A double blind, randomised, multicentre comparison of two doses of intravenous iloprost in the treatment of Raynaud''s phenomenon secondary to connective tissue diseases.

OBJECTIVE--To compare low (0.5 ng/kg/min) and standard dose (2 ng/kg/min) iloprost (a stable carbacyclin analogue of prostacyclin) in patients with Raynaud''s phenomenon secondary to connective tissue disorders. DESIGN--Double blind, random allocation, three six hour infusions on consecutive days. Follow up period eight weeks. SETTING--Rheumatology units, five teaching hospitals. PATIENTS--55 Patients with Raynaud''s phenomenon (greater than seven attacks per week), 32 secondary to well documented classical progressive systemic sclerosis (American Rheumatism Association criteria), 11 CREST syndrome, 5 mixed connective tissue disease, 1 rheumatoid arthritis, 1 Sjögren''s syndrome, 1 childhood dermatomyositis, and 4 abnormal nailfold capillaroscopy and antibody profiles but no definite diagnosis. INTERVENTIONS--All other treatment for Raynaud''s phenomenon was discontinued two weeks before entry. 28 Patients were randomly allocated to receive the low dose, 27 the standard dose. Differing dilutions allowed infusion rates to be started at 10 ml/h with increments of 10 ml/h every 15 minutes until infusion rates reached 0.5 ng/kg/min and 2 ng/kg/min respectively. MAIN OUTCOME MEASURE(s)--Reduction in frequency, duration, and severity of attacks of Raynaud''s phenomenon. Assessment of ulcer and ischaemic lesion healing. RESULTS--Both dosage regimens were equally effective in reducing severity, frequency, and duration of Raynaud''s attacks. Ulcer healing occurred to similar degree in both treatment groups (standard dose 44%, low dose 39%). Low dose was associated with significantly fewer side effects. CONCLUSIONS--Both dosage regimens reduce severity of Raynaud''s phenomenon and encourage ulcer healing. Low dose was associated with fewer side effects and was better tolerated by the patients.     

Thirty down,only ten to go?! Awareness and influence of a 10-year time frame in TTO

Background

Time trade-off (TTO) exercises typically present respondents with a limited time horizon, for example 10 years, thus implicitly considerably reducing remaining life expectancy for the average respondent. It is unclear how this affects health state valuations.

Aim

The aim of the study is to investigate how awareness of the reduced life span implied by a 10-year TTO affects health state valuations, using an experimental design.

Methods

Two Web-based questionnaires (Q1 and Q2) were administered in a sample representative of the Dutch population. Both questionnaires contained three 10-year TTO exercises valuing three distinct health states, specified using the EQ-5D. Q1 used a TTO instruction not explicitly emphasizing the fact that remaining life expectancy was reduced to 10 years, while in Q2 respondents were explicitly made aware of this fact by emphasizing their implied age of death. Respondents answering Q1 were asked retrospectively whether they had been aware of their reduced life span due to the 10-year TTO.

Results

In total, 656 respondents completed the questionnaires (Q1: 339 and Q2: 317). The average age of the respondents was 43 years and 51 % of respondents were male. The average numbers of years traded off for the respondents of Q1 were for TTO1 0.443, TTO2 0.552, and TTO3 2.083 years. For the respondents of Q2, these averages were lower, i.e., TTO1 0.401 (p = 0.085 vs. Q1), TTO2: 0.546 (p = 0.036 vs. Q1), and TTO3: 1.467 years (p = 0.000 vs. Q1). Fifty-seven percent of respondents in Q1 confirmed that they were aware of the reduced life span. This spontaneous awareness had a limited and mixed influence on results. The generalized negative binomial regression analysis, explaining the time traded off showed that age, subjective life expectancy, and questionnaire Q2 (vs. Q1) were negatively associated with the years traded off, whereas education and worse health states in the TTO exercise had a significant positive impact on the years traded off. The probit model investigating the impact on the willingness to trade showed that age (?), education (+), subjective life expectancy (?), questionnaire Q2 versus Q1 (?), the interaction between Q2 and male gender (+), and worse health states in the TTO exercise (+) had a significant impact on the willingness to trade.

Conclusion

These findings emphasize the importance of expected and implied life expectancy in TTOs.     

Plasma-derived mannose-binding lectin shows a direct interaction with C1-inhibitor

MBL-deficiency has been associated with an increased frequency and severity of infection, in particular in children and under immunocompromized conditions. In an open uncontrolled safety and pharmacokinetic MBL-substitution study using plasma-derived MBL (pdMBL) in MBL-deficient pediatric oncology patients, we found that despite MBL trough levels above 1.0 μg/ml MBL functionality was not efficiently restored upon ex vivo testing.     

Incidence of calcaneal apophysitis in the general population

Background

Calcaneal apophysitis, or Sever’s disease, is a traction apophysitis. It is a frequent cause of heel pain in children. Knowledge about the exact incidence of calcaneal apophysitis in the general population, however, is lacking.

Design

Cross-sectional study.

Methods

From 34 general practices, records of patients between 6 and 17 years old, visiting the general practitioner (GP), were analysed. Diagnoses of calcaneal apophysitis were counted using computerised registration networks of GPs in 2008, 2009 and 2010.

Results

There were 16,383 SOAP files searched and a number of 61 children with calcaneal apophysitis were established over the years 2010, 2009 and 2008, showing an incidence of 3.7 in 1,000 registered patients.

Conclusion

This is the first report on incidence rates of calcaneal apophysitis in general practice. With an incidence of 3.7 in 1,000 registered patients, it is a common pathologic entity, which requires more research on pathophysiology and therapy. The actual incidence may even be higher due the strict inclusion criteria of this study.