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Background: Dupilumab, a fully human monoclonal antibody targeting the alpha subunit of IL-4 was recently approved for the treatment of moderate-to-severe atopic dermatitis (AD) in adult patients. Objective: To assess dupilumab effectiveness and safety in adults with moderate-to-severe AD in a real-life Italian multicentre retrospective cohort. Methods: Adult moderate-to-severe AD patients, referring to 39 Italian centers, received dupilumab in the context of a national patient access program. Disease assessment was performed at baseline, after 4 and 16 weeks of treatment using Eczema-Area-and-Severity-Index (EASI) score, itch and sleep numerical-rating-score (itch-NRS, sleep-NRS) and Dermatology-Life-Quality-Index (DLQI). Results: A total of 109 (71 M/38F) patients was studied. There was a significant reduction in EASI score, itch-NRS, sleep-NRS and DLQI from baseline to week 4 and a further significant decline to week 16. EASI 50, EASI75 and EASI90 were achieved by 59.6%, 28.4% and 9.3% of patients at 4 weeks and by 87.2%, 60.6% and 32.4% of them at 16 weeks, respectively. Adverse events were experienced by 19.2% (21/109) of the patients and they were all mild in intensity, being conjunctivitis the most common side effect. Conclusions: Dupilumab significantly improved disease severity, pruritus, sleep loss and quality of life with an acceptable safety profile.

Background and aim: Over 80% (365/454) of the nation’s centers participated in the Italian Society of Nephrology COVID-19 Survey. Out of 60,441 surveyed patients, 1368 were infected as of April 23rd, 2020. However, center-specific proportions showed substantial heterogeneity. We therefore undertook new analyses to identify explanatory factors, contextual effects, and decision rules for infection containment. Methods: We investigated fixed factors and contextual effects by multilevel modeling. Classification and Regression Tree (CART) analysis was used to develop decision rules. Results: Increased positivity among hemodialysis patients was predicted by center location [incidence rate ratio (IRR) 1.34, 95% confidence interval (CI) 1.20–1.51], positive healthcare workers (IRR 1.09, 95% CI 1.02–1.17), test-all policy (IRR 5.94, 95% CI 3.36–10.45), and infected proportion in the general population (IRR 1.002, 95% CI 1.001–1.003) (all p < 0.01). Conversely, lockdown duration exerted a protective effect (IRR 0.95, 95% CI 0.94–0.98) (p < 0.01). The province-contextual effects accounted for 10% of the total variability. Predictive factors for peritoneal dialysis and transplant cases were center location and infected proportion in the general population. Using recursive partitioning, we identified decision thresholds at general population incidence ≥ 229 per 100,000 and at ≥ 3 positive healthcare workers. Conclusions: Beyond fixed risk factors, shared with the general population, the increased and heterogeneous proportion of positive patients is related to the center’s testing policy, the number of positive patients and healthcare workers, and to contextual effects at the province level. Nephrology centers may adopt simple decision rules to strengthen containment measures timely.

BACKGROUND The anti-tumour necrosis factor (TNF)-α adalimumab is the only licenced biologic for moderate-to-severe hidradenitis suppurativa (HS). No predictors of response have been identified so far. OBJECTIVES To identify clinical parameters predicting response to adalimumab and confirm its efficacy/safety. METHODS The data of 389 patients with HS treated with adalimumab in 21 Italian centres were reviewed. Sex, age at onset/diagnosis/baseline, body mass index, smoking, phenotype, previous treatments, concomitant antibiotics and 'therapeutic delay', defined as the time from HS onset to adalimumab initiation, were assessed. Response to adalimumab and its impact on quality of life (QoL) were evaluated using the Hidradenitis Suppurativa Clinical Response (HiSCR) and the Dermatology Life Quality Index (DLQI) or the Visual Analogue Scale for pain (VAS pain), respectively. Logistic regression analysis was performed. RESULTS The therapeutic delay correlated to lack of response to adalimumab at week 16 [odds ratio (OR) 1·92 for therapeutic delay > 10 years; 95% confidence interval (CI) 1·28-2·89; P = 0·0016). HiSCR was achieved in 43·7% and 53·9% patients at week 16 and 52, respectively. Significant reductions in both DLQI and VAS pain were found between week 16 vs. baseline (P < 0·0001 for both) and week 52 vs. baseline (P < 0·0001 for both). Previous immunosuppressants inversely correlated to HiSCR at week 52 (OR = 1·74, 95% CI 1·04-2·91, P = 0·0342). CONCLUSIONS Inverse correlation between therapeutic delay and clinical response was found, supporting early adalimumab use and providing evidence for a 'window of opportunity' in HS treatment. Adalimumab efficacy and safety were confirmed, along with patients' QoL improvement. Immunosuppressants could negatively influence the response to adalimumab inducing a switch to non-TNF-α-driven pathways.

Background Determining the trends and treatment outcomes of TB in health facilities is very important to inform better management of the disease and control efforts. Nevertheless, data from the rural, urban and suburban settings of Ethiopia show variability and inconsistency. This study was designed to evaluate trends and treatment outcomes of tuberculosis patients at Tepi Health Center and to identify the predictors of unsuccessful treatment outcome. Method Retrospective review of TB cases registered in Tepi health center between June 2011 and May 2018 was conducted using data extracted from medical records of TB patients. Structured data extraction form was prepared and used to extract socio-demographic, clinical and outcome data of study cases. Case definition and the treatment outcome of patients were ascertained and reported in accordance with World Health Organization guideline. Binary logistic regression model was fit to identify predictors of unsuccessful outcome. Results A total of 1651 TB patients registered at Tepi Public Health Center in between June 2011 and May 2018, were included in the study. Of all 924 (56%) were males and 1053 (63.8%) cases were in between the age range of 15 and 35 years. HIV-status of 1019 TB cases were unknown and 189 (11.4%) of participants were HIV-positive. Four hundred fifty seven (27.7%) cases were diagnosed with extra pulmonary TB (EPTB) and 1194 (72.3%) were pulmonary TB patients out of which, 376 (73.6%) were smear-positive pulmonary TB (PTB+). Overall treatment success rate (TSR) of patients was 80.4% (1327/1651), while it was 84.8% (134/158), 80.2% (410/511), and 78.3% (148/189) among the transfer-in, PTB+, and HIV + cases, respectively. Higher numbers of successful treatment outcomes were recorded among new patients (82.7%) and EPTB cases (84.7%). The cure rate were 73.6% (376/511) and 18% (34/189) among patients with PTB+ and HIV+, respectively. Multiple logistic regression analysis indicated that residence sites (OR 0.763 (0.584, 0.996) and TB/HIV co-infection (OR 0.661 (0.444, 0.985), were significantly associated with the treatment outcome. Rural residence was 27.1% less likely to have successful treatment. There was significant heterogeneity in the odds of having successful treatment outcomes across years of initiating treatment. Conclusion Treatment success rate among study cases was lower than the WHO’s target and further efforts like availability of TB clinics in nearby sites and reducing rate of HIV infection should be made to improve rate of successful treatment outcome.

This corrects the article DOI: 10.23736/S0392-0488.17.05584-5.

none 11 BACKGROUND/AIMS: Iodide efflux from thyroid cells into the follicular lumen is essential for the synthesis of thyroid hormones, however, the pathways mediating this transport have only been partially identified. A calcium-activated pathway of iodide efflux has long been recognized, but its molecular identity unknown. Anoctamin 1 (ANO1) is a calcium-activated chloride channel (CaCC), and this study aims to investigate its contribution to iodide fluxes in thyroid cells. METHODS: RT-PCR, immunohistochemistry, and live cell imaging with the fluorescent halide biosensor YFP-H148Q/I152L were used to study the expression, localization and function of ANO1 in thyroid cells. RESULTS: ANO1 mRNA was detected in human thyroid tissue and FRTL-5 thyrocytes, and ANO1 protein was localized to the apical membrane of follicular cells. ATP induced a transient loss of iodide from FRTL-5 cells that was dependent on the mobilization of intracellular calcium, and was inhibited by CaCC/ANO1 inhibitors and siRNA against ANO1. Calcium-activated iodide efflux was also observed in CHO cells over-expressing the Sodium Iodide Symporter (NIS) and ANO1. CONCLUSION: ANO1 in thyrocytes functions as a calcium-activated channel mediating iodide efflux, and may contribute to the rapid delivery of iodide into the follicular lumen for the synthesis of thyroid hormones following activation by calcium-mobilizing stimuli. Iosco C;Cosentino C;Sirna L;Romano R;Cursano S;Mongia A;Pompeo G;di Bernardo J;Ceccarelli C;Tallini G;Rhoden KJ Iosco C;Cosentino C;Sirna L;Romano R;Cursano S;Mongia A;Pompeo G;di Bernardo J;Ceccarelli C;Tallini G;Rhoden KJ

Recent studies have shown that biological drugs approved for treating psoriasis and psoriatic arthritis are not effective in all patients, and that variations in the genome have been associated with different clinical responses or side effects. HLA-Cw6 gene is associated with more severe and early-onset psoriasis. Recent reports have shown that HLA-Cw6 status predicts efficacy of some biologic treatments in psoriasis patients. The Phase 3b SUPREME study (NCT02394561) demonstrated the efficacy of secukinumab in patients with moderate-to-severe plaque-type psoriasis, irrespective of HLA-Cw6 status at week 24. This article is protected by copyright. All rights reserved.

IntroductionAuthorship parasitism (ie, no authors affiliated with the country in which the study took place) occurs frequently in research conducted in low-income and middle-income countries, despite published recommendations defining authorship criteria. The objective was to compare characteristics of articles exhibiting authorship parasitism in sub-Saharan Africa to articles with author representation from sub-Saharan African countries.MethodsA bibliometric review of articles indexed in PubMed published from January 2014 through December 2018 reporting research conducted in sub-Saharan Africa was performed. Author affiliations were assigned to countries based on regular expression algorithms. Choropleth maps and network diagrams were created to determine where authorship parasitism occurred, and multivariable logistic regression was used to determine associated factors.ResultsOf 32 061 articles, 14.8% (n=4754) demonstrated authorship parasitism, which was most common among studies from Somalia (n=175/233, 75.1%) and Sao Tome and Principe (n=20/28, 71.4%). Authors affiliated with USA and UK institutions were most commonly involved in articles exhibiting authorship parasitism. Authorship parasitism was more common in articles: published in North American journals (adjusted OR (aOR) 1.26, 95% CI 1.07 to 1.50) than in sub-Saharan African journals, reporting work from multiple sub-Saharan African countries (aOR 8.41, 95% CI 7.30 to 9.68) compared with work from upper-middle income sub-Saharan African countries, with 10 authors, and was less common in articles published in French (aOR 0.60, 95% CI 0.41 to 0.85) than English.ConclusionsAuthorship parasitism was common in articles reporting research conducted in sub-Saharan Africa. There were reliable predictors of authorship parasitism. Investigators and institutions in high-income countries, as well as funding agencies and journals should promote research from sub-Saharan Africa, including its publication, in a collaborative and equitable manner.

BACKGROUND The epidemiologic trends of cutaneous melanoma are similar in several countries with a Western-type lifestyle, where there is a progressively increasing incidence and a low but not decreasing mortality - even increasing in selected cases, especially in the older age groups. Also in Tuscany there is a steady rise in the incidence with prevalence of in situ and invasive thin melanomas, with also an increase of thick melanomas. It is necessary to reduce the frequency of thick melanomas to reduce specific mortality. The objective of the current survey has been to compare, in the Tuscany population, by a case-case study, thin and thick melanoma cases, trying to find out those personal and tumor characteristics which may help to customize preventive interventions. METHODS The study included nine centers involved in the melanoma diagnosis. A consecutive series of incident invasive melanomas diagnosed in a period of about 18 months (July 2010 to December 2011) was collected and matched according in a ratio of one thick melanoma (cutoff thickness: 1 mm) every two thin melanomas. The investigators filled in a questionnaire on patients' self-reported sun exposure, way of melanoma detection, awareness and performance of self-skin examination, as well as propensity to prevention in general. RESULTS The results of this survey confirm that older age and the lower education level are associated with a later detection. The habit of performing skin self-examination is crucial in the early diagnosis of thick melanoma. The results of this survey seem to suggest that population aged over 50 years, with few total and few atypical nevi, and limited sun exposure and burning are at higher risk of late diagnosis. It can be assumed that part of the population is not effectively reached by prevention campaigns because they do not recognize themselves as being at risk for skin cancers. CONCLUSIONS In order to achieve a higher rate of early diagnosis of skin melanoma, a new strategy must be implemented. It could be useful to rethink educational campaigns - which seem to unintentionally leave out subjects more at risk for melanoma - and to renew the active involvement of the general practitioners.

Background: Adrenal incidentalomas (AIs) are a “disease of modern technology” with a prevalence of ~5%, expected to increase as imaging modalities become more sensitive and widely available. While the majority of AIs are benign, ~15% are malignant or associated with hormone over secretion, thus all AIs require prompt investigation. The recommended diagnostic testing for AIs is validated in healthy outpatient subjects, with no established algorithm for the inpatient/critical illness setting. Clinical Case: A 66 year-old male with hypertension and type 2 DM, recent myocardial infarction, presented in cardiogenic shock. His course was complicated by an episode of cardiac arrest with successful resuscitation. Due to inotrope and intra-aortic balloon pump dependency, he was urgently evaluated for left ventricular assist device (LVAD). A non-contrast abdominal CT obtained during pre-LVAD workup, showed a 2.4 x 1.9 cm right adrenal nodule of indeterminate density. The review of systems was positive for erectile dysfunction, and negative for easy bruising, facial plethora, fractures, proximal muscle weakness or weight changes. Physical examination revealed absence of Cushingoid features. Laboratory testing showed an abnormal overnight 1mg dexamethasone suppression test (DST) (12.1 mcg/dL , n: < 1.8 mcg/dL), elevated ACTH (75pg/mL, n: 7-69pg/mL), elevated AM serum cortisol (40.7 mcg/dL, n: 5-23 mcg/dL), elevated PM serum cortisol (21.7 mcg/dL, n: 3-15 mcg/dL). He had normal 24-hour urinary free cortisol, serum DHEAS, plasma renin activity and aldosterone concentration. Repeat adrenal CT scan showed a 1.6 x 1.9 cm R adrenal nodule, non-contrast density 33 HU, venous phase 99 HU and delayed phase 55 HU (washout 45%) concerning for pheochromocytoma. However, plasma and urine metanephrines and catecholamines were normal. The absence of Cushingoid features and evidence of ACTH dependent hypercortisolism with normal diurnal variation (despite an abnormal DST) ruled out Cushing’s syndrome, and the patient successfully underwent LVAD surgery. A literature review revealed only 2 AI cases evaluated during critical illness. While both cases had an abnormal DST without normal diurnal variation, only one case had similar ACTH dependent hypercortisolemia. Conclusion: This case illustrates the dilemma surrounding the evaluation of AIs in the setting of critical illness, the lack of inpatient/critical illness specific guidelines and the importance of clinical assessment. Furthermore, it suggests a possible diagnostic approach that can be considered in similar clinical situations.

Psoriasis (PSO) is traditionally defined as an immune-mediated, inflammatory dermatological disease characterized by a chronic-relapsing course and associated with multifactorial inheritance (genetic predisposition and influence of various environmental factors). Considered until recently a dermatological disease only, today PSO is correctly known as a systemic one because of the involvement of multiple organs with important impact on social life and relationships. PSO is found in the 0.3-4.6% of the world's population, while its prevalence in the Italian population is estimated at 2.8%. Therefore, if we consider that in Tuscany more than 100,000 people out of 3,672,202 suffer of psoriasis, it is of paramount importance to focus on a shared clinical and therapeutic protocol to manage the disease. With the aim of ensuring diagnostic-therapeutic suitability, high levels of care and standardization of treatment, a unique clinical-therapeutic management model has been developed and validated in Tuscany, involving all accredited regional dermatological centers. Among the possible alternatives to be implemented in the treatment of patients with mild, moderate-severe psoriasis, UVBnb phototherapy is widely used alone or in association with other systemic and non-systemic devices. Despite this, there is still no universally shared therapeutic protocol. In this context the CO.FO.TO working group (Consensus Fototerapia Toscana) is born with the aim of defining and validating the main guidelines in the use of phototherapy with UVBnb in psoriasis; the guidelines are based both on the real-life experience of the different centers of reference in the region and on the revision of the recent literature.

Background Understanding genetic variations is important in predicting treatment response and forms the basis for identifying new pharmacogenetic and pharmacogenomic targets for psoriasis treatment. There are limited data on the efficacy of secukinumab in relation to genetic markers. Objectives To evaluate the efficacy and safety of secukinumab 300 mg in HLA-Cw6-positive (Cw6-POS) and HLA-Cw6-negative (Cw6-NEG) patients with moderate-to-severe chronic plaque-type psoriasis. Methods SUPREME was a 24-week, phase IIIb study with an extension period up to 72 weeks. Primary end point was Psoriasis Area Severity Index (PASI) 90 response rate after 16 weeks. Results In total, 434 patients were recruited: 185 (42·6%) were Cw6-POS and 246 (56·7%) were Cw6-NEG (three not assessed). Mean ± SD age was 45·2 ± 13·2 years (Cw6-POS 42·7 ± 13·1; Cw6-NEG 47·2 ± 12·9). The baseline PASI score was comparable between the cohorts [Cw6-POS 20·7 ± 8·99; Cw6-NEG 21·5 ± 9·99 (P = 0·777)]. At week 16, PASI 90 was achieved in 80·4% of Cw6-POS and 79·7% of Cw6-NEG patients (difference 0·76; 95% confidence interval -7·04 to 8·23). No differences in absolute PASI at week 16 (Cw6-POS 1·36 ± 3·58; Cw6-NEG 1·18 ± 2·29) were observed. The overall safety profile of secukinumab was consistent with that previously reported. No statistically significant difference was detected in the rate of treatment-emergent adverse events [Cw6-POS 42·7%; Cw6-NEG 49·6% (P = 0·295)]. A high PASI 90 response was achieved with secukinumab with a fast reduction in absolute PASI. Conclusions Determination of HLA-Cw6 status for secukinumab therapy is unnecessary, as it is highly effective regardless of HLA-Cw6 status.

Purpose Medication errors in oncology may cause severe damage to patients, professionals, and the environment. The Italian Ministry of Health issued Raccomandazione 14 to provide guidelines for prevention of errors while using antineoplastic drugs. This work aimed at analyzing Raccomandazione 14 through the different viewpoints of the hospital pharmacist, the nurse, the oncologist, and the hospital director. Methods Twenty-seven Italian healthcare organizations participated in a self-assessment survey evaluating compliance with Raccomandazione 14 within the oncology, hematology, and pharmacy departments. Results The self-assessment results showed a general acknowledgement of the need for centralized management of anticancer agents. The specific responsibility of the pharmacist on the centralized management of anticancer drugs from preparation to disposal emerged as a critical point. The nurse, beyond the skills in drug administration and prevention of extravasation, also plays a fundamental role in educating and supporting the patient. The physicians, who are attentive to scientific, clinical, and regulatory criteria in prescribing and monitoring the therapies, are called upon to improve awareness on the importance of sharing standardized procedures with other professionals, to minimize medication error occurrence. The implementation of a complete computerized management from prescribing to drug administration and follow-up was highlighted. Multidisciplinary groups were constituted across the nation by professionals dedicated to the implementation of electronic health records and drug history and medical reconciliation processes. Conclusions Our analysis of the Ministerial Raccomandazione 14 urges implementation of the resources for ensuring quality and safety during prescription, preparation, and administration of anticancer drugs.

Pregnancy represents a unique physiologic period, with significant implications on the cardiovascular system (Wanga S, Silversides C, Dore A, Can J Cardiol 32:78–85, 2016). Although rare, aortic disease is a known potential complication of pregnancy. Aortic dissection and rupture can be of particular concern for pregnant women with underlying connective tissue disorders (Kamel H, Roman MJ, Pitcher A, and Devereux RB, Circulation 134:527–33, 2016). In the next chapter, we will explore aortic disease in pregnancy, including pathophysiology, epidemiology, and specific conditions. We will pay particular interest to aortic dissection and rupture, given the increased incidence in pregnancy, and the devastating potential consequences.

Background: Autoimmune comorbidities and circulating autoantibodies have been observed in vitiligo patients, but differences in rate are present according to countries in which the studies were performed, perhaps owing to ethnic diversities or different trigger factors. Objective: To estimate the prevalence of circulating autoantibodies and overt autoimmune diseases in a fairly large sample of Italian vitiligo patients. Methods: 175 outpatients affected by vitiligo and referred to nine dermatological centers were included in the study. Patients were offered routine blood test, serological testing for thyroid function and search for autoantibodies. Results: At least one circulating autoantibody was detected in 61 (41.8%) of 146 subjects who underwent laboratory tests. Anti-thyroperoxidase (25.6%), anti-thyroglobulin (23.4%), antinuclear antibodies (16.8%) and anti-gastric parietal cell antibodies (7.8%) were the most noticed autoantibodies. 74 (41.5%) autoimmune comorbidities, mainly autoimmune thyroiditis (37%), were reported. Conclusion: The prevalence of autoimmune comorbidities and circulating autoantibodies in this study was in agreement with other surveys conducted on Caucasian patients.

Objective To translate and perform the cultural adaptation of the tool Functional Assessment of Chronic Illness Therapy – Cervical Dysplasia (FACIT-CD) to the Portuguese language. Methods A descriptive cross-sectional study, with translation and cultural adaptation of the assessment tool performed according to international guidelines and the Functional Assessment of Chronic Illness Therapy (FACIT) protocol group. It involved eight experts, six from Brazil, one from Portugal and one from the United States. After translation and back-translation of the tool, the semantic analysis process was carried out. We randomly included 20 women aged between 18 and 70 years with altered cervical cytology exam, seen at the Department of Prevention and Gynecologic Oncology - Hospital de Câncer de Barretos. Results The sample consisted of women with low education level. In the first pre-test, ten women participated and half of them considered the questions CD1, CD2 and CD3 as difficult, because they did not understand the meaning of the term “pelvic area”. The question CD5, “I worry about spreading the infection”, was also considered difficult to understand by five women. After the reconsideration of the expert committee and FACIT group, the second pre-test was performed. At this stage, we concluded that the previously raised understanding problems had been solved. Conclusion The translated version of FACIT-CD in universal Portuguese language is equivalent to the original version in English and was easily understood by patients with cervical intraepithelial neoplasia. RESUMO Objetivo Traduzir e adaptar o instrumento Functional Assessment of Chronic Illness Therapy – Cervical Dysplasia (FACIT-CD), para a língua portuguesa. Métodos Estudo descritivo, transversal, com metodologia de tradução e adaptação cultural de instrumento de avaliação, realizado por meio de diretrizes internacionais e seguindo o protocolo do grupo Functional Assessment of Chronic Illness Therapy (FACIT). Envolveu oito especialistas, sendo seis nativos do Brasil, um de Portugal e um dos Estados Unidos. Ao término do processo de tradução e retrotradução, deu-se início ao processo de análise semântica. Foram incluídas aleatoriamente 20 mulheres entre 18 e 70 anos com exame de citologia cervical alterado, atendidas no Departamento de Prevenção e Ginecologia Oncológica do Hospital de Câncer de Barretos. Resultados A amostra foi composta por mulheres com baixa escolaridade. No primeiro pré-teste participaram dez mulheres, sendo que a metade considerou as questões CD1, CD2 e CD3 difíceis por não compreenderem o significado do termo “região pélvica”. A questão CD5, “Estou preocupada em disseminar a infecção”, também foi considerada de difícil entendimento por cinco mulheres. Após as reconsiderações do comitê de especialistas e do grupo FACIT, foi realizado o segundo pré-teste. Nesta fase, pode-se concluir que os problemas de entendimento anteriores foram resolvidos. Conclusão A versão traduzida do FACIT-CD é equivalente à versão original em inglês e em língua portuguesa universal, sendo facilmente compreendida pelas pacientes com neoplasia intraepitelial cervical.

Background: The occurrence of cervical intraepithelial neoplasia (CIN) is associated with changes in health-related quality of life, including psychological factors, such as fear and shame, and changes in sexuality and sexual satisfaction, such as decreased sexual desire and frequency of sexual intercourse. Personal relationships are the most affected because CIN is sexually transmitted and many women tend to blame their partner for disease transmission. The aim of this study was to evaluate the psychometric properties of the FACIT-CD questionnaire in Brazilian women diagnosed with CIN. Methods: The properties of the FACIT-CD questionnaire were tested on a sample of 439 women seen at the Department of Prevention of Barretos Cancer Hospital, including 329 patients who were diagnosed with CIN and 110 women who were not diagnosed with the disease. The analysed parameters included internal consistency (Cronbach's alpha), reproducibility (intraclass correlation coefficient), structural validity, convergent validity (correlation with the SF-12 and EORTC QLQ-CX24 questionnaires), discriminant validity (according to disease status, and self-rating of health), sensitivity, and responsiveness. Results: The Cronbach alpha values of the FACIT-CD scales were higher than 0.70 with the exception of the relationship scale (0.66). The FACIT-CD reproducibility was satisfactory, with variation in the intraclass correlation coefficients ranging between 0.50 and 0.83, although the 95% confidence interval (CI) was lower than 0.40 (0.33-0.64) on the treatment satisfaction scale. Regarding structural validity, only one item on the physical well-being scale was not kept in the original domain. The expected correlations between the FACIT-CD and SF-12 were not confirmed, whereas the correlations between the FACIT-CD and EORTC QLQ-CX24 were confirmed. The questionnaire was able to discriminate the groups according to disease status and self-rating of health. The sensitivity was low for the relationship scale and moderate for the other scales. The responsiveness of the FACIT-CD questionnaire varied between the groups that denominate the self-perception of health as no change, improvement or worsening. Conclusion: Our results are encouraging and indicate that the FACIT-CD questionnaire is a promising tool for the analysis of the quality of life of women with CIN., The postdoctoral fellowship was supported by Sao Paulo Research Foundation (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo - FAPESP, Sao Paulo, Brazil). Process number: FAPESP 2014/10158-3. The funding body had no role in the design of the study and collection, analysis and interpretation of data and in writing the manuscript., info:eu-repo/semantics/publishedVersion

Background Psoriasis is traditionally defined as an inflammatory chronic-relapsing disease of the skin. As widely demonstrated, this disease is also associated with multiple comorbidities: arthropathy, inflammatory bowel disease, metabolic, cardiovascular, ocular and psychological disorders. The disease also has a significant impact on patients' quality of life, whose work ability decreases considerably with clear consequences for the social costs. Therefore, if we consider that in Tuscany, more than 100,000 people out of 3,672,202 suffer from psoriasis, it is of paramount importance focusing the attention on a rational model of clinical and therapeutic management of the disease. All the leading experts in Tuscany have come together with the aim of defining unanimously accepted regional guidelines for the diagnosis, treatment, follow-up and management of psoriasis, and of providing practical guidance/protocol on diagnosis, treatment, follow-up and management of special cases of moderate-to-severe plaque psoriasis. Methods In a working group formed ad hoc, the main topics have been discussed and approved by plenary vote. Results Diagnosis must include a proper general health condition overview, a careful evaluation of skin and joints, the assessment and management of other comorbidities and the definition of disease severity. With regards to the therapy the best time to start a systemic treatment, the therapeutic goal, the most appropriate drug and blood tests to be performed in case of moderate severe-psoriasis have been taken into account. During follow-up, proper monitoring of systemic therapy and its management in the long term has also been suggested. Eventually, the experts have addressed the problem of how to manage the disease in special conditions, such as during surgery, pregnancy, in children and in case of infections (HBV, HCV, HIV). Conclusions The main aim of this Consensus was to find agreement on the criteria for diagnosis, treatment and follow-up of psoriasis, shared by all the Dermatologic Therapy Units of Tuscany. A need to create an easier way for the patient to access specialized dermatology outpatient services, and to reduce the waiting list and costs related to the management of psoriasis has been stressed. Most importantly, during the Consensus all of the participants agreed on the central role of the patient, and on the need of a multidisciplinary management of the disease which requires communication among specialists and regional centers in order to build on existing experience.

Background: It is believed that vitiligo has an impact on the overall patient quality of life (QoL). Objective: To estimate QoL in a fairly large sample of Italian vitiligo patients by using the Dermatology Life Quality Index (DLQI) questionnaire. Methods: One hundred and sixty-one vitiligo patients referred to 9 dermatological centers were offered to participate by filling in the Italian version of the DLQI questionnaire. Results: The mean total DLQI score was 4.3 (SD ±4.9; range: 0-22). In multivariate analysis, DLQI >5 was associated with female gender, stability of the disease over time and involvement of the face at disease onset. Conclusions: The impairment of QoL is overall limited in Italian vitiligo patients, especially if it is compared with results from other available studies. This could be due to cultural and ethnic characteristics of the sample.

The article describes the development of a numerical material model of ceramic matrix composite (CMC) reinforced by bundles of thousands of short carbon fibres and produced by means of a liquid silicon infiltration process. The objective of the article is the development of a numerical mesoscale model that considers the material as a simple bi-phasic composite constituted by an isotropic matrix with differently sized inclusions. The distinctive material microstructure that complicates the development of such a model is presented and the issues represented by the generation of the finite element models and by the identification of the effective properties of the constituent phases are discussed. In the presented approach, models are generated by numerically simulating the packing of bundles and phases are identified by means of tests and numerical analyses, which are performed on long fibre-reinforced specimens and on specimens subjected to a thermal process for the elimination of carbon reinforcement. The approach is applied to find out the parameters of a homogenized orthotropic model for CMC plates. The obtained results show that the numerical packing simulations can generate models with a realistic distribution of size, shape and orientation of the bundles. The mesoscale model and the phase properties identified by the proposed numerical and experimental procedure are validated by considering the stiffness of standard CMC specimens obtained in three-point bending tests. According to the results, the developed methodologies can be considered as a promising approach for a reliable prediction of short fibre-reinforced CMC elastic properties.

TPS396 Background: Currently, the challenge is to reach a consensus on the best way to sequence different therapies for mCRPC patients (pts) in terms of efficacy and tolerability. Radium223 is a novel survival-prolonging targeted-α-therapy, but timing of its use in the treatment sequence of mCRPC remains an unanswered question, given the wide availability of therapeutic options Methods: This is a prospective, multicenter, randomized phase II study in symptomatic bone-only mCRPC pts who progressed after any androgen deprivation therapy, abiraterone and/or enzalutamide. Pts will be randomized 1:1 to receive radium223 initially followed by docetaxel+prednisone at the time of progression, or docetaxel+prednisone initially followed by radium223 at progression. In both treatment arms, the second step will be optional according to clinical evolution of disease (clinical deterioration and/or development of visceral metastases); however, each patient that will not enter in the second step will be still evaluable for the objectives of the study. No stratification factor will be used for randomization. Primary endpoint is to determine the better tolerated sequencing between radium223 and docetaxel in terms of health-related quality of life after completing the sequence and separately after each treatment. Based on primary endpoint, considering a type I error 0.1, type II error 0.2, proportion of responder pts in the standard arm 0.1 and in the experimental arm of 0.4, and assuming 10% loss to follow-up, a total of 70pts (35 for each arm) will be enrolled in the study. The study duration will be 36months; 15months of accrual, and 1 year of follow-up on the last participant enrolled. Secondary endpoints are to compare overall/progression-free/total progression free survival in pts treated with sequential therapy between radium223 and docetaxel. Additional secondary objective is to identify predictive factors for radium223 therapy, including potential circulating biomarkers through the plasma collection from all enrolled pts at different timepoints and the early prognostic role of functional imaging, such as PET with choline and/or PSMA. Clinical trial information: NCT03230734.

Sweet’s syndrome, or acute febrile neutrophilic dermatosis, is an uncommon severe cutaneous condition, not previously associated with allopurinol therapy. We describe the case of an 87-year-old woman with hyperuricemia who developed classic Sweet’s syndrome manifestations 8 days after being treated with allopurinol. Patient’s symptoms included fever, painful edema in the hands and lower limbs with non-pruritic erythematous plaques topped by pus-filled skin blisters, right eye conjunctivitis, splenomegaly and joint pain. At the emergency department, blood tests showed neutrophilic leukocytosis, inflammatory state and altered liver function. During hospitalization, she received unsuccessful treatments with two different antibiotics (namely ceftriaxone and levofloxacin), while treatment with intravenous methylprednisolone produced a rapid clinical remission of symptoms, cutaneous lesion pain improvement, normalization of her body temperature and her blood values returned to normal. Use of the Naranjo adverse drug reaction probability scale indicated a probable relationship between the patient’s development of Sweet’s syndrome and allopurinol therapy. Because the signs and symptoms of Sweet’s syndrome resemble an infectious process, the correct diagnosis may be delayed and inappropriate treatment regimen with antibiotics may often precede glucocorticoid therapy.

Psoriasis is a chronic and relapsing inflammatory skin disease, clinically characterized by erythematous and scaly plaques. Treatment approach is mainly driven by disease severity, though several factors should be considered in order to identify the optimal therapeutic choice. Mild psoriasis may be treated with a wide array of topical agents including corticosteroids, vitamin D analogs, keratolytics, and calcipotriol/betamethasone propionate compound. Because guidelines may not provide practical indications regarding the therapeutic approach, the use of topical agents in psoriasis is more individually tailored. In order to homogenize the standard of care, at least in a local setting, we collected the real-life-based recommendations for the use of topical therapies from an expert panel, the Tuscany Consensus Group on Psoriasis, representing all leading centers for psoriasis established in Tuscany. With this document, this consensus group sought to define principles guiding the selection of therapeutic agents with straightforward recommendations derived from a real-life setting.

Background: Diabetic patients are at particular high risk of developing ischemic heart disease and treatment with statins have shown significant benefit in reducing ischemic events within this population. Unfortunately, racial and gender inequities in the provision of medical care remain a

Author(s): Shackelford, J Ryan; Sirna, Megan; Mangurian, Christina; Dilley, James W; Shumway, Martha | Abstract: ObjectivePersons with serious mental illness have increased rates of chronic medical conditions, have limited access to primary care, and incur significant health care expenditures. Few studies have explored providing medical care for these patients in the ambulatory mental health setting. This study describes a real-world population of mental health patients receiving primary care services in a community mental health clinic to better understand how limited primary care resources are being utilized.MethodChart review was performed on patients receiving colocated primary care (colocation group, N = 143) and randomly chosen patients receiving mental health care only (mental-health group, N = 156) from January 2006 through June 2011. Demographic and mental and physical health variables were assessed.ResultsCompared to the mental-health group, the colocation patients had more psychiatric hospitalizations (mean = 1.07 vs 0.23, P l .01), were more likely to be homeless (P l .01), and were more likely to require intensive case management (P l .01). Interestingly, the colocation group was not more medically ill than the mental-health group on key metabolic measures, including mean body mass index (colocation = 27.8 vs mental-health = 28.7, P = .392), low-density liprotein (colocation = 110.0 vs mental-health = 104.4, P = .480), and glucose (colocation = 94.1 vs mental-health = 109.2, P = .059). The most common medical disorders in the colocation group were related to metabolic syndrome.ConclusionsColocated primary care services were allocated on the basis of severity of psychiatric impairment rather than severity of medical illness. This program serves as a model for other systems to employ for integrated primary and behavioral health services for patients with serious mental illness.

Background Although cervical cancer is ​​the second most common tumor among Brazilian women, studies that evaluate the quality of life of these women are still scarce. This situation is explained by the lack of specific and validated tools for this purpose in Portuguese (Brazil). The aim of this study was to evaluate the psychometric properties of the Portuguese version of the FACT-CX (Functional Assessment of Cancer Therapy-Cervix) questionnaire in a population of Brazilian women with cervical cancer. Methods The psychometric properties of the FACT-CX questionnaire were tested in a sample of 100 women diagnosed with cervical cancer who were previously treated in the Barretos Cancer Hospital. We analyzed the internal consistency (Cronbach's alpha), reproducibility (intraclass correlation coefficient - ICC), confirmatory factor analysis, convergent validity (correlation with the SF-36 questionnaire), and discriminant validity by disease stage and two questions related to self-perception of health was also performed. Results The scales had Cronbach´s alpha coefficients ranging from 0.61 to 0.80. However, three scales did not have a statistically significant coefficient greater than 0.70. The ICC ranged from 0.68 to 0.82 and all considered satisfactory. Factor analysis did not generate consistent components. The FACT-G and FACT-CX total scores had good internal consistency and reproducibility, and also correlated well with the General Health and Vitality scales of the SF-36. However, only two FACT-CX scales had a significant correlation with SF-36. Discriminant analysis showed that FACT-CX failed to discriminate groups according to clinical stage but was able to divide the women according to the self-perception of health. Conclusion FATC-CX total score had good internal consistency, reproducibility and discriminant validity. In addition, it correlated well with General Health and Vitality scales of SF-36. However, three scales had questionable internal consistency and only two had significant correlation with SF-36.

Our purpose was to evaluate the vasodilating responses of atherosclerotic coronary arteries using intraoperative high-frequency (12 MHz) epicardial echocardiography. We obtained continuous high-frequency epicardial echocardiographic recordings during surgery, and determined cross-sectional lumen area from 17 coronary arterial segments (12 patients). Nitroglycerin (100 to 400 micrograms/min) was administered intravenously to reduce mean (+/- SEM) arterial pressure 14 +/- 1.8 mm Hg. The cross-sectional arterial images were classified using 3 different parameters: arterial lumen area, percentage of the arterial wall circumference that was atherosclerotic (wall thickness0.7 mm), and presence of an eccentrically shaped arterial lumen (maximal/minimal luminal diameter1.5). Nine arterial segments had small (5.0 mm2) arterial lumens (1.7 +/- 0.40 mm2 [+/- SEM; range 0.6 to 3.9]). With nitroglycerin, the luminal area increased 0.8 +/- 0.28 mm2 (range 0 to 2.5), and 39 +/- 12.1% (range 0 to 117). The remaining 8 segments had larger (5.0 mm2) lumens (8.7 +/- 0.91 mm2 [range 5.0 to 11.9]). With nitroglycerin the luminal area increased 4.3 +/- 1.11 mm2 (range 1.4 to 11.4), and 51 +/- 10.2% (range 16 to 96). Seven arterial segments had eccentric lumens; mean maximal/minimal ratio was 1.8 +/- 0.08 (range 1.6 to 2.0). The area increased 39 +/- 7.3% (range 16 to 71) with nitroglycerin. In the 10 concentrically shaped lumens (maximal/minimal lumen diameters 1.3 +/- 0.04 [range 1.1 to 1.5]), nitroglycerin increased luminal area by 48 +/- 12.6% (range 0 to 117) (p = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

The chemical assessment of the complete disulphide bridge pattern in the beta-chain of human recombinant follicotropin (betaFSH) was accomplished by integrating classical biochemical methodologies with mass spectrometric procedures. A proteolytic strategy consisting of a double digestion of native betaFSH using the broad-specificity protease subtilisin first, followed by trypsin, was employed. The resulting peptide mixture was directly analysed by FAB-MS, leading to the assignment of the first three disulphide bridges. The remaining S-S bridges were determined by HPLC fractionation of the proteolytic digest followed by ESMS analysis of the individual fractions. The pattern of cysteine couplings in betaFSH was determined as: Cys3-Cys5l, Cys17-Cys66, Cys20-Cys104, Cys28-Cys82, Cys32-Cys84 and Cys87-Cys94, confirming the arrangement inferred from the crystal structure of the homologous betaCG. A subset of the S-S bridge pattern comprising Cys3-Cys51, Cys28-Cys82 and Cys32-Cys84 constitutes a cysteine knot motif similar to that found in the growth factor superfamily.

Objective To assess the risk factors for delayed diagnosis of uterine cervical lesions. Materials and Methods This is a case-control study that recruited 178 women at 2 Brazilian hospitals. The cases (n = 74) were composed of women with a late diagnosis of a lesion in the uterine cervix (invasive carcinoma in any stage). The controls (n = 104) were composed of women with cervical lesions diagnosed early on (low- or high-grade intraepithelial lesions). The analysis was performed by means of logistic regression model using a hierarchical model. The socioeconomic and demographic variables were included at level I (distal). Level II (intermediate) included the personal and family antecedents and knowledge about the Papanicolaou test and human papillomavirus. Level III (proximal) encompassed the variables relating to individuals’ care for their own health, gynecologic symptoms, and variables relating to access to the health care system. Results The risk factors for late diagnosis of uterine cervical lesions were age older than 40 years (odds ratio [OR] = 10.4; 95% confidence interval [CI], 2.3–48.4), not knowing the difference between the Papanicolaou test and gynecological pelvic examinations (OR, = 2.5; 95% CI, 1.3–4.9), not thinking that the Papanicolaou test was important (odds ratio [OR], 4.2; 95% CI, 1.3–13.4), and abnormal vaginal bleeding (OR, 15.0; 95% CI, 6.5–35.0). Previous treatment for sexually transmissible disease was a protective factor (OR, 0.3; 95% CI, 0.1–0.8) for delayed diagnosis. Conclusions Deficiencies in cervical cancer prevention programs in developing countries are not simply a matter of better provision and coverage of Papanicolaou tests. The misconception about the Papanicolaou test is a serious educational problem, as demonstrated by the present study.

Background: Millions of workers are exposed to polycyclic aromatic hydrocarbons (PAHs) and it is known that the kidney is a target for toxic chemicals. We have evaluated neutrophil gelatinase-associated lipocalin (NGAL) as a potential marker of tubular damage and have used it, with sister chromatid exchange (SCE) analysis, to evaluate carcinogenic risk in a group of workers from an oil refinery. Methods: NGAL and SCE analysis were evaluated in 160 subjects. Exposed subjects were divided into three groups, according to levels of exposure to PAHs: 40 highly exposed workmen (WM), 40 less exposed office workers (OW), and 40 subjects (GE) living in Gela. The control group included 40 healthy subjects (HS). Results: WM, OW and GE showed higher NGAL levels than HS. WM had higher levels of NGAL than the OW and GE groups; in ROC analysis, serum NGAL showed a good diagnostic profile (sensitivity 87.5%; specificity 100.0%), as did urinary NGAL (sensitivity 90.0%; specificity 92.5%). Moreover, regarding SCE analysis, WM showed higher values than HS. A direct correlation between SCE and serum NGAL was found in WM, the group most exposed to PAHs. Conclusion: The high values of NGAL are an expression of damage to the renal tubule determined by exposure to PAHs. Compared to the other groups studied, chromosomal aberrations – expressed as SCE – were increased in WM, the group most exposed to PAHs, indicating genotoxic damage. NGAL may also play a role in the process of carcinogenesis having a direct correlation with the number of SCEs.

Coronary artery disease and ischemic cerebrovascular disease are leading causes of morbidity and mortality in the United States. Coronary artery disease often coexists with asymptomatic carotid artery atherosclerosis, transient ischemic attacks, or ischemic stroke. Numerous studies have shown that mortality from all forms of ischemic cerebrovascular disease is primarily due to coronary artery disease. Thus, there is increasing interest in identifying coronary artery disease in patients with cerebrovascular disease, including those without clinical manifestations of heart disease. We review the use of current noninvasive techniques to detect coronary artery disease and present practical approaches to screen for ischemic heart disease. Current diagnostic imaging methods for potential cardioembolic sources of cerebral infarction are also discussed.

BACKGROUND Association of thyroid dysfunction with plasma homocysteine levels and vitamin B(12) has previously been reported. We evaluated these associations in the elderly in San Teodoro, a mountainous village of Sicily. METHODS Subjects (n=279) aged 60-85 years (119 males and 160 females) were examined using self-reported signs, clinical examination and laboratory tests. RESULTS Hypothyroidism and/or goiter were two characteristics that were not associated with a significant change in homocysteine when compared with euthyroidism and the absence of goiter. Vitamin B(12) was significantly higher in subjects in the first quartile of the thyroid-stimulating hormone distribution, compared with those in the fourth quartile (371+/-207 vs. 297+/-196 pmol/L, p=0.0121). Homocysteine was significantly higher in the first quartile of the free tri-iodothyronine distribution compared to the third quartile (18.0+/-5.7 vs. 16.0+/-6.2 micromol/L, p=0.0130) and was correlated with log tri-iodothyronine in euthyroid subjects (p=0.0254). In multivariate analysis, homocysteine was associated with vitamin B(12) (p=0.0014), folate (p

Synopsis: The cardiovascular disease (CVD) evaluator is a web-based expert system with a patented methodology. It interfaces an individual patient profile with literature. It uses CV disease risk scoring systems, guidelines, and clinical trials data. Once an individual data point (clinical, lipid profile, if available emerging risk factors) is entered, the system makes specific diagnostic and therapeutic recommendations. The references are cited and linked to the journal article. Purpose: First clinical decision support system for evidence based lipid and hypertension management. Methods: The outcomes of 200 patients (112 with CHD), whose initial lipid, hypertension management decisions were aided by the system (within 6 months of its implementation in August 2006) were compared with those of 200 control group managed by physicians .The primary end point was the achievement of both target LDL-C and non HDL-C at any point. The secondary end point was 5year combined CV death, nonfatal myocardial infarction, cerebrovascular accident, any revascularization. Fisher’s exact test was used for statistical analysis. Results: A total of 71 of the 112 patients with CHD in the study group and 46 of 110 patients in the control group reached the primary end point (P5 .001). As to the patients without CHD, 58 of the 88 in the study group vs. 41 in the control group achieved the primary point (P 5 .03). There were 45 combined events in the CHD arm of control group over 5 years versus 24 in the CAD arm of the study group

Background Errors in drug treatment are the leading cause of injury in hospitalised patients. According to international studies, medicines errors are multifactorial and involve various health professionals. Purpose To improve the flow of prescriptions in the surgical area, introducing more checking steps and reducing errors by using FMEA (Failure Mode and Effect Analysis), a proactive approach to risk management. Materials and methods The project involved 8 departments in the surgical area (Abdominal Pelvic Surgery, Breast Care, Anaesthesia and Intensive Care, Thoracic Surgery, Reconstructive Surgery, General Surgery, Head and Neck Surgery, Gynaecology). Each department participated in interdisciplinary teams (doctors, nurses, pharmacists), in collaboration with Quality and Risk Management Services. The eight teams developed the project through participation in classroom training and practical exercises. The project was broken down into several stages: detailed analysis of the pharmacological process in all the individual activities; assessment by a risk index; definition of containment plans; monitoring of the efficacy of containment plans. Process analysis and risk mapping highlighted that that the priority risks identified are more related to the stages of transcription and communication within the department. Results A total of 49 priority risks were identified, and each division developed an average of 3 independent containment plans, which led to some changes of activity in the pharmacological process. The overall risk index has been reduced by 13.5%, while the impact on priority risks led to a reduction of the value of risk indexes by 26%. Conclusions At the end of the first monitoring phase, results were presented to all departments in a plenary session. Risk indexes calculated to date are approximate and represent a partial result that should be confirmed at the end of containment plans. These first encouraging results are almost entirely due to a multidisciplinary approach, taking charge of only priority risks, and succeeding in significantly improving communication. No conflict of interest.

Background Prescription errors, especially in oncology, may lead to clinical, financial and organisational damage. A second check by the pharmacist before preparation may prevent errors and related harm to the patient. Purpose To measure the effectiveness of pharmacist intervention in preventing errors and creating a safety-oriented vision in healthcare givers. Materials and methods Near miss reports, resulting from serious errors in the prescription of non-muscle infiltrating bladder cancer (NMIBC) instillation treatments, were collected by software (Vitruvio 2.0) during the second half of 2012 (Jun–Dec). Errors were analysed and presented to urologists during their departmental meetings. In the first half of 2013 (Jan–Jun) data collection was repeated, observing and analysing data using the same criteria as the previous six months. Results The incidence of serious errors in 2012 was 6.6% of total prescriptions (35/530). The main mistake was ‘incorrect dose’ (14), the second one was ‘organisational error’ including double prescription, wrong date and others (13) and the third more frequent error was ‘wrong active’ prescription (8). We identified the practice of using a duplication function in prescribing with subsequent data change in the prescription form as the main cause predisposing to error. Data were analysed and discussed during the urology department meeting, after the meeting we collected data for an additional 6 months. The results of the second period (2013) showed a strong reduction in the incidence of serious errors (7/441). Organisational errors were the most frequent, (5) typology, while there was a marked reduction of ‘dose errors’ (1) or ‘wrong active’ prescription (1). Conclusions The pharmacist intervention not only produced a prevention in terms of possible harm to the patient (incidence reduction = 24.04%), but even produced an improvement in clinical practice and safety orientation of the culture amongst clinical personnel. No conflict of interest.

Iron overload is associated with long-term cardiac iron accumulation and tissue changes such as fibrosis. To determine short-term iron-dependent changes in expression of genes associated with iron homeostasis and fibrosis we measured mRNA on Northern blots prepared from cultured rat neonatal cardiomyocytes and non-myocytes (fibroblasts) as a function of iron loading and chelation. Transferrin receptor mRNA was reduced in myocytes exposed to various concentrations of iron for 3 days and this decline was associated with a 63% decline in iron-response element (IRE) binding of iron regulatory protein-1, indicating that myocytes utilize IRE-dependent mechanisms to modulate gene expression. In myocytes iron caused a dose-dependent decline in mRNAs coding for transforming growth factor- beta(1)(TGF- beta(1)), biglycan, and collagen type I while plasminogen activator inhibitor-1 mRNA was unaffected by iron loading and decorin mRNA doubled. Total TGF- beta bioactivity was also decreased by iron loading. Thus, the effects of iron loading on genes related to cardiac fibrosis are gene-specific. Addition of deferoxamine for 1 day did not have any significant effect on any of these genes. Parallel changes in gene expression were exhibited by non-myocytes (fibroblasts), where chelation also decreased TGF- beta(1)mRNA and activity, and mRNA for collagen type I and biglycan, and collagen synthesis. In addition to these changes in transcripts associated with matrix formation the mRNA of the metabolic enzyme glyceraldehyde-3-phosphate dehydrogenase was unaffected by iron loading but doubled in both cell types upon treatment with deferoxamine. These findings suggest that in both cardiac myocytes and non-myocyte fibroblasts gene expression is coupled to intracellular iron pools by gene-specific and IRE-dependent and idependent mechanisms. This linkage may influence matrix deposition, a significant component of cardiac injury.

Background The lack of management software for patients undergoing chemotherapy suggested to us that we should investigate errors that have occurred at all stages of the process: prescription, transcription, preparation, distribution and administration of treatment. Purpose To encourage reports and classify the errors, in order to develop a computerised system of internal management of chemotherapy which can reduce the risk of error at all stages. Materials and Methods Two reporting channels were established: one for major errors, such as prescriptions or preparations containing incorrect drugs or dosages, improper units of measurement, diluents incompatible with the active ingredient, improper administration. These errors are shared in corporate software with the Risk Management Office. The second concerns minor errors, prescriptions containing compilation errors, incomplete compilation of the treatment regimen, incomplete administration of treatment; these errors are reported in an internal Excel file. Results From January to September 2012, 73 major errors were reported from a total of 30406 preparations. Some of these were: prescription of paclitaxel instead of docetaxel, vinorelbine written as vinblastine; preparation of a 5-fluorouracil weekly dose in a two-day infusor, administration of paclitaxel bag to the wrong patient. In 85% of these cases the intervention of pharmacist avoided the error. 468 minor errors were reported, including 447 prescription errors, 3 transcription errors, 8 for lack of a cheque of the output treatment and 10 for incomplete delivery of the treatment. Conclusions This analysis allowed us to draw a picture of the most frequent types of error. Most of them concerned the prescription stage, which we hope to minimise with the implementation of a computerised prescribing system. This will also cut down the transcription and administration errors by reading the barcode of the preparation with a patient wristband. The reduced number of preparation errors can be attributed to the use of an automated system for chemotherapy preparation. No conflict of interest.

Coronary arterial remodeling is a compensatory mechanism that may limit the adverse effects of coronary obstructive lesions by expansion of the entire vascular segment. To determine if this compensatory anatomic change occurs in patients, high-frequency epicardial echocardiography using a 22 MHz transducer was performed during open heart surgery in 33 patients (10 with normal coronary arteries undergoing valvular surgery and 23 with coronary atherosclerosis). From stop-frame videotape high-frequency epicardial echocardiographic images cross-sectional measurements of luminal area and total arterial area (lumen. intima, media and dense adventitia) were made in the patients with atherosclerosis at the site of arterial lesions and from the most proximal portion of the same artery. Remodeling was defined as enlargement of the total arterial area. In normal arteries measurements were made from proximal and midarterial locations. In the patients with normal coronary arteries, total arterial area, as determined by high-frequency echocardiography, decreased from the proximal site to the midportion of the artery (from 10.4 ± 0.9 to 8.4 ± 1.0 mm2, p < 0.05), luminal area also decreased (from 6.0 ± 0.6 to 4.5 ± 0.7 mm2, p < 0.05). In patients with coronary arterial lesions, luminal area also decreased from the proximal site to the arterial lesion site (from 5.3 ± 0.6 to 2.3 ± 0.3 mm2, p < 0.05), but total arterial area increased (from 11.6 ± 1.0 to 13.0 ± 1.0 mm2, p < 0.05). Of the 25 coronary arteries evaluated, only 4 had angiographic evidence of coronary collateral formation. These data indicate that coronary arterial remodeling is an important compensatory mechanism in obstructive coronary disease. In most patients, arterial remodeling occurs before angiographically detectable coronary collateral vessels develop.

Individuals with nonvalvular atrial fibrillation are at increased risk of stroke. The Stroke Prevention in Atrial Fibrillation Study is a 15-center randomized clinical trial examining the risks and benefits of low-intensity warfarin (prothrombin time of 1.3-1.8 times control) and aspirin (325 mg/day) in patients with constant or intermittent atrial fibrillation. Candidates for anticoagulation (group I) are randomized to receive warfarin in an open-label fashion, aspirin, or placebo; the last two treatments are given in a double-blind fashion. Warfarin-ineligible patients (group II) are randomized to receive aspirin or placebo in a double-blind fashion. Primary end points are ischemic stroke and systemic embolism. Secondary end points are death, transient ischemic attack, myocardial infarction, and unstable angina pectoris. Analysis is based on the intention-to-treat principle. The anticipated rate of primary end points in patients receiving placebo is 6%/yr. The sample size of 1,644 patients is based on a projected reduction in the rate of primary end points of 50% by warfarin and of 33% by aspirin (beta = 0.2, alpha = 0.05). Patient entry commenced in June 1987 and will continue for 3 years, with an additional year of follow-up. High-risk subsamples identified by clinical and echocardiographic criteria are sought prospectively.