Point and Interval Estimators of the Target Dose in Clinical Dose-Finding Studies with Active Control.

In a clinical dose finding study with active control a new drug with several dose levels is compared with an active comparator drug. The main focus of such studies often lies on the estimation of a target dose that leads to the same efficacy as the control. This article investigates the finite sample properties of the maximum likelihood estimation of the target dose and compares several approaches for constructing corresponding confidence intervals under the assumption of a linear dose-response curve and normal error terms. Furthermore, the impact of deviations from the model assumptions regarding the error distribution is explored.

Effects of transcutaneous spinal direct current stimulation in idiopathic restless legs patients.

BACKGROUND: Transcutaneous spinal direct current stimulation (tsDCS) is a new non-invasive technique to modulate spinal cord activity. The pathophysiological concept of primary RLS proposes increased spinal excitability. OBJECTIVE: This pilot study used tsDCS to reduce pathologically enhanced spinal excitability in RLS patients and to thereby ameliorate clinical symptoms. METHODS: 20 patients with idiopathic RLS and 14 healthy subjects participated in this double-blinded, placebo-controlled study. All participants received one session of cathodal, anodal and sham stimulation of the thoracic spinal cord for 15 min (2.5 mA) each, in randomized order during their symptomatic phase in the evening. The soleus Hoffmann-reflex with Hmax/Mmax-ratio and seven different H2/H1-ratios (of two H-reflex responses to double stimuli) were measured. The RLS symptoms were assessed by a visual analogue scale (VAS). All parameters were measured before and twice after tsDCS. RESULTS: RLS patients showed increased H2/H1-ratios during their symptomatic phase in the evening. Application of anodal stimulation led to a decreased H2/H1-ratio for 0.2 and 0.3 s interstimulus intervals in patients. Furthermore, application of anodal and cathodal stimulation led to a reduction in restless legs symptoms on the VAS, whereas application of sham stimulation had no effects on either the VAS or on the H2/H1-ratio in patients. VAS changes did not correlate with changes of H2/H1-ratios. CONCLUSIONS: This is the first tsDCS study in idiopathic RLS, which resulted in short-lasting clinical improvement. Furthermore, our results support the pathophysiological concept of spinal cord hyperexcitability in primary RLS and provide the basis for a new non-pharmacological treatment tool.

Discrepancies between medical oncologists and surgeons in assessment of resectability and indication for chemotherapy in patients with colorectal liver metastases.

BACKGROUND: Multidisciplinary discussion of the treatment of patients with colorectal liver metastases (CRLM) is advocated currently. The aim of this study was to investigate medical oncologists' and surgeons' assessment of resectability and indication for chemotherapy, and the effect of an educational intervention on such assessment. METHODS: Medical histories of 30 patients with CRLM were presented to ten experienced medical oncologists and 11 surgeons at an initial virtual tumour board meeting (TB1). Treatment recommendations were obtained from each participant by voting for standardized answers. Following lectures on the potential of chemotherapy and surgery, assessment was repeated at a second virtual tumour board meeting (TB2), using the same patients and participants. RESULTS: Overall, 630 answers (21 × 30) were obtained per tumour board meeting. At TB1, resectability was expected more frequently by surgeons. Participants changed 56·8 per cent of their individual answers at TB2. Assessment shifted from potentially resectable to resectable CRLM in 81 of 161 and from unresectable to (potentially) resectable CRLM in 29 of 36 answers. Preoperative chemotherapy was indicated more often by medical oncologists, and overall was included in 260 answers (41·3 per cent) at TB1, compared with only 171 answers (27·1 per cent) at TB2. Medical oncologists more often changed their decision to primary resection in resectable patients (P = 0·006). Postoperative chemotherapy was included in 51·9 and 52·4 per cent of all answers at TB1 and TB2 respectively, with no difference in changes between medical oncologists and surgeons (P = 0·980). CONCLUSION: Resectability and indication for preoperative chemotherapy were assessed differently by medical oncologists and surgeons. The educational intervention resulted in more patients deemed resectable by both oncologists and surgeons, and less frequent indication for chemotherapy.

Risk prediction of very early recurrence, death and progression after acute ischaemic stroke.

BACKGROUND AND PURPOSE: Early recurrent strokes lead to extended hospitalization and high number of complications. We investigated three stroke scores, the Essen Stroke Risk Score (ESRS), the ABCD(2) and the Recurrence Risk Estimator at 90 days (RRE-90) for their prognostic value to predict early recurrent stroke, death and progressive stroke. METHODS: Clinical and radiological data from 1727 consecutive patients with ischaemic stroke, being admitted to the stroke unit, were evaluated retrospectively. Predictive value of stroke scores was tested for early recurrence within 7 days, death and progressive stroke expressed as observational risk and area under the receiver operator curve (AUROC). RESULTS: Early recurrent stroke occurred in 56 patients (3.2%), 40 patients (2.3%) died within the first 7 days and 125 patients (7.2%) had a progressive stroke. ESRS was not predictive for early recurrence, death or progressive stroke. ABCD(2) score was predictive for death (P<0.01; χ(2); AUROC, 0.65; 0.58-0.72), and progressive stroke (P<0.001; χ(2); AUROC, 0.70; 0.66-0.74). RRE-90 predicted early recurrent stroke (P<0.001; χ(2); AUROC, 0.65; 0.58-0.73), early death (P<0.001; χ(2); AUROC, 0.72; 0.66-0.78) and progressive stroke (P<0.001; χ(2); AUROC, 0.66; 0.61-0.71). CONCLUSIONS: RRE-90 bears high potential to not only predict early recurrence but also death and progression after ischaemic stroke. ABCD(2) appears to be useful to predict risk of death and progression. These findings have relevant clinical implications for early triage of patients being admitted to stroke units.

An appraisal of the current and potential value of web 2.0 contributions to continuing education in oral implantology.

OBJECTIVE: To systematically assess the informational value, quality, intention, source and bias of web 2.0 footage whose aim is peer-to-peer education about oral implantology. METHODS: YouTube (http://www.youtube.com) was scanned on 15 October 2010 for oral implantology-related videos using an adequately pre-defined search query. Search results were filtered with the system-generated category 'education' and the additional criterion 'most viewed'. Only those videos with at least 1000 views were included (total 124, of which 27 were excluded because they were not related to implantology). Filtered videos were discussed and rated with particular regard to the educational needs of potential groups of addressees [(i) undergraduates and laymen, (ii) dentists without or currently undergoing a specialisation in oral implantology and (iii) dentists who have completed a specialisation in the field of oral implantology] by a jury consisting of (i) an accredited post-graduate university instructor with 22 years of professional teaching experience in the field of implantology, (ii) a university lecturer in dentistry/orthodontics with 10 years teaching experience and (iii) a university haematologist/oncologist. They were required to fill out a questionnaire for each video. The data were statistically analysed using non-parametric ANOVA (α = 5%) and a sign test (α = 0.05/3 = 0.017). RESULTS: The YouTube scan produced 1710 results in the category 'EDU'. The analysis revealed that there is a wide range of instructional footage on this topic, but with highly variable range in quality and informational value. Footage intention was to large proportions (47.4%) a mixture of education and advertisement. Its usefulness differed significantly for the three groups of addressees, offering greater novelty to undergraduates and post-graduates. CONCLUSION: YouTube and similar social media websites may have a potential capacity and value in complementing continuing education in the technique of oral implantology. As a means of achieving an acceptable level of knowledge about the topic when used alone, it should not be considered to be suitable at this point in time.