Endocrine therapy with or without radical prostatectomy for T1b-T3N0M0 prostate cancer

BACKGROUND: We retrospectively compared the 5-year survival rates of T1b-T3N0M0 prostate cancer patients treated either by endocrine therapy plus radical prostatectomy or endocrine therapy alone. METHODS: Clinical T1b-T3N0M0 prostate cancer patients were enrolled at 104 institutions in Japan. They were assigned to study 1 (n = 176), if they were indicated to prostatectomy, if not indicated, they were assigned to study 2 (n = 151). The indication of prostatectomy was based on the clinical judgement of physicians and/or patients. Those assigned to study 1 underwent prostatectomy and adjuvant endocrine therapy with or without preoperative androgen deprivation. Those assigned to study 2 were treated with leuprorelin acetate with or without chlormadinone acetate. They were followed-up every 3 months until death or for 5 years and over. RESULTS: Those assigned to study 1 were younger (mean age 67.2 vs 75.7 years), less advanced in clinical stage, and had lower prostate specific antigen levels (mean 43.8 vs 103.6 ng/mL). Death for any reason was observed less frequently in study 1 (n = 29, 16%) than study 2 (n = 50, 33%), and the 5-year overall survival rate was higher in study 1 (87 vs. 68%). However, prostate cancer deaths were comparatively seldom (9% in study 1 and 7% in study 2), resulting in the identical 5-year cause specific survival rate in both study groups (91%). In both study groups the overall survival was almost equal to the natural survival of age-matched men. CONCLUSIONS: Endocrine therapy offers a reasonable survival rate in T1b-T3 prostate cancer patients within a 5-year follow-up. Observation will be extended to determine 10-year outcomes.     

Large femoral bone loss after hip revision using the uncemented proximally porous-coated Bi-Metric prosthesis: 22 hips followed for a mean of 6 years

Background and purpose Periprosthetic bone loss after uncemented femoral hip revision is a matter of concern. We have used a proximally porous- and hydroxyapatite-coated prosthesis (Bi-Metric) in revision since 1989 and now we report the bone changes. This prosthesis is intended to distribute the forces more evenly and to avoid proximal femoral unloading.Methods 22 patients were unilaterally reoperated because of aseptic loosening. Only patients with a healthy contralateral hip were included. Mean age at revision was 69 (55–80) years. Bone defects were graded by Gustilo-Pasternak and Endo-Klinik classifications. Clinical assessment was performed with Harris hip score. We used radiographs and dual-energy X-ray absorptiometry to evaluate migration, femoral remodeling, and bone mineral density after 72 (30–158) months.Results The mean Harris hip score was 74 (30–100) points at follow-up. Mild thigh discomfort was present in 1 patient and moderate thigh pain in 3 patients. There was no loosening or subsidence. Osteolysis seen at revision had diminished in 19 of the 22 hips at follow-up. We noted a large reduction in bone mineral density. It was most pronounced in Gruen regions 1, 2, 6, and 7.Interpretation Revision with this stem is a reliable procedure; however, we noted a large degree of proximal bone loss that could lead to later mechanical complications or fractures.     

Results of a Survey of 5,700 Patient Monopolar Radiofrequency Facial Skin Tightening Treatments: Assessment of a Low-Energy Multiple-Pass Technique Leading to a Clinical End Point Algorithm

INTRODUCTION: Monopolar radiofrequency is an effective means of nonsurgical facial skin tightening. OBJECTIVE: The objective of this study was to determine whether using larger tips at lower energy and multiple passes, using patient feedback on heat sensation and treating to a clinical end point of visible tightening, would yield better results than single passes with small tips at high energy, as measured by patient and physician satisfaction. METHODS: Fourteen physicians from four specialties were surveyed to determine the answers to the following three questions. (1) Is patient's feedback on heat sensation a valid and preferred method for optimal energy selection? (2) Do multiple passes at moderate energy settings yield substantial and consistent efficacy? (3) Is treating to a clinical end point of visible tightening predictable of results? RESULTS: A total of 5,700 patient treatments were surveyed. Comparisons were made using the original algorithm of high-energy, single pass to the new algorithm of lower energy and multiple passes with visible tightening as the end point of treatment. Using the original treatment algorithm, 26% of patients demonstrated immediate tightening, 54% observed skin tightening 6 months after treatment, 45% found the procedure too painful, and 68% of patients found the treatment results met their expectations. With the new multiple-pass algorithm, 87% observed immediate tightening, 92% had the tightening six months after treatment, 5% found the procedure too painful, while 94% found the treatment results met their expectations. CONCLUSIONS: Patient feedback on heat sensation is a valid, preferable method for optimal energy selection in monopolar radiofrequency skin-tightening treatments.     

Intermittent short courses of cyclosporin (Neoral®) for psoriasis unresponsive to topical therapy: a 1-year multicentre, randomized study

We performed a 1-year study to determine whether intermittent short courses of the microemulsion formulation of cyclosporin (Neoral) could effectively control plaque psoriasis and whether tapering or abrupt cessation of cyclosporin therapy would influence time to relapse. Four hundred patients with plaque psoriasis were included in this open, multicentre, randomized study. All patients commenced cyclosporin at a dose of 2.5 mg/kg daily. Cyclosporin dosage could be increased to a maximum of 5 mg/kg daily. Treatment was continued until clearance of psoriasis or for a maximum of 12 weeks. Patients were then randomly assigned either to stop cyclosporin abruptly or to have the dose reduced by 1 mg/kg daily each week until cessation. On relapse, patients were given another course of cyclosporin. Patients were followed for at least 1 year, during which they could receive as many treatment courses as necessary. The number of patients who required one, two, three and four treatment courses was 400, 259, 117 and 26, respectively. The median time to relapse after the end of the first treatment period was 109 days in the group of patients randomized to stop cyclosporin abruptly and 113 days in patients randomized to taper off cyclosporin (P = 0.038). More than 30% of patients had not relapsed 6 months after having stopped treatment. After each treatment course, the Kaplan-Meier probability of achieving 75% or more reduction in disease area by day 84 of treatment was 83%, 76%, 73% and 66%, respectively. Mean serum creatinine concentration and blood pressure did not show any clinically significant changes over time. Our results show that intermittent short-course therapy with Neoral, when used in conjunction with topical therapy, is well tolerated and provides effective control of plaque psoriasis for 1 year. Tapering off cyclosporin on treatment cessation induces a slight delay in psoriasis relapse.     

The management of moderate to severe atopic dermatitis in adults with topical fluticasone propionate

This study was designed to investigate a long-term therapeutic strategy for the management of recurring atopic dermatitis (AD) in adults using fluticasone propionate (FP) ointment (Cutivate^TM) whereby FP could help to prevent a relapse of AD once symptoms were under control. Adult patients with chronic, moderate to severe AD entered this multicentre study. All patients were initially treated with FP 0.005% (g/g) ointment in two different regimens. Patients whose AD had been completely healed by these treatments then entered a long-term treatment phase applying FP or placebo ointment once daily, two times per week for 16 weeks to 'known' healed lesions. By the end of the initial treatment period, mean SCORAD values had significantly ( P  < 0.0005) improved from baseline. Patients who entered the maintenance phase and were treated with intermittent FP for up to 16 weeks, demonstrated its superior efficacy ( P  = 0.018) over placebo, maintaining the improvements achieved after the initial treatment phase, reducing risk of relapse and delaying time to relapse ( P  = 0.013). No significant changes were detected in either treatment group in serum cortisol levels or in skin thickness measurements. Intermittent FP applied two times per week maintained a significant level of control, and delayed relapse of AD by comparison with placebo.     

Prospective evaluation of a prostacyclin-sparing aspiring formulation and heparin/warfarin in aspirin users with unstable angina or non-Q wave myocardial infarction at rest

The aim of this trial was to compare the efficacy of combinationantithrombotic therapy with a prostacyclin-sparing aspirin plusanticoagulation versus conventional aspirin plus anticoagulation,when added to antianginal therapy, in patients with unstableangina or non-Q wave myocardial infarction already being treatedwith aspirin. In a double-blind (for the aspirin) study, 144prior aspirin users were randomized; 72 patients received controiled-release,prostacyclin-sparing aspirin 75 mg daily plus anticoagulation(intravenous heparin followed by warfarin to maintain the internationalnormalized ratio at 2–3), and 72 patients received conventionalaspirin 75 mg daily plus the same anticoagulation. Controlled-releaseaspirin was formulated to preserve endothelial cell prostacyclinsynthesis. Trial therapy was begun by 13.2 ± 12.3 h ofqualifying pain, and continued for 12 weeks. The frequency of recurrent angina with electrocardiographicchanges, myocardial infarction, or death, was analysed by intentionto treat. At 12 weeks, events were     

SITE VARIABILITY IN A MULTISITE GERIATRIC DEPRESSION TRIAL

We studied differences in outcome and characteristics among 29 clinical sites of a multisite, double-blind antidepressant trial for geriatric depression. Six hundred and seventy-one outpatients aged 60 years or older (mean±SD=67.7±5.7) met DSM-III-R criteria for unipolar major depression, had baseline 17-item Hamilton Depression Rating Scale (HAMD₁₇) scores ≥16 and were randomized to fluoxetine (20 mg daily) or placebo. Effect sizes (ESs, expressed as mean differences between effects divided by the pooled standard deviation of the differences) were calculated for each site using selected outcome measures. ES ranged from 1.84 (favoring fluoxetine) to −0.91 (favoring placebo) for incidence of remitters (endpoint HAMD₁₇ total score of ≤8). A large, positive ES favoring fluoxetine for remission rates (ES≥0.65) was found at only six sites, moderate ES (0.35–0.64) at eight and small ES (0–0.34) at seven; ES favored placebo (<0) at eight of 29 sites. Private clinics showed an overall HAMD₁₇ ES for change scores more than twice that of university sites. These results suggest that individual practitioners may have vastly different clinical experiences in large, multisite trials for geriatric depression. Interrater reliability, subject selection, recruitment, inadequate or fixed dosing, few patients per site, brief study duration, heterogeneity of geriatric depression, financial incentive and characteristics of individual sites may contribute to response variability.