Safety and efficacy of salvage low-dose-rate brachytherapy for prostate bed recurrences following radical prostatectomy.

PURPOSE: To report efficacy in our series of nodular recurrences in the post-surgical bed that underwent salvage low-dose-rate (LDR) brachytherapy. MATERIAL AND METHODS: Patients with radical prostatectomy (RP) who had biochemical failure with nodular recurrence detected by DRE, ultrasound, and pelvic CT and then salvaged with LDR (125)I brachytherapy were included. Nodular recurrences were biopsy confirmed adenocarcinoma, and patients had no evidence of nodal or distant metastasis on imaging including bone scan. Follow up was at least every 6 months with a serial prostate specific antigen (PSA). RESULTS: Twelve patients had salvage LDR brachytherapy with median age 69 years (range 59-86) and median pre-salvage PSA of 4.22 ng/ml. Nodule biopsy Gleason score was 7, 8, or undifferentiated. Median rectal V100 was 0.00 cc. Compared to pre-salvage, patients reported no additional genitourinary (GU) toxicity. After a median 35 months post-salvage follow up (range 10-81 months), patients had a median PSA nadir of 0.72 ng/ml (range 0.01-22.4). At 6 months post salvage, 90% of patients had a PSA below pre-salvage levels. At last follow up, 4 patients had PSA control. CONCLUSIONS: There was a trend to improved biochemical relapse free survival for lower Gleason score and pre-salvage PSA, which may be indicative of the lack of or only low volume metastatic disease. LDR brachytherapy is an effective salvage technique and can be considered in well selected patients allowing for dose escalation to the nodular recurrence.

Long-Term Efficacy and Toxicity of Low-Dose-Rate ¹²5I Prostate Brachytherapy as Monotherapy in Low-, Intermediate-, and High-Risk Prostate Cancer.

PURPOSE/OBJECTIVES: To report long-term efficacy and toxicity for a single-institution cohort of patients treated with low-dose-rate prostate brachytherapy permanent implant (PI) monotherapy. METHODS AND MATERIALS: From 1996 to 2007, 1989 patients with low-risk (61.3%), intermediate-risk (29.8%), high-intermediate-risk (4.5%), and high-risk prostate cancer (4.4%) were treated with PI and followed up prospectively in a registry. All patients were treated with (125)I monotherapy to 144 Gy. Late toxicity was coded retrospectively according to a modified Common Terminology Criteria for Adverse Events 4.0 scale. The rates of biochemical relapse-free survival (bRFS), distant metastasis-free survival (DMFS), overall survival (OS), and prostate cancer-specific mortality (PCSM) were calculated. We identified factors associated with late grade ≥3 genitourinary (GU) and gastrointestinal (GI) toxicity, bRFS, DMFS, OS, PCSM, and incontinence. RESULTS: The median age of the patients was 67 years, and the median overall and prostate-specific antigen follow-up times were 6.8 years and 5.8 years, respectively. The overall 5-year rates for bRFS, DMFS, OS, and PCSM were 91.9%, 97.8%, 93.7%, and 0.71%, respectively. The 10-year rates were 81.5%, 91.5%, 76.1%, and 2.5%, respectively. The overall rates of late grade ≥3 GU and GI toxicity were 7.6% and 0.8%, respectively. On multivariable analysis, age and prostate length were significantly associated with increased risk of late grade ≥3 GU toxicity. The risk of incontinence was highly correlated with both pre-PI and post-PI transurethral resection of the prostate. CONCLUSIONS: Prostate brachytherapy as monotherapy is an effective treatment for low-risk and low-intermediate-risk prostate cancer and appears promising as a treatment for high-intermediate-risk and high-risk prostate cancer. Significant long-term toxicities are rare when brachytherapy is performed as monotherapy.

Evaluation of warfarin management with international normalized ratio self-testing and online remote monitoring and management plus low-dose vitamin k with genomic considerations: a pilot study.

STUDY OBJECTIVES: As better international normalized ratio (INR) control and self-testing reduce events in warfarin-treated patients, and vitamin K supplementation may improve INR control, our primary objective was to evaluate the effect of a system combining frequent INR self-testing with online remote monitoring and management (STORM2) and low-dose vitamin K supplementation on INR control; our secondary objectives were to assess the impact of STORM2 on clinician time and to evaluate the influence of pharmacogenomics on INR stability and warfarin dose after vitamin K supplementation. DESIGN: Prospective pre- and postintervention study. SETTING: Freestanding clinical research center. PATIENTS: Fifty-five patients treated with long-term warfarin therapy who were referred from four anticoagulation clinics and seven medical practices. INTERVENTION: All patients performed weekly INR self-testing and received vitamin K 100 µg/day and online anticoagulation management for 1 year. MEASUREMENTS AND MAIN RESULTS: INR control and time required for anticoagulation management were assessed, and an analysis of warfarin dosing and INR stability by genetic polymorphism subgroup (vitamin K epoxide reductase complex 1 [VKORC1] and cytochrome P450 2C9 isoenzyme) was performed; vitamin K product content was also analyzed. The percentage of time that the INR is within the time in therapeutic range (TTR) improved from 56% before the intervention to 81% after the intervention (p<0.0001), and time spent at extreme INR values of lower than 1.5 or higher than 5 was reduced from 3.1% to 0.4% (p=0.01). Clinician time was less than 10 minutes per four patient visits per month. Genetic polymorphisms did not correlate with INR stability or the increase in warfarin dose after vitamin K supplementation. The content of the vitamin K product, however, was only 34-76% of the labeled amount. Patients with the GG VKORC1 genotype required a higher warfarin dose than predicted by the genomic-based dosing chart in the warfarin package insert. CONCLUSION: The 25% point improvement in TTR with STORM2 is a greater improvement than reported previously with other efforts to improve TTR. STORM2 required a minimum amount of clinician time. Pharmacogenomics were not predictive of improved INR control or the magnitude of the warfarin dose after vitamin K supplementation, although the content of the product was unreliable. Patients with the GG VKORC1 genotype required a higher warfarin dose than predicted by the product information. The potential clinical impact of improved INR control with this method warrants comparisons with conventionally managed warfarin and with the new oral anticoagulants.

Impact of a new method of warfarin management on patient satisfaction, time, and cost.

STUDY OBJECTIVE: International normalized ratio self-testing with online remote monitoring and management (STORM2) is an alternative to anticoagulation clinic management, but the patient's perspective of this method has not been evaluated in the United States; thus we sought to evaluate the impact of STORM2 on patient satisfaction, time, and cost. DESIGN: Prospective pre- and postintervention study. SETTING: Freestanding clinical research center. PATIENTS: Forty-three patients treated with long-term warfarin therapy and monitored initially in the anticoagulation clinic setting and then with STORM2, referred from 11 medical practices. INTERVENTION: Patients were asked to complete a survey and the Duke Anticoagulation Satisfaction Scale (DASS) before (at baseline) and after at least 3 months of STORM2 (at follow-up). MEASUREMENTS AND MAIN RESULTS: Patient satisfaction and time were assessed by survey and the DASS. Costs were measured from the patient's perspective. Overall 90% of responders preferred STORM2 to traditional clinic management. The DASS questions indicated that patients were more satisfied with their anticoagulation treatment and more likely to recommend oral anticoagulation to a friend after experiencing STORM2. In addition, patients found STORM2 to be less complicated and more convenient than traditional clinic management. For each traditional monthly visit, patients drove 20 miles and expended a total of 1.8 hours; using 55¢/mile for mileage reimbursement and $15/hour for lost wages, the cost for each visit was $38. The total cost for four STORM2 visits per month was $10, for a net savings of $28 per patient per month. A total of 76% of patients were willing to pay additional money to eliminate a monthly clinic visit. CONCLUSION: STORM2 is more convenient, less complicated, preferred by patients, and saves patients time and money compared with clinic management.

The application of vinylogous iminium salt derivatives to efficient formal syntheses of the marine akaloids lamellarin G trimethyl ether and ningalin B.

Studies directed at the synthesis of lamellarin G trimethyl ether and ningalin B via vinylogous iminium salt derivatives are described. The successful strategy relies on the formation of a 2,4-disubstituted pyrrole or a 1,2,3,4-tetrasubstituted pyrrole from a vinylogous iminium salt or vinylogous iminium salt derivative. Subsequent transformations of these highly substituted pyrroles lead to efficient and regiocontrolled formal syntheses of the respective pyrrole containing natural products.

The Application of Vinylogous Iminium Salt Derivatives and Microwave Accelerated Vilsmeier-Haack Reactions to Efficient Relay Syntheses of the Polycitone and Storniamide Natural Products.

Studies directed at the synthesis of polycitone and storniamide natural products via vinylogous iminium salts and microwave accelerated Vilsmeier-Haack formylations are described. The successful strategy relies on the formation of a 2,4-disubstituted pyrrole or a 2,3,4-trisubstituted pyrrole from a vinamidinium salt or vinamidinium salt derivative followed by formylation at the 5-position of the pyrrole. Subsequent transformations of the selectively formylated pyrroles lead to efficient and regiocontrolled relay syntheses of the respective pyrrole containing natural products.

A systematic review of randomized control trials evaluating the effectiveness of interactive computerized asthma patient education programs.

BACKGROUND: Educating patients with asthma about the pathophysiology and treatment of their disease is recommended. In recent years, several computer programs have been developed to provide this education. These programs take advantage of the population's increasing skill with computers and the growth of the Internet as a source of health care information. OBJECTIVE: To evaluate the effectiveness of published interactive computerized asthma patient education programs (CAPEPs) that have been subjected to randomized controlled trials (RCTs). DATA SOURCES: The PubMed, ERIC, CINAHL, Psychinfo, and Clinicaltrials.gov databases were searched (through October 3, 2005) using the following terms: asthma, patient, education, interactive, and computer. STUDY SELECTION: RCTs in English that evaluated the effect of an interactive CAPEP on the following primary end points were included in the study: hospitalizations, acute care visits, rescue inhaler use, or lung function. Secondary end points included asthma knowledge and symptoms. Trials were screened by title and abstract before full text review. Two independent investigators used a standardized data extraction form to identify the articles chosen for full review. RESULTS: Nine of 406 citations met inclusion criteria. Four CAPEPs were computer games, 7 only studied children, and 4 focused on urban populations. One study each showed that the intervention reduced the number of hospitalizations, acute care visits, or rescue inhaler use. Two studies reported lung function improvements. Four studies showed improvement in asthma knowledge, and 5 studies reported improvements in symptoms. CONCLUSIONS: Although interactive CAPEPs may improve patient asthma knowledge and symptoms, their effect on objective clinical outcomes is less consistent.