73, group I) or the left internal thoracic artery and radial artery (n = 178, group II). A mean of 4.0 (group I) versus 4.3 (group II) coronary vessels were anastomosed per patient. One week (n = 92) and 6 months (n = 28) after the operation, flow was measured in the proximal left internal thoracic artery with a Doppler guide wire. Maximum flow was determined after injection of adenosine (30 microg). RESULTS The in-hospital mortality was 2.7% (group I) versus 2.3% (group II). At angiography (n = 142, 56.6%) the patency rate was 96.3% (group I) versus 98.2% (group II). There was no significant difference between baseline flow, maximum flow, and coronary flow reserve between the 2 groups. Coronary flow reserve increased in both groups within the first 6 postoperative months (group I, 1.85 +/- 0.31 vs 2.77 +/- 0.77, P =.0002; group II, 1.82 +/- 0.4 vs 2.53 +/- 0.73, P =.009). CONCLUSION Both variants of T grafts allow for complete arterial revascularization with good perioperative results. The flow reserve of the proximal internal thoracic artery is adequate for multiple coronary anastomoses irrespective of the choice of the second arterial graft.

A graphical tool for locating inconsistency in network meta-analyses

BackgroundIn network meta-analyses, several treatments can be compared by connecting evidence from clinical trials that have investigated two or more treatments. The resulting trial network allows estimating the relative effects of all pairs of treatments taking indirect evidence into account. For a valid analysis of the network, consistent information from different pathways is assumed. Consistency can be checked by contrasting effect estimates from direct comparisons with the evidence of the remaining network. Unfortunately, one deviating direct comparison may have side effects on the network estimates of others, thus producing hot spots of inconsistency.MethodsWe provide a tool, the net heat plot, to render transparent which direct comparisons drive each network estimate and to display hot spots of inconsistency: this permits singling out which of the suspicious direct comparisons are sufficient to explain the presence of inconsistency. We base our methods on fixed-effects models. For disclosure of potential drivers, the plot comprises the contribution of each direct estimate to network estimates resulting from regression diagnostics. In combination, we show heat colors corresponding to the change in agreement between direct and indirect estimate when relaxing the assumption of consistency for one direct comparison. A clustering procedure is applied to the heat matrix in order to find hot spots of inconsistency.ResultsThe method is shown to work with several examples, which are constructed by perturbing the effect of single study designs, and with two published network meta-analyses. Once the possible sources of inconsistencies are identified, our method also reveals which network estimates they affect.ConclusionOur proposal is seen to be useful for identifying sources of inconsistencies in the network together with the interrelatedness of effect estimates. It opens the way for a further analysis based on subject matter considerations.

Radiofrequency ablation as first-line treatment in patients with early colorectal liver metastases amenable to surgery.

Objective:Aiming at avoidance of futile surgery, we have tested whether radiofrequency ablation (RFA) may be used as first-line treatment in patients with colorectal metastases (CRLM) occurring within the first year after colorectal surgery. Summary Background Data:Surgical resection is the standard treatment in patients with CRLM. Major retrospective analyses have identified the interval between colorectal surgery and the occurrence of CRLM to be of prognostic importance. So far, it is unknown whether survival of the respective patients is hampered if RFA is used as first-line treatment. Methods:According to a clinical pathway, we have treated patients with CRLM detected within the first year after colorectal surgery preferentially by RFA (n = 28). Resection (n = 82) was performed in patients who were deemed not amenable to RFA due to number, size, or location of metastatic lesions. The diameter of lesions differed between the groups. All other characteristics of patients and lesions were comparable. Local recurrence and new hepatic lesions were treated with repeated RFA or surgery whenever possible. Results:Local recurrence at the site of ablation or resection occurred in 32% and 4% (P < 0.001), new metastases apart from the site of previous treatment in 50% and 34% (P = 0.179), and systemic recurrence in 32% and 37% (P = 0.820) of the patients after RFA and surgery, respectively. Time to progression was significantly shorter in patients primarily treated with RFA (203 vs. 416 days; P = 0.017). After primary treatment, 9 RFA patients and 8 surgery patients were amenable to repeated RFA or repeated surgery resulting in identical rates of disease-free patients and identical 3-year overall survival in both treatment groups: 67% and 60%, respectively; P = 0.93. Conclusions:Despite striking differences in local tumor recurrence and shorter time to progression, survival in patients with early CRLM does not depend on the mode of primary hepatic treatment.

Development of the standard reference plane for the Heidelberg retina tomograph.

Abstract Background: Topometry of the optic disc is the quantitative assessment of the structure of the optic nerve head by means of three- dimensional parameters. The parameter values depend on definitions of intraocular reference planes. Purpose: To describe the development of intraocular reference planes in laser scanning tomography for the Heidelberg Retina Tomograph (HRT) using image intrinsic data with a fixed offset reference plane (320 µm) and to present a contour-line-based ”flexible” standard reference plane (”SRP”) for calculation of intrapapillary stereometric parameters taking the interindividual variability of optic disc topography into account.Methods: Ten-degree triple images were obtained by laser scanning tomography from 99 glaucoma eyes and 180 normal eyes. The images were evaluated to assess the variability of height measurements of an optic disc border contour-line segment (6° width) corresponding to the site of the papillo-macular bundle as indicated by the average optic disc surface inclination angle. Results: The average optic disc surface inclination angle was –7°±3° below the horizontal meridian (0°). The 6° wide contour-line segment for the SRP was chosen according to the average surface inclination angle (–10° to –4°). The reproducibility of the SRP-segment height measurements was 16.0±10.8 µm for normal eyes and 23.4±18.0 µm for glaucoma eyes. To ensure that the automatic reference level determination for intrapapillary parameters remained below the disc border height, we defined the SRP level at a 50 µm offset (>2 SD of average segment height reproducibility in glaucoma) added to the individual height position of the 6° contour line segment. Conclusion: The flexible standard reference plane allows for automatic determination of intrapapillary variables once a disc border contour line is interactively defined. In contrast to a fixed offset reference plane (e.g. 320 µm below the mean retina height), the interindividual variability of optic disc topography (oblique insertion, glaucomatous surface flattening) is respected at the cost of the need for an accurate optic disc border outline.

Irradiation Induces a Biphasic Expression of Pro-Inflammatory Cytokines in the Lung

Background and Purpose:The precise pathophysiological mechanisms of radiation-induced lung injury are poorly understood, but have been shown to correlate with dysregulation of different cytokines. The purpose of this study was to evaluate the time course of the pro-inflammatory cytokines tumor necrosis factor-(TNF-)α, interleukin-(IL-)1α and IL-6 after whole-lung irradiation.Material and Methods:The thoraces of C57BL/6J mice were irradiated with 12 Gy. Treated and control mice were sacrificed at 0.5, 1, 3, 6, 12, 24, 48, 72 h, 1, 2, 4, 8, 16, and 24 weeks post irradiation (p. i.). Real-time multiplex RT-PCR (reverse transcriptase polmyerase chain reaction) was established to evaluate the expression of TNF-α, IL-1α and IL-6 in the lung tissue of the mice. For histological analysis, lung tissue sections were stained by hematoxylin and eosin.Results:Multiplex RT-PCR analysis revealed a biphasic expression of these pro-inflammatory cytokines in the lung tissue after irradiation. After an initial increase at 1 h p. i. for TNF-α and at 6 h p. i. for IL-1α and IL-6, the mRNA expression of these pro-inflammatory cytokines returned to basal levels (48 h, 72 h, 1 week, 2 weeks p. i.). During the pneumonic phase, TNF-α, IL-1α and IL-6 were significantly elevated and revealed their maximum at 8 weeks p. i. Histopathologic evaluation of the lung sections obtained within 4 weeks p. i. revealed only minor lung damage in 5–30% of the lung tissue. By contrast, at 8, 16, and 24 weeks p. i., 70–90% of the lung tissue revealed histopathologically detectable organizing alveolitis.Conclusion:Irradiation induces a biphasic expression of pro-inflammatory cytokines in the lung. The initial transitory cytokine response occurred within the first hours after lung irradiation with no detectable histopathologic alterations. The second, more persistent cytokine elevation coincided with the onset of histologically discernible organizing acute pneumonitis.Hintergrund und Ziel:Die genaue Pathophysiologie der strahleninduzierten Lungenschädigung ist bislang nur unvollständig geklärt, scheint aber mit einer Dysregulation verschiedener Zytokine assoziiert zu sein. Das Ziel dieser experimentellen Studie war es, den zeitlichen Expressionsverlauf der proinflammatorischen Zytokine Tumor-Nekrose-Faktor-(TNF-)α, Interleukin-(IL-)1α und IL-6 nach Lungenbestrahlung zu untersuchen.Material und Methodik:Bei C57BL/6J-Mäusen wurde eine Ganzlungenbestrahlung mit 12 Gy durchgeführt. Die Versuchstiere und unbestrahlte Kontrolltiere wurden zu unterschiedlichen Zeitpunkten (0,5, 1, 3, 6, 12, 24, 48, 72 h bzw. 1, 2, 4, 8, 16 und 24 Wochen) nach Bestrahlung getötet. Im Lungengewebe wurde die mRNA-Expression von TNF-α, IL-1α und IL-6 mit Hilfe der Real-Time-multiplex-RT-PCR (Reverse-Transkriptase-Polymerase-Kettenreaktion) quantifiziert. Für die histologische Beurteilung der Lungenpräparate wurde eine Hämatoxylin-Eosin-Färbung durchgeführt.Ergebnisse:Im Rahmen der strahleninduzierten Lungenschädigung konnte mit Hilfe der Multiplex-RT-PCR eine biphasische Expression dieser proinflammatorischen Zytokine nachgewiesen werden. Nach einem initialen Anstieg—bereits 1 h nach Bestrahlung für TNF-α und nach 6 h für IL-1α und IL-6—ging die Zytokinexpression auf Ausgangswerte zurück. Während der Pneumonitisphase war die mRNA-Expression von TNF-α, IL-1α und IL-6 signifikant erhöht und ereichte 8 Wochen nach Bestrahlung ihr Maximum. Während sich bis zu 4 Wochen nach Bestrahlung histopathologisch nur eine geringe Lungenschädigung in 5–30% des Gesamtlungengewebes beobachten ließ, waren nach 8, 16 bzw. 24 Wochen 70–90% des Gesamtlungengewebes im Sinne einer radiogenen Pneumonitis geschädigt.Schlussfolgerung:Im Rahmen der radiogenen Lungenreaktion konnte eine biphasische Expression der proinflammatorischen Zytokine nachgewiesen werden. Die initiale Zytokinerhöhung erfolgte in den ersten Stunden nach Lungenbestrahlung, ohne dass histopathologisch eine Lungenschädigung nachweisbar war. Die zweite, länger persistierende Zytokinerhöhung (einige Wochen nach Bestrahlung) korrelierte mit dem Beginn einer histologisch nachweisbaren radiogenen Pneumonitis.

Standard treatment of female patients with breast cancer decreases substantially for women aged 70 years and older: a German clinical cohort study

BACKGROUND Standard treatment of patients with breast cancer decreases with age and older persons are mostly excluded from clinical trials. We hypothesized that non-adherence to treatment guidelines occurs for women aged > or =70 years and changes overall survival (OAS) and disease-free survival (DFS). PATIENTS AND METHODS We enrolled 1922 women aged > or =50 years with histologically confirmed invasive breast cancer treated at the University of Ulm from 1992 to 2005. Adherence to guidelines and effects on OAS and DFS for women aged > or =70 years was compared with that for younger women (50-69 years). RESULTS Women >70 years less often received recommended breast-conserving therapy (70-79 years: 74%-83%; >79 years: 54%) than women aged < or =69 years (93%). Non-adherence to the guidelines on radiotherapy (<70 years: 9%; 70-79 years: 14%-27%; >79 years: 60%) and chemotherapy (<70 years: 33%; 70-79 years: 54%-77%; > 79 years: 98%) increased with age. Omission of radiotherapy significantly decreased OAS [< or =69 years: hazard ratio (HR) = 3.29; P <0.0001; > or =70 years: HR = 1.89; P = 0.0005] and DFS (< or =69 years: HR = 3.45; P <0.0001; > or =70 years: HR = 2.14; P <0.0001). OAS and DFS did not differ significantly for adherence to surgery, chemotherapy, or endocrine therapy. CONCLUSION Our study confirms that substandard treatment increases considerably with age. Omission of radiotherapy had the greatest impact on OAS and DFS in the elderly population.

Autoantibodies against GLEA2 and PHF3 in glioblastoma: tumor-associated autoantibodies correlated with prolonged survival.

Using serological identification of recombinantly expressed tumor antigens (SEREX), we identified several autoantibodies against glioma‐expressed antigens including GLEA1, GLEA2 and PHD‐finger protein3 (PHF3). Analysing sera of 62 glioblastoma patients, we found an antibody response against GLEA1 in 15 sera (24.2%), against GLEA2 in 30 sera (48.4%) and against PHF3 in 35 sera (56.5%). Relating patient survival to the occurrence of autoantibodies against either GLEA1, GLEA2 or PHF3, we found a significant prolonged survival for glioblastoma patients positive for autoantibodies against GLEA2 (p = 0.0115) and PHF3 (p = 0.0031), respectively. The median survival of patients with GLEA2 antibodies was increased to 17.4 months and for patients with PHF3 antibodies to 14.7 months, as compared to 7.2 months for patients without GLEA2 or PHF3 antibodies. There was no significant correlation between patient survival and GLEA1‐autoantibodies (p = 0.1611). Herein we present autoantibodies that are: (i) most frequent in glioblastoma patients; (ii) specific for glioblastoma‐associated antigens; and (iii) significantly correlated with prolonged survival in patients with glioblastoma.