Stefan Gräber

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.

Valve Configuration Determines Long-Term Results After Repair of the Bicuspid Aortic Valve

Background— Reconstruction of the regurgitant bicuspid aortic valve has been performed for >10 years, but there is limited information on long-term results. We analyzed our results to determine the predictors of suboptimal outcome. Methods and Results— Between November 1995 and December 2008, 316 patients (age, 49±14 years; male, 268) underwent reconstruction of a regurgitant bicuspid aortic valve. Intraoperative assessment included extent of fusion, root dimensions, circumferential orientation of the 2 normal commissures (>160°, ≤160°), and effective height after repair. Cusp pathology was treated by central plication (n=277), triangular resection (n=138), or pericardial patch (n=94). Root dilatation was treated by subcommissural plication (n=100), root remodeling (n=122), or valve reimplantation (n=2). All patients were followed up echocardiographically (cumulative follow-up, 1253 years; mean, 4±3.1 years). Clinical and morphological parameters were analyzed for correlation with 10-year freedom from reoperation with the Cox proportional hazards model. Hospital mortality was 0.63%; survival was 92% at 10 years. Freedom from reoperation at 5 and 10 years was 88% and 81%; freedom from valve replacement, 95% and 84%. By univariable analysis, statistically significant predictors of reoperation were age (hazard ratio [HR]=0.97), aortoventricular diameter (HR=1.24), effective height (HR=0.76), commissural orientation (HR=0.95), use of a pericardial patch (HR=7.63), no root replacement (HR=3.80), subcommissural plication (HR=2.07), and preoperative aortic regurgitation grade 3 or greater. By multivariable analysis, statistically significant predictors for reoperation were age (HR=0.96), aortoventricular diameter (HR=1.30), effective height (HR=0.74), commissural orientation (HR=0.96), and use of a pericardial patch (HR=5.16). Conclusions— Reconstruction of bicuspid aortic valve can be performed reproducibly with good early results. Recurrence and progression of regurgitation, however, may occur, depending primarily on anatomic features of the valve.

Heart rate reduction by If-inhibition improves vascular stiffness and left ventricular systolic and diastolic function in a mouse model of heart failure with preserved ejection fraction

AIMS In diabetes mellitus, heart failure with preserved ejection fraction (HFPEF) is a significant comorbidity. No therapy is available that improves cardiovascular outcomes. The aim of this study was to characterize myocardial function and ventricular-arterial coupling in a mouse model of diabetes and to analyse the effect of selective heart rate (HR) reduction by If-inhibition in this HFPEF-model. METHODS AND RESULTS Control mice, diabetic mice (db/db), and db/db mice treated for 4 weeks with the If-inhibitor ivabradine (db/db-Iva) were compared. Aortic distensibility was measured by magnetic resonance imaging. Left ventricular (LV) pressure-volume analysis was performed in isolated working hearts, with biochemical and histological characterization of the cardiac and aortic phenotype. In db/db aortic stiffness and fibrosis were significantly enhanced compared with controls and were prevented by HR reduction in db/db-Iva. Left ventricular end-systolic elastance (Ees) was increased in db/db compared with controls (6.0 ± 1.3 vs. 3.4 ± 1.2 mmHg/µL, P < 0.01), whereas other contractility markers were reduced. Heart rate reduction in db/db-Iva lowered Ees (4.0 ± 1.1 mmHg/µL, P < 0.01), and improved the other contractility parameters. In db/db active relaxation was prolonged and end-diastolic capacitance was lower compared with controls (28 ± 3 vs. 48 ± 8 μL, P < 0.01). These parameters were ameliorated by HR reduction. Neither myocardial fibrosis nor hypertrophy were detected in db/db, whereas titin N2B expression was increased and phosphorylation of phospholamban was reduced both being prevented by HR reduction in db/db-Iva. CONCLUSION In db/db, a model of HFPEF, selective HR reduction by If-inhibition improved vascular stiffness, LV contractility, and diastolic function. Therefore, If-inhibition might be a therapeutic concept for HFPEF, if confirmed in humans.

Effect of Subchondral Drilling on the Microarchitecture of Subchondral Bone Analysis in a Large Animal Model at 6 Months

Background: Marrow stimulation techniques such as subchondral drilling are clinically important treatment options for symptomatic small cartilage defects. Little is known about whether they induce deleterious changes in the subchondral bone. Hypothesis: Subchondral drilling induces substantial alterations of the microarchitecture of the subchondral bone that persist for a clinically relevant postoperative period in a preclinical large animal model. Study Design: Controlled laboratory study. Methods: Standardized full-thickness chondral defects in the medial femoral condyles of 19 sheep were treated by subchondral drilling. Six months postoperatively, the formation of cysts and intralesional osteophytes was evaluated. A standardized methodology was developed to segment the ovine subchondral unit into reproducible volumes of interest (VOIs). Indices of bone structure were determined by micro–computed tomography (micro-CT). Results: Analysis of the microarchitecture revealed the absence of zonal stratification in the ovine subarticular spongiosa, permitting an unimpeded and simultaneous analysis of the entire subchondral trabecular network. Subchondral drilling led to the formation of subchondral bone cysts (63%) and intralesional osteophytes (26%). Compared with the adjacent unaffected subchondral bone, drilling induced significant alterations in nearly all parameters for the microarchitecture of the subchondral bone plate and the subarticular spongiosa, most importantly in bone volume, bone surface/volume ratio, trabecular thickness, separation, pattern factor, and bone mineral density (BMD) (all P ≤ .01). Conclusion: The data show that the ovine subchondral bone can be reliably evaluated using micro-CT with standardized VOIs. We report that subchondral drilling deteriorates the microarchitecture both of the subchondral bone plate and subarticular spongiosa and decreases BMD. These results suggest that the entire osteochondral unit is altered after drilling for an extended postoperative period. Clinical Relevance: The subchondral bone remains fragile after subchondral drilling for longer durations than previously expected. Further evaluations of structural subchondral bone parameters of patients undergoing marrow stimulation are warranted.

Strategic information management plans: the basis for systematic information management in hospitals

Information management in hospitals is a complex task. In order to reduce complexity, we distinguish strategic, tactical, and operational information management. This is essential, because each of these information management levels views hospital information systems from different perspectives, and therefore uses other methods and tools. Since all these management activities deal only in part with computers, but mainly with human beings and their social behavior, we define a hospital information system as a sociotechnical subsystem of a hospital. Without proper strategic planning it would be a matter of chance, if a hospital information system would fulfil the information strategies goals. In order to support strategic planning and to reduce efforts for creating strategic plans, we propose a practicable structure.

Aortic root and cusp configuration determine aortic valve function

OBJECTIVE Normalisation of aortic root and cusp configuration is a prerequisite for successful aortic valve repair (AVR). Using transthoracic echocardiography, we studied aortic root dimensions relative to body size in normal subjects and AVR patients. METHODS Aortic roots of healthy volunteers (n=130, age 27.9 ± 16.9 years) were examined for aortoventricular (AV), sinus (S), sinutubular-junction diameters (ST) and effective height (height difference between the AV plane and central coaptation point, eH) by transthoracic echocardiography. In 651 patients, after AVR residual aortic valve insufficiency (AI) and eH were determined. The relationships between eH versus root dimensions and eH versus residual AI were analysed by analysis of variance with Bonferroni post hoc testing. RESULTS Root dimensions correlated with each other and body size (r=0.74-0.91). In addition, a correlation between AV (r=0.73), sinus diameter (r=0.76), body height (r=0.77), body surface area (r=0.81) and eH was found. After AVR, eH was 9.8 ± 0.9 mm in 235 patients without postoperative AI, 9.4 ± 1.1mm in 370 with mild AI, 7.9 ± 1.4mm in 43 patients with moderate AI and 6 ± 1mm in three patients with severe AI. The difference in means of effective height between the groups was significant (p<0.005). Of 497 AVR patients with an eH ≥ 9 mm, 309 had no or trivial AI, 186 had mild AI and only two had moderate AI. CONCLUSIONS Parameters of aortic root dimensions follow a seemingly constant pattern in humans of different sizes. Effective height has a constant relationship to root dimensions and body size. In AVR, normalisation of eH leads to a high probability of normal or near-normal aortic valve function.

DNA Repair Alterations in Children With Pediatric Malignancies: Novel Opportunities to Identify Patients at Risk for High-Grade Toxicities

PURPOSE To evaluate, in a pilot study, the phosphorylated H2AX (γH2AX) foci approach for identifying patients with double-strand break (DSB) repair deficiencies, who may overreact to DNA-damaging cancer therapy. METHODS AND MATERIALS The DSB repair capacity of children with solid cancers was analyzed compared with that of age-matched control children and correlated with treatment-related normal-tissue responses (n = 47). Double-strand break repair was investigated by counting γH2AX foci in blood lymphocytes at defined time points after irradiation of blood samples. RESULTS Whereas all healthy control children exhibited proficient DSB repair, 3 children with tumors revealed clearly impaired DSB repair capacities, and 2 of these repair-deficient children developed life-threatening or even lethal normal-tissue toxicities. The underlying mutations affecting regulatory factors involved in DNA repair pathways were identified. Moreover, significant differences in mean DSB repair capacity were observed between children with tumors and control children, suggesting that childhood cancer is based on genetic alterations affecting DSB repair function. CONCLUSIONS Double-strand break repair alteration in children may predispose to cancer formation and may affect childrens susceptibility to normal-tissue toxicities. Phosphorylated H2AX analysis of blood samples allows one to detect DSB repair deficiencies and thus enables identification of children at risk for high-grade toxicities.

Atrial fibrillation and heart rate independently correlate to microalbuminuria in hypertensive patients

AIMS To investigate the relationship between microalbuminuria (MAU) and atrial fibrillation (AF) and to further evaluate whether the heart rate dependency of MAU in patients without AF is maintained in patients with a history of AF. METHODS AND RESULTS The International Survey Evaluating Microalbuminuria Routinely by Cardiologists in patients with Hypertension (I-SEARCH) included 18,900 patients without and 1705 patients with a history of AF suffering from hypertension and other risk factors for cardiovascular disease in 26 countries worldwide from September 2005 to March 2006. Heart rate, blood pressure, urinary albumin excretion, and an estimated glomerular filtration rate were determined among other parameters. The prevalence of MAU was higher at higher heart rate in both patients with and without a history of AF. Prevalence of MAU was about 10% higher in patients with a history of AF (P < 0.001). Male gender, the presence of diabetes mellitus, a higher heart rate, and a higher diastolic blood pressure were independently associated with increased odds for MAU in patients without and with a history of AF. CONCLUSION The prevalence of MAU in hypertensive patients with cardiovascular risk factors is related to heart rate and significantly higher in patients with a history of AF.

THE IMPACT OF INDIVIDUAL IN VIVO REPAIR OF DNA DOUBLE-STRAND BREAKS ON ORAL MUCOSITIS IN ADJUVANT RADIOTHERAPY OF HEAD-AND-NECK CANCER

PURPOSE To evaluate the impact of individual in vivo DNA double-strand break (DSB) repair capacity on the incidence of severe oral mucositis in patients with head-and-neck cancer undergoing adjuvant radiotherapy (RT) or radiochemotherapy (RCT). PATIENTS AND METHODS Thirty-one patients with resected head-and-neck cancer undergoing adjuvant RT or RCT were examined. Patients underwent RT of the primary tumor site and locoregional lymph nodes with a total dose of 60-66 Gy (single dose 2 Gy, five fractions per week). Chemotherapy consisted of two cycles of cisplatin and 5-fluorouracil. To assess DSB repair, γ-H2AX foci in blood lymphocytes were quantified before and 0.5 h, 2.5 h, 5 h, and 24 h after in vivo radiation exposure (the first fraction of RT). World Health Organization scores for oral mucositis were documented weekly and correlated with DSB repair. RESULTS Sixteen patients received RT alone; 15 patients received RCT. In patients who developed Grade≥3 mucositis (n=18) the amount of unrepaired DSBs 24 h after radiation exposure and DSB repair half-times did not differ significantly from patients with Grade≤2 mucositis (n=13). Patients with a proportion of unrepaired DSBs after 24 h higher than the mean value + one standard deviation had an increased incidence of severe oral mucositis. CONCLUSIONS Evaluation of in vivo DSB repair by determination of γ-H2AX foci loss is feasible in clinical practice and allows identification of patients with impaired DSB repair. The incidence of oral mucositis is not closely correlated with DSB repair under the evaluated conditions.

The relationships of markers of cholesterol homeostasis with carotid intima-media thickness.

Background The relationship of cholesterol homeostasis and carotid intima-media thickness (cIMT) is unknown. To address this, we assessed markers of cholesterol homeostasis (serum plant sterols and cholesterol precursor concentrations as surrogate measures of cholesterol absorption and synthesis, respectively) and cIMT in a middle-aged, statin-naive population. Methods In this prospective study of primary prevention cIMT was measured by ultrasound in 583 hospital employees aged 25–60 years without prevalent cardiovascular disease or lipid-modifying medication. The serum concentrations of plant sterols (as markers of cholesterol absorption) were measured by gas-liquid chromatography. Lathosterol serum concentrations were quantitated to assess hepatic cholesterol synthesis. Results cIMT correlated positively with serum cholesterol (r = 0.22, P<0.0005) and lathosterol-to-cholesterol (r = 0.18, P<0.001). In contrast, plant sterols, as markers of cholesterol absorption, showed a weak negative correlation to cIMT measurements (r = −0.18; P<0.001 for campesterol-to-cholesterol). Stratifying subjects by serum sterol levels, we found that cIMT increased continuously over quintiles of serum cholesterol (P<0.0005) and was positively associated to serum lathosterol-to-cholesterol levels (P = 0.007), on the other hand, plant sterol levels showed a weak negative association to cIMT (P<0.001 for campesterol-to-cholesterol). Conclusions In this population without prevalent cardiovascular diseases or lipid-modifying medication, markers of increased endogenous cholesterol synthesis correlated positively with cIMT, while markers of cholesterol absorption showed a weakly negative correlation. These data suggest that not only total serum cholesterol levels but also differences in cholesterol homeostasis are associated with cIMT.