In Global Health Research, Is It Legitimate To Stop Clinical Trials Early on Account of Their Opportunity Costs?

This debate examines the ethics of reallocating resources invested in existing trials of older products into new trials of more scientifically advanced products

A generative-oriented model-driven design environment for customizable video surveillance systems

To tackle the growing complexity and huge demand for tailored domestic video surveillance systems along with a high demanding time-to-market expectation, engineers at IVV Automação, LDAa are exploiting video surveillance domain as families of systems that can be developed following a pay-as-you-go fashion rather than developing an ex-nihilo new product. Several and different new functionalities are required for each new product’s hardware platforms (e.g., ranging from mobile phone, PDA to desktop PC) and operating systems (e.g., flavors of Linux, Windows and MAC OS X). Some of these functionalities have special economical constraints of development time and memory footprint. To better accommodate all the above listing requirements, a model-driven generative software development paradigm supported by mainstream tools is proposed to offer a significant leverage in hiding commonalities and configuring variabilities across families of video surveillance products while maintaining the new product quality.This work was funded through the Competitive Factors Operational Program COMPETE and through national funds though the Science and Technology Foundation - FCT, within the project: FCOMP-01-0124-FEDER-022674. This work was developed in cooperation with IVV Automation; all support and means provided by the company is acknowledged

РЕЗУЛЬТАТЫ ИСПОЛЬЗОВАНИЯ СОФОСБУВИРА В КОМБИНАЦИИ С ЛЕДИПАСВИРОМ ИЛИ ДАКЛАТАСВИРОМ ДЛЯ ЛЕЧЕНИЯ ХРОНИЧЕСКОГО ГЕПАТИТА С В РЕСПУБЛИКЕ БЕЛАРУСЬ

To evaluate the efficacy of therapy with sofosbuvir in combination with ledipasvir or daclatasvir, the results of treatment of 299 patients with chronic hepatitis C, including 128 non-responders to combined interferon plus ribavirin therapy, who have prognostically unfavorable single nucleotide polymorphisms 39743165T> G (rs8099917) and 39738787C> T (rs12979860) of interleukin-28B gene, were analyzed. 57 people had liver cirrhosis. 80,9% (242) had genotype 1 of hepatitis C virus, 5% (15) – genotype 2, 13,7% (41) – genotype 3, and 0,4% (1) – genotype 4.All 299 patients, who adhered to the recommendations of the European Association for the Study of the Liver 2016 and the American Association for the Study of the Liver Disease 2017, achieved a sustained virologic response 12 weeks after the end of therapy. The clinical case of treatment failure, associated with the lack of confirmation of the elimination of hepatitis C virus by means of highly sensitive polymerase chain reaction methods and with the later identified amino acid substitution in position Y93H of NS5A (resistance to NS5A inhibitors), is shown.It is necessary to carry out monitoring of effectiveness of therapy only by means of highly sensitive polymerase chain reaction (from 10 ME/ml). If the virus elimination delays in patients with advanced stages of liver fibrosis it is needed to use the prolonged schemes of treatment. Repeated treatment of patients with existence of a mutation of Y93H requires the use of new NS5A inhibitors or combined drugs.С целью оценки эффективности терапии препаратами софосбувир в комбинации с ледипасвиром или даклатасвиром были проанализированы исходы лечения 299 пациентов с хроническим гепатитом С, включая 128 ранее неудачно пролеченных интерферонами и рибавирином, а также имеющих прогностически неблагоприятные однонуклеотидные полиморфизмы 39743165T>G (rs8099917) и 39738787C>T (rs12979860) гена интерлейкин-28В. У 57 пациентов был диагностирован цирроз печени, 128 пациентов были ранее неудачно пролечены интерферонами и рибавирином. У 80,9% (242) был первый генотип вируса, у 5% (15) – второй, у 13,7% (41) – третий, у 0,4% (1) – четвертый.В результате исследования было отмечено, что все 299 пациентов, которые придерживались рекомендаций European Association for the Study of the Liver 2015, 2016 и American Association for the Study of the Liver Disease 2017, достигли устойчивого вирусологического ответа через 12 недель после окончания терапии. Приведен клинический случай неудачного лечения, связанный с отсутствием подтверждения элиминации вируса гепатита С при помощи высокочувствительных методов полимеразной цепной реакции и с позднее выявленной аминокислотной заменой в позиции Y93H NS5A (резистентность к ингибиторам NS5A).Мониторинг эффективности терапии необходимо проводить только при помощи высокочувствительных методик полимеразной цепной реакции (от 10 МЕ/мл) и при задержке элиминации вируса у пациентов с продвинутыми стадиями фиброза печени использовать пролонгированные схемы лечения. Для повторного лечения пациентов с наличием мутации Y93Н необходимы новые препараты ингибиторов NS5A или комбинированных препаратов.

RESULTS OF THE USE OF SOFOSBUVIR IN COMBINATION WITH LEDIPASVIR OR DACLATASVIR FOR CHRONIC HEPATITIS C TREATMENT IN THE REPUBLIC OF BELARUS

To evaluate the efficacy of therapy with sofosbuvir in combination with ledipasvir or daclatasvir, the results of treatment of 299 patients with chronic hepatitis C, including 128 non-responders to combined interferon plus ribavirin therapy, who have prognostically unfavorable single nucleotide polymorphisms 39743165T> G (rs8099917) and 39738787C> T (rs12979860) of interleukin-28B gene, were analyzed. 57 people had liver cirrhosis. 80,9% (242) had genotype 1 of hepatitis C virus, 5% (15) – genotype 2, 13,7% (41) – genotype 3, and 0,4% (1) – genotype 4.All 299 patients, who adhered to the recommendations of the European Association for the Study of the Liver 2016 and the American Association for the Study of the Liver Disease 2017, achieved a sustained virologic response 12 weeks after the end of therapy. The clinical case of treatment failure, associated with the lack of confirmation of the elimination of hepatitis C virus by means of highly sensitive polymerase chain reaction methods and with the later identified amino acid substitution in position Y93H of NS5A (resistance to NS5A inhibitors), is shown.It is necessary to carry out monitoring of effectiveness of therapy only by means of highly sensitive polymerase chain reaction (from 10 ME/ml). If the virus elimination delays in patients with advanced stages of liver fibrosis it is needed to use the prolonged schemes of treatment. Repeated treatment of patients with existence of a mutation of Y93H requires the use of new NS5A inhibitors or combined drugs