Cross-sectional evaluation of pharmaceutical care competences in nurse education: how well do curricula prepare students of different educational levels?

BACKGROUND: Nurses play an important role in interprofessional pharmaceutical care. Curricula related to pharmaceutical care, however, vary a lot. Mapping the presence of pharmaceutical care related domains and competences in nurse educational programs can lead to a better understanding of the extent to which curricula fit expectations of the labour market. The aim of this study was to describe 1) the presence of pharmaceutical care oriented content in nursing curricula at different educational levels and 2) nursing students' perceived readiness to provide nurse pharmaceutical care in practice. METHODS: A quantitative cross-sectional survey design was used. Nursing schools in 14 European countries offering educational programs for levels 4-7 students were approached between January and April 2021. Through an online survey final year students had to indicate to what extent pharmaceutical care topics were present in their curriculum. RESULTS: A total of 1807 students participated, of whom 8% had level 4-5, 80% level 6, 12% level 7. Up to 84% of the students indicated that pharmaceutical care content was insufficiently addressed in their curriculum. On average 14% [range 0-30] felt sufficiently prepared to achieve the required pharmaceutical care competences in practice. In level 5 curricula more pharmaceutical care domains were absent compared with other levels. CONCLUSIONS: Although several pharmaceutical care related courses are present in current curricula of level 4-7 nurses, its embedding should be extended. Too many students perceive an insufficient preparation to achieve pharmaceutical care competences required in practice. Existing gaps in pharmaceutical care should be addressed to offer more thoroughly prepared nurses to the labour market.

Exploring the education in cultural competence and transcultural care in Spanish for nurses and future nurses: a scoping review and gap analysis.

BACKGROUND: Globalization and population migration have led to increasingly culturally diverse societies, which has made nursing education in cultural competence and transcultural care a priority. This includes the ability to provide person-centered and culturally congruent care, even within one's own culture. However, this sort of training has been developed and implemented in practice comparatively more by English-speaking societies. Therefore, the aim of this study was to identify the existing educational initiatives for nurses and future ones in cultural competence and transcultural care in Spanish and explore their didactic characteristics in terms of teaching and learning formats, contents, skills, and evaluation methods at different academic levels. METHODS: A scoping review was carried out by following the specific PRISMA recommendations and those of the Joanna Briggs Institute guidance throughout PudMed, Web of Science, Embase, Google Scholar, and Cinahl databases and also gray literature in the form of official documentation that later was complemented with a gap analysis including training programs published by Spanish and Latin-American educational institutions and the approaches of key academic informants. RESULTS: The published evidence on nursing training in cultural competence or related topics in Spanish-speaking higher education for nurses is limited. Specific nursing programs in Spanish-speaking universities are primarily found in Spain, with fewer options available in Latin America. These contents are offered either as optional subjects or immersed in other courses and mainly taught in theoretical sessions. Practice in real contexts is supposed to be evaluated transversally under the cultural scope according to national educational recommendations though barely visible in students' evaluation reports. Even though postgraduate training dedicated to these issues exists, it is still limited, mixed with other contents, and generally depends on a few researchers investigating and publishing on the topic from very specific universities. CONCLUSIONS: It is essential to establish a common global strategy including Spanish-speaking countries in nurses' higher education and professional training on topics focused on cultural competence as well as the provision of nurses' social and cultural sensitivity towards their own culture and to define whether those that currently exist are effective. It is also crucial that this training was evaluated in practice in order to achieve enough impact on students, health organizations, and population health.

Massive Release of CD9+ Microvesicles in Human Immunodeficiency Virus Infection, Regardless of Virologic Control.

BACKGROUND: The role of extracellular vesicles (EVs) in human immunodeficiency virus (HIV) pathogenesis is unknown. We examine the cellular origin of plasma microvesicles (MVs), a type of ectocytosis-derived EV, the presence of mitochondria in MVs, and their relationship to circulating cell-free mitochondrial deoxyribonucleic acid (ccf-mtDNA) in HIV-infected patients and controls. METHODS: Five participant groups were defined: 30 antiretroviral therapy (ART)-naive; 30 ART-treated with nondetectable viremia; 30 elite controllers; 30 viremic controllers; and 30 HIV-uninfected controls. Microvesicles were quantified and characterized from plasma samples by flow cytometry. MitoTrackerDeepRed identified MVs containing mitochondria and ccf-mtDNA was quantified by real-time polymerase chain reaction. RESULTS: Microvesicle numbers were expanded at least 10-fold in all HIV-infected groups compared with controls. More than 79% were platelet-derived MVs. Proportions of MVs containing mitochondria (22.3% vs 41.6%) and MV mitochondrial density (706 vs 1346) were significantly lower among HIV-infected subjects than controls, lowest levels for those on ART. Microvesicle numbers correlated with ccf-mtDNA levels that were higher among HIV-infected patients. CONCLUSIONS: A massive release of platelet-derived MVs occurs during HIV infection. Some MVs contain mitochondria, but their proportion and mitochondrial densities were lower in HIV infection than in controls. Platelet-derived MVs may be biomarkers of platelet activation, possibly reflecting pathogenesis even in absence of HIV replication.

Measurement properties of the EQ-5D-Y administered through a smartphone app in children with asthma: a longitudinal questionnaire study.

BACKGROUND: Asthma impacts children's physical, emotional, and psychosocial Health-Related Quality of Life (HRQL). The EQ-5D-Y is a generic econometric instrument developed to measure HRQL in children. OBJECTIVE: Evaluation of feasibility, validity, reliability, and responsiveness of EQ-5D-Y descriptive system and utility index to allow the assessment of HRQL in children with asthma, aged 8-11 years (self-response version) or under 8 years old (proxy-response version). METHODS: We used data from baseline to 10 months of follow-up of an observational, prospective study of children with persistent asthma recruited by pediatricians in Spain (2018-2020). HRQL instruments were administered through a smartphone application: ARCA app. The EQ-5D-Y is composed of a 5-dimension descriptive system, a utility index ranging from 1 to - 0.5392, and a general health visual analogue scale (EQ-VAS). The Pediatric Asthma Impact Scale (PROMIS-PAIS) includes 8 items, providing a raw score. Construct validity hypotheses were stated a priori, and evaluated following two approaches, multitrait-multimethod matrix and known groups' comparisons. Reliability and responsiveness subsamples were defined by stability or change in EQ-VAS and the Asthma Control Questionnaire (ACQ), to estimate the intraclass correlation coefficient (ICC) and the magnitude of change over time. RESULTS: The EQ-5D-Y was completed at baseline for 119 children (81 self-responded and 38 through proxy response), with a mean age of 9.1 (1.7) years. Mean (SD) of the EQ-5D-Y utility index was 0.93 (0.11), with ceiling and floor effects of 60.3% and 0%, respectively. Multitrait-multimethod matrix confirmed the associations previously hypothesized for the EQ-5D-Y utility index [moderate with PROMIS-PAIS (0.38) and weak with ACQ (0.28)], and for the EQ-5D-Y dimension "problems doing usual activities" [moderate with the ACQ item (0.35) and weak with the PROMIS-PAIS item (0.17)]. Statistically significant differences were found in the EQ-5D-Y between groups defined by asthma control, reliever inhalers use, and second-hand smoke exposure, with mostly moderate effect sizes (0.45-0.75). The ICC of the EQ-5D-Y utility index in the stable subsamples was high (0.81 and 0.79); and responsiveness subsamples presented a moderate to large magnitude of change (0.68 and 0.78), though without statistical significance. CONCLUSIONS: These results support the use of the EQ-5D-Y as a feasible, valid, and reliable instrument for evaluating HRQL in children with persistent asthma. Further studies are needed on the responsiveness of the EQ-5D-Y in this population.

Economic evaluation of CPD activities for healthcare professionals: A scoping review.

CONTEXT: Continuing professional development (CPD) activities for healthcare professionals are central to the optimisation of patient safety and person-centred care. Although there is some evidence on the economics of healthcare professionals training, very little is known about the costs and benefits of CPD. METHODS: This study aimed to review the research evidence on economic evaluations of CPD activities for healthcare professionals. CINAHL, MEDLINE/PubMed, Scopus, Econlit and Web of Science databases were used to identify articles published between 2010 and 2021. RESULTS: Of the 6791 titles identified, 119 articles met the inclusion criteria and were included in this scoping review. The majority of articles were partial economic evaluations of CPD programmes (n = 70); half were from the USA. Studies that included multiple professions were most prevalent (n = 54), followed by nurses (n = 34) and doctors (n = 23). Patient outcomes were the most commonly reported outcome (n = 51), followed by change in clinical practice (n = 38) and healthcare professionals' knowledge gain (n = 19). CONCLUSIONS: There is an urgent call for more evidence regarding the economic evaluations of CPD. This is particularly important in view of the rising costs of healthcare globally. The majority of studies included in this review did not provide detailed information on the evaluations and many focused exclusively on the cost of CPD activities rather than outcomes.

Dynamics of creatinine estimated glomerular filtration rate using one or more antiretrovirals that inhibit creatinine tubular secretion.

BACKGROUND: Cobicistat, dolutegravir and rilpivirine are all modest inhibitors of proximal tubular creatinine secretion (IPTCrS) and hence a moderate and early non-progressive creatinine estimated glomerular filtration rate (Cr-eGFR) reduction has been observed in clinical trials. Data regarding the impact of combination of those drugs on Cr-eGFR, in the clinical practice, are scarcely known. METHODS: Changes in Cr-eGFR after starting darunavir/cobicistat alone or in combination with dolutegravir and/or rilpivirine were studied in a nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat. The relationship between Cr-eGFR changes over time and the use of darunavir/cobicistat alone or darunavir/cobicistat plus dolutegravir and/or rilpivirine adjusted by different HIV patient's characteristics, socio-demographics, HIV severity and use of tenofovir concomitant medication other than antiretrovirals was explored through univariate and multivariate analyses. RESULTS: The analysis included 725 patients. At 48 weeks, the combination of two or more IPTCrS (darunavir/cobicistat with rilpivirine and/or dolutegravir) was associated with higher decreases in Cr-eGFR [adjusted median difference (±SD) -3.5 ± 1.6 (95% CI -6.6 to -0.3), P = 0.047], and a decrease up to or higher than 15 mL/min/1.73 m2 was more frequent [adjusted OR 3.233 (95% CI 1.343-7.782), P = 0.009], with respect to darunavir/cobicistat alone. The Cr-eGFR changes between darunavir/cobicistat and darunavir/cobicistat with rilpivirine and/or dolutegravir showed more significant decreases in patients taking two or more IPTCrS at 12, 24 and 48 weeks. (ClinicalTrials.gov: NCT03042390). CONCLUSIONS: Concomitant use of darunavir/cobicistat plus IPTCrS dolutegravir, rilpivirine, or both produced an additive effect in the expected Cr-eGFR decrease.

Addition of Maraviroc Versus Placebo to Standard Antiretroviral Therapy for Initial Treatment of Advanced HIV Infection: A Randomized Trial.

Background: Patients diagnosed with advanced HIV infection have a poor prognosis despite initiation of combined antiretroviral therapy (c-ART). Objective: To assess the benefit of adding maraviroc, an antiretroviral drug with immunologic effects, to standard c-ART for patients with advanced disease at HIV diagnosis. Design: Randomized controlled trial. (ClinicalTrials.gov: NCT01348308). Setting: Clinical sites in France (n = 25), Italy (n = 5), and Spain (n = 20). Participants: 416 HIV-positive, antiretroviral-naive adults with CD4 counts less than 0.200 × 109 cells/L and/or a previous AIDS-defining event (ADE). Intervention: C-ART plus placebo or maraviroc (300 mg twice daily with dose modification) for 72 weeks. Measurements: The primary end point was first occurrence of severe morbidity (new ADE, selected serious infections, serious non-ADE, immune reconstitution inflammatory syndrome, or death). Prespecified secondary outcomes included primary outcome components, biological and pharmacokinetic measures, and adverse events graded 2 or higher. Results: 409 randomly assigned participants (207 in the placebo group and 202 in the maraviroc group) who received more than 1 dose were included in the analysis. During 72 weeks of follow-up, incidence of severe morbidity was 11.1 per 100 person-years in the maraviroc group and 11.2 per 100 person-years in the placebo group (hazard ratio, 0.97 [95% CI, 0.57 to 1.67]). Incidence of adverse events graded 2 or higher was 36.1 versus 41.5 per 100 person-years (incidence rate ratio, 0.87 [CI, 0.65 to 1.15]). Limitations: Sixty-four participants discontinued therapy during follow-up. The study was not designed to evaluate time-dependent outcomes or effect modification. Conclusion: Addition of maraviroc to standard c-ART does not improve clinical outcomes of patients initiating therapy for advanced HIV infection. Primary Funding Source: INSERM-ANRS (French National Agency for Research on AIDS).

Diversification of Biscutella ser. Biscutella (Brassicaceae) followed post-Miocene geologic and climatic changes in the Mediterranean basin.

Biscutella ser. Biscutella (= ser. Lyratae Malin.) is a group of mostly annual or short-lived perennial plants, with petals gradually tapering at the base and lateral intrastaminal nectaries, endemic to the Mediterranean basin and the Middle East. Recent taxonomic work has revealed that a relative morphological homogeneity occurs in Europe and Asia, but a high plasticity is found in N Africa for most of the characters traditionally used for taxonomic arrangements. This fact had generally led to overestimation of the number of taxa, which currently is reduced to ten (namely 7 species and 3 additional varieties), some of them being narrow endemics. In the present contribution, on the basis of a previous detailed morphological study carried out by the authors, the first comprehensive phylogeny based on 47 DNA sequence data including concatenation of two plastid (rpl32-trnL and trnV) and one nuclear (ITS) regions, together with the first time-calibrated phylogenetic tree, allows reappraisal of evolutionary and biogeographic relationships among the accepted taxa in the series. According to all evidence gathered in the present study, the current distribution of B. ser. Biscutella, mostly centred in the southern parts of the Mediterranean basin and the Middle East, suggests that it evolved in relation with the major geological and climatic events occurred in the Mediterranean basin and Eurasia within the last 20 million years. The origin of Biscutella is dated ca 18.75 Mya, and the radiation of the series triggered ca 5.87 Mya with the Messinian Salinity Crisis. Rapid diversification occurred coetaneously to the Intensification of Northern Hemisphere Glaciation (ca 2.86 Mya) onwards, with parallel large-amplitude aridity cycles in Africa and southwestern Asia. In recent times, the divergence of lineages became faster in the W Mediterranean (ca 1.54 to 0.43 Mya), mostly related to geographical and ecological patterns of specialisation. In many cases, the distribution of the current species is apparently linked to ancient glacial refuges in S Mediterranean basin.

Pandemic lockdown, healthcare policies and human rights: integrating opposed views on COVID-19 public health mitigation measures.

The issue of the COVID-19 pandemic occupies the agenda of the whole world. The pivot of this pandemic is a crucial element that has become almost as important as the virus itself, namely the lockdown. Although, the rationale for lockdown is well-sustained by strong epidemiological arguments, exploring the 'other' unwanted consequences of the contemporary COVID-19 pandemic is mandatory for coagulating a robust agreed position against the numerous problems generated by the SARS-CoV-2 virus. Starting from the rationale of the lockdown, in this paper we explored and exposed the other consequences of the COVID-19 pandemic measures such as the use or abuse of human rights and freedom restrictions, economic issues, marginalized groups and eclipse of all other diseases. Our scientific attempt is to coagulate a stable position and integrate current opposing views by advancing the idea that rather than applying the uniform lockdown policy, one could recommend instead an improved model targeting more strict and more prolonged lockdowns to vulnerable risk/age groups while enabling less stringent measures for the lower-risk groups, minimizing both economic losses and deaths. Rigorous (and also governed by freedom) debating may be able to synchronize the opposed perspectives between those advocating an extreme lockdown (e.g., most of the epidemiologists and health experts), and those criticizing all restrictive measures (e.g., economists and human rights experts). Confronting the multiple facets of the public health mitigation measures is the only way to avoid contributing to history with yet another failure, as seen in other past epidemics.

Moving beyond unsolicited consultation: additional impact of a structured intervention on mortality in Staphylococcus aureus bacteraemia.

BACKGROUND: Some evidence-based bundles have tried to standardize the management of Staphylococcus aureus bacteraemia (SAB) to improve the outcome. The aim of our study was to analyse the additional impact on mortality of a structured intervention in patients with SAB. METHODS: Compliance with the bundle was evaluated in an ambispective cohort of patients with SAB, which included a retrospective cohort [including patients treated before and after the implementation of a bacteraemia programme (no-BP and BP, respectively)] and a prospective cohort (i-BP), in which an additional specific intervention for bundle application was implemented. Multivariate logistic regression was used to measure the influence of the independent variables including compliance with the bundle on 14 and 30 day crude mortality. RESULTS: A total of 271 adult patients with SAB were included. Mortality was significantly different among the three groups (no-BP, BP and i-BP): mortality at 14 days was 18% versus 7% versus 2%, respectively, P = 0.002; and mortality at 30 days was 20% versus 12% versus 5%, respectively, P = 0.011. The factors associated with 14 and 30 day mortality in multivariable analysis were heart failure (OR = 7.63 and OR = 2.27, respectively), MRSA infection (OR = 4.02 and OR = 4.37, respectively) and persistent bacteraemia (OR = 11.01 and OR = 7.83, respectively); protective factors were catheter-related bacteraemia (OR = 0.16 and OR = 0.19, respectively) and >75% bundle compliance (OR = 0.15 and OR = 0.199, respectively). Time required to perform the intervention and the follow-up was 50 min (IQR 40-55 min) per patient. CONCLUSIONS: High-level compliance with a standardized bundle of intervention for management of SAB that requires little time was associated with lower mortality at 14 and 30 days.

Short- versus long-course therapy in gram-negative bacilli bloodstream infections.

Bacteremia due to gram-negative bacilli (GNB) is one of the most frequent causes of admission and prolongation of hospital stay. Nevertheless, optimal duration of antibiotic treatment is not clearly established. We designed an observational, prospective study of a cohort of adult patients with uncomplicated GNB bacteremia. They were classified according to the duration of treatment in short (7-10 days) or long (> 10 days) course. Mortality and bacteremia recurrence rate were evaluated, and propensity score for receiving short-course treatment was calculated. A total of 395 patients met eligibility criteria including 232 and 163 who received long- and short-course therapy, respectively. Median age was 71 years, 215 (54.4% male) and 51% had a urinary source. Thirty-day mortality was 12%. In multivariate analysis by logistic regression stratified according to propensity score quartile for receiving short-course therapy showed no association of duration of treatment with 30-day mortality or 90-day recurrence rate. Based on the results observed in our cohort, short-course therapy could be as safe and effective as longer courses.

Availability and perceived usefulness of guidelines and protocols for subcutaneous hydration in palliative care settings.

AIMS AND OBJECTIVES: To evaluate the availability of, adherence to, and perceived usefulness of guidelines and protocols for managing hydration and subcutaneous hydration in palliative care settings. BACKGROUND: Hydration at the end of life and the use of a subcutaneous route to hydrate generate some controversy among health professionals for different reasons. Having guidelines and protocols to assist in decision-making and to follow a standard procedure may be relevant in clinical practice. DESIGN: Cross-sectional telephone survey, with closed-ended and open-ended questions designed specifically for this study. METHODS: Data were obtained from 327 professionals, each from a different palliative care service. Mean, standard deviation, minimum and maximum were calculated for continuous variables; frequency distributions were obtained for categorical variables. A qualitative content analysis was performed on the open-ended questions. The article adheres to the STROBE guidelines for reporting observational studies. RESULTS: Only 24.8% of the participants had guidelines available to assist in making decisions regarding hydration, and 55.6% claimed to follow them 'always or almost always'. Of the participants, 38.8% had subcutaneous hydration protocols available, while 78.7% stated that they 'always or almost always' followed these protocols. The remaining participants considered the protocols as useful tools despite not having them available. CONCLUSIONS: Only 25% of the participants' services had guidelines for hydration, and less than 40% had protocols for subcutaneous hydration. However, adherence was high, especially in cases where protocols existed. Among the participants who did not have guidelines and protocols, attitudes were mostly favourable, but mainly as a reference and support for an individualised clinical practice. RELEVANCE TO CLINICAL PRACTICE: Guidelines and protocols on hydration in palliative care may be more useful as a solid reference and support for individualised practice than as instruments for standardising care. From this perspective, their development and availability in palliative care services are recommended.

Effectiveness of ceftazidime/avibactam as salvage therapy for treatment of infections due to OXA-48 carbapenemase-producing Enterobacteriaceae.

Background: Experience in real clinical practice with ceftazidime/avibactam is limited, and there are even fewer data on infections due to OXA-48-producing Enterobacteriaceae. Methods: We designed an observational study of a prospectively collected cohort of adult patients receiving ceftazidime/avibactam in our centre. Only the first treatment course of each patient was analysed. Efficacy and safety were evaluated as 14 and 30 day mortality, recurrence rate at 90 days, resistance development and occurrence of adverse effects. Results: Fifty-seven patients were treated with ceftazidime/avibactam. The median age was 64 years (range 26-86), 77% were male and the median Charlson index was 3. The most frequent sources of infection were intra-abdominal (28%), followed by respiratory (26%) and urinary (25%). Thirty-one (54%) patients had a severe infection (defined as presence of sepsis or septic shock). Most patients received ceftazidime/avibactam as monotherapy (81%) and the median duration of treatment was 13 days. Mortality at 14 days was 14%. In multivariate analysis, the only mortality risk factor was INCREMENT-CPE score >7 (HR 11.7, 95% CI 4.2-20.6). There was no association between mortality and monotherapy with ceftazidime/avibactam. The recurrence rate at 90 days was 10%. Ceftazidime/avibactam resistance was not detected in any case and only two patients developed adverse events related to treatment. Conclusions: Ceftazidime/avibactam shows promising results, even in monotherapy, for the treatment of patients with severe infections due to OXA-48-producing Enterobacteriaceae and limited therapeutic options. The emergence of resistance to ceftazidime/avibactam was not observed.

Eradication of hepatitis C virus and non-liver-related non-acquired immune deficiency syndrome-related events in human immunodeficiency virus/hepatitis C virus coinfection.

We assessed non-liver-related non-acquired immunodeficiency syndrome (AIDS)-related (NLR-NAR) events and mortality in a cohort of human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected patients treated with interferon (IFN) and ribavirin (RBV), between 2000 and 2008. The censoring date was May 31, 2014. Cox regression analysis was performed to assess the adjusted hazard rate (HR) of overall death in responders and nonresponders. Fine and Gray regression analysis was conducted to determine the adjusted subhazard rate (sHR) of NLR deaths and NLR-NAR events considering death as the competing risk. The NLR-NAR events analyzed included diabetes mellitus, chronic renal failure, cardiovascular events, NLR-NAR cancer, bone events, and non-AIDS-related infections. The variables for adjustment were age, sex, past AIDS, HIV transmission category, nadir CD4+ T-cell count, antiretroviral therapy, HIV RNA, liver fibrosis, HCV genotype, and exposure to specific anti-HIV drugs. Of the 1,625 patients included, 592 (36%) had a sustained viral response (SVR). After a median 5-year follow-up, SVR was found to be associated with a significant decrease in the hazard of diabetes mellitus (sHR, 0.57; 95% confidence interval [CI], 0.35-0.93; P = 0.024) and decline in the hazard of chronic renal failure close to the threshold of significance (sHR, 0.43; 95% CI, 0.17-1.09; P = 0.075). CONCLUSION: Our data suggest that eradication of HCV in coinfected patients is associated not only with a reduction in the frequency of death, HIV progression, and liver-related events, but also with a reduced hazard of diabetes mellitus and possibly of chronic renal failure. These findings argue for the prescription of HCV therapy in coinfected patients regardless of fibrosis stage. (Hepatology 2017;66:344-356).

Understanding life experiences of people affected by Crohn's disease in Spain. A phenomenological approach.

BACKGROUND AND OBJECTIVES: People affected by Crohn's disease must adapt their lives to their new chronic condition, and therefore, understanding such experience can be helpful in planning effective interventions for the affected ones. The aim of this study was to gain an insight into such experience and how they adapted in different areas of their lives, particularly in a family-centred culture such as the Spanish one. METHOD: A descriptive phenomenological study was conducted through in-depth interviews to 19 people diagnosed of Crohn's disease in the province of Alicante (Spain). Once the interviews were transcribed, data were analysed using Colaizzi's seven-step method. RESULTS: Five emergent themes were identified: self-protection against the unknown cause; self-training; learning to live with Crohn's disease; perceived losses associated to Crohn's disease; and relationship with others. The results portrayed a chronically ill patient who is unconscious about the chronicity and consequently must develop strategies to keep living a similar life like the one lived before. CONCLUSIONS: This study revealed that people affected by Crohn's disease struggle with the fact of being a chronic patient with uncertainty about the illness and need to learn living with a chronic condition that limits their daily lives. Furthermore, the lack of Crohn's disease a professional in charge of these people's Cares such as the specific nursing role existing in other countries support in the Spanish Health System determines the loneliness those diagnosed experience to cope with the new situation.

Defining the HLA class I-associated viral antigen repertoire from HIV-1-infected human cells.

Recognition and eradication of infected cells by cytotoxic T lymphocytes is a key defense mechanism against intracellular pathogens. High-throughput definition of HLA class I-associated immunopeptidomes by mass spectrometry is an increasingly important analytical tool to advance our understanding of the induction of T-cell responses against pathogens such as HIV-1. We utilized a liquid chromatography tandem mass spectrometry workflow including de novo-assisted database searching to define the HLA class I-associated immunopeptidome of HIV-1-infected human cells. We here report for the first time the identification of 75 HIV-1-derived peptides bound to HLA class I complexes that were purified directly from HIV-1-infected human primary CD4(+) T cells and the C8166 human T-cell line. Importantly, one-third of eluted HIV-1 peptides had not been previously known to be presented by HLA class I. Over 82% of the identified sequences originated from viral protein regions for which T-cell responses have previously been reported but for which the precise HLA class I-binding sequences have not yet been defined. These results validate and expand the current knowledge of virus-specific antigenic peptide presentation during HIV-1 infection and provide novel targets for T-cell vaccine development.

Plasma mitochondrial DNA levels are inversely associated with HIV-RNA levels and directly with CD4 counts: potential role as a biomarker of HIV replication.

OBJECTIVES: To evaluate plasma mitochondrial DNA (mtDNA) levels among HIV-infected patients and its potential role as a biomarker of residual viral replication. METHODS: HIV-infected patients on follow-up at a reference hospital in north-west Spain were selected. DNA was isolated from plasma samples and mtDNA levels were assessed using a quantitative real-time PCR assay. HIV-RNA levels and CD4+ cell counts were evaluated in the same blood samples used for plasma mtDNA quantification. Epidemiological and clinical variables were included for the analysis. RESULTS: A total of 235 HIV-infected patients were included. Mean plasma mtDNA levels were 217 ±âŸ656 copies/µL for naive (31.9%) and 364 ±âŸ939 copies/µL for HIV-infected patients receiving ART and with suppressed viraemia (P = 0.043). Among the latter, mean plasma mtDNA levels were 149 ±âŸ440 copies/µL for those with low-level viraemia (LLV; HIV-RNA 20-200 copies/mL), 265 ±âŸ723 copies/µL for those with detected-not-quantified (DNQ) viraemia (HIV-RNA <20 copies/mL) and 644 ±âŸ1310 copies/µL for those with not-detected (ND) viraemia. Of note, a linear trend (P = 0.006) was observed among virologically suppressed (LLV, DNQ and ND) patients. ND patients had higher mtDNA levels compared with LLV patients (P = 0.057). Moreover, mtDNA levels were inversely associated with HIV-RNA levels (Spearman's rho -0.191, P = 0.003) and directly associated with CD4+ counts (Spearman's rho 0.131, P = 0.046). CONCLUSIONS: Increased plasma mtDNA levels are associated with lower HIV-RNA levels and higher CD4+ cell counts. Among ART-suppressed patients, mtDNA levels were significantly higher in those with complete virological suppression (ND) than in those with LLV. These data suggest that plasma mtDNA levels might serve as a biomarker of residual HIV replication.

Efficacy and safety of direct antiviral agents in a cohort of cirrhotic HCV/HIV-coinfected patients.

Background: New direct-acting antiviral agents (DAAs) have shown great efficacy and tolerability in clinical trials and real-life cohorts. However, data are scarce regarding efficacy and safety in cirrhotic HCV/HIV-coinfected patients. Methods: A multicentre prospective analysis was performed in 13 Spanish hospitals, including all cirrhotic HCV/HIV-coinfected patients starting DAA combinations from January to December 2015. Sustained virological response 12 weeks after treatment (SVR12) was analysed. Withdrawal due to toxicity and/or hepatic decompensation and change in liver stiffness measurement (LSM) after HCV treatment were evaluated. Results: Patients (n = 170) were mostly male (n = 125; 74.3%) with the following HCV genotype (Gt) distribution: Gt-1a, 68 (40%); Gt-1b, 21 (12.4%); Gt-4, 47 (27.6%); and Gt-3, 26 (15.3%). Baseline median LSM was 20.6 kPa (IQR 16.1-33.7) and log10 HCV-RNA 6.1 IU/mL (IQR 5.7-6.5). Most patients had a Child-Pugh class A score (n = 127; 74.7%) and 28 (16.5%) had prior hepatic decompensation. There were 89 (52.4%) pretreated patients with 40.4% (n = 36) of null responders. Preferred regimens were as follows: sofosbuvir/ledipasvir + ribavirin, 43 (25.3%) patients; sofosbuvir + simeprevir + ribavirin, 34 (20%); sofosbuvir/ledipasvir, 26 (15.3%) and sofosbuvir + daclatasvir + ribavirin, 25 (14.7%). Overall SVR12 was 92.9% (158/170), without differences between genotypes. Pretreated patients had lower SVR12 rates compared with naive (88.8% versus 97.5%; P = 0.026). Treatment failures were as follows: 7 (4.1%) relapses; 2 (1.2%) lost to follow-up; 1 (0.6%) toxicity-related discontinuation; 1 (0.6%) hepatic decompensation; and 1 (0.6%) viral breakthrough. On-treatment hepatic decompensation was recorded in four (2.4%) patients (encephalopathy and ascites, two each). Paired LSM in 33 patients showed a decrease of 5.6 kPa (95% CI 1.8-9.2; P = 0.004). Conclusions: In our cohort of cirrhotic HCV/HIV-coinfected patients, DAAs were highly safe and efficacious. Viral eradication was associated with a significant decrease in liver stiffness.

Hepatic safety of maraviroc in HIV-1-infected patients with hepatitis C and/or B co-infection. The Maraviroc Cohort Spanish Group.

INTRODUCTION: Limited data is available regarding the hepatic safety of maraviroc in patients co-infected with HIV and HCV and/or HBV. Our objective was to compare the hepatic safety profile and fibrosis progression in HIV-mono-infected patients and co-infected with HCV and/or HBV treated with maraviroc. METHODS: Retrospective multicentre cohort study of HIV-infected patients receiving treatment with a maraviroc-containing regimen in 27 hospitals in Spain. RESULTS: A total of 667 patients were analyzed, of whom 313 were co-infected with HCV (n=282), HBV (n=14), or both (n=17). Maraviroc main indications were salvage therapy (52%) and drug toxicity (20%). Grade 3-4 hypertransaminasaemia (AST/ALT >5 times ULN) per 100 patient-years of maraviroc exposure, was 5.84 (95% CI, 4.04-8.16) and 1.23 (95% CI, 0.56-2.33) in co-infected and HIV-mono-infected patients, respectively (incidence rate ratio, 4.77; 95% CI, 2.35-10.5). However, the degree of aminotransferase abnormalities remained stable throughout the study in both groups, and no significant between-group differences were seen in the cumulative proportion of patients showing an increase in AST/ALT levels greater than 3.5 times baseline levels. No between-group differences were seen in liver fibrosis over time. With a maraviroc median exposure of 20 months (IQR, 12-41), two patients (0.3%) discontinued maraviroc because of grade 4 hepatitis, and other 2 died due to complications associated to end-stage-liver disease. CONCLUSIONS: Maraviroc-containing regimens showed a low incidence of hepatitis in a large Spanish cohort of HIV-infected patients, including more than 300 patients co-infected with HCV and/or HBV. Co-infection did not influence the maximum liver enzyme level or the fibrosis progression throughout the study.

Costs and cost-efficacy analysis of the 2016 GESIDA/Spanish AIDS National Plan recommended guidelines for initial antiretroviral therapy in HIV-infected adults.

INTRODUCTION: GESIDA and the AIDS National Plan panel of experts suggest preferred (PR), alternative (AR), and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for the year 2016. The objective of this study is to evaluate the costs and the efficacy of initiating treatment with these regimens. METHODS: Economic assessment of costs and efficiency (cost/efficacy) based on decision tree analyses. Efficacy was defined as the probability of reporting a viral load <50copies/mL at week 48 in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug resistance studies) during the first 48 weeks. The payer perspective (National Health System) was applied, only taking into account differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting is Spain and the costs correspond to those of 2016. A sensitivity deterministic analysis was conducted, building three scenarios for each regimen: base case, most favourable, and least favourable. RESULTS: In the base case scenario, the cost of initiating treatment ranges from 4663 Euros for 3TC+LPV/r (OR) to 10,894 Euros for TDF/FTC+RAL (PR). The efficacy varies from 0.66 for ABC/3TC+ATV/r (AR) and ABC/3TC+LPV/r (OR), to 0.89 for TDF/FTC+DTG (PR) and TDF/FTC/EVG/COBI (AR). The efficiency, in terms of cost/efficacy, ranges from 5280 to 12,836 Euros per responder at 48 weeks, for 3TC+LPV/r (OR), and RAL+DRV/r (OR), respectively. CONCLUSION: Despite the overall most efficient regimen being 3TC+LPV/r (OR), among the PR and AR, the most efficient regimen was ABC/3TC/DTG (PR). Among the AR regimes, the most efficient was TDF/FTC/RPV.