Doxycycline versus prednisolone as an initial treatment strategy for bullous pemphigoid: a pragmatic non-inferiority randomised controlled trial

Background: Bullous pemphigoid (BP) is a blistering skin disorder with increased mortality. We tested whether a strategy of starting treatment with doxycycline conveys acceptable short-term blister control whilst conferring long-term safety advantages over starting treatment with oral corticosteroids. Methods: Pragmatic multi-centre parallel-group randomised controlled trial of adults with BP (≥3 blisters ≥2 sites and linear basement membrane IgG/C3) plus economic evaluation. Participants were randomised to doxycycline (200 mg/day) or prednisolone (0·5 mg/kg/day). Localised adjuvant potent topical corticosteroids (<30 g/week) was permitted weeks 1-3. The non-inferiority primary effectiveness outcome was the proportion of participants with ≤3 blisters at 6 weeks. We assumed that doxycycline would be 25% less effective than corticosteroids with a 37% acceptable margin of noninferiority. The primary safety outcome was the proportion with severe, life-threatening or fatal treatment-related adverse events by 52 weeks. Analysis used a regression model adjusting for baseline disease severity, age and Karnofsky score, with missing data imputed. Results: 132 patients were randomised to doxycycline and 121 to prednisolone from 54 UK and 7 German dermatology centres. Mean age was 77·7 years and 68.4% had moderate to severe baseline disease. For those starting doxycycline, 83/112 (74·1%) had ≤3 blisters at 6 weeks compared with 92/101 (91·1%) for prednisolone, a difference of 18·6% favouring prednisolone (upper limit of 90% CI, 26·1%, within the predefined 37% margin). Related severe, life-threatening and fatal events at 52 weeks were 18·5% for those starting doxycycline and 36·6% for prednisolone (mITT analysis), an adjusted difference of 19·0% (95% CI, 7·9%, 30·1%, p=0·001). Conclusions: A strategy of starting BP patients on doxycycline is non-inferior to standard treatment with oral prednisolone for short-term blister control and significantly safer long-term

The branch of hawthorn tree /

460 copies. No. B/15.Poems.Fields.--Towns.--Sensitive plants.--The branch of hawthorn tree.--The pale cast.Mode of access: Internet.conv as

Phase 2 Trial of Paclitaxel, 13-cis Retinoic Acid, and Interferon Alfa-2b in the Treatment of Advanced Stage or Recurrent Cervical Cancer

OBJECTIVE: Overexpression of bcl-2 is a mechanism of drug resistance in cervical cancer. Agents that downregulate bcl-2 may decrease tumor cell threshold and sensitize tumor cells to chemotherapy. The objective of this multi-institutional phase II trial was to evaluate the efficacy and toxicity of paclitaxel and bcl-2 modulators (13-cis retinoic acid and interferon alfa-2b) in patients with advanced-stage or recurrent cervical cancer. METHODS/MATERIALS: Patients had biopsy-proven metastatic, first relapse, or persistent cervical cancer with no prior chemotherapy except for chemosensitizing agents. The treatment consisted of oral 13-cis retinoic acid 1 mg/kg and subcutaneous interferon alfa-2b 6 mU/m(2), days 1-4, and intravenous paclitaxel 175 mg/m(2), day 4 until disease progression or adverse events prohibited treatment. The primary endpoint was overall response rate. RESULTS: Thirty-three patients were enrolled between March 2001 and June 2009. Thirty-one patients were eligible for evaluation of treatment response. Twenty-seven patients (82%) received prior concurrent chemoradiation or radiotherapy alone before study enrollment. The overall response rate was 30% (six complete responses, four partial responses). Furthermore, seven patients (21%) had stable disease. Grade 3 or 4 adverse events included neutropenia (n=16, 48%), febrile neutropenia (n=1, 3%), and anemia (n=1, 3%). There were no treatment-related deaths. The median progression-free survival was 3.4 months (95% CI, 2.0-7.4 months), and overall survival was 11.2 months (95% CI, 7.5-26.2 months). Of six patients with complete responses, five survived more than two years. CONCLUSIONS: Combination therapy with paclitaxel, 13-cis retinoic acid, and interferon alfa-2b is feasible and safe in treating patients with advanced and recurrent cervical cancer

Generalized linear mixed models for ordered responses in complex multilevel structures: effects beneath the school or college in education

The complexities of educational processes and structure and the need for disentangling effects beneath the level of the school or college are discussed. Ordinal response multilevel crossed random-effects models for educational grades are introduced. Weighted random effects for teacher contributions are then added. Estimation methodology is reviewed. Specially written macros for quasi-likelihood with second-order terms are described. The application discusses General Certificate of Education at advanced level grades cross-classified by student and teaching group within a number of institutions. The methods handle teacher effects where several teachers contribute to provision and where each teacher deals with several groups. Some methodological lessons are drawn for sparse data and the use of extra-multinomial variation. Developments of the analysis yield conclusions about the sources of variation in educational progress, and particularly the effect of teachers. Copyright 2005 Royal Statistical Society.