World Health Organization (WHO) defines tropical diseases as all diseases that occur solely, or principally, in the tropics’ [Historically, tropical medicine emerged from a multidisciplinary background as a result of progress in the areas of public health and hygiene, travel and exploration, biology and evolution, and the germ theory of disease . The Wortropics’ . WHO’s fTropical Medicine and Infectious Disease. It has been endorsed as the Official Journal of The Australasian College of Tropical Medicine (ACTM) and its joint Faculties of Travel Medicine and Expedition and Wilderness Medicine. Both MDPI and the ACTM are celebrating anniversaries this year, being 20 and 25 years old respectively, and are both proud of their respective traditions in the world of publishing. The Australasian College of Tropical Medicine has partnered with long term electronic publisher, MDPI, to develop an international, scientific, open access journal of tropical medicine and infectious disease to be published quarterly online. We have named this new journal, MDPI publishes 150 peer reviewed, scientific, open access, electronic journals in a broad range of fields. It has offices in four cities, being headquartered in Basel, Switzerland and having additional offices in China and Spain. MDPI is a member of all the major professional publisher associations, including OASPA, STM, or COPE and has a strong track record in building the indexing and abstracting support for each of its journals . Part ofAnnals of the ACTM since 1995, initially as conference proceedings and then as a peer-reviewed journal from 2002. All of these are available online [Dictionary of Tropical Medicine [The ACTM is particularly excited about this project being launched in its 25th Anniversary Year. The ACTM itself has been publishing the e online . The ColTropical Medicine and Infectious Disease is to publish authoritative and original articles, critical and systematic reviews, editorials, perspectives, short communications, commentaries, book reviews, letters to the editor and special issues on all aspects of tropical medicine and tropical infectious disease. All articles will be submitted through MDPI’s excellent online journal submission platform and are subject to editorial and peer-review. The MPDI Editorial Process is extremely rigorous [The aim of rigorous , but it Tropical Medicine and Infectious Disease will publish on all tropical diseases of global significance, as well as neglected tropical diseases, as defined from time-to-time by the WHO. The scope of the journal includes, but is not limited to clinical tropical medicine, tropical infectious diseases, parasitology and entomology, bacteriology, mycology and virology, epidemiological and social science studies, chemotherapy and pharmacology, immunology, disease prevention, control and elimination, emerging and re-emerging infectious diseases, emerging public health threats, and global health and One Health.We are very proud to welcome our foundation international Editorial Board, an extremely talented group of more than 20 senior academics and clinicians from six continents with global outreach. We also warmly welcome our Assistant Editor, Anna Liu, who has championed the development of the journal and will be a key contact for both contributors and Editorial Board members. The team will be led by our Editor-in-Chief, John Frean from South Africa, and our Deputy Editor-in-Chief, Peter A. Leggat, AM, from Australia. We will be reviewing and building our Editorial Board and reviewing teams in the coming years and the Editor-in-Chief would welcome nominations from interested leaders in the fields of tropical medicine and infectious disease. We are also looking forward to receiving your research, reviews and other scholarly contributions and we welcome suggestions or ideas that can enhance this new journal.Tropical Medicine and Infectious Disease. On behalf of the Editorial Board, we invite you to submit your manuscripts and suggestions for Special Issues and guest editorials to


Journal of Global Health, we are committed to ensuring that all processes during the publication of articles in our journal have the same level of transparency and responsibility. As we expect from our authors and reviewers to declare their possible conflicts of interest in relation to the manuscript under consideration for publication in the journal, we also need to declare our commitments and relations that may influence the editorial review process. When one of the decision-making editors submits an article to the Journal, it is reviewed independently from the editor, who has no access to or influence on the review process and editorial decision-making. This is always indicated in the Competing Interests declaration at the end of the published article.As the editors of the As the next step in increasing the transparency of the editorial conflicts of interest  and in oProf. Marušić is fully employed by the University of Split School of Medicine, where she holds a tenured position as Professor and Chair of the Department of Research in Biomedicine and Health. She receives funding support for research from the Croatian Science Foundation and the European Commission under the Horizon 2020 programme.Prof. Marušić holds a position as the Editor in Chief. She occasionally reimburses small travel expenses related to Journal’s work.Honorary Professor, College of Medicine and Veterinary Medicine, University of Edinburgh, Edinburgh, Scotland, UKVisiting Professor, School of Medicine, University of Sao Paulo, Sao Paulo, BrazilPresident, European Association of Science Editors (until June 2018)Steering Group, EQUATOR NetworkCo-Chair, Cochrane Scientific CommitteeResearch Coordinator, Cochrane CroatiaBalkan Medical JournalAdvisory Board Member, the Prof. Rudan is employed by the University of Edinburgh, where he holds a position as Professor and Co-Director of the Centre for Global Health Research. He is also co-Director of the WHO Collaborating Centre in Population Health Research and Training. He currently receives research funding support from the Gates Foundation.Prof. Rudan holds a position as the co-Editor in Chief. He occasionally reimburses small expenses related to Journal’s work, including travel and consumables.Prof. Rudan has numerous technical advisor appointments to WHO, UNICEF and the World Bank.Prof. Campbell is employed by the University of Edinburgh, where he holds a position as Professor and Co-Director of the Centre for Global Health Research. He is also co-Director of the WHO Collaborating Centre in Population Health Research and Training and co-Director of the NIHR Global Respiratory Health Unit. He currently receives research funding support from the European Commission (Innovative Medicines Initiative), WHO, UK NIHR, Cancer Research UK, UK MRC, Sanofi (for work on specific GI and respiratory infections) and the Gates Foundation.Prof. Rudan holds a position as the co-Editor in Chief. He occasionally reimburses small expenses related to Journal’s work, including travel and consumables.Member, MRC Africa Research Excellence Fund (AREF), College of Experts, since 2016Member, WHO PIP burden of disease advisory group, since 2015Member of international Scientific Advisory Group, INDEPTH network, since 2014Member of Expert Advisory Group for “The Making of Genomic Medicine Wellcome Trust Programme; University of Edinburgh), since 2013Member, Public Health, Health Services Research and Primary Care  Research Excellence Framework (REF), 2018-2021Numerous technical advisor appointments to WHO in the past 5 years


Scientific Reports7; Article number: 4295710.1038/srep42957; published online: 02212017; updated: 07042018Jonathan Collins was omitted from the author list in the original version of this Article. This has been corrected in the PDF and HTML versions of the Article, and in the accompanying Supplementary Data file.The Author Contributions section now reads:“Dennis Ma and Siyaram Pandey contributed to the conception and design of experiments, execution of experiments, analysis of data, and preparation of the manuscript. Daniel Tarade, Tyler Gilbert, Christopher Pignanelli, Fadi Mansour, Scott Adams, Kyle Stokes, Alexander Dowhayko, and Megan Noel contributed to the execution of experiments and preparation of the manuscript. Sergey Vshyvenko, Jonathan Collins and Tomas Hudlicky synthesized and provided PST analogs for this study and contributed to the preparation of the manuscript. James McNulty provided natural PST for this study and contributed to the preparation of the manuscript”.


The authors of the paper “Performance, Acceptability, and Usability of Respiratory Rate Timers and Pulse Oximeters When Used by Frontline Health Workers to Detect Symptoms of Pneumonia in Sub-Saharan Africa and Southeast Asia: Protocol for a Two-Phase, Multisite, Mixed-Methods Trial” :e10191), made a mistake in the final stage of proofreading. Kevin Baker should have been listed as affiliated with the Karolinska Institute in Stockholm, Sweden. This affiliation has also been updated to include the Department of Public Health Sciences for all affiliated authors and now reads as follows:Department of Public Health Sciences, Karolinska Institute, Stockholm, SwedenAdditionally, Kevin Baker's address as the corresponding author for this paper has been changed to reflect this new affiliation.The correction will appear in the online version of the paper on the JMIR website on March 7, 2019, together with the publication of this correction notice. Because this was made after submission to PubMed, PubMed Central, and other full-text repositories, the corrected article also has been resubmitted to those repositories.


Lichen is a common chronic inflammatory dermatitis that can affect the skin, mucous membranes and phaneres. The simultaneous involvement of the three compartments is rare and testifies to the severity and activity of the disease. We present a case of this triple involvement. However, the complete muco-cutaneous and phanerienic forms are rare, testify to the severity of the disease and justify a systemic treatment and a regular and long-term monitoring view the risk of degeneration of the mucous lesions. We report the case of this 60-old-man, followed for papular dermatosis, hyperpigmentary, very itchy, generalized, with involvement of the genital mucosa, in the form of erosive balanitis and nails of the hands and feet. The cutaneous histology was in favor of lichen. The biological examinations did not show any dysthyroidism, liver or autoimmune diseases. The patient was placed on systemic and topical corticosteroids. A pigmentogenic evolution of the cutaneous lesions, a beginning of bleaching of the nail lesions and a resistance of the genital lesions were noted.


The reassessment of technologies and services offered by healthcare systems is recent initiative and still without a widely adopted and evaluated method. To a better understanding of this process in Brazil, we have described the health technology reassessment (HTR) performed by the National Committee for Health Technology Incorporation (Conitec) into Brazilian public health system (SUS).A documental, exploratory, descriptive, retrospective study with qualitative-quantitative approach regarding the HTR performed by Conitec from January 2012 to November 2017.After applying the criteria of inclusion and exclusion, we selected 47 technologies for this study. The vast majority of the demands (41 demands) came from the public sector, and only six from the private sector. Most of the requests referred to the exclusion of specific indication; followed by extension of use, withdraw of the technology from SUS, maintenance, and restriction of use. The dimensions of analysis found in the recommendation reports were scientific evidence on efficacy, effectiveness and safety, disease-related issues, issues related to the use of technology, costs, and social participation. However, these dimensions were not included in all analysis, and a standardized structure of the reports has not been observed. The most relevant decision factors considered for decision-making were efficacy, safety and use of the technology.During a six-year period of Conitec actuation, we could find some reassessments of technologies that are available in SUS. We observed that these activities had enabled progress, however, they are still not yet structured, with gaps in the selection process, and the assessment since no methodology and criteria for proper conduct were established. The process of Health Technology Assessment (HTA) considers primarily the results of efficacy studies, mostly from randomized clinical studies. However, despite being essentials, these studies often point out a high degree of uncertainty to the real benefits to the population, which, in many cases, is not proportional to the resources invested ,2. This According to the Brazilian Institute of Geography and Statistics (IBGE), between 2013 and 2014, the final consumption of health goods and services rose from 8.2% to 8.7% of Gross Domestic Product (GDP). In 2015, the health expenditures were R$ 546 billion (9.1% of GDP), with 79.2% of health services and 19% of medicines. The rest referred to the consumption of other medical, ophthalmological, and dental materials. Considering these data, approximately one-fifth of health expenditures is related to the use of medicinal drugs, only surpassed by hospital cost, outpatient and preventive services and sanitary surveillance [It is essential to define tools that can support decision-makers in the adoption and re-evaluation of technologies within health systems. Among many reasons for this approach, we can cite the prospects for an increase in the use of drugs and other health technologies to meet the demands of a population that are progressively expanding associated with an increase in the prevalence of chronic degenerative diseases, together with the highly complex and contextualized analysis for selection of technologies and services.Regarding the adoption of new technologies, there has been much effort in the study of methods used by Health Technology Assessment (HTA) agencies and how to improve them, so that this process can apprehend all the relevant aspects of the intervention in a given context. Consequently, more objective and transparent methodologies and criteria that take into account the perspectives of different stakeholders have been developed and validated in several countries to optimize the allocation of resources and contribute to more consistent decisions before society –7.On the other hand, studies on reassessment methodologies to monitor and evaluate the use of technologies are less frequent and have only recently become available; more precisely, since 2006 . The heaSuch a process is fundamental to the quality of care offered to the patient and the sustainability of the health system, as resources could be reinvested in more useful or less expensive health services. Within the technology lifecycle, this phase aims at finding technologies that present inferior results to those that subsidize their adoption or even interventions that are ineffective or harmful to the patient or the health service . Hence, Some studies were conducted targeting low-value practices, which, according to Colla and colleagues, are "the use of care that is unlikely to benefit the patient given the cost, available alternatives, and preferences of the patient" . Prasad In another review, Niven and colleagues have reported cardiovascular diseases, arthritis, and menopause as the most common target conditions in de-adoption studies–discontinuation of current clinical practice. The most researched therapies were cyclooxygenase-2 inhibitors (COX-2) and other non-steroidal anti-inflammatory drugs (NSAIDs), hormone replacement therapy and percutaneous coronary intervention .Considering that the low-value practices are a potential waste and can be harmful to the patient’s health, some countries  have already begun monitoring the technology after a certain period past its implementation in the health care system –16.During the French health system reform, there was a review of the complete list of reimbursed drugs and those considered ineffective were withdrawn from the health system. In addition to this strategy, there were also others like greater access to average European prices for innovative drugs, stimulation of discounts for over-prescription drugs and programs to increase the prescription of generic medicines. The result of HTR and the further decision not to reimburse the ineffective medications represented an estimated savings of 450 million euros/year, in addition to the savings generated by the implementation of the other reform initiatives (1.7 billion euros / year—period from 2003 to 2007) .These data about the French health system emphasize that combining several strategies to improve technologies management, results in a significant impact on economic resources. However, the sustainability of health systems involves other aspects beyond the financials ones ; such as the continuity of the provided services  and the obtained benefits  . These aIn Brazil, the National Committee for Health Technology Incorporation (Conitec) was established in 2011 to improve the decision-making process in HTA. The primary purpose of this committee is advising the Ministry of Health on decisions related to the adoption, disinvestment or changes in the use of health technologies in SUS, as well as the development or update of clinical protocols or therapeutic guidelines . ConitecConitec creation has promoted advances in the institutionalization of HTA in the Brazilian health system, due to the rationality and use of clinical and economic evidence in decisions about the inclusion of new technologies in SUS. Some studies on the work of the Committee have been published with the purpose of outlining the evaluation process, the demands, and the recommendations about the adoption of technologies –12. HoweTherefore, the present study aimed to analyze and characterize the process of HTR carried out by Conitec, focusing on the dimensions of analysis, criteria and decision factors that were relevant for the Committee recommendations.This study is the first step of our project. The full project consists of 5 steps: 1- Review of the current state of HTR carried out by Conitec; 2- Systematic review of the literature; 3- Development of a RTS framework; 4- Pilot study using the RTS framework; 5- Evaluation of the results, adjustments and validation of the RTS framework.We carried out a documental, exploratory, descriptive, retrospective study with qualitative-quantitative approach regarding the HTR performed by Conitec from January 2012 to November 2017.The study comprised the following steps:Selection and classification of technologies;Data extraction;Data analysis.Description of the HTR process and Conitec recommendations from the analysis of (i) consistency in the report on presenting analysis of dimension and criteria as evidence, issues related to the context of disease and technology, costs, public consultation, and others–and (ii) the decision factors for Conitec recommendations.Most of the final decisions were issued as “adoption” or “no adoption” of technology, regardless of the technology is already available in n SUS. Thus, for selecting the reassessed technologies, the types of evaluation requests, and so the final decisions, were reclassified based on the availability of the technology in SUS for the assessed indications, as shown in the All technologies available in SUS, and that were reassessed for an indication already approved within the health system.Health technologies: drugs, vaccines, health devices, and procedures.Reassessed technologies: health technologies  available in SUS, assessed in the same presentation and for the same indication.The reassessment request/decision was an extension of use/not extension of use ; maintenance/delisting from SUS (items c and f), restriction of use (item d); maintenance/exclusion of indication (item e).The exclusion criteria were as follows:Clinical protocols and therapeutic guidelines were not included. Each inclusion, exclusion, and change of use of technologies when drawing up or revising the protocols go through the same process of evaluation of other technologies and are contained in the set of technologies evaluated .New health technologies (in SUS context): technologies that were not available in SUS during the assessment period.Drugs with new concentration, new pharmaceutical form and new route of administration were also considered as new technologies for the health system, and, therefore, excluded from the present study.Technologies with a new indication, although already available in the health system for other clinical situations.The public data were collected directly from the recommendation reports available on the Committee website (January 2012 until November 2017) , namely:Technology name;Amount of technologies by decision: the analysis unit was defined as being the reassessed technology, even in cases where the demand or decision was related to more than one technology;Type of technology: drug, vaccine, device, procedure;Type of applicant: public sector  and private sector ;Indication;Type of assessment (reclassification as described in the method): new technology, new presentation, extension of use (new indication), extension of use , maintenance, restriction of use, exclusion of indication, delisting, exclusion of the International Classification of Diseases (ICD) from the protocol, protocol/guideline approval;Dimensions of analysis and criteria in the recommendation report;Decision factors for the recommendation; andFinal decision.The data related to the dimensions of analysis and criteria were extracted considering the main items in recommendation reports. The data related to the decision factors were collected from the items “final considerations” and “final recommendation” when the reports presented them. For reports that did not have a standardized structure, the above information was extracted from the full reading of the reports.Statistical analysis was performed using the frequency of the dimensions of analysis, criteria and decision factors presented in the recommendation reports. Then the findings were organized in tables with narrative description and discussion.Conitec had assessed 333 technologies, which includes drugs, vaccines, devices, procedures, and clinical protocols from January 2012 until November 2017 . Among oAfter applying the inclusion and disinvestment criteria described in the method, 47 health technologies were selected (14.1%), whose requests/decisions referred to a reassessment .Among the 47 technologies included in the study, 44 (93.6%) were drugs, two (4.2%) procedures and one vaccine (2.1%). Regarding the type of claimant, 41 (87%) demands originated from the public sector and only six (12.8%) from the private sector. The public demands–from the Ministry of Health and affiliated institutions–related to the extension, restriction, maintenance of use, exclusion of indication or complete delisting from SUS. All these public requests had a favorable recommendation, except the demand for widening the age range for mammography as a breast cancer screening method, which the judgment was unfavorable. All the private demands from pharmaceutical laboratories were to increase the use of the medication; three of them had received a favorable decision and three, unfavorable.Regarding the reason of the requests, the exclusion of some specific indication  was the most mentioned reason. In such cases, the technologies remained in the health system for the previously approved use. Fourteen requirements (29.8%) were made to the extension of the use of a given technology, twelve (25.5%) to delisting from SUS and maintenance and restriction, a request each (2.1%).Rheumatoid arthritis, HIV/AIDS, and hepatitis C were the indications for which most of the technologies were reassessed with seventeen (36.2%), ten (21.2%) and six (12.8%) demand, respectively. The other indications were Crohn's disease (two), multiple sclerosis (two), hepatitis B (two), breast cancer (one) epidermoid carcinoma (one), cystic fibrosis and exocrine pancreatic disease (one), Gaucher disease (one), hepatitis A (one), malaria (one) and congenital syphilis (one).The dimensions of analysis and the criteria for organizing the results were defined based on the information collected. Then, the data were structured according to the dimensions presented in the reports: context regarding the disease and technology, scientific evidence, costs, and social participation Tables  and 3.A little more than half of the evaluations  addressed aspects related to the disease, like its evolution, epidemiological data, diagnosis and treatment offered by the health system. The amount of technology used within the public system was taken into consideration in eight cases (17%). Issues concerning the implementation of technology as the availability of the technology in the Brazilian market, drug thermolability, storage and logistics for distribution and changes on the indications approved by the National Agency of Sanitary Surveillance–ANVISA were considered only in a few analyses .Clinical protocol development or updating had subsidized decisions on 22 technologies (46.8%), all relative to the exclusion of specific technology indication or delisting from SUS. International documents as reports of HTA and clinical protocols had based decisions on an extension of use (change in the treatment line or wide age range) of six technologies (12.8%).Scientific evidence about efficacy, effectiveness or safety were presented in 26 technologies assessment (55.3%). All the reports without scientific evidence were related to decisions of exclusion of the technology from SUS or exclusion of specific indication for a technology. The justifications for these cases were as follows: adjustments in the clinical protocol (14 technologies) with wrong recommendations (drugs recommended to treat conditions without indication in the package insert or without data from scientific literature); replacement of obsolete drugs (seven technologies), unavailability in the market (two technologies), stability/storage (one technology). In nineteen cases that the scientific evidence was lacking, the arguments supporting the decision were related to less efficacy or safety, along with others factors, however, no scientific data were presented in the reports.Of all assessments, clinical results extracted from the SUS database were used only in comparing the performance of interferon beta in the treatment of multiple sclerosis. Follow-up data of around ten years of patients using interferon beta for the treatment of multiple sclerosis in SUS demonstrated a statistically lower performance for intramuscular interferon beta as compared to another interferon beta regarding effectiveness (relapses and death outcomes) and treatment adherence.The budget impact estimates supported 16 decisions (34%)—twelve for extended use  of HIV/AIDS drugs, rheumatoid arthritis, multiple sclerosis, hepatitis A and hepatitis C and another four to an exclusion from the SUS of technologies for HIV/AIDS, hepatitis C and malaria. Seven of these assessments (15%) also used economic studies; being three cost-minimization studies, three cost-effectiveness study, and one a cost-efficacy comparison. All these seven evaluations were related to the requests for extension of use–six cases were for a change treatment line of drugs for rheumatoid arthritis, multiple sclerosis and AIDS, and one for the widening the age range for hepatitis A vaccine.In what concerns the public consultation, thirteen (27.6%) of the assessed technologies had undergone this phase.Although various information was taken into account for Conitec deliberation, some criteria were regarded as crucial for the decision-making Tables  and 3. CQuestions of adhesion, including dosage, route of administration and tolerability, impacted in the evaluations for restriction of use of intramuscular interferon beta, expansion of use of dolutegravir, darunavir and raltegravir, and exclusion of the medicaments fosamprenavir, didanosine, telaprevir and boceprevir from SUS list and exclusion of indications for the use of injectable interferon alfa-2b in the treatment of hepatitis B.In some delisted drugs, like telaprevir, boceprevir, stavudine, indinavir, and didanosine obsolescence was perceived, and more efficient and safer drugs substituted them. The medicament molgramostim, that was not marketed in Brazil due to its adverse events, was also delisted. The obsolescence was also verified in the evaluation of some specific indications of filgrastim and epoetin alfa–situations of complications with the use of telaprevir and boceprevir. With the exclusion of telaprevir and boceprevir, filgrastim and epoetin alfa lost their utility for this indication, although they remained in SUS for other conditions.For most technologies , the criterion of efficacy was essential for the Committee to decide on extension of use (fourteen technologies), exclusion of specific indication for the use of a technology (seventeen technologies), delisting from SUS (nine technologies), maintenance in the health system and restriction of use (one technology each).The fourteen drugs for which the efficacy was essential for decision of extension of use were, related mainly to HIV/AIDS, rheumatoid arthritis and hepatitis C . The other indications were: Gaucher disease, multiple sclerosis, breast neoplasm, and hepatitis A. In the cases of exclusion of indication (17 drugs), this criterion was used majority for drugs for rheumatoid arthritis treatment (14 drugs). At last, the efficacy of drugs for HIV/AIDS (5 drugs) and hepatitis C (2 drugs) was relevant for the de-listing decision-making. So, the relevance of this criterion was observed mainly for drugs related to HIV/AIDS, rheumatoid arthritis and hepatitis, independent of the kind of recommendation.Five technologies did not consider efficacy as a deciding factor for the recommendation. These drugs were related to exclusion from the SUS  and exclusion of indication (Two drugs for hepatitis C).Data effectiveness from the scientific literature and the SUS data were relevant in seven assessment for extension, exclusion, and restriction of use. To evaluate the comparison of the efficacy of interferon beta, we used data from SUS that resulted in the restriction of intramuscular beta interferon use. For the extension of the treatment period with sofosbuvir and daclatasvir, real-world evidence obtained from European patient cirrhotic genotype 3 who received treatment for hepatitis C during 24 weeks showing higher therapeutic successful results rates were essential ,23. Due Information about safety supported the extension of the use of seven technologies, decisions about the exclusion of nine technologies from SUS and exclusion of one specific indication. The extensions of use referred to the change of line , increase in the treatment period (sofosbuvir and daclatasvir) and the increase of age group . In general, the delisted technologies were replaced by others, to maintain options in SUS, so, patients were not uncovered .The costs were relevant for nine recommendations. The budget impact was considered a decision factor in seven decisions about the expansion of use–raltegravir (two decisions), tocilizumab (two decisions), sofosbuvir, daclatasvir and hepatitis A vaccine–and in the exclusions of telaprevir and boceprevir from SUS. The economic evaluation was taken into account to support the extension of use of hepatitis A vacccine.Other information were used to ratify the Committee's recommendations, such as the expansion of indications for registration with the ANVISA , lack of registration in Brazil (Pancrelipase and molgramostim), logistics of the program (Hepatitis A vaccine) and thermolability (Ritonavir).In order to analyze and describe the process of HTR performed by Conitec, 47 technologies were selected. Several requests for reassessment originated in the Ministry of Health, Health Departments and other institutions that comprise SUS, aimed at adapting the technologies within the health system. There were a few private requests—a sixth as compared to the public, and all were to change the treatment line for which the technology was already being offered by the SUS. Therefore, the private requirements did not aim to fully analyze the interventions within the system, but extend it use to a higher number of people.There was only one decision, to the public demands, contrary to the request for widening the age range for mammography as a method of breast cancer prevention because of the uncertainty benefits to the population. For a private application, half of the deliberations was favorable and half-unfavorable to the extension of use.Yuba et al. study evaluated the recommendations of all Conitec evaluations from 2012 to 2016  and alsoRegarding the reason of the requests, the exclusion of some specific indication was the most mentioned reason, followed by extension of the use of a technology and delisting from SUS. These results reflect a worldwide trend in using HTR, which is not focusing on the total exclusion of technology, but rather on refining clinical indications to optimize technology usage and the resources allocation within a healthcare system. In the UK, The National Institute for Health and Clinical Excellence is going towards this direction, having concluded that in practice, few technologies are prone to total disinvestment . In New Conversely, in France, the most active country in adopting the complete disinvestment strategy, a comprehensive review of all 4,490 drugs listed between 2000 and 2004 was conducted. As a result, 835 drugs were excluded from the national list  and 617 drugs had a reduction of reimbursement rate from 65 to 35%. There were contestations by the industry and between 2003 and 2006, a reevaluation of 723 drugs that were previously withdrawn from the list confirmed that 525 of them were insufficient [In Latin America, Agirrezabal et al. named some local disinvestment initiatives, although most of them did not present a comprehensive description of the process used in finding, prioritizing, evaluating, implementing, and the results of the disinvestment. Four studies referred to Brazilian cases, and only one was considered as a potential disinvestment approach . In thisSuch results illustrate and emphasize the difficulty in removing technologies already available in the healthcare system, making it necessary to combine scientific data, in these cases, more detailed and extensive, with the stakeholders' interests. However, generating data that contradict some practices is not always enough, since many physicians continue to administer treatments proven ineffective and even harmful to patients .In this context, policymakers may play a key role in regulating the use of such technologies, and therefore should consider the adoption of active forms of disinvestment, not only those aimed at total exclusion, but also the restriction treatment to subgroups, price or reimbursement rate reductions, encouragement of generic prescribing .Regarding the indication of requests, the vast majority of the technologies reviewed were related to rheumatoid arthritis, HIV/AIDS, and hepatitis, which, along with oncology, represent the leading health topics for new adoption requests . ConsideThus, as highlighted above, reassessments were made based on demands, the vast majority presented by the Ministry of Health itself and departments or organizations linked to SUS. Demand-based assessment is limited by the fact that it does not systematize all technologies that need to be adjusted in the face of new evidence  and those that should be excluded because they are ineffective or unsafe.Studies on disinvestment methodologies point out that the initial stages of selection and prioritization are fundamental to generate greater transparency and enable all technologies to be reviewed ,31,32. SHowever, setting the goal of the HTR program is required to decide on how to select and prioritize technologies, as Sustainability in Health care by Allocating Resources Effectively (SHARE) program in Australia advocates. In this case, "the aim of the SHARE Program was to establish organization-wide, systematic, integrated, transparent, evidence-based systems and processes for decision-making about disinvestment in the context of resource allocation at Monash Health" .Other initiatives that have been implemented in Australia sought to refine the indications for resource allocation to ineffective or inappropriately applied health care practices, to subsidize decision-related to ineffective drugs and vaccines in the Pharmaceutical Benefits Scheme (PBS), also, to maximize the patients’ health and the supply sustainability. Some of these programs implemented in a local, regional and national level reported recommendations after RTS, such as: disinvestment of assisted reproduction technologies (in vitro fertilization and intracytoplasmic sperm injection), vitamin B12 and folate tests, discontinuation of public funding of kyphoplasty and percutaneous vertebroplasty for vertebral compression, revisions of colonoscopy items, surgical treatment for obesity, pulmonary artery catheterization, catheterization in ophthalmology, and restriction in the rules for screening for cervical cancer ,36.In Sweden, the nation-wide “Uncertainties and Disinvestment Project” was designed to identify scientific uncertainties, to inform and support decision makers in prioritizing and allocating resources within the health services. As a result, there was disinvestment of arthroscopy in arthritis, a corticosteroid to lateral epicondylitis and, clinical replacement versus routine replacement of peripheral venous catheters. In the UK, NICE recommendations based programmes aimed to inform about the financial aspect of resources utilization, safety, effectiveness and health care quality process. Another initiative in the UK intended to reconfigured services to provide more health gain at a reduced total cost .Another point highlighted is the setting of deadlines for HTR, not observed in the Conitec process. Citing the example of other countries a recent systematic review of the sustainability programs and innovations have shown, in most of the studies, that the first evaluations were conducted after two years of the technology implementation ,37. The The dimensions of analysis found in the recommendation reports were scientific evidence on efficacy, effectiveness or safety, disease-related issues, issues related to the use of technology, costs, and social participation. However, these dimensions were not included in all analysis, and a standardized structure of the reports has not been observed.To decision-making, the criteria of efficacy safety and use of the technology were the most relevant for the set of evaluations. These data are in conformance to the primary concern of the health systems from France, Australia, New Zealand, Canada and the UK, that is, to identify safety and efficacy problems that were not previously identified or underestimated in a randomized clinical trial . BesidesAnother critical point to be mentioned was the lack of social participation through public consultation in most of the decisions. Although the argument that some technologies can have a fast-track appraisal process, the rules for this type of evaluation are not well defined. Thus, such technologies were reassessed regardless of the stakeholders' value and preference, which may compromise the legitimacy and acceptability of the decision. In order to achieve greater acceptance of decisions and to identify the potential impacts in the society, HTR process could involve the politicians, clinicians, speciality societies, health system leaders, industry, and patients . In the The decision-making oriented by the results of the technology performance, although not being observed as a regular practice by CONITEC, in other countries, some strategies have been adopted in this sense. Negotiation for price reduction and reduction of reimbursement rates has usually been implemented in countries such as Canada, France, Australia and New Zealand after analyzing the results of technology performance ,39. In aManaged entry agreements (MEAs) contractual agreements also have been used when uncertainty regarding the clinical effectiveness, safety or resource use associated with a technology is high. This kind of agreement distributes the risk of uncertainty between the payers and the manufacturer. In this case, additional further evidence generation is required . FollowiAs limitations to the present study, we point out the reclassification of the decision types by the authors as there is no definition of the term "reassessment" in SUS, and this may not reflect the perspective of the technicians and managers who participate in the Conitec deliberations. Moreover, the arguments described in the reports might not explicitly portray the justifications for the decision-making presented during the Committee meeting.The reassessment process has appeared among other strategies for reducing the use of ineffective, less effective or unsafe practices and, consequently, to avoid a resources waste. The results of Conitec six years of work presented initiatives with this goal. Although positive results were obtained, this activity is not yet structured, with gaps regarding the selection phase and reassessment of SUS list of technologies, since it has not been identified method and criteria for its conduction.Therefore, this study reinforces the need to prioritize structuring actions in within the SUS that improve the management of technologies, both those recently incorporated and also these adopted before the establishment of the Committee. Thus, it is suggested the implantation of a monitoring program and HTR, with endorsed methodology and that it contemplates in deepened way implementation questions (barriers and facilitators), stakeholder perspectives, and scientific, social, ethical, and legal questions. Such actions need, inevitably, short-term time and resources, but might add long-term gains in efficiency ,44.Finally, we expect that this study can contribute to the formulation of a systematic, transparent, and objective process for a revision of the list of technologies offered by the Brazilian Public Health System–SUS. Such process can be helpful in defining the "true" value of a given technology in real conditions of use, contributing to better quality in the healthcare and sustainability of the healthcare system.S1 Table(XLSX)Click here for additional data file.


Cardiovascular disease (CVD), including coronary artery disease (CHD) and stroke, is the leading cause of death and disease burden globally . An estiOverall, the increasing global burden of disease is alarming and we are challenged with the need for scalable solutions that address prevention and ongoing management. Solutions lie in changes in the individual, family, communities and broader society. Such solutions need to overcome the barriers of distance, capacity and resourcing, while being simple and meaningful to people. Major advances in affordable technology offer an opportunity to maximise effectiveness and reach of health care. In the past decade, there has been rapid proliferation in the number of people who are able to access the Internet, with 4.1 billion people using the Internet globally, increasing from 3.7 billion Internet users in late 2017 . The escAs such, e-Health encompasses the provision of health-related services, hardware devices and software. Examples include the use of the Internet, Bluetooth devices, remote monitoring devices, wearable devices, text-messages and smartphone apps, amongst others. In recent years, there has been rapid expansion of these in the development and delivery of strategies aiming to address a number of health needs across different medical conditions. These strategies include education of patients and healthcare providers, data collection, diagnostics and screening, patient monitoring, treatment support, behavioural change support and communication between patients, health professionals and health services . CurrentMedical Sciences is to explore potential opportunities for e-Health in CVD research and management. The special edition includes a variety of original research papers and reviews that cover development and implementation of several e-Health strategies. All are aimed at using technology to increase reach and enable better delivery of CVD prevention and management.The aim of this Special Edition of The paper by Wang et al.  assessedThe paper by Dowie et al.  reports The paper by Clark et al.  highlighMedical Sciences offers a variety of examples on how e-Health data and strategies can potentially be used to improve the delivery and reach of healthcare. Future research and health services reviews will no doubt continue to explore, define and determine the evidence-base for e-Health and its ultimate contribution in the years to come.In conclusion, the current special edition of


Ophiocordyceps sinensis (Berk.) G.H. Sung, J.M. Sung, Hywel-Jones & Spatafora, an entomogenous fungus endemic to the Tibetan Plateau, is one of the best known medicinal fungi in China and around the world. It has been documented in literature for hundreds of years and officially classified as a drug in the Chinese Pharmacopeia  and HKAS  and on examination of literature of more than 3600 publications. A total of 203 localities at county level for O. sinensis were recorded and analyzed. Among them, 106 were considered as confirmed distribution sites, 65 as possible distribution sites, 29 as excluded distribution sites, and three as suspicious distribution sites for the fungus  to southern regions and subsequently to northern areas  to organize the survey of the species occurrence through administrative division with the support from the government from prefecture level down to every country, township and village, marking the production area to each mountain, finding the dates of emerging and terminating of the stroma, calculating annual yields based on real harvest; (ii) to determine the site for long-term field observation based on the habitat, fungal genetic background, transportation and living facilities at the location, to conduct the long-term observation with climate, soil and environment factors and also physical, chemical and biological characters, e.g., temperature, humidity, precipitation, organic matter, soil texture, pH, vegetation types, biomass, community structure, animals, soil microbes, and so on, and to monitor the occurrence of the fungus and its host insects, as well as the harvest grazing and human activities; (iii) to establish special natural reserves for the fungus and to carry out the management for sustainable uses of the fungal resources, including local laws and government regulations, time and methods of harvesting, measures for improvement of grassland for the fungus and its host insects, etc.; (iv) to construct the comprehensive database for recording and management of the fungus, its host insects, and the grassland for its survival and reproduction.The extensive survey and long-term field observation for O. sinensis is largely consumed in its dried form as a stroma emerged from a sclerotium which is covered by the exoskeleton of caterpillar larva. The maturity of the stroma is considered very important to the quality of the product. The immature specimens with stromata protruded from intact and solid sclerotium are much more welcomed than those with well grown or mature stromata because the nutritional reserves within stromata have been exhausted. To maintain the medicinal value, the stromata and sclerotia of O. sinensis are harvested before they start to produce and release the spores for reproduction. It is an urgent need to manage the natural resources of O. sinensis which have limited natural production but are so extensively harvested by human overexploitation.Along with market demands,


Dear Editor,Capecitabine is a chemotherapeutic fluoropyrimidine that acts as a prodrug, being metabolized into 5-fluorouracil through an enzymatic cascade, and is used for treatment of solid colorectal, gastric, and breast tumors. Its use has become popular in recent years due to its similar efficacy when compared to 5-fluorouracil, with a more tolerable toxicity profile and the convenience of oral administration.2/daily. She developed a rash on her face, neck, and scalp after six weeks of capecitabine use. The patient did not present fever, arthralgia, or myalgia. Physical examination showed erythematous, scaly patches along the V-line of the upper chest and interscapular region; there was also diffuse erythema in the androgenetic alopecia region, which pointed to a photosensitive component , and capecitabine was defined as the offending drug.Topical treatment with betamethasone and sun-protective measures were taken and, after capecitabine cessation, the patient showed great improvement of the skin lesions.SCLE is characterized by erythemato-squamous and annular lesions, with remarkable photosensitivity, typically associated with elevated serum levels of anti-Ro antibodies. It can be categorized as drug-induced or idiopathic, both forms being indistinguishable in clinical, serological, and histological aspects.Since the first report of drug-induced SCLE, associated with the use of hydrochlorothiazide, a growing number of medications have been described as culprits for the syndrome.A PubMed and MEDLINE review showed only eight cases of capecitabine-induced SCLE in the literature, and there have been no cases reported in Brazil up to now. This may be caused by an under-reported number of cases and/or may be attributed to our limited experience with the agent, which was only approved by the Brazilian Health Surveillance Agency , the country's organ responsible for drug regulation, in 2015, for the treatment of colorectal, stomach, and breast cancers.Although the pathogenesis behind capecitabine-induced SCLE remains unknown, its growing use in different types of cancer proves necessary the report of dermatological manifestations of the drug. The recognition of this side effect by dermatologists is vital, so that drug-induced SCLE may be included early in the differential diagnosis of patients who are using capecitabine and present skin lesions.None declared.Aroni Rocha: Approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; critical review of the literature; critical review of the manuscript.Hiram Larangeira de Almeida Jr.: Approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; intellectual participation in propaedeutic and/or therapeutic conduct of the cases studied; critical review of the literature; critical review of the manuscript.Gustavo Zerwes: Approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of the cases studied; critical review of the literature; critical review of the manuscript.Umberto Lopes de Oliveira Filho: Approval of the final version of the manuscript; conception and planning of the study; elaboration and writing of the manuscript; effective participation in research orientation; intellectual participation in propaedeutic and/or therapeutic conduct of the cases studied; critical review of the literature; critical review of the manuscript.None declared.


Leishmaniasis represents the important public health problem in the world. One of the main objectives of World Health organization is capacity building of managers and authorities who are involved with diseases control activities.The course was conducted in Esfahan Health Research and Training Center (E.H.R.T.C) in summer 2005 and 2009. The course carried out jointly by the Ministry of Health and Medical Education (MOH) of Iran, World Health Organization-Eastern Mediterranean Regional Office (WHO-EMRO) and School of Public health, Tehran University of Medical Sciences (SPH-TUMS) and designed for medical officers, senior technicians and managers involved in leishmaniasis control. Prior to initiate the course, pre-test evaluations including different subjects on leishmaniasis and its control were carried out. The examinations include multiple choice questions. The duration of the course was 3 weeks. A total of 206 contact hours were taught. The main subjects were Basic epidemiology, Leishmaniasis parasitology, Leishmaniasis entomology, control of vectors and reservoirs, principles of integrated pest management, Field work and Planning. Different methods of teaching including lecture, laboratory, workshop, team work, field exercise and presentation were used. Requirement for achievement of the course was to have at least 60% of the total mark for awarding the diploma certificate.A total of 45 participants from Iraq, Afghanistan and Iran graduated from this course.The course is providing the skill for managers, how to combat against disease in their country and is parallel to the policy of the leishmaniasis control for capacity building in endemic areas of their countries. Leishmania and is transmitted to animals and humans through the bite of certain species of female sand flies  occurs in two forms, Anthroponothic Cutaneous Leishmaniasis (ACL) and Zoonotic Cutaneous Leishmaniasis (ZCL) . The incThe main elements of cutaneous and visceral leishmaniasis control programs in the Islamic Republic of Iran have focused on the establishment of a national committee for leishmaniasis control, are as follows:Strengthening the leishmaniasis surveillance system and establishing a laboratory network from the national to peripheral level, establishment of standard diagnosis and treatment centers, provision of educational programs for different social levels and revision of the national guideline, standardization of case definition and treatment results, early diagnosis and rapid treatment of patients accompanied by dressing wounds to prevent sand fly bites, reservoir control programmes, collecting the rubble and rubbish tips and vector control programs, applying direct agglutination test in periphery levels for visceral leishmaniasis diagnosis, identification and collection of infected owned and stray dogs in visceral leishmaniasis endemic foci, intersectional coordination with related organizations and institutions . LeishmaThe course was organized jointly by the Ministry of Health and Medical Education, Islamic Republic of Iran, The School of Public Health and National Institute of Health Research, Tehran University of Medical Sciences, World Health Organization, Eastern Mediterranean Region (EMRO). It provided the participants with the knowledge and skills in different aspects of leishmaniasis and its control, through small group work, field exercises, exchange of experiences and discussions with qualified specialists.Description, history and geographical distribution of leishmaniasis in the world and Eastern Mediterranean Regional Office (EMRO), Epidemiology of leishmaniasis in Iran and neighboring countries, effects of climate change and disaster on leishmaniasis situation.Clinical manifestation and treatment of old world cutaneous and visceral leishmaniasis: physical systematic, interleisonal, oral drugs, management of visceral leishmaniasisNatural immunity and Acquired immunity, Experience of vaccination in leishmaniasis, serological surveillance of asymptomatic visceral leishmaniasis and case detection, leishmaniasis surveillance in Iran.Methods of studies on human disease: rates, ratios, proportions, prevalence and incidence of leishmaniasis, data presentation: common statistical tests, tables, graphs, charts.Phlebotomus genus.An overview of vectors and reservoirs of leishmaniasis, biology and ecology of sand flies, Taxonomy of sand flies, identification criteria, explaining of identification keys. Identification of sand fly genera: different sub-genera of Leishmania parasites, molecular entomology of leishmaniasis vectors.Sampling methods of sand flies: sucking tube, CDC light traps, funnel traps, sticky oil traps and other techniques, preservation, mounting and identification of sand flies, collection of sand flies on human and animal baits, dissection of sand flies for detection and isolation of Rodent leishmaniasis, biosystematics of rodents, identification of main reservoir hosts, biology, ecology, distribution and behavior of rodents, criteria for incriminating rodents as reservoirs, methods of field and laboratory studies of reservoirs of cutaneous and visceral leishmaniasis, canine visceral leishmaniasis, molecular epizootiology of rodent leishmaniasis.50 and LT90 using Probit analysis, insecticides recommended by WHO against leishmaniasis vectors, formulation of insecticides for residual spraying, measurement and calculation of insecticides for impregnation of bed nets and curtains, safe use and judicious use of insecticides and precaution measures, insecticide storage (condition of safe storage), space spraying, Ultra Low Volume (ULV), thermal fog.Different methods of prevention and control of cutaneous and visceral leishmaniasis, methods for evaluation of leishmaniasis control, different methods for elimination of stray dogs, Leishmanization and its effectiveness in the control of CL in Iran, Vaccine for visceral leishmaniasis, principals of integrated pest management (IPM planning), rodenticides and environmental management and sanitation, destroying of chenopods, different methods of rodent control, insecticide susceptibility tests on sand flies, calculation of LTPhlebotomus genus (laboratory practice), collection of sand flies by different methods , carrying of traps from the field to laboratory, dissection of collected sand flies for detection and isolation of Leishmania parasites, mounting, identification of collected sand flies, collection of rodents by Sherman traps in the field and carrying of them to the laboratory, identification of collected rodent reservoirs, preparations of smears from the ear of each rodent, fixation of slides, staining with Giemsa microscopic examination of slides, isolation of parasites from infected rodents, measurement of rodenticides for application in the field circumstances, preparing of poisoned bait, education of workers, domestic dog examination and control, field application of rodenticides, its monitoring and evaluation impact, visiting households in 3 villages for case finding, examination of people for the presence of ulcers or scars, recording the necessary information on the related forms, preparing smears from ulcers, fixation of slides, staining with Giemsa, microscopically examination of slides, visiting health centers for examination and treatment of patients of CL in Esfahan, different methods of prevention and control of cutaneous and visceral leishmaniasis, methods for evaluation of leishmaniasis control, principals of integrated pest management, Integrated Pets Management (IPM) planning, different methods of rodent control, insecticide susceptibility tests on sand flies, calculation of LT50 and LT90 using probit analysis, insecticides recommended by WHO against leishmaniasis vectors, formulation of insecticides for residual spraying, measurement and calculation of insecticides for preparation of bed nets and curtains, safe use and judicious use of in insecticides and precaution measures, space spraying, ULV, thermal fog, different parts and function of Hudson pump and thermal fog, measurement and calculation of insecticides for impregnation of bed nets and curtains , practical work for indoor residual spraying at the station, collection of sand flies by aspirator from the villages, carrying out insecticide susceptibility tests by WHO standard method on collected sand flies, results of susceptibility tests on sand flies: recording and analysis, suggestion of a control program for an Anthroponetic Cutaneous Leishmaniasis (ACL) focus, suggestion of a control program for a Zoonotic Cutaneous Leishmaniasis (ZCL) focus, suggestion of a control program for a Visceral leishmaniasis (VL) focus.Collection of sand flies by different methods from outdoors and indoors in a rural district (field work) around Esfahan, carrying of traps from the field to laboratory, preservation and mounting of collected sand flies, identification of sand fly genera: different sub-genera of In evaluating the training course, almost all the training units in the module were covered during the period. There were adequate facilities for the delivery of lectures. These include a well-furnished spacious room for lectures with adequate audio-visual equipment. These include a white board, a slide projector and screen and a dedicated computer for the training. Each participant was provided with a copy of the relevant books and handouts. The participants were given practical field experience and laboratory demonstrations. The laboratory was well equipped with dissecting and compound microscopes which made it possible for each participant to individually and independently do the laboratory work. There was enough reference collection of sandflies available for practical work. All the facilitators tried to make the course as participatory as possible and there was very good relationship between the facilitators and the participants. Almost all the participants through verbal communication rated the entire course as very good, delivery of lectures as excellent and practical demonstrations and fieldwork as good. The onsite accommodation for participants enabled all the activities to be organized on time.In general, based on the assessments and interviews, also considering the fact that most of the participants were programme managers and medical health professionals who have had very little knowledge on entomology, vector and reservoir control, the course achieved its purpose of providing them with basic information needed for decision making in disease control activities in their respective countries. The participants and facilitators for the first time shared experiences with regard to vector control activities between different countries. We will recommend that all the participants should be monitored and given the necessary support to enable them contribute to diseases control and elimination activities in their respective countries.


The European Brain Council (EBC) serves as a pan-European platform, bringing together brain researchers, patient advocates, scientists, and clinicians around a common vision for the “brain space.” At the heart of our advocacy work are accelerating brain research, raising awareness of the challenges associated with brain disorders, reducing stigma and discrimination, and supporting science. Our mission revolves around promoting brain research and brain health at the European level to the benefit of people living with neurological and psychiatric disorders.Brain disorders are highly prevalent diseases that impose a tremendous burden on European society. In 2010, more than 1 in 3 European citizens were affected by a mental or neurological disease , but also to ensure the creation of an appropriate and functioning structure that would enable brain research to be prioritized and efficiently addressed.- The adoption of a brain mission. This idea, suggested by the high-level group, was taken on board of the program proposal and is currently looked into by the European Commission, European Parliament, and the EU member states. The Brain Mission, as proposed by EBC, is aimed to serve as a guiding paper in this process .www.ebra.eu) (Grant agreement No 825348). The overall idea underpinning EBRA is to coordinate and synergize brain research projects and initiatives at both European and global level in order to foster the efficiency of efforts in brain research. EBRA brings together the brain research community at large, the major brain research initiatives, research funding networks, and all relevant stakeholders at the European level and beyond, to ensure the overall delivery of the research potential. Therefore, EBRA was created as platform that would catalyze coordination between brain researchers, clinicians, patients, governments, funders, and public institutions, while fostering global initiatives. EBRA consortium is led by EBC and brings together the Joint Programming on Neurodegenerative Diseases, the Human Brain Project, and the ERANET Neuron. For the next 3 years, the Consortium will work to align and coordinate research strategies across European and global brain initiatives; facilitate the launching of research projects in specific areas in active clusters, and help them to collaborate effectively, share data, and access research infrastructures; and increase the brain research visibility and promote the uptake of EBRA results to key stakeholders.Amidst these political discussions, in November 2018 the EBC launched an EU-funded project The European Brain Research Area (EBRA, Brain research in Europe is a rapidly evolving field, and it has always been at the forefront of science. Nonetheless, the inherent complexity of the nervous system has made our translational capacity more challenging, hence requiring a higher level of integration. EBC, through its EBRA project, remains committed to supporting the strategic vision of favoring a sustained open research community, with high level of collaboration and knowledge-sharing across the borders of various disciplines, to improve the quality of life of all citizens living with a brain condition in Europe.


In the article titled “Efficacy and Safety of Sipjeondaebo-Tang for Anorexia in Patients with Cancer: A Pilot, Randomized, Double-Blind, Placebo-Controlled Trial” , there wThis error in the reporting was brought to the attention of the journal by Professor Edzard Ernst, Emeritus Professor of Complementary Medicine, University of Exeter. The journal and the authors apologize for this misreporting of the conclusions.


Biology and biotechnology have changed dramatically during the past 20 years, in part because of increases in computational capabilities and use of engineering principles to study biology. The advances in supercomputing, data storage capacity, and cloud platforms enable scientists throughout the world to generate, analyze, share, and store vast amounts of data, some of which are biological and much of which may be used to understand the human condition, agricultural systems, evolution, and environmental ecosystems. These advances and applications have enabled: (1) the emergence of data science, which involves the development of new algorithms to analyze and visualize data; and (2) the use of engineering approaches to manipulate or create new biological organisms that have specific functions, such as production of industrial chemical precursors and development of environmental bio-based sensors. Several biological sciences fields harness the capabilities of computer, data, and engineering sciences, including synthetic biology, precision medicine, precision agriculture, and systems biology. These advances and applications are not limited to one country. This capability has economic and physical consequences, but is vulnerable to unauthorized intervention. Healthcare and genomic information of patients, information about pharmaceutical and biotechnology products in development, and results of scientific research have been stolen by state and non-state actors through infiltration of databases and computer systems containing this information. Countries have developed their own policies for governing data generation, access, and sharing with foreign entities, resulting in asymmetry of data sharing. This paper describes security implications of asymmetric access to and use of biological data. Advances in computer science, engineering, and data science have changed research, development, and application of biology and biotechnology in the United States and internationally. Examples of changes include: (a) increased reliance on internet connectivity for research and laboratory operations  the 2018 update of the European Union General Data Protection Regulation  how the data may be exploited by adversaries and what consequences result from this exploitation; and (2) what potential negative effects may arise from digitalization of biotechnology and advanced computation of biological data . Strategies for bridging the biological, cyber, information, and data security include: (a) collaboration between the biological and cybersecurity communities; (b) end-to-end risk assessments; (c) data-specific risk and vulnerability assessments; and (d) application of the NIST Cybersecurity Framework for protecting biological data.Given these potential vulnerabilities, the cybersecurity and biotechnology communities must engage to create best practices and processes to protect data and mitigate risk while reaping the benefits of computing technology applications to biotechnology.Formal collaboration between the biotechnology and biological, information, data, and cyber security communities would enhance efforts toward identification of risks and vulnerabilities associated with data management, provenance, and integrity, and risk mitigation strategies. Technologies are readily available to protect data, but their use must be harmonized worldwide, because protecting data in one database is ineffective if another database remains vulnerable to external threats. Furthermore, organizations may evade regulatory requirements and industry standards in protecting data because of perceived lack of cost savings for implementing cybersecurity measures or lack of awareness of the risks, which could lead to investor, intruder, or adversary access to sensitive information that may be stored in databases or transferred between computers. These vulnerabilities may be exacerbated by limitations of national laws to other sovereign states, and differences in interpretation of the types of data included in the scope of existing laws. These risks could be addressed by conducting an end-to-end risk assessment of the software and equipment involved in the data pipeline within individual organizations, between organizations, and across countries.End-to-end assessments of the data storage, processing, and transport pipeline can identify outstanding vulnerabilities and technical gaps that may be addressed with currently available cyber, information, and data security solutions. This process would enable identification of gaps for which these measures are insufficient and of institutions that are responsible for implementing controls. Without this type of assessment, vulnerabilities may exist along the pipeline without its users' knowledge. A lack of rigorous analysis makes biological data vulnerable to acquisition or alteration by witting adversaries, potentially resulting in theft of intellectual property for commercial gain, foreign government acquisition of genomic data from large portions of a population for undefined purpose or compromise of software and data integrity. At least one country promotes acquisition of data though legitimate commercial practices , talent promotion programs  are critical for reaping the benefits and minimizing the vulnerabilities of advanced electronic computation and mass connectivity. In 2014, the White House explored technology needs for protecting the security and privacy of exposed data, including healthcare data  Cybersecurity Framework to all systems of storage, processing and transport of biological data would help explore where, how, and by whom data is processed with the goal of protecting valuable scientific and health information (National Institute of Standards Technology, These suggestions describe various approaches toward protecting biological data from unauthorized acquisition and use, enhancing efforts to preserve data integrity and provenance, and enabling future benefit of biotechnological advances.KB and PS contributed equally to this manuscript. The concepts, conclusions, and recommendations were generated jointly by the authors and built on their respective expertise in the biological sciences and biosecurity, and computer science and cybersecurity.KB was employed by Gryphon Scientific. PS was employed by Promontory Financial Group, which is an IBM Company. The authors declare that the paper was written in the absence of any commercial or financial relationships that would constitute a conflict of interest.


However, this option has been associated with strong medical, ethical, legal, religious, and media or public concerns and discussions, as in the case of Maltese conjoined twins operated on in the 2000s in the UK -5. In thNowadays, tertiary centers specialized for the treatment of conjoined twins have been established all over the globe ,7 and thCroatian Medical Journal, is both an exciting medical story and evidence of an important success of Croatian medicine. The authors clearly describe the entire diagnostic and treatment process: they recognized conjoined twin fetuses early in the 11th week of gestation, followed them through pregnancy, and confirmed their findings with magnetic resonance imaging (The case report by Grizelj et al on a successful separation of conjoined twins at the University Hospital Center Zagreb , publishThis case clearly shows that a highly dedicated and experienced team of health care professionals, with the help of modern and advanced technology, may recognize, follow, and successfully treat even the extremely complex cases. All this being said, let me congratulate the Croatian team on this outstanding clinical accomplishment, which was not only based on the right and timely clinical decisions, but also reflects the team's high sensitivity to ethical and legal aspects of the case and their professional interaction with the public and media.


Reproductive health is vital for human and infertility is also one of the most important challenges in the reproductive system. Infertility is one of the most common chronic health disorders, regardless of age. The Minimum Data Set (MDS) helps to manage infertility by monitoring and evaluating infertility interventions based on collecting data.The development of MDS is an essential objective in order to implement an infertility monitoring system for the creation of standardized and effective data management through the provision of comprehensive and identical data elements for infertility.This is a descriptive cross-sectional study conducted in 2017. The data has been collected from infertility clinics in the world, as well as WHO, CDC, ASRM, and ESHRE reports.In order to decide on data elements, the Delphi technique was used using a questionnaire that contained data elements which were distributed among 12 experts including one reproductive endocrinology and infertility fellow, six obstetrician-gynecologists, two reproductive biologists, two urologists and one community medicine specialist using the 5 point Likert scale. The questionnaire was divided into two categories: managerial and clinical, each with 4 sections, and 60 and 940 data elements, respectively.MDS is an essential tool for evaluating the infertility process. Using this tool will provide an opportunity to develop a set of quality care criteria that can be used to ensure the quality of infertility care. One of the key issues is the global emphasis on public health policies and programs to increase the population and provide affordable, safe and well-planned and effective services for families . AccordiInfertility is one of the six maternal diseases/consequences which has been neglected in developing countries . InfertiTherefore, in order to fully understand the effects of infertility and measure progress in reducing this problem and to cope with the growth management of data and information, attention to the collection, analysis, interpretation, and use of infertility data are of great importance . MeanwhiThis is a descriptive cross-sectional study conducted in 2017. Information resources, including related articles, reports and forms related to infertility clinics and texts were searched using the following keywords: minimum data set, MDS, core data, infertility, infertility form, IVF registry, ART registry, surveillance system, monitoring system in the PubMed database, Scopus, Cochrane and WHO, CDC and Google scholar websites from 1978 to 2017. Collected data, according to the standards set of American National Standard Institute (ANSI), previous articles and references book were classified into managerial and clinical categories , 24-26 aThe purpose of this research is to develop the MDS required for a national infertility monitoring system in order to accelerate and facilitate the prevention, diagnosis, and follow-up of infertility.This study is a research project as a part of the Maryam zahmatkeshan Ph.D. thesis approved by Tehran University of Medical Sciences. Also, the ethics committee of the university approved this study (IR.TUMS.SPH.REC.1396.4142). Verbal informed consent was obtained from all subjects before the study.SPSS 16 software was used to analyze the data.Of the 12 experts, 75% were female, and 25% were male. MDS was divided into two categories of managerial and clinical, each with 4 sections. The total number of final data elements in the managerial groups was 60 and 940 in the clinical groups. Examples of the managerial and clinical data elements that were accepted as the final set (over 75%) are listed in Clinical data elements were categorized into four parts:Medical history: Causes of Infertility, Sexual history , Previous Examinations, Previous Diseases, Treatments, Tests, Surgeries, Medication, Social History, Family History, and Pregnancy History.Treatment plan: Cycle Characteristics of the Treatment, Specifications of Eggs, Embryos/Blastocyst Profile, Treatments Treatment results: Pregnancy and Childbirth, ComplicationsDonor information.Infertility affects over 15% of couples in reproductive age, and the prevalence of infertility in the world is increasing . An accuIn this study, based on the results obtained by using the Delphi technique, the majority of relevant experts agreed with the proposed model and it is considered suitable for infertility centers. Therefore, the proposed model as the final model of this research is recommended, and its implementation is recommended to infertility centers.Various studies point to the importance of MDS in the development of information management system in different areas such as burns , trauma Identification of the minimum data set is the first step to standardize and integrate the data used in the diagnosis and can be useful in evaluating it . MDS proConsidering the adverse effects of infertility, designing and implementing a comprehensive and appropriate infertility data set model in centers can be an essential step in the creation of infertility monitoring system for high-quality and proper treatment, regular planning for controlling and preventing infertility, allocating credit to infertility centers and clinics and doing research. MDS helps infertility management by providing continuous care of patients, establishing a link between care providers and analyzing the effectiveness of patient care and the community of infertile patients. Through the use of MDS organized as designated forms, patient identification indicators, efficiency indicators of the care process and the quality of the services provided as well as outcome indicators, fertility management was improved. In addition, it will be possible to develop policies, prevent and control infertility and, consequently, improve the quality of care and save costs.It is clear that an important issue in preventing infertility is having access to credible and powerful information systems such as an infertility monitoring system. Although some countries develop and implement infertility management systems, data cannot be compared correctly due to differences in data and lack of international standards. Therefore, the provision of such standards will lead to the development of these systems in other countries.The authors would like to thank all the specialists from the Fasa University of Medical Sciences who participated or otherwise contributed to this study.The authors confirm that there are no conflicts of interest.


Zinc is one of the most important essential trace elements. It is involved in more than 300 enzyme systems and is an indispensable participant in many biochemical processes. Zinc deficiency causes a number of disorders in the human body, the main ones being the delay of growth and puberty, immune disorders, and cognitive dysfunctions. There are over two billion people in the world suffering from zinc deficiency conditions. Acyzol, a zinc-containing medicine, developed as an antidote against carbon monoxide poisoning, demonstrates a wide range of pharmacological activities: Anti-inflammatory, reparative, detoxifying, immunomodulatory, bacteriostatic, hepatoprotective, adaptogenic, antioxidant, antihypoxic, and cardioprotective. The presence of zinc in the composition of Acyzol suggests the potential of the drug in the treatment and prevention of zinc deficiency conditions, such as Prasad’s disease, immune system pathology, alopecia, allergodermatoses, prostate dysfunction, psoriasis, stomatitis, periodontitis, and delayed mental and physical development in children. Currently, the efficiency of Acyzol in the cases of zinc deficiency is shown in a large number of experimental studies. So, Acyzol can be used as a highly effective drug for pharmacologic therapy of a wide range of diseases and conditions and it opens up new perspectives in the treatment and prevention of zinc deficiency conditions.  Essential trace elements, including zinc as a special one, are the functional basis of many enzyme systems; therefore, their deficiency has a negative effect on cell viability. There are approximately 3000 proteins interacting with zinc ,2, a conZinc essentially preserves the structure of DNA, RNA, and ribosomes. As a component of the aminoacyl-tRNA synthetases and the protein chain elongation factor, it plays an important role in the translation process and thus, it is indispensable in many key stages of gene expression. Therefore, nutritional or genetic zinc deficiency disrupts the functioning of all cell cycle phases and genetic apparatus function. In fact, zinc deficiency may result in stunted growth and delay in physical and mental development.Zinc plays a major role in the hormonal status in the human body by directly affecting the production and activity of the hormones of thymus, thyroid glands and pancreas. Zinc regulates several glycolytic processes avoiding diseases, such as type 2 diabetes mellitus and plays an important role in the processes of insulin binding to hepatocytes and lipoprotein synthesis ,14. ZincSalmonella enteritidis, Lysteria monocytogenes, Candida albicans, Toxoplasma gondii, which would increase the risk of incidence of pneumonia, malaria, tuberculosis, measles and other infectious diseases  is a zinc-containing drug with high bioavailability, low toxicity and good tolerability, which was synthesized in the Irkutsk Institute of Chemistry of Siberian Branch of the Russian Academy of Sciences. The structural formula of the compound is shown in Acyzol has a large therapeutic window and it is safe under prolonged (90 days) daily intramuscular injection, intragastrically and peroral administration to experimental animals including mice, rats, and dogs. Acyzol application does not cause pathological changes of biochemical parameters and has no negative effect on the physiological systems of the body and on the structure of the internal organs. The tested formulations are non-irritating; they do not cause allergic reactions, do not have embryotoxic and teratogenic properties, do not affect reproductive function in animals. Acyzol is protected by 14 patents of the Russian Federation.Acyzol is a powerful antidote against acute poisoning with lethal doses of CO, carbon monoxide or carbon oxide, and other products of combustion. It accelerates their elimination from the body and reduces the severity of the intoxication, which contributes to the success of subsequent medical interventions  . The druEffectiveness of Acyzol for the prevention and treatment of toxicohypoxic encephalopathies (TSEs), aggravating the progress of acute intoxications caused by CO and other combustion products, has been studied in experiments and in clinical trials. Administration of Acyzol (intramuscular injections of 6% solution 3 times daily for 7−10 days) to patients suffering from CO poisoning is beneficial for reduction of neurological complications. The favorable outcome from TSEs is due to an increase in the CO elimination, correction of non-specific changes in the blood cell composition, stabilization of peroxidation of lipids (POL) and antioxidant system (AOS) POL/AOS, and the elimination of compensatory reactions of the blood circulatory system ,92,93.The mechanism of Acyzol action is due to its influence on the cooperative interaction of the hemoglobin subunits, thereby resulting in the reduction of the relative hemoglobin affinity to carbon monoxide and improvement of the oxygen-binding (decreasing of Hill’s constant) and gas-transport functions of the blood ,94. The A direct chemical effect of the main component of the drug on the blood has been proved by the bio-crystallization method. The effect shows itself in the conversion of heme and globin part of the blood hemoglobin into the product, having an altered protein structure. In this case, the oxyglobin characteristic spectrum is observed. It is consists of the following absorption bands: 414 nm (Soret band), and two ones in the areas of 540 nm and 575 nm (α and β-bands). These α- and β-bands almost completely disappear from the spectrum after interaction of Acyzol with blood, indicating the changes of the heme part of hemoglobin, due to the influence of Acyzol  95]. In. In95]. Acyzol is a highly effective zinc-containing drug that provides anti-inflammatory, reparative, detoxifying, immunomodulatory, and bacteriostatic effects. Experimental and clinical studies demonstrate a large therapeutic window of Acyzol. In addition, Levedeva et al. showed the hepatoprotective, adaptogenic, antioxidant, and other cardioprotective activity of Acyzol . The druInterestingly, animal models of hypoxia showed a protective effect of Acyzol . Briefly, Acyzol was administered in a wide dose range (10–150 mg/kg) in mice under various acute hypoxic conditions including hypobaric hypoxia (AHBH), hypoxia with hypercapnia (AHwHc), and hemic hypoxia (AHeH) see  98,99].,99.98,99Acyzol, as a highly effective antihypoxic drug, protects the body in the conditions of low oxygen partial pressure and insufficient oxygenation of hemoglobin, and provides resistance to hypoxia of organs , which are the most sensitive to it ,94.Experimental and clinical studies demonstrate the possibility of creating Acyzol formulations for external use , which will be effective in the treatment of skin diseases  and diseases of mucous membranes .The presence of zinc shows that Acyzol may be used as a promissory for the treatment and prevention of ZDC including Prasad’s disease, immunodeficiencies, alopecia, allergodermatoses, prostate dysfunction, psoriasis, stomatitis, periodontitis, delayed mental and physical development in children, etc. At present, the effectiveness of Acyzol for ZDC correction has been shown on the huge factual material . The use of Acyzol formulations as a pharmacologic agent for pneumonia treatment resulted from acute poisoning with neurotropic agents significantly reduced the mortality rates see  91,99].,99.91,99Similar hepatoprotrotective effect of Acyzol and Silymarin was shown in the preclinical studies, thus providing a rationale for use of Acyzol in complex therapy of toxic hepatitis and hepatosis  100]..100].The study of cardioprotective effectiveness of Acyzol demonstrated pronounced therapeutic effect of the drug in the case of experimental catecholamine myocarditis. Increased contractile activity of the myocardium and decrease in the overload of the right heart were observed; that led to the regression of inflammatory changes in the cardiomycytes, reduced severity of cytolysis and increased intensity of tissue respiration . In the During therapy with Acyzol, an increase in the amplitude of the R, T waves was observed compared to the normal state, which may indicate an increase in the contractile activity of the myocardium. A decrease in the amplitude of the P, R, T waves and an increase in atrioventricular conductivity were also noted  . The results of the study of hemodynamics and organ-specific characteristics on the model of cardiopathic amyloidosis induced by administration of Freund’s adjuvant to male Wistar rats weighing 350−400 g and aged 18−24 months show that administration of Acyzol 30 mg/kg intragastrically for 60 days causes a positive preventive effect .The study of psoriatic patients carried out by Abramova TV, Batkaeva EA (2006) showed the efficacy of Acyzol when it administered in a dose of 120 mg 1 time a day for 10 days on the background of the conventional therapy for that disease that included hyposensitization drugs, vitamins, hepatoprotective agents, sedatives, ultraviolet irradiation, and external ointment treatment . AdminisThe course of Acyzol application for 2 months in a dose of 2 capsule (40 mg Zn) per day by military men with a low level of physical development, weight deficit, and increased morbidity level has improved functional status and increased the adaptive capacity of the body. In particular, pulmonary capacity, chest circumference at inspiration and expiration, Erismann index and other functional and physical characteristics of the body have increased . The couExperimental and clinical studies during the treatment of periodontal disease  of varying severity have shown that the use of Acyzol is accompanied by a rapid recovery and stable remission, both in an experimental laboratory and in the clinic . The higWhen patients suffering from type 2 diabetes received Acyzol, a decrease in their blood glucose levels was observed, a month after the start of the treatment .Prophylactic administration of Acyzol is an effective way of the toxic effect correction in the case of chronic lead poisoning. It has been shown that, subcutaneous and intragastric administration of Acyzol in a dose of 30 mg/kg to male Wistar rats reduces lipid peroxidation (LPO) processes, increases the activity of the antioxidant defense enzymes  in blood plasma and reduces malondialdehyde (MDA) content in the membranes of erythrocytes  40]..40].Acyzol as an antihypoxic agent can be used for the treatment of many diseases involving ischemia and hypoxia of viscera, i.e., in medical and surgical practice, in urology, gynecology, dermatology, and for the treatment of functional impotence. Due to its antihypoxic and antioxidant effects, Acyzol can be used in emergency medicine, in surgery for the correction of metabolic acidosis, and for the protection of cell membranes from the effects of LPO products. Acyzol can be recommended for introduction in the obstetric practice as an effective remedy for fetal hypoxia.The application of Acyzol is promising for sports medicine, because the drug increases subjects’ performance and endurance in the training process, owing to zinc replenishment in the enzyme systems, optimization of tissue respiration, and the improvement of the oxygen binding properties of the blood. Acyzol can be recommended for regenerative medicine as a drug that enhances the level of functional reserves of the organism .Zinc-containing preparation of Acyzol acts as a highly effective drug for the pharmacologic therapy of a wide range of diseases and conditions, including hypoxia, toxicohypoxic encephalopathy, periodontal, immune, and heart pathologies. The use of Acyzol opens up new perspectives in the treatment and prevention of ZDC.


The correct statement is: A de-identified dataset is provided in the Supporting Information files. Please contact the corresponding author Peibin Zeng , the Fundamental Research Funds for the Central Universities. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript. The publisher apologizes for the errors.


The European Board of Ophthalmology (EBO), founded in London in 1992, is a permanent working group of the Ophthalmology Subspecialty Section of the European Union of Medical Specialists (UEMS).The Board has the role of supervising the level of education in Ophthalmology in the European Union. EBO intends to obtain standards of education, and to harmonize knowledge and training across Europe. The main mean for EBO to realize that, alongside the EBO exam, CME control, and Grants is the accreditation of centers aspiring to reach the standards required.The National Delegates of Romania to EBO, Cornel Stefan, MD, PhD, and Assoc. Prof. Marian Burcea, MD, PhD, supported the Department of Ophthalmology of “Dr. Carol Davila” Central Military Emergency University Hospital to apply for EBO accreditation.On the 8th and 9th April, an Evaluation Committee from EBO came to Bucharest. The members of the Committee, Tina Xirou, MD, PhD, from Athens, Greece, and Prof. Andreas Wedrich, MD, PhD, from Graz, Austria, spent two days in the Clinic, following the daily activities, mainly the activities of the residents.The staff involved in residents’ training was assessed . The logistics of training – dedicated spaces, access to textbooks, paper and electronic journals, internet access, time in daily schedule for study seemed to be very important for the assessors. The presence of a simulator for ophthalmic surgery with open access  was much appreciated.For almost three hours, there was a discussion with the residents. During this talk, a lot of topics were clarified: numbers of residents in clinic, number of residents in each year of training, resident/ staff ratio, number of patients/ year, number of surgeries/ year, number of patients in different areas of ophthalmology , the opportunity – or not – to follow some time in each of these subspecialties.The clinic obtained a very good evaluation for the diagnostic and therapeutic equipments, which were considered above the level of many units from western countries.The global impression was positive and the assessors presented their data to EBO Accreditation Committee. Two months later, the Department of Ophthalmology of “Dr. Carol Davila” Central Military Emergency University Hospital became the first EBO accredited centre in Romania.Editor-in-ChiefMihail Zemba, MD, PhD