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Objectives: Second-generation direct-acting antivirals (DAAs) have shown high efficacy in the treatment of chronic hepatitis C virus (HCV) infections in clinical trials. This study aimed to estimate the effectiveness in real-life conditions and their capacity to eliminate HCV infection in the general population., Methods: In this observational cohort study, patients with active HCV infection who commenced DAA treatment between 2015 and 2020 in Navarre, Spain, were studied. Sustained virological response (SVR), defined as an undetectable viral load 12 weeks after the end of treatment, was evaluated until the end of 2021., Results: Of a total 1366 HCV-infected patients that commenced treatment, 19.3% (n = 263) were HIV-coinfected. After the first DAA treatment, SVR was achieved in 96.6% (n = 1320/1366) of patients and in 97.7% (95% confidence interval [CI] 96.6%-98.3%) of those who completed treatment (per-protocol analysis; n = 1320/1351). SVR was achieved in 97.9% (n = 1066/1089) and 96.9% (n = 254/262) of mono-infected and HIV-coinfected patients, respectively. Thirty-one patients had virological failure due to non-response (n = 19), poor compliance (n = 9), and with adverse events (n = 3). Of 27 patients that received a second treatment, 24 attained SVR (one after a third treatment), two died, and one that did not achieve SVR declined a third treatment. Three patients were re-infected, re-treated, and achieved SVR. At the end of the study, 1344 patients (98.4%, 95% CI 97.6%-98.9%) had achieved SVR, and only 1.8% needed more than one course of treatment. All patients who completed the treatment and were followed-up achieved SVR., Conclusion: With DAAs, SVR was achieved in all patients with active HCV infection who completed follow-up, and a second course of treatment was only necessary in a small proportion of patients. Adherence to treatment is essential for HCV infection elimination.

Background: There is currently much uncertainty regarding the most optimal treatment for COVID-19. This study analyze the change in the clinical condition of patients hospitalized for severe COVID-19 pneumonia and treated with remdesivir in a real-life setting, based on the WHO Ordinal Scale. Clinical complications, treatment safety, and impact of other associated drugs were also analyzed., Methods: We conducted an observational, retrospective study including patients treated with remdesivir. The need for admission to the ICU, the length of ICU and hospital stay, and the need for ventilatory support were analyzed. The laboratory parameters, drugs administered concomitantly, and difference in the length of hospital stay according to the concomitant treatment received were also evaluated. A univariate and multivariate Cox regression analysis was performed to analyze associated factors., Results: A total of 92 patients were included. The mean length of hospital stay was 15 days, and 90% of the patients had been discharged from the hospital 28 days after starting treatment with remdesivir. The likelihood of hospital discharge among patients not presenting with hypertension as a comorbidity was significantly higher than that of those with this condition (HR = 3.19, P = 0.008). Nineteen patients had to be admitted to the ICU (mean of 18 days). Approximately 11% required invasive mechanical ventilation (mean of 22 days). Almost 37% of the patients received high-flow oxygen therapy and 14% non-invasive mechanical ventilation. Four deaths were recorded within the first week. Main adverse events were increases in transaminase and creatinine levels. Nosocomial infections were more frequent when remdesivir was combined with immunosuppressive drugs., Conclusions: Patients with severe COVID-19 pneumonia and treated with remdesivir require relatively prolonged hospital stays, many with a need for ventilatory support and, in a considerable proportion of cases, admission to the ICU. However, the observed survival rate is high, and the drug is well tolerated., Competing Interests: The authors have declared that no competing interests exist.

To date, there is no consensus regarding palivizumab prophylaxis for respiratory syncytial virus infection. The purpose of this study is to assess the effectiveness of palivizumab prophylaxis to prevent respiratory syncytial virus-related infection consultations and hospitalizations in high-risk children <2 y. We studied children <2 y of age with risk factors who had indication of palivizumab prophylaxis over eight epidemic seasons (2011-2012 to 2018-2019) in Navarra, Spain. Children positives for respiratory syncytial virus by reverse-transcription polymerase chain reaction were compared to negative testers. Palivizumab was indicated in 1,214 children <2 y of age with risk factors during 2011-2012 to 2018-2019 seasons. A total of 142 high-risk children tested for respiratory syncytial virus were included in the study. From the 35 respiratory syncytial virus-positive confirmed cases, 20 (57%) had received palivizumab versus 82 (77%) from the 107 negative controls. The effectiveness of prophylactic palivizumab was 70% (95% CI, 19%-90%) in preventing confirmed clinical infection and 82% (95% CI, 29%-96%) in preventing hospitalized cases. Our results show that palivizumab is notably effective for preventing laboratory-confirmed cases of respiratory syncytial virus and hospitalization in high-risk children <2 y of age. For children who have received palivizumab, the risk of getting sick remains high; thus, other preventive measures are necessary.

Background: hepatitis C virus (HCV) antibody tests have been performed since the 90s, although HCV-RNA (viral load) determination was not always performed. Some of these patients may be actively infected and not be aware of it. Here, we describe a procedure to capture these subjects and complete their diagnosis., Methods: the historical laboratory results of Navarra were reviewed and individuals who were positive for antibodies against HCV (anti-HCV) and had not undergone HCV-RNA testing were identified. In September 2018, each general practitioner (GP) was informed about their patients and given precise instructions for completing the diagnosis. The procedure was assessed until December 2019., Results: two hundred and eighty-nine anti-HCV positive patients were detected for whom active infection had not been discarded. Two were HIV-positive and six had already died. GPs were asked to assess the remaining 281 subjects. By the end of 2019, a new blood test had been performed in 187 (67 %) patients, 5 % decided not to do it, 4 % were living outside of Navarra, 3 % could not be contacted and the GP considered that it was not justified in 2 % of cases. Thus, 19 % remained to be contacted. From the 187 assessed patients, active infection was confirmed in 52 (28 %) individuals, 40 % were false positives and HCV-RNA was undetectable in 31 %. Regarding the 52 actively infected subjects, 34 had already initiated antiviral therapy and three were hospitalized due to decompensated cirrhosis, from which one patient died., Conclusions: the strategy to recapture individuals with an incomplete HCV infection diagnosis was effective to detect active infections and subsequent initiation of antiviral therapy.

Introduction: There is little information on whether direct-acting antiviral (DAA) treatment can improve liver fibrosis or change glucose and lipid profile in patients with chronic hepatitis C (CHC). We aimed to evaluate the impact of sustained virologic response (SVR) on liver stiffness, glucose and lipid levels., Methods: 445 monoinfected CHC patients started treatment with interferon-free DAA therapy from January 2015 to February 2017. Transient elastography (TE), fibrosis scores, glucose and lipid levels were analyzed at baseline and 48 weeks post-treatment (SVR48)., Results: The SVR rate was 97.7%. Finally, we evaluated 369 patients who achieved SVR and had reliable TE measurements. Median liver stiffness significantly decreased from 9.3 (IQR 7.3-14.3)kPa at baseline to 6.4 (IQR 4.9-8.9) at SVR48 (p<0.0001). 54.7% of the cohort presented fibrosis regression. Median FIB4 score regressed from 2.0 (IQR 1.1-3.3) to 1.3 (IQR 0.9-2.0) (p<0.0001). Median APRI and Forns values significantly decreased from 0.9 (IQR 0.5-1.7) to 0.3 (IQR 0.2-0.4) and from 6.2 (5.0-7.5) to 4.9 (IQR 3.8-5.9) (p<0.001), respectively. Mean levels of total cholesterol and LDL-C increased from 172mg/dL and 101.5mg/dL to 191mg/dL and 117.5mg/dL (p<0.0001), respectively. In the sub-group of patients with pre-diabetes or diabetes, mean glucose levels decreased from 142.7mg/dL at baseline to 127.2mg/dL at SVR48 (p<0.001)., Discussion: SVR reduces liver stiffness based on TE and fibrosis scores, in patients treated with DAA. Our results show elevated total cholesterol and LDL-C and decreased glucose levels at SVR48., (Copyright © 2020 Elsevier España, S.L.U. All rights reserved.)

Background: Cellulosimicrobium species, formely known as Oerskovia species, are gram-positive bacilli belonging to the order Actinomycetales. They rarely cause human infections. The genus comprises two pathogenic species in humans: C. cellulans and C. funkei. Based on a case report, we provide a review of the literature of infections caused by Cellulosimicrobium/Oerskovia, in order to improve our knowledge of this unusual infection., Case Presentation: An 82-year-old woman with aortic prosthetic valve presented to the hospital with fever and heart failure. Further work up revealed the diagnosis of C. cellulans infective endocarditis (IE). The strain was identified by MALDI-TOF MS, API Coryne and 16S rRNA sequencing. The patient was deemed not to be an operative candidate and died despite the antibiotic therapy 35 days after admission., Conclusions: Reviewing cases of Cellulosimicrobium species infections and communicating the successful and unsuccessful clinical experiences can assist future healthcare providers. Our case and those previously reported indicate that Cellulosimicrobium species usually infect immunocompromised patients or foreign body carriers. The most frequent pattern of infection is central venous catheter related bacteremia. The optimal treatment should include foreign body removal and valve surgery should be considered in case of IE.

Background : The aim of this study was to describe the natural long-term course of end-stage liver disease associated with chronic hepatitis C (HCV) infection by measuring survival and complication rates in the era prior to the arrival of new direct-acting antiviral (DAA) drugs. Methods : A retrospective population-based cohort study was designed to establish the follow-up of patients hospitalized for a decompensated cirrhotic event or hepatocellular carcinoma using electronic records from hospital discharge databases from 2009 to 2015. Their survival was compared with a sex, age and non-liver mortality excess matched simulation of the general Spanish population. Results : A total of 253 patients were included in the study. Among those with decompensated cirrhosis (n = 151) the hospital admission rate was 1.88 per patient-year with a mortality rate of 0.16 per patient-year. Mean survival was 4.10 years for patients with decompensated cirrhosis, and 1.75 for non-transplanted hepatocellular carcinoma, compared to 18.39 years for the general population. Conclusion : Our results show the complexity and rapid progression of end-stage liver disease associated with HCV infection. The considerable loss of life expectancy associated with the development of decompensated cirrhosis in patients with chronic HCV infection in the absence of viral clearance through treatment is acutely evident.

Purpose: To compare health-related quality of life (HRQoL) between hepatitis C patients who achieve sustained virological response (SVR) to direct-acting antivirals and a sex- and age-paired sample of the general population., Methods: HRQoL was evaluated in patients recruited in Navarre, Spain, from May 2016 to April 2017 at baseline and after SVR, using the EQ-5D-5L questionnaire. Both results were compared to those of general population of the same sex and age obtained from the 2011/12 National Health Survey in Spain. Observed/expected (O/E) ratios for health dimensions and differences between O-E in EQ-5D utility and visual analogical scale (VAS) scores were calculated., Results: 206 patients were studied. Before treatment, patients had more problems than the general population in every domain of EQ-5D-5L, except in self-care dimension (O/E = 1.1). After SVR, patients continued having more limitation, especially for usual activities (O/E = 3.1), anxiety/depression (O/E = 2.8) and EQ-5D utility (- 0.086, p < 0.001); however, differences in VAS score between patients and general population disappeared (74.8 vs 76.5, p = 0.210). F0-F1 patients with SVR had minor differences with the general population in EQ-5D-5L dimensions, utility and VAS score. Although cirrhotic patients also reduced that difference, they still had worse HRQoL, especially in usual activities, self-care, EQ-5D utility (- 0.152, p < 0.001) and VAS score (- 8.5, p = 0.005)., Conclusions: HRQoL of chronic hepatitis C patients remains lower than that of the general population despite viral clearance, with primary problems in usual activities and anxiety/depression. Knowledge of these on-going problems despite cure serves to guide healthcare interventions and patient's follow-up.

Background and Aim: new direct-acting antivirals (DAAs) achieve high and sustained virological response (SVR) rates, although the long-term effect on patient health-related quality of life (HRQoL) is unknown. This study aimed to evaluate the impact of hepatitis C virus (HCV) clearance with DAAs on HRQoL after one year of follow-up., Methods: this was a prospective observational study of chronic hepatitis C patients who started DAA treatment between May 2016 and April 2017 and completed the EQ-5D-5L questionnaire at baseline, 12 (post-12) and 48 (post-48) weeks after the end of treatment. Patients with SVR were analyzed in order to investigate factors associated with changes in HRQoL., Results: a total of 199 patients were enrolled, 65% were male, 29% had cirrhosis and 32% had HIV co-infection. The proportion of patients with problems in mobility (from 35% to 21%, p = 0.002), usual activities (26% to 11%, p < 0.001), pain/discomfort (60% to 35%, p < 0.001) and anxiety/depression (57% to 35%, p < 0.001) decreased from the baseline to post-48. The median baseline and post-48 EQ-5D utility and visual analogue scale (VAS) score increased from 0.857 to 0.932 (p < 0.001) and from 70.0 to 90.0 (p < 0.001), respectively. HRQoL improvement was observed in all subgroups of patients. According to the multivariate analyses, patients with F2-F4 fibrosis had a higher utility and VAS score improvement at post-48 than F0-F1 patients, and females had a greater improvement in the VAS score. Age ≥ 65 years and HIV co-infection were associated with a lower gain in VAS score (all p < 0.05)., Conclusions: hepatitis C virus clearance with DAAs is associated with important long-term improvements in HRQoL. Four of the five EQ-5D-5L dimensions, as well as the utility value and VAS score significantly improved one year after successful treatment with DAAs.

Background: The World Health Organization set targets to eliminate hepatitis C virus (HCV) infection through detection and treatment of all cases by 2030. This study aimed to describe the progress and difficulties in the elimination of HCV infection in Navarra, Spain., Methods: Using electronic healthcare databases, we performed a population-based prospective cohort study to describe changes in the prevalence of diagnosed active HCV infection at the beginning of 2015 and the end of 2017, the rate of new diagnoses and the rate of post-treatment viral clearance (PTVC) during this period., Results: At the beginning of 2015 there were 1503 patients diagnosed with positive HCV-RNA, 2.4 per 1000 inhabitants, and at the end of 2017 the prevalence had decreased by 47%. In the study period, 333 (18 per 100,000 person-years) new positive HCV-RNA cases were detected, but only 76 (23%; 4.2 per 100,000 person-years) did not have anti-HCV antibodies previously detected. Prevalent cases and new diagnoses of active infection were more frequent in men, people born in 1950-1979, HIV-infected patients and in those with lower income levels. Among patients with HCV-RNA, 984 achieved PTVC (22.7 per 100 person-years). PTVC was less frequent in patients born before 1940, in immigrants and in patients with lower income levels., Conclusions: The prevalence of diagnosed active HCV infection has dropped by almost half over three years, because the number of patients with PTVC was much higher than the number of new diagnoses. Interventions specifically targeted at population groups with less favourable trends may be necessary., Competing Interests: The authors have declared that no competing interests exist.

Background: Direct-acting antivirals (DAA) have demonstrated high efficacy to achieve sustained virological response (SVR) in chronic hepatitis C patients. We aim to assess the change in health-related quality of life (HRQoL) among patients successfully treated, and to identify predictors of this variation., Methods: In a prospective observational study, patients with chronic hepatitis C who started DAA therapy between May 2016 and April 2017 completed the EQ-5D-5L questionnaire at baseline and 12 weeks after the end of therapy before knowing the virological result. Analysis included all patients with SVR., Results: Median baseline EQ-5D-5L scores of the 206 enrolled patients were 0.857 utility and 70.0 visual analogue scale (VAS). Following SVR, a reduction occurred in the proportion of patients with mobility problems (35% vs 24%, p = 0.012), pain/discomfort (60% vs 42%, p<0.001) and anxiety/depression (57% vs 44%, p = 0.012), with an increase in utility (+0.053, p<0.001) and VAS (+10, p<0.001). Score improvements were also observed in cirrhotic (+0.048 utility, p = 0.027; +15 VAS, p<0.001) and HIV co-infected patients (+0.039 utility, p = 0.036; +5 VAS, p = 0.002). In multivariate analyses, middle age (45-64 years) and baseline anxiety/depression were associated to greater improvement in utility after SVR, and moderate-advanced liver fibrosis and cirrhosis to greater increase in VAS score. Low baseline values were associated to greater improvements in utility value and VAS score., Conclusions: The cure of chronic hepatitis C infection with DAA has a short term positive impact on HRQoL with improvement in mobility, pain/discomfort, anxiety/depression, utility value and VAS score. Patients with poor baseline HRQoL were the most beneficed., Competing Interests: The authors have declared that no competing interests exist.

The high initial cost of antivirals against hepatitis C prompted development of the "Strategic Plan for Tackling Chronic Hepatitis C in the Spanish National Health System". The objective of this study was the economic evaluation of the first two years of its application in Navarre, Spain. The change in the natural history of hepatitis C produced by the sustained virological response (SVR) was compared to an alternative without treatment and modeled with patient-level data. By means of a discrete events simulation model, the cost-effectiveness and the budget impact analysis of the treatment program were measured from the perspective of the Navarre Health Service. Of 656 patients treated, 98% had SVR. The average cost of the treatments was 18,743 euros per patient. The incremental cost-effectiveness ratio (ICER) with discount was 5,346 euros per quality-adjusted life years, which became more efficient as the stage of fibrosis increased until it reached levels of dominance in stage 4 fibrosis. The associated costs for chronic liver disease decreased as the benefit of the treatment was expressed. The implementation of the Strategic Plan is cost-effective, with an ICER well below the threshold, since the cost of treatment is largely compensated by savings in long-term health expenditure. The budgetary impact foresees a net saving from the third year on. The two key parameters were the decrease in the price of the treatment and the SVR in nearly 100% of the patients.

Objective: To estimate the prevalence of hepatitis C virus (HCV) infection in Navarra, Spain, as well as to distinguish between diagnosed and undiagnosed infections., Methods: A study was conducted on patients scheduled for surgery unrelated to HCV infection. They were all tested for HCV antibodies, under a routine scheme, from January 2014 to September 2016. Patients with a positive result by enzyme immunoassay were confirmed using immunoblot and/or HCV-RNA. Previous laboratory results were also taken into account. The prevalence was adjusted to the sex and age structure of the Navarra population., Results: The study included a total of 7,378 patients with a median age 46 years, of whom 50% women. HCV antibodies were detected in 69 patients, which is a prevalence in the population of 0.83% (95% confidence interval: 0.64-1.05), and was higher in men (1.11%) than in women (0.56%; P=.0102). Among the HCV positive patients, 67 (97%) had had another previous positive result. Population prevalence of previous positive HCV was 0.80%, and was 0.03% for a new diagnosis. Of the HCV positive patients, 78% had detectable HCV-RNA. It was estimated that 0.65% of the population had had detectable HCV-RNA, and 0.51% continued to have it when recruited into the study., Conclusion: Previous estimates of prevalence of HCV infection should be revised downwards. Only a small proportion of HCV positive patients remain undiagnosed, and only a small part have active infection., (Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Objectives: The increased survival of HIV-infected individuals has resulted in a premature aging of this population, with the consequent development of premature age-related comorbidities and risk factors. We aimed to describe the prevalence of age-related comorbidities and cardiovascular risk factors in older adults with HIV infection on antiretroviral therapy (ART)., Methods: A retrospective cross-sectional study was undertaken in a cohort of HIV patients aged ≥50 years on ART in September 2016 in Spain. The prevalence of comorbidities (liver cirrhosis, respiratory diseases, cancer, cardiovascular, diabetes, and kidney and bone disorders) and risk factors (smoking, dyslipidemia, and arterial hypertension) was captured., Results: Among the 339 patients included in the study, any comorbidity was present in 52%, the most common being cirrhosis (19%), chronic lung disease (13%), and diabetes mellitus (11%). Over three quarters (78%) had any risk factor: dyslipidemia (55%) and smoking (44%). A higher prevalence of cardiovascular disease was seen in patients ≥60 years in comparison to those aged 50-59 years (23% vs 8%, p = 0.001). Of all study patients, 44% took more than three drugs in addition to their ART, while 29% received no additional pharmacological interventions., Conclusions: Comorbidities and risk factors for chronic diseases are very common in HIV-infected patients aged ≥50 years and increase with age, so they should be early considered in the clinical management of these patients. It is important to encourage healthy lifestyles to prevent comorbidities and to control risk factors. Concomitant treatments with ART should be carefully monitored to prevent drug interactions, adverse effects, and patient adherence failures.

Objectives: Direct acting antivirals (DAA) are extremely effective to treat chronic hepatitis C. The aim of this study was to evaluate, by using objective variables, the safety of DAA combinations under clinical practice conditions., Methods: A retrospective study was carried out in mono-infected patients with chronic hepatitis C treated with DAA between January and December 2015 in our centre. Discontinuations, treatment modifications, deaths and laboratory parameters were studied (liver function tests, hemoglobin, creatinine and lipid profile at baseline, weeks 4, 8 and post 12). Temporal variation of laboratory parameters was analyzed by t-test for paired data, and comparison between groups was made by t-test for independent samples and ANOVA., Results: 227 patients were included (40.5% cirrhotic). Sustained virological response (SVR) was achieved in 97.3% of patients. In only one case was the antiviral medication suspended due to toxicity, and there were no voluntary treatment discontinuations. The use of ribavirin (RBV) was associated with mild transient hyperbilirubinemia (41.2%) and anemia (32.6%, with RBV dose reduction in 7.9% of cases). There was an elevation in total cholesterol and LDL-cholesterol (LDL-C) during and after treatment: mean increase of 23 mg/dL (0.59 mmol/L) and 22 mg/dL (0.57 mmol/L), respectively in post 12 (p < .0001). An increment of 20% of patients with cholesterol levels over optimal figures was observed after DAA completion., Conclusion: DAA have an optimum safety profile in real life conditions, with infrequent discontinuation and minor laboratory alterations.

Background: Second-generation direct-acting antivirals (DAA) have shown high sustained virologic response (SVR) for the treatment of chronic hepatitis C in clinical trials. The objective of this study is to estimate DAA effectiveness in treatment of this disease., Methods: Hepatitis C virus (HCV) monoinfected patients and HCV-human immunodeficiency virus (HIV) coinfected pa-tients who started interferon-free DAA based regimens during 2015 were included. The primary effectiveness outcome was SVR, defined as an undetectable viral load 12 weeks after the end of treatment., Results: A total of 293 patients were enrolled, and 52 (17.7%) were HIV coinfected. HCV 1b genotype was the most prevalent in monoinfected patients (41.5%) and 1a in HIV coinfected patients (40.4%). The proportion of cirrhosis was higher among HIV coinfected patients (69.2% vs 41.1%; p<0.0001), mostly Child-Pugh A. SVR was achieved by 96.9% of patients (284/293), in an intention-to-treat analysis (CI 95%: 94.9-98.9), in which just 4 people had virologic failure. Both naïve and pretreated patients had SVR higher than 95%, and in most of subgroups, according to the presence of cirrhosis, HIV coinfection and HVC genotype, effectiveness rates were near or above 90%., Conclusions: DAA are highly effective, with similar or higher rates of SVR than that found in clinical trials, and even among difficult to treat populations.