Unblinded Assessment Research Articles

Meniscus Induced Cartilaginous Damage and Non-linear Gross Anatomical Progression of Early-stage Osteoarthritis in a Canine Model

Background:The predictable outcome of the anterior cruciate ligament transection (ACLT) canine model, and the similarity to naturally occurring osteoarthritis (OA) in humans, provide a translatable method for studying OA. Still, evidence of direct meniscus-induced cartilaginous damage has not been identified, and gross-anatomical blinded scoring of early-stage OA has not been performed.Objective:A gross anatomical observation and statistical analysis of OA progression to determine meniscus induced cartilaginous damage, to measure the macroscopic progression of OA, and to address matters involving arthroscopic and surgical procedures of the knee.Method:Unblinded assessment and blinded scoring of meniscal, tibial, femoral, and patellar damage were performed for control and at four time points following unilateral ACLT: 3-week (N=4), 8-week (N=4), 12-week (N=5), and 25-week (N=4). Mixed-model statistics illustrates damage (score) progression; Wilcoxon rank-sum tests compared time-point scores; and Wilcoxon signed-rank tests compared ACLT and contralateral scores, and meniscus and tibia scores.Result:Damage was manifest first on the posterior aspect of the medial meniscus and subsequently on the tibia and femur, implying meniscal damage can precede, coincide with, and aggravate cartilage damage. Damage extent varied chronologically and was dependent upon the joint component. Meniscal damage was evident at 3 weeks and progressed through 25-weeks. Meniscal loose bodies corresponded to tibial cartilage damage location and extent through 12 weeks, followed by cartilage repair activity after complete meniscal degeneration.Conclusion:This study provides additional information for understanding OA progression, identifying OA biomarkers, and arthroscopic and meniscectomy procedures.

Can we reduce bias in open-label trials when blinded outcome assessment is not possible? An example from the trigger trial

Blinded outcome assessment is a key component of randomised trials, as unblinded assessment can lead to bias. However, in some circumstances blinded assessment may be difficult to achieve. In these situations, it may be useful to modify the outcome definition to remove the most subjective elements, thereby reducing the risk of bias. This is the approach used in TRIGGER, an open-label cluster-randomised trial in patients with acute upper gastrointestinal bleeding. The primary clinical outcome was further bleeding. Blinded outcome assessment was impossible, as all clinicians throughout a hospital were aware of the treatment allocation due to the use of cluster-randomisation, and given the emergency nature of the condition, it was not possible to compile relevant information to send to an adjudication committee in a blinded matter. We therefore modified the outcome definition to remove subjective events (e.g. if a patient vomited blood, whether it was ‘fresh’ enough to indicate a new bleed), leaving only relatively objective events (the presence vs. absence of blood in the patient's upper gastrointestinal tract, based on a visual inspection by endoscopy). We collected both outcomes (including vs. removing subjective events) during the trial, and compared the estimated treatment effects from both. Including subjective events led to an odds ratio (OR) of 0.83 (95% CI 0.50 to 1.37), compared to an OR of 0.50 (95% CI 0.32 to 0.78) after removing subjective events. The ratio of odds ratios was 1.66, indicating that including subjective events may biased the treatment effect upwards by 66%.

Acne Treatment Based on Selective Photothermolysis of Sebaceous Follicles with Topically Delivered Light-Absorbing Gold Microparticles

The pathophysiology of acne vulgaris depends on active sebaceous glands, implying that selective destruction of sebaceous glands could be an effective treatment. We hypothesized that light-absorbing microparticles could be delivered into sebaceous glands, enabling local injury by optical pulses. A suspension of topically applied gold-coated silica microparticles exhibiting plasmon resonance with strong absorption at 800 nm was delivered into human pre-auricular and swine sebaceous glands in vivo, using mechanical vibration. After exposure to 10–50 J cm−2, 30 milliseconds, 800 nm diode laser pulses, microscopy revealed preferential thermal injury to sebaceous follicles and glands, consistent with predictions from a computational model. Inflammation was mild; gold particles were not retained in swine skin 1 month after treatment, and uptake in other organs was negligible. Two independent prospective randomized controlled clinical trials were performed for treatment of moderate-to-severe facial acne, using unblinded and blinded assessments of disease severity. Each trial showed clinically and statistically significant improvement of inflammatory acne following three treatments given 1–2 weeks apart. In Trial 2, inflammatory lesions were significantly reduced at 12 weeks (P=0.015) and 16 weeks (P=0.04) compared with sham treatments. Optical microparticles enable selective photothermolysis of sebaceous glands. This appears to be a well-tolerated, effective treatment for acne vulgaris.

Variation in response to short-term antidepressant treatment between patients with continuous and non-continuous cycling bipolar disorders

ObjectivesThe study aimed to compare effectiveness and safety of short-term antidepressant treatment between patients with continuous (CCC) and non-continuous (N-CCC) cycling bipolar disorders. MethodsThe study sample included 101 patients with bipolar disorder, 22 (21.8%) CCC and 79 (78.2%) N-CCC. Response was defined as a HDRS21 total score <7 at 12 weeks of treatment and remission as a ≥50% reduction of baseline HDRS21 total score sustained for 8 weeks. ResultsCompared with N-CCC patients, CCC patients achieved a significantly lower percentage of response (respectively 50% vs. 82.3%, χ²=9.6, p=0.002) and remission (respectively 40.9% vs. 69.6%, χ²=6.11, p=0.013). Adjusted logistic regression analysis indicated that CCC patients were 4.3 times more likely to be non-responders and 3.3 times more likely to be non-remitters than N-CCC patients. ConcerningAD safety, 1 (5.0%) CCC patient committed a suicide attempt and AD-emerging switch was observed in 2 patients with N-CCC (2.5%) and in 1 with CCC (4.5%). LimitationsThe observational nature of the study, retrospective assessment of course, and unblinded outcomes assessment. ConclusionsOur findings indicate that the presence or absence of a free interval identifies two different forms of bipolar disorders with different response not only to prophylactic treatment, as previously reported, but also to short-term ADs. We submit that clinicians should take into consideration their patients׳ pattern of cycling when prescribing short-term AD treatment. Moreover, subtypes of bipolar disorders might be used as moderators of treatment response in studies assessing the efficacy or the effectiveness of antidepressant treatment.

EEG neurofeedback treatments in children with ADHD: an updated meta-analysis of randomized controlled trials.

Objective: We undertook a meta-analysis of published Randomized Controlled Trials (RCT) with semi-active control and sham-NF groups to determine whether Electroencephalogram-neurofeedback (EEG-NF) significantly improves the overall symptoms, inattention and hyperactivity/impulsivity dimensions for probably unblinded assessment (parent assessment) and probably blinded assessment (teacher assessment) in children with Attention Deficit Hyperactivity Disorder (ADHD).Data sources: A systematic review identified independent studies that were eligible for inclusion in a random effects meta-analysis.Data extraction: Effect sizes for ADHD symptoms were expressed as standardized mean differences (SMD) with 95% confidence intervals.Results: Five identified studies met eligibility criteria, 263 patients with ADHD were included, 146 patients were trained with EEG-NF. On parent assessment (probably unblinded assessment), the overall ADHD score (SMD = −0.49 [−0.74, −0.24]), the inattention score (SMD = −0.46 [−0.76, −0.15]) and the hyperactivity/impulsivity score (SMD = −0.34 [−0.59, −0.09]) were significantly improved in patients receiving EEG-NF compared to controls. On teacher assessment (probably blinded assessment), only the inattention score was significantly improved in patients receiving EEG-NF compared to controls (SMD = −0.30 [−0.58, −0.03]).Conclusions: This meta-analysis of EEG-NF in children with ADHD highlights improvement in the inattention dimension of ADHD symptoms. Future investigations should pay greater attention to adequately blinded studies and EEG-NF protocols that carefully control the implementation and embedding of training.

Short-term antidepressant treatment of bipolar depression: Are ISBD recommendations useful in clinical practice?

ObjectivesThe study aimed to test the effectiveness of the ISBD Guidelines for short-term AD treatment of BP depression. MethodsThe study sample included 255 patients with mood disorders (154 UP, 49 BP-I, 52 BP-II). Response was defined as a HDRS21 total score<7 at 12 weeks of treatment and remission as a ≥50% reduction of baseline HDRS21 total score sustained for 8 weeks. ResultsResponse was achieved by 64.9% of patients with UP disorder, 75.5% of patients with BP-I disorder and 75.0% with BP-II disorder without significant differences (χ²=3.0, p=0.219). The remission rate did not differ significantly among groups (χ²=3.8, p=0.151). The dropout rate was significantly higher for patients with UP (18.2%) than for patients with BP-I (2%) and BP-II (7.7%) disorder (χ²=10.1, p=0.006). Concerning AD safety, one patient with BP-I depression committed a suicide attempt and AD-emerging switch was observed in 2.9% of patients, 2 with BP-I and 1 with BP-II disorder. LimitationsThe observational nature of the study and unblinded outcomes assessment. ConclusionsOur findings confirm the usefulness of ISBD Guidelines for short-term AD treatment of BP depression. These patients appear to have similar response and remission rate to those observed in UP depression and do not exhibit significant switch rates or risk of suicide. Our results are limited to patients with pure bipolar depression (excluding those with broadly defined mixed states), treated with ADs-mood stabilizers combination. We suggest to partially modify ISBD Recommendations 1 and 4, to include potential responders and to improve safety.

Controlling Parkinson's Disease With Adaptive Deep Brain Stimulation

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson's disease by optimizing stimulation in real time according to fluctuating disease and medication state. In the present realization of adaptive DBS we record and stimulate from the DBS electrodes implanted in the subthalamic nucleus of patients with Parkinson's disease in the early post-operative period. Local field potentials are analogue filtered between 3 and 47 Hz before being passed to a data acquisition unit where they are digitally filtered again around the patient specific beta peak, rectified and smoothed to give an online reading of the beta amplitude. A threshold for beta amplitude is set heuristically, which, if crossed, passes a trigger signal to the stimulator. The stimulator then ramps up stimulation to a pre-determined clinically effective voltage over 250 msec and continues to stimulate until the beta amplitude again falls down below threshold. Stimulation continues in this manner with brief episodes of ramped DBS during periods of heightened beta power. Clinical efficacy is assessed after a minimum period of stabilization (5 min) through the unblinded and blinded video assessment of motor function using a selection of scores from the Unified Parkinson's Rating Scale (UPDRS). Recent work has demonstrated a reduction in power consumption with aDBS as well as an improvement in clinical scores compared to conventional DBS. Chronic aDBS could now be trialed in Parkinsonism.

Controlling Parkinson's disease with adaptive deep brain stimulation.

Adaptive deep brain stimulation (aDBS) has the potential to improve the treatment of Parkinson's disease by optimizing stimulation in real time according to fluctuating disease and medication state. In the present realization of adaptive DBS we record and stimulate from the DBS electrodes implanted in the subthalamic nucleus of patients with Parkinson's disease in the early post-operative period. Local field potentials are analogue filtered between 3 and 47 Hz before being passed to a data acquisition unit where they are digitally filtered again around the patient specific beta peak, rectified and smoothed to give an online reading of the beta amplitude. A threshold for beta amplitude is set heuristically, which, if crossed, passes a trigger signal to the stimulator. The stimulator then ramps up stimulation to a pre-determined clinically effective voltage over 250 msec and continues to stimulate until the beta amplitude again falls down below threshold. Stimulation continues in this manner with brief episodes of ramped DBS during periods of heightened beta power.Clinical efficacy is assessed after a minimum period of stabilization (5 min) through the unblinded and blinded video assessment of motor function using a selection of scores from the Unified Parkinson's Rating Scale (UPDRS). Recent work has demonstrated a reduction in power consumption with aDBS as well as an improvement in clinical scores compared to conventional DBS. Chronic aDBS could now be trialed in Parkinsonism.

The Effects of Peroneal Nerve Functional Electrical Stimulation Versus Ankle-Foot Orthosis in Patients With Chronic Stroke

Background. Evidence supports peroneal nerve functional electrical stimulation (FES) as an effective alternative to ankle-foot orthoses (AFO) for treatment of foot drop poststroke, but few randomized controlled comparisons exist. Objective. To compare changes in gait and quality of life (QoL) between FES and an AFO in individuals with foot drop poststroke. Methods. In a multicenter randomized controlled trial (ClinicalTrials.gov #NCT01087957) with unblinded outcome assessments, 495 Medicare-eligible individuals at least 6 months poststroke wore FES or an AFO for 6 months. Primary endpoints: 10-Meter Walk Test (10MWT), a composite of the Mobility, Activities of Daily Living/Instrumental Activities of Daily Living, and Social Participation subscores on the Stroke Impact Scale (SIS), and device-related serious adverse event rate. Secondary endpoints: 6-Minute Walk Test, GaitRite Functional Ambulation Profile (FAP), Modified Emory Functional Ambulation Profile (mEFAP), Berg Balance Scale (BBS), Timed Up and Go, individual SIS domains, and Stroke-Specific Quality of Life measures. Multiply imputed intention-to-treat analyses were used with primary endpoints tested for noninferiority and secondary endpoints tested for superiority. Results. A total of 399 subjects completed the study. FES proved noninferior to the AFO for all primary endpoints. Both the FES and AFO groups improved significantly on the 10MWT. Within the FES group, significant improvements were found for SIS composite score, total mFEAP score, individual Floor and Obstacle course time scores of the mEFAP, FAP, and BBS, but again, no between-group differences were found. Conclusions. Use of FES is equivalent to the AFO. Further studies should examine whether FES enables better performance in tasks involving functional mobility, activities of daily living, and balance.

Adaptive deep brain stimulation in advanced Parkinson disease

Objective: Brain–computer interfaces (BCIs) could potentially be used to interact with pathological brain signals to intervene and ameliorate their effects in disease states. Here, we provide proof-of-principle of this approach by using a BCI to interpret pathological brain activity in patients with advanced Parkinson disease (PD) and to use this feedback to control when therapeutic deep brain stimulation (DBS) is delivered. Our goal was to demonstrate that by personalizing and optimizing stimulation in real time, we could improve on both the efficacy and efficiency of conventional continuous DBS.Methods: We tested BCI-controlled adaptive DBS (aDBS) of the subthalamic nucleus in 8 PD patients. Feedback was provided by processing of the local field potentials recorded directly from the stimulation electrodes. The results were compared to no stimulation, conventional continuous stimulation (cDBS), and random intermittent stimulation. Both unblinded and blinded clinical assessments of motor effect were performed using the Unified Parkinson's Disease Rating Scale.Results: Motor scores improved by 66% (unblinded) and 50% (blinded) during aDBS, which were 29% (p = 0.03) and 27% (p = 0.005) better than cDBS, respectively. These improvements were achieved with a 56% reduction in stimulation time compared to cDBS, and a corresponding reduction in energy requirements (p < 0.001). aDBS was also more effective than no stimulation and random intermittent stimulation.Interpretation BCI-controlled DBS is tractable and can be more efficient and efficacious than conventional continuous neuromodulation for PD. Ann Neurol 2013;74:449–457

Influence of Patient Race and Ethnicity on Clinical Assessment in Patients With Affective Disorders

Rates of clinical diagnoses of schizophrenia in African American individuals appear to be elevated compared with other ethnic groups in the United States, contradicting population rates derived from epidemiologic surveys. To determine whether African American individuals would continue to exhibit significantly higher rates of clinical diagnoses of schizophrenia, even after controlling for age, sex, income, site, and education, as well as the presence or absence of serious affective disorder, as determined by experts blinded to race and ethnicity. A secondary objective was to determine if a similar pattern occurred in Latino subjects. Ethnicity-blinded and -unblinded diagnostic assessments were obtained in 241 African American individuals (mean [SD] age, 34.3 [8.1] years; 57% women), 220 non-Latino white individuals (mean [SD] age, 32.7 [8.5] years; 53% women), and 149 Latino individuals (mean [SD] age, 33.5 [8.0] years; 58% women) at 6 US sites. Logistic regression models were used to determine whether elevated rates of schizophrenia in African American individuals would persist after controlling for various confounding variables including blinded expert consensus diagnoses of serious affective illness. Six academic medical centers across the United States. Six hundred ten psychiatric inpatients and outpatients. Relative odds of unblinded clinical diagnoses of schizophrenia in African American compared with white individuals. A significant ethnicity/race effect (χ(2)(2)=10.4, P=.01) was obtained when schizophrenia was narrowly defined, controlling for all other predictors. The odds ratio comparing African American with non-Latino white individuals was significant (odds ratio=2.7; 95% CI, 1.5-5.1). Similar differences between African American and white individuals occurred when schizophrenia was more broadly defined (odds ratio=2.5; 95% CI, 1.4-4.5). African American individuals did not differ significantly from white individuals in overall severity of manic and depressive symptoms but did evidence more severe psychosis. African American individuals exhibited significantly higher rates of clinical diagnoses of schizophrenia than non-Latino white subjects, even after controlling for covariates such as serious affective disorder.

Translational neuroscience requires better design and analysis of preclinical studies

AbstractAnimal models are often used to obtain a better understanding of psychiatric, neurodegenerative, and neurodevelopmental disorders. Despite many years of research, these models have not led to many novel therapies or treatments. Translating results between species will always be difficult, and it is argued that inappropriate statistical analyses, failure to identify the experimental unit, lack of random assignment to treatment conditions, and unblinded assessment of outcomes contribute to the low rate of translating preclinical in vivo studies into successful therapies. It is known that these shortcomings can generate biased estimates, too many false positives and false negatives, and unreproducible results. These issues have been raised repeatedly, but have largely gone unheeded by scientists. Two recommendations are made to improve the situation.

Blinded versus unblinded assessments of risk of bias in studies included in a systematic review

The importance of appraising the risk of bias of studies included in systematic reviews is well-established. However, uncertainty remains surrounding the method by which risk of bias assessments should be conducted. Specifically, no summary of evidence exists as to whether blinded (i.e. the assessor is unaware of the study author's name, institution, sponsorship, journal, etc.) versus unblinded assessments of risk of bias yield systematically different assessments in a systematic review. To determine whether blinded versus unblinded assessments of risk of bias yield systematically different assessments in a systematic review. We searched MEDLINE (1966 to September week 4 2009), CINAHL (1982 to May week 3 2008), All EBM Reviews (inception to 6 October 2009), EMBASE (1980 to 2009 week 40) and HealthStar (1966 to September week 4 2009) (all Ovid interface). We applied no restrictions regarding language of publication, publication status or study design. We examined reference lists of included studies and contacted experts for potentially relevant literature. We included any study that examined blinded versus unblinded assessments of risk of bias included within a systematic review. We extracted information from each of the included studies using a pre-specified 16-item form. We summarized the level of agreement between blinded and unblinded assessments of risk of bias descriptively. We calculated the standardized mean difference whenever possible. We included six randomized controlled trials (RCTs). Four studies had unclear risk of bias and two had high risk of bias. The results of these RCTs were not consistent; two demonstrated no differences between blinded and unblinded assessments, two found that blinded assessments had significantly lower quality scores, and another observed significantly higher quality scores for blinded assessments. The remaining study did not report the level of significance. We pooled five studies reporting sufficient information in a meta-analysis. We observed no statistically significant difference in risk of bias assessments between blinded or unblinded assessments (standardized mean difference -0.13, 95% confidence interval -0.42 to 0.16). The mean difference might be slightly inaccurate, as we did not adjust for clustering in our meta-analysis. We observed inconsistency of results visually and noted statistical heterogeneity. Our review highlights that discordance exists between studies examining blinded versus unblinded risk of bias assessments at the systematic review level.The best approach to risk of bias assessment remains unclear, however, given the increased time and resources required to conceal reports effectively, it may not be necessary for risk of bias assessments to be conducted under blinded conditions in a systematic review.

Climbing STAIRs towards clinical trials with a novel PARP-1 inhibitor for the treatment of ischemic stroke

Climbing STAIRs towards clinical trials with a novel PARP-1 inhibitor for the treatment of ischemic stroke

PERISCOPE study: predicting post-operative pulmonary complications in Europe

PERISCOPE study: predicting post-operative pulmonary complications in Europe

Cognitive behavioural treatment of insomnia in individuals with persistent persecutory delusions: A pilot trial

Background and ObjectivesInsomnia is a putative causal factor for persecutory thinking. Recent epidemiological studies show a strong association of insomnia and paranoia. The clinical implication is that reducing insomnia will reduce paranoid delusions. This study, evaluating for the first time the treatment of insomnia in individuals with persecutory delusions, provides a test of this hypothesis. It was predicted that a brief cognitive behavioural intervention for insomnia (CBT-I) for individuals with persistent persecutory delusions and sleep difficulties would not only reduce the insomnia but that it would also reduce the paranoia. MethodsFifteen patients with persistent persecutory delusions and insomnia in the context of a psychotic disorder were each individually given a standard-format, four-session CBT-I intervention. Outcome assessments were conducted at pre-treatment, post-treatment and one-month follow-up. ResultsThere were no missing data. Following the intervention, significant reductions were found in levels of insomnia and the persecutory delusions. The effect sizes were large, and the changes were maintained at the follow-up. At least two-thirds of participants made substantial improvements in insomnia and approximately half showed substantial reductions in the persecutory delusions. There were also reductions in levels of anomalies of experience, anxiety and depression. LimitationsThe main limitations are the absence of a control group and unblinded assessments. A more methodologically rigorous evaluation of this intervention is now warranted. ConclusionsThese preliminary findings suggest that CBT-I can be used to treat insomnia in individuals with persecutory delusions and that, consistent with the hypothesised causal role, it also lessens the delusions.

Recent developments in treatment for simple bone cysts

The purpose of this paper is to review treatment strategies for simple bone cysts (SBCs). Recent studies have focused on disrupting the wall of the cyst in combination with injectable bone substitutes. Bone substitutes are minimally invasive, provide an osteoconductive scaffold, and are relatively easy to use. Many of these studies, however, have methodological issues (uncontrolled, not randomized, unblinded outcome assessment, or short-term follow-up) and inconsistent radiographic outcomes making it difficult to determine the benefits of these newer treatment strategies. Based on a single randomized clinical trial, steroids are the only evidence-based treatment for SBCs. Further basic science is needed to understand the pathoetiology and to develop future biologic solutions. Multimodal treatment strategies with opening of the medullary canal and disruption of the cyst wall, filling defect with a bone substitute, and possible biologic treatment of the cyst membrane may be the best strategy. When considering cysts of the lower extremity, structural support may be required in addition to treatment of the cyst.

Early Versus Late Stabilization of the Spine in the Polytrauma Patient

Systematic review. To determine whether early spinal stabilization in the multiple trauma patient is safe and does not increase morbidity or mortality. There is no consensus regarding the timing of surgical stabilization of the injured spine, especially in patients with multiple trauma. Designing and performing randomized clinical trials to evaluate early versus late surgery is difficult. Between January 1990 and July 2009, a computer-aided search using the keywords Spine or Spinal, Trauma, Spinal Cord Injury, and Surgery was done that included MEDLINE, EMBASE, HealthSTAR, Cumulative Index to Nursing and Allied Health Literature, Cochrane Database of Systematic Reviews, ACP Journal Club, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, PsycINFO, and PsychLit. Articles dealing only with neurologic improvement that did not mention other non-neurologic factors that were affected by early surgery were excluded. The authors selected and assessed the studies to be included in the analysis. An unblinded assessment of the quality of the study was done using the Gradeing of Recommendation, Assessment, Development and Evaluation approach to rank each article for its relevance to the topic. Eleven articles directly comparing 2 cohorts that had early or late surgery were identified. All of the studies evaluated consistently demonstrated shorter hospital and intensive care unit length of stays, fewer days on mechanical ventilation, and lower pulmonary complications in patients who are treated with early spine decompression and stabilization. These advantages are more marked in patients with polytrauma. Data regarding morbidity and mortality rates are more variable. There is strong evidence within the literature that early surgical stabilization consistently leads to shorter hospital stays, shorter intensive care unit stays, less days on mechanical ventilation, and lower pulmonary complications. This effect is more evident in patients who have more severe injuries as measured by Injury Severity Score. This benefit is seen in both, spinal cord injured and noncord-injured patients. There is also some evidence that early stabilization does not increase the complication rates compared to late surgery.

The Hand Eczema Trial (HET): design of a randomised clinical trial of the effect of classification and individual counselling versus no intervention among health-care workers with hand eczema

BackgroundHand eczema is the most frequently recognized occupational disease in Denmark with an incidence of approximately 0.32 per 1000 person-years. Consequences of hand eczema include chronic severe eczema, prolonged sick leave, unemployment, and impaired quality of life. New preventive strategies are needed to reduce occupational hand eczema.Methods/DesignWe describe the design of a randomised clinical trial to investigate the effects of classification of hand eczema plus individual counselling versus no intervention. The trial includes health-care workers with hand eczema identified from a self-administered questionnaire delivered to 3181 health-care workers in three Danish hospitals. The questionnaire identifies the prevalence of hand eczema, knowledge of skin-protection, and exposures that can lead to hand eczema. At entry, all participants are assessed regarding: disease severity (Hand Eczema Severity Index); self-evaluated disease severity; number of eruptions; quality of life; skin protective behaviour, and knowledge of skin protection. The patients are centrally randomised to intervention versus no intervention 1:1 stratified for hospital, profession, and severity score. The experimental group undergoes patch and prick testing; classification of the hand eczema; demonstration of hand washing and appliance of emollients; individual counselling, and a skin-care programme. The control group receives no intervention. All participants are reassessed after six months. The primary outcome is observer-blinded assessment of disease severity and the secondary outcomes are unblinded assessments of disease severity; number of eruptions; knowledge of skin protection; skin-protective behaviour, and quality of life.Trial registrationThe trial is registered in ClinicalTrials.Gov, NCT01012453.

Knowledge of Treatment Group Does Not Bias Assessment of Time to Seizure in an Animal Model of Cocaine Poisoning

Blinded outcome assessment decreases bias in human clinical trials. The necessity of blinded outcome assessment on animal studies is unknown. The authors determined the effect of knowledge of treatment group on assessment of time to seizure in an animal model of cocaine poisoning. Four subjects observed 20 animal experiments where all animals were administered a high dose of cocaine and placebo. For each experiment, two of the observers were told the animal had been treated with placebo and two were told the animal had been treated with a medication expected to delay the onset of seizures. Each observer recorded the time from cocaine administration to onset of seizure. The median time to seizure was compared between observers told the animal received placebo and those told the animal received active treatment. Seizures were reported by all subjects in 12 animals and by no subjects in five animals, and there was disagreement in three animals. The reported median time to seizure was similar for observers told that the animals were treated with placebo and those told they were treated with study medication. It is feasible to determine whether unblinded assessments are biased in an animal study. Knowledge of treatment group did not bias the assessment of time to seizure in this animal model.