204 research outputs found
Performance Comparison of Enterprise Applications on Mobile Operating Systems
Due to the advances in mobile phone technology, Smartphones have the ability to access web services within applications the user interacts with to retrieve and send information from and to web services. As Smartphones have grown in popularity, the utilisation of both new web services and web services already in place will also grow. This paper provides a comparison of the two main types of web services, SOAP and REST. We evaluate the performance of using SOAP and REST on a smartphone. The tests performed include the time taken to perform a web service call, the RAM used making a web service call and the data transmitted and received while making a web service call
Profile of once-daily darunavir/cobicistat fixed-dose combination for the treatment of HIV/AIDS
Altres ajuts: AC has received honoraria, speakers' fees and/or funds for research from Bristol-Myers Squibb, Abbvie, Gilead Sciences, Janssen-Cilag, MSD, and ViiV Healthcare. JN has received honoraria, speakers' fees and/or funds for research from Abbvie, Gilead Sciences, Janssen-Cilag, MSD, and ViiV Healthcare.Efficacy is the main objective of antiretroviral treatment and adherence is one of the cornerstones to achieve it. For this reason, treatment simplification is of key importance with regard to antiretroviral regimens. Rezolsta® (darunavir/cobicistat) is the first fixed-dose combination containing a protease inhibitor approved for HIV treatment. This coformulation includes darunavir, a protease inhibitor that has shown its efficacy and safety in naïve and treatment-experienced patients, and cobicistat, the new pharmacokinetic enhancer that is expected to replace ritonavir. Bioequivalence between ritonavir and cobicistat as darunavir boosters has been shown in studies involving healthy volunteers. Furthermore, efficacy and safety of darunavir/cobicistat observed in phase III studies, including naïve and pretreated patients without darunavir-associated resistance mutations, are comparable to historical data of darunavir/ritonavir 800/100 mg once-daily formulation. Adverse events with darunavir/cobicistat are scarce and mild, and basically include skin reactions and gastrointestinal disturbances. Although small increases in plasma creatinine are expected in patients receiving cobicistat due to the inhibition of creatinine transporters in kidney tubules, actual glomerular filtrate rate remains unaltered. Cobicistat does not have an inducer effect on metabolic pathways and shows much more selective inhibition than ritonavir. Therefore, isoenzyms different from CYP3A4 are supposed to be less affected by cobicistat, and thus fewer drug-drug interactions are expected
Mortality due to non-AIDS-defining cancers among people living with HIV in Spain over 18 years of follow-up
Cancer; HIV; MortalityCáncer; VIH; MortalidadCàncer: VIH; MortalitatPurpose
Our aim was to describe non-AIDS-defining cancer (NADC) mortality among people living with HIV (PLWH), to compare it with that of the general population, and to assess potential risk factors.
Methods
We included antiretroviral-naive PLWH from the multicentre CoRIS cohort (2004–2021). We estimated mortality rates and standardised mortality ratios (SMRs). We used cause-specific Cox models to identify risk factors.
Results
Among 17,978 PLWH, NADC caused 21% of all deaths observed during the follow-up. Mortality rate due to NADC was 1.58 (95%CI 1.36, 1.83) × 1000 person-years and lung and liver were the most frequent cancer-related causes of death. PLWH had 79% excess NADC mortality risk compared to the general population with the highest SMR found for Hodgkin lymphoma, anal and liver cancers. The SMRs decreased with age and were the highest in age groups under 50 years. The most important prognostic factor was low CD4 count, followed by smoking, viral hepatitis and HIV transmission through heterosexual contact or injection drug use.
Conclusion
Non-AIDS cancers are an important cause of death among PLWH. The excess mortality related to certain malignancies and the association with immunodeficiency, smoking, and coinfections highlights the need for early detection and treatment of cancer in this population.Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature. This research was supported by CIBER -Consorcio Centro de Investigación Biomédica en Red- (CB21/13/00091), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea – NextGenerationEU, the Gilead Scholarship Program for Biomedical Research (GLD19_00106) and the ISCIII- Miguel Servet CP19CIII—00002 contract
Drv Concentrations And Viral Load In Csf In Patients On Drv/r 600/100 Or 800/100mg Once Daily Plus Two Nrti
Introduction
Darunavir/r (DRV/r) is currently used at a dose of 800/100 mg once daily (OD) in a high proportion of patients. Pharmacokinetic data suggest that 600/100 OD may be effective, reducing toxicity and cost. However, drug concentrations in reservoirs such as cerebrospinal fluid (CSF) might not be adequate to inhibit viral replication. We aimed to evaluate concentrations of DRV and HIV‐1 viral load (VL) in CSF patients receiving DRV 600/100 mg OD.
Methods
DRV600 is an ongoing randomized open study comparing DRV/r 800/100 mg (DRV800) vs 600/100 mg (DRV600) OD plus TDF/FTC or ABC/3TC in 100 virologically suppressed patients (eudraCT 2011‐006272‐39). Here we present the results of a CSF sub‐study. A lumbar puncture (LP) was performed in participating patients after at least six months of inclusion in the study, 20–28 hours after a dose of DRV/r. VL (PCR, LOD 40 copies/mL) was determined in CSF and in plasma. DRV concentrations were quantified in CSF by liquid chromatography mass spectrometry (LC/MS/MS) and in plasma using high‐performance liquid chromatography (HPLC).
Results
Sixteen patients were included (eight in each arm). All DRV600 patients and four out of eight DRV800 patients received TDF/FTC, and the other four ABC/3TC. 75% were males, median (range) age was 48 (17–71) years, CD4 cell count 532 cells/mL (190–1,394). Median total time on DRV/r was 30 (11–57) months, and since the beginning of the study 8 (6–12) months in DRV800 and 10 (7–12) months in DRV600 patients. LP was performed a median of 26 (24–28) hours after the last DRV/r+TVD or KVX dose. In DRV600 patients the median DRV plasma levels were 1,674 (326–3,742) ng/mL, CSF levels 17.08 (5.79–30.19) ng/mL and DRV CSF:plasma ratio 0.0084 (0.0028–0.0388), while in the DRV800 arm, median DRV plasma levels were 1,707 (958–3,910) ng/mL, CSF levels 13.23 (3.47–32.98) ng/mL and DRV CSF:plasma ratio 0.0104 (0.0018–0.0262). All patients had VL<40 copies/mL in plasma and 14 patients VL<40 copies/mL in CSF. Two patients (1 in each arm, and taking TDF/FTC) had detectable VL in CSF (280 and 159 c/mL). These patients had the lowest CSF DRV concentrations (5.47 and 3.47 ng/mL), with plasma DRV concentrations of 802 and 958 ng/mL respectively.
Conclusions
CSF DRV concentrations and CSF VL were similar between patients receiving DRV/r 800/100 mg or 600/100 mg OD. Low CSF DRV concentrations might be associated with viral escape in CNS. This may be taken into account in patients receiving OD DRV/r. Larger studies should confirm these findings
Identification of HIV-reservoir cells with reduced susceptibility to antibody-dependent immune response
HIV; Infectious disease; ReservoirVIH; Malalties infeccioses; ReservoriVIH; Enfermedades infecciosas; ReservorioHuman immunodeficiency virus (HIV) establishes a persistent infection in heterogeneous cell reservoirs, which can be maintained by different mechanisms including cellular proliferation, and represent the main obstacle to curing the infection. The expression of the Fcγ receptor CD32 has been identified as a marker of the active cell reservoirs in people on antiretroviral therapy (ART), but if its expression has any role in conferring advantage for viral persistence is unknown. Here, we report that HIV-infected cells expressing CD32 have reduced susceptibility to natural killer (NK) antibody-dependent cell cytotoxicity (ADCC) by a mechanism compatible with the suboptimal binding of HIV-specific antibodies. Infected CD32 cells have increased proliferative capacity in the presence of immune complexes, and are more resistant to strategies directed to potentiate NK function. Remarkably, reactivation of the latent reservoir from antiretroviral-treated people living with HIV increases the pool of infected CD32 cells, which are largely resistant to the ADCC immune mechanism. Thus, we report the existence of reservoir cells that evade part of the NK immune response through the expression of CD32.This study was supported by the Spanish Secretariat of Science and Innovation and FEDER funds (grants SAF2015-67334-R and RTI2018-101082-B-I00 [MINECO/FEDER]), the Spanish “Ministerio de Economia y Competitividad, Instituto de Salud Carlos III” (ISCIII, PI17/01470), GeSIDA and the Spanish AIDS network Red Temática Cooperativa de Investigación en SIDA (RD16/0025/0007), the Fundació La Marató TV3 (grants 201805-10FMTV3 and 201814-10FMTV3) and the Gilead fellowships GLD19/00084 and GLD18/00008. M.B is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CP17/00179). A.A-G is supported by the Spanish Secretariat of Science and Innovation Ph.D. fellowship (BES-2016–076382). The funders had no role in study design, data collection, and analysis, the decision to publish, or preparation of the manuscript
Results From England's 2018 Report Card on Physical Activity for Children and Youth
The Active Healthy Kids England 2018 Report Card provides an updated “state of the nation” resource regarding performances on the provision of, and support for, physical activity opportunities for children and young people. Specifically, in this paper we present and discuss key findings from the 2018 Report Card, a release that serves to revise our 2014 and 2016 report cards via the same systematic approach that incorporates best current data. To this end, these data include national surveys, peer-review outputs, and a variety of nonacademic sources including online content and reports from government and nongovernment organizations
Multidisciplinary, evidence-based consensus guidelines for human papillomavirus (HPV) vaccination in highrisk populations, Spain, 2016
Introduction: Although human papillomavirus (HPV) routine vaccination programmes have been implemented around the world and recommendations have been expanded to include other high-risk individuals, current recommendations often differ between countries in Europe, as well as worldwide. Aim: To find and summarise the best available evidence of HPV vaccination in high-risk patients aiding clinicians and public health workers in the day-to-day vaccine decisions relating to HPV in Spain. Methods: We conducted a systematic review of the immunogenicity, safety and efficacy/effectiveness of HPV vaccination in high-risk populations between January 2006 and June 2016. HPV vaccination recommendations were established with levels of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: A strong recommendation about HPV vaccination was made in the following groups: HIV infected patients aged 9-26 years; men who have sex with men aged 9-26 years; women with precancerous cervical lesions; patients with congenital bone marrow failure syndrome; women who have received a solid organ transplant or hematopoietic stem cell transplantation aged 9-26 years; and patients diagnosed with recurrent respiratory papillomatosis. Conclusions: Data concerning non-routine HPV vaccination in populations with a high risk of HPV infection and associated lesions were scarce. We have developed a document to evaluate and establish evidence- based guidelines on HPV vaccination in highrisk populations in Spain, based on best available scientific evidence
Multidisciplinary, evidence-based consensus guidelines for human papillomavirus (HPV) vaccination in high-risk populations, Spain, 2016.
Introduction: Although human papillomavirus (HPV) routine vaccination programmes have been implemented around the world and recommendations have been expanded to include other high-risk individuals, current recommendations often differ between countries in Europe, as well as worldwide. Aim: To find and summarise the best available evidence of HPV vaccination in high-risk patients aiding clinicians and public health workers in the day-to-day vaccine decisions relating to HPV in Spain. Methods: We conducted a systematic review of the immunogenicity, safety and efficacy/effectiveness of HPV vaccination in high-risk populations between January 2006 and June 2016. HPV vaccination recommendations were established with levels of evidence according to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Results: A strong recommendation about HPV vaccination was made in the following groups: HIV infected patients aged 9-26 years; men who have sex with men aged 9-26 years; women with precancerous cervical lesions; patients with congenital bone marrow failure syndrome; women who have received a solid organ transplant or hematopoietic stem cell transplantation aged 9-26 years; and patients diagnosed with recurrent respiratory papillomatosis. Conclusions: Data concerning non-routine HPV vaccination in populations with a high risk of HPV infection and associated lesions were scarce. We have developed a document to evaluate and establish evidence-based guidelines on HPV vaccination in high-risk populations in Spain, based on best available scientific evidence
KLRG1 expression on natural killer cells is associated with HIV persistence, and its targeting promotes the reduction of the viral reservoir
HIV infection; HIV reservoir; ImmunotherapyInfección por VIH; Reservorio de VIH; InmunoterapiaInfecció per VIH; Reservori de VIH; ImmunoteràpiaHuman immunodeficiency virus (HIV) infection induces immunological dysfunction, which limits the elimination of HIV-infected cells during treated infection. Identifying and targeting dysfunctional immune cells might help accelerate the purging of the persistent viral reservoir. Here, we show that chronic HIV infection increases natural killer (NK) cell populations expressing the negative immune regulator KLRG1, both in peripheral blood and lymph nodes. Antiretroviral treatment (ART) does not reestablish these functionally impaired NK populations, and the expression of KLRG1 correlates with active HIV transcription. Targeting KLRG1 with specific antibodies significantly restores the capacity of NK cells to kill HIV-infected cells, reactivates latent HIV present in CD4+ T cells co-expressing KLRG1, and reduces the intact HIV genomes in samples from ART-treated individuals. Our data support the potential use of immunotherapy against the KLRG1 receptor to impact the viral reservoir during HIV persistence.The project leading to these results has received funding from “la Caixa” Banking Foundation under the project code LCF/PR/HR20-00218. This study was also supported by the Agencia Estatal de Investigación project PID2021-123321OB-I00 funded by MCIN/AEI/10.13039/501100011033/FEDER, UE; The Spanish “Ministerio de Economia y Competitividad, Instituto de Salud Carlos III” (ISCIII, PI20/00160); and the Gilead fellowships GLD19/00084, GLD18/00008, GLD21-00049, and GLD22/00152. Part of the methodology was developed with the support of the grant 202104-30-31 from Fundació la Marató de TV3. M.B. is supported by the Miguel Servet program funded by the Spanish Health Institute Carlos III (CPII22/00005). A.A.-G. was supported by the Spanish Secretariat of Science and Innovation Ph.D. fellowship (BES-2016-076382). D.P. was supported by the VHIR Ph.D programme 2020. Spanish Secretariat of Science and Innovation Ph.D. fellowship. E.M.G. was supported by the Ramón y Cajal Program (RYC2018-024374-I) funded by the Spanish Secretariat of Science and Innovation, by the Comunidad de Madrid Talento Program (2017-T1/BMD-5396), and by the project PID2021-127899OB-I00 funded by MCIN /AEI /10.13039/501100011033/ FEDER, UE. We thank Dr. Joan Puñet from the flow cytometry core at the Vall d’Hebron Research Institute for his technical and scientific expertise. The funders had no role in study design, data collection, and analysis, the decision to publish, or preparation of the manuscript
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