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Background: Recent reports indicate that the isoxazoline compounds have the potential to provide safe and effective treatment of canine generalized demodicosis, a condition that has been traditionally difficult to cure. Controlled field studies are needed to confirm this potential. A study was therefore initiated to investigate the efficacy of a single oral or spot-on treatment with fluralaner, an isoxazoline, compared with multiple topical treatments with imidacloprid-moxidectin, in dogs naturally affected by generalized demodicosis., Methods: Veterinary clinics in 5 European countries enrolled 134 dogs diagnosed with generalized demodicosis. Dogs were randomized to treatment with either fluralaner chewables, fluralaner spot-on, or topical imidacloprid-moxidectin in a 2:2:1 ratio. Both fluralaner formulations were administered once, at the approved dose rate, on Day 0. Imidacloprid-moxidectin was administered per label on Day 0, and every 4 weeks, more frequently if necessary. At each visit (Days 0, 28, 56, 84), dogs were monitored for demodectic mites using deep skin scrapings and observed for health and for severity of skin lesions. Treatment was considered efficacious if more than 90% of the dogs were free of live mites at both Days 56 and 84., Results: Of 124 dogs completing the study, 57 were diagnosed with juvenile-onset demodicosis and 67 with the adult-onset form. A single treatment with oral or spot-on fluralaner was efficacious, each eliminating mites from at least 98.0% of treated dogs on Days 56 and 84. Against juvenile-onset demodicosis, efficacy of the oral and spot-on formulations was 96.0% and 100%, respectively, and against adult-onset demodicosis 100% and 96.7%. Multiple administrations of imidacloprid-moxidectin were not efficacious, eliminating mites from 87.5% of dogs (92.0% with juvenile-onset demodicosis cured; 81.8% with adult-onset demodicosis). All groups showed a marked reduction in skin lesions by Day 28, with continuing clinical improvement at each subsequent visit through Day 84. There were no treatment-related adverse events., Conclusions: A single administration of fluralaner chewables or fluralaner spot-on is highly effective against with juvenile-onset and adult-onset forms of generalized canine demodicosis. Topically applied imidacloprid-moxidectin at weekly to monthly intervals over the 84-day study did not achieve the proportion of mite-free dogs required to demonstrate efficacy.

We have encountered pancreatic tumors with unique histologic features, which do not conform to any of the known tumors of the pancreas or other anatomical sites. We aimed to define their clinicopathologic features and whether they are characterized by recurrent molecular signatures. Eight cases were identified; studied histologically and by immunohistochemistry. Selected cases were also subjected to whole-exome sequencing (WES; n = 4), RNA-sequencing (n = 6), Archer FusionPlex assay (n = 5), methylation profiling using the Illumina MethylationEPIC (850k) array platform (n = 6), and TERT promoter sequencing (n = 5). Six neoplasms occurred in females. The mean age was 43 years (range: 26-75). Five occurred in the head/neck of the pancreas. All patients were treated surgically; none received neoadjuvant/adjuvant therapy. All patients are free of disease after 53 months of median follow-up (range: 8-94). The tumors were well-circumscribed, and the median size was 1.8 cm (range: 1.3-5.8). Microscopically, the unencapsulated tumors had a geographic pattern of epithelioid cell nests alternating with spindle cell fascicles. Some areas showed dense fibrosis, in which enmeshed tumor cells imparted a slit-like pattern. The predominant epithelioid cells had scant cytoplasm and round-oval nuclei with open chromatin. The spindle cells displayed irregular, hyperchromatic nuclei. Mitoses were rare. No lymph node metastases were identified. All tumors were positive for vimentin, CD99 and cytokeratin (patchy), while negative for markers of solid pseudopapillary neoplasm, neuroendocrine, acinar, myogenic/rhabdoid, vascular, melanocytic, or lymphoid differentiation, gastrointestinal stromal tumor as well as MUC4. Whole-exome sequencing revealed no recurrent somatic mutations or amplifications/homozygous deletions in any known oncogenes or tumor suppressor genes. RNA-sequencing and the Archer FusionPlex assay did not detect any recurrent likely pathogenic gene fusions. Single sample gene set enrichment analysis revealed that these tumors display a likely mesenchymal transcriptomic program. Unsupervised analysis (t-SNE) of their methylation profiles against a set of different mesenchymal neoplasms demonstrated a distinct methylation pattern. Here, we describe pancreatic neoplasms with unique morphologic/immunophenotypic features and a distinct methylation pattern, along with a lack of abnormalities in any of key genetic drivers, supporting that these neoplasms represent a novel entity with an indolent clinical course. Given their mesenchymal transcriptomic features, we propose the designation of "sclerosing epithelioid mesenchymal neoplasm" of the pancreas.

Background: Searching for health information online is increasingly common and is an obvious source of information about oral combined hormonal contraceptives (CHCs) and their risks. However, little is known about how publicly available websites address the risks of CHCs, particularly venous thromboembolism (VTE)., Objective: The aim was to explore the information available to women about VTE and other risks of CHCs on websites available through commonly used search engines., Methods: A qualitative study was conducted to explore whether and how websites about CHCs in Denmark, Germany, Netherlands, Slovakia, Spain, and the United Kingdom make reference to VTE and other CHC risks. A systematic search procedure was adopted across the six countries, based on relevant keywords. The search was carried out using the Google search engine by fluent/native speakers of each language. A content analysis approach was conducted to extract information from the selected websites., Results: A total of 357 websites were reviewed. Nearly all (343/357, 96.1%) the websites mentioned VTE as a risk of CHCs, with approximately half referring to other side effects as well. One-fifth (92/357, 25.8%) of the websites provided suggestions about the best contraceptive method to use, and only a minority (23/357, 6.4%) recommended women discuss CHCs with their health professionals. Sites were generally run by the media (110/357 30.8%) or medical services from nongovernmental organizations (140/357, 39.2%). Only a minority of websites referred to organizations such as the European Medicines Agency (11/357, 3.1%)., Conclusions: Despite the large number of websites containing information about oral CHCs and their risks, particularly VTE, only a limited number referred to information from accredited health agency sources. We argue this is a missed opportunity for accredited health agencies to share high-quality information to assist women using CHCs to make informed decisions about contraception., (©Paula Gomes Alves, Irene Petersen, Fiona Stevenson. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 18.03.2019.)

Objective: To determine pregnant women and new mothers' perception of risks in pregnancy., Design, Settings and Participants: This was a large-scale multinational survey including 9113 pregnant women and new mothers from 18 countries in Europe, North America and Australia., Main Outcomes: Risk perception scores (0-10) for harmful effects to the fetus were derived for: (1) medicines (over-the-counter medicine and prescribed medicine), (2) food substances (eggs and blue veined cheese), (3) herbal substances (ginger and cranberries) (4) alcohol and tobacco, and (5) thalidomide., Results: Overall, 80% (6453/8131) of women perceived the risk of giving birth to a child with a birth defect to be ≤ 5 of 100 births. The women rated cranberries and ginger least harmful (mean risk perception scores 1.1 and 1.5 of 10, respectively) and antidepressants, alcohol, smoking and thalidomide as most harmful (7.6, 8.6, 9.2 and 9.4 out of 10, respectively). The perception varied with age, level of education, pregnancy status, profession and geographical region. Noticeably, 70% had not heard about thalidomide, but of those who had (2692/9113), the risk perception scores were 0.4-0.5 points lower in women below 25 years compared to women aged 26-30 years., Conclusions: In general, women perceived the risks of giving birth to a child with birth defects low, but there were substantial disparities between women's perceived risks and the actual risks when it comes to over-the-counter agents against nausea and prescribed medication. The study revealed that few women knew of thalidomide, suggesting that the general awareness among women of the teratogenic effects of thalidomide is declining, but it has left a general scepticism about safety of medication in pregnancy. This may have some severe consequences if women are left without medical treatments in pregnancy., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

HPV has been identified not only in gynaecological carcinomas but also in tumors of other organs, especially of the oropharynx and upper aero-digestive tract. In this study we focused on the available literature on HPV in lung carcinomas. In total, 53 publications reporting on 4508 cases were reviewed and assessed for the following parameters: continent and region of the study, number of cases, detection method, material type, HPV type, histological subtype and number of the HPV-positive cases. Overall, the mean incidence of HPV in lung cancer was 24.5%. While in Europe and the America the average reported frequencies were 17% and 15%, respectively, the mean number of HPV in asian lung cancer samples was 35.7%. There was a considerable heterogeneity between certain countries and regions. Particular high frequencies of up to 80% were seen in Okinawa (Japan) and Taichung (Taiwan). However, there were also discrepant results within the same region pointing to methodological differences and the need for validation. All lung cancer subtypes were affected and especially the high risk types 16, 18, 31 and 33 as well as the low risk types 6 and 11 were found, the later mainly in association with squamous cell carcinomas. The data suggest that HPV is the second most important cause of lung cancer after cigarette smoking and strongly argues for additional research on this issue.