Putting patients at the center of kidney care transitions: PREPARE NOW, a cluster randomized controlled trial.

Care for patients transitioning from chronic kidney disease to kidney failure often falls short of meeting patients' needs. The PREPARE NOW study is a cluster randomized controlled trial studying the effectiveness of a pragmatic health system intervention, 'Patient Centered Kidney Transition Care,' a multi-component health system intervention designed to improve patients' preparation for kidney failure treatment. Patient-Centered Kidney Transition Care provides a suite of new electronic health information tools (including a disease registry and risk prediction tools) to help providers recognize patients in need of Kidney Transitions Care and focus their attention on patients' values and treatment preferences. Patient-Centered Kidney Transition Care also adds a 'Kidney Transitions Specialist' to the nephrology health care team to facilitate patients' self-management empowerment, shared-decision making, psychosocial support, care navigation, and health care team communication. The PREPARE NOW study is conducted among eight [8] outpatient nephrology clinics at Geisinger, a large integrated health system in rural Pennsylvania. Four randomly selected nephrology clinics employ the Patient Centered Kidney Transitions Care intervention while four clinics employ usual nephrology care. To assess intervention effectiveness, patient reported, biomedical, and health system outcomes are collected annually over a period of 36 months via telephone questionnaires and electronic health records. The PREPARE NOW Study may provide needed evidence on the effectiveness of patient-centered health system interventions to improve nephrology patients' experiences, capabilities, and clinical outcomes, and it will guide the implementation of similar interventions elsewhere. TRIAL REGISTRATION: NCT02722382.

Stat5 gene dosage in T cells modulates CD8+ T-cell homeostasis and attenuates contact hypersensitivity response in mice.

BACKGROUND: Contact hypersensitivity assay (CHS) faithfully models human allergies. The Stat5 transcription factors are essential for both lymphocyte development and acute immune responses. Although consequences of Stat5 ablation and transgenic overexpression for the lymphocyte development and functions have been extensively studied, the role of Stat5 gene dosage in contact allergies has not been addressed. OBJECTIVE: We investigated the effect of Stat5 gene dosage modulation in contact allergies using CHS in mice. METHODS: Transgenic animals heterozygous for the germline Stat5 null allele were subjected to CHS. To dissect cell type sensitive to Stat5 gene dosage, animals with Stat5 haplo-insufficiency in T cells, where one Stat5 allele was removed by Lck-Cre-mediated deletion (Stat5(ΔT/+)), were tested by CHS. Frequency of T cells, B cells, and monocytes were analyzed in Stat5(ΔT/+) and wild-type animals by flow cytometry. Proliferation of Stat5(ΔT/+) CD8(+) T cells was studied in vitro by stimulation with IL-4 and IL-2 cytokines, and changes in the expression of Stat5 target genes were assayed by quantitative real-time PCR assay. RESULT: Haplo-insufficiency of Stat5 in T cells leads to the reduction in CD8(+) T cells in all lymphoid organs and attenuates CHS response. Stat5(ΔT/+) CD8(+) T cells failed to fully activate Stat5-dependent expression of cell cycle/survival target genes, such as Bcl2 and Pim1, and to proliferate efficiently in response to IL-2 and IL-4 cytokine. CONCLUSION: Our data identify Stat5 as a dose-dependent regulator of CD8(+) T-cell functions in contact allergies and suggest that modulation of Stat5 dosage could be used to target contact allergies in humans.

[Parameters to improve the specificity of the prostate-specific antigen. Early detection of prostate cancer]. / Parameter zur Verbesserung der Spezifität des prostataspezifischen Antigens. Früherkennung des Prostatakarzinoms.

PURPOSE: The aim of the study was to improve the case detection rate of prostate cancer for patients who had unremarkable palpation findings and a PSA value in the range of 4 to 10 ng/ml by combination of the parameters total PSA (tPSA), f/tPSA ratio, prostate volume, PSA density, patient's age and transrectal ultrasound findings. METHODS: Sextant biopsy of the prostate was performed for 619 patients aged 45-75 years who had unremarkable palpation findings and PSA values in the range of 4 to 10 ng/ml. The f/tPSA ratio was determined, transrectal ultrasound examination was performed, the prostate volume was measured and the PSA density calculated. The relationship between the various test variables - and their combination - and the histology results was investigated using logistic regression. RESULTS: Prostate cancer was detected in 131 of 619 patients. Analysis of the aforementioned test variables by means of logistic regression revealed that the combination of the parameters f/tPSA ratio, PSA density and patient's age can significantly increase the sensitivity and specificity of PSA in predicting prostate cancer compared with the use of these parameters on an individual basis. With an assumed limit value of 5% for performance of punch biopsy, 31% of biopsies could be avoided in practice. In such a case, only 3% of instances of prostate cancer would have gone undetected. CONCLUSION: The combined use of f/tPSA ratio, PSA density and patient's age can significantly enhance the case detection sensitivity for the PSA range of 4 to 10 ng/ml.

[Free/total PSA ratio in clinical and ambulatory application. Are different cutoffs justified?]. / Der Quotient f/t-PSA in klinischer und ambulanter Anwendung. Sind unterschiedliche Grenzwerte gerechtfertigt?

Especially in the setting of total prostate-specific antigen (PSA) in the intermediate range of 4-10 ng/ml and a negative digital rectal examination, the use of the free/total (F/T) PSA ratio has proved to be an effective tool in prostate cancer screening. Whole blood should be analyzed as soon as possible after venipuncture to ensure optimal effectiveness of the F/T PSA ratio. If an immediate serum analysis is not possible, the serum should be frozen or stored at a maximum of 4 degrees C for a short period. Otherwise, when applying the F/T PSA cutoffs as recommended in the literature to a cohort with delayed analysis, a lack of specificity arises, and the initial advantage of reducing biopsies is minimized. To prevent loss of quality in a setting with delayed F/T PSA measurement, we recommend that physicians compare their own data critically with presented results and eventually adapt the cutoffs individually.

[The value of urinary cytology in the diagnosis of high grade urothelial tumors]. / Stellenwert der Urinzytologie in der Diagnostik von High-grade-Urotheltumoren.

Urinary cytology is a non-invasive adjunct to cystoscopy in the diagnosis of bladder cancer. In order to assess the diagnostic accuracy of urinary cytology as an office-based method for clinically relevant high grade (G3) bladder cancer, three nationwide cytology survey tests were performed. Urine specimens from seven patients, three patients with high grade (G3) bladder cancer and four patients with urinary tract infections, were collected. A total of 1,000 cytology slides were produced from each urine specimen. Each set contained five slides (two malignant, three benign) which were sent to all participating German urologists. Three nationwide tests were performed from 1998-2000. The specimen sets were kept the same for the first and second test and in the third test two new slides were introduced. In addition to validity, the reliability was calculated for the first and second test as interobserver and intraobserver reliability according to Cohen's kappa statistics. Due to the change of two specimens in the third test in 2000 only sensitivity and specificity were calculated. A total of 335 urologists took part in the first survey test, 329 in the second and 292 in the third The sensitivity for G3 cytologies was 81.34% in the first, 87.08% in the second and 85.1% in the third survey test and the specificity was 85.87%, 83.58% and 89.15%, respectively. Interobserver reliability showed a weighted kappa value of 0.58 for the first and 0.59 for the second survey test. Calculation of intraobserver reliability was possible for 169 urologists taking part in the first and second survey test and showed a mean kappa value of 0.62. The results of the three nationwide urinary cytology tests indicate that urinary cytology has a high sensitivity in the detection of clinically relevant high grade bladder cancer. The kappa values achieved demonstrate a clear agreement of cytological diagnoses.

The f/t-PSA ratio in diagnosis of in-patients and out-patients: a unitary cutoff value is not useful!

PURPOSE: In the prostate specific antigen (PSA) range of 4-10 ng/ml after a negative digital rectal examination, the PSA value indicates a lack of specificity with a carcinoma detection rate of roughly 20%. To improve the biopsy/carcinoma ratio, the interdisciplinary consensus recommends free PSA (fPSA) measurement. This does not take into account the pre-analysis when the cutoff value is established for biopsy indication. METHODS: In the present study, an in-patient cohort whose blood samples were immediately analysed was compared with an out-patient cohort whose sample processing was delayed by between 24 and 48 h. RESULTS: The in-patient cohort comprises 382 patients with 99 prostate carcinomas, the out-patient cohort 987 patients with 235 carcinomas. In the in-patient cohort a sensitivity of 90% with a cutoff value of 25% for the f/t-PSA ratios is achieved with the theoretical possibility of reducing the number of punch biopsies by 34.6%. A sensitivity of 90% in the out-patient cohort necessitates a cutoff value of 18% for the f/t-PSA ratios. The specificity is 35.3% with a possible biopsy reduction of 29.1%. CONCLUSIONS: The cutoff values from cohorts with an immediate fPSA measurement cannot be adopted for a typical out-patient cohort whose analyses are delayed. On the contrary, an individual adjustment is necessary which corresponds to the pre-analysis.

[Percutaneous embolization of the kidney: indications and clinical results]. / Perkutane Totalembolisation der Niere: Indikationen und klinische Ergebnisse.

OBJECTIVE: Renal embolisation offers a minimal invasive means of renal ablation under primary palliative indication. We evaluated our experience with this technique in a series of 40 patients. PATIENTS AND METHODS: From 1996 to 2002 a total of 40 patients underwent total embolisation of the kidney. Our patients encompassed 15 females and 25-males (median age: 68 years, 46 - 89 years). In 15 patients indication for embolisation was to ablate a non-functioning kidney following obstruction due to advanced cancer, in 9 patients preoperatively with advanced renal cell carcinomas invading the vena cava, in 8 patients for control of hematuria and in 8 patients with non-operable advanced renal cancers. The embolisation was carried out in DAS-technique with a 7 Fr. selective catheter and central placement of macrocoils, from 2000 on we additionally performed a peripheral embolisation with polyvinylalcohol (PVA) particles. The intervention took place in epidural anesthesia. RESULTS: Perioperatively in all patients a complete occlusion of the renal artery as well as acessory arteries (n = 6) could be documented radiographically, perioperative complications were not observed. A post-embolisation syndrome occured in 32 patients. Reinterventions with repeat embolisation became necessary in 5 patients (persistent urine production-n = 4, persistent hematuria-n = 1). SUMMARY: The combined central and peripheral embolisation of the kidney in epidural anesthesia is a valuable means in selected patients under palliative indication for defunctionalisation of the kidney as well as control of hematuria.

Clinical usefulness of free PSA in early detection of prostate cancer.

OBJECTIVE: Measurement of serum prostate-specific antigen (PSA) is widely used as an aid in early detection of prostate cancer. Most patients with prostate cancer and a PSA level less than 10.0 ng/ml have early-stage disease. Thus, the detection of prostate cancer in its potentially curable stages requires the use of low PSA cutoffs, inevitably leading to many unnecessary biopsies. The combined use of free PSA and total PSA increases specificity of early detection. To develop risk assessment guidelines and a cutoff value of ratio of free (f) to total (t) PSA with a high predictive value for prostate cancer in men to whom the test would be applied in real life practice, a multicenter early detection trial was initiated. PATIENTS AND METHODS: In one week in November 1997, 963 urologists prospectively examined 11,644 men between 45 and 75 years by digital rectal examination (DRE) and prostate-specific antigen with 4.0 ng/ml as cutoff. Data of physical examination were collected by questionnaire. At this time participants were not aware of their PSA values. Suspicious findings were further investigated with sextant biopsy. Prostate volume was determined with transrectal ultrasound (TRUS). Different cutoff levels were correlated to age and detection rate. RESULTS: From1,115 biopsied men, the data of 633 men fulfilled the criteria DRE-negative, TRUS-estimated volume, and PSA 4.0-10.0 ng/ml. In that cohort 91 cancers were detected. Percentage of fPSA was significantly more predictive of cancer than tPSA (p < 0.001). The area under the ROC curve was 0.72 for percent fPSA (% fPSA) and 0.62 for total PSA. The cancer risk nearly doubled using a cutoff of 10% fPSA, the median %PSA level of the detected cancers. A better discrimination of cancer and noncancer especially in the age group above 70 years is possible. Using a cutoff of 16% fPSA increases positive predictive value (PPV) to 25% missing only 4% of cancers. Nearly 45% of the biopsies could be avoided. In the age group 45-69 years, a cutoff of 20% fPSA leads to PPV of 15%, missing 6% of cancers. Unnecessary biopsies could be avoided in 12%. CONCLUSIONS: Using % fPSA in early detection of prostate cancer reduces the number of unnecessary biopsies, especially in men with negative rectal examination in the PSA range of 4.0-10.0 ng/ml. In order to diminish biopsy rate in men 70 years or older a cutoff of 16% fPSA should be used. A cutoff of 20% fPSA in men younger than 70 years is recommended to increase sensitivity in that age group.

Early detection of prostate cancer in Germany: a study using digital rectal examination and 4.0 ng/ml prostate-specific antigen as cutoff.

OBJECTIVE: While international screening studies for prostate cancer are by now almost reaching the estimated number of recruitments mandatory for the necessary power to investigate an effect on mortality of prostate cancer, no statistical figures on the detection of prostate cancer in Germany - apart from historical data before the use of prostate-specific antigen (PSA) are available. In order to generate a database and to investigate the diagnostic efficacy of the primarily practice-based urological care system, a case finding study designed as a nationwide longitudinal early detection trial was initiated. METHODS: In one week in November 1997, 963 urologists prospectively examined 11,644 men between 45 and 75 years of age by digital rectal examination (DRE) and PSA with 4.0 ng/ml as cutoff. Data of family history and physical examination were collected by questionnaire. At this time participants were not aware of their PSA value. PSA was determined in the study center. Indication for sextant biopsy was a PSA value above 4.0 ng/ml or a suspicious lesion on DRE. Any indicated biopsy not performed had to be clarified. In a second questionnaire results of prostate biopsy, treatment and tumor status were documented. RESULTS: The mean age of the study population was 62 years (median 62). The PSA median was 1.4 ng/ml with 82.8% presenting with < 4.0 ng/ml, 12.8% with 4-10 ng/ml and 4.4% with >10 ng/ml. From 1,115 men (47.7%) biopsied, 262 cancers were detected resulting in a detection rate of 23.5%. While 399 men refused biopsy, further investigation was not recommended in 387 men by their urologist, because prostatitis or benign hyperplasia was thought to be the cause for elevated PSA. From the 143 patients undergoing radical prostatectomy, 93 (65%) cancers were organ confined. T(1c) cancers with elevated PSA > 10 ng/ml could be treated with curative intent in 44% only. The positive predictive value (PPV) was estimated to be 16% for DRE alone (14/90), 17% for PSA alone (143/819) and 51% for the combination of both (105/206). In that cohort, use of age-adjusted PSA values and PSA density increased the PPV of PSA testing nonsignificantly. CONCLUSIONS: Significant higher PPV indicated that utilizing a combination of both DRE and PSA is most effective in the early detection of prostate cancer. Unnecessary biopsies can be avoided using either age-adjusted PSA value or PSA density, but the PPV is not significantly changed and potentially curable cancer is missed in up to 25%. Given the substantial variability of the diagnostic approach despite the study design, uniform guidelines are necessary to ensure countrywide sufficient screening.

Tonsillar carcinoma in a renal graft recipient treated with cyclosporine A.

We report a right-sided tonsillar carcinoma in a 33-year-old renal graft recipient on cyclosporine A plus low dose prednisolone treatment. The patient had been a life-long non-smoker and alcohol abstainer. The undifferentiated rapidly growing tumour became manifest in the fifth year after transplantation. The clue to the early recognition of this aggressive tumour (T2N0M0G3) resulting in a hitherto favourable outcome after excision and irradiation above all lied in the alertness of the patient himself.

[Experiences after 2 years of the federal operating cost rate directive]. / Erfahrungen nach zwei Jahren Bundespflegesatzverordnung.

The Federal Directive on Operating Cost Rates (BPflV) has now been in force for more than two years. An initial stocktaking with regard to the likely benefits and the costs associated with implementing the Directive properly therefore seems appropriate. The present paper is confined to experience gained at the Tübingen Clinic in the course of compiling diagnostic statistics for 1986 and 1987.

[The regulation of the circulatory system in the early postoperative period after open-heart surgery during physical therapy and orthostatic exercise (author's transl)]. / Postoperatives Verhalten der Herz- und Kreislaufregulation nach Herzoperationen unter Muskelarbeit und orthostatischer Belastung.

17 patients, who underwent open heart procedures, were examined during and after standardized exercises at the first, second and third postoperative day. At 10 defined time intervals the following parameters were measured: arterial blood pressure, right and left atrial pressure and in the pulmonary artery, arterial and venous blood gases and cardiac output by thermodilution. Oxygen consumption and cardiac index were calculated. The results show that the majority of patients after open heart surgery are well able to adjust to additional work load even early postoperatively.