Suchergebnisse

Objective: Gastrointestinal adverse effects occur in 20-30% of patients with metformin-treated type 2 diabetes, leading to premature discontinuation in 5-10% of the cases. Gastrointestinal intolerance may reflect localized high concentrations of metformin in the gut. We hypothesized that reduced transport of metformin via the plasma membrane monoamine transporter (PMAT) and organic cation transporter 1 (OCT1) could increase the risk of severe gastrointestinal adverse effects. Research design and methods: The study included 286 severe metformin-intolerant and 1,128 metformin-tolerant individuals from the IMI DIRECT (Innovative Medicines Initiative: DIabetes REsearCh on patient straTification) consortium. We assessed the association of patient characteristics, concomitant medication, and the burden of mutations in the SLC29A4 and SLC22A1 genes on odds of intolerance. Results: Women (P < 0.001) and older people (P < 0.001) were more likely to develop metformin intolerance. Concomitant use of transporter-inhibiting drugs increased the odds of intolerance (odds ratio [OR] 1.72, P < 0.001). In an adjusted logistic regression model, the G allele at rs3889348 (SLC29A4) was associated with gastrointestinal intolerance (OR 1.34, P = 0.005). rs3889348 is the top cis-expression quantitative trait locus for SLC29A4 in gut tissue where carriers of the G allele had reduced expression. Homozygous carriers of the G allele treated with transporter-inhibiting drugs had more than three times higher odds of intolerance compared with carriers of no G allele and not treated with inhibiting drugs (OR 3.23, P < 0.001). Use of a genetic risk score derived from rs3889348 and SLC22A1 variants found that the odds of intolerance were more than twice as high in individuals who carry three or more risk alleles compared with those carrying none (OR 2.15, P = 0.01). Conclusions: These results suggest that intestinal metformin transporters and concomitant medications play an important role in the gastrointestinal adverse effects of metformin. ; This article is freely available via Open Access. Click on the Publisher URL to access it via the publisher's site. ; The work leading to this publication has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115317 (DIRECT), resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and an in-kind contribution from the European Federation of Pharmaceutical Industries and Associations. E.R.P. holds a Wellcome Trust New Investigator Award (102820/Z/13/Z). ; published version, accepted version, submitted version

Nadiyah Alshehri,1,2 Anwar E Ahmed,3 Nagarajkumar Yenugadhati,2,4 Sundas Javad,2,4 Khalid Al Sulaiman,1 Hasan M Al-Dorzi,5 Majed Aljerasiy,4 Motasim Badri2,4 1Pharmaceutical Care Department, Ministry of National Guard- Health Affairs, Riyadh, Saudi Arabia; 2Department of Epidemiology & Biostatistics, College of Public Health and Health Informatics, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 3Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD, USA; 4King Abdullah International Medical Research Center, King Saud Bin-Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia; 5Intensive Care Department, College of Medicine King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi ArabiaCorrespondence: Nadiyah AlshehriDepartment of Epidemiology & Biostatistics, College of Public Health and Health Informatics, King Saud bin Abdulaziz University for Health Sciences, P.O. Box: 47323, Riyadh 11552, Saudi ArabiaEmail alshehrina2@ngha.med.saBackground: Vancomycin is one of the most common therapeutic agents for treating gram-positive infections, particularly in critically ill patients. The aim of this study was to identify factors associated with initial therapeutic vancomycin trough levels and mortality in a tertiary-care intensive care unit (ICU).Methods: This retrospective study evaluated 301 adult ICU patients admitted to King Abdulaziz Medical City in Riyadh between October 1, 2017 and December 31, 2018 with confirmed gram-positive infections and received intravenous vancomycin. Vancomycin trough levels of 15– 20 mg/L for severe infections and 10– 15 mg/L for less severe infections were considered therapeutic.Results: The patients were relatively older with a mean age of 60 (SD ± 20) years. Initial vancomycin trough levels were therapeutic in 168 (55.8%). Factors associated with initial therapeutic vancomycin trough levels were female gender (adjusted odds ratio [aOR]=2.575), older age (aOR=1.024), receiving a loading dose (aOR=2.445), having bacteremia (aOR=2.061), and high platelet count (aOR=1.003). On the other hand, the increase of estimated glomerular filtration rate (eGFR) (aOR=0.993) and albumin levels (aOR=0.944) were associated with lower odds of initial therapeutic vancomycin trough levels. Factors associated with higher mortality were female gender (adjusted hazard ratio [aHR]=2.630), increased body weight (aHR=1.021), cancer (aHR=3.451), and high APACHE II score (aHR=1.068).Conclusion: The study identified several factors associated with achieving initial therapeutic vancomycin trough levels (i.e. older age, female gender, receiving a loading dose, bacteremia, high platelets count, low eGFR and albumin level). These factors should be considered in the dosing of vancomycin in critically ill patients with gram-positive infections.Keywords: vancomycin dosage, pharmacokinetics, renal function, serum trough levels, mortality

Salwa Massad,1 Marina Tucktuck,2 Ranin Dar Khawaja,3,4 Hadil Dalloul,1 Khalid Abu Saman,1 Rand Salman,1 Rawan Kafri,1 Hatem Khammash5,6 1Research Unit, Palestinian National Institute of Public Health, Ramallah, Palestine; 2School of Medicine, St. George's University, Grenada, West Indies; 3Epidemiology and Public Health, Swiss Tropical and Public Health Institute (Swiss THP), Basel, Switzerland; 4Faculty of Medicine, University of Basel, Basel, Switzerland; 5Neonatology Department, Makassed Hospital, Jerusalem, Palestine; 6Pediatric Department, Al-Quds University, Jerusalem, PalestineCorrespondence: Salwa MassadResearch Unit, Palestinian National Institute of Public Health, Ministry of Health Building, 1st Floor, Qadora Street, Ramallah, PalestineTel +970 2 296 6842/7Fax +970 2 296 6852Email salwamassad@gmail.comIntroduction: Geopolitical segregation of Palestine has left a fragile healthcare system with an unequal distribution of services. Data from the Gaza Strip reflect an increase in infant mortality that coincided with a significant increase in neonatal mortality (12.0 to 20.3 per 1000 live births).Objective: A baseline study was carried out to evaluate available resources in neonatal units throughout Palestine.Study Design: A cross-sectional, hospital-based study was conducted in 2017 using the World Health Organization's "Hospital care for mothers and newborn babies: quality assessment and improvement tool." Data on the main indicators were updated in 2018.Results: There were 38 neonatal units in Palestine: 27 in the West Bank, 3 in East Jerusalem, and 8 in the Gaza Strip. There was an uneven geographic distribution of incubators in relation to population and births that was more marked in the Gaza Strip; 79% of the neonatal units and 75% of the incubators were in the West Bank. While almost all hospitals with neonatal units accepted very and extremely low birth weight and admitted out-born neonatal cases, there was a shortage in the availability of incubators with humidifiers, high-frequency oscillatory ventilation, mechanical ventilators with humidifiers and isolation wards. There was also a considerable shortage in neonatologists, neonatal nurses, and pediatric subspecialties.Conclusion: Almost all the neonatal units accepted extremely low birth weight neonatal cases despite not being ready to receive these newborns due to considerable shortages in human resources, equipment, drugs, and essential blood tests, as well as frequent disruptions in the availability of based amenities. Together, these factors contribute to the burden of providing quality care to newborns, which is further exacerbated by the lack of referral guidelines and challenges to timely referrals resulting from Israeli measures. Ultimately, this contributes to suboptimal care for neonates and negatively impacts future health outcomes.Keywords: neonatal services, Palestine, assessment, hospitals

PUBLISHED ; Ireland is small country with a population of 4.8M which spent 6.9% of its gross domestic product on healthcare in 2018. Health services are provided through a twin track approach ?all public services are largely free to those eligible (32.44% in 2019) and private patients pay for most services. Most of the expenditure on medicines is paid by the government while visits to General Practitioners (GPs) are an out-of-pocket expense for private patients under 70 years of age, and private health insurance provides cover for most hospital services. Healthcare professionals in the primary care sector contract to provide public services with the Health Services Executive (HSE) which is responsible for the day-to-day running of the service. Primary care teams began to be formed in 2001 to try to link and integrate the provision of care but since these are led by GPs neither community pharmacists nor dentists joined these teams. The focus of policy remained the primary care team until a proposal to create a public health service to provide universal health coverage called Sl?intecare was agreed in 2017. However, implementation of Sl?intecare has been slow and piecemeal. The government regularly devises policies to control prescribing and the HSE, together with other regulators has implemented genericsubstitution and preferred drugs and limited access to expensive drugs through schemes for particular patient groups. A programme called Healthy Ireland has taken on the health promotion policies but pharmacists have been excluded from most programmes although some campaigns have included them. Community pharmacy organisations have tried to develop pharmacy services and while a few which are targeted at specified patient groups, such as opioid substitution, emergency administration of certain drugs, emergency hormonal contraception and seasonal influenza vaccination have been remunerated for public patients by the HSE, other services have not. GP organisations defend their members? scope of practice and seek to influence policy makers to channel schemes and services through general practice. There is no professional body to represent pharmacists that is independent of any trade union responsibilities and this has weakened the profession?s advocacy. Pharmacists are one of the most trusted group of professionals in Ireland and have maintained their practices throughout periods of recession and declining income from government. Whether pharmacists can argue that the optimisation of a patient?s medicines depends upon their contribution and will benefit the health service remains an open question.

Hypertension is the leading risk factor for cardiovascular disease and leading cause of premature death globally. In 2008, approximately 40% of adults were diagnosed with hypertension, with more than 1.5 billion people estimated to be affected globally by 2025. Hypertension disproportionally affects low- and middle-income countries, where the prevalence is higher and where the health systems are more fragile. This qualitative study explored patients' experiences on the management and control of hypertension in rural Bangladesh, Sri Lanka and Pakistan. We conducted sixty semi-structured interviews, with 20 participants in each country. Hypertensive individuals were recruited based on age, gender and hypertensive status. Overall, patients' reported symptoms across the three countries were quite similar, although perceptions of hypertension were mixed. The majority of patients reported low knowledge on how to prevent or treat hypertension. The main barriers to accessing health services, as reported by participants, were inadequate services and poor quality of existing facilities, shortage of medicine supplies, busyness of doctors due to high patient load, long travel distance to facilities, and long waiting times once facilities were reached. Patients also mentioned that cost was a barrier to accessing services and adhering to medication. Many patients, when asked for areas of improvement, reported on the importance of the provider-patient relationship and mentioned valuing doctors who spent time with them, provided advice, and could be trusted. However, most patients reported that, especially at primary health care level and in government hospitals, the experience with their doctor did not meet their expectations. Patients in the three countries reported desire for good quality local medical services, the need for access to doctors, medicine and diagnostics and decreased cost for medication and medical services. Patients also described welcoming health care outreach activities near their homes. Areas of improvement could focus on reorienting community health workers' activities; involving family members in comprehensive counseling for medication adherence; providing appropriate training for health care staff to deliver effective information and services for controlling hypertension to patients; enhancing primary health care and specialist services; improving supplies of hypertensive medication in public facilities; taking into account patients' cultural and social background when providing services; and facilitating access and treatment to those who are most vulnerable. ; The study is supported by a research award: Grant Ref No: MR/N006178/1 from the MRC/DFId/Wellcome Trust, UK.

Jian Wu,1,2 Xiang Tao,3,4 Hong Zhang,5 Xiang-Hua Yi,1 Yin-Hua Yu4 1Department of Pathology, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, People's Republic of China; 2Department of Pathology, Gongli Hospital, Second Military Medical University, Shanghai 200135, People's Republic of China; 3Department of Pathology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai 200032, People's Republic of China; 4Department of Gynecology, Obstetrics and Gynecology Hospital, Fudan University, Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Shanghai, 200011, People's Republic of China; 5Department of Pharmacy, Tongji Hospital, Tongji University School of Medicine, Shanghai 200065, People's Republic of ChinaCorrespondence: Xiang Tao Email tutufoliage@hotmail.comHong Zhang Email Hongzh97@tongji.edu.cnObjective: The aim of this study was to evaluate whether estrogen promoted the proliferation and invasion of endometrial carcinoma (EC) cells through paracrine FGFs in endometrial stromal cells (ESCs).Patients and Methods: We screened gene alterations in a primary ESC culture after 10 nM estrogen treatment using an Agilent mRNA microarray. We knocked down stromal FGF18 expression in a co-culture system and aimed to explore the contribution of E2-induced stromal FGF18 to the proliferation and invasion of EC cells. To determine the effective receptors and detailed downstream signaling of FGF18, we co-cultured estrogen-treated hESCs with FGFR1-, FGFR2-, FGFR3- or FGFR4-knockdown Ishikawa cells. Finally, we detected FGF18 expression in clinical samples, including several primary cultures of different ESCs and a series of tissue microarrays (TMAs) of 90 patients with EC.Results: A few genes altered significantly in estrogen-treated primary ESCs, but only FGF18 was noticeably enhanced among the FGF family genes. Knockdown of FGF18 expression in hESCs inhibited the promoting effect of FGF18 on the proliferation and invasion of EC cells. FGF18 bound FGFR2 and FGFR3 in Ishikawa cells to activate downstream ERK and Akt pathways and to promote the viability of EC cells. The FGF18-FGFR2 and FGF18-FGFR3 pathways had close correlations with Survivin and CD44V6 expression but not with P53. Primary ESCs of endometrioid EC (EEC, type I EC) had higher FGF18 expression than ESCs of normal endometrium (NE), endometrial atypical hyperplasia (EAH) and type II EC.Conclusion: Estrogen induced FGF18 in ESCs to promote the proliferation and invasion of EC cells, and FGFR inhibitors should be considered as promising candidate targets for EC treatment.Keywords: FGF18, paracrine, proliferation, invasion, endometrial stromal cells, ESCs, endometrial carcinoma, EC

Con el inicio de la intervención norteamericana y el establecimiento de la pseudorepublica la orientación de los servicios de salud en la isla sufrió cambios en su concepción y orientación. La atención a la salud que durante el gobierno español descansaba en enfermerías de orden religioso, otras entidades estatales y médicos de ejercicio privado, fue remodelada por una medicina centrada en las especialidades como la epidemiología. Con los objetivos de caracterizar el panorama de la salud en Cienfuegos durante la etapa neocolonial, y de identificar aquellos lugares actuales de Cienfuegos que poseen relación con la historia de la salud en la provincia durante la república neocolonial; se presenta esta investigación titulada: "Memorias de la Salud Pública en Cienfuegos: Etapa neocolonial". Para su realización se utilizaron 10 referencias bibliográficas de las distintas fuentes de información. Se concluyó que durante el establecimiento de la república en 1902 no se suscitaron acciones de mayor trascendencia en el campo de la salud, con respecto a 1998; todo discurría bajo un eje central constitucional con servicios muy limitados económicamente: el Hospital La Caridad que tomó el nombre de Hospital Civil Luis Perna en lo gubernamental, mientras que por la medicina privada se fueron diversificando distintos tipos de entidades y servicios polarizados en el sector urbano ; With the beginning of the North American intervention and the establishment of the pseudo-republic, the health services un- derwent changes in conception and orientation in the island. During the Spanish government, the health care was based on reli- gious nursing centers. Other state entities and the service provided by private doctors were modified by a medicine focused on specialties such as epidemiology. This research which is entitled: "Memories of Public Health in Cienfuegos: Neocolonial stage, was aimed at characterizing the health situation in Cienfuegos during the neocolonial stage, as well as identifying those places in Cienfuegos that, at present, are related to the history of health in the province during the neocolonial republic. To conduct the study, 10 bibliographical references taken from different sources of information were used. We concluded that there were no actions of greater importance in the field of health during the establishment of the Republic in 1902 compared to the year 1998; everything occurred under a constitutional framework in a context of economically limited services: Hospital La Caridad was named Luis Perna Civil Hospital in the governmental sector, while different types of polarized entities and services in the urban sector were diversified by private medicine

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the aetiology of coronavirus disease 2019 (COVID19) pandemic. ICEP4 purified compound (ICEP4) is a recently discovered furocoumarin-related purified compound coming from roots and seeds of Angelica archangelica (herbal drug). ICEP4-related herbal preparations have been extensively used as active herbal ingredient in traditional medicine treatments in several European countries. Extraction method of patent pending ICEP4 (patent application no. GB2017123.7) has previously shown strong manufacturing robustness, long-lasting stability, and repeated chemical consistency. Here we show that ICEP4 presents a significant in vitro cytoprotective effect in highly virulent-SARS-CoV-2 challenged Vero E6 cellular cultures, using doses of 34.5 and 69 μM. No dose-related ICEP4 toxicity was observed in Vero E6 cells, M0 macrophages, B, CD4+ T and CD8+ T lymphocytes, Natural Killer (NK) or Natural Killer T (NKT) cells. No dose-related ICEP4 inflammatory response was observed in M0 macrophages quantified by IL6 and TNFα release in cell supernatant. No decrease in survival rate was observed after either 24 hr acute or 21-day chronic exposure in in vivo toxicity studies performed in C. elegans. Therefore, ICEP4 toxicological profile has demonstrated marked differences compared to others vegetal furocoumarins. Successful ICEP4 doses against SARS-CoV-2-challenged cells are within the maximum threshold of toxicity concern (TTC) of furocoumarins as herbal preparation, stated by European Medicines Agency (EMA). The characteristic chemical compounding of ICEP4, along with its safe TTC, allow us to assume that the first-observation of a natural antiviral compound has occurred. The potential druggability of a new synthetic ICEP4-related compound remains to be elucidated. However, well-established historical use of ICEP4-related compounds as herbal preparations may point towards an already-safe, widely extended remedy, which may be ready-to-go for large-scale clinical trials under the EMA emergency regulatory pathway. To the best of the authors' knowledge, ICEP4-related herbal drug can be postulated as a promising therapeutic treatment for COVID19. ; Iratxe Uranga-Murillo is supported by a predoctoral contract from Aragón Government. ii Dr. Maykel Arias is supported by a Juan de la Cierva postdoctoral contract. iii Dr. Julian Pardo´s laboratory is funded by FEDER (Fondo Europeo de Desarrollo Regional, Gobierno de Aragón -Group B29_17R-, Ministerio de Ciencia, Innovación e Universidades - MCNU-, Agencia Estatal de Investigación -SAF2017‐83120‐C2‐1‐R-), Instituto de Salud Carlos III, Fundación Inocente Inocente, ASPANOA and Carrera de la Mujer de Monzón. ; No

© The Author(s). ; [Background]: Acute myeloid leukemia (AML) is the most common acute leukemia in adults and has an unacceptably low cure rate. In recent years, a number of new treatment strategies and compounds were developed for the treatment of AML. There were several randomized controlled clinical trials with the objective to improve patients' management and patients' outcome in AML. Unfortunately, these trials are not always directly comparable since they do not measure the same outcomes, and currently there are no core outcome sets that can be used to guide outcome selection and harmonization in this disease area. The HARMONY (Healthcare Alliance for Resourceful Medicine Offensive against Neoplasms in Hematology) Alliance is a public-private European network established in 2017 and currently includes 53 partners and 32 associated members from 22 countries. Amongst many other goals of the HARMONY Alliance, Work Package 2 focuses on defining outcomes that are relevant to each hematological malignancy. Accordingly, this pilot study will be performed to define a core outcome set in AML. ; [Methods]: The pilot study will use a three-round Delphi survey and a final consensus meeting to define a core outcome set. Participants will be recruited from different stakeholder groups, including patients, clinicians, regulators and members of the European Federation of Pharmaceutical Industries and Associations. At the pre-Delphi stage, a literature research was conducted followed by several semi-structured interviews of clinical public and private key opinion leaders. Subsequently, the preliminary outcome list was discussed in several multi-stakeholder face-to-face meetings. The Delphi survey will reduce the preliminary outcome list to essential core outcomes. After completion of the last Delphi round, a final face-to-face meeting is planned to achieve consensus about the core outcome set in AML. ; [Discussion]: As part of the HARMONY Alliance, the pilot Delphi aims to define a core outcome set in AML on the basis of a multi-stakeholder consensus. Such a core outcome set will help to allow consistent comparison of future clinical trials and real-world evidence research and ensures that appropriate outcomes valued by a range of stakeholders are measured within future trials. ; This work was funded through the Innovative Medicines Initiative 2 joint undertaking and listed under grant agreement 116026. This joint undertaking receives support from the European Union's Horizon 2020 research and innovation program and the EFPIA. An additional cash grant was obtained from Bayer AG for conducting the Delphi survey development

Chilot Kassa Mekonnen,1 Bezenaw Yimer Mekonnen,2 Habtamu Sewunet Mekonnen1 1Department of Medical Nursing, School of Nursing, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia; 2Department of Emergency and Critical Care Nursing, School of Nursing, College of Medicine and Health Sciences, University of Gondar, Gondar, EthiopiaCorrespondence: Chilot Kassa Mekonnen Email chilotkassa.m@gmail.comIntroduction: As hypertension is a chronic cardiovascular disease that contributes to a high proportion of morbidity and mortality worldwide, favorable knowledge is crucial to control it.Objective: The objective of this study was thus to assess knowledge and associated factors of blood pressure control among hypertensive patients at the chronic illness follow-up Clinic of the University of Gondar comprehensive-specialized hospital, Gondar, Ethiopia.Methods: An institution-based cross-sectional study was conducted from March to April 2018. A systematic random sampling technique was used to select participants. Bi-variable and multivariable logistic regressions were done to assess the relationship between dependent and independent variables. The adjusted odds ratio with a 95% confidence interval was used to determine the presence and strength of association between covariates and the outcome variable.Results: A total of 404 participants took part in the study with a response rate of 97.3%. The overall good knowledge about blood pressure control was 51.7% (95% CI=46.3–56.8). Females were 3.79 (AOR= 3.79, 95% CI: (1.55, 9.28)) more knowledgeable about blood pressure control than males. In the multivariable analysis, the odds of being knowledgeable were 2.80 (AOR= 2.80, 95% CI (1.44, 5.46)), 8.05 (AOR=8.05, 95% CI (2.93, 22.10)), and 7.53 (AOR=7.53, 95% CI (2.52, 22.49)) for can read and write, secondary, preparatory and above education, respectively, compared to cannot read and write. Occupation was significantly associated with the knowledge of plod pressure control. For example, merchants 7.66 (AOR=7.66, 95% CI (3.01, 19.47)), government employee 6.33 (AOR=6.33, 95% CI (1.90, 22.07)), and self-employed 4.58 (AOR=4.58, 95% CI (1.80, 11.70)) times more likely to be knowledgeable than farmers, respectively. Participants with family history of hypertension were 2.36 (AOR=2.36, 95% CI (1.42, 3.92)) times more knowledgeable than their counterparts.Conclusion: In this study, knowledge of blood pressure control was lower compared to the finding of a study done at Bishoftu hospital, Ethiopia. But it is higher than studies in other African countries. Both pharmacological and non-pharmacological awareness is vital for blood pressure control.Keywords: blood pressure control, hypertension, knowledge, Ethiopia

Emilian Damian Popovici,1,2 Dana Gabriela Negru,3 Teodora Olariu,4 Mariana Nagy,5 Sorin Dinu,6 Gabriela Oprisan,6,7 Lavinia Zota,8 Luminita Mirela Baditoiu11Epidemiology Department, "Victor BabeÅŸ" University of Medicine and Pharmacy, TimiÅŸoara, Romania; 2National Institute of Public Health, Regional Public Health Centre, TimiÅŸoara, Romania; 3Private Medical Epidemiology Practice, Arad, Romania; 4Arad County Clinical Hospital, Arad, Romania; 5Department of Mathematics and Computer Science, "Aurel Vlaicu" University of Arad, Arad, Romania; 6Molecular Epidemiology Laboratory, Cantacuzino National Medical – Military Institute of Research and Development, Bucharest, Romania; 7Faculty of Pharmacy, "Titu Maiorescu" University, Bucharest, Romania; 8National Institute of Public Health, National Centre for Surveillance and Control of Communicable Diseases, Bucharest, RomaniaCorrespondence: Emilian Damian PopoviciEpidemiology Department, "Victor BabeÅŸ" University of Medicine and Pharmacy, No. 2, Piata Eftimie Murgu, TimiÅŸoara 300041, RomaniaTel +40 74 420 6030Fax +40 25 649 2101Email epidemio@umft.roPurpose: This study shows the epidemiological profile of the first gastroenteritis outbreak of GII.P17 in the Romanian territory. An outbreak with such large amplitude in a European territory was previously undocumented.Patients and methods: Using a cross-sectional design, with the susceptible-infected-recovered (SIR) deterministic compartmental model for a fixed population, and the cluster method for establishing the high-incidence zones, we carried out our investigation by means of questionnaires containing personal data, affected collectivities, disease onset and duration, symptoms displayed, medical assistance provided, previous antibiotic intake where applicable, food consumption and water sources, and sanitation conditions. The confirmation of cases was done based on the typical norovirus gastroenteritis symptomatology and using three laboratory confirmations (by molecular diagnosis) for GII.P17-GII.17 genotype noroviruses from three patients.Results: A gastroenteritis outbreak occurred in October–November 2015, affecting 328 people in Arad, a county in Western Romania, covering 44 neighbouring localities with a total population of 35,440 people. The study detected an inter-human transmission of the infection, with an intrafamilial risk of disease of 2.26 (95% CI 1.76 to 2.90) compared with the community transmission (in school collectivity). The basic reproduction number Ro dropped from 1.26 to 0.18 during weeks 43:44, after controlling the transmission by decontamination and isolation.Conclusion: SIR made it possible to highlight the expansion of the emerging norovirus strain infection from community to family collectivities. This study provides practical solutions to limit disease cases, even in the absence of etiology, and shows the importance of sometimes underestimated traditional control methods.Keywords: norovirus, GII.17_Kawasaki, SIR, basic reproduction number

An analysis of the organization of the veterinary service of the Kyiv region was carried out and brief information on the number of veterinary specialists in the governorate during the specified period was provided. It was established that the impetus for proper organization of veterinary medicine of the Kyiv region at the end of the XIX — beginning of the XX centuries was a complicated epizootic situation. Indeed, more than thirty infectious diseases were registered by veterinary staff in the Kyiv Governorate during this period, including glanders of horses, anthrax of cattle and horses, rabies of dogs, and the like. These diseases are registered annually in county of the governorate with a different percentage of manifestations. Anthrax was the most widely distributed, manifestating itself for many years with a large percentage of death. After all, by 1882 there were only 4 veterinary physicians in the whole governorate (2 provincial and 2 for rural population). Such a number of veterinary physicians in the governorate could not deal with widespread epizootics. Common at that time epizootics forced the provincial government to improve veterinary medicine. Only in 1882, there were opened 12 positions of veterinary physicians, and during almost 30 years there were opened more than 100 medical and paramedical positions. In addition to county veterinary physicians, there were provincial and junior provincial, special, station, district doctors and openings for veterinary paramedicsKeywords: Kyiv region, Kyiv Governorate, Veterinary service, Veterinary physician, Veterinary and Sanitary activities. ; Зроблено аналіз організації ветеринарної служби Київщини і подано короткі відомості щодо кількості ветеринарних фахівців у губернії у зазначений період. Встановлено, що поштовхом для правильної організації ветеринарної медицини Київщини кінця ХІХ – початку ХХ ст. була складна епізоотична ситуація. Адже в цей період у Київській губернії ветеринарним персоналом реєструвалось більше тридцяти заразних захворювань, зокрема сап коней, сибірка великої рогатої худоби і коней, сказ собак тощо. Ці хвороби щорічно реєструвалися у повітах губернії з різним відсотком прояву. Найбільшого поширення набула сибірка, яка проявлялася впродовж багатьох років з великим відсотком загибелі. Адже, до 1882 року на всю губернію було всього 4 ветеринарних лікарі (2 губернські і 2 для сільського населення). Така кількість ветеринарних лікарів у губернії не могла боротися з поширеними епізоотіями. Поширені на той час епізоотії змусили губернську управу покращити ветеринарну справу. Лише у 1882 році було відкрито 12 посад ветеринарних лікарів, а протягом майже 30 років відкрито більше 100 лікарських і фельдшерських посад. Окрім повітових ветеринарних лікарів були губернський і молодший губернський, надштатні, пунктові, дільничні лікарі та виділені посади ветеринарних фельдшерів Ключові слова: Київщина, Київська губернія, ветеринарна служба, ветеринарно-санітарні діяльність.

Manuel Diaz-Llopis,1–5 Maria Dolores Pinazo-Duran,2,3,6–9 Loreto Diaz-Guiñon,5 Miriam Rahhal-Ortuño,10 Mercedes Perez-Ramos,8,9 Rosabel Bosch,8,9 Roberto Gallego-Pinazo,11,12 Rosa Dolz-Marco,11,12 Teresa Diaz-Guiñon,5 María Diaz,1,5 Francisco Javier Romero,13 Angel Cisneros10 1University of Valencia, Valencia, Spain; 2Ophthalmology Unit, Faculty of Medicine, University of Valencia, Valencia, Spain; 3Molecular Ophthalmology Unit, Faculty of Medicine, University of Valencia, Valencia, Spain; 4Consellería de Sanitat (Valencian Regional Health Ministry), Valencian Autonomous Government, Valencia, Spain; 5IOVA – Valencia Ophthalmology Institute, Valencia, Spain; 6Hospital Universitario Doctor Peset, Valencia, Spain; 7Santiago Grisolía Eye Research Laboratory, FISABIO, Valencia, Spain; 8Specialised Medical Centre Alboraya, Valencia, Spain; 9Specialised Medical Centre Monteolivete, Valencia, Spain; 10Department of Ophthalmology, La Fe Hospital, Valencia, Spain; 11IMED Hospital, Valencia, Spain; 12Oftalvist Clinic, Valencia, Spain; 13European University of Valencia, Valencia, Spain Purpose: To investigate the safety and efficacy of sterile isotonic seawater washes vs standard treatment with carmellose artificial tears in dry eye syndrome (DES). Patients and methods: This is a randomized multicenter prospective study with 12 weeks of follow-up. A group of patients with DES (N=60) were treated with seawater spray (Quinton®) five times daily, and another similar group (N=60) were treated with carmellose artificial tears eyedrops (Viscofresh® 0.5%) five times a day. The parameters studied and measured were as follows: Ocular Surface Disease Index questionnaire score, Schirmer I test (without anesthesia) score, tear osmolarity (TearLab®), tear breakup time, tear meniscus height (meniscography OCT), fluorescein corneal staining score (National Eye Institute scale), lissamine green conjunctival staining score, and levels of IL-1 beta and IL-6 in tears (Luminex® 200). Results: In the group treated with seawater, symptoms decreased by 68%, and the decrease was 26% statistically superior to the group treated with carmellose artificial tears eyedrops (P<0.001). Levels of IL-1 beta and IL-6 in tears significantly decreased in the seawater group compared to the carmellose artificial tears group (19%/17% vs 52%/51%) (P<0.001). There were no statistically significant differences in the other measured parameters. There were no cases of poor tolerance or side effects. Conclusion: Administration of seawater is more effective than treatment with carmellose artificial tears in reducing symptoms and pro-inflammatory molecules (IL-1 beta and IL-6) in tears of patients with DES. Keywords: dry eye syndrome, isotonic seawater, artificial tears, carmellose, IL-1 beta, IL-6, quality of life

Robert J Barry,1,2 Freda Sii,1,3 Alice Bruynseels,1 Joseph Abbott,4 Richard J Blanch,1–2,5 Caroline J MacEwen,6 Peter Shah1,3,7–81Department of Ophthalmology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 2Neuroscience and Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK; 3Birmingham Institute for Glaucoma Research, Institute of Translational Medicine, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK; 4Department of Ophthalmology, Birmingham Children's Hospital NHS Foundation Trust, Birmingham, UK; 5Academic Department of Military Surgery and Trauma, Royal Centre for Defence Medicine, Dundee, UK; 6Department of Ophthalmology, Ninewells Hospital and Medical School, Dundee, UK; 7University College London, London, UK; 8Centre for Health and Social Care Improvement, School of Health and Wellbeing, University of Wolverhampton, Wolverhampton, UKPurpose: Worldwide, as many as 6 million children annually sustain ocular trauma, with up to a quarter of a million children requiring hospitalization. Management of pediatric ocular trauma differs from that in adults, both in terms of initial assessment and acute intervention, with significant variation in practice between different centers. Patterns of healing and long-term outcomes are also very different for children compared to adults. In order to develop effective protocols for management, it is first necessary to understand current trends in presentation and treatment.Methods: We conducted a prospective, observational study of pediatric ocular trauma presenting to UK-based ophthalmologists over a one-year period; reporting cards were distributed by the British Ophthalmic Surveillance Unit, and clinicians were asked to report cases of acute orbital and ocular trauma in children aged 16 years or less requiring inpatient or day-case admission. A validated, standardized questionnaire was sent to reporting ophthalmologists to collect data on clinical features and initial management of injury.Results: Eighty-six episodes of pediatric ocular trauma were reported. Trauma involving the globe was reported in 66/86 patients (76.7%), of which 40/66 (60.1%) were open-globe. Trauma to the anterior segment was reported in 57/86 (66.3%), and posterior segment in 23/86 patients (26.7%). Twenty-five of 86 (29.1%) patients sustained severe trauma defined as having best-corrected visual acuity worse than 6/60 Snellen (incidence 0.19 per 100,000 population).Conclusions: There has been no improvement in the incidence or severity of pediatric ocular injury rates over the past 25 years. Eye-care providers must be able to provide the necessary services for assessment and management of severe pediatric ocular trauma in the emergency setting.Keywords: childhood eye injury, incidence, management, penetrating eye injury, perforating eye injury, presentation, prevention

Yanhai Xi,*,1 Tingwang Jiang,*,2 Yinglan Yu,3 Jiangmin Yu,1 Mintao Xue,1 Ning Xu,1 Jiankun Wen,1 Weiheng Wang,1 Hailong He,1 Yan Shen,3 Daquan Chen,4 Xiaojian Ye,1 Thomas J Webster51Department of Spine Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China; 2Department of Immunology and Microbiology, Institution of Laboratory Medicine of Changshu, Changshu 215500, Jiangsu, People's Republic of China; 3Department of Pharmaceutics, Center for Research Development and Evaluation of Pharmaceutical Excipients and Generic Drugs, China Pharmaceutical University, Nanjing, People's Republic of China; 4Department of Pharmaceutics, School of Pharmacy, Yantai University, Yantai 264005, People's Republic of China; 5Department of Chemical Engineering, Northeastern University, Boston, MA, USA*These authors contributed equally to this workIntroduction: Curcumin (CUR) is a general ingredient of traditional Chinese medicine, which has potential antitumor effects. However, its use clinically has been limited due to its low aqueous solubility and bioavailability. In order to improve the therapeutic effect of CUR on osteosarcoma (i.e., bone cancer), a multifunctional micelle was developed here by combining active bone accumulating ability with tumor CD44 targeting capacity.Methods: The CUR loaded micelles were self-assembled by using alendronate-hyaluronic acid-octadecanoic acid (ALN-HA-C18) as an amphiphilic material. The obtained micelles were characterized for size and drug loading. In addition, the in vitro release behavior of CUR was investigated under PBS (pH 5.7) medium containing 1% Tween 80 at 37â"ƒ. Furthermore, an hydroxyapatite (the major inorganic component of bone) affinity experiment was studied. In vitro antitumor activity was evaluated. Finally, the anti-tumor efficiency was studied.Results: The size and drug loading of the CUR loaded ALN-HA-C18 micelles were about 118 ± 3.6 nm and 6 ± 1.2%, respectively. CUR was released from the ALN-HA-C18 micelles in a sustained manner after 12 h. The hydroxyapatite affinity experiment indicated that CUR loaded ALN-HA-C18 micelles exhibited a high affinity to bone. CUR loaded ALN-HA-C18 micelles exhibited much higher cytotoxic activity against MG-63 cells compared to free CUR. Finally, CUR loaded ALN-HA-C18 micelles effectively delayed anti-tumor growth properties in osteosarcoma bearing mice as compared with free CUR.Conclusion: The present study suggested that ALN-HA-C18 is a novel promising micelle for osteosarcoma targeting and delivery of the hydrophobic anticancer drug CUR.Keywords: curcumin, alendronate, hyaluronic acid, osteosarcoma