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Long-term effectiveness and tolerability of dolutegravir/lamivudine in treatment-naive people with HIV: an analysis of a multicentre cohort at 96 weeks.
No full text20.500.12530/87885To evaluate the long-term effectiveness, persistence and tolerability of dolutegravir (DTG)/lamivudine (3TC), compared with the most frequently prescribed first-line treatment regimens, among antiretroviral-naive people with HIV from CoRIS, a multicentre cohort in Spain, in 2018-23. We used multivariable regression models to compare viral suppression (VS) (HIV RNA viral load Of 2359 participants, DTG/3TC was prescribed in 472 (20.0%), bictegravir/tenofovir alafenamide (TAF)/emtricitabine (FTC) in 1134 (48.1%), DTG + tenofovir disoproxil fumarate/FTC in 300 (12.7%), DTG/abacavir/3TC in 273 (11.6%) and darunavir/cobicistat/TAF/FTC in 180 (7.6%). At 96 weeks from treatment initiation, 94.0% of participants initiating with DTG/3TC achieved VS, and the mean increase in CD4 cell counts was 295.5 cells/μL (95% CI: 269.9-321.1). During the first 96 weeks after DTG/3TC initiation, 9.8% and 1.3% discontinued their initial regimen, overall and due to AEs, respectively. In multivariable analyses, we did not find significant differences in VS or increase in CD4 cell counts among participants initiating with DTG/3TC compared with other regimens. Initiating ART with a regimen other than DTG/3TC was associated with a higher risk of treatment discontinuation, overall and due to AEs. Among treatment-naive people with HIV from this large multicentre cohort, DTG/3TC had similar effectiveness and better persistence and tolerability than those of the most frequently prescribed first-line regimens at 96 weeks
Correction: Prediction model for major bleeding in anticoagulated patients with cancer-associated venous thromboembolism using machine learning and natural language processing.
No full text20.500.12530/8791
Material suplementario de la Revisión selectiva de los tratamientos psicológicos empíricamente apoyados para problemas de salud pediátricos 2
No full textEtapas, características y resultados de la búsqueda de la bibliografía para los problemas de salud pediátricos y acuerdo interjueces con respecto a la clasificación del nivel de evidencia y grado de recomendación de los tratamientos psicológicos revisados para cada problema de salud de la Revisión selectiva de los tratamientos psicológicos empíricamente apoyados para problemas de salud pediátrico
Mitochondrial Changes Induced by SGLT2i in Lymphocytes from Diabetic Kidney Transplant Recipients: A Pilot Study
No full textIncluido en la Base de Datos PubMed (PMID: 40244220) y el Repositorio PubMed Central (PMCID: PMC11989945)Sodium-glucose co-transporter 2 inhibitors (SGLT2i) preserve cardiac and renal function by mechanisms that are not completely elucidated. Among other things, SGLT2i promote nutrient-deprivation signalling, which might affect the immune function. As the fate of immune cells is controlled by their metabolism, we aimed to study the mitochondrial integrity of lymphocytes isolated from renal transplant recipients with type 2 diabetes (T2D) upon SGLT2i therapy instauration and six-month follow up. In this real-world pilot study, the mitochondrial respiration of isolated peripheral blood mononuclear cells was monitored in a Seahorse XFp extracellular-flux analyzer and cells were photographed with a confocal microscope. Mitochondrial mass, membrane potential, and superoxide content of lymphocyte subpopulations were measured by flow cytometry (MitoTrackerTM Green, TMRM, and MitoSOXTM Red probes). Leveraging in vivo conditions of immune cells, we evaluated their metabolic profiles associated with immune activation. Herein, we identified changes in redox homeostasis with sustained membrane polarization, and an increased mitochondrial biogenesis upon PHA stimulation that significantly correlated with changes in body weight and LDL-cholesterol levels, and a resultant compensatory mitochondrial function of lymphocytes. Our data suggest novel mechanisms induced by SGLT2i to modulate immune cells, which probably underlie the observed beneficial effects in kidney transplant recipients. Nonetheless, further mechanistic studies are required to extend these exploratory findings and encourage the use of this therapeutic strategy.S
Cariprazine and Cognition in Patients with Schizophrenia and Bipolar Disorder: A Systematic Review.
No full text20.500.12530/87852Cariprazine (CAR), an antipsychotic with partial agonism at the D3 receptor and higher affinity than dopamine, has shown significant procognitive effects in preclinical animal studies. This study systematically reviews CAR's effects on cognitive measures in patients with schizophrenia and bipolar disorder. Two independent reviewers systematically searched PubMed, Web of Science, Scopus, and the Cochrane Library up to May 2024, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Additional studies were found by hand searching the references of included studies. Eligible studies were randomized controlled trials (RCTs) in English that assessed CAR's effects on cognition in patients with schizophrenia or bipolar disorder. Quality was assessed using the Jadad scale. Out of 139 reports, 5 studies (involving 6,104 patients with schizophrenia or bipolar disorder) were included. In schizophrenia, CAR showed better cognitive outcomes (mainly indirect measures) than placebo (PBO) in both early and late stages. It also outperformed risperidone and aripiprazole in attention-related cognitive tests. In bipolar disorder, CAR improved cognition compared to PBO (also using indirect measures). Most studies found the greatest cognitive benefits with low doses of CAR (1.5-3 mg/d). CAR improved cognitive measures compared to PBO and other D2 antagonists or partial agonists in RCTs, especially in patients with greater baseline impairment. Thus, CAR may be a promising option for enhancing cognition in schizophrenic and bipolar patients; though, more trials using specific cognitive assessment tools are needed. PROSPERO CRD42023485028
A Phase III Randomized Trial of Integrated Genomics and Avatar Models for Personalized Treatment of Pancreatic Cancer: The AVATAR Trial.
No full text20.500.12530/87854Pancreatic ductal adenocarcinoma (PDAC) has limited treatment options. We compared the efficacy of comprehensive precision medicine against that of the conventional treatment in PDAC. We report a phase III trial of advanced PDAC in which patients were randomized (1:2) to a conventional treatment treated at physician's discretion (arm A) or to precision medicine (arm B). Subjects randomized to arm B underwent a tumor biopsy for whole-exome sequencing and to generate avatar mouse models and patient-derived organoids for phenotypic drug screening, with final treatment recommended by the molecular tumor board. The primary objective was median overall survival (OS). A total of 137 patients were enrolled with 125 randomized, 44 to arm A and 81 to arm B. Whole-exome sequencing was performed in 80.3% (65/81) patients of arm B, with potentially actionable mutations detected in 21.5% (14/65). Experimental models were generated in 16/81 patients (19.8%). Second-line treatment was administered to 39 patients in the experimental arm, but only four (10.2%) received personalized treatment, whereas 35 could not receive matched therapy because of rapid clinical deterioration, delays in obtaining study results, or the absence of actionable targets. The median OS was 8.7 and 8.6 months (P = 0.849) and the median progression-free survival was 3.8 and 4.3 months (P = 0.563) for the conventional and experimental arms, respectively. Notably, the four patients who received personalized treatment had a median OS of 19.3 months. Personalized medicine was challenging to implement in most patients with PDAC, limiting the interpretation of intention-to-treat analysis. Survival was improved in the subset of patients who did receive matched therapy
Circulating Tfh cells are differentially modified by abatacept or TNF blockers and predict treatment response in rheumatoid arthritis.
No full textCD4+CXCR5+PD-1hi follicular helper T (Tfh) cells dwell in the germinal centres (GCs) of lymphoid organs and participate in RA pathogenesis. The frequency of their circulating counterparts (cTfh frequency) is expanded in RA and correlates with the pool of GC Tfh cells. Our objective was to study the effect of abatacept (ABT) or TNF blockers (TNFbs) on the cTfh frequency in RA. Peripheral blood was drawn from seropositive, long-standing RA patients chronically receiving conventional synthetic DMARDs (csDMARDs; n = 45), TNFb (n = 59) or ABT (n = 34) and healthy controls (HCs; n = 137). Also, patients with an incomplete response to csDMARDs (n = 41) who initiated TNFb (n = 19) or ABT (n = 22) were studied at 0 and 12 months. The cTfh frequency was examined by cytometry. As compared with HCs, an increased cTfh frequency was seen in seropositive, long-standing RA patients chronically receiving csDMARDs or TNFb but not ABT. After changing from csDMARDs, the cTfh frequency did not vary in patients who were given TNFb but decreased to HC levels in those given ABT. In the ABT group, the baseline cTfh frequency was higher for patients who attained 12-month remission (12mr) vs those who remained active (12ma): 0 month cut-off for remission >0.38% [sensitivity 92%, specificity 90%, odds ratio (OR) 25.3]. Conversely, in the TNFb group, the baseline cTfh frequency was lower for 12mr vs 12ma: 0 month cut-off for non-remission >0.44% (sensitivity 67%, specificity 90%, OR 8.5). ABT but not TNFb was able to curtail the cTfh frequency in RA. A higher baseline cTfh frequency predicts a good response to ABT but a poor response to TNFb
Multiscale modelling of active hydrogel elasticity driven by living polymers: softening by bacterial motor protein FtsZ.
No full textWe present a neo-Hookean elasticity theory for hybrid mechano-active hydrogels, integrating motor proteins into polymer meshes to create composite materials with active softening due to modulable chain overlaps. Focusing on polyacrylamide (PA) hydrogels embedded with FtsZ, a bacterial cytokinetic protein powered by GTP, we develop a multiscale model using microscopic Flory theory of rubbery meshes through mesoscopic De Gennes' scaling concepts for meshwork dynamics and phenomenological Landau's formalism for second-order phase transitions. Our theoretical multiscale model explains the active softening observed in hybrid FtsZ-PA hydrogels by incorporating modulable meshwork dynamics, such as overlapping functionality and reptation dynamics, into an active mean-field of unbinding interactions. The novel FtsZ-based metamaterial and companion multiscale theory offer insights for designing, predicting, and controlling complex active hydrogels, with potential applications in technology and biomedicine
Benefit-Risk Trade-offs and Patient Preferences for Therapy Selection in Ulcerative Colitis: a Multicountry Preference Study.
No full textTo help navigate the complex treatment landscape of ulcerative colitis (UC), we quantified the benefit-risk trade-offs that patients were willing to make when choosing treatment. Patients completed an online discrete choice experiment. Eligible patients had a UC diagnosis for ≥6 months, were aged ≥18 years, and resided in France, Germany, Italy, Spain, or the UK. Patients chose between 2 hypothetical treatments set up to ensure trade-offs were made. Clinical trial data, literature review, and patient interviews identified treatment attributes. Relative attribute importance (RAI) scores and maximum acceptable risks were generated. A patient-centric benefit-risk assessment of 200 mg of filgotinib was conducted as an example to show how measured trade-offs can be used. Overall, 631 patients participated; patients had a mean age of 42.2 years and were predominantly male (75.3%). Achieving and maintaining clinical remission was the most important factor for patients (RAI 32.4%); to achieve this, patients were willing to accept slightly higher risks of blood clots, serious infections, and malignancies compared with lower risk treatment profiles. Patients also valued the convenience of oral treatments, avoiding steroids, and the ability to attend school/work. The patient-centric benefit-risk assessment suggested patients are significantly more likely to prefer Janus kinase 1 preferential inhibitor filgotinib over placebo. Achieving clinical remission was the highest treatment priority for patients. To attain this, patients were willing to accept some slightly higher risk treatment profiles. Patient choices in the benefit-risk assessment suggested patients were significantly more likely to prefer filgotinib over placebo
Impact of pharmaceutical care on hospital readmissions for heart failure: a randomised trial.
No full text20.500.12530/87908To evaluate the impact of pharmaceutical care on the number of readmissions and visits to the emergency department due to heart failure 30 days after hospital discharge, based on a programme of continuous pharmaceutical care throughout the care process, and to assess the differences between the control and intervention groups at 90 days after discharge (number of readmissions and visits to the emergency department, time from discharge to new readmission or visit to the emergency department). A single-centre experimental longitudinal prospective open and parallel-group study with balanced randomisation (1:1) was carried out in a tertiary hospital in Spain. Patients with a diagnosis of primary or decompensated heart failure admitted to the Cardiology Service or the Heart Failure and Vascular Risk Unit were recruited between March 2019 and November 2021 and randomly assigned, using a randomised block model, to the control (standard care) or intervention (continuing care model) groups. Epidemiological, clinical and pharmacology data were recorded. As a measure of association, we used the mean difference and the Student's t-test. A p value of 296 patients were included (150 randomised to the control group, 146 to the intervention group). The results showed no significant differences between the control and intervention groups in the number of readmissions and visits to the emergency department during the 30 days after discharge (p=0.092), but a statistically significant difference was seen at 90 days (p=0.043). The number of days until the first visit to the emergency department or readmission was higher in the intervention group (p=0.021). Continuous care and follow-up by the pharmacist 30 days after discharge has a neutral impact on hospital readmissions and visits to the emergency department of patients with heart failure, but it is positive in the 90 days following discharge