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.

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.

[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.

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.

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.

[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.

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.

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.

Contribution of androgens to the gender difference in leptin production in obese children and adolescents.

Recent studies demonstrated significantly higher serum leptin concentrations in females as compared with males, even after correction for differences in body fat mass. The aim of our study was to measure serum leptin concentrations in a large group of obese children and adolescents to determine the possible role of sex steroid hormones on both leptin serum concentrations and production in human adipocytes. Obese girls were found to have significantly higher leptin concentrations than boys at the same degree of adiposity (25.2+/-14.1 vs. 17.2+/-12.6 ng/ml, P < 0.001). In a multiple regression analysis with age and body mass index (percent body fat) as fixed variables, it turned out that testosterone had a potent negative effect on serum leptin in boys, but not in girls. In vitro experiments using newly developed human adipocytes in primary culture showed that both testosterone and its biologically active metabolite dihydrotestosterone are able to reduce leptin secretion into the culture medium by up to 62%. Using a semiquantitative reverse transcriptase-PCR method, testosterone was found to suppress leptin mRNA to a similar extent. These results suggest that, apart from differences in body fat mass, the higher androgen concentrations in obese boys are responsible for the lower leptin serum concentrations compared with obese girls.

[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.

Association between C-reactive protein and features of the metabolic syndrome: a population-based study.

OBJECTIVE: To assess the association of circulating levels of C-reactive protein, a sensitive systemic marker of inflammation, with different components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: Total cholesterol (TC), HDL cholesterol, triglycerides, uric acid, BMI , and prevalence of diabetes and hypertension were assessed in 747 men and 956 women aged 18-89 years who were participating in the population-based National Health and Nutrition Survey, which was carried out in former West Germany in 1987-1988. RESULTS: There was a statistically significant positive crude correlation between C-reactive protein and TC (R = 0.19), TG (R = 0.29), BMI (R = 0.32), glucose (R = 0.11), and uric acid (R = 0.14) (all P < 0.0001). A negative correlation was found between C-reactive protein and HDL cholesterol (R = 0.13, P < 0.0001). The age-adjusted geometric means of C-reactive protein concentrations in subjects grouped according to the presence of 0-1, 2-3, and > or =4 features of the metabolic syndrome were 1.11, 1.27, and 2.16 mg/l, respectively, with a statistically highly significant trend (P < 0.0001). CONCLUSIONS: The data suggest that a variety of features of the metabolic syndrome are associated with a systemic inflammatory response.

Body composition in 5-18-y-old obese children and adolescents before and after weight reduction as assessed by deuterium dilution and bioelectrical impedance analysis.

The aim of the present study was to develop an equation for the prediction of total body water (TBW) from bioelectrical impedance analysis (BIA) in obese children and adolescents before and after weight reduction. In 146 obese subjects with a mean age of 12.7 +/- 3.0 y (5.5-17.8 y), TBW was measured by using deuterium dilution as well as the resistance index (RI; ht2/resistance) using BIA before and after weight loss. Initially, the RI correlated well with measured TBW (r2 = 0.92, P < 0.001). A multiple-regression analysis using forward stepwise selection of the variables RI, sex, age, weight, height, and waist-hip ratio revealed that the equation TBW = 0.35 x RI + 0.27 x age + 0.14 x weight - 0.12 predicts most accurately individual values of TBW before weight loss (adjusted r2 = 0.96, SEE = 1.9 L) with a mean error of predicted TBW of 1.40 +/- 1.38 L. This equation was validated in 1000 random samples (bootstrap-sampling method), giving a mean r2 of 0.95. During the weight-reduction program, which included an energy-restricted diet and an extensive exercise program, the patients lost 7.7 +/- 3.2 kg, leading to a small decrease in TBW of 0.4 +/- 1.5 L. When the developed prediction equation was applied to the data after weight loss, an r2 value of 0.94 between measured and calculated TBW and a mean error of 2.18 +/- 1.89 L was obtained. Validation of the equation in 1000 random samples after weight loss again gave a mean r2 value of 0.95. Individual changes in predicted TBW correlated only weakly with those of measured TBW (r = 0.21, P < 0.05). Thus, individual TBW values before and after weight loss can be predicted by BIA with acceptable accuracy by using the developed equation. However, prediction of small individual changes in TBW during weight loss is not possible by BIA.

Body-fat distribution and changes in the atherogenic risk-factor profile in obese adolescent girls during weight reduction.

We examined the effect of the pattern of body-fat distribution on the modification of atherogenic risk factors in obese adolescent girls during weight reduction. During the 6-wk program, which included a mixed diet of 4321 kJ/d and intensive physical exercise, the girls lost 8.5 +/- 2.4 kg and their waist-to-hip ratio (WHR) decreased from 0.86 +/- 0.05 to 0.81 +/- 0.05 (P < 0.01). Significant reductions were observed for total cholesterol, LDL cholesterol, uric acid, fasting insulin, and systolic and diastolic blood pressure. Girls with abdominal obesity (WHR > 0.88) had greater reductions in serum cholesterol, LDL cholesterol, and uric acid than did girls with gluteal-femoral obesity (WHR < 0.81). In a multivariate-regression analysis these differences could be partly explained by the greater weight loss of the girls with abdominal obesity. These results suggest that during weight reduction girls with abdominal obesity exhibit more beneficial changes in the atherogenic-risk-factor profile than do girls with gluteal-femoral obesity, partly because of a greater weight loss.

Systemic scleroderma. Multicenter trial of 1 year of treatment with recombinant interferon gamma.

OBJECTIVE: To confirm significant improvement of the skin score in systemic sclerosis by treatment with interferon gamma in a larger group of patients and to investigate on a molecular level the influence of interferon gamma on collagen type I messenger RNA expression. DESIGN: Open, noncontrolled multicenter study. SETTING: Five outpatient clinics specializing in the care of systemic scleroderma. PATIENTS: Thirty-two patients suffering from the diffuse or limited form of systemic sclerosis and progressive disease were recruited; 20 patients finished the study. INTERVENTION: Each patient received interferon gamma, 50 micrograms subcutaneously 3 times a week for 1 year. MAIN OUTCOME MEASURE: Skin score, collagen type I messenger RNA in skin biopsy specimens. RESULTS: The patients who completed the study showed an unchanged median skin score after 1 year of therapy. In addition, similar collagen type I messenger RNA levels were detected in skin biopsy specimens taken from involved skin before and after therapy in these patients. CONCLUSIONS: Treatment of systemic scleroderma with interferon gamma is associated with stabilization of the skin score and lack of worsening of visceral involvement.

[The Göttingen Risk, Incidence and Prevalence (GRIPS) study. Recommendations for the prevention of coronary heart disease]. / Göttinger Risiko-, Inzidenz- und Prävalenzstudie (GRIPS). Empfehlungen zur Prävention der koronaren Herzkrankheit.

The Göttingen Risk-, Incidence- and Prevalence Study (abbreviated GRIPS) consists of several epidemiological projects, among which project B is currently the most important one. Project B is a prospective cohort study, which was started in 1982 by a baseline investigation, including approximately 6000 men aged 40 to 60 years. Follow-up investigations were performed in 1985 and 1987 in order to record reasons of death and incidences of newly developed diseases. Further follow-up investigations are planned for 1990 and 1992. Until now incidence data of death and diseases are available for a 5-year observation period (January 1982-December 1986), and for more than 95% of the original study participants. The results clearly indicate that plasma levels of LDL-cholesterol, followed by plasma concentrations of total cholesterol and apoprotein B are the predominant predictors for the risk of coronary artery diseases (CAD; i.e. fatal and non fatal myocardial infarction as well as sudden coronary death and chronic coronary heart disease). Further significantly positive associations to the incidence of myocardial infarction (MI) were found for the following parameters: Systolic and diastolic blood pressure, family history of premature MI, cigarette smoking, plasma levels of triglycerides, VLDL-cholesterol and blood glucose. Plasma concentrations of HDL-cholesterol and apo A1 showed an inverse relationship to the MI incidence and--somewhat weaker--the same was true for the frequency of alcohol consumption and of physical leisure activity. Besides LDL-cholesterol, total cholesterol and apoprotein B the following parameters showed significantly positive associations to the risk of chronic coronary heart disease: Systolic as well as diastolic blood pressure and--to a lesser extent--the plasma levels of triglycerides, VLDL-cholesterol and blood glucose. An inverse relationship to the incidence rate of chronic coronary heart disease was found for HDL-cholesterol, apo A1 and the frequency of physical leisure activity. Based on the epidemiological results from GRIPS, additionally considering results from other epidemiologic studies and pathophysiological findings a diagnostic strategy was developed for the early recognition of patients at increased coronary risk. LDL-cholesterol is the most important variable in this diagnostic schedule but the coronary status and the individual profile of further risk factors (i.e. positive family history of premature myocardial infarction, hypertension, diabetes mellitus, cigarette smoking, increased plasma levels of triglyceride rich lipoproteins or Lp(a) as well as decreased plasma concentrations of HDL-cholesterol or apo A1) are additionally taken into account.

[Risk of myocardial infarct in 40 to 60-year-old males in relation to potential risk factors of atherosclerosis. Intermediate evaluation of the Göttingen risk, incidence and prevalence study following a 5-year observation period]. / Myokardinfarktrisiko bei 40- bis 60jährigen Männern in Abhängigkeit von potentiellen Risikofaktoren der Atherosklerose. Zwischenauswertungen der Göttinger Risiko-, Inzidenz- und Prävalenzstudie (GRIPS) nach einem 5jährigen Beobachtungszeitraum.

The main part of the Göttingen risk, incidence and prevalence study (GRIPS) is a prospective cohort-study (GRIPS-project B). In 1982 about 6,000 male subjects aged 40-60 years underwent an extensive, baseline examination. The incidences of death and disease are being recorded in this collective by regular follow-up investigations. A five-year observation period has now been completed for more than 95% of the original study participants. During this period 107 subjects, who had no symptoms of atherosclerotic diseases in 1982, developed fatal or non fatal myocardial infarction (MI). In the present evaluation this incidence group is compared to those study participants, who remained free of atherosclerotic diseases until December 1986 (reference group: n = 5160). The results indicate that LDL-cholesterol is the predominant predictor of MI-risk among all variables investigated. Additional risk factors of significance were as follows (in the rank order of their importance): positive family history of MI, hyperglycemia, low HDL-cholesterol, increased levels of triglyceride-rich-lipoproteins, hypertension, cigarette-smoking. For the most important risk-factor, LDL-cholesterol, 190 mg/dl seem to be a useful threshold value for therapeutic intervention according to the present data from GRIPS-project B. However, if additional risk-factors or definitive coronary artery disease are present, LDL-cholesterol levels below 140 mg/dl should be the therapeutic aim.

[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.

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.