Estado actual de la detección e intervención temprana en psicosis

La posibilidad de intervenir precozmente en los trastornos psicóticos y alterar con ello el tradicional curso negativo de la enfermedad está generando un creciente interés en la comunidad científica y profesional. En este trabajo, presentamos el momento en que se encuentran las investigaciones y los desarrollos clínicos y de organización de servicios en las distintas fases iniciales de la enfermedad, describiendo tanto las nuevas formas de intervención como sus primeros y esperanzadores resultados.Early intervention in psychotic disorders in order to alter their typical negative course is nowadays creating a growing interest in the scientific and professional community. In this paper, the state of the art in research and clinical implementation, and the organization of services for the several early phases of the illness are presented; and new methods of intervention as well as the first and promising results are described.Ministerio de Ciencia y Tecnología BSO2002-0343

La investigación cognitiva del síndrome esquizofrénico

Se revisan las anomalías cognitivas observadas en la esquizofrenia y, específicamente, los déficit encontrados en diversos procesos automáticos y controlados: el filtrado de la información, la atención y vigilancia, la formación de conceptos y la memoria. Se describen también diversos paradigmas experimentales utilizados para el estudio de los procesos ejecutivos centrales; y, finalmente, se describe un modelo cognitivo para las conductas anormales y los síntomas clínicos de la esquizofrenia (delirios, desorganización, alucinaciones y la pérdida del sentimiento de identidad personal) que sugiere que pueden estar ligados a un trastorno básico de la percepción holística o la interpretación de contextos.This review provides a perspective of cognitive disturbances found in schizophrenia and, particularly, of deficits found in several automatic and controlled processes: information filtering, attention and vigilance, concept formation and memory. Several experimental paradigms employed in the study of central executive processes are also described; and, finally, a cognitive model of abnormal behaviours and clinical symptoms of schizophrenia (delusions, disorganization, hallucinations, and the loss of a sense of personal identity) are outlined suggesting that they may be linked to a basic disturbance in comprehensive knowledge or context perception.Ministerio de Ciencia y Tecnología BSO2002-0343

Aplicación de la terapia contextual basada en la persona a un caso complejo de esquizofrenia

Antecedentes: las terapias psicológicas están siendo cada vez más importantes en la esquizofrenia, y no como meras adjuntas a la medicación. La psicoterapia de la esquizofrenia está cobrando nueva vida a la luz de desarrollos fenomenológicos y psicológicos centrados en la persona. Método: se presenta un caso complejo, de abigarrada sintomatología y larga duración, sin que hasta ahora la medicación produjera cambios clínicos significativos. La formulación del caso de acuerdo con la terapia cognitiva basada en la persona permitió entender los síntomas psicóticos en el contexto biográfico y llevar a cabo una terapia centrada en la recuperación del sentido del yo y de la vida. Resultados: al final de la terapia y en el seguimiento de un año las experiencias psicóticas habían desaparecido prácticamente o dejado de ser perturbadoras y la paciente se había reintegrado en la vida social. Conclusiones: los síntomas psicóticos cobran sentido en el contexto biográfico. Esto puede servir a la explicación psicopatológica y a una ayuda terapéutica significativa, más centrada en la recuperación que en el mero sostenimiento, que fácilmente termina en "abandono" asistencial y existencial. La terapia psicológica muestra ser viable en casos complejos atendidos en dispositivos públicos.Background: Psychological therapies are becoming more and more important in schizophrenia, and not as mere adjuncts to medication. The psychotherapy of schizophrenia is taking on a new lease of life in the wake of person-based phenomenological and psychological developments. Method: The case in question was a complex one, with variegated symptomatology that had persisted over many years. Approaching the case from the perspective of person-based cognitive therapy allowed us to understand the psychotic symptoms in the biographical context and to apply a therapy focused on the patient's recovery of her sense of self and of life. Results: At the end of the therapy and throughout the 12-month follow-up, the psychotic experiences had practically disappeared, or ceased to be disturbing, and the patient had become re-integrated in social life. Conclusions: Psychotic symptoms take on meaning in the biographical context. Adopting this perspective can aid the psychopathological explanation of the disorder and provide significant therapeutic help, more focused on recovery. Psychological therapy has shown itself to be viable in complex cases treated within the public-sector healthcare context

Influence of drug–drug interactions on effectiveness and safety of direct-acting antivirals against hepatitis C virus

[Abstract] Objectives Direct-acting antivirals are the recommended treatment for hepatitis C-infected patients. Drug–drug interactions with concomitant treatments can cause lack of effectiveness and/or safety. The objective of this study is to characterise drug–drug interactions of direct-acting antivirals and to analyse their influence both on the effectiveness of antiviral treatment and on the overall safety of pharmacological treatment in hepatitis C-infected patients. Methods Observational and prospective cohort study for 3 years in the pharmaceutical care outpatient consultation of a general hospital, undertaking detection, evaluation and management of drug–drug interactions by clinical pharmacists and physicians. The main outcome measures were sustained virologic response at week 12 for effectiveness and serious drug-related adverse events for safety. Multivariate statistical analysis applied to: (a) patient basal characteristics related to presence of drug–drug interactions; (b) previous antiviral treatments, viral genotype, cirrhosis, decompensations and presence of drug–drug interactions related to the effectiveness of direct-acting antivirals. Results Of a total of 1092 patients, the majority of them were men, around 60 years old and HCV-genotype 1 mono-infected, with a high basal viral load, naive to antiviral treatment, treated with ledipasvir/sofosbuvir and without cirrhosis. 24.5% had drug–drug interactions. Proton pump inhibitors were the concomitant drugs that caused the most drug–drug interactions. Age ≥65 years and direct-acting antivirals based on protease inhibitors were independently related to the presence of drug-drug interactions (p≤0.012). All (100%) of the therapeutic recommendations based on detected drug–drug interactions were implemented; 97.7% of patients with interactions versus 99.0% without them reached sustained virologic failure (p=0.109). The serious adverse events rates were 1.5% and 1.3% in patients with and without drug-drug interactions, respectively (p=0.841). Conclusions Drug–drug interactions are frequent among hepatitis C-infected patients receiving treatment with direct-acting antivirals. However, the collaboration between physicians and clinical pharmacists makes it possible to detect, evaluate, avoid or clinically manage these drug–drug interactions, in order to maintain whole treatment therapeutic safety and the effectiveness of direct-acting antivirals

Clinical experience with the integrase inhibitors Dolutegravir and Elvitegravir in HIV-infected patients: efficacy, safety and tolerance

[Abstract] Two integrase inhibitors (INSTIs), dolutegravir (DTG) and elvitegravir/cobicistat (EVG/COBI), have joined recently the pharmacotherapy arsenal against HIV. This study evaluated the efficacy and tolerability of these INSTIs in the last two years. A retrospective observational study in patients who started DTG or EVG/COBI from January 2015 to January 2017 at a reference hospital in north-western Spain was done. Epidemiological, clinical and immunovirological data were recorded. A statistical analysis was performed with SPSS software. A total of 542 DTG (n = 275)- or EVG/COBI (n = 267)-based therapies were initiated during the study period. Overall, more than 90% of naïve and pre-treated patients had virological suppression in both groups after 48 weeks of initiation of treatment per-protocol snapshot analysis. During follow-up, 10.2% of patients were treated with DTG and 4.5% of those treated with EVG discontinued due to adverse events (AE). In the case of DTG mainly related to neuropsychiatric disturbances (70.4%) and for EVG/COBI with gastrointestinal discomfort (50%). Female sex [HR 2.255 (95%CI 1.121–4.535), p = 0.023] and DTG treatment [HR 2.453 (95%CI 1.221–4.931), p = 0.012] were associated with AE discontinuations. Specifically for neuropsychiatric events, DTG treatment [HR 5.906 (95%CI 1.954–17.846), p = 0.002] and receiving abacavir/lamivudine/DTG [HR 4.380 (95%CI 1.348–14.233), p = 0.014] were identified as predictive risk factors for treatment discontinuations in two different multivariate analyses. A high percentage of AE discontinuations not previously described in clinical trials has been observed, especially with DTG. Female gender and DTG treatment were identified as risk factors for AE discontinuation. DTG-based therapies, especially in combination with abacavir/lamivudine, were associated with an increased risk of treatment discontinuation due to neuropsychiatric AE.Instituto de Salud Carlos III; CPII14/00014Instituto de Salud Carlos III; PI10/02166Instituto de Salud Carlos III; PI13/02266Instituto de Salud Carlos III; CM13/00328Instituto de Salud Carlos III; CM15/00233Instituto de Salud Carlos III; PI16/0215

Treatment with tenofovir alafenamide fumarate worsens the lipid profile of HIV‐infected patients versus treatment with tenofovir disoproxil fumarate, each coformulated with elvitegravir, cobicistat, and emtricitabine

[Abstract] Two elvitegravir/cobicistat‐based therapies combined with emtricitabine/tenofovir disoproxil fumarate (EVG/c/FTC/TDF) or emtricitabine/tenofovir alafenamide fumarate (EVG/c/FTC/TAF) are currently available for HIV patients. This study evaluated the modifications in the lipid profile of patients who received these treatments in the last three years at our institution. A retrospective observational study in HIV‐infected patients who received EVG/c/FTC/TDF or EVG/c/FTC/TAF from January 2015 to January 2018 at a reference hospital in northwestern Spain was carried out. Epidemiological, clinical and immunovirological data were recorded. A statistical analysis was performed using SPSS software. A total of 384 EVG/c‐based therapies were initiated during the study period, 151 EVG/c/FTC/TDF and 233 EVG/c/FTC/TAF. A significantly negative influence in all the lipid profile parameters in experienced patients and total cholesterol (TC), and LDL‐C in naïve patients were observed after 48 weeks of treatment with EVG/c/FTC/TAF, while these parameters remained stable in the EVG/c/FTC/TDF group. During follow‐up, a greater proportion of patients had lipid levels above the normal range (63.1% TC, 56.2% LDL‐C) and new lipid‐modifying drugs were prescribed (11.9%) in the EVG/c/FTC/TAF group. The number of cardiovascular risk factors (OR 1.66 [95% CI 1.01‐2.72]; P = 0.043) was recognised as an independent predictor of lipid‐lowering prescription for patients treated with both EVG/c/FTC/TDF and EVG/c/FTC/TAF. For patients treated with EVG/c/FTC/TAF, the mean total cholesterol to HDL ratio in the first 48 weeks of the study treatment was associated with a higher likelihood of lipid‐lowering prescription in multivariate analysis (OR 1.6 [95% CI 1.12‐2.52]; P = 0.011). Significant changes in lipid profile have been observed in patients who have received EVG/c/FTC/TAF. It was necessary to prescribe almost twice the number of lipid‐lowering drugs to patients who received EVG/c/FTC/TAF (11.9%) vs EVG/c/FTC/TDF (4.7%)

Discontinuation due to neuropsychiatric adverse events with efavirenz- and dolutegravir-based antiretroviral therapy: a comparative real-life study

Obervational study[Abstract] Objectives: Despite the high efficacy of antiretroviral treatment, no drug is free from adverse events (AEs). Efavirenz (EFV) and dolutegravir (DTG) are antiretroviral drugs for which neuropsychiatric adverse events (NPAEs) have been described. This study evaluated the safety and tolerability of DTG-based and EFV-based antiretroviral regimens in HIV-infected patients. Methods: A retrospective observational study was carried out in HIV-infected patients who started DTG- or EFV-based antiretroviral treatment from January 2008 to December 2018 at a reference hospital in north-western Spain. Epidemiological, clinical and immunovirological data were recorded. A statistical analysis was performed with SPSS software. Results: A total of 282 DTG- and 148 EFV-based therapies were initiated. During follow-up, statistically significant differences have been found between the rate of patients who discontinued DTG and EFV due to AEs (12.1% vs 35.8%, p<0.001) and the main AEs in both groups, NPAEs (8.2% vs 25.0%, p<0.001). Female gender (OR 2.610 (95% CI 1.327 to 5.133), p=0.005) was associated with discontinuations due to AEs. Patients with documented psychiatric disorders were at higher risk of discontinuation due to NPAEs (OR 4.782 (95% CI 1.190 to 19.220), p=0.027). The multivariate analysis showed a 61.2% risk reduction in benzodiazepine prescriptions in patients treated with DTG. In both groups, patients needed consultation and follow-up in the psychiatry unit (16.9% in the EFV group and 8.9% in the DTG group, p=0.021). Conclusions: We found a high rate of discontinuations due to AEs and NPAEs, prescription of benzodiazepines and a requirement for consultation in a psychiatric unit in both treatment groups, especially with EFV

Renal profile of patients treated with elvitegravir/ cobicistat/emtricitabine/tenofovir alafenamide fumarate and dolutegravir/abacavir/lamivudine: 120-week results from a real-world cohort

[Abstract] Elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide fumarate (EVG/c/FTC/TAF) and dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) are currently available for HIV patients. Objectives: This study evaluated modifications in the renal safety profile in a large real-world cohort of patients who had received EVG/c/FTC/TAF or DTG/ABC/3TC. Methods: A retrospective observational study of HIV-infected patients who received EVG/c/FTC/TAF or DTG/ABC/3TC between March 2015 and June 2019 at a reference hospital in north-western Spain was conducted. Epidemiological, clinical, immunovirological data and information regarding antiretroviral therapy were recorded. The statistical differences between treatments were calculated. Results: A total of 457 patients were evaluated, 266 using EVG/c/FTC/TAF and 191 using DTG/ABC/3TC. Up to week 120, serum creatinine improved in both study groups among experienced patients (EVG/c/FTC/TAF 1.01±0.24 vs 0.91±0.19, p<0.001; DTG/ABC/3TC 1.08±0.24 vs 1.02±0.31, p<0.001), while in naïve patients serum creatinine remained stable compared with baseline. Statistically significant differences were found in serum creatinine when comparing both treatments at week 48 in experienced (0.94±0.21 vs 1.09±0.28, p<0.001) and naïve patients (0.89±0.16 vs 1.06±0.20, p=0.001), and among experienced patients at week 120 (0.91±0.19 vs 1.02±0.31, p=0.015) for the EVG/c/FTC/TAF and DTG/ABC/3TC groups, respectively. During the follow-up, 39 patients in EVG/c/FTC/TAF and 33 in DTG/ABC/3TC (p=0.449) discontinued treatment. The main reason for stopping treatment was adverse events, which were similar in both groups. Conclusions: During the follow-up, patients experienced changes that were not clinically relevant in both treatment groups. Differences in renal events were not found

Creación de minivideos docentes modulares (MDM) basados en las transparencias minimalistas (TM) despertando la actitud activa de los estudientes, a través de tablets y smartphones

Memoria ID-345. Ayudas de la Universidad de Salamanca para la innovación docente, curso 2013-2014

Effectiveness of an intervention for improving drug prescription in primary care patients with multimorbidity and polypharmacy:Study protocol of a cluster randomized clinical trial (Multi-PAP project)

This study was funded by the Fondo de Investigaciones Sanitarias ISCIII (Grant Numbers PI15/00276, PI15/00572, PI15/00996), REDISSEC (Project Numbers RD12/0001/0012, RD16/0001/0005), and the European Regional Development Fund ("A way to build Europe").Background: Multimorbidity is associated with negative effects both on people's health and on healthcare systems. A key problem linked to multimorbidity is polypharmacy, which in turn is associated with increased risk of partly preventable adverse effects, including mortality. The Ariadne principles describe a model of care based on a thorough assessment of diseases, treatments (and potential interactions), clinical status, context and preferences of patients with multimorbidity, with the aim of prioritizing and sharing realistic treatment goals that guide an individualized management. The aim of this study is to evaluate the effectiveness of a complex intervention that implements the Ariadne principles in a population of young-old patients with multimorbidity and polypharmacy. The intervention seeks to improve the appropriateness of prescribing in primary care (PC), as measured by the medication appropriateness index (MAI) score at 6 and 12months, as compared with usual care. Methods/Design: Design:pragmatic cluster randomized clinical trial. Unit of randomization: family physician (FP). Unit of analysis: patient. Scope: PC health centres in three autonomous communities: Aragon, Madrid, and Andalusia (Spain). Population: patients aged 65-74years with multimorbidity (≥3 chronic diseases) and polypharmacy (≥5 drugs prescribed in ≥3months). Sample size: n=400 (200 per study arm). Intervention: complex intervention based on the implementation of the Ariadne principles with two components: (1) FP training and (2) FP-patient interview. Outcomes: MAI score, health services use, quality of life (Euroqol 5D-5L), pharmacotherapy and adherence to treatment (Morisky-Green, Haynes-Sackett), and clinical and socio-demographic variables. Statistical analysis: primary outcome is the difference in MAI score between T0 and T1 and corresponding 95% confidence interval. Adjustment for confounding factors will be performed by multilevel analysis. All analyses will be carried out in accordance with the intention-to-treat principle. Discussion: It is essential to provide evidence concerning interventions on PC patients with polypharmacy and multimorbidity, conducted in the context of routine clinical practice, and involving young-old patients with significant potential for preventing negative health outcomes. Trial registration: Clinicaltrials.gov, NCT02866799Publisher PDFPeer reviewe