Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

“Bring Your Own Device” for Formative Assessment

A high school teacher used three websites—Edmodo, Socrative, and Kahoot!– to gather information about students' learning.</jats:p

<i>In situ</i> colonization of polyvinyl chloride, brass, and copper by <i>Legionella pneumophila</i>

A sampling device (Robbins device) was used to expose brass, copper, and polyvinyl chloride plugs to potable water contaminated by Legionella pneumophila serogroup 1. Plugs were removed at approximately 1-week intervals and cultured. The colonization rates were polyvinyl chloride, 70; copper, 31; and brass, 25%. Quantitative cultures revealed that polyvinyl chloride was most heavily colonized, whereas brass was least colonized. We conclude that materials used in plumbing systems are readily colonized by Legionella and that the Robbins device provides a means for testing such materials in an in situ setting. Key words: Legionella, colonization, plumbing materials. </jats:p

Virulence of patient and water isolates of <i>Legionella pneumophila</i> in guinea pigs and mouse L929 cells varies with bacterial genotype

Thirteen isolates of Legionella pneumophila serogroup 1 (five from patients, eight from water) were screened for their virulence in guinea pigs after intraperitoneal injection and for their infectivity in L929 mouse cells. Since these isolates included three monoclonal antibody subtypes and four genotypes, the relative influence of these parameters on the pathogenicity of naturally occurring L. pneumophila could be assessed. There was no correlation between infectivity in the L929 assay and virulence for guinea pigs. The source of the isolate, patient or environmental, as well as the isolate's monoclonal antibody subtype did not correlate with virulence. At the p &lt; 0.05 level, isolates with genotype IIb (20-MDa plasmid and EcoRI fragmentation pattern b) were significantly more virulent (mean log LD50 6.84) than genotype VIb (100-MDa plasmid, pattern b), IIId (72- and 96-MDa plasmids, pattern d) or Oc (no detectable plasmid, pattern c) isolates. Genotype IIId isolates were the least virulent (mean log LD50 9.49). Plasmid-containing isolates were more infective than plasmidless ones in L929 cells (p = 0.0001). We conclude that our strain types of L. pneumophila exhibit a gradation in virulence for guinea pigs and that infectivity in L929 cells does not correlate with virulence for guinea pigs.Key words: Legionella, virulence, genotype, plasmids. </jats:p

Description and Demonstration of CBT for ADHD in Adults

ADHD in adulthood is a valid, prevalent, distressing, and interfering condition. Although medications help treat this disorder, there are often residual symptoms after medication treatment, and, for some patients, they are contraindicated. Compared to other disorders, such as mood and anxiety disorders, there are few resources available for clinicians wishing to conduct cognitive-behavioral treatment for this problem. The present manuscript provides a description of our cognitive-behavioral approach to treat ADHD in adulthood, which we have developed and tested in our clinic (Safren, Otto, et al., 2005), and for which detailed therapist and client guides exist (Safren, Perlman, Sprich, & Otto, 2005; Safren, Sprich, Perlman, & Otto, 2005). To augment the description of treatment, the present article provides video component demonstrations of several core modules that highlight important aspects of this treatment. This description and the accompanying demonstrations are intended as a practical guide to assist therapists wishing to conduct such a treatment in the outpatient setting

Genomic Stability of <i>Legionella pneumophila</i> Isolates Recovered from Two Cardiac Transplant Patients with Nosocomial Legionnaires' Disease

Pulsed-field gel electrophoresis revealed that multiple consecutive isolates of Legionella pneumophila from two cardiac transplant patients remained genomically stable, despite exposure to host defenses and antimicrobial agents. </jats:p