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Purpose Hyponatremia is the most frequent electrolytic disorder in clinical practice. In addition to neurological symptoms, hyponatremia, even when mild/moderate and chronic, has been related to other manifestations, such as bone demineralization and increased risk of fractures. To better elucidate tissue alterations associated with reduced serum sodium concentration [Na+], we developed an in vivo model of hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis. Methods and results Hyponatremia was induced in Foxn1nu/nu mice by subcutaneous infusion of the vasopressin analog 1-deamino [8-D-arginine] vasopressin (dDAVP) for 14 days via osmotic mini-pumps. Mice in the control group were infused with isotonic saline solution. Serum [Na+] progressively decreased, with a nadir of 123.4 ± 2.3 mEq/L (mean ± SD, dDAVP 0.3 ng/h) and 111.6 ± 4.7 mEq/L (mean ± SD, dDAVP 0.5 ng/h). Evident signs of liver steatofibrosis were observed at histology in hyponatremic mice. Accordingly, the expression of proteins involved in lipid metabolism (SREBP-1, PPARα and PPARγ) and in myofibroblast formation (αSMA and CTGF) significantly increased. Furthermore, heme oxygenase 1 expression was up-regulated in Kupffer and hepatic stellate cells in the liver of hyponatremic mice. Testis alterations were also observed. In particular, the thickness of the seminiferous epithelium appeared reduced. The expression levels of PCNA and PTMA, which are involved in DNA replication and germ cells maturation, were markedly reduced in the testis of hyponatremic mice. Conclusion Overall, these findings shed new light on the possible consequences of chronic hyponatremia and prompt a more thorough evaluation of hyponatremic patients.

Purpose Hyponatremia, the most frequent electrolyte alteration in clinical practice, has been associated with a worse prognosis in cancer patients. On the other hand, a better outcome has been related to serum sodium normalization. In vitro studies have shown that low extracellular sodium promotes cancer cells proliferation and invasiveness. Tolvaptan, a selective vasopressin receptor type 2 (V2) antagonist, has been effectively used in the last decade for the treatment of hyponatremia secondary to the Syndrome of Inappropriate Antidiuresis. A few in vitro data suggested a direct role of tolvaptan in counteracting cancer progression, so far. The aim of this study was to evaluate the effect and the mechanism of action of tolvaptan in cell lines from different tumours [i.e. colon cancer (HCT-8), hepatocarcinoma (HepG2), neuroblastoma (SK-N-AS)]. Methods and results First, we showed that these cell lines express the V2 receptor. Tolvaptan significantly reduced cell proliferation with an IC50 in the micromolar range. Accordingly, reduced levels of cAMP, of the catalytic α subunit of PKA, and a reduced pAKT/AKT ratio were observed. Tolvaptan effectively inhibited cell cycle progression, whereas it induced apoptotis. Furthermore, it reduced cell invasiveness. In particular, anchorage-independent growth and the activity of collagenases type IV were blunted in the three cell lines. Accordingly, tolvaptan counteracted the RhoA/ROCK1–2 pathway, which has a pivotal role in regulating cell movement. Conclusions Overall, these findings indicate that tolvaptan effectively inhibits tumour progression in vitro. Further studies should clarify whether the V2 receptor might be considered a possible target in anti-cancer strategies in the future.

SummaryBackgroundCOVID-19 vaccination is efficacious at protecting against severe COVID-19 outcomes in the general population. However, vaccine hesitancy (unwillingness for vaccination despite available vaccination services) threatens public health. Individuals taking immunosuppression for psoriasis have been prioritised for COVID-19 vaccination, however there is a paucity of information on vaccine hesitancy in this population, including contributing factors. While global healthcare has been severely disrupted in the pandemic, the impact on access to psoriasis care and whether this may negatively influence vaccine uptake, is underexplored.ObjectivesTo explore organisational and individual factors associated with COVID-19 vaccine hesitancy in individuals with psoriasis.MethodsIndividuals with psoriasis, identified through global patient organisations and social media, completed a cross-sectional self-reported online survey. The primary outcome was COVID-19 vaccine hesitancy. Logistic regression was used to examine the association between predictor variables (organisational and individual factors) and outcome.ResultsSelf-reported data from 802 individuals with psoriasis across 89 countries were available (65.6% female, median age 51 years [IQR 37-61], 43.7% taking systemic immunosuppression). Eight percent (n=63) reported vaccine hesitancy. Those reporting vaccine hesitancy were younger, more likely to be of non-white ethnicity, non-UK resident, have a lower BMI, not taking systemic immunosuppression and with shorter disease duration compared to those not reporting vaccine hesitancy. The commonest reasons for vaccine hesitancy were concerns regarding vaccine side-effects, that the vaccine is too new or that psoriasis may worsen post-vaccination. Forty percent (n=322) reported that their psoriasis care had been disrupted by the pandemic. These individuals were younger, of non-white ethnicity, with shorter duration and more severe psoriasis. Disruption to psoriasis care was associated with vaccine hesitancy (unadjusted OR 2.97 (95%CI 1.23-7.13), p=0.015), although not statistically significant in the adjusted model.ConclusionA minority of individuals with psoriasis from our study reported COVID-19 vaccine hesitancy. Similar to general population trends, vaccine hesitancy in our psoriasis sample is most common in younger age and ethnic minority groups. Our data highlight patient concerns regarding COVID-19 vaccination, which are important to address during patient-clinician interactions to help optimise vaccine uptake and mitigate risks from the ongoing pandemic in individuals with psoriasis.Key pointsWhat’s already known about this topic?The COVID-19 vaccine is highly efficacious at protecting against severe COVID-19 outcomes in the general population. Vaccine hesitancy (unwillingness to receive vaccination despite available vaccination services) poses a major threat to global public health and is more common in women, younger age and ethnic minority groups in the general population.Individuals with psoriasis taking systemic immunosuppression were considered at high risk of severe COVID-19 outcomes and prioritised for vaccination, however there is a paucity of information on vaccine hesitancy in this group, including contributing factors.While global healthcare has been severely disrupted by the COVID-19 pandemic, access to psoriasis care and its potential impact on vaccine hesitancy is underexplored.What does this study add?A substantial proportion (40%) of individuals with psoriasis reported disrupted access to psoriasis care during the COVID-19 pandemic. Disrupted care was most commonly reported in younger age and ethnic minority groups.COVID-19 vaccine hesitancy was reported by a minority (8%) of individuals with psoriasis. Those reporting vaccine hesitancy were younger and more likely to be of non-white ethnicity, in keeping with trends in the general population.The commonest reasons for vaccine hesitancy were concerns regarding vaccine side effects, that the vaccine is too new or that psoriasis may worsen post-vaccination. These concerns are important to address during patient-clinician interactions to help mitigate risks from the ongoing pandemic in individuals with psoriasis.

Hyponatremia, the most frequent electrolyte alteration in clinical practice, has been associated with a worse prognosis in cancer patients. On the other hand, a better outcome has been related to serum sodium normalization. In vitro studies have shown that low extracellular sodium promotes cancer cells proliferation and invasiveness. Tolvaptan, a selective vasopressin receptor type 2 (VFirst, we showed that these cell lines express the VOverall, these findings indicate that tolvaptan effectively inhibits tumour progression in vitro. Further studies should clarify whether the V

BACKGROUND: Different lifestyle and dietetic factors have been linked with the onset and severity of acne. OBJECTIVE: To assess the complex interconnection between dietetic variables and acne. METHODS: This was a reanalysis of data from a case-control study by using a semantic connectivity map approach. 563 subjects, aged 10-24 years, involved in a case-control study of acne between March 2009 and February 2010, were considered in this study. The analysis evaluated the link between a moderate to severe acne and anthropometric variables, family history and dietetic factors. Analyses were conducted by relying on an artificial adaptive system, the Auto Semantic Connectivity Map (AutoCM). RESULTS: The AutoCM map showed that moderate-severe acne was closely associated with family history of acne in first degree relatives, obesity (BMI ≥ 30), and high consumption of milk, in particular skim milk, cheese/yogurt, sweets/cakes, chocolate, and a low consumption of fish, and limited intake of fruits/vegetables. CONCLUSION: Our analyses confirm the link between several dietetic items and acne. When providing care, dermatologists should also be aware of the complex interconnection between dietetic factors and acne.

Prospective systematic analyses of the clinical presentation of bullous pemphigoid (BP) are lacking. Little is known about the time required for its diagnosis. Knowledge of the disease spectrum is important for diagnosis, management and inclusion of patients in therapeutic trials.The primary aims of the study were: (i) to characterize the clinical features of BP at time of diagnosis; and (ii) to assess the diagnostic delay in BP and its impact on prognosisAll new cases of BP diagnosed in Switzerland between 1 January 2001 and 31 December 2002 were prospectively registered by means of a standardized data collection form.One hundred-seventeen patients with BP were included in the study. 97cases (82.9%) had typical features with vesicles, blisters and/or erosions at time of diagnosis, while in the remaining cases (17.1%) only excoriations, eczematous and/or urticarial infiltrated lesions were observed. Head/neck as well as palmo-plantar involvement were found in up to 20% of patients, while mucosal lesions were present in 14.5% of the cases. Diagnosis was made after a mean of 6.1 months after the first symptoms. In patients, in whom the diagnostic delay was 4 months or more (defined as late diagnosis group), lesions were more often limited to one body area. The type of lesions did not affect the diagnostic delay. Diagnosis was made more rapidly in patients with limb involvement compared to those without. The calculated mortality rate in the early and late diagnosis group was 18.9% and 17.9%, respectively, without significant difference.BP often presents with bullous lesions at time of diagnosis after a mean diagnostic delay of 6 months. Nevertheless, up to 20% of patients lack obvious blistering and postbullous erosions, mimicking thus a variety of inflammatory dermatoses. Localized disease is associated with an increased diagnostic delay, which has however no impact on prognosis.

On the occasion of the 70th annual meeting of the American Academy of Dermatology in San Diego the ILDS Executive Committee hosted a cocktail reception in the evening of 18 March. The reception, held at the Marriott Hotel on an evening of several competing attractions, was well attended by friends of the ILDS, who stopped by for a drink and a chat. Jean Bolognia and Chris Griffiths acted as official ILDS meeters and greeters for the guests. Our president, Wolfram Sterry gave a short speech of welcome and provided an update for those present on the recent achievements of and plans for the ILDS. The announcement of the Berlin summit was particularly well received by our member societies. Jerry Shapiro then took the floor to apprise us of the arrangements for the Vancouver World Congress, these too were greeted with enthusiasm...

Clinical research involves studying patients with a view to improving their care. It enhances the health system, benefits both patients and physicians, and represents the «natural» form of investigation for physicians. It can be conducted at both large and small sites. On initiating a line of research, a specific question should be formulated in terms of PICO (patient, intervention, comparison, and outcome). Each of these components should be precisely defined. The question will subsequently be assessed using the FINER mnemonic (that is, whether it is feasible, interesting, novel, ethical, and relevant). If shortcomings are detected, the research question can be refined or rejected directly. When we have an appropriate question, the next step will be to write our protocol with the assistance of someone trained in clinical research methodology.

Clinical research involves studying patients with a view to improving their care. It enhances the health system, benefits both patients and physicians, and represents the «natural» form of investigation for physicians. It can be conducted at both large and small sites. On initiating a line of research, a specific question should be formulated in terms of PICO (patient, intervention, comparison, and outcome). Each of these components should be precisely defined. The question will subsequently be assessed using the FINER mnemonic (that is, whether it is feasible, interesting, novel, ethical, and relevant). If shortcomings are detected, the research question can be refined or rejected directly. When we have an appropriate question, the next step will be to write our protocol with the assistance of someone trained in clinical research methodology.

© IJTech 2018. This study proposes a method of optimizing the dry storage design for nuclear-spent fuel from the G.A. Siwabessy research reactor at National Nuclear Energy Agency of Indonesia (BATAN). After several years in a spent fuel pool storage (wet storage), nuclear spent fuel is often moved to dry storage. Some advantages of dry storage compared with wet storage are that there is no generation of liquid waste, no need for a complex and expensive purification system, less corrosion concerns and that dry storage is easier to transport if in the future the storage needs to be sent to the another repository or to the final disposal. In both wet and dry storage, the decay heat of spent fuel must be cooled to a safe temperature to prevent cracking of the spent fuel cladding from where hazardous radioactive nuclides could be released and harm humans and the environment. Three optimization scenarios including the thermal safety single-objective, the economic single-objective and the multi-objective optimizations are obtained. The optimum values of temperature and cost for three optimization scenarios are 317.8K (44.7°C) and 11638.1 US$ for the optimized single-objective thermal safety method, 337.1K (64.0°C) and 6345.2 US$ for the optimized single-objective cost method and 325.1K (52.0°C) and 8037.4 US$ for the optimized multi-objective method, respectively.

Huanglongbing (HLB), caused by the bacteria ‘Candidatus Liberibacter spp’, is one of the most destructive diseases for citrus production around the world. Early diagnosis of diseased citrus trees is of utmost importance for the control of HLB. Molecular techniques, such as PCR, offer quick and specific detection and identification of ‘Ca. Liberibacter spp.’. Furthermore, different sets of primers have been used for detection of ‘Ca. Liberibacter asiaticus’, the main agent of HLB. However, neither of the described sets of primers may detect all cases of HLB. Thus, conventional PCR using three common sets of primers, A2/J5, OI1/OI2c, and Lp1c/HP1, which amplify fragments of 703 pb, 1200 pb, and 2400 pb, respectively, were examined for HLB diagnosis. A total of 969 samples from different citrus cultivars, tree ages and regions of the State of Parana, Brazil, were included in this study. The total number of samples tested positive for HLB by any set of primers were 598, representing 61.7% of the samples examined. Among these positive samples, 96.7% were identified with the primers A2/J5, 86.6% with OI2c/OI1, and 81.4% with HP1/Lp1c. When combined, 99.8% of the samples were HLB positive based on the sets of primers A2/J5 and OI2c/ OI1. Based on the results obtained, the set of primers A2/J5 showed the highest efficiency in the detection of HLB for the bacterium that occurs in the State of Parana, Brazil.

Cutaneous reactions represent in many surveillance systems, the most frequent adverse events attributable to drugs. The spectrum of clinical manifestations is wide and virtually encompasses any known dermatological disease. The introduction of biological agents and so-called targeted therapies has further enlarged the number of reaction patterns especially linked with cytokine release or in balance. The frequency and clinical patterns of cutaneous reactions are influenced by drug use, prevalence of specific conditions (e.g., HIV infection) and pharmacogenetic traits of a population, and they may vary greatly among the different populations around the world. Studies of reaction rates in cohorts of hospitalized patients revealed incidence rates ranging from, 1 out 1000 to 2 out 100 of all hospitalized patients. For drugs such as aminopenicillines and sulfamides the incidence of skin reactions is in the order of 3-5 cases out of 100 exposed people. Although the majority of cutaneous reactions are mild and self-limiting, there are reactions such as Stevens Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), and drug reaction with eosinophilia and systemic symptoms (DRESS) which are associated with significant morbidity and mortality. Surveillance systems routed on sound epidemiologic methodology, are needed to raise signals and to assess risks associated with specific reactions and drug exposures. Identification of risk factors for adverse reactions and appropriate genetic screening of groups at higher risk may improve the outcomes of skin reactions.

BACKGROUND: Several national prospective registries of psoriatic patients treated with systemic therapies are running, with the aim of describing the population treated, safety and effectiveness of these treatments, especially biologics. Psonet is an initiative to pool data from these registries. OBJECTIVES: To describe psoriasis therapy in Psonet countries, using baseline data of patients included in these registries. METHODS: We collected data from Psocare (Italy), Dermbio (Denmark), Biobadaderm (Spain), Clalit Health Services (Israel), Australasian Psoriasis Registry, Psobest (Germany), and AMC Medical Center Registry (Netherlands). We described previous use of drugs at the time that patients started a new classic systemic drug or any biologic drug. RESULTS: Data from 20,232 patients was pooled in our analysis (9,668 treated with biologics, 10,564 with other systemic therapies). At a given time in the life course of psoriasis, we have shown large between country heterogeneity on the previous use of systemic drugs for psoriasis and relevant rates of use of biologic drugs in potentially off-label use (first line use and use in psoriasis forms different from plaque psoriasis). Variability in therapy is larger than variability in available patient characteristics likely to influence therapy. CONCLUSIONS: We have shown the presence of large heterogeneity on the use of systemic drugs for psoriasis in participating countries, including differences in patient access to biologics amongst the participating countries. This might be an indicator of unwarranted clinical variation in some countries: a marker of inefficient or less safe use of systemic drugs for psoriasis, and requires further study

Although sun exposure is a strong risk factor for skin cancer, tanning is very popular among adolescents. Awareness of skin cancer and sun exposure might influence sun protective behaviours in this population.To investigate the awareness of skin cancer and sun-safe practices among Italian adolescents.A questionnaire about knowledge of skin cancer, perceived severity of sun rays/skin cancer and behaviour toward sun protection was administered to 1204 secondary school students. Predictors of these three components were assessed by case-control analyses considering different combinations of answers. Multiple logistic regression models were used to this scope.The majority of participants had heard of skin cancer in the past (97.0%), correctly identified possible causes (58.6%) and names (64.2%) of skin cancers and judged appropriately the perceived danger of sunrays (70.2%) and skin cancer (80.6%). Nonetheless, students' behaviour was poor: only 13.5% stated to always use sun-safe practices and 39.1% never used any. Independent predictors of proper knowledge were: Lyceum school, and family or TV/media as information source; of appropriate perceived severity: Lyceum school, a darker skin type, and dermatologists as information source; of acceptable behaviour: female sex, a darker skin type, and dermatologists or general practitioners (GPs) as information source.Despite a fairly good knowledge about skin cancer and sun exposure, students' behaviour was unsatisfactory. Knowledge is not sufficient to produce a positive behaviour, as determinants of these two aspects are different. Dermatologists and GPs should be considered as key-figures for future multicomponent intervention strategies in this field.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are immunologically mediated, severe cutaneous adverse reactions involving cytotoxic T cells, natural killer cells and various mediators. In large studies, up to 15% of SJS/TEN occurred in patients with chronic corticosteroid use. It is unclear if this prior exposure to corticosteroids modified the disease course.To evaluate whether systemic corticosteroid usage prior to the onset of SJS/TEN modified the clinical course and outcome. If a disease-modifying effect is present, information from such an analysis may have implications on the therapeutic use of corticosteroids in SJS/TEN.This is a case-control study based on data collected in the EuroSCAR and RegiSCAR studies. Ninety-two cases of SJS/TEN with exposure to corticosteroids prior to the onset of disease, and 321 randomly selected SJS/TEN patients without prior exposure were included. Primary outcomes included progression of disease, disease severity and mortality. A secondary analysis of latency between the beginning of drug use and the onset of disease, based on exposure to a single high-risk drug, was also performed.On multivariate analysis, cases with prior exposure to corticosteroids had a longer progression of disease by 2·2 days [95% confidence interval (CI) 1·1-3·2]. The disease severity and mortality outcome were unaffected. In addition, there is evidence that corticosteroids delayed the onset of SJS/TEN in patients with exposure to high-risk drugs by 7·1 days (CI -0·2 to 14·5).The prior use of corticosteroids prolonged the period of disease progression without influencing the disease severity or mortality. In addition, when SJS/TEN is preceded by use of a single high-risk drug, the latency between the drug intake and the onset of SJS/TEN may also be increased. These findings suggest that corticosteroids have a mild impact on the course of SJS/TEN, and further studies are required to clarify any potential therapeutic effects.

Intraoperative transfusion of red blood cells (RBC) is associated with adverse outcome after LT in adult patients. This relationship in pediatric patients has not been studied in depth, and its analysis is the scope of this study. Forty-one variables associated with outcome, including blood product transfusions, were studied in a cohort of 243 pediatric patients undergoing a cadaveric LT between 2002 and 2009 at the General Hospital of Bergamo. Multivariate stepwise Cox proportional hazards models were adopted with adjustment by propensity scores to minimize factors associated with the use of blood products. Median age at transplant was 1.37 yr. In uni- and multivariate analyses, perioperative transfusion of FFP and RBC was an independent risk factor for predicting one-yr patient and graft survival. The effect on one-yr survival was dose-related with a hazard ratio of 3.15 for three or more units of RBC (p = 0.033) and 3.35 for three or more units of FFP (p = 0.021) when compared with 1 or no units transfused. The negative impact of RBC and FFP transfusion was confirmed by propensity score-adjusted analysis. These findings may have important implications for transfusion practice in the LT pediatric recipients.

A negative impact on vitiligo patients in terms of quality of life (QoL) has been suggested. The aim of this report was to study the QoL in a sample of Italian vitiligo patients by using the Dermatology Life Quality Index (DLQI) questionnaire.A sample of forty seven vitiligo subjects, identified among 34,740 potential conscripts resident in southern Italy underwent the Italian version of the DLQI questionnaire.The median total DLQI score was 1 (IQR: 2; mean: 1.82). In univariate analysis, DLQI total score was significantly influenced by the clinical course of vitiligo, disease extension over the body, and location on face and/or hands. Multivariate analysis using logistic stepwise regression showed that only the localization on the hands and on the face influenced significantly the mean DLQI.Our study conducted on a random sample of individuals affected by vitiligo selected from the general young male population in Italy, does not document a large impact of vitiligo on QoL. However, variations exist and the location of lesions on the face and/or hands may impact on QoL. Population-based studies are not affected by selection biases connected with seeking medical care and should be more widely performed.

Changes in financing health care delivery, including the adoption of diagnosis-related groups (DRG), has deeply influenced dermatological practice across Europe.To define the current status of dermatological care in the Lombardy Region, Italy, and compare the status of 2009 to that of 2001.Data were analysed from the annual reports of the Healthcare General Department of the Lombardy Region; legislative and administrative data were taken into consideration.Beds for inpatients in Dermatologic Wards decreased from 251.7 (2001) to 49.07 (2009). In 2009, a large proportion of inpatients with skin diseases were admitted to non-dermatological departments. Beds for day-hospital activities increased from 55.9 (2001) to 61.0 (2009), and the proportion of admissions for surgical purposes progressively increased. In addition, the complexity and quality of surgical procedures increased, in view of the need to justify a day-hospital admission. The total number of services for outpatients increased from 1,090,052 (2001) to 1,503,692 (2009); in addition, the weighted numbers (an indicator of complexity) increased from 2,117,000 (2001) to 3,644,032 (2009). The number of dermatologists with unlimited contracts decreased, and the number of low paid scholarship recipients and external consultants increased. Three of six medical faculties currently do not have a university department of Dermatology.Over the last decade, the number of patients hospitalized in Dermatological Departments has declined; moreover, patients hospitalized with dermatological disorders have been increasingly admitted to wards with a non-dermatologist attending physician.

It is stated that patients with vitiligo have an increased risk of developing autoimmune diseases.The aim of this study was to estimate the prevalence of autoantibodies or overt autoimmune diseases in a group of vitiligo patients examined among a sample deemed to be representative of the general population of young men living in southern Italy.A total of 60 vitiligo patients were identified among 34,740 potential conscripts visited to evaluate their fitness to compulsory service in Italian Navy, obtaining a prevalence of 0.17% (95% CI: 0.13-0.22), which was deemed the prevalence of vitiligo in the Italian general population of the same age and sex. Forty of these vitiligo patients underwent blood test including also the search of the main autoantibodies.Circulating autoantibodies were detected in 42.5% of subjects. Anti-thyroglobulin antibodies were documented in 27.5%, anti-thyroperoxidase in 22.5%, anti-smooth muscle in 17.3%, anti-nuclear, anti-mitochondrial and anti-gastric parietal cells in 2.5% respectively. Only in two cases (5%) an overt thyroid disease was diagnosed. No significant association between the extension of the skin involved ⁄ clinical course of the disease and circulating autoantibodies was detected. Circulating autoantibodies (particularly anti-thyroid antibodies) were statistically associated with a lower duration of the disease.In agreement with other studies, autoantibodies in the lack of clinical manifestations have been frequently observed in our vitiligo patients, especially during the early phase of the disease. The clinical significance of this finding seems to be limited, with the possible exception of thyroid disease, and it needs further exploration, through large cohort studies.

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Several new therapeutic options for psoriasis have been tested in clinical trials in recent years. Choice of comparator, study duration and outcome measures are critical for interpreting application of trial results to clinical practice.We examined whether these trial aspects have changed substantially in recent years in comparison with the past.A systematic search and evaluation of all randomized controlled trials (RCTs) for psoriasis published from January 2001 up to December 2006 in 14 leading medical and dermatological journals, compared with those published from 1977 to 2000.There were 140 RCTs of psoriasis in the period 2001-2006 and 249 in the period 1977-2000. The proportion of placebo-controlled studies increased from 44.6% to 69.3%. The median study duration increased from 7 weeks to 12 weeks. The proportion of studies adopting the Psoriasis Area and Severity Index score as an outcome increased from 30.6% to 57.7%, while the number of studies incorporating a quality of life measure increased from only one (0.4%) to 12 studies (7.7%). The proportion of studies sponsored by pharmaceutical companies increased from 61.0% to 73.7%.Despite the increased number of new options, the number of head-to-head comparative trials has decreased and most trials focus on short-term effects, probably reflecting the increased influence of industrial sponsorship on the research agenda.

To the authors' knowledge, limited data are available from Mediterranean populations concerning risk factors for malignant melanoma. A few Italian case-control studies have produced conflicting results regarding the association between malignant melanoma and pigmentary traits, sunburns, and melanocytic nevi.A case-control study was conducted within the framework of the Italian Group for Epidemiologic Research in Dermatology (GISED). Twenty-seven centers in the north and south of Italy participated. A total of 542 cases and 538 controls were entered onto the study. A standardized questionnaire was administered to cases and controls. Cases and controls also were examined by trained dermatologists who were required to count the number of melanocytic nevi (those measuringor = 2 mm and6 mm in greatest dimension, separately) and to make judgments regarding pigmentary traits.In the multivariate analysis, eye and skin color, propensity to sunburn, history of sunburns before age 15 years, and solar lentigines all were associated with malignant melanoma. In addition, the risk of melanoma increased with the number of melanocytic nevior = 2 mm. Nevi6 mm in greatest dimension had effects on risk that appeared to be independent from the effects of smaller nevi (2-6 mm).The results of the current study largely are similar to those obtained in northern European countries, the U.S., and Australia and provide further evidence of the importance of selected pigmentary traits, sun exposure, and the number of melanocytic nevi in the risk of cutaneous malignant melanoma.

Cutaneous manifestations are frequently reported in association with drug use. The aim of this study was to analyse the skin reactions reported to the spontaneous surveillance systems of four Italian regions (Friuli Venezia Giulia, Lombardy, Sicily and the Veneto), and correlate the reports with estimated drug consumption during the same period, paying particular attention to the reactions to antimicrobial agents and nonsteroidal anti-inflammatory drugs (NSAIDs).All of the adverse drug reactions (ADRs) reported spontaneously between January 1996 and December 1997 to the surveillance systems of four Italian regions (a total population of about 20 million people) were analysed by a panel of experts including dermatologists. On the basis of the Critical Term List of the World Health Organization (WHO), the reactions were classified as either serious or nonserious events. Drug consumption was expressed as a daily defined dose (DDD)/1000 inhabitants/day.A total of 2224 adverse skin reaction reports (44.7% of all of the reported ADRs) were identified, making a reporting rate of about 5.5 per 100 000 inhabitants/year. The female/male ratio was 1.58, and the reporting rate progressively increased with age. The drug categories with the highest number of cutaneous reactions were antimicrobials, followed by NSAIDs, analgesics and radiology contrast media. There was a total of 372 (16.9%) serious reaction reports, the most frequent being angioedema (171 cases), erythema multiforme (68 cases) and photosensitivity (37 cases). Co-trimoxazole, followed by the cephalosporins and fluoroquinolones, were associated with the highest consumption-related reporting rate among the antimicrobials, and aspirin and dipyrone among the NSAIDs and analgesics.Spontaneous reports from four Italian regions revealed that the skin was the organ most frequently affected by ADRs. The paper shows the validity of a regional decentralized system in Italy.

There is still controversy about whether all antiepileptic drugs are associated with the severe cutaneous reactions Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN). We have studied the role of antiepileptic drugs in SJS and TEN, taking into account potential cofactors that might confound or modify the risk.The case-control study in France, Italy, Germany, and Portugal identified cases of SJS/TEN that developed when the patient was not in hospital and were validated by an expert committee. Controls were patients admitted to the same hospital as the case for an acute illness or an elective procedure.73 (21%) of the 352 SJS/TEN cases and 28 (2%) of the 1579 controls reported intake of antiepileptic drugs. Among the 73 exposed SJS and TEN patients, 36 reported intake of phenobarbital, 14 of phenytoin, 21 of carbamazepine, 13 of valproic acid, and three of lamotrigine. Risk was highest in the first 8 weeks after onset of treatment. For individual antiepileptic drugs the univariate relative risk of SJS/TEN for 8 weeks or less of use was 57 (95% CI 16-360; multivariate risk 59 [12-302]) for phenobarbital; 91 (26-infinity) for phenytoin; 120 (34-infinity) for carbamazepine; 25 (5.6-infinity) for lamotrigine, and 24 (5.9-infinity) for valproic acid. The result for valproic acid was based on four case users, all of whom reported concurrent use of other associate drugs. The univariate relative risk for more than 8 weeks of use was 6.2 (2.4-17.0; multivariate risk 2.1 [0.5-9.3]) for phenobarbital, 1.2 (0-5.4) for phenytoin, 0.4 (0.02-2.1) for carbamazepine, and 7.0 (2.4-21.0; multivariate risk 2.0 [0.3-15.0]) for valproic acid.SJS and TEN are associated with short-term therapy with phenytoin, phenobarbital, and carbamazepine. The association with valproic acid seems to be confounded by concomitant short-term therapy with other causal drugs. Lamotrigine also has the potential for severe skin reactions. The period of increased risk is largely confined to the first 8 weeks of treatment.

The aim of this study was to analyse the reliability and the inter-observer agreement of dermoscopy in the diagnosis of melanocytic skin lesions. Nine dermatologists, with a different training experience and who routinely used dermoscopy in different hospitals in Italy, evaluated clinical and dermoscopy photographs of 15 melanocytic lesions (four invasive melanomas, four histologically common naevi, and seven naevi with histological atypia). A further series of dermoscopic photographs of 40 melanocytic lesions was evaluated to quantify inter-observer concordance in recognizing dermoscopic criteria. Compared to the true (histological) diagnosis, clinical diagnosis (categories: melanoma, common naevus, atypical naevus) was correct in 40% of cases (range, 27-53%). The percentage raised to 55% (40-73%) by the use of dermoscopy, with an average improvement of 15.6%. Concerning melanoma, clinical diagnosis resulted in a sensitivity of 41.9%, specificity of 77.8%, positive predictive value (PPV) of 36.1%, negative predictive value (NPV) of 81.8%. By using dermoscopy, an improvement of diagnostic performance was found (sensitivity 75%, specificity 88.8%, VPP 71.0%, VPN 90.7%). The inter-observer agreement in melanoma diagnosis, by using dermoscopy, was similar to that obtained by clinical examination (k statistics = 0.54 and 0.52, respectively). Concerning dermoscopic criteria, the best agreement among observers was found for pseudopods, a dermoscopic parameter related to the radial growth phase of melanoma. We conclude that dermoscopy is an useful tool for a non-invasive diagnosis of melanocytic skin lesions, improving the diagnostic performance compared to clinical examination.

Epidemiology, by imposing methodologic control and a numerate approach, can provide major contributions to"capture" and understand psoriasis. Certainly, more efficient research strategies in many areas are needed, and consensus should be reached on critical issues such as case classification and onset definition. Multidisciplinary research work and large study networks are requested to progress in a systematic way. One of the ultimate goals of epidemiologic investigations is to identify causes, with a view to developing preventive strategies. It is plausible that the possibility of modulating clinical expressiveness of the disease instead of treating active lesions may become available to clinicians (disability prevention) based on future etiologic research.

To conduct a prospective case-control study about causative factors of severe bullous erythema multiforme, Stevens-Johnson syndrome, and toxic epidermal necrolysis, we needed to define criteria for classifying the cases and standardize the collection of data so that cases could be reliably diagnosed according to this classification. Based on review of case histories and photographs of patients, a group of experts proposed a classification based on the pattern of erythema multiforme-like lesions (categorized as typical targets, raised or flat atypical targets, and purpuric macules) and on the extent of epidermal detachment. An atlas illustrating this classification that included photographs and schematic drawings was developed. We compared the evaluations of 28 cases by four nonphysicians relying on the atlas with the evaluations of the same cases by five experts not using the atlas to determine the usefulness of this atlas for classifying cases according to our nosologic schema.The following consensus classification in five categories was proposed: bullous erythema multiforme, detachment below 10% of the body surface area plus localized "typical targets" or "raised atypical targets"; Stevens-Johnson syndrome, detachment below 10% of the body surface area plus widespread erythematous or purpuric macules or flat atypical targets; overlap Stevens-Johnson syndrome-toxic epidermal necrolysis, detachment between 10% and 30% of the body surface area plus widespread purpuric macules or flat atypical targets; toxic epidermal necrolysis with spots, detachment above 30% of the body surface area plus widespread purpuric macules or flat atypical targets; and toxic epidermal necrolysis without spots, detachment above 10% of the body surface area with large epidermal sheets and without any purpuric macule or target. Using the atlas, the nonexperts showed excellent agreement with the experts.This study suggests that an illustrated atlas is a useful tool for standardizing the diagnosis of acute severe bullous disorders that are attributed to drugs or infectious agents. Whether the five categories proposed represent distinct etiopathologic entities will require further epidemiologic and laboratory investigations.

We report a case of segmental lentiginosis (unilateral lentiginosis), that is, asymmetric distribution of lentigines on one side of the body, in a 23-year-old woman. Lesions involved the right side of the face and the cervical region, mostly within the area of division of the trigeminal nerve. Histologic examination disclosed a lentiginous pattern as well as some nests of melanocytes at the dermal-epidermal junction (so-called jentigo pattern). Similar cases have been described in the literature under the term "zosteriform lentiginous nevus," which in our opinion makes for confusion since the same term has also been used to describe cases that fit the diagnostic criteria for speckled lentiginous nevus (nevus spilus).

We conducted a survey of clinical trials to assess the scientific evidences presented for the practical use of dinitrochlorobenzene, squaric acid dibutylester, and diphencyprone in the treatment of alopecia areata. Twenty-six papers published between January 1977 and January 1988, in English, French, and Italian were selected. We used a standardized protocol of evaluation, which focused principally on the reporting of methods. Twelve papers were uncontrolled studies. Of the controlled studies, 11 had a self-controlled design, two studies involved the use of parallel concurrent controls, and seven were randomized trials. With regard to criteria for entry, follow-up schedules, and criteria for evaluation of response to treatment, the studies were scored generally poorly; therapeutic regimen, patients' characteristics, withdrawals, and description of side effects in these studies were rated more highly. In light of our results, further and better-designed studies are needed for acceptance of dinitrochlorobenzene, squaric acid dibutylester, and diphencyprone in current therapy.