Comparison of three forms of teaching - a prospective randomized pilot trial for the enhancement of adherence.

OBJECTIVE: Adherence of young adults to preventive programmes is low. The following study compares three different educational concepts to increase toothbrushing adherence in young adults. METHODS: Nine vocational school classes (157 young adults) were randomly assigned to three different 60-min approaches: (I) Education by a dentist, (II) Peer-teaching and (III) 'Adherence triangle concept' uniting dentists, teachers and participants as equal partners in intervention planning combined with peer teaching. Follow-up was 1 week for approaches I and II, and 1 week, 3 and 9 months for approach III. Adherence was defined as reported change from the childhood toothbrushing technique to adult technique. Adherence was evaluated using anonymous questionnaires and by diary analysis. RESULTS: After instruction, 90% of participants (approaches I-III) showed the desired behaviour in practice and theory. Reported adherence after 1 week with approach I was 28.5%, with approach II 39% and with approach III 95%. Prolonged follow-up of approach III yielded 76% after 3 months and 68% after 9 months. Adherence using approach III was significantly higher (P ≤ 0.001) than using approach I and II after 1 week. Adherence rates with approach III after 9 months were still higher than those of approaches I and II after 1 week. CONCLUSIONS: The 'adherence triangle' concept enhanced reported adherence significantly in comparison with previous studies and the one-dimensional concepts of approaches I and II. The tools of the adherence triangle concept seem worthwhile to be considered when planning new preventive action.

Myocardial protection in cardiac surgery patients requiring prolonged aortic cross-clamp times: a single-center evaluation of clinical outcomes comparing two blood cardioplegic strategies.

AIM: The aim of this study was to evaluate the impact of intermittent warm (IWC) versus intermittent cold blood cardioplegia (ICC) in high-risk patients that require prolonged periods of aortic cross-clamping during on-pump cardiac surgery. METHODS: From 3527 consecutive patients undergoing on-pump cardiac surgery, 520 patients were retrospectively identified that required prolonged aortic cross-clamp ≥ 75 min. Myocardial protection was performed with ICC (N.=280) or IWC (N.=240). Groups were compared regarding clinical outcomes, myocardial injury (CK-MB, cTnT) and multivariate analysis was performed to assess the impact of applied cardioplegia on 30-day all-cause mortality, cardiac death, perioperative myocardial injury (PM) and major adverse cardiac events (MACE). RESULTS: Demographic data, mean logistic Euroscore, aortic-cross-clamping and CPB time were comparable between groups. Patients with ICC needed more intraoperative defibrillations, had more postoperative blood transfusions and a prolonged hospital stay when compared to the IWC-group (P < 0.05). Thirty-day all-cause mortality tended to be higher in IWC (11% vs. 6%; P = 0.083) with significantly higher cardiac mortality (9% vs. 4%; P=0.015) compared to ICC. Myocardial injury was more pronounced in the IWC-group with a higher incidence of PMI (IWC: 17% vs. ICC:6%; P < 0.05) and MACE (IWC:37% vs. ICC:25%; P < 0.05). Groups did not differ regarding other postoperative clinical outcomes. Multivariate analysis revealed IWC to be independently predictive (P < 0.05) for 30-day all-cause mortality (OR:2.42; 95% CI:1.04-5.05), cardiac death (OR:3.57; 95% CI:1.49-8.85), MACE (OR:1.87; 95% CI:1.22-2.87) and PMI (OR:3.46; 95% CI:1.86-6.41). CONCLUSION: ICC results in less myocardial damage and reduced postoperative cardiac mortality and morbidity in patients requiring extended periods of aortic-cross-clamping during on-pump cardiac surgery, suggesting superior cardioprotection when compared to IWC.

Neurospora circadian rhythms in space: a reexamination of the endogenous-exogenous question.

To test the functioning of circadian rhythms removed from periodicities of the earth's 24-hour rotation, the conidiation rhythm of the fungus Neurospora crassa was monitored in constant darkness during spaceflight. The free-running period of the rhythm was the same in space as on the earth, but there was a marked reduction in the clarity of the rhythm, and apparent arrhythmicity in some tubes. At the current stage of analysis of our results there is insufficient evidence to determine whether the effect seen in space was related to removal from 24-hour periodicities and whether the circadian timekeeping mechanism, or merely its expression, was affected.

What is the value of available risk-scores in predicting postoperative complications after aorto-iliac surgery? A prospective non randomized study.

AIM: With an aging population, atherosclerotic manifestations are steadily increasing. Beside the anatomical and pathophysiological preoperative risk-factors accompanying perioperative risk-factors like patient's age, length of operation, blood loss and skill of the surgeon, all need to be accounted for when assessing the risk of morbidity and mortality after vascular surgery. The demand for cost effectiveness may make a risk-score system useful. The aim of the present study was, therefore, to prospectively apply various scoring systems in order to estimate outcome in patients undergoing aortobifemoral surgery due to arterial occlusive disease at the aorto-iliac level. METHODS: A prospective non randomized study was carried out. The SPSS 9.0 statistical package for Windows and, for nominal data, chi-squared-tests were used to compare rates between groups. For continuous data analysis of variance (ANOVA) was performed. When appropriate, a multivariate analysis with binary-regression by Wald was used. Sensitivity and specificity was done using ROC-curves. P < 0.05 was considered significant. From May 1996 to June 2000, 107 patients were included in the study. Besides basic data, all postoperative complications were noted according to a specific definition. Four different risk-scoring systems were used: ASA-classification; the acute physiology and chronic health evaluation (APACHE-II) system; the physiological and operative severity score for enumeration of mortality and morbidity (POSSUM) classification and, finally, the simplified acute physiology score (SAPS) classification. RESULTS: We found no significant correlation between risk-scores and outcome. None of the scoring systems used was able to predict mortality. The independent factors that influenced the postoperative complication rate were operating time, blood loss, intraoperative assisted ventilation time and age. The endpoint using the relative operating characteristic (ROC) curves analysis was either mortality or morbidity. CONCLUSIONS: It can be concluded that none of the systems analyzed separately was useful for determining morbidity and mortality. We still lack a system, that can be used preoperatively in an individual case and the vascular surgeon still has to build up his own clinical judgement or to transfer a clinical judgement.

Photoperiodic time measurement and a graded response in a cockroach.

Almost exclusively, photoperiodic insects respond to a given photoperiod in one of two ways: a "long-day" response or a "short-day" response. Intermediate responses occur only at a very restricted range of photoperiods (often less than 30 min) and are generally population phenomena rather than intermediate responses of individuals. In contrast, individuals of the wood roach, Parcoblatta pennsylvanica, show intermediate responses over a broad range of photoperiods. We examined the effect of constant light, constant darkness, and photoperiods ranging from 10 to 18 hr of light per 24 hr on growth rate as measured by weight gain, and found a robust photoperiodic response. Nymphs raised in photoperiods with light periods (photophases) from 0 to 12 hr gained little weight, whereas those in LD 18:6 were almost 15 times heavier. This is the first report of a photoperiodic response curve for a cockroach. Interestingly, there was a linear relationship between the duration of the photophase and weight gain over a broad range of photoperiods (LD 12:12 to LD 18:6; r2 = 0.99). Statistical analysis showed that the intermediate responses were attributable to individuals' growing at an intermediate rate. Another interesting observation was that all larval stages appeared to be capable of perceiving and responding to photoperiodic signals. The results of further experiments using non-24-hr photoperiods were consistent with the existence of a circadian component in the photoperiodic time measurement in this species.

Aftereffects of entrainment on the period of the pacemaker in the eye of the mollusk Bulla gouldiana.

The authors examined the "aftereffects" of entrainment of Bulla gouldiana to 11 h light:11 h dark (LD 11:11) (T22) or LD 13:13 (T26) on the period (tau) of the circadian rhythm of impulse activity recorded in vitro from the eye in constant darkness. When both eyes remained attached to the cerebral ganglion, the average period was 23.9 +/- 0.62 h (mean +/- SD, n = 6) for animals from T22 and 24.9 +/- 0.54 h for animals from T26. The 1-h difference between the periods of the T26 and the T22 animals was significant (p < .01, t test). When eyes were isolated from the cerebral ganglion by severing the optic nerve, the difference in average period between eyes from T22 and eyes from T26 animals was 2.2 h (23.3 +/- 0.72 h [n = 7] vs. 25.5 +/- 0.62 [n = 6], p < .001). When eyes remained attached to the brain but uncoupled from the contralateral eye, the aftereffect of entrainment to non-24-h light cycles was intermediate. For T22 animals, tau was 23.9 +/- 0.29 h (n = 6), whereas for the T26 animals, tau = 25.2 +/- 0.48 h (n = 7). The results show that isolated eyes can express aftereffects and indicate that coupling between ocular pacemakers and efferent signals from the cerebral ganglion diminish the effects of entrainment on the free-running period of the rhythm from the eye.

Influence of puberty on muscle area and cortical bone area of the forearm in boys and girls.

The aim of the current study is to analyze the interaction of the muscle and bone system (muscle-bone unit) during puberty in males and females by computed tomography of the nondominant forearm. The data presented here are the first results from 318 healthy children (159 boys and 159 girls), aged 6-22 yr, and 336 adults (parents) participating in the DONALD Study (Dortmund Nutritional and Anthropometric Longitudinally Designed Study). Cortical area (CA) of the radius representing bone strength and muscle area (MA) representing muscle strength were measured with peripheral quantitative computed tomography (XCT 2000; Stratec, Pforzheim, Germany). A single slice measurement at a site corresponding to 65% of the ulnar length proximal to the radial endplate was used. MA and CA of the radius have been determined by a built-in software algorithm using density differences. There was a strong correlation between MA (x) and CA (y) in all children, adolescents, and adults (y = 0.019x + 10.93; r2 = 0.77). Before puberty, boys and girls displayed a similar relation between MA and CA. CA in relation to MA was greater in girls than in boys during puberty. Analysis of covariance was performed investigating the dependency of CA on MA, five pubertal stages, sex, and interaction of sex and pubertal stages. MA representing muscle strength was the strongest predictor of CA (P < 0.001) representing bone mass. Pubertal stage (P < 0.001) and interaction of pubertal stage*sex (P = 0.002) also had a significant influence on CA. r2 of the model was 0.85. These data suggest that in pubertal girls and women rather than in pubertal boys and men an additional factor shifts the relationship between MA and CA to higher values of cortical area. The present data confirm previous studies of the influence of puberty and estrogens or related factors on the muscle-bone interaction.

Hypertension guidelines and their limitations--the impact of physicians' compliance as evaluated by guideline awareness.

OBJECTIVE: The initial step of an optimal therapeutic strategy for patients with arterial hypertension is the recognition and acceptance of new recommendations by the physicians themselves. This guideline awareness of the physicians has never been evaluated in detail. DESIGN: The awareness of content of current recommendations in hypertension diagnosis, treatment and treatment control was therefore assessed in primary care physicians using a questionnaire. The guidelines of the German Hypertension Society were used as the reference standard. PARTICIPANTS: A total of 24 899 German physicians, including all internists, all cardiologists and 22% of general practitioners were contacted in a nationwide survey. MAIN OUTCOME MEASURES: The number of answers in agreement with the guideline was used as a measure of guideline awareness. Adequate awareness of content of guideline recommendations was defined as the correct answer to five out of eight questions; the correct answers had to include the appropriate definition of hypertension. RESULTS: The analysis was based on 11 547 returned questionnaires (47.1%). An adequate guideline awareness was found in 23.7% of the total study population, especially in 37.1% of cardiologists, in 25.6% of internists and in 18.8% of general practitioners. While the guideline awareness was significantly influenced by the duration of private practice, regional and municipal factors had only minor influence on the results. CONCLUSION: The impact of hypertension guidelines on actual medical knowledge is modest. Thus, the information strategies about current treatment guidelines must be improved and tailored to the needs of physicians in clinical practice to ultimately improve patient care.

A new and accurate prediction model for growth response to growth hormone treatment in children with growth hormone deficiency.

OBJECTIVE: To identify parameters which predict individual growth response to recombinant human GH (rhGH) therapy and to combine these parameters in a prediction model. DESIGN: Fifty-eight prepubertal patients with GH deficiency (17 females) participated in this prospective multicenter trial with 1 year of follow-up. METHODS: Auxological measurements, parameters of GH status and markers of bone metabolism were measured at baseline and at 1, 3 and 6 months after the start of rhGH treatment. Correlations with height velocity during the first 12 months of treatment (HV+12) were calculated. Prediction models were derived by multiple regression analysis. RESULTS: The model which best predicted HV+12 combined the following parameters: pretreatment bone age retardation as a fraction of chronological age, pretreatment serum levels of IGF-I, urinary levels of deoxypyridinoline (a marker of bone resorption) after 1 month of treatment and height velocity after 3 months of treatment. This model explained 89% of the variation in HV+12 with a standard deviation of the residuals of 0.93 cm/year. Defining successful rhGH therapy as a doubling of pretreatment height velocity, the model had a specificity of 90% and a sensitivity of 100% in predicting therapeutic success. CONCLUSIONS: This model is an accurate and practicable tool to predict growth response in GH-deficient children. It may help to optimize rhGH therapy by individual dose adjustment and contribute to improved overall outcomes.

Epidemiology of erectile dysfunction: results of the 'Cologne Male Survey'.

The last few decades have seen a marked increase in mean life expectancy in Central Europe. This has made elderly people and their quality of life a matter of ever-increasing medical concern. Available data from the United States and Scandinavia relating to erectile dysfunction (ED) do not enable us to draw valid conclusions about the current situation in Germany. The aim of the present study was to evaluate the epidemiology of male sexuality in Germany, and the proportion of men who need medical treatment because of increased suffering from this.A newly developed and validated questionnaire on male erectile dysfunction was mailed to a representative population sample of 8000 men, 30-80 y of age in the Cologne urban district. The response included 4489 evaluable replies (56.1%). The response rates in different age groups ranged from 49.2% to 68.4%. Regular sexual activity was reported by 96.0% (youngest age group) to 71.3% (oldest group). There were 31.5%-44% of responders who were dissatisfied with their current sex life. The prevalence of ED was 19.2%, with a steep age-related increase (2.3-53.4%) and a high co-morbidity of ED with hypertension, diabetes, pelvic surgery and 'lower urinary tract symptoms'. When treatment need was defined by co-occurrence of ED and dissatisfaction with sex life, 6.9% men required treatment for ED. Oral treatment of ED was preferred by 73.8% of respondents. There were 46.2% respondents who were willing to contribute more than DM 50 (25 Euro) per month for ED treatment. We conclude that regular sexual activity is a normal finding in advanced age. ED is a frequent disorder, contributing to dissatisfaction with sex life in a considerable proportion of men. The high burden of ED is reflected in willingness to pay for treatment. ED is frequently associated with chronic diseases. Therefore adequate diagnostic workup is essential, to offer patients individually adapted treatment. General non-reimbursability of treatment for ED appears to be unacceptable.

Epidemiology of Peyronie's disease.

Francois Gigot de la Peyronie, surgeon to Louis XV of France, has become synonymous with the rather enigmatic though not uncommon condition of Peyronie's disease (PD), a localized connective tissue disorder of the penile tunica albuginea. The true prevalence of Peyronie's disease is unknown. Therefore, we decided to perform an evaluation of existing epidemiological data. A prevalence rate of 3.2% was determined in male inhabitants of the greater Cologne area. This is much higher than revealed by the data reported up to now, thus rendering the accepted prevalence rates of 0.3% to 1% untenable. The actual prevalence of Peyronie's disease may be even higher, considering many patients' reluctance to report this embarrassing condition to their physicians. Along these lines, most clinicians note that the number of Peyronie's patients has increased since the advent of oral sildenafil. Comparably high prevalences are known for diabetes and urolithiasis, suggesting a greater frequency of this rare disease than formerly believed.

Nocturnal illumination does not necessarily stimulate the photoperiodic response, despite mimicking the effects of constant light on the circadian system in the male Syrian hamster.

In an effort to determine the inductive component(s) of photic input in long day seasonal breeders, adult male Syrian hamsters (Mesocricetus auratus) were exposed to one of nine lighting conditions for a duration of 10 weeks: a light-dark cycle of 14 hours of light followed by 10 hours of dark (LD 14:10, a long photoperiod); LD 10:14 (a short photoperiod); a high frequency light-dark cycle of 1 hour of light and 1 hour of dark (LD 1:1); a higher frequency light-dark cycle of 1 minute of light and 1 minute of dark (LD 1m:1m); constant light (LL); constant dark (DD); feedback lighting (LDFB; a condition that illuminates the cage in response to locomotor activity); a feedback lighting neighbor control (LDFB NC; the animal receives the same light pattern as a paired animal in LDFB, but has no control over it); or reverse feedback lighting (rLDFB; a condition that darkens an illuminated cage in response to locomotor activity). Exposure to LL, LD 1:1, LD 1m:1m, LDFB and rLDFB significantly and similarly lengthened the free-running period of the locomotor rhythm when compared to the period of animals in DD. The paired tests and accessory reproductive glands weights, spermiogenesis, seminiferous tubule diameter and serum concentrations of testosterone, prolactin, LH and FSH, suggest that LD 14:10, LL, LD 1:1, rLDFB and LDFB NC maintain reproductive function in the Syrian hamster, while LD 10:14, DD, LD 1m:1m and LDFB do not. It is known that as little as two 1-second pulses of light are stimulatory if coincident with the subjective night (17.22). Thus, it is not surprising that LD 1:1 is stimulatory. LD 1m:1m is not stimulatory, however, despite an identical quanta of light per 24 hours and similar phase relationship. It appears that mere light exposure during the subjective night is not necessarily reproductively inductive. It would also appear that behaviorally generated light-dark cycles can be (i.e., LDFB), but are not necessarily (i.e., rLDFB) inhibitory to the maintenance of the reproductive system in long day breeders. Furthermore, the lighting pattern derived from LDFB is stimulatory if given exogenously (i.e., LDFB NC). Although it is not understood why light exposure that is coincident with the subjective night (i.e., LD 1m:1m and LDFB) is not stimulatory in long day breeders, a possible hypothesis is that an internal coincidence model is involved in the photoperiodic response and that multiple transitions during the subjective night may cause a dissociation of internal oscillations which must be in phase for light to be stimulatory.

Gravity and light effects on the circadian clock of a desert beetle, Trigonoscelis gigas.

Circadian function is affected by exposure to altered ambient force environments. Under non-earth gravitational fields, both basic features of circadian rhythms and the expression of the clock responsible for these rhythms are altered. We examined the activity rhythm of the tenebrionid beetle, Trigonoscelis gigas, in conditions of microgravity (microG; spaceflight), earth's gravity (1 G) and 2 G (centrifugation). Data were recorded under a light-dark cycle (LD), constant light (LL), and constant darkness (DD). Free-running period (tau) was significantly affected by both the gravitational field and ambient light intensity. In DD, tau was longer under 2 G than under either 1 G or microG. In addition, tauLL was significantly different from tauDD under microG and 1 G, but not under 2 G.

[Digital selenium radiography: a comparison of the picture quality of thoracic images in normal and reduced image formats based on the structural anatomical details]. / Digitale Selenradiographie: Vergleich der Bildqualität von Thoraxaufnahmen in normalem und verkleinertem Bildformat anhand anatomischer Detailstrukturen.

PURPOSE: Is there a loss of information when using selenium radiographic images displayed with reduced image format compared to full format? METHOD: Digital selenium radiographic chest images in two planes were obtained in 35 patients for medical reasons. The digital data sets of each patient were separately displayed in full format on two different films and were printed in reduced format on one film. The format was reduced to 61% of the full format using an acquisition matrix of 2166 x 2488 pixels, an image display matrix of 4000 x 5000 pixels and a film format of 43 x 49 cm. All images were anonymously evaluated by four independent readers using a questionnaire concerning anatomic structures. RESULTS: Format reduction did not result in a loss of information in diagnostically relevant anatomic details. CONCLUSIONS: Displaying digital selenium radiographic data sets of thoracic view in two planes on one film presumably does not lead to a loss of diagnostic information. This procedure may help to reduce film costs.

The association between baseline lung function and bronchial responsiveness to methacholine.

It has been reported that females show an increased frequency of bronchial hyperresponsiveness (BHR) compared to males and that this difference is abolished after taking into account differences in baseline FEV1. The aim of our study was to analyse how the distribution of BHR in males and females depends on the definition of BHR. Special emphasis was paid to the question whether the prevalence rates of BHR according to different definitions were related to baseline characteristics of the subjects and baseline lung function in the same manner. We analysed the data obtained within the European Community Respiratory Health Survey (ECRHS) in the Eastern German population sample of Erfurt aged 20-65 years (n = 931). In logistic regression analyses of different definitions of BHR, we used as parameters age, height, gender, smoking habits, baseline forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and FEV1 as a percent of FVC (FEV1% FVC). Symptoms and reported diagnosis of asthma did not significantly depend on gender or age. When BHR was defined as the provocative dose causing a 20% fall in FEV1, BHR was more prevalent in females than in males (27.6% vs. 13.2%). Similar gender differences were found when defining BHR via a 10% fall in FEV1 or by using corresponding cut-off values of the linear dose-response slopes of the percent decline in FEV1 (DRS). Multiple linear regression analyses of various transformations of the DRS also indicated a higher degree of BHR in females. Independently of the definition chosen, however, the gender difference in the prevalence of BHR disappeared when height and FEV1 or FEV1% FVC or appropriate combinations were included in the model. The reciprocally transformed DRS showed the best resolution of the spectrum of bronchial responsiveness. These data are compatible with the hypotheses that (1) estimates of the distribution of BHR are distorted by differences in the methacholine dosage per lung size and that (2) airway geometry affects the measurement of BHR. It appears that these factors and not intrinsic differences in BHR between males and females contribute to the gender differences in the prevalence of BHR. Furthermore, our data support the superiority of the dose response slope for the analysis of bronchial responsiveness in epidemiologic surveys.

Human fetal adiponectin and retinol-binding protein (RBP)-4 levels in relation to birth weight and maternal obesity.

Recent studies suggest that the perinatal period is a sensitive part in human development with respect to the pathogenesis of metabolic diseases in adulthood. Neonates, who are either small or large for gestational age (SGA or LGA) have a greater risk of developing obesity and insulin resistance in later life. The term "perinatal priming" is used to describe this phenomenon. Therefore, in the present study we first aimed to investigate if birth weight influences fetal adiponectin and RBP-4 metabolism. Umbilical cord blood was obtained form 40 neonates born on term+/-4 weeks and the adipokine concentrations in the serum were measured. In this analysis adiponectin but not RBP-4 levels showed a positive significant correlation to birth weight. Since maternal preconceptional obesity is associated with an increased birth weight and the risk for LGA neonates, we further aimed to investigate, if the maternal nutritional state influences fetal adiponectin and RBP-4. Therefore umbilical cord blood levels of the adipokines were correlated to maternal preconceptional BMI. In this analysis, neither adiponectin nor RBP-4 levels showed a significant correlation. Taken together, in the present study for the first time we directly compare fetal adiponectin and RBP-4 levels in respect to birth weight and maternal preconceptional BMI. Our data suggest that (1) adiponectin is more likely to have a role in perinatal priming of obesity and insulin resistance than RBP-4 and (2) that birth weight has a greater impact on fetal adipokine serum levels than maternal preconceptional obesity.

[Prophylaxis of contrast-induced nephropathy with N-acetylcysteine]. / N-Acetylcystein in der Prophylaxe der Kontrastmittel-induzierten Nephropathie.

PURPOSE: Clinical trials evaluating N-acetylcysteine (NAC) for the prevention of radiocontrast-induced nephropathy (RCN) have reported mixed results. Despite formerly published meta-analyses and due to currently published RCTs, time has come to re-evaluate the current evidence of preventing RCN by administering NAC. METHODS: We performed a computerized search without restricted to a language to identify relevant published randomized clinical trials that evaluated N-acetylcysteine for the prevention of radiocontrast-induced nephropathy. Abstracted data from each trial included assessments of clinical outcomes, trial quality, and additional characteristics. The primary outcome of interest was the incidence of nephropathy after contrast administration. Data were combined using random effects models with the performance of standard tests to assess for heterogeneity and publication bias. Subgroup analyses were also performed. RESULTS: Twenty-eight trials involving 3 604 patients met our inclusion criteria. Trials varied in patient demographic characteristics, inclusion criteria, dosing regimens, and trial quality. The summary risk ratio for contrast-related nephropathy was 0.69 (95 % confidence interval: 0.57 to 0.82; P = 0.02), a statistically significant trend towards benefit in patients treated with N-acetylcysteine. This effect varied, however, across the 28 trials, and only eight of the 28 trials demonstrated significant results although higher-quality trials demonstrated a stronger benefit for N-acetylcysteine in general, few reported important elements of study design, such as concealment of allocation, placebo-controls, or double-blinding. Heterogenity was unexplained by subgroup analyses. SUMMARY AND CONCLUSIONS: N-acetylcysteine (NAC) may reduce the incidence of contrast-related nephropathy, but this finding is reported inconsistently across currently available trials. Large high-quality, clinical trials are needed before the application of N-acetylcysteine can be recommended in general for this indication.

A comparison of two methods for adaptive interim analyses in clinical trials.

Recently, two methods for planning and conducting two-stage procedures were proposed (Bauer and Köhne, 1994, Biometrics 50, 1029-1041; Proschan and Hunsberger, 1995, Biometrics 51, 1315-1324). Both procedures allow the termination of the trial with the early acceptance of H0 in the absence of a treatment effect after performing the first stage of the study. Furthermore, the observed treatment effect at stage I can be used for planning and redesigning the second stage of the study in a way that protects the Type I error rate. The exact Type I error rate of the Proschan and Hunsberger approach is derived. It is shown that the two methods lead to similar decision rules with negligibly small differences in power and expected sample size. In terms of providing design tools and practical applicability, however, they differ. The practical performance of the procedures is discussed and recommendations for their use are given.

Adaptive sample size calculations in group sequential trials.

A method for group sequential trials that is based on the inverse normal method for combining the results of the separate stages is proposed. Without exaggerating the Type I error rate, this method enables data-driven sample size reassessments during the course of the study. It uses the stopping boundaries of the classical group sequential tests. Furthermore, exact test procedures may be derived for a wide range of applications. The procedure is compared with the classical designs in terms of power and expected sample size.

Resampling-based methods for the analysis of multiple endpoints in clinical trials.

We consider multivariate tests for comparing two treatments with multiple endpoints. The test decision is drawn from the simultaneous consideration of the univariate tests for the single endpoints. A general class of these tests, called cut-off tests, can be given, which, however, can lead to highly conservative procedures because the dependencies among the endpoints are not taken into account. In applying resampling-based methods considerable improvements for these tests can be achieved. Resampling-based cut-off tests are proposed which are sensitive against a treatment difference in a single endpoint, in a subgroup of endpoints, or in all endpoints. The results of Monte Carlo simulations demonstrate that a remarkable gain in statistical power as compared to the crude simultaneous consideration can be reached. In particular, for the multivariate one-sided test situation the proposed tests can be recommended. As an example the application of the tests is demonstrated by data from a clinical trial.