Long-term efficacy and safety of alemtuzumab in patients with RRMS: 12-year follow-up of CAMMS223

Journal of Neurology - In the phase 2 CAMMS223 trial (NCT00050778), alemtuzumab significantly improved clinical and MRI outcomes versus subcutaneous interferon beta-1a over 3 years in...     

Hypofractionated accelerated CT-guided interstitial Ir-HDR-Brachytherapy as re-irradiation in inoperable recurrent cervical lymphadenopathy from head and neck cancer

Background

Despite significant improvements in the treatment of head and neck cancer (HNC), lymph node recurrences remain a clinical challenge after primary radiotherapy. The value of interstitial (IRT) brachytherapy (BRT) for control of lymph node recurrence remains unclear. In order to clarify its role a retrospective review was undertaken on the value of computed tomography (CT)-guided IRT high-dose-rate (HDR)-BRT in isolated recurrent disease from HNC.

Patients and methods

From 2000 to 2007, 74 patients were treated for inoperable recurrent cervical lymphadenopathy. All patients had previously been treated with radical radiotherapy or chemoradiation with or without surgery. The HDR-BRT delivered a median salvage dose of 30.0 Gy (range, 12.0-36.0 Gy) in twice-daily fractions of 2.0-5.0 Gy in 71 patients and of 30.0 Gy (range, 10.0-36.0 Gy) in once-daily fractions of 6.0-10.0 Gy in three patients.

Results

The overall and disease-free survival rates at one, two and three years were 42%, 19%, 6%, and 42%, 37% and 19%, respectively. The local control probability at one, two and three years was 67% at all three time points. Grade III-IV complications occurred in 13% of patients.

Conclusions

In patients with inoperable recurrent neck disease from HNC, hypofractionated accelerated CT-guided IRT-HDR-BRT can play an important role in providing palliation and tumor control.     

Nocebo in clinical trials for depression: A meta-analysis

Nocebo refers to adverse events (AEs) related to negative expectations that medical treatment will likely harm instead of heal and can be assessed in placebo-controlled randomized clinical trials (RCTs). We sought to examine the AEs following placebo administration in RCTs for depression (D). After a systematic Medline search for RCTs in depression published in the last decade we assessed percentages of placebo-treated patients reporting at least one AE or discontinuing due to placebo intolerance and searched for factors influencing nocebo's extent. Data were extracted from 21 RCTs fulfilling search criteria. Of 3255 placebo-treated patients, 44.7% (95% CI: 22.3–68.3%) reported at least one AE, and 4.5% (95% CI: 3.4–5.8%) discontinued placebo treatment due to intolerance. AE rates in placebo and active drug treated patients were correlated quantitatively (r=0.915, p<0.001) and qualitatively, but not dropout rates (r=0.047). We conclude that almost one out of 20 placebo treated patients discontinued treatment due to AEs, indicating a significant nocebo in trials for depression treatment adversely affecting adherence and efficacy of current treatments in clinical practice, with additional implications for trial designing.     

Comparative velocity investigations in cerebral arteries and aneurysms: 3D phase‐contrast MR angiography,laser Doppler velocimetry and computational fluid dynamics

In western populations, cerebral aneurysms develop in approximately 4% of humans and they involve the risk of rupture. Blood flow patterns are of interest for understanding the pathogenesis of the lesions and may eventually contribute to deciding on the most efficient treatment procedure for a specific patient. Velocity mapping with phase‐contrast magnetic resonance angiography (PC‐MRA) is a non‐invasive method for performing in vivo measurements on blood velocity. Several hemodynamic properties can either be derived directly from these measurements or a flow field with all its parameters can be simulated on the basis of the measurements. For both approaches, the accuracy of the PC‐MRA data and subsequent modeling must be validated. Therefore, a realistic transient flow field in a well‐defined patient‐specific silicone phantom was investigated. Velocity investigations with PC‐MRA in a 3 Tesla MR scanner, laser Doppler velocimetry (LDV) and computational fluid dynamics (CFD) were performed in the same model under equal flow conditions and compared to each other. The results showed that PC‐MRA was qualitatively similar to LDV and CFD, but showed notable quantitative differences, while LDV and CFD agreed well. The accuracy of velocity quantification by PC‐MRA was best in straight artery regions with the measurement plane being perpendicular to the primary flow direction. The accuracy decreased in regions with disturbed flow and in cases where the measurement plane was not perpendicular to the primary flow. Due to these findings, it is appropriate to use PC‐MRA as the inlet and outlet conditions for numerical simulations to calculate velocities and shear stresses in disturbed regions like aneurysms, rather than derive these values directly from the full PC‐MRA measured velocity field. Copyright © 2009 John Wiley & Sons, Ltd.     

Nocebo in Headaches: Implications for Clinical Practice and Trial Design

The term nocebo refers to a harmful, unpleasant or undesirable adverse event a subject manifests after receiving an inert dummy drug or placebo. This reaction is originating by the patients fear and negative expectation that medical treatment most likely will produce unfavorable consequences instead of healing. Like placebo, nocebo shares key functions in pain conditions. Two recent systemic meta-analyses searched for nocebo in trials for prevention of migraine and tension-type headache and revealed that 1 out of 20 patients treated with placebo withdraw treatment due to adverse effects. Additionally, adverse events in placebo groups mirrored the adverse events expected of the active medication studied, confirming that pretrial suggestions induce the adverse events in placebo-treated patients. Therefore, nocebo reduces the study population by 10% and limits the treatment outcomes in randomized controlled trials for primary headaches. The potential implications of this substantial nocebo effect for both trial designing and clinical practice are discussed in this article.     

Computerised pathology test order entry reduces laboratory turnaround times and influences tests ordered by hospital clinicians: a controlled before and after study

OBJECTIVE: To assess the impact of a computerised pathology order entry system on laboratory turnaround times and test ordering within a teaching hospital. METHODS: A controlled before and after study compared test assays ordered from 11 wards two months before (n = 97 851) and after (n = 113 762) the implementation of a computerised pathology order entry system (Cerner Millennium Powerchart). Comparisons were made of laboratory turnaround times, frequency of tests ordered and specimens taken, proportions of patients having tests, average number per patient, and percentage of gentamicin and vancomycin specimens labelled as random. RESULTS: Intervention wards experienced an average decrease in turnaround of 15.5 minutes/test assay (range 73.8 to 58.3 minutes; p<0.001). Reductions were significant for prioritised and non-prioritised tests, and for those done within and outside business hours. There was no significant change in the average number of tests (p = 0.228), or specimens per patient (p = 0.324), and no change in turnaround time for the control ward (p = 0.218). Use of structured order screens enhanced data provided to laboratories. Removing three test assays from the liver function order set resulted in significantly fewer of these tests being done. CONCLUSIONS: Computerised order entry systems are an important element in achieving faster test results. These systems can influence test ordering patterns through structured order screens, manipulation of order sets, and analysis of real time data to assess the impact of such changes, not possible with paper based systems. The extent to which improvements translate into improved patient outcomes remains to be determined. A potentially limiting factor is clinicians' capacity to respond to, and make use of, faster test results.     

Guidelines for the organization of headache education in Europe: the headache school II

In order to promote education on headache disorders, European Headache Federation (EHF) in conjunction with National Headache Societies organizes educational courses meeting uniform standards according to previous published guidelines. Based on six headache summer schools’ experience, an EHF subcommittee has reviewed these guidelines, and here the revised version is presented. The goals remain the same: quality courses that will attract physicians and neurologists seeking to increase their knowledge, skills, and understanding in the area of primary and secondary headache. Detailed guidelines, a day-to-day program, and a multiple-choice test battery have now been outlined. It is recommended to include practical sessions with patient interviews and hands-on demonstrations of non-pharmacological treatment strategies. For countries that want a ‘low cost’ education program, a Video School program of a similar scientific standard has been developed. To be certified for CME credits, patronage, and financial support from EHF, it is highly recommended to adhere to the suggested teaching strategies. We hereby aim to promote and professionalize the education in headache disorders and endorse the educational courses meeting uniform standards of excellence.