Background. The preservative methylchloroisothiazolinone (MCI)/methylisothiazo- linone (MI) is an important allergen, and has thus been subject to regulation in some areas of exposure, mainly in cosmetics. Objectives. To examine whether a decline in sensitization prevalence and intensity of elicitation (by the patch test) can be observed, either overall, or in certain subgroups defined by causative exposures. Methods. On the basis of long-term contact allergy surveillance data collected by the Information Network of Departments of Dermatology (www.ivkd.org), 1992-2010, in the course of 171 883 consultations, the time trend of (different grades of) positive patch test reactions to MCI/MI (0.01% aqua) was examined in an age-stratified analysis. Results. The overall frequency of positive patch test reactions was 2.33%(95% confidence interval 2.26-2.4%). No significant overall trend of positive reactions or of the distribution of +,++ and +++ reactions (p > 0.05) was observed, similarly to what was found for patients in whom cosmetics were recorded as causative exposure (p = 0.55). In contrast, in patients with occupational contact dermatitis who were < 40 years of age, a significant increase in prevalence, by 0.87 percentage points per decade, was identified (p = 0.018). Conclusions. Both applications of MCI/MI, cosmetic and industrial, should be the target of further preventive efforts.

Contact allergy (CA) surveillance networks provide information to a multitude of stakeholders, which is indispensable for evidence-based decision-making in the field of prevention. Methods and results of the German surveillance system on CA are reviewed and discussed with reference to other systems. The German network structure comprises 56 departments of dermatology and includes all patients who are patch-tested for suspected CA. Data analysis considers the results of patch testing and further pertinent information for each patient. Following aspects are addressed:(i) the description of the clinical population,(ii) evaluation of patch test reactions,(iii) relationship between patch test results and population characteristics. Trend analyses on chromate (decreasing), epoxy resin (increasing) and nickel (heterogeneous) served as examples for surveillance system analyses, with the identification of sentinel events, as well as proof of success or failure of prevention. In addition, external data sources can be used such as sales data of patch test preparations to estimate frequencies of sensitization on a population level. National prescription data of drugs and statistics of labelling of preservatives on cosmetics can be included, the latter two approaches allowing for risk estimates conferred by specific allergens.

The Chevreul illusion is a well-known 19(th) century brightness illusion, comprising adjacent homogeneous grey bands of different luminance, which are perceived as inhomogeneous. It is generally explained by lateral inhibition, according to which brighter areas projected to the retina inhibit the sensitivity of neighbouring retinal areas. Lateral inhibition has been considered the foundation-stone of early vision for a century, upon which several computational models of brightness perception are built. One of the last strongholds of lateral inhibition is the Chevreul illusion, which is often illustrated even in current textbooks. Here we prove that lateral inhibition is insufficient to explain the Chevreul illusion. For this aim, we placed the Chevreul staircase in a luminance ramp background, which noticeably changed the illusion. In our psychophysical experiments, all 23 observers reported a strong illusion, when the direction of the ramp was identical to that of the staircase, and all reported homogeneous steps (no illusion) when its direction was the opposite. When the background of the staircase was uniform, 14 saw the illusion, and 9 saw no illusion. To see whether the change of the entire background area or that of the staircase boundary edges were more important, we placed another ramp around the staircase, whose direction was opposite to that of the original, larger ramp. The result is that though the inner ramp is rather narrow (mean = 0.51 deg, SD = 0.48 deg, N = 23), it still dominates perception. Since all conditions of the lateral inhibition account were untouched within the staircase, lateral inhibition fails to model these perceptual changes. Area ratios seem insignificant; the role of boundary edges seems crucial. We suggest that long range interactions between boundary edges and areas enclosed by them, such that diffusion-based models describe, provide a much more plausible account for these brightness phenomena, and local models are insufficient.

PURPOSE The Ziprasidone Observational study of car DIAC Outcomes (ZODIAC), a large simple trial comparing ziprasidone versus olanzapine in real-world use, showed no difference in risk of sudden death. Upon the request of the US Food and Drug Administration, 205 fatal events were readjudicated applying ICD-10 coding rules for sudden death. METHODS A readjudication committee coded three domains (witness to death, time of symptom onset to death, and most likely cause of death) for use within algorithms consistent with ICD-10 rules. Relative risks (RR) and corresponding 95%CI were calculated for persons randomized to ziprasidone versus olanzapine, comparing 1-year incidence of sudden death, using multiple definitions. RESULTS Data on symptom onset to death and diagnosis of specific cardiac arrhythmias required by the ICD-10 rules were often lacking. Sensitivity analyses were conducted to explore the impact of cases suggestive of cardiac origin but missing data required by ICD-10 sudden death codes. Overall, the readjudicated data matched the study's initial findings, with no significant difference in 1-year mortality between ziprasidone and olanzapine for sudden death not otherwise specified and sudden cardiac death (R96.0 or R96.1 or I46.1; RR = 1.11, 95%CI 0.45- 2.77). CONCLUSIONS After outcome readjudication, ZODIAC found no difference in the risk of sudden death among those randomized to ziprasidone versus olanzapine. However, unlike hospital-based studies, fatal events in general population studies often occur outside hospital and often lack the clinical detail needed for the exact determination of symptom onset and event. Epidemiological evaluations of sudden death need to consider the limitations of the available data.

Background. Occupational contact allergy is a common problem in the cleaning industry. Objectives. To identify the most frequent occupation-associated allergens and time trends in contact allergy in female cleaners. Methods. We analysed the patch test data concerning 803 female cleaners, who were evaluated for occupational contact dermatitis in 45 dermatological departments contributing to the Information Network of Departments of Dermatology (IVDK) from 1996 to 2009. Female patients, except cleaners, with occupational dermatitis (n = 14494) and female controls without occupational dermatitis (n = 64736) patch tested during this time period formed the control groups. Results. One hundred and fifty-six (19.4%) cleaners had past or present atopic dermatitis. Six hundred and fifty-five (81.6%) cleaners suffered from occupational hand dermatitis. Allergic contact dermatitis was diagnosed in 249 (31%) of the cleaners. As compared with the control group without occupational dermatitis, female cleaners were significantly more often sensitized to occupationally relevant allergens such as rubber additives, especially thiurams [11.6%, 95% confidence interval (CI) 9.1-14.1 vs. 1.5%, 95% CI 1.4-1.6], zinc diethyldithiocarbamate (3.4%, 95% CI 2.1-4.7 vs. 0.4, 95% CI 0.3-0.4), and mercaptobenzothiazole (1.8, 95% CI 0.7-2.9 vs. 0.5, 95% CI 0.4-0.6), as well as formaldehyde (3.4, 95% CI 2.0-4.7 vs. 1.4%, 95% CI 1.3-1.5). No differences were seen in patterns of sensitization to occupational allergens in younger (≤40 years of age) and older (>40 years of age) female cleaners. Conclusion. Formaldehyde and rubber additives such as thiurams, zinc diethyldithiocarbamate and mercaptobenzothiazole are occupationally relevant allergens in female cleaners. Prevention strategies are needed to address the problem.

BACKGROUND Adverse reactions to permanent hair dyes are frequent, and primarily result from sensitization to p-phenylenediamine (PPD). OBJECTIVES To investigate the degree of cross-reactivity to a chemically similar dye, hydroxyethyl-p-phenylenediamine sulfate (HPPS), and whether this might be a dyeing alternative for patients who are sensitive to PPD. METHOD HPPS was patch tested in two concentrations in a total of 216 patients suspected of having contact dermatitis caused by hair dyes and/or hair cosmetics. A regular use test with a hair dye containing HPPS was suggested to every patient who had had an adverse reaction to a PPD hair dye in the past. RESULTS Forty of 216 (19.9%) patients reacted to 1% PPD, whereas only 2/216 (0.9%) showed a positive reaction to 1% HPPS. Reactivity to 2% HPPS was only slightly higher (5/216, 2.3%). On the basis of the 43 PPD-positive patients, the reactivity to 2% HPPS amounted to 12%; the corresponding figure for toluene-2,5-diamine was 15%(5/33). In a use test on two PPD-positive patients with a hair dye containing HPPS, no adverse reaction was seen, even after several years of regular dyeing. CONCLUSIONS. HPPS may be an alternative hair dye for individuals not tolerating PPD-containing dyes. However, cross-reactivity with PPD and other aromatic amines may occur. HPPS is also a known sensitizer, and the risk of de novo sensitization can only be assessed by a controlled study on a large panel and under regular use conditions.

Decision-making in child and youth mental health (CYMH) care requires recommendations that are developed through an efficient and effective method and are based on credible knowledge. Credible knowledge is informed by two sources: scientific evidence, and practice-based evidence, that reflects the "real world" experience of service providers. Current approaches to developing these recommendations in relation to CYMH will typically include evidence from one source or the other but do not have an objective method to combine the two. To this end, a modified version of the Grading Recommendations Assessment, Development and Evaluation (GRADE) approach was pilot-tested, a novel method for the CYMH field. GRADE has an explicit methodology that relies on input from scientific evidence as well as a panel of experts. The panel established the quality of evidence and derived detailed recommendations regarding the organization and delivery of mental health care for children and youth or their caregivers. In this study a modified GRADE method was used to provide precise recommendations based on a specific CYMH question (i.e. What is the current credible knowledge concerning the effects of parent-implemented, early intervention with their autistic children?). Overall, it appeared that early, parent-implemented interventions for autism result in positive effects that outweigh any undesirable effects. However, as opposed to overall recommendations, the heterogeneity of the evidence required that recommendations be specific to particular interventions, based on the questions of whether the benefits of a particular intervention outweighs its harms. This pilot project provided evidence that a modified GRADE method may be an effective and practical approach to making recommendations in CYMH, based on credible knowledge. Key strengths of the process included separating the assessments of the quality of the evidence and the strength of recommendations, transparency in decision-making, and the objectivity of the methods. Most importantly, this method combined the evidence and clinical experience in a more timely, explicit and simple process as compared to previous approaches. The strengths, limitations and modifications of the approach as they pertain to CYMH, are discussed.

BACKGROUND There is no general agreement on whether cocamidopropyl betaine (CAPB) is a skin sensitizer. OBJECTIVE To examine the evidence for CAPB being a (non-)sensitizer. METHODS This was a retrospective analysis of data on patch testing with CAPB 1% aqua collected by the Information Network of Departments of Dermatology from 1996 to 2009, with a focus on the patch test reaction profile, and demographic and clinical features of CAPB positives, supplemented by a literature review. RESULTS Eighty-three thousand eight hundred and sixty-four patients were patch tested with CAPB 1% aqua, yielding 2.16%[95% confidence interval (CI) 2.06-2.26%] positive (2.03%+ and 0.13%++/+++) and 4.6% non-allergic reactions. Thus, the reaction index was-0.368 and the positivity ratio was 94.2%. Reproducibility on synchronous patch testing (n = 6534) was poor [Cohen's kappa: 0.29 (95% CI 0.25-0.32)] and results upon retesting (n = 1157) were almost non-reproducible [kappa: 0.12 (95% CI 0.05-0.19]. Multifactorial logistic regression analysis revealed an increased risk associated with being male and aged ≥40 years, with atopic dermatitis, with scalp dermatitis, with being a hairdresser, and with a 48-hr patch test application. When only ++ or +++ reactions were used as a conservative outcome, only the elevated risk in males and in patients with atopic dermatitis remained significant. CONCLUSION The vast majority of positive reactions to CAPB are presumably false positive. Allergic reactions are very rare. This would support the notion of CAPB being 'not a significant skin sensitizer', in line with current classification systems.

BACKGROUND p-Phenylenediamine (PPD) 1% in petrolatum has been shown in a prospective study to elicit late reactions in 1.5% of routine patch tests, which may be indicative of patch test sensitization. OBJECTIVES To assess the frequency of late reactions to reduced PPD patch test concentrations. METHODS In 1838 patients, PPD was tested at three concentrations (0.5% pet., group I; 0.4% pet., group II; and 0.35% pet., group III). Patch tests were read on D1 (D2) to D3 (D4); additional late readings were performed on D7, D14, and D21. Patients who were not able to return for all scheduled late readings were telephoned on D7, D14, and D21, and questioned about a reaction at the patch test sites. RESULTS Data of 1666 patients (1069 women and 597 men) were eligible. Late reactions were observed in 9 patients, 3 in group I (0.49%) and 5 in group II (0.63%). In 7 of 8 of the patients with late reactions, patch tests were applied for 48 hr. On retesting, 4 of 5 patients became positive at D2 or D3. CONCLUSIONS The occurrence of late reactions to PPD may be influenced by patch test concentration and duration. PPD 0.4-0.5% pet. may cause late reactions indicative of active sensitization.