Nal-IRI with 5-fluorouracil (5-FU) and leucovorin or gemcitabine plus cisplatin in advanced biliary tract cancer - the NIFE trial (AIO-YMO HEP-0315) an open label, non-comparative, randomized, multicenter phase II study.

BACKGROUND: Biliary tract cancer (BTC) has a high mortality. Primary diagnosis is frequently delayed due to mostly unspecific symptoms, resulting in a high number of advanced cases at the time of diagnosis. Advanced BTCs are in principle chemotherapy sensitive as determined by improved disease control, survival and quality of life (QoL). However, median OS does not exceed 11.7 months with the current standard of care gemcitabine plus cisplatin. Thereby, novel drug formulations like nanoliposomal-irinotecan (nal-IRI) in combination with 5- fluorouracil (5-FU)/leucovorin may have the potential to improve therapeutic outcomes in this disease. METHODS: NIFE is an interventional, prospective, randomized, controlled, open label, two-sided phase II study. Within the study, 2 × 46 patients with locally advanced, non-resectable or metastatic BTC are to be enrolled by two stage design of Simon. Data analysis will be done unconnected for both arms. Patients are allocated in two arms: Arm A (experimental intervention) nal-IRI mg/m2, 46 h infusion)/5-FU (2400 mg/m2, 46 h infusion)/leucovorin (400 mg/m2, 0.5 h infusion) d1 on 14 day-cycles; Arm B (standard of care) cisplatin (25 mg/m2, 1 h infusion)/gemcitabine (1000 mg/m2, 0.5 h infusion) d1 and d8 on 21 day-cycles. The randomization (1:1) is stratified for tumor site (intrahepatic vs. extrahepatic biliary tract), disease stage (advanced vs. metastatic), age (≤70 vs. > 70 years), sex (male vs. female) and WHO performance score (ECOG 0 vs. ECOG 1). Primary endpoint of the study is the progression free survival (PFS) rate at 4 months after randomization by an intention-to-treat analysis in each of the groups. Secondary endpoints are the overall PFS rate, the 3-year overall survival rate, the disease control rate after 2 months, safety and patient related outcome with quality of life. The initial assessment of tumor resectability for locally advanced BTCs is planned to be reviewed retrospectively by a central surgical board. Exploratory objectives aim at establishing novel biomarkers and molecular signatures to predict response. The study was initiated January 2018 in Germany. DISCUSSION: The NIFE trial evaluates the potential of a nanoliposomal-irinotecan/5-FU/leucovorin combination in the first line therapy of advanced BTCs and additionally offers a unique chance for translational research. TRIAL REGISTRATION: Clinicaltrials.gov NCT03044587. Registration Date February 7th 2017.

[Formal sample size calculation and its limited validity in animal studies of medical basic research]. / Die limitierte Aussagekraft formaler Fallzahlplanung im Rahmen von Tierversuchen der medizinischen Grundlagenforschung.

Animal studies are highly relevant for basic medical research, although their usage is discussed controversially in public. Thus, an optimal sample size for these projects should be aimed at from a biometrical point of view. Statistical sample size calculation is usually the appropriate methodology in planning medical research projects. However, required information is often not valid or only available during the course of an animal experiment. This article critically discusses the validity of formal sample size calculation for animal studies. Within the discussion, some requirements are formulated to fundamentally regulate the process of sample size determination for animal experiments.

Analgesic drug use associated with statin prescription--a cross-sectional study in primary care settings.

BACKGROUND: To investigate whether features of muscular complaints (MC) differ between receivers of a statin prescription and non-receivers. To analyze the relationship between analgesics prescription, statin prescription and/or musculoskeletal disorders. METHODS: Cross-sectional study. Consecutive patients in offices of family practitioners were interviewed using a standardized questionnaire. Target variables: Rates of features of MC in patients with or without a statin prescription and rates of analgesic drug prescription in patients with or without statin prescription and/or musculoskeletal disorders. Odds ratios (adjusted for age, sex, and socio-economic status) were calculated using logistic regression analysis. RESULTS: 1135 patients in 26 general practitioners' offices were asked to participate, and 1031 patients agreed. Features of MC did not differ between the two groups of patients. Analgesic prescription was found to be associated with statin prescription in patients without musculoskeletal disorders (OR 2.2, CI 1.1-4.7 without statin, OR 2.5, CI 0.9-6.9 with statin) and particularly in those with musculoskeletal disorders (OR 5.2, CI 2.9-9.3 without statin, OR 9.3, CI 4.5-19.1 with statin). CONCLUSIONS: Analgesic prescriptions are probably positively associated with statin prescription. Assuming that analgesics attenuate MC, an even stronger association between MC and statin use seems likely. The results generate the hypothesis that statin use contributes to analgesic use in primary care patients.

[Maintenance of health and relief for caregivers of elderly with dementia by using "initial case management": experiences from the Lighthouse Project on Dementia, Ulm, ULTDEM-study]. / Gesunderhaltung und Entlastung pflegender Angehöriger von Demenzkranken durch ein "initiales Case Management": Erfahrungen aus dem Ulmer Leuchtturmprojekt Demenz (ULTDEM-Studie).

BACKGROUND: When facing the well-known demographic development with an increasing number of people suffering from dementia, there is a need of programmes to support nursing relatives and care at home. Many support services have been established in the past few years but they are rarely used by the relatives and the patients. The purpose of the Lighthouse Project Ulm (ULTDEM Study) was to prove the effectiveness of a single advisory approach in order to provide support services after care level classification and to relieve the burden placed on relatives caring for family members suffering from dementia ("initial case management"). METHODS: The ULTDEM Study is a prospective, open, randomized, controlled, interventional study with different parallel outcome measures (burden of caring, quality of life and mood). After the randomization, the interventional group was given comprehensive, individual advice about available treatment possibilities for dementia patients. Control group participants received standard treatment. Inclusion criteria were application of a care level (0 or 1) as well as dementia diagnosis. All participants (patients/relatives) underwent an initial and a 6 month comprehensive assessment. RESULTS: Our results show that a single advisory approach does not lead to a significant difference in outcome measures in interventional and control groups. Those tendencies described have to be interpreted as clinically not relevant. Although utilization of support services increases, it remains similar in both study groups. A confirmatory interpretation has not been possible due to a lack of adjustment to the findings regarding multiple testing and an insufficient degree of recruitment. Possible causes will be discussed such as premature intervention during the course of the disease, a lack of intervention blinding, recruitment bias and lack of an influence on adherence with regard to the use of support services. IMPLICATIONS: The study demonstrates that there is a substantial information deficit for persons affected by dementia and their relatives. Innovative ways still have to be developed to ensure that this information actually reaches the target audience.

Cryobiopsy increases the diagnostic yield of endobronchial biopsy: a multicentre trial.

Forceps, brushes or needles are currently the standard tools used during flexible bronchoscopy when diagnosing endobronchial malignancies. The new biopsy technique of cryobiopsy appears to provide better diagnostic samples. The aim of this study was to evaluate cryobiopsy over conventional endobronchial sampling. A total of 600 patients in eight centres with suspected endobronchial tumours were included in a prospective, randomised, single-blinded multicentre study. Patients were randomised to either sampling using forceps or the cryoprobe. After obtaining biopsy samples, a blinded histological evaluation was performed. According to the definitive clinical diagnosis, the diagnostic yield for malignancy was evaluated by a Chi-squared test. A total of 593 patients were randomised, of whom 563 had a final diagnosis of cancer. 281 patients were randomised to receive endobronchial biopsies using forceps and 282 had biopsies performed using a flexible cryoprobe. A definitive diagnosis was achieved in 85.1% of patients randomised to conventional forceps biopsy and 95.0% of patients who underwent cryobiopsy (p<0.001). Importantly, there was no difference in the incidence of significant bleeding. Endobronchial cryobiopsy is a safe technique with superior diagnostic yield in comparison with conventional forceps biopsy.

Needs-oriented discharge planning for high utilisers of psychiatric services: multicentre randomised controlled trial.

AIMS: Attempts to reduce high utilisation of mental health inpatient care by targeting the critical time of hospital discharge are rare. In this study, we test the effect of a needs-oriented discharge planning intervention on number and duration of psychiatric inpatient treatment episodes (primary), as well as on outpatient service use, needs, psychopathology, depression and quality of life (secondary). METHODS: Four hundred and ninety-one adults with a defined high utilisation of mental health care gave informed consent to participate in a multicentre RCT carried out at five psychiatric hospitals in Germany (Düsseldorf, Greifswald, Regensburg, Ravensburg and Günzburg). Subjects allocated to the intervention group were offered a manualised needs-led discharge planning and monitoring intervention with two intertwined sessions administered at hospital discharge and 3 months thereafter. Outcomes were assessed at four measurement points during a period of 18 months following discharge. RESULTS: Intention-to-treat analyses showed no effect of the intervention on primary or secondary outcomes. CONCLUSIONS: Process evaluation pending, the intervention cannot be recommended for implementation in routine care. Other approaches, e.g. team-based community care, might be more beneficial for people with persistent and severe mental illness.

[Intraobserver and interobserver reliability of introital ultrasound after tension-free vaginal tape (TVT) procedure]. / Reliabilität der Introitussonografie nach Einlage eines spannungsfreien Vaginalbands nach dem TVT-Verfahren.

PURPOSE: To date, the evaluation of TVT by ultrasound has not been standardized. The aim of this observational study was to evaluate the intraobserver and interobserver variability of introital ultrasound. MATERIALS AND METHODS: Follow-up was performed for 202 patients after TVT procedure. The tape was characterized by the position in relation to urethral length (%) and the distance to the hypoechoic center of the urethra (mm). Furthermore, we assessed the shape of the tape (straight, curved or folded). All evaluations were performed by two experienced examiners (A, B) at rest and during Valsalva maneuver. All sonograms were archived digitally without measurement results. After 6 to 12 months, the sonograms were re-evaluated by one investigator (A). Depending on the first investigator, the results were compared as intraobserver (A-A) or interobserver (B-A) agreement. The first results were blinded for the second measurement. Agreement concerning the distances was assessed using the intraclass correlation coefficient (ICC). The concordance of the descriptive evaluation of the shape of the tape was characterized by the kappa coefficient (KC). RESULTS: The tape was regularly identified as an echogenic structure dorsal to the urethra. The intraobserver reliability concerning the position of the tape in relation to urethral length showed good reproducibility (at rest ICC 0.90, Valsalva maneuver: ICC 0.96). For the distance between the tape and the urethra at rest (ICC 0.83), there was also good reproducibility, but not during Valsalva maneuver (ICC 0.74). The shape of the tape showed only moderate reproducibility with accordance of 81 % at rest (KC 0.68) and of 79 % during Valsalva maneuver (KC 0.6). The interobserver comparisons showed good concordance in measuring the POS at rest (ICC 0.93), and during Valsalva maneuver (ICC 0.89), and the DIS at rest (ICC 0.89), and during Valsalva maneuver (ICC 0.87). The congruence of the estimation of the shape was 71 % at rest (KC 0.44) and 72 % during Valsalva maneuver (KC 0.49). CONCLUSION: The characterization of the TVT in the sagittal view by introital ultrasound shows good reproducibility with respect to position and distance, but not shape.

MESNA (sodium 2-mercaptoethanesulfonate) for prevention of contrast medium-induced nephrotoxicity - controlled trial.

BACKGROUND: The purpose of this study was to examine the efficacy of sodium 2-mercaptoethanesulfonate (MESNA), a reactive oxygen scavenger, in at-risk patients given radiographic contrast agents. Contrast-induced nephropathy (CIN) is a common complication of radiographic procedures; reactive oxygen species (ROS) could play a key role. METHODS: We conducted a randomized, double-blinded, placebo-controlled trial in 100 patients with stable serum creatinine levels ≥ 150 µmol/l. They received an infusion of either 1,600 mg of MESNA (n = 51) or placebo (n = 49) plus 0.9% saline prior to and after contrast administration. CIN was defined as a ≥ 25% increase in serum creatinine after 48 h compared to baseline. RESULTS: CIN occurred in 7 patients in the placebo group and none in the MESNA group (p = 0.005). The adjusted odds ratio for CIN was 0.17 (95% confidence interval 0.03 - 0.80, p = 0.026) in the MESNA group compared to the placebo group. Cystatin C concentrations decreased slightly in the MESNA group but increased in the control group (p < 0.05). CONCLUSION: MESNA plus volume expansion before and during contrast exposure was effective in this single-center study for preventing CIN compared to volume expansion alone.

Analgesia and pulmonary function after lung surgery: is a single intercostal nerve block plus patient-controlled intravenous morphine as effective as patient-controlled epidural anaesthesia? A randomized non-inferiority clinical trial.

BACKGROUND: Thoracic epidural anaesthesia (EDA) is regarded as the 'gold standard' for postoperative pain control and restoration of pulmonary function after lung surgery. Easier, less time-consuming, and, perhaps, safer is intercostal nerve block performed under direct vision by the surgeon before closure of the thoracotomy combined with postoperative i.v. patient-controlled analgesia with morphine. We hypothesized that this technique is as effective as thoracic EDA. METHODS: The study was designed as a single-centre, open labelled, randomized non-inferiority trial. A total of 92 patients undergoing elective lung surgery were randomly assigned to the epidural (n=47) or intercostal group (n=45), and 83 patients completed the study. Pain scores, inspiratory vital capacity, forced vital capacity (FVC), forced expiratory volume in the first second (FEV1), and peak expiratory flow rate (PEFR) were assessed during the first four postoperative days. RESULTS: Median treatment differences regarding pain scores at rest failed to demonstrate non-inferiority of the intercostal nerve block at the first postoperative day. Patients of the intercostal group reported significantly higher pain scores on coughing during the first and second postoperative days. The epidural group had a significantly higher median FVC, FEV1, and PEFR values on the second postoperative day. No difference was found in pulmonary complications, length of hospital stay, or in-hospital deaths. CONCLUSIONS: In patients undergoing lung surgery, single intercostal nerve block plus i.v. patient-controlled analgesia with morphine is not as effective as patient-controlled EDA with respect to pain control and restoration of pulmonary function.

Comparison of panorama ultrasonography, conventional B-mode ultrasonography, and computed tomography for measuring liver size.

PURPOSE: The objective of the present study is to compare the utility of extended field-of-view ultrasonography and conventional B-mode ultrasonography for determining liver size. MATERIALS AND METHODS: The liver size in the medioclavicular line (MCL) was determined in 104 inpatients (females: n = 47; males: n = 57) using both ultrasound methods (Philips HDI 5000). The liver size measured in computed tomography (CT; MX 8000 IDT, Philips) served as the gold standard. The body mass index (BMI), ultrasound scanning conditions, and hepatomegaly identified by CT were evaluated as possible factors affecting the measurement accuracy of the sonographic methods. RESULTS: The standard deviation of the differences between the measured pairs of values shows less dispersion in B-mode ultrasonography (18.7 mm) than panorama ultrasonography (20.8 mm). The mean value of differences between the measured pairs (bias) in the ultrasonographic methods compared to CT is considerably higher in panorama sonography (15.3 mm; SD = 20.8) than in B-mode ultrasonography (0.27 mm; SD = 18.7). A paired t-test of the mean values shows a significant difference between the ultrasonographic methods (p < 0.0001). In diagnosing or excluding hepatomegaly, B-mode sonography is consistent with CT findings in 84 (80.8 %) of 104 patients and panorama ultrasonography is consistent with CT findings in 77 (74.0 %) of 104 patients. Ultrasonographic methods show moderate agreement with each other (Kappa = 0.4265). Higher BMI and limited scanning conditions lead to an increase in the mean difference of measured pairs of values (bias) as well as to an increase in standard deviation of the differences (dispersion). CONCLUSION: The determination of liver size in the medioclavicular line using panorama ultrasonography often leads to the false-positive diagnosis of hepatomegaly. Therefore, the method should not be recommended for routine diagnostic scans. In cases of significant hepatomegaly, however, panorama ultrasonography offers superior visualization compared to conventional B-mode ultrasonography.

Comparison of sonographically measured bowel wall vascularity, histology, and disease activity in Crohn's disease.

The purposes of this study was to provide a retrospective comparison of semiquantitatively measured bowel wall vascularity by power Doppler sonography, endoscopic-histopathological biopsy findings, and disease activity in patients with confirmed Crohn's disease. Thirty-two out of 1,332 patients with histologically confirmed Crohn's disease (18 female, 14 male; mean age 38.8 years) met the inclusion criteria: ileocolonoscopy with biopsy and power Doppler sonographic determination of bowel wall vascularity with assessment of disease activity within a period of 5 days. Sonographic determination of bowel wall vascularity was based on a semiquantitative score. Endoscopic bowel wall biopsy specimens were assessed using a self-developed inflammation score and the disease activity was calculated using Crohn's disease activity index (CDAI). A significant association (p < 0.05) was shown for results of histology and bowel wall vascularity in the terminal ileum (kappa = 0.66; sensitivity 95%; specificity 69%). There was no observed association between CDAI and histology, although there was an association between CDAI and bowel wall vascularity (sensitivity 82%). Increased bowel wall vascularity in the terminal ileum measured by power Doppler ultrasound reflects inflammatory activity in histologically examined bowel wall. Power Doppler ultrasound may be able to monitor activity changes of the bowel wall determined by pharmaceutical treatment.

[The necessity of validating regression models--characterization of the most important methods]. / Validierung von Regressionsmodellen: Notwendigkeit und Beschreibung der wichtigsten Methoden.

In rehabilitation research regression models are often used in analysing the effects of several independent factors on important outcomes in rehabilitation. But the results of such models are rarely used in rehabilitation practice for diagnosis or prognosis of patient outcomes. The main reason for this is the fact that the applicability of such models for new patient data is often unknown. A good fit of the model with respect to the data used in modeling does not guarantee a well-fitting model in the future. Thus, it is necessary to examine the performance of the model for new patient data. This examination is called model validation. The main aspect in model validation is the investigation of the prediction error caused by a too optimistic estimation of the model parameters. This prediction error is due to the twofold use of the data set: for estimating the regression coefficients AND for examining the model fit. In this paper this error is discussed and the main methods for regression model validation are presented. Finally an example illustrates the effects of model validation for prognostic purposes in a logistic regression model estimating the risk of early retirement after in-patient rehabilitation.

[Logistic regression: a useful tool in rehabilitation research]. / Die logistische Regression - ein vielseitiges Analyseinstrument rehabilitationswissenschaftlicher Forschung.

Regression analysis is a frequently used tool to examine associations between a dependent (outcome) variable and one or more independent variables. The resulting model enables prediction of an unobserved outcome based on the observed independent variables. In rehabilitation research the dependent variable is quite often dichotomous, i. e. having just two parameter values (e. g. capable of work: yes/no). For such an outcome variable, the logistic regression model can be applied, having specific advantages in interpreting the model parameters with respect to risk factor analysis. In this paper the basics of the logistic regression model, interpretation of the model parameters and special aspects of modelling are presented. Subsequently the logistic regression model is applied to an example dataset for estimating the risk of early retirement after inpatient rehabilitation.

Low discomfort and pain associated with intensified insulin therapy in children and adolescents.

OBJECTIVE: Discomfort during insulin injection and self-monitoring of blood glucose (SMBG) is a potential obstacle in diabetes therapy, but its prevalence and extent in relation to clinical variables is uncertain. RESEARCH DESIGN AND METHODS: We prospectively assessed treatment-associated discomfort and pain in an unselected cohort of patients (60 boys and 52 girls; mean age 14.6+/-3.0 years, mean A1C 8.0+/-1.4%) with type 1 diabetes and multiple daily self-injections of insulin, using visual analogue/verbal rating scales (range, 0-10) and a six-item questionnaire. RESULTS: Pain during insulin injection was absent to very low in 91.9% of patients, and its intensity was independent of age, gender, diabetes duration, current A1C, injection volume, or type of insulin. Injection was more unpleasant than SMBG in 64.2% of patients (mean difference of pain score, 1.0+/-1.7, p<0.0001). Injection into the upper arm was less painful than into the thigh and abdomen. Surprisingly, painlessness of injection and SMBG was not judged an important treatment goal by 22.0 and 32.9% of patients, respectively. Logistic difficulties (41.2% of responses) and time requirements (23.8%), but not pain (10.1%), were considered most relevant problems. CONCLUSIONS: In young patients with access to optimized diabetes care, pain during insulin injection and SMBG is infrequent or mild, and not widely perceived as problematic, thus encouraging the use of multiple daily injection treatment.

Distance to achieve steady state walking speed in frail elderly persons.

This study aims to determine the length of the gait initiation phase before achieving steady state walking in frail older people. Based on body fixed sensors, habitual walking was analysed in 116 community-dwelling older persons (mean age 83.1 years, 84% women). The start of steady state walking was identified using an algorithm taking into account speeds from consecutive strides. On average, participants reached a walking speed of 0.66 m/s after an acceleration phase of 1.43 m (89% after 2.47 m). When spatio-temporal variables were calculated from 4, 6, 8, 10, or 20 consecutive stride cycles after achieving steady state, similar values were observed for mean gait speed and stride length. The variability of these factors differed depending on the number of gait cycles. Assessments of steady state gait in frail elderly people should therefore exclude the first 2.5m of walking. If gait variability is to be assessed, it is recommended that more than 20 stride cycles be used.

[Interobserver agreement in the assessment of pulmonary infiltrates on chest radiography in community-acquired pneumonia]. / Detektion pneumonischer Infiltrate bei ambulant erworbener Pneumonie: Ubereinstimmung in der Befundung der Röntgen-Thoraxaufnahme.

PURPOSE: To assess interobserver agreement (IOA) in the diagnosis of pulmonary infiltrates on chest x-rays for patients with community-acquired pneumonia (CAP). MATERIALS AND METHODS: From 7/2002 to 12/2005, 806 adults with CAP were included in the multicenter study "CAPNETZ" (7 hospitals). Inclusion criteria were clinical signs of pneumonia and pulmonary opacification on chest x-rays. Each x-ray was reevaluated by two radiologists from the university hospital in consensus reading against the interpreter at the referring hospital in regard to: presence of infiltrate (yes/no/equivocal), transparency (50%), localization, and pattern of infiltrates (alveolar/interstitial). The following parameters were documented: digital or film radiography, hospitalization, fever, findings of auscultation, microbiological findings. RESULTS: The overall IOA concerning the detection of infiltrates was 77.7% (n=626; CI 0.75-0.81), the infiltrates were not verified in 16.4% (n=132) by the referring radiologist with equivocal findings in 5.9% (n=48). The IOA of the different clinical centers varied between 63.2% (n=38, CI 0.48-0.78) and 92.3% (n=65, CI 0.86-0.99). The IOA for the diagnosis of infiltrates was significantly higher for inpatients with 82.6% (n=546; CI 0.80-0.85) than for outpatients with 55.2 % (n=80; CI 0.47-0.63), p<0.0001. The IOA of infiltrates with a transparency >50% was 95.1% (n=215; CI 0.92-0.98) versus 80.4% (n=403; CI 0.77-0.84) for infiltrates with a transparency >50% (p<0.0001). In patients with positive auscultation, the IOA was higher (p=0,034). Chest x-rays of patients with antibiotic therapy or an alveolar infiltrate showed more equivocal findings compared to patients without these features. CONCLUSION: There is considerable interobserver variability in the diagnosis of pulmonary infiltrates on chest radiographs. The IOA is higher in more opaque infiltrates, positive auscultation and inpatients.

Pubertal development in obese children and adolescents.

OBJECTIVE: To investigate clinical and laboratory markers of pubertal development in a large sample of obese children and adolescents. METHODS: Analysis of parameters of sexual maturation in 1232 obese individuals (582 boys) aged 6-18 years (mean 13.0+/-2.42 years). Clinical evaluation of pubertal stage and determination of bone age in a subset (227 patients). RESULTS: Mean Height--standard deviation scores (height-SDS) was positive during childhood and reached zero approximately at age 14 years followed by a turn to negative mean height-SDS in both genders. Accordingly, bone age was accelerated until age 14. No significant differences in average time points of occurrence of pubic hair stages PH 2 to PH 4 in boys and PH 2 to PH 5 in girls were observed as compared to references of the First Zurich Longitudinal Study. In girls, breast stage B 3 was reached earlier (11.6 vs 12.2 years, P=0.03). In boys, mean volume of testis revealed no significant deviation from reference. Mean dehydroepiandrosterone sulfate (DHEAS) levels were elevated in boys (within age ranges 8-10 years and 12-16 years, P<0.02) and in girls (within age ranges 6-8 years and 12-18 years, P<0.005) and mean testosterone levels in boys >12 years were lower as compared to reference ranges (all P-values <0.0001). CONCLUSION: The study data suggest normal development of pubarche and gonadarche in obese German boys and normal timing of pubarche in girls. Breast development in obese girls seems to be slightly advanced. In obese boys, an obvious dissociation of clinical and laboratory parameters of pubertal development was observed. Despite significantly increased height-SDS and increased DHEAS levels, gonadal development was normal and testosterone levels were decreased. Elevated DHEAS levels in both genders may contribute to the acceleration of bone maturation, a lower final body height and could increase cardiovascular risk.

[Organization of methodological support and cross-project research activities in multicenter research programmes - experiences of the centers for methodological support within the "rehabilitation science" research network]. / Organisation methodischer Beratung und projektübergreifender Forschungsaktivitäten in multizentrischen Forschungsprogrammen - Erfahrungen der Methodenzentren im Verbundforschungsprogramm Rehabilitationswissenschaften.

On completion of the funding period of six years within the federal programme for research in medical rehabilitation, an evaluative summary is given of the work performed and the experiences made in the cross-sectional projects offering methodological support. While specific research profiles had prevailed in each of the eight regional research networks, two institutions had been implemented with similar task assignments within all networks; i. e., (i) a central office, and (ii) a center for methodological support (CMS) had been available in order to enhance methodological research infrastructure and research quality of the clinical projects. This article outlines the support offered as well as further tasks of the CMS. Further, it is argued that organized, scientifically based methodological support and consultation should be part of any research network. Finally, a number of important aspects are discussed which should be taken into account to enhance research quality in medical rehabilitation in the future.

Gait analysis and WOMAC are complementary in assessing functional outcome in total hip replacement.

OBJECTIVE: To investigate the correlation between objective and subjective evaluation of patients with total hip replacement. DESIGN: Prospective preliminary trial comparing the Western Ontario and McMaster University questionnaire (WOMAC) and gait analysis preoperatively and three months postoperatively. SETTING: A German academic orthopaedic centre specializing in total hip replacement surgery. SUBJECTS: Seventeen patients (median age 70 years) with hip osteoarthritis. INTERVENTION: All patients had had a primary unilateral total hip replacement. MAIN MEASURES: WOMAC questionnaire to assess self-perceived health status and gait analysis to determine objective gait parameters. RESULTS: Performance of walking as well as subjective judgement of health status improved following surgery (gait speed P = 0.0222; stride length P = 0.038; stance phase ratio P = 0.0466; WOMAC P < 0.0001). However, the correlation between gait parameters and WOMAC was poor (r = -0.27 or less). Correlation between changes of walking parameters and WOMAC was bad to good (r = 0.01 to r = -0.72). CONCLUSION: The WOMAC questionnaire might not reflect walking performance. The addition of gait analysis is recommended to gain objective information about the quality of gait.

[Prediction of premature pension after stationary rehabilitation due to adipositas--a prognostic model based on routinely collected data of the State Insurance Institution of Baden-Württemberg]. / Vorhersage vorzeitiger Berentung nach stationärer Rehabilitation wegen Adipositas -- ein Prognosemodell basierend auf Routinedaten der Landesversicherungsanstalt Baden-Württemberg.

Up to 60 % of the German population can be marked as obese. Due is to its frequency and its associated diseases like cardiovascular disorders and disorders of the musculoskeletal system adipositas is a severe burden on the German health care system. This burden is caused by costs of the disease and costs due to premature pensioning. In this study logistic regression modelling has been performed by means of routinely collected data of patients of the regional statutory pension insurance institute Landesversicherungsanstalt Baden-Württemberg (LVA-BW) rehabilitated due to adipositas (n = 599). The aim was to detect influential variables for the prognosis of premature pensioning (n = 135). The data of the patients were obtained from a research database of the "RehaNet" project which includes data of the standardized discharge report of the Federation of German Pension Insurance Institutes and quality assurance questionnaires of the LVA-BW. Three variables remain in the model after a step-down procedure for modelling by logistic regression. The selected variables are age (in years), the physician's statement about the patients limitations of movement after rehabilitation (yes/no) and about the patients ability to work in future (more/less than half-day). After internal validation of the model by bootstrap methods the model achieves a sensitivity of 73 %, a specificity of 87 %, a positive and a negative predictive value of 57 and 93 % respectively. The area under the curve (AUC) of the ROC analysis is 0.87, so the model achieves a good prognostic value. Thus, this model is a valuable test for the exclusion of possible premature pension while or after rehabilitation due to adipositas. It was found that the situation of "no premature pensioning" of patients rehabilitated due to adipositas can be predicted quite accurately with little information (three variables). This reveals a perspective for further research in the possibility of an early, risk-adapted and individualised intervention after stationary rehabilitation for adipositas to keep employment.