[Randomized controlled trials terminated prematurely: beneficial therapy effects]. / Vorzeitiger Abbruch randomisierter kontrollierter Studien : Vorteilsbedingter Therapieeffekt.

Randomized controlled trials (RCTs) stopped prematurely for beneficial therapy effects are becoming increasingly more prevalent in the urological literature and often receive great attention in the public and medical media. Urologists who practice evidence-based medicine should be aware of the potential bias and the different reasons why and how early termination of RCTs can and will affect the results. This review provides insights into the challenges clinical urologists face by interpreting the results of prematurely terminated RCTs.

[The likelihood ratio: estimation of the impact of a diagnostic test on treatment decision]. / Die "likelihood ratio" : Beeinflussung der Therapieentscheidung durch einen diagnostischen Test.

Likelihood ratios (LRs) can be used to assess in an efficient manner the change of a pre-test probability to the post-test probability of a disease based on a given test result. For any clinical question or condition of interest, the diagnostic benefit can be calculated for each diagnostic test allowing to compare the performance of different diagnostic tests. Urologists should become familiar with the use of LR to promote a more evidence-based application of diagnostic test for different clinical scenarios. This review provides insights in the calculation and use of LR.

[Kaplan-Meier analysis in urological practice]. / Kaplan-Meier-Analysen in der urologischen Praxis.

Kaplan-Meier curves and estimates of survival are the most common way to present survival data in medicine, especially for cohorts with different lengths of follow-up. Moreover, Kaplan-Meier curves present a frequently used general graphic approach to display time-to-event outcomes. A solid understanding of how Kaplan-Meier curves are generated and how they should be analyzed and interpreted is of great importance to appraise urological literature in daily clinical practice. This article describes the basic principles of Kaplan-Meier analysis, possible variants and pitfalls. Improved knowledge of Kaplan-Meier analysis can help to improve Evidence-based urology and its application in patient care.

[Use and interpretation of the number needed to treat in urological practice]. / Verwendung und Bedeutung der "number needed to treat" in der urologischen Praxis.

The number needed to treat (NNT) is a useful way for clinicans to describe the benefit or harm of a treatment as well as the costs involved. When interpreting the NNT it is essential to use the NNT in a clinically equivalent and appropriate setting. When evaluating the consequences of a treatment clinicians should make sure that the patients being treated have the same risk profile asthe study patients. Differences in duration of follow-up and baseline risks can cause significant changes in the NNT; therefore, NNT should be evaluated in addition to relative risk differences and baseline risk to reduce any ambivalence in the assessment of a treatment. This review provides insights into the assessment and clinical use of NNT in the practice.

[Use of PubMed to improve evidence-based medicine in routine urological practice]. / Die Verwendung von PubMed zur Verbesserung evidenzbasierter Medizin in der Urologie.

Applying evidence-based medicine in daily clinical practice is the basis of patient-centered medicine and knowledge of accurate literature acquisition skills is necessary for informed clinical decision-making. PubMed is an easy accessible, free bibliographic database comprising over 21 million citations from the medical field, life-science journals and online books. The article summarizes the effective use of PubMed in routine urological clinical practice based on a common case scenario. This article explains the simple use of PubMed to obtain the best search results with the highest evidence. Accurate knowledge about the use of PubMed in routine clinical practice can improve evidence-based medicine and also patient treatment.

[Confidence intervals and p-values in urology: interpretation and misinterpretation]. / Konfidenzintervalle und p-Werte in der Urologie : Interpretation und Fehlinterpretation.

Confidence intervals and p-values are widely used in the urological literature to describe and interpret outcomes. However, several readers, authors and reviewers are unfamiliar with the true interpretation of these values. P-values determine statistical significance of data. Confidence intervals characterize a range of values in which the true effect size is suggested to be with a given degree of certainty. An independent but complementary interpretation of both values is important in studies with and without statistical significance. Based on a clinical case scenario this article discusses the interpretation as well as common pitfalls in interpretation of p-values and confidence intervals. An accurate assessment of these statistical cornerstones is fundamental for a correct interpretation of the urological literature and thus important aspects of evidence-based urology.

High intrathecal bupivacaine for severe pain in the head and neck.

BACKGROUND: Severe pain in the head and neck is associated with a lowered quality of life and conventional pain therapy often does not provide adequate relief. The aims of this study were to investigate the efficacy, pain relief, benefits and adverse effects of intracisternal or high cervical (IHC) administration of bupivacaine in patients with severe pain in the head, neck and face regions. METHODS: Between 1990 and 2005, 40 patients (age 27-84 years) were treated with continuous IHC infusions of bupivacaine for various non-cancer (n=15) or cancer-related (n=25) refractory pain conditions (duration 1 month-18 years) in the head, neck, mouth and shoulder regions. RESULTS: Visual analogue scale scores and opioid requirements decreased markedly after the start of the treatment and remained lowered throughout the study. No tachyphylaxis for bupivacaine was observed. Major side effects were few and most often transient. Most patients showed unchanged or improved mobility. There was no mortality, neurological damage or other severe events attributable to procedures in the study protocol. CONCLUSION: For patients with severe and refractory pain in areas innervated by cranial and upper cervical nerves, cervical high spinal analgesia can provide safe and effective analgesia.

Apical soft tissue biopsies predict biochemical failure in radical perineal prostatectomy patients with apical cancer involvement.

The aim of the study was to prospectively assess the role of apical soft tissue biopsies in radical perineal prostatectomy (RPP) patients with documented apical prostate cancer (PCA) involvement. Between June 1998 and May 1999, 77 consecutive men with localized PCA and documented invasion of the prostatic apex underwent RPP by a single surgeon. Soft tissue biopsies were systematically obtained from the prostatic fossa overlying the apex at the time of surgery. Time to biochemical failure was calculated using the Kaplan-Meier method. The rates of positive apical margins and positive apical soft tissue biopsies were 23.4% (18/77) and 15.6% (12/77). The sensitivity, specificity and positive predictive value of positive apical margins for residual apical disease as determined by apical soft tissue biopsy were 41.7, 80, and 28%, respectively. The overall biochemical failure rate was 28.6% (22/77) with a median follow-up of 51 months (range 3-73 months). The 36-month biochemical recurrence-free survival rate was 55.9+/-14.9% for patients with positive apical biopsies and 78.7+/-5.3% for those with negative biopsies (P=0.023). In conclusion, positive apical soft tissue biopsy is an independent predictor of biochemical failure in patients with apical PCA who undergo RPP. Positive apical surgical margins poorly predict residual apical disease that is frequently identifiable by apical soft tissue biopsy. Apical soft tissue biopsies should therefore be obtained in patients with known extensive apical cancer involvement at the time of RPP.

Timing and patterns of recurrences and deaths from prostate cancer following adjuvant pelvic radiotherapy for pathologic stage T3/4 adenocarcinoma of the prostate.

To determine the timing and patterns of late recurrence after radical prostatectomy (RP) alone or RP plus adjuvant radiotherapy (RT). Between 1970 and 1983, 159 patients underwent RP for newly diagnosed adenocarcinoma of the prostate and were found to have positive surgical margins, extracapsular extension and/or seminal vesicle invasion. Of these, 46 received adjuvant RT and 113 did not. The RT group generally received 45-50 Gy to the whole pelvis, then a boost to the prostate bed (total dose of 55-65 Gy). In the RP group, 62% received neoadjuvant/adjuvant androgen deprivation vs 17% in the RT group. Patients were analyzed with respect to timing and patterns of failure. Only one patient was lost to follow-up. The median follow-up for surviving patients was nearly 20 years. The median time to failure in the surgery group was 7.5 vs 14.7 years in the RT group (P=0.1). Late recurrences were less common in the surgery group than the RT group (9 and 1% at 10 and 15 years, respectively vs 17 and 9%). In contrast to recurrences, nearly half of deaths from prostate cancer occurred more than 10 years after treatment. Deaths from prostate cancer represented 55% of all deaths in these patients. Recurrences beyond 10 years after RP in this group of patients were relatively uncommon. Despite its long natural history, death from prostate cancer was the most common cause of mortality in this population with locally advanced tumors, reflecting the need for more effective therapy.

Metastatic prostate cancer presenting as an asymptomatic neck mass.

Prostate cancer often metastasizes to the regional lymph nodes, but metastases to distant supradiaphragmatic lymph nodes are uncommon. Rare case reports describe cervical lymph node metastases as the first clinical manifestation of prostate cancer, but only in the setting of widely disseminated disease. We present the unusual case of an 84-y-old male with a known history of prostate cancer and recurrent disease limited to the left supraclavicular lymph nodes.

The ASCUS : SIL ratio and the reference laboratory pathologist.

The atypical squamous cells of undetermined significance (ASCUS) : squamous intraepithelial lesion (SIL) ratio was proposed to monitor laboratory use of the ASCUS diagnosis. This study addresses problems associated with comparing pathologists by this means. An intuitive example showed the ASCUS : SIL ratio depends on the prevalence of smears from patients who actually have SIL. In this study of 2000 cervical smears, each of five pathologists made 400 diagnoses. Differences among proportions of SIL diagnoses were statistically significant; differences among proportions of ASCUS diagnoses were not. Had an ASCUS : SIL ratio upper limit of 3.0 been used, two pathologists would have been misidentified as having high ASCUS diagnosis rates. Unlike the situation for laboratories, potential variability in SIL prevalence requires caution in the use of this ratio in assessing pathologists. An alternative measure that is independent of prevalence, the ASCUS : SIL odds ratio, is posited.

[Vasectomy today: a review of 1,275 vasectomies in 10 years]. / Vasektomie heute. Eine Bestandserhebung nach 1275 Vasektomien in 10 Jahren.

We report on a large series of 1,275 patients who underwent outpatient vasectomy performed by a single urological surgeon within a 10-year period. In addition, the results of a prospective questionnaire-based study on 217 patients regarding their opinions and motivation, and the financial aspects of the vasectomy are discussed. The mean age was 37.0+/-5.9 years. A total of 98.4% of the patients had an uneventful postoperative course. The average duration of sick leave was 2.2+/-0.21 days. During the study period, the length of sick leave dropped significantly from 2.63 (1990/91) to 1.1 days (1998/99; P=0.001). Efficacy was documented with azoospermia rates of 96.6% and 98.5% in patients who presented for two and three sperm examinations, respectively. A vast majority of patients (94.6%) felt that the procedure should be covered by their health insurance, although 88.1% stated they would also pay by themselves. A minority of patients (0.7%: 9/1,275) subsequently considered vasectomy reversal. The wish to reverse the vasectomy was significantly associated with a younger patient age. In conclusion, outpatient vasectomy provides a safe and reliable form of contraception at low cost. Overall satisfaction in appropriately counselled patients is very high. Based on these findings, further attempts to propagate vasectomy as a timely form of contraception are medically and socioeconomically recommended.

Probability models and the applicability of statistical procedures in the identification of chromosomal fragile sites.

Böhm et al. (1995, Human Genetics 95, 249-256) introduced a statistical model (named FSM--fragile site model) specifically designed for the identification of fragile sites from chromosomal breakage data. In response to claims to the contrary (Hou et al., 1999, Human Genetics 104, 350-355; Hou et al., 2001, Biometrics 57, 435-440), we show how the FSM model is correctly modified for application under the assumption that the probability of random breakage is proportional to chromosomal band length and how the purportedly alternative procedures proposed by Hou, Chang, and Tai (1999, 2001) are variations of the correctly modified FSM algorithm. With the exception of the test statistic employed, the procedure described by Hou et al. (1999) is shown to be functionally identical to the correctly modified FSM and the application of an incorrectly modified FSM is shown to invalidate all of the comparisons of FSM to the alternatives proposed by Hou et al. (1999, 2001). Last, we discuss the statistical implications of the methodological variations proposed by Hou et al. (2001) and emphasize the logical and statistical necessity for fragile site identifications to be based on data from single individuals.

Ureteroscopic management of lower-pole renal calculi: technique of calculus displacement.

PURPOSE: We review our technique of ureteroscopic management of lower pole renal calculi with Nitinol basket displacement and holmium laser stone fragmentation. METHODS: Lower pole calculi are identified with a 7.5F flexible ureteroscope. In patients in whom the laser fiber reduces ureteroscopic deflection, precluding reentry into the lower pole, a Nitinol basket or grasper is used to displace the calculi into an upper pole calix for easier fragmentation. RESULTS: The Nitinol device can be passed into the lower pole through the fully deflected ureteroscope without any loss of deflection. Irrigation is significantly reduced by the basket, but this factor does not impede stone retrieval. CONCLUSIONS: Ureteroscopic management of lower pole stones is a reasonable alternative to SWL or percutaneous nephrolithotomy in low-volume stone disease. If the stone cannot be fragmented in situ, Nitinol basket capture through a fully deflected ureteroscope into a less dependent position facilitates stone fragmentation.

Cerebral blood volume (CBV) in humans during normo- and hypocapnia: influence of nitrous oxide (N(2)O).

BACKGROUND: It is generally argued that variations in cerebral blood flow create concomitant changes in the cerebral blood volume (CBV). Because nitrous oxide (N(2)O) inhalation both increases cerebral blood flow and may increase intracranial pressure, it is reasonable to assume that N(2)O acts as a general vasodilatator in cerebral vessels both on the arterial and on the venous side. The aim of the current study was to evaluate the effect of N(2)O on three-dimensional regional and global CBV in humans during normocapnia and hypocapnia. METHODS: Nine volunteers were studied under each of four conditions: normocapnia, hypocapnia, normocapnia + 40-50% N(2)O, and hypocapnia + 40-50% N(2)O. CBV was measured after (99m)Tc-labeling of blood with radioactive quantitative registration via single photon emission computer-aided tomography scanning. RESULTS: Global CBV during normocapnia and inhalation of 50% O(2) was 4.25 +/- 0.57% of the brain volume (4.17 +/- 0.56 ml/100 g, mean +/- SD) with no change during inhalation of 40-50% N(2)O in O(2). Decreasing carbon dioxide (CO(2)) by 1.5 kPa (11 mmHg) without N(2)O inhalation and by 1.4 kPa (11 mmHg) with N(2)O inhalation reduced CBV significantly (F = 57, P < 0.0001), by 0.27 +/- 0.10% of the brain volume per kilopascal (0.26 +/- 0.10 ml x 100 g(-1) x kPa(-1)) without N(2)O inhalation and by 0.35 +/- 0.22% of the brain volume per kilopascal (0.34 +/- 0.22 ml x 100 g(-1) x kPa(-1)) during N(2)O inhalation (no significant difference). The amount of carbon dioxide significantly altered the regional distribution of CBV (F = 47, P < 0.0001), corresponding to a regional difference in Delta CBV when CO(2) is changed. N(2)O inhalation did not significantly change the distribution of regional CBV (F = 2.4, P = 0.051) or Delta CBV/Delta CO(2) in these nine subjects. CONCLUSIONS: Nitrous oxide inhalation had no effect either on CBV or on the normal CBV-CO(2) response in humans.

Indications for admission to the surgical intensive care unit after radical cystectomy and urinary diversion.

PURPOSE: We analyzed the practice of mandatory surgical intensive care unit admission after radical cystectomy, and defined objective criteria to predict active treatment requirements and surgical intensive care unit stay. MATERIALS AND METHODS: We retrospectively reviewed the records of 115 consecutive patients admitted to the surgical intensive care unit after radical cystectomy and urinary diversion during the 36-month study period of January 1996 to December 1998. An Acute Physiology and Chronic Health Evaluation II score was calculated from postoperative patient parameters at admission to the unit. Active treatment mandating admission was defined as postoperative invasive cardiopulmonary monitoring, administration of vasopressors or inotropic medications, monitoring or treatment for life threatening complications, or mechanical ventilation for longer than 12 hours. We analyzed the correlation of outcome variables with the requirements for active treatment and surgical intensive care unit stay, and developed a stratification model of low versus high risk. Low risk was defined as a calculated likelihood of less than 10% for requiring active treatment postoperatively. RESULTS: Mean stay in the surgical intensive care unit plus or minus standard error was 34.4 +/- 3.1 hours. No active treatment was required in 63.5% of patients during the stay. The evaluation score, intraoperative complications and number of intraoperative transfusions were the strongest predictors of required postoperative active treatment. By combining these variables we developed a clinically applicable algorithm to stratify patients into a low and a high risk category. In patients at low and high risk the active treatment rate was 5.9% and 42.8% (p = 0.001), and the mean stay was 24.6 +/- 2.2 and 38.7 +/- 4.5 hours (p = 0.039), respectively. CONCLUSIONS: Mandatory surgical intensive care unit admission of all patients after radical cystectomy and urinary diversion does not appear indicated. A subset of patients at low risk for requiring active treatment may be identified who may be safely treated in an intermediate care setting after initial postoperative observation in the recovery room. The results of our retrospective analysis and risk stratification model should be validated in a prospective trial.