Direct-acting antivirals ombitasvir / paritaprevir / ritonavir + dasabuvir with or without ribavirin in hepatitis C virus (HCV) genotype 1-infected treatment-naive or treatment-experienced patients with or without cirrhosis : Real-life experience in Lithuania and Latvia

Publisher Copyright: © 2018, Hepatitis Monthly.Background: The current international multicentre open-label, uncontrolled, real-world retrospective study aimed at evaluating the effectiveness and safety of ombitasvir / paritaprevir / ritonavir + dasabuvir ± ribavirin (3D therapy) in treatment-naive and treatment-experienced hepatitis C virus (HCV) genotype 1-infected (GT1) patients. Methods: Adult patients with chronic HCV GT1 infection, scheduled for 3D therapy according to therapeutic guidelines, were eligible. Demographic and clinical data were collected retrospectively by reviewing individuals health records. The primary effectiveness endpoint was the sustained virological response at 12 weeks following the end of treatment (SVR12). Results: The participants in the current study consisted of 134 patients with HCV GT1 infection, including 10 liver transplant recipients. SVR12 was achieved in 120 (96.8%) non-transplant and all liver transplant patients (100%). Significant improvement in liver function tests were observed. Among 4 treatment failures, 2 patients were non-responders and 2 patients relapsed. OBV/PTV/r + DSV ± RBV regimen was well tolerated in most patients with treatment discontinuation due to adverse events in 3 patients. The most frequent adverse events were asthenia (25.8%), fatigue (16.1%), skin pruritus (12.9%), and dyspepsia (11.3%). Conclusions: The current real-life study demonstrated the effectiveness and safety of OBV/PTV/r + DSV ± RBV in patients with HCV GT1, including patients with cirrhosis, a liver transplant recipient and the one who failed previous antiviral therapies.publishersversionPeer reviewe

Pooperacinio stemplės ir skrandžio ar stemplės ir plonosios žarnos jungties nesandarumo gydymas išsiplečiančiais stentais

Arnoldas Krasauskas1, Renatas Aškinis1, Saulius Cicėnas1,2, Tamara Tyrina1, Ramūnas Ambrozaitis1, Eugenijus Stratilatovas1 1Vilniaus universiteto Onkologijos institutas, Santariškių g. 1, LT-08660 Vilnius El paštas: [email protected] 2Vilniaus universiteto Medicinos fakulteto Reabilitacijos, sporto medicinos ir slaugos institutas Įvadas: Po rezekcinių operacijų stemplės ir skrandžio ar stemplės ir žarnos jungties nesandarumas yra grėsmingiausia komplikacija, pasireiškianti iki 27 % operuotų ligonių. Ji gali būti mirtina iki 9 % tokių ligonių dėl infekcijos ir negalėjimo valgyti. Nuo 2005 m. fistulei panaikinti pradėjome į jungties spindį implantuoti išsiplečiančius silikonu dengtus stentus. Darbo tikslas – įvertinti, ar šis būdas tinka pooperacinių fistulių sukeltoms komplikacijoms gydyti. Ligoniai ir metodai: Vilniaus universiteto Onkologijos institute nuo 2005 iki 2009 metų buvo atlikta 417 stemplės ir skrandžio rezekcinių operacijų dėl onkologinių ligų. Po skrandžio pašalinimo operacijų atsirado 2,87 % fistulių, po stemplės operacijų – 21,65 % fistulių. Per šį laikotarpį 15 ligonių buvo implantuota 21 stentas dėl pooperacinių jungties fistulių: 4 (26,67 %) ligoniams – po Akyama operacijų, 7 (46,67 %) – po Lewis operacijų ir 4 (26,7 %) – po gastrektomijos. Spindis buvo protezuojamas maždaug po 17 dienų nustačius fistulę (nuo 3 iki 60 dienų). Buvo naudojami išsiplečiantys silikonu dengti plastikinio ar nitinolinio karkaso stentai. Dviem (13,3 %) ligoniams stentai keisti po 1 kartą ir dviem (13,3 %) – po 2 kartus. Rezultatai: Mirčių po šių procedūrų nebuvo. Tiriant rentgenu 6 (40 %) ligoniams po stento implantavimo kontrastinio skysčio tekėjimo pro fistulę nematyta, 4 (26,67 %) – gautas dalinis efektas, o 1 (6,67 %) – tik sumažėjęs geriamojo kontrastinio skysčio kiekio pratekėjimas fistule. Vidutiniškai po 5 dienų (3–14 dienų) 3 (20 %) ligoniams stentai pašalinti dėl nestabilios jų padėties ir 1 (6,7 %) ligonei – dėl nestabilios stento padėties sukelto kraujavimo iš jungties kraštų. Dviem (13,3 %) ligoniams stentai pasišalino savaime, 1 (6,7 %) ligonei stentas pašalintas laparotomijos būdu, nes buvo įstrigęs terminalinėje klubinės žarnos srityje. Vienas (6,67 %) ligonis atvyko tik po vienerių metų dėl sutrikusio (IV°) rijimo, sukelto randinio susiaurėjimo. Jam stentas pašalintas laparotomijos būdu, suformuota nauja stemplės ir plonosios žarnos jungtis. Šešiems (40 %) ligoniams stentai pašalinti nelikus jungties nesandarumo vidutiniškai po 47 parų (29–127 dienų) endoskopinės procedūros metu. Išvados: Stemplės ir skrandžio ar stemplės ir žarnos jungties protezavimas implantuojant į spindį išsiplečiančius silikonu dengtus stentus yra saugus ir efektyvus būdas fistulių okliuzijai bei jų sukeltoms komplikacijoms gydyti. Vienuolikai (73,3 %) iš 15 ligonių būklė pagerėjo dėl greičiau išnykusios infekcijos. Šeši (54,5 %) iš 11 ligonių galėjo valgyti jau kitą dieną po procedūros. Dviem (13,3 %) ligoniams įdėjus stentą įvyko komplikacijų. Po 6 mėn. ir vėliau 4 (26,67 %) geros būklės ligoniams reikėjo chirurginės intervencijos galutinei fistulių sukeltų komplikacijų korekcijai. Pagrindiniai žodžiai: pooperacinė fistulė, stentavimas, savaime išsiplečiantis stentas. Treatment of postoperative esophagogastrostomy/esophagoenterostomy leaks by using self-expanding stents Arnoldas Krasauskas1, Renatas Aškinis1, Saulius Cicėnas1,2, Tamara Tyrina1, Ramūnas Ambrozaitis1, Eugenijus Stratilatovas1 1Institute of Oncology, Vilnius University, Santariškių str., 1, LT-08660 Vilnius, Lithuania E-mail: [email protected] 2Vilnius University, Faculty of Medicine, Institute of Rehabilitation, Sport Medicine and Nursing Background: Esophagogastrostomy/esophagoenterostomy leak is a major complication after esophagectomy or gastrectomy and could causes an up to 9 % postopertive mortality. Since 2005, we use self-expanding stents for the occlusion of anastomotic leaks. The objective is to analyse the usefulness of this method for the treatment of anastomotic fistulas. Patients and methods: From 2005 to 2009, 417 esophageal resections and gastrectomies for oncology patiens were made. After gastectomies, there were 2.87% and after oesophageal resection 21.65 % of anastomotic leaks. Twenty-one silicon-covered self-expanding stents were placed for 15 patients: for 4 patients (26.67 %) after Akyama type operations, 7 (46.67 %) after Lewis type operations and 4 (26.67 %) after gastrectomies. For 4 (26.67 %) patients, leaks were complicated with neck fistulas, 2 (13.3 %) with peritonitis, 8 (53.3%) with empyema and tracheoesophageal fistula. The median interval between detecting the fistula and stenting were 17 days (range, 3–60 days). We used silicon-covered plastic or nitinol armed self-expanding stents. For 2 (13.3 %) patients we replaced stents once and for 2 (13.3 %) twice. Results: Postinterventional esophagogram demonstrated full coverage of the leak in 6 (40 %) patients, and 1 (6.67 %) showed only a lower volume flow of the swallowed contrast. In 4 (26.67 %) patients, in the horizontal posistion we observed retrogradic contrast effusion. In 4 (26.67 %) patients, stents were removed on average after 5 days (range 3–14 days) of instability and for 1 (6.7 %) after a volatile situation caused by bleeding from the edges of the fistula. Two (13.3 %) stents moved down to gut, 1 (6.7 %) need laparotomy because it was stuck in the ileum terminale. One (6.67 %) patient came after 1 year with IV° dysphagia. We performed laparotomy to remove the stent and a new anastomosis to treat stenosis. Six (40 %) stents were removed during endoscopic procedures without residual leaks on average after 47 days (range 29–127 days). Conclusions: Silicon-covered self-expanding stent is an effective method of occluding postoperative esophagogastrostomy/esophagoenterostomy leaks. In 11 (73.3 %) of 15 patients, the condition improved because of accelerated healing of infectious complications. 6 (54.5 %) of 11 patients could begin eating next day after the procedure. There were only 2 (13.3 %) stent implantation-related complications. After 6 months and later in good condition 4 (26.67 %) patients had a surgical intervention for the final correction of fistulas-caused complications. Key words: esophagogastrostomy leaks, esophagoenterostomy leaks, self-expanding stents

Epidemiology of Lyme Disease in a Highly Endemic European Zone

Background and objective: Lyme disease, also known as Lyme borreliosis (LB), is a tick-borne infectious disease caused by the spirochete bacteria Borrelia. The risk of infection depends on the geographical area, ecological factors, and human behavior. Clinical manifestations of Lyme borreliosis have a wide range, but the most frequent clinical symptom, which is also a diagnostic symptom, is a skin rash called erythema migrans (EM). The disease is very common worldwide. In Lithuania, the disease frequency is 99.9 cases per 100,000 population (Centre for Communicable Diseases and AIDS, Lithuania, 2017). The main aim of this study was to obtain the baseline characteristics of the disease regarding the infected Lithuanian population. Materials and Methods: We analyzed data from the Centre for Communicable Diseases and AIDS about all Lyme disease (A69.2) diagnosed patients over a three-year period (from 2014 to 2016) in Lithuania. Results: In 2014–2016, 7424 (crude incidence rate 85.4) cases with LB were diagnosed in Lithuania. Most of them (4633 (62.4%)) were identified in women. Older people were more likely to suffer from LB. Urban residents were 2.6 times more often affected that those living in villages. Tick bites were primarily observed in high season months, from May to September (90%), with the highest peak in July. There was a higher number of observed tick bites (p = 0.003) in the urban residents. Erythema migrans occurred in 75.6% LB cases, while other symptoms did not exceed a quarter of all LB cases. There were 7353 (99.6%) cases where LB was confirmed via clinical symptoms and/or laboratory tests. Also, 1720 (23.2%) patients were tested for LB immunoglobulins. Conclusions: This study found a high incidence of Lyme disease in Lithuania. We elucidated the baseline characteristics regarding the infected Lithuanian population which may ease medical clinicians’ work on new Lyme diagnoses

Genotype Distribution and Characteristics of Chronic Hepatitis C Infection in Estonia, Latvia, Lithuania, and Ukraine : The RESPOND-C Study

Publisher Copyright: © 2023 by the authors.Background and objectives: Since 2013, highly effective direct-acting antiviral (DAA) treatment for chronic hepatitis C (CHC) has become available, with cure rates exceeding 95%. For the choice of optimal CHC treatment, an assessment of the hepatitis C virus (HCV) genotype (GT) and liver fibrosis stage is necessary. Information about the distribution of these parameters among CHC patients in Estonia, Latvia, and Lithuania (the Baltic states) and especially in Ukraine is scarce. This study was performed to obtain epidemiologic data regarding CHC GT and fibrosis stage distribution for better planning of resources and prioritization of patients for DAA drug treatment according to disease severity in high-income (the Baltic states) and lower-middle-income (Ukraine) countries. Materials and methods: The retrospective RESPOND-C study included 1451 CHC patients. Demographic and disease information was collected from medical charts for each patient. Results: The most common suspected mode of viral transmission was blood transfusions (17.8%), followed by intravenous substance use (15.7%); however, in 50.9% of patients, the exact mode of transmission was not clarified. In Ukraine (18.4%) and Estonia (26%), transmission by intravenous substance use was higher than in Lithuania (5%) and Latvia (5.3%). Distribution of HCV GT among patients with CHC was as follows: GT1—66.4%; GT3—28.1; and GT2—4.1%. The prevalence of GT1 was the highest in Latvia (84%) and the lowest in Ukraine (63%, p < 0.001). Liver fibrosis stages were distributed as follows: F0—12.2%, F1—26.3%, F2—23.5%, F3—17.1%, and F4—20.9%. Cirrhosis (F4) was more prevalent in Lithuanian patients (30.1%) than in Estonians (8.1%, p < 0.001). Conclusions: This study contributes to the knowledge of epidemiologic characteristics of HCV infection in the Baltic states and Ukraine. The data regarding the patterns of HCV GT and fibrosis stage distribution will be helpful for the development of national strategies to control HCV infection in the era of DAA therapy.Peer reviewe

Evaluation of cost-effective strategies for rabies post-exposure vaccination in low-income countries

&lt;b&gt;Background:&lt;/b&gt; Prompt post-exposure prophylaxis (PEP) is essential in preventing the fatal onset of disease in persons exposed to rabies. Unfortunately, life-saving rabies vaccines and biologicals are often neither accessible nor affordable, particularly to the poorest sectors of society who are most at risk and upon whom the largest burden of rabies falls. Increasing accessibility, reducing costs and preventing delays in delivery of PEP should therefore be prioritized.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Methodology/Principal Findings:&lt;/b&gt; We analyzed different PEP vaccination regimens and evaluated their relative costs and benefits to bite victims and healthcare providers. We found PEP vaccination to be an extremely cost-effective intervention (from $200 to less than$60/death averted). Switching from intramuscular (IM) administration of PEP to equally efficacious intradermal (ID) regimens was shown to result in significant savings in the volume of vaccine required to treat the same number of patients, which could mitigate vaccine shortages, and would dramatically reduce the costs of implementing PEP. We present financing mechanisms that would make PEP more affordable and accessible, could help subsidize the cost for those most in need, and could even support new and existing rabies control and prevention programs.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions/Significance:&lt;/b&gt; We conclude that a universal switch to ID delivery would improve the affordability and accessibility of PEP for bite victims, leading to a likely reduction in human rabies deaths, as well as being economical for healthcare providers.&lt;p&gt;&lt;/p&gt

The burden of respiratory infections among older adults in long-term care:a systematic review

BACKGROUND: Respiratory infections among older adults in long-term care facilities (LTCFs) are a major global concern, yet a rigorous systematic synthesis of the literature on the burden of respiratory infections in the LTCF setting is lacking. To address the critical need for evidence regarding the global burden of respiratory infections in LTCFs, we assessed the burden of respiratory infections in LTCFs through a systematic review of the published literature. METHODS: We identified articles published between April 1964 and March 2019 through searches of PubMed (MEDLINE), EMBASE, and the Cochrane Library. Experimental and observational studies published in English that included adults aged ≥60 residing in LTCFs who were unvaccinated (to identify the natural infection burden), and that reported measures of occurrence for influenza, respiratory syncytial virus (RSV), or pneumonia were included. Disagreements about article inclusion were discussed and articles were included based on consensus. Data on study design, population, and findings were extracted from each article. Findings were synthesized qualitatively. RESULTS: A total of 1451 articles were screened for eligibility, 345 were selected for full-text review, and 26 were included. Study population mean ages ranged from 70.8 to 90.1 years. Three (12%) studies reported influenza estimates, 7 (27%) RSV, and 16 (62%) pneumonia. Eighteen (69%) studies reported incidence estimates, 7 (27%) prevalence estimates, and 1 (4%) both. Seven (27%) studies reported outbreaks. Respiratory infection incidence estimates ranged from 1.1 to 85.2% and prevalence estimates ranging from 1.4 to 55.8%. Influenza incidences ranged from 5.9 to 85.2%. RSV incidence proportions ranged from 1.1 to 13.5%. Pneumonia prevalence proportions ranged from 1.4 to 55.8% while incidence proportions ranged from 4.8 to 41.2%. CONCLUSIONS: The reported incidence and prevalence estimates of respiratory infections among older LTCF residents varied widely between published studies. The wide range of estimates offers little useful guidance for decision-making to decrease respiratory infection burden. Large, well-designed epidemiologic studies are therefore still necessary to credibly quantify the burden of respiratory infections among older adults in LTCFs, which will ultimately help inform future surveillance and intervention efforts

Influenza in long-term care facilities

Long-term care facility environments and the vulnerability of their residents provide a setting conducive to the rapid spread of influenza virus and other respiratory pathogens. Infections may be introduced by staff, visitors or new or transferred residents, and outbreaks of influenza in such settings can have devastating consequences for individuals, as well as placing extra strain on health services. As the population ages over the coming decades, increased provision of such facilities seems likely. The need for robust infection prevention and control practices will therefore remain of paramount importance if the impact of outbreaks is to be minimised. In this review, we discuss the nature of the problem of influenza in long-term care facilities, and approaches to preventive and control measures, including vaccination of residents and staff, and the use of antiviral drugs for treatment and prophylaxis, based on currently available evidence. This article is protected by copyright. All rights reserved

Intradermal influenza vaccination of healthy adults using a new microinjection system: a 3-year randomised controlled safety and immunogenicity trial

<p>Abstract</p> <p>Background</p> <p>Intradermal vaccination provides direct and potentially more efficient access to the immune system via specialised dendritic cells and draining lymphatic vessels. We investigated the immunogenicity and safety during 3 successive years of different dosages of a trivalent, inactivated, split-virion vaccine against seasonal influenza given intradermally using a microinjection system compared with an intramuscular control vaccine.</p> <p>Methods</p> <p>In a randomised, partially blinded, controlled study, healthy volunteers (1150 aged 18 to 57 years at enrolment) received three annual vaccinations of intradermal or intramuscular vaccine. In Year 1, subjects were randomised to one of three groups: 3 μg or 6 μg haemagglutinin/strain/dose of inactivated influenza vaccine intradermally, or a licensed inactivated influenza vaccine intramuscularly containing 15 μg/strain/dose. In Year 2 subjects were randomised again to one of two groups: 9 μg/strain/dose intradermally or 15 μg intramuscularly. In Year 3 subjects were randomised a third time to one of two groups: 9 μg intradermally or 15 μg intramuscularly. Randomisation lists in Year 1 were stratified for site. Randomisation lists in Years 2 and 3 were stratified for site and by vaccine received in previous years to ensure the inclusion of a comparable number of subjects in a vaccine group at each centre each year. Immunogenicity was assessed 21 days after each vaccination. Safety was assessed throughout the study.</p> <p>Results</p> <p>In Years 2 and 3, 9 μg intradermal was comparably immunogenic to 15 μg intramuscular for all strains, and both vaccines met European requirements for annual licensing of influenza vaccines. The 3 μg and 6 μg intradermal formulations were less immunogenic than intramuscular 15 μg. Safety of the intradermal and intramuscular vaccinations was comparable in each year of the study. Injection site erythema and swelling was more common with the intradermal route.</p> <p>Conclusion</p> <p>An influenza vaccine with 9 μg of haemagglutinin/strain given using an intradermal microinjection system showed comparable immunogenic and safety profiles to a licensed intramuscular vaccine, and presents a promising alternative to intramuscular vaccination for influenza for adults younger than 60 years.</p> <p>Trial registration</p> <p>Clinicaltrials.gov NCT00703651.</p

Systematic review of influenza resistance to the neuraminidase inhibitors

<p>Abstract</p> <p>Background</p> <p>Antivirals play a critical role in the prevention and the management of influenza. One class of antivirals, neuraminidase inhibitors (NAIs), is effective against all human influenza viruses. Currently there are two NAI drugs which are licensed worldwide: oseltamivir (Tamiflu^®) and zanamivir (Relenza^®); and two drugs which have received recent approval in Japan: peramivir and laninamivir. Until recently, the prevalence of antiviral resistance has been relatively low. However, almost all seasonal H1N1 strains that circulated in 2008-09 were resistant to oseltamivir whereas about 1% of tested 2009 pandemic H1N1 viruses were found to be resistant to oseltamivir. To date, no studies have demonstrated widespread resistance to zanamivir. It seems likely that the literature on antiviral resistance associated with oseltamivir as well as zanamivir is now sufficiently comprehensive to warrant a systematic review.</p> <p>The primary objectives were to systematically review the literature to determine the incidence of resistance to oseltamivir, zanamivir, and peramivir in different population groups as well as assess the clinical consequences of antiviral resistance.</p> <p>Methods</p> <p>We searched MEDLINE and EMBASE without language restrictions in September 2010 to identify studies reporting incidence of resistance to oseltamivir, zanamivir, and peramivir. We used forest plots and meta-analysis of incidence of antiviral resistance associated with the three NAIs. Subgroup analyses were done across a number of population groups. Meta-analysis was also performed to evaluate associations between antiviral resistance and clinical complications and symptoms.</p> <p>Results</p> <p>We identified 19 studies reporting incidence of antiviral resistance. Meta-analysis of 15 studies yielded a pooled incidence rate for oseltamivir resistance of 2.6% (95%CI 0.7% to 5.5%). The incidence rate for all zanamivir resistance studies was 0%. Only one study measured incidence of antiviral resistance among subjects given peramivir and was reported to be 0%. Subgroup analyses detected higher incidence rates among influenza A patients, especially for H1N1 subtype influenza. Considerable heterogeneity between studies precluded definite inferences about subgroup results for immunocompromised patients, in-patients, and children. A meta-analysis of 4 studies reporting association between oseltamivir-resistance and pneumonia yielded a statistically significant risk ratio of 4.2 (95% CI 1.3 to 13.1, p = 0.02). Oseltamivir-resistance was not statistically significantly associated with other clinical complications and symptoms.</p> <p>Conclusion</p> <p>Our results demonstrate that that a substantial number of patients may become oseltamivir-resistant as a result of oseltamivir use, and that oseltamivir resistance may be significantly associated with pneumonia. In contrast, zanamivir resistance has been rarely reported to date.</p

Training in infectious diseases across Europe in 2021 - a survey on training delivery, content and assessment

Objectives: To define the status of infectious diseases (ID) as an approved specialty in Europe; to enumerate the number of specialists (in general and in relation to the overall population) and specialist trainees and describe the content, delivery and evaluation of postgraduate training in ID in different countries.Methods: Structured web-based questionnaire surveys in March 2021 of responsible national authorities, specialist societies and individual country representatives to the Section of Infectious Diseases of the European Union for Medical Specialties. Descriptive analysis of quantitative and qualitative responses.Results: In responses received from 33/35 (94.3%) countries, ID is recognized as a specialty in 24 and as a subspecialty of general internal medicine (GIM) in eight, but it is not recognized in Spain. The number of ID specialists per country varies from <5 per million inhabitants to 78 per million inhabitants. Median length of training is 5 years (interquartile range 4.0–6.0 years) with variable amounts of preceding and/or concurrent GIM. Only 21.2% of countries (7/33) provide the minimum recommended training of 6 months in microbiology and 30% cover competencies such as palliative care, team working and leadership, audit, and quality control. Training is monitored by personal logbook or e-portfolio in 75.8% (25/33) and assessed by final examinations in 69.7% (23/33) of countries, but yearly reviews with trainees only occur in 54.5% (18/33) of countries.Conclusions: There are substantial gaps in modernization of ID training in many countries to match current European training requirements. Joint training with clinical microbiology (CM) and in multidisciplinary team working should be extended. Training/monitoring trainers should find greater focus, together with regular feedback to trainees within many national training programmes.peer-reviewe