Post-acute phase and sequelae management of epidermal necrolysis: an international, multidisciplinary DELPHI-based consensus.

BACKGROUND: Long-term sequelae are frequent and often disabling after epidermal necrolysis (Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN)). However, consensus on the modalities of management of these sequelae is lacking. OBJECTIVES: We conducted an international multicentric DELPHI exercise to establish a multidisciplinary expert consensus to standardize recommendations regarding management of SJS/TEN sequelae. METHODS: Participants were sent a survey via the online tool "Survey Monkey" consisting of 54 statements organized into 8 topics: general recommendations, professionals involved, skin, oral mucosa and teeth, eyes, genital area, mental health, and allergy workup. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). Results were analyzed according to the RAND/UCLA Appropriateness Method. RESULTS: Fifty-two healthcare professionals participated. After the first round, a consensus was obtained for 100% of 54 initially proposed statements (disagreement index < 1). Among them, 50 statements were agreed upon as 'appropriate'; four statements were considered 'uncertain', and ultimately finally discarded. CONCLUSIONS: Our DELPHI-based expert consensus should help guide physicians in conducting a prolonged multidisciplinary follow-up of sequelae in SJS-TEN.

European recommendations for management of immune checkpoint inhibitors-derived dermatologic adverse events. The EADV task force 'Dermatology for cancer patients' position statement.

The introduction of immune checkpoint inhibitors (ICIs) opened a new era in oncologic therapy. The favourable profile of ICIs in terms of efficacy and safety can be overshadowed by the development of immune-related adverse events (irAEs). Dermatologic irAEs (dirAEs) appear in about 40% of patients undergoing immunotherapy and mainly include maculopapular, psoriasiform, lichenoid and eczematous rashes, auto-immune bullous disorders, pigmentary disorders, pruritus, oral mucosal lesions, hair and nail changes, as well as a few rare and potentially life-threatening toxicities. The EADV task force Dermatology for Cancer Patients merged the clinical experience of the so-far published data, incorporated the quantitative and qualitative characteristics of each specific dirAEs, and released dermatology-derived, phenotype-specific treatment recommendations for cutaneous toxicities (including levels of evidence and grades of recommendation). The basic principle of management is that the interventions should be tailored to serve the equilibrium between patients' relief from the symptoms and signs of skin toxicity and the preservation of an unimpeded oncologic treatment.

Supportive care in the acute phase of Stevens-Johnson syndrome and toxic epidermal necrolysis: an international, multidisciplinary Delphi-based consensus.

BACKGROUND: Supportive care is the cornerstone of management of adult and paediatric Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). However, consensus on the modalities of supportive care is lacking. OBJECTIVES: Our aim in this international multicentric Delphi exercise was to establish a multidisciplinary expert consensus to standardize recommendations regarding supportive care in the acute phase of SJS/TEN. METHODS: Participants were sent a survey via the online tool SurveyMonkey, consisting of 103 statements organized into 11 topics: multidisciplinary team composition, suspect drug management, infection prevention, fluid resuscitation and prevention of hypothermia, nutritional support, pain and psychological distress management, management of acute respiratory failure, local skincare, ophthalmological management, management of other mucosa, and additional measures. Participants evaluated the level of appropriateness of each statement on a scale of 1 (extremely inappropriate) to 9 (extremely appropriate). The results were analysed according to the RAND/UCLA Appropriateness Method. RESULTS: Forty-five participants from 13 countries (on three continents) participated. After the first round, a consensus was obtained for 82.5% of the 103 initially proposed statements. After the second round, a final consensus was obtained for 102 statements. CONCLUSIONS: We have reached an international Delphi-based consensus on best supportive care practice for SJS/TEN. Our expert consensus should help guide physicians in treating patients with SJS/TEN and thereby improve short-term prognosis and the risk of sequelae.

Multidrug-resistant and extensively drug-resistant Neisseria gonorrhoeae in Canada, 2012-2016.

BACKGROUND: Neisseria gonorrhoeae have acquired resistance to many antimicrobials, including third generation cephalosporins and azithromycin, which are the current gonococcal combination therapy recommended by the Canadian Guidelines on Sexually Transmitted Infections. OBJECTIVE: To describe antimicrobial susceptibilities for N. gonorrhoeae circulating in Canada between 2012 and 2016. METHODS: Antimicrobial resistance profiles were determined using agar dilution of N. gonorrhoeae isolated in Canada 2012-2016 (n=10,167) following Clinical Laboratory Standards Institute guidelines. Data were analyzed by applying multidrug-resistant gonococci (MDR-GC) and extensively drug-resistant gonococci (XDR-GC) definitions. RESULTS: Between 2012 and 2016, the proportion of MDR-GC increased from 6.2% to 8.9% and a total of 19 cases of XDR-GC were identified in Canada (0.1%, 19/18,768). The proportion of isolates with decreased susceptibility to cephalosporins declined between 2012 and 2016 from 5.9% to 2.0% while azithromycin resistance increased from 0.8% to 7.2% in the same period. CONCLUSION: While XDR-GC are currently rare in Canada, MDR-GC have increased over the last five years. Azithromycin resistance in N. gonorrhoeae is established and spreading in Canada, exceeding the 5% level at which the World Health Organization states an antimicrobial should be reviewed as an appropriate treatment. Continued surveillance of antimicrobial susceptibilities of N. gonorrhoeae is necessary to inform treatment guidelines and mitigate the impact of resistant gonorrhea.

Ionization-Induced Self-Channeling of an Ultrahigh-Power Subnanosecond Microwave Beam in a Neutral Gas.

Ionization-induced self-channeling of a ≤500 MW, 9.6 GHz, <1 ns microwave beam injected into air at ∼4.5×10^{3} Pa or He at ∼10^{3} Pa is experimentally demonstrated for the first time. The plasma, generated by the impact ionization of the gas driven by the microwave beam, has a radial density distribution reducing towards the beam axis, where the microwave field is highest, because the ionization rate is a decreasing function of the microwave amplitude. This forms a plasma channel which prevents the divergence of the microwave beam. The experimental data obtained using various diagnostic methods are in good agreement with the results of analytical calculations, as well as particle in cell Monte Carlo collisional modeling.

Darier disease in Israel: combined evaluation of genetic and neuropsychiatric aspects.

BACKGROUND: Darier disease (DD) is a rare genodermatosis caused by heterozygous mutations in the ATP2A2 gene. It has been associated with neuropsychiatric manifestations. OBJECTIVES: To investigate the genetic basis of Israeli patients with DD, and its association with the neuropsychiatric phenotype. METHODS: A cohort of 32 families comprising 74 affected individuals and 13 unaffected family members was recruited from the Haemek Dermatology Department and other dermatology clinics in Israel. The individuals were evaluated by detailed questionnaires, physical examination and genetic analysis. The main outcome measures were genetic mutations, psychiatric profile and their association. RESULTS: Twenty-three mutations in ATP2A2 were scattered over the entire gene, 14 of them novel. Two families shared the same mutation. Twenty-one patients (28%) had a history of psychiatric disorders, most of them mood disorders. Another seven patients (9%) were highly suspected of having a psychiatric disorder; 21 (28%) reported suicidal thoughts and five (7%) had attempted suicide. The psychiatric phenotype demonstrated inter- and intrafamilial variability, and was not associated with disease severity, family history of psychiatric disease or mutation location. CONCLUSIONS: The cohort demonstrated genetic heterogeneity with no mutation cluster along the gene, and a high prevalence of psychiatric disorders. Although no clear genotype-phenotype correlation was found, the results point to a major effect of genetic background on psychiatric phenotype, together with other modifiers.

Anomalous Diffraction in Cold Magnetized Plasma.

Cold magnetized plasma possesses an anisotropic permittivity tensor with a unique dispersion relation that for adequate electron density and magnetic field results in anomalous diffraction of a right-hand circularly polarized beam. In this work, we demonstrate experimentally anomalous diffraction of a microwave beam in plasma. Additionally, decreasing the electron density enables observation of the transition of the material from a hyperbolic to a standard material. Manipulation of the control parameters will enable plasma to serve as a reconfigurable metamaterial-like medium.

Surveillance for Lyme disease in Canada, 2009 to 2012.

OBJECTIVES: To summarize the first four years of national surveillance for Lyme disease in Canada from 2009 to 2012 and to conduct a preliminary comparison of presenting clinical manifestations in Canada and the United States. METHODS: The numbers and incidence of reported cases by province, month, year, age and sex were calculated. Logistic regression was used to examine trends over time. Acquisition locations were mapped and presenting clinical manifestations reported for jurisdictions where data was available. Variations by province, year, age and sex as well as presenting clinical symptoms were explored by logistic regression. An initial comparative analysis was made of presenting symptoms in Canada and the United States. RESULTS: The numbers of reported cases rose significantly from 144 in 2009 to 338 in 2012 (coefficient = 0.34, standard error = 0.07, P <0.05), mostly due to an increased incidence of infections acquired in Canada. More cases were classified as 'confirmed' (71.5%) than 'probable' (28.5%). Most cases occurred in locations where vector tick populations were known to be present. More men than women were affected (53.4% versus 46.6%), incidence was highest in adults aged 55 to 74 years and in children aged five to 14 years. Most cases (95%) were acquired from April to November. Of cases acquired in endemic areas, 39.7% presented with manifestations of early Lyme disease, while 60.3% had manifestations of disseminated Lyme disease. There were significant differences among age groups, sexes and provinces in the frequencies of reported clinical manifestations. The proportion of cases acquired in endemic areas presenting with early Lyme disease was lower than that reported in the US. CONCLUSION: Lyme disease incidence is increasing in Canada. Most cases are acquired where vector tick populations are spreading and this varies geographically within and among provinces. There is also variation in the frequency of age, season and presenting manifestations. The lower proportion of cases presenting with early Lyme disease in Canada compared with the US suggests lower awareness of early Lyme disease in Canada, but this requires further study.

Surveillance summary of hospitalized pediatric enterovirus D68 cases in Canada, September 2014.

BACKGROUND: Enterovirus D68 (EV-D68) has been detected infrequently and has not been associated with severe disease in Canada. In the early fall of 2014, following an unusual case increase in the United States, clusters of EV-D68 among children and some adults manifesting severe symptoms were reported in Canada. OBJECTIVE: To provide an initial epidemiological summary of pediatric cases hospitalized with EV-D68 in Canada. METHODS: A time-limited surveillance pilot was conducted collecting information on pediatric cases (less than 18 years of age) hospitalized with EV-D68 between September 1 and 30, 2014. RESULTS: In total, 268 cases were reported from Ontario (n=210), Alberta (n=45), and British Columbia (n=13). Of the 268 reported cases, 64.9% (n=174) were male; the sex difference was statistically significant (p<0.01). Age was reported for 255 cases, with a mean age for males of 5.4 years and for females of 5.3 years. For cases with data available, 6.8% (18/266) were admitted to an intensive care unit. Of those where clinical illness was recorded, respiratory illness alone was present in 98.3% (227/231), neurologic illness alone was present in 0.4% (n=1), and both illnesses were present in 0.9% of cases (n=2); cases with neither respiratory nor neurologic illness were rare (n=1). Of the 90 cases with additional clinical information available, 43.3% were reported as having asthma. No deaths were reported among the 268 cases. CONCLUSION: The EV-D68 outbreak in Canada in September 2014 represents the beginning of a novel outbreak associated with severe illness in children. These findings provide the first epidemiological summary of severe cases of EV-D68 as an emergent respiratory pathogen in Canada. The continued investigation of this pathogen is necessary to build on these results and capture the full spectrum of associated illness.

Learning disabilities in Darier's disease patients.

BACKGROUND: Neuropsychiatric features and intellectual difficulties have been reported in studies of Darier's disease. Learning disabilities have never been reported or evaluated systematically in these patients. OBJECTIVE: To assess the prevalence of learning disabilities in 76 patients with Darier's disease, and cognitive functioning in 19 of them. METHODS: The data were collected by two methods: a questionnaire, as part of a larger study on the clinical characteristics of 76 patients; and neuropsychological measures for the assessment of learning disabilities in 19 of them. RESULTS: Thirty-one of the 76 patients reported learning disabilities (41%) and 56 (74%) reported a family history of learning disabilities. Significant differences were found between the 19 patients evaluated on cognitive tasks and a control group of 42 skilled learners on subtraction and multiplication tasks. Six (32%) of the 19 were identified as having reading difficulties and five (26%) exhibited low performance on the Concentration Performance Test. All patients had general cognitive ability in the average range. CONCLUSIONS: Findings suggest an association between Darier's disease and learning disabilities, a heretofore unreported association, pointing to the need to obtain personal and family history of such disabilities in order to refer cases of clinical concern for further study.

Outbreak of E. coli O157:H7 associated with lettuce served at fast food chains in the Maritimes and Ontario, Canada, Dec 2012.

BACKGROUND: Identification and control of multi-jurisdictional foodborne illness outbreaks can be complex because of their multidisciplinary nature and the number of investigative partners involved. OBJECTIVE: To describe the multi-jurisdictional outbreak response to an E. coli O157:H7 outbreak in Canada that highlights the importance of early notification and collaboration and the value of centralized interviewing. METHODS: Investigators from local, provincial and federal jurisdictions, using a national outbreak response protocol to clarify roles and responsibilities and facilitate collaboration, conducted a rapid investigation that included centralized re-interview of cases, descriptive methods, binomial probability, and traceback findings to identify the source of the outbreak. RESULTS: There were 31 laboratory confirmed cases identified in New Brunswick, Nova Scotia, and Ontario. Thirteen cases (42%) were hospitalized and one case (3%) developed hemolytic uremic syndrome; there were no deaths. Due to early notification a coordinated investigation was initiated before laboratory subtyping was available. Re-interview of cases identified 10 cases who had not initially reported exposure to the source of the outbreak. Less than one week after the Outbreak Investigation Coordinating Committee was formed, consumption of shredded lettuce from a fast food chain was identified as the likely source of the illnesses and the implicated importer/processor initiated a precautionary recall the same day. CONCLUSION: This outbreak investigation highlights the importance of early notification, prompt re-interviewing and collaboration to rapidly identify the source of an outbreak.

Bacteriological aspects of Darier's disease.

BACKGROUND: There are no established data on the prevalence of bacterial colonization of lesional skin, nares and perineum in Darier's disease (DD), or its contribution to the clinical manifestations of the disease. OBJECTIVE: To determine the prevalence of bacterial colonization of lesional skin and Staphylococcus aureus (S. aureus) in nares and perineum in 75 patients with DD, the association of these parameters with disease and patient characteristics, and the features of the bacterial skin infection in this group. METHODS: Medical interviews and physical examinations were performed. Bacteria were isolated from swabs taken from lesional skin, nares and perineum. RESULTS: S. aureus was isolated in 68%, 47% and 22% of lesional skin, nares and perineum cultures respectively. Subjects with positive S. aureus culture from lesional skin and/or nares had a statistically significant higher percentage of skin area affected and a more severe disease than patients with negative culture. Thirty of the 75 patients (40%) recalled bacterial skin infection, most often on the chest. CONCLUSIONS: Patients with DD have high prevalence of S. aureus colonization in lesional skin and nares, with a correlation between disease severity and extent of the colonization. Further studies examining the consequences of S. aureus eradication in those sites may establish the need for S. aureus lesional skin and nares colonization screening and eradication as part of the treatment of DD exacerbations.

Health-related quality of life among Darier's disease patients.

BACKGROUND: Darier's disease (DD) is an autosomal dominant skin disorder characterized by persistent eruption of hyperkeratotic papules. The effect of DD on quality of life (QOL) has been assessed in only one study, which found no correlation between the Dermatology Life Quality Index (DLQI) score and clinical severity of the disease. The correlation between health-related quality of life (HRQL) and other diseases and patient characteristics has not been studied. OBJECTIVES: To examine the HRQL of patients with DD and to evaluate the association between HRQL scores and disease and patient characteristics. METHODS: A total of 74 DD patients completed three QOL questionnaires: DLQI, EQ-5D, and one specially designed for the study. The data reported in this study were collected as part of a larger study on the clinical characteristics of DD; the socio-demographic and clinical data were used in the statistical analysis of the current study. RESULTS: Mean DLQI was 5.41 ± 5.57 and the mean EQ-Visual Analogue Scale (VAS), was 70.84 ± 19.25. DLQI and EQ-VAS were significantly associated with skin area affected, disease severity, age at onset of DD and a seborrhoeic distribution pattern of DD. Stepwise linear regression showed skin area affected to be the most significant variable in the predication of DLQI (beta = 0.183; SE = 0.04; P < 0.001), and disease severity the most significant variable in the predication of EQ-VAS (beta = -9.15; SE = 3.21; P < 0.006). CONCLUSIONS: Darier's disease has a negative impact on HRQL of patients and the HRQL is associated with various disease characteristics, mainly skin area affected and clinical severity.

Observation of magnetically induced transparency in a classical magnetized plasma.

We report the first demonstration of magnetically induced transmission in an opaque magnetized plasma. Magnetically induced transmission in a plasma is a classical analog to the electromagnetically induced transparency in atomic systems. The transmission of radiation through an axially magnetized plasma is obtained by applying an additional one dimensional transverse spatial periodic magnetic field. The transverse-periodic magnetic field uncouples the right-hand electromagnetic wave from interacting with plasma electrons, rendering the plasma band-stop transparent. This provides means to control the extent of absorption of electromagnetic radiation in magnetized plasma.