Quality assurance guidelines for interstitial hyperthermia.

Quality assurance (QA) guidelines are essential to provide uniform execution of clinical hyperthermia treatments and trials. This document outlines the clinical and technical consequences of the specific properties of interstitial heat delivery and specifies recommendations for hyperthermia administration with interstitial techniques. Interstitial hyperthermia aims at tumor temperatures in the 40-44 °C range as an adjunct to radiation or chemotherapy. The clinical part of this document imparts specific clinical experience of interstitial heat delivery to various tumor sites as well as recommended interstitial hyperthermia workflow and procedures. The second part describes technical requirements for quality assurance of current interstitial heating equipment including electromagnetic (radiative and capacitive) and ultrasound heating techniques. Detailed instructions are provided on characterization and documentation of the performance of interstitial hyperthermia applicators to achieve reproducible hyperthermia treatments of uniform high quality. Output power and consequent temperature rise are the key parameters for characterization of applicator performance in these QA guidelines. These characteristics determine the specific maximum tumor size and depth that can be heated adequately. The guidelines were developed by the ESHO Technical Committee with participation of senior STM members and members of the Atzelsberg Circle.

3D fluoroscopic image estimation using patient-specific 4DCBCT-based motion models.

3D fluoroscopic images represent volumetric patient anatomy during treatment with high spatial and temporal resolution. 3D fluoroscopic images estimated using motion models built using 4DCT images, taken days or weeks prior to treatment, do not reliably represent patient anatomy during treatment. In this study we developed and performed initial evaluation of techniques to develop patient-specific motion models from 4D cone-beam CT (4DCBCT) images, taken immediately before treatment, and used these models to estimate 3D fluoroscopic images based on 2D kV projections captured during treatment. We evaluate the accuracy of 3D fluoroscopic images by comparison to ground truth digital and physical phantom images. The performance of 4DCBCT-based and 4DCT-based motion models are compared in simulated clinical situations representing tumor baseline shift or initial patient positioning errors. The results of this study demonstrate the ability for 4DCBCT imaging to generate motion models that can account for changes that cannot be accounted for with 4DCT-based motion models. When simulating tumor baseline shift and patient positioning errors of up to 5 mm, the average tumor localization error and the 95th percentile error in six datasets were 1.20 and 2.2 mm, respectively, for 4DCBCT-based motion models. 4DCT-based motion models applied to the same six datasets resulted in average tumor localization error and the 95th percentile error of 4.18 and 5.4 mm, respectively. Analysis of voxel-wise intensity differences was also conducted for all experiments. In summary, this study demonstrates the feasibility of 4DCBCT-based 3D fluoroscopic image generation in digital and physical phantoms and shows the potential advantage of 4DCBCT-based 3D fluoroscopic image estimation when there are changes in anatomy between the time of 4DCT imaging and the time of treatment delivery.

Impact of immunosuppression on the development of Epstein-Barr virus (EBV) viremia after pediatric liver transplantation.

OBJECTIVES: Pediatric liver transplant (OLT) patients are at risk of posttransplant lymphoproliferative disease (PTLD) from Epstein-Barr virus (EBV). This study examined the impact of induction and immunosuppression on EBV viremia. METHODS: A retrospective chart review was performed on 197 pediatric patients and induction regimen, immunosuppression levels, and EBV viremia were documented for 1 year post-OLT. Logistic regression models determined associations between induction, immunosuppression, and EBV. RESULTS: Fifty six percent of patients developed EBV viremia. Incidence of EBV viremia was 73% with antithymocyte globulin (ATG), 63% with daclizumab, and 39% for neither, though the trend was not significant [ATG: odds ratio (OR) 0.19; 95% confidence interval (CI) 0.024-1.58; P = .125; daclizumab OR; 1.07; 95% CI 0.270-4.23; P = .925]. Tacrolimus immunosuppression levels were supratherapeutic 28.7% of the time; however, only supratherapeutic tacrolimus levels between 0 and 2 weeks increased EBV viremia at 2 to 4 weeks post-OLT (OR 1.80; 95% CI 1.10-2.94; P = .02). Three patients developed PTLD. CONCLUSIONS: The use of ATG and daclizumab induction likely does not play a role in the development of EBV viremia. Supratherapeutic tacrolimus levels 0 to 2 weeks post-OLT impact the development of EBV viremia at 2 to 4 weeks. The incidence of PTLD was low, suggesting better EBV and immunosuppression monitoring plays an important role in reducing PTLD.

Improving the use of venous thromboembolism prophylaxis in an Australian teaching hospital.

INTRODUCTION: Hospital-acquired venous thromboembolism (VTE) is a potentially fatal complication of hospitalisation, with meta-analyses and guidelines supporting the use of proven prophylactic measures (graduated compression stockings (GCS) and anticoagulants). Despite this, prophylaxis is underutilised and represents one of the largest gaps between evidence and current clinical practice. METHODS: All episodes of VTE complicating hospitalisation were ascertained prospectively as part of a quality improvement programme over 3.5 years with a view to designing interventions to improve the use of prophylaxis and reduce the rate of VTE. Interventions initially centred upon highlighting the burden of VTE, the extent of failure to apply guideline evidence into practice, and the development and application of a hospital-wide risk assessment tool. Later interventions sought to build the risk-assessment tool into routine clinical care and enhanced feedback on VTE to clinical teams. RESULTS: The annual rate of VTE fell in all the years following the intervention (2001), from 2.57 per 1000 cost-weighted separations to a nadir of 1.87 in 2003, with the difference being statistically significant (RR 0.68, 0.47 to 0.99, p = 0.04). The proportion of patients receiving anticoagulant prophylaxis increased (48% to 74%, p = 0.01) but there was no change in the measured use of GCS. There was a marked increase in the use of risk assessment for VTE in the ward setting (7.7% to 100%, p<0.001) during the programme. CONCLUSION: Affordable and accessible interventions can improve the application of VTE prophylaxis guidelines into daily hospital care and are associated with reductions in this potentially life-threatening complication.

Perineural invasion is associated with increased relapse after external beam radiotherapy for men with low-risk prostate cancer and may be a marker for occult, high-grade cancer.

PURPOSE: To investigate the risk of postradiotherapy prostate-specific antigen (PSA) failure on the basis of pretreatment risk factors in prostate cancer patients with and without perineural invasion (PNI) in prostate biopsy specimens and to explain the observation that otherwise low-risk patients with PNI experience decreased freedom from PSA failure after external beam radiotherapy (RT). METHODS AND MATERIALS: The study cohort consisted of 381 patients who underwent RT between 1989 and 2000 for clinically localized prostate cancer. A single genitourinary pathologist scored the absence or presence of PNI on all prostate biopsy specimens. Patients were divided into low-, intermediate- and high-risk subgroups on the basis of their 1992 American Joint Committee on Cancer T-stage, pretreatment PSA level, and Gleason score. Cox regression uni- and multivariate analyses were performed to evaluate whether the presence or absence of PNI in the biopsy specimen was a predictor of the time to post-RT PSA failure for patients in each pretreatment risk group. PSA failure was defined using the American Society for Therapeutic Radiology and Oncology consensus definition. Actuarial PSA failure-free survival was estimated using the Kaplan-Meier method, and comparisons were performed using the log-rank test. RESULTS: Cox regression univariate analysis revealed that PNI was a significant predictor of the time to PSA failure in the low-risk (p = 0.04) and high-risk (p = 0.03) cohorts. The 5-year PSA failure-free survival rate was 50% vs. 80% (p = 0.04) in low-risk patients, 70% vs. 75% (p = 0.72) in intermediate-risk patients, and 29% vs. 53% (p = 0.03) in high-risk patients with and without PNI, respectively. Cox regression multivariate analysis within the high-risk group revealed that a PSA level > or =20 ng/mL (p = 0.01) and Gleason score > or =8 (p = 0.02), but not PNI, were the only significant predictors of the time to PSA failure after RT. However, an association was found between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 8-10 (p = 0.06). The association was stronger between the presence of PNI in the needle biopsy specimen and a biopsy Gleason score of 7-10 (p = 0. 033). CONCLUSION: A decrement in PSA outcome after RT for low-risk patients with PNI-positive biopsy specimens was found. The association between PNI and high Gleason score provides a possible explanation for the loss of statistical significance of PNI in the Cox regression multivariate analysis of the high-risk cohort. The data suggest that PNI found in the biopsy specimen of an otherwise low-risk patient predicts for occult high-grade disease that is missed owing to the sampling error associated with prostate biopsy. The association between PNI and a high Gleason score argues for the use of more aggressive therapy, such as hormonal therapy with RT and/or dose escalation, in these select patients.

The association between synthetic bedding and adverse respiratory outcomes among skin-prick test positive and skin-prick test negative children.

BACKGROUND: Synthetic bedding has been associated with increased child wheeze and also higher allergen levels in several studies. We aimed to examine whether the association between synthetic bedding and adverse respiratory outcomes was more evident among skin-prick test (SPT) positive children. METHODS: A cross-sectional survey involving a population sample of 758 (81% of eligible) school children aged 8-10 years from randomly selected schools in the Australian Capital Territory in 1999. Parental questionnaires for ISAAC respiratory symptoms and child bedding were obtained. SPT results of 10 common allergens were available on 722 of the subjects (77% of those eligible). Synthetic pillow or quilt use was termed synthetic upper bedding. RESULTS: Synthetic quilt use was associated with asthma (Adjusted Odds Ratio 1.67 (1.05, 2.65)), recent wheeze (AOR 1.63 (1.03, 2.59)) and allergic rhinoconjunctivitis (AOR 2.11 (1.33, 3.34)) among SPT-positive children. However, these associations were not apparent for SPT-negative children. Similarly, increasing synthetic upper bedding use was associated with more than 12 episodes of wheeze among SPT-positive children (AOR 1.69 (1.08, 2.64), P=0.02, per category) but not SPT-negative children (AOR 0.77 (0.26, 2.21), P=0.6, per category). CONCLUSION: The apparent association between synthetic upper bedding and adverse respiratory outcomes was evident among SPT-positive but not SPT-negative children. Prospective intervention studies that aim to examine the effect of upper bedding composition on child asthma among SPT-positive children are required.

The relationship between low level nitrogen dioxide exposure and child lung function after cold air challenge.

BACKGROUND: Nitrogen dioxide (NO(2)) or home gas appliance use has been inconsistently associated with adverse respiratory outcomes in childhood. OBJECTIVES: (i) To examine the contribution of home gas appliance type and personal NO(2) exposure. (ii) To examine the relationship between NO(2) exposure and child lung function and respiratory history. (iii) To assess whether these relationships vary by house dust mite sensitization status. METHODS: A cross-sectional survey of 344 children (71% of the eligible group) with a mean age of 9.1 years from four randomly selected schools in the Australian Capital Territory from July to September 1999. Study measurements included a parental questionnaire, NO(2) exposure by passive gas samplers, skin prick testing for 10 aeroallergens and lung function at rest and after cold air challenge. RESULTS: Total NO(2) exposure was low with a mean concentration of 10.1 ppb. No associations were found between NO(2) exposure or gas appliance use and asthma, wheeze or baseline lung function. Personal NO(2) exposure was associated with a reduction in forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) after cold air challenge (adjusted difference - 0.12% (- 0.23% to - 0.01%) per 1 ppb increase). After exclusion of children who had home heating changed because of asthma, gas heater use was also significantly associated with a reduction in this measure (adjusted difference - 2.0% (- 3.7% to - 0.2%)). There was some evidence that these reductions were greater among the non-mite-sensitized children. CONCLUSIONS: The effect of low-level NO(2) exposure on these respiratory outcomes was not marked. The possible effect of low-level NO(2) exposure on non-specific bronchial reactivity requires confirmation. Future studies on NO(2) and respiratory health should include measures of house dust mite sensitization and bronchial hyper-responsiveness.

Use of computerized tomography and chest x-rays in evaluating efficacy of aerosolized recombinant human DNase in cystic fibrosis patients younger than age 5 years: a preliminary study.

The aim of this study was to evaluate the ability of high-resolution computerized tomography (HRCT) of the chest and chest x-rays (CXR) to determine efficacy of inhaled recombinant human DNase (rhDNase) in cystic fibrosis (CF) patients younger than 5 years of age. A randomized, double-blind, placebo-controlled pilot study of 12 patients with CF younger than 5 years of age, attending the University of Michigan Cystic Fibrosis Center (Ann Arbor, MI) was conducted. The changes in the HRCT and CXR score from baseline to day 100 of therapy were assessed using a previously validated scoring system. The mean changes of HRCT scores between the rhDNase and placebo groups were found to be significant at the 95% level, with mean change +/- SE mean of - 1.00 +/- 0.53 and 0.58 +/- 0.24 for rhDNase and placebo groups, respectively (P = 0.02). The difference in CXR score was not significant between the two groups. An analysis was performed to relate HRCT subscores to CXR score; only thickening of the intra-interlobular septae was significantly correlated with the total CXR score (r = - 0.7, P < 0.01). There was improvement in the parents' assessments of the patients' well-being, with improvement in physical activity, decreased cough, sleep quality, and appetite in those subjects receiving rhDNase. We conclude that the administration of rhDNase was associated with improvement in the HRCT scan in CF patients younger than 5 years of age. Findings indicate that HRCT of the chest is useful and sensitive in studying responses to therapy in patients with CF lung disease. To our knowledge, this is the first report of the use of HRCT to assess the effectiveness of a therapeutic modality in so young a CF patient population.

Immune consequences of intraocular administration of modified adenoviral vectors.

To investigate the immune consequences of intraocular administration of modified adenoviral vectors, C57BL/6 normal and retinal degeneration C57BL/6 (rd/rd) mice were immunized with subcutaneous, subretinal, vitreal, or anterior chamber injections of replication-deficient adenovirus (AdV) containing the Escherichia coli beta-galactosidase gene (AdV-LacZ). Fourteen days after the initial inoculation, the animals were immune challenged with an injection of AdV-LacZ in the right ear pinna. Antigen-induced delayed type hypersensitivity (DTH) was measured by determining relative ear swelling. Normal C57BL/6 mice immunized with subretinal, vitreal, or anterior chamber injections did not demonstrate a DTH response. The rd/rd C57BL/6 mice injected in the anterior chamber with the viral construct also did not respond with DTH in a manner similar to normal mice responding to intraocular injection and subsequent challenge. However, the rd/rd C57BL/6 mice immunized by the subretinal or vitreal route did respond to immune challenge with a DTH response. Histologic examination of the eyes showed a lack of infiltration by inflammatory cells. Although these results suggest that the potential for immune consequences is reduced when modified adenoviral vectors are used in the normal ocular environment, these vectors used in the vitreal cavity of rd/rd animals may induce a systemic response to the vectors.

Prognostic implications for gadolinium enhancement of the meninges in low-grade astrocytomas of childhood.

BACKGROUND: Persistent gadolinium enhancement on MRI of the meninges in some children with low-grade astrocytomas (LGA) is a widely recognized phenomenon. The relationship of this finding with the clinical course is unclear. METHODS: From a consecutive cohort of 282 children with pathologically confirmed LGA we identified all patients with asymptomatic gadolinium enhancement of the meninges found on surveillance MRI. A nested case-control study was performed, comparing patients with meningeal enhancement to controls without enhancement. RESULTS: Twenty-one children were identified with meningeal enhancement. The median follow-up was 5.2 years with enhancement noted for a median of 2.2 years. The 5-year overall survival for this cohort was 91.2% (Greenwood SE 8.0%), and the 5-year progression-free survival was 20.9% (SE 11.9%). Five patients are now free of disease, while 15 continue to have stable disease. The overall and progression-free survival was not significantly different compared to controls. CONCLUSIONS: Gadolinium enhancement of the meninges on MRI may occur in a significant number of children with LGA, particularly juvenile pilocytic astrocytoma, but does not appear to affect progression-free or overall survival. Change in management based on this finding alone is unwarranted.

Tuberculosis notifications in Australia, 1998.

Since the inception of the National Mycobacterial Surveillance System (NMSS) in 1991, annual crude notification rates for tuberculosis have remained stable at between 5 and 6 per 100,000 population. In 1998, there was a total of 923 TB notifications in Australia of which 884 were new TB cases, and 39 relapsed cases. The corresponding annual crude notification rate for new and relapsed TB was 4.72 and 0.21 per 100,000 respectively. Seventy-seven percent of notifications that had a country of birth reported were overseas born. In keeping with trends observed over recent reporting years, the populations for which notified TB rates are highest include the overseas born from high prevalence countries and Indigenous Australians. The lowest rates of disease have continued to be reported in the non-Indigenous, Australian born population. Surveillance reports over the last seven years indicate that the rate of disease in this population is gradually declining.

The clinical utility of the percent of positive prostate biopsies in predicting biochemical outcome following external-beam radiation therapy for patients with clinically localized prostate cancer.

PURPOSE: An investigation was performed of the clinical utility of the percent of positive prostate biopsies in predicting prostate-specific antigen (PSA) outcome following external-beam radiation therapy (RT) for men with PSA-detected or clinically palpable prostate cancer. METHODS AND MATERIALS: A Cox regression multivariable analysis was used to determine whether the percent of positive prostate biopsies provided clinically relevant information about PSA outcome following external beam RT in 473 men while accounting for the previously established risk groups based on the pretreatment PSA level, biopsy Gleason score, and the 1992 American Joint Commission on Cancer (AJCC) clinical T stage. RESULTS: Controlling for the known prognostic factors, the percent of positive prostate biopsies added clinically significant information (p = 0.02) regarding time to PSA failure following RT. Specifically, 76% of the patients in the intermediate risk group (1992 AJCC T(2b) or biopsy Gleason 7 or PSA > 10 ng/mL and < or = 20 ng/mL) could be classified into either an 30% or 85% 5-year PSA control cohort using the preoperative prostate biopsy data. CONCLUSION: The previously validated stratification of PSA outcome following radical prostatectomy (RP) using the percent of positive prostate biopsies in intermediate-risk patients is also clinically significant for men treated with external beam RT. The percent positive prostate biopsies should be considered in conjunction with the PSA level, biopsy Gleason score, and 1992 AJCC clinical T stage when counseling patients with newly diagnosed and clinically localized prostate cancer about PSA outcome following RP or external beam RT.

Feasibility and patient tolerance of a novel transrectal ultrasound hyperthermia system for treatment of prostate cancer.

This report describes patient tolerance and toxicity of a transrectal ultrasound hyperthermia system used with external beam radiation therapy in treatment of locally advanced prostate cancer. Nine patients with clinical T2B-T3B (4th edition AJCC criteria) disease received external beam radiation therapy, with two hyperthermia treatments scheduled at least 1 week apart during the first 4 weeks of radiation. Five patients also received hormonal therapy. Interstitial and anterior rectal wall thermometry were performed. Median temperature for each treatment (T50) was 40.8 degrees C and mean CEM T90 = 43 degrees C was 3.4 min. Rectal wall temperature was maintained at < or = 40 degrees C. Treatment duration was limited in three of 17 sessions due to positional discomfort which was alleviated with light IV sedation and use of a 'New Life' mattress (Comfortex, Inc. Winoba, MN, USA). Acute toxicity was limited to NCI common toxicity criteria grade 1 and no excess toxicity was noted with full course radiation therapy +/- hormonal therapy. These findings are consistent with those reported in a previous phase I trial assessing this device. Given the favourable toxicity profile demonstrated to date, modification of treatment parameters for this ongoing phase II study have been instituted that should further the efficacy of transrectal ultrasound hyperthermia for treatment of prostate cancer.

Tuberculosis notifications in Australia, 1999.

Australia has one of the lowest incidence of tuberculosis in the world. The crude annual notification rate for tuberculosis (TB) has remained stable at between 5 and 6 per 100,000 population since 1991. In 1999, there were a total of 1,159 TB notifications in Australia of which 1,117 were new TB cases, and 42 were relapsed cases. The corresponding annual notification rate for new and relapsed TB was 5.9 and 0.2 per 100,000 population respectively. People born overseas accounted for 83 per cent of the notified cases. TB notification rates remain highest among overseas-born residents from high prevalence countries, and indigenous Australians. The lowest rates of disease are in the non-indigenous, Australian born population and data from the last 7 years indicate that the rate of tuberculosis in this population is continuing to fall.

Clinical utility of percent-positive prostate biopsies in predicting biochemical outcome after radical prostatectomy or external-beam radiation therapy for patients with clinically localized prostate cancer.

BACKGROUND AND PURPOSE: The clinical utility of the percentage of positive prostate biopsies in predicting prostate specific antigen (PSA) outcome after radical prostatectomy (RP) or external-beam radiation therapy (EBRT) for men with PSA-detected or palpable prostate cancer is not established. METHODS: A Cox regression multivariable analysis was used to determine whether percent-positive prostate biopsies provided clinically relevant information about PSA outcome after RP in 960 men, while accounting for the previously established risk groups based on the pretreatment PSA concentration biopsy Gleason score, and the 1992 American Joint Commission on Cancer clinical T stage. RESULTS: In the intermediate-risk group, 80% of the patients (stage T(2b) or biopsy Gleason 7 or PSA 10-20 ng/mL) could be classified into either an 11% or an 86% 4-year PSA control cohort using the preoperative prostate biopsy data. These findings were validated using an independent surgical (N = 823) and radiation (N = 473) data set. Percent-positive prostate biopsies added clinically significant information regarding time to PSA failure after RP. CONCLUSIONS: The percentage of positive prostate biopsies should be considered in conjunction with the PSA level, biopsy Gleason score, and clinical T stage when counseling patients with newly diagnosed and clinically localized prostate cancer about PSA outcome after RP or EBRT.

Metastatic and nonmetastatic models of retinoblastoma.

To generate animal models of retinoblastoma that closely resemble metastatic and nonmetastatic human disease for the purposes of examining tumor biology and developing alternate treatments, human retinoblastoma cell lines were injected into the vitreal cavities of immunodeficient mice. Two reproducible animal models with contrasting biological behaviors analogous to human retinoblastoma have been developed. The Y79 retinoblastoma model demonstrated specific tumor evolution similar to that seen in human invasive and metastatic disease. Y79 retinoblastoma cells formed intraocular tumors that were initially confined to the vitreal cavity. Tumors progressively invaded the retina, subretinal space, choroid, optic nerve head, and anterior chamber of the eye. Tumors progressed into the subarachnoid space and focally invaded the brain. Metastases were detected in the contralateral optic nerve. Large tumors developed extraocular extensions. The histology of the tumors showed a poorly differentiated pattern with high mitotic rate, foci of necrosis, and calcification. The WERI-Rb model more closely resembled nonmetastatic human retinoblastoma. WERI- Rb tumors were localized in the eye with only anterior choroidal invasion at late stages. To examine potential biological differences in vitro, the retinoblastoma cell lines were cocultured with adherent choroid cells or adherent glioma cells which represent the targets of invasive retinoblastoma in vivo. Consistent with the in vivo observations, Y79 cells but not WERI-Rb cells adhere specifically to both the choroidal and the glioma cell lines.

Utilizing predictions of early prostate-specific antigen failure to optimize patient selection for adjuvant systemic therapy trials.

PURPOSE: Prostate-specific antigen (PSA) failure within 2 years after radical prostatectomy (RP) has been shown to be a clinically significant predictor of distant failure. This study was performed to estimate 2-year PSA failure rates on the basis of readily available clinical and pathologic factors to identify patients for whom effective adjuvant systemic therapy is needed. PATIENTS AND METHODS: A Cox regression multivariable analysis was used to determine whether the percentage of positive prostate biopsies, PSA level, and the pathologic findings at RP in 1,728 men provided clinically relevant information about PSA outcome after RP. A bootstrapping technique with 2,000 replications was used to provide 95% confidence intervals for the predicted 2-year PSA failure rates, which were determined on the basis of the independent clinical and pathologic predictors of PSA outcome. RESULTS: The independent predictors of time to PSA failure included a percentage of positive prostate biopsies of greater than 34% (P: < or =.009), PSA level greater than 10 ng/mL (P: < or =.01), seminal vesicle invasion (P: =. 02), prostatectomy Gleason score of 8 to 10 (P: =.04), and positive surgical margins (P: =.0001). Predictions of 2-year PSA failure rates and bootstrap estimates of the 95% confidence intervals were arranged in a tabular format, stratified by independent clinical and pathologic predictors of PSA outcome. CONCLUSION: Patients who are most likely to benefit from effective adjuvant systemic therapy after RP can be identified using readily available clinical and pathologic data.

Biochemical outcome following external beam radiation therapy with or without androgen suppression therapy for clinically localized prostate cancer.

CONTEXT: Combined treatment using radiation therapy (RT) and androgen suppression therapy (AST) is used to treat men with clinically localized adenocarcinoma of the prostate, but outcome using this combined therapy compared with RT alone is not known. OBJECTIVE: To determine the relative efficacy of RT plus AST vs RT alone among men with clinically localized prostate cancer. DESIGN, SETTING, AND PATIENTS: Retrospective cohort study of 1586 men with prostate cancer who were treated between January 1989 and August 1999 using 3-dimensional conformal RT with (n = 276) or without (n = 1310) 6 months of AST. MAIN OUTCOME MEASURE: Relative risk (RR) of prostate-specific antigen (PSA) failure (defined according to the American Society for Therapeutic Radiology and Oncology consensus statement), by treatment and high-, intermediate-, or low-risk group based on serum PSA level, biopsy Gleason score, and 1992 American Joint Commission on Cancer clinical tumor category. RESULTS: Estimates of 5-year PSA outcome after RT with or without AST were not statistically different among low-risk patients (P =.09), whereas intermediate- and high-risk patients treated with RT plus AST had significantly better outcomes than those treated with RT alone (P<.001 and =.009, respectively). The RR of PSA failure in low-risk patients treated with RT plus AST was 0.5 (95% confidence interval [CI], 0.3-1.1) compared with patients treated with RT alone. The RRs of PSA failure in intermediate-risk and high-risk patients treated with RT plus AST compared with RT alone were 0.2 (95% CI, 0. 1-0.3) and 0.4 (95% CI, 0.2-0.8), respectively. CONCLUSIONS: Our data suggest a significant benefit in 5-year PSA outcomes for men with clinically localized prostate cancer in intermediate- and high-risk groups treated with RT plus AST vs those treated with RT alone. Results from prospective randomized trials currently under way are needed to validate these findings. JAMA. 2000;284:1280-1283

Long-term effects of asthma education for physicians on patient satisfaction and use of health services.

This randomized clinical trial evaluated the long-term impact of an interactive seminar for physicians based on principles of self-regulation on clinician behaviour, children's use of health services for asthma, and parent's views of physician performance. Seventy-four general practice paediatricians, and 637 of their asthma patients aged 1-12 yrs, were randomized to treatment or control. Children and parents were blind to physicians' participation. Data were collected at baseline and follow-up through self-administered surveys (paediatricians), telephone interviews (parents) and medical records. The seminar focused on development of communication and teaching skills and use of therapeutic medical regimens for asthma as outlined in the National Asthma Education and Prevention Program guidelines. Approximately 2 yrs postintervention, treatment group physicians were more likely than control physicians to: use protocols for delivering asthma education (odds ratio (OR) 4.9, p=0.2), write down for patients how to adjust medicines when symptoms change (OR 5.7, p=0.05), and provide more guidelines for modifying therapy (OR 3.8, p=0.06). Parents scored treatment group physicians higher than control physicians on five specific positive communication behaviours. Children seen by treatment group physicians had fewer hospitalizations (p=0.03) and those with higher levels of emergency department (ED) use at baseline had fewer subsequent ED visits (p=0.03). No differences regarding the number of office visits were noted. There were no significant differences found between treatment and control group physicians in the amount of time spent with patients during office visits (26 versus 29 min) or in the number of patients treated with anti-inflammatory medicine. It is concluded that interactive asthma seminars for paediatricians had significant long-term benefits for their asthma care.