Search

Objective: Tyrosine kinase inhibitors (TKIs) have successfully changed the natural course of chronic myeloid leukaemia (CML). Although they are highly effective drugs, their clinical benefit is conditioned by adherence. This study aims to analyse the adherence of CML patients treated with TKIs and to identify the main factors influencing their adherence to TKIs treatment., Material and Methods: An 8-month prospective, observational, multicentre study which included patients diagnosed with CML on treatment with TKIs attending the outpatient departments (OPD) of the Pharmacy Services of the participating hospitals. Adherence was assessed using two methods: the Simplified Medication Adherence Questionnaire (SMAQ) and the register of treatment dispensations from the OPDs. To analyse the predictors of adherence, a questionnaire was developed to report demographic and socio-economic information on the patients., Results: A total of 130 patients enrolled in this study. Adherence rate was 56.9% (n = 74) among individuals, not conditioned by the type of drug used: imatinib (54.8%), nilotinib (63.6%) or dasatinib (54.3%) ( p  =  0.67 ). The patient educational level ( p  =  0.047 ) and employment status ( p  =  0.028 ) were predictors of non-adherence to treatment., Conclusions: Adherence is one of the most relevant parameters affecting the effectiveness of highly effective chronic treatments. Approximately half of our patients showed inadequate adherence to treatment with TKIs, with employment status and the individual's level of education emerging as the determining factors., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: The addition of imatinib to the therapeutic arsenal for chronic myeloid leukaemia (CML) has changed the natural course of the disease, in such a way that it is now considered a chronic pathology. However, to achieve therapeutic success, it is necessary to reach adequate plasma concentrations to ensure efficacy and safety.In this study, we aimed to evaluate the plasma concentration of imatinib, analysing its influence on effectiveness and safety in patients with CML., Methods: We performed a descriptive, multicentre study in which imatinib plasma levels from patients diagnosed with CML between 2019-2020 were analysed. An optimal therapeutic range of 750-1500 ng/mL was established for the stratification of patients, according to their minimum plasma concentrations measured at steady state (Cssmin)., Results: A total of 28 patients were included, of whom only 39.3% (n = 11) showed Cssmin within the therapeutic range. 100% of patients with Cssmin >750 ng/mL achieved an optimal molecular response, while only 50% of patients with Cssmin <750 ng/mL achieved an optimal molecular response ( p  = 0.0004). The toxicity rate was 36.4% for patients with Cssmin >1500 ng/mL and 5.9% for those with Cssmin <1500 ng/mL ( p  = 0.039)., Conclusions: This study aimed to describe the correlation between the toxicity and effectiveness of imatinib according to its Cssmin in routine clinical practice conditions. Based on our findings, it would be certainly justified to monitor patient plasma concentrations of imatinib on a daily routine basis in our hospitals.

Introduction: Patient-reported outcomes (PROs) use, via a computer registry, allows patients to report their symptoms enabling the detection of early signs of progression of the disease. For such a record, the patient needs to show certain skills in new technologies use. The present study aimed to analyse the perception and degree of digital literacy of patients undergoing oncological treatment in an Oncology Day Hospital (ODH)., Methods: A cross-sectional descriptive study was performed, where the degree of literacy of patients attending antineoplastic treatment at the ODH was examined by means of an anonymous survey., Results: A total of 122 patients have been included in the study. The proportion of subjects who use the electronic mail (TM) and the Internet on a daily basis was 45.1% and 70.5%, respectively, and up to 77.9% from the subjects considered that the use of digital 2.0 strategies could help improve communication between healthcare professional and patient.The TM was determined by the age, educational level and employment status of the individual. Furthermore, the age of the patients conditioned their perception of the usefulness of the web 2.0 tools (T2.0)., Conclusion: This study allowed us to establish a target patient profile to conduct the efficient monitoring of cancer progression by PROs. The results have shown that approximately 60% of the patients in our population could be potential candidates to receive PROs-based health care. This approach enables earlier detection of symptoms and signs of progression and consequently, improves health outcomes for cancer patients.

Asparaginase (ASNase) use as a tumour-inhibitor drug has changed completely the natural course of paediatric acute lymphoblastic leukaemia (ALL) in such a way that it represents a paradigm shift in ALL management. ASNase treatment emergence has significantly improved pathologic responses and increased survival rates of ALL patients. Although different ASNase forms are currently available, only the pegylated form (PEG-ASNase) is recommended by relevant clinic guides. PEG-ASNase form shows longer elimination half-life, reducing the number of administrations, along with an enhanced safety profile. In spite of all of these advantages, PEG-ASNase elevated cost limits enormously its use. PEG-ASNase is commercialised as a lyophilised powder which according to the manufacturer it is stable for 24 hours once reconstituted, as a result, the leftover is usually discarded. In this study we analysed the enzymatic stability of reconstituted PEG-ASNase after conservation in three different temperature conditions for 5 and 14 days, aiming to take advantage of the remaining leftover for the subsequent administration. Our results have shown that PEG-ASNase is stable at 4°C, -20°C and -80°C for at least 14 days, retaining the 95% from the initial enzymatic activity in all three storage temperatures. According to our results, it is feasible to reuse the remaining content of PEG-ASNase vial after reconstitution, which means a 50% reduction of its cost for paediatric patient treatment and, consequently, removes the main barrier to use this drug in a wider population.

The Alternative Model for Personality Disorders defined in Diagnostic and Statistical Manual of Mental Disorders-Fifth edition ( DSM-5 ) has recently attracted considerable interest in empirical research, with different hypotheses being proposed to explain the discordant results shown in previous research. Empirical network analysis has begun to be applied for complementing the study of psychopathological phenomena according to a new perspective. This article applies this analysis to personality facets measured in a sample of 626 patients with mental disorders and a 1,034 normative sample, using the Personality Inventory for DSM-5 . The results reveal five substructures partially equivalent to domains defined in the DSM-5 . Discordant facets (suspiciousness, hostility, rigid perfectionism, attention seeking, and restricted affectivity) play the role of connectors between substructures. Invariance between clinical and community networks was found except for the connection between unusual beliefs and perceptual dysregulation (stronger in the clinical sample). Considering the strength centrality index, anxiousness, emotional lability, and depressivity can be highlighted for their relative importance within both clinical and normative networks.

The International Classification of Diseases-11th revision (ICD-11) classification of personality disorders is the official diagnostic system that is used all over the world, and it has recently been renewed. However, as yet very few data are available on its performance. This study examines the Personality Inventory for ICD-11 (PiCD), which assesses the personality domains of the system, and the Standardized Assessment of Severity of Personality Disorder (SASPD), which determines severity. The Spanish versions of the questionnaires were administered to a community ( n = 2,522) and a clinical sample ( n = 797). Internal consistency was adequate in the PiCD (α = .75 to .84) but less so in the SASPD (α = .64 and .73). Factor analyses suggested a unidimensional or bidimensional structure for severity, while revealing that the personality trait qualifiers are organized into four factors: negative affectivity, detachment, dissociality, and a bipolar domain of disinhibition-anankastia. The mutual relationships between traits and severity were analyzed, as well as the ability of the whole system to identify clinical subjects. Although further improvements are required, the results generally support the use of the PiCD and the SASPD and help substantiate the new ICD-11 taxonomy that underlies them.

Background: To compare effectiveness and safety of initial antiretroviral therapy (ART) among premenopausal and postmenopausal women living with HIV aged 45-60 years from the cohort of the Spanish HIV/AIDS Research Network (CoRIS) who initiated ART between 2004 and 2015., Methods: Multivariable regression models were used to compare post- versus premenopausal women regarding viral suppression (≤50 copies/ml), change in CD4 + T-cell count and time to treatment change (TC) at 48 and 96 weeks after ART initiation., Results: Among 230 women, 154 (67%) were premenopausal at ART initiation. The most frequent initial regimen was tenofovir disoproxil fumarate/emtricitabine/efavirenz prescribed in 49 (32%) premenopausal and 22 (29%) postmenopausal women. The proportion of TC was 35.7% and 30.3% at 48 weeks and 51.3% and 47.4% at 96 weeks, for pre- and postmenopausal women, respectively. There were no significant differences in CD4 + T-cell count changes from ART initiation, viral load suppression, time to TC or reason for TC between both groups. The main reason for TC was occurrence of an adverse event, followed by simplification, in both groups., Conclusions: ART effectiveness and safety did not differ significantly between pre- and postmenopausal women.

Colorectal cancer is the second most common cancer in Europe. Most antineoplastic regimens in first-line treatment involve 5-fluorouracil or oral prodrug capecitabine, combined with other antineoplastic agents such as oxaliplatin or irinotecan. It is well known that 5-fluorouracil and capecitabine are agents that can be toxic in cases of decreased dihydropyrimidine dehydrogenase activity because this enzyme is the main limiting factor in the metabolism of both agents. In this paper, we describe the case of a patient who developed severe toxicity to 5-fluouracil and who had a mutation in the gene encoding the enzyme dihydropyrimidine dehydrogenase.

The Personality Inventory for DSM-5 (PID-5) measures the trait part (Criterion B) of the alternative model for personality disorders proposed in Section III of DSM-5. Although its psychometric properties have proven adequate thus far, evidence is limited in other languages and in clinical samples. The Spanish PID-5 was examined in two samples comprising 446 clinical and 1,036 community subjects. Facet scales showed good internal consistency in both samples (median α = .86 and .79) and were unidimensional under exploratory and confirmatory approaches. They were also able to distinguish between clinical and community subjects with a mean standardized difference of z = 0.81. All facets except for Risk Taking were unipolar, such that the upper poles indicated pathology and the lower poles reflected normality, rather than the opposite pole of abnormality. The entire PID-5 hierarchical structure, from one to five factors, was confirmed in both samples with Tucker's congruence coefficients over .95.

Background: Gender-specific data on the management of HIV infection are scarce. Further, an increase in the proportion of new HIV diagnoses in older persons has been observed. Using data from the CoRIS cohort, we compared immunovirological responses and survival in HIV-infected men and women who started their first combination antiretroviral therapy (cART) when aged < /≥50 years., Methods: We used multivariable logistic, linear and Cox regression, adjusting for potential confounders and including an interaction between age and sex, to assess differences in immunovirological responses and mortality, respectively., Results: At 96 weeks, among subjects <50 years, women were less likely than men to achieve virological response (VR; adjusted OR [aOR] 0.77, 95% CI 0.60, 0.99) and among women, older individuals were more likely to achieve VR than the younger ones (aOR 1.96; 95% CI 1.15, 3.34). Initiating cART at ≥50 years was associated with lower increases in CD4 + T-cell count both in men (-65.8; 95% CI -91.3, -40.3) and women (-37.7; 95% CI -79.7, 4.4) and women showed higher increases than men in both subjects aged <50 (21.8; 95% CI -1.9, 45.5) and ≥50 years at cART initiation (49.9; 95% CI 19.9, 79.9). A higher risk of death in men ≥50 was observed (adjusted hazard ratio [aHR] 2.69; 95% CI 1.73, 4.21), but not in women (aHR 1.49; 95% CI 0.70, 1.14). Women experienced lower mortality than men <50 (0.66; 95% CI 0.41, 1.07) and in those ≥50 (0.37; 95% CI 0.14, 0.93)., Conclusions: Sex and age at cART initiation have a noticeable association with both virological and immunological responses and mortality. Age ≥50 is associated with poorer immunological response and higher mortality but this effect is less pronounced in women than in men.

Long life expectancy and wide development of therapies have increased the number of patients under artificial treatment for lost kidney function or dialysis. Different options for vascular access are suitable for receiving this therapy. The use of tunneled catheters has consequently increased complications related to its use. A difficult retrieval of catheters caused by a hard fibrin sheath along its trajectory is a common drawback. Herein, we report a woman with suspicion of hemodialysis catheter infection and an irretrievable Tesio catheter. A novel technique using a Fogarty arterial catheter allowed a successful retrieval and avoided an aggressive management.

Background: The aim of this study was to assess the short-term and long-term consequences of stopping antiretroviral therapy (ART) in patients with preserved immune function., Methods: This was a randomized 144-week follow-up CD4⁺ T-cell-count-guided treatment-interruption trial. HIV-1-infected adults with plasma HIV-1 RNA<50 copies/ml, CD4⁺ T-cell count >500 cells/μl and nadir CD4⁺ T-cell count >100 cells/μl were randomized to continuous treatment (CT) or treatment interruption (TI) until CD4⁺ T-cell count decreased to <350 cells/μl. The primary end points were AIDS-defining illnesses, death, CD4⁺ T-cell count <200 cells/μl, or virological failure after restarting ART., Results: A total of 106 patients were included, 50 in the CT arm and 56 in the TI arm. A trend to a higher rate of primary end points was observed in the TI group (26.8% versus 14%, difference 12.8%, 95% CI -2.3, 27.8; P=0.105). In addition, 10 patients presented clinical events related with HIV rebound, including 8 cases of thrombocytopaenia. The CD4⁺ T-cell count significantly decreased in the TI group (even in patients with persistently high CD4⁺ T-cell counts and no clinical events) versus the CT group (median change -408 cells/μl versus -21.5 cells/μl; P<0.001), whereas a significant increase in CD8⁺ T-cell count was observed (256 cells/μl versus -59 cells/μl; P<0.001). The time to ART re-initiation was significantly associated with nadir and baseline CD4⁺ T-cell counts., Conclusions: Discontinuation of ART in patients with preserved immune function is followed by significant immunological impairment even in those with no clinical events, and may be associated with an increased risk of HIV-related complications. Hence, patients who stop ART voluntarily should be closely monitored, regardless of their CD4⁺ T-cell count.

Background: Structured antiretroviral therapy interruption (TI) is discouraged because of poorer AIDS and non-AIDS-related outcomes, but is often inevitable in clinical practice. Certain strategies could reduce the emergence of resistance mutations related to TI., Methods: A total of 106 HIV-1-infected patients on stable HAART with undetectable plasma viral load were randomized to therapy continuation (n=50) or CD4(+) T-cell-guided TI (n=56). Staggered interruption involved stopping non-nucleoside reverse transcriptase inhibitors (NNRTIs) 7 days before the nucleoside backbone. Genotypic resistance testing (GRT) was performed on proviral DNA from peripheral blood mononuclear cells (PBMCs) at baseline and before each TI, and on plasma RNA after each TI., Results: At baseline, GRT on PBMCs detected mutations in nine patients and only two major mutations were identified. GRT on plasma samples performed after TIs showed nucleoside reverse transcriptase inhibitors (NRTI), NNRTI and protease inhibitor major resistance associated mutations in 10/56, 3/46 and 1/8 patients receiving these drugs, respectively. Only in two patients had the same mutations been observed in GRT on PBMCs at baseline. Three patients presented virological failure after resumption of therapy, all receiving NNRTIs. In one of them, resistance mutations detected at failure had been also observed previously in GRT on plasma after TI., Conclusions: Staggered interruption of NNRTIs 7 days before the nucleoside backbone does not avoid resistance emergence completely, but does not necessarily lead to virological failure after treatment resumption. Plasma HIV-1 RNA genotype after the interruption and the patient's treatment history seem to be more useful than baseline proviral DNA genotype to assess the risk of virological failure after restarting therapy.

Background: Data supporting a link between body-fat distribution changes and cardiovascular disease risk in HIV-infected patients are scarce and contradictory. We evaluated endothelial dysfunction, an early event in the development of atherosclerosis, and pro-atherosclerotic plasma biomarkers in HIV-infected patients with lipodystrophy., Methods: HIV-infected patients with and without lipodystrophy were prospectively enrolled. Endothelial function was measured through flow-mediated dilatation (FMD) of the brachial artery. Plasma levels of several biomarkers of inflammation, endothelial activation and coagulation associated with adipose tissue and endothelial dysfunction were determined., Results: The study included 110 patients, 55 of them with lipodystrophy. FMD was significantly lower in patients with lipodystrophy than in those without lipodystrophy (median [IQR] 3.1% [0.4-8.9] versus 6.3% [3.3-10.7]; P=0.004). Patients with isolated lipoatrophy exhibited the lowest FMD (2.6% [0-6.6]; P(Kruskal-Wallis)=0.02). Lipodystrophy was associated with significantly higher plasma levels of interleukin 6 (IL-6) and plasminogen activator inhibitor 1 (PAI-1) and lower levels of adiponectin; severe lipodystrophy was associated with higher concentrations of vascular cell adhesion molecule 1 (sVCAM-1). There was an inverse correlation between FMD and IL-6 (Spearman's rho =-0.26; P=0.007). In a multivariate regression model with the lowest quartile of FMD as the dependent variable and lipodystrophy, traditional cardiovascular risk factors, 10-year Framingham risk score, pro-atherosclerotic biomarkers and HIV-related variables as predictors, the only independent predictor of endothelial dysfunction was lipodystrophy (odds ratio 5.22, 95% confidence interval 1.76-15.46; P=0.003)., Conclusions: Lipodystrophy is associated with endothelial dysfunction, independently of the presence of traditional cardiovascular risk factors. This finding and the accompanying profile of pro-atherosclerotic biomarkers support an increased cardiovascular risk in HIV-infected patients with lipodystrophy.

Objective: To determine whether an association existed between lopinavir (LPV) plasma concentrations and changes in body fat composition., Design: A prospective, non-randomized study., Setting: HIV clinic of a University Hospital., Subjects, Participants: HIV-infected subjects who had virological failure on protease inhibitor-containing regimens. Twenty-two consecutive patients were enrolled, 19 completed 24 weeks of treatment and 16 completed the full 48-week study period., Intervention: Patients were treated with LPV/ritonavir (LPV/r) in combination with other antiretroviral agents. LPV trough plasma concentrations were measured at baseline and weeks 4, 8, 12, 24, 36 and 48. Body fat composition was quantified by computerized tomographic scanning at baseline, and weeks 24 and 48., Results: LPV trough concentrations correlated with absolute and proportional changes in limb fat from baseline to week 48. Significant differences were found in mean LPV trough concentrations between patients losing less than 5% of limb fat, those experiencing a limb fat loss between 5 and 20%, and those losing more than 20% at week 24 [mean (SD), 4.67 (1.67); 8.57 (1.77); 9.49 (2.67) microg/ml, respectively; P=0.013] and week 48 [mean (SD), 4.5 (2.24); 7.04 (1.77); 9.7 (2.8) microg/ml, respectively; P=0.027]. Most patients losing more than 5% of limb fat during LPV/r therapy had mean LPV trough concentrations > or = 8 microg/ml., Conclusions: In patients receiving salvage therapy with LPV/r there was an association between LPV plasma trough concentrations and limb fat loss. The risk of peripheral limb fat loss may be greater among patients achieving higher LPV trough concentrations.