We evaluated the effect of combination therapy with zidovudine (AZT) plus zalcitabine (ddC) in hu... more We evaluated the effect of combination therapy with zidovudine (AZT) plus zalcitabine (ddC) in human immunodeficiency virus type 1 (HIV-1)-infected patients who had not previously received antiretroviral treatment ('naive' patients). The immunological and virological parameters evaluated were CD4 cell count, syncytium-inducing (SI) viral phenotype and plasma HIV-1 RNA copies/ml (HIV viral load). A total of 75 patients entered the study, with CD4 cell counts between 200 and 500 cells/mm3. All received zidovudine (200 mg) plus zalcitabine (0.75 mg) three times daily for 24 weeks. Treatment was well tolerated. However, four patients presented with anaemia (haemoglobin < 10.0 g/dl) and one patient had both anaemia and neutropenia (0.8 x 10(9) neutrophils/l). Combination therapy with zidovudine plus zalcitabine resulted in a pronounced improvement of virological and immunological markers. Approximately 25% of patients achieved undetectable plasma HIV RNA levels (< 200 copies/ml) at week 24. At the end of the study (24 weeks) a significant reduction (> 0.5 log) of plasma HIV RNA was observed in approximately 70% of patients and in 50% an even greater decrease (> 1 log) was achieved. The most significant decrease in mean plasma HIV RNA levels was observed at week 4, whereas the highest increase in CD4 cell count was found at week 24. Approximately 80% of patients who showed baseline plasma HIV RNA levels below 20000 copies/ml had less than 5000 copies/ml at week 24. The plasma HIV RNA reduction observed at week 4 was significantly maintained at week 24. Therefore, we can rapidly select those who will not respond to therapy and adjust the treatment after a short interval. Our study supports the idea of early therapy because all patients who reached undetectable levels of plasma HIV RNA at week 24 had at baseline a median plasma HIV RNA load of 2560 copies/ml. In conclusion, zidovudine in combination with zalcitabine was well tolerated in the majority of patients and led to a significant reduction in plasma HIV RNA copies in most of the patients with initial viraemia lower than 20000 copies/ml.
Treatment of human immunodeficiency virus type 1 (HIV-1)-infected patients with combination drug ... more Treatment of human immunodeficiency virus type 1 (HIV-1)-infected patients with combination drug regimens results in a reduction of plasma viral load to levels below the limit of detection. To investigate the genomic fluctuations in HIV-1 populations from long-term responders to antiviral therapies we analyzed the viral sequence evolution of env and pol genes from sequential peripheral blood mononuclear cell (PBMC) DNA samples of three infected patients. Analyses of sequences covering the V3 and flanking env regions obtained from blood samples at the beginning of the therapy and at 14 or 24 months from baseline revealed that HIV-1 quasispecies continue to evolve in the three patients following combination antiretroviral therapy. Minor drug-resistant mutant subpopulations were also searched for and found in one patient. Interestingly, no minor resistant subpopulations were found in the other two patients despite the fact that they showed evidence of ongoing viral replication. Finally, the genetic analysis of the env gene shows a reduction in PBMC env viral population diversity after long-term response to the therapy in all the patients analyzed.
The Journal of Gambling Business and Economics, May 23, 2013
Although most individuals who gamble do so without any adverse consequences, some individuals dev... more Although most individuals who gamble do so without any adverse consequences, some individuals develop a recurrent, maladaptive pattern of gambling behaviour, often called pathological gambling or gambling disorder, that is associated with financial losses, disruption of family and interpersonal relationships, and co-occurring psychiatric disorders. Identifying whether different types of gambling modalities vary in their ability to lead to maladaptive patterns of gambling behaviour is essential to develop public policies that seek to balance access to gambling opportunities with minimizing risk for the potential adverse consequences of gambling behaviour. Until recently, assessing the risk potential of different types of gambling products was nearly impossible. ASTERIG, initially developed in Germany in 2006-2010, is an assessment tool to measure and to evaluate the risk potential of any gambling product based on scores on ten dimensions. In doing so, it also allows a comparison to be drawn between the addictive potential of different gambling products. Furthermore, the tool highlights where the specific risk potential of each specific gambling product lies. This makes it a valuable tool at the legislative, case law, and administrative levels as it allows the risk potential of individual gambling products to be identified and to be compared globally and across 10 different dimensions of risk potential. We note that specific gambling products should always be evaluated rather than product groups (lotteries, slot machines) or providers, as there may be variations among those product groups that impact their risk potential. For example, slot machines may vary on the amount of jackpot, which may influence their risk potential.
We report the integrated proviral LTR sequence variation in four patients on highly active antire... more We report the integrated proviral LTR sequence variation in four patients on highly active antiretroviral therapy (HAART). Integrated proviral fragments of LTR taken from four time points were PCR amplified from PBMCs and 10 to 12 individual clones were sequenced for each time point. Intrasample genetic distances and phylogenetic reconstruction of all LTR sequences demonstrated that 1-2 years of successful HAART did not significantly reduce the genetic repertoire of the integrated reservoir of HIV-1.
Objective. e To test the reliability and validity of the DIGS in Spanish population. Methods. e I... more Objective. e To test the reliability and validity of the DIGS in Spanish population. Methods. e Inter-rater and test-retest reliability of the Spanish version of DIGS was tested in 95 inpatients and outpatients. The resultant diagnoses were compared with diagnoses obtained by the LEAD (Longitudinal Expert All Data) procedure as ''gold standard''. The kappa statistic was used to measure concordance between blind inter-raters and between the diagnoses obtained by LEAD procedure and through the DIGS. Results. e Overall kappa coefficient for inter-rater reliability was 0.956. The kappa value for individual diagnosis varied from major depression ¼ 0.877 to schizophrenia ¼ 1. Test-retest reliability was 0.926. Kappa for all individual target diagnoses ranged from 0.776 (major depression) to 1. Kappa between LEAD procedure and DIGS ranged from 0.704 (major depression) to 0.825 (bipolar I disorder). Conclusion. e Most of the DSM-IV major psychiatric disorders can be assessed with acceptable to excellent reliability with the Spanish version of the DIGS interview. The Spanish version of DIGS showed an acceptable to excellent concurrent validity. Giving the good reliability and validity of Spanish version of DIGS it should be considered to identify psychiatric phenotypes for genetics studies.
Revista de investigación y educación en ciencias de la salud, May 30, 2020
Resumen: El Juego Patológico se define como una conducta de juego recurrente y persistente que de... more Resumen: El Juego Patológico se define como una conducta de juego recurrente y persistente que deteriora todas las áreas de la vida. Está considerado un importante problema de salud pública. El objetivo del trabajo es describir las características sociodemográficas, conducta de juego e impulsividad de una muestra de pacientes que solicitó iniciar tratamiento en la Unidad de Ludopatía del Hospital Universitario Ramón y Cajal. La muestra estuvo compuesta por 19 pacientes (89.5% hombres) con diagnóstico de JP según criterios diagnósticos DSM-5. Los resultados muestran que la media de edad fue de 39.89 años, en su mayoría estaban solteros, tenían estudios secundarios o universitarios y se encontraban en situación laboral activa; la edad media de inicio al juego fue de 24.21 años y la evolución del problema de 5.16 años; la modalidad de juego online estaba presente en el 42.1% de los casos, siendo las apuestas deportivas la principal actividad de juego practicada (42.1%); tienen en su mayoría deudas (78.9%) que ascienden de media a 12263.16€; y puntúan elevado en todas la subescalas de impulsividad. Como conclusión, exponer que, si bien el paciente que solicita tratamiento sigue siendo un hombre soltero y laboralmente activo, cada vez más son más numerosos aquellos que tienen estudios universitarios, que comienzan a jugar a una edad cada vez más temprana y cuya principal actividad de juego ya no son las máquinas tragaperras, sino las apuestas deportivas, que estarían detrás de gran parte de los problemas relacionados con el juego en la actualidad.
Los estudios farmacogenéticos mejoran nuestros conocimientos sobre las consecuencias funcionales ... more Los estudios farmacogenéticos mejoran nuestros conocimientos sobre las consecuencias funcionales de las variantes genéticas, ayudándonos a identificar aquellos pacientes predispuestos a la aparición de determinados efectos secundarios o, por el contrario, ...
The International journal of social psychiatry, 2022
BACKGROUND Traumatic life events (TLEs) are one of the most robust environmental risk factors for... more BACKGROUND Traumatic life events (TLEs) are one of the most robust environmental risk factors for the onset of first-episode psychosis (FEP). AIMS To explore TLEs in FEP patients and healthy controls (HC), to analyze gender differences and to examine whether TLEs were associated with sociodemographic, clinical and psychofunctional variables in all FEP sample and split by age. METHODS Descriptive and cross-sectional study. Three hundred and thirty-five FEP and 253 HC were recruited at 16 Spanish mental health research centers. The Traumatic Experiences in Psychiatric Outpatients Questionnaire was administered. RESULTS We found a higher number of TLEs in FEP than in HC, and the proportion of individuals with three or more TLEs was significantly higher in the FEP group. No differences were found in terms of gender and age. There was no relationship between total number of TLEs and psychotic symptomatology and functional outcomes. CONCLUSIONS The number and cumulative TLEs should be tak...
Relapses are frequent in the first years following a first episode of schizophrenia (FES), being ... more Relapses are frequent in the first years following a first episode of schizophrenia (FES), being associated with a higher risk of developing a chronic psychotic disorder, and poor clinical and functional outcomes. The identification and intervention over factors associated with relapses in these early phases are timely and relevant. In this study, 119 patients in remission after a FES were closely followed over three years. Participants came from the 2EPS Project, a coordinated, naturalistic, longitudinal study of 15 tertiary centers in Spain. Sociodemographic, clinical, treatment and substance abuse data were analyzed. 49.6% of the participants relapsed during the 3-years follow-up. None of the baseline demographic and clinical characteristics analyzed showed a statistically significant association with relapses. 22% of patients that finished the follow-up without relapsing were not taking any antipsychotic. The group that relapsed presented higher mean antipsychotics doses (381.93 vs. 242.29 mg of chlorpromazine equivalent/day, p = 0.028) and higher rates of antipsychotic polytherapy (28.6% vs. 13%, p < 0.001), benzodiazepines use (30.8% vs. 8.5%, p < 0.001), side effects reports (39.2% vs. 25%, p = 0.022), psychological treatment (51.8% vs. 33.9%, p = 0.03), and cannabis consumption (93.2% vs. 56.7%, p < 0.001). Clozapine use was notably higher in the group that reminded in remission (21.7% vs. 8.2%, p < 0.019). These findings may guide clinicians to detect subgroups of patients with higher risk to present a second episode of psychosis, focusing on measures to ensure an adequate treatment or facilitating cannabis use cessation. This study supports future research to identify relapse prevention strategies for patients in early phases of schizophrenia.
The relationship between psychotic symptoms and global measures of functioning has been widely st... more The relationship between psychotic symptoms and global measures of functioning has been widely studied. No previous study has assessed so far the interplay between specific clinical symptoms and particular areas of functioning in first-episode psychosis (FEP) using network analysis methods. A total of 191 patients with FEP (age 24.45 ± 6.28 years, 64.9% male) participating in an observational and longitudinal study (AGES-CM) comprised the study sample. Functioning problems were assessed with the WHO Disability Assessment Schedule (WHODAS), whereas the Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity. Network analysis were conducted with the aim of analysing the patterns of relationships between the different dimensions of functioning and PANSS symptoms and factors at baseline. According to our results, the most important nodes were "conceptual disorganization", "emotional withdrawal", "lack of spontaneity and flow of conversation", "delusions", "unusual thought content", "dealing with strangers" and "poor rapport". Our findings suggest that these symptoms and functioning dimensions should be prioritized in the clinical assessment and management of patients with FEP. These areas may also become targets of future early intervention strategies, so as to improve quality of life in this population.
We evaluated the effect of combination therapy with zidovudine (AZT) plus zalcitabine (ddC) in hu... more We evaluated the effect of combination therapy with zidovudine (AZT) plus zalcitabine (ddC) in human immunodeficiency virus type 1 (HIV-1)-infected patients who had not previously received antiretroviral treatment ('naive' patients). The immunological and virological parameters evaluated were CD4 cell count, syncytium-inducing (SI) viral phenotype and plasma HIV-1 RNA copies/ml (HIV viral load). A total of 75 patients entered the study, with CD4 cell counts between 200 and 500 cells/mm3. All received zidovudine (200 mg) plus zalcitabine (0.75 mg) three times daily for 24 weeks. Treatment was well tolerated. However, four patients presented with anaemia (haemoglobin < 10.0 g/dl) and one patient had both anaemia and neutropenia (0.8 x 10(9) neutrophils/l). Combination therapy with zidovudine plus zalcitabine resulted in a pronounced improvement of virological and immunological markers. Approximately 25% of patients achieved undetectable plasma HIV RNA levels (< 200 copies/ml) at week 24. At the end of the study (24 weeks) a significant reduction (> 0.5 log) of plasma HIV RNA was observed in approximately 70% of patients and in 50% an even greater decrease (> 1 log) was achieved. The most significant decrease in mean plasma HIV RNA levels was observed at week 4, whereas the highest increase in CD4 cell count was found at week 24. Approximately 80% of patients who showed baseline plasma HIV RNA levels below 20000 copies/ml had less than 5000 copies/ml at week 24. The plasma HIV RNA reduction observed at week 4 was significantly maintained at week 24. Therefore, we can rapidly select those who will not respond to therapy and adjust the treatment after a short interval. Our study supports the idea of early therapy because all patients who reached undetectable levels of plasma HIV RNA at week 24 had at baseline a median plasma HIV RNA load of 2560 copies/ml. In conclusion, zidovudine in combination with zalcitabine was well tolerated in the majority of patients and led to a significant reduction in plasma HIV RNA copies in most of the patients with initial viraemia lower than 20000 copies/ml.
Treatment of human immunodeficiency virus type 1 (HIV-1)-infected patients with combination drug ... more Treatment of human immunodeficiency virus type 1 (HIV-1)-infected patients with combination drug regimens results in a reduction of plasma viral load to levels below the limit of detection. To investigate the genomic fluctuations in HIV-1 populations from long-term responders to antiviral therapies we analyzed the viral sequence evolution of env and pol genes from sequential peripheral blood mononuclear cell (PBMC) DNA samples of three infected patients. Analyses of sequences covering the V3 and flanking env regions obtained from blood samples at the beginning of the therapy and at 14 or 24 months from baseline revealed that HIV-1 quasispecies continue to evolve in the three patients following combination antiretroviral therapy. Minor drug-resistant mutant subpopulations were also searched for and found in one patient. Interestingly, no minor resistant subpopulations were found in the other two patients despite the fact that they showed evidence of ongoing viral replication. Finally, the genetic analysis of the env gene shows a reduction in PBMC env viral population diversity after long-term response to the therapy in all the patients analyzed.
The Journal of Gambling Business and Economics, May 23, 2013
Although most individuals who gamble do so without any adverse consequences, some individuals dev... more Although most individuals who gamble do so without any adverse consequences, some individuals develop a recurrent, maladaptive pattern of gambling behaviour, often called pathological gambling or gambling disorder, that is associated with financial losses, disruption of family and interpersonal relationships, and co-occurring psychiatric disorders. Identifying whether different types of gambling modalities vary in their ability to lead to maladaptive patterns of gambling behaviour is essential to develop public policies that seek to balance access to gambling opportunities with minimizing risk for the potential adverse consequences of gambling behaviour. Until recently, assessing the risk potential of different types of gambling products was nearly impossible. ASTERIG, initially developed in Germany in 2006-2010, is an assessment tool to measure and to evaluate the risk potential of any gambling product based on scores on ten dimensions. In doing so, it also allows a comparison to be drawn between the addictive potential of different gambling products. Furthermore, the tool highlights where the specific risk potential of each specific gambling product lies. This makes it a valuable tool at the legislative, case law, and administrative levels as it allows the risk potential of individual gambling products to be identified and to be compared globally and across 10 different dimensions of risk potential. We note that specific gambling products should always be evaluated rather than product groups (lotteries, slot machines) or providers, as there may be variations among those product groups that impact their risk potential. For example, slot machines may vary on the amount of jackpot, which may influence their risk potential.
We report the integrated proviral LTR sequence variation in four patients on highly active antire... more We report the integrated proviral LTR sequence variation in four patients on highly active antiretroviral therapy (HAART). Integrated proviral fragments of LTR taken from four time points were PCR amplified from PBMCs and 10 to 12 individual clones were sequenced for each time point. Intrasample genetic distances and phylogenetic reconstruction of all LTR sequences demonstrated that 1-2 years of successful HAART did not significantly reduce the genetic repertoire of the integrated reservoir of HIV-1.
Objective. e To test the reliability and validity of the DIGS in Spanish population. Methods. e I... more Objective. e To test the reliability and validity of the DIGS in Spanish population. Methods. e Inter-rater and test-retest reliability of the Spanish version of DIGS was tested in 95 inpatients and outpatients. The resultant diagnoses were compared with diagnoses obtained by the LEAD (Longitudinal Expert All Data) procedure as ''gold standard''. The kappa statistic was used to measure concordance between blind inter-raters and between the diagnoses obtained by LEAD procedure and through the DIGS. Results. e Overall kappa coefficient for inter-rater reliability was 0.956. The kappa value for individual diagnosis varied from major depression ¼ 0.877 to schizophrenia ¼ 1. Test-retest reliability was 0.926. Kappa for all individual target diagnoses ranged from 0.776 (major depression) to 1. Kappa between LEAD procedure and DIGS ranged from 0.704 (major depression) to 0.825 (bipolar I disorder). Conclusion. e Most of the DSM-IV major psychiatric disorders can be assessed with acceptable to excellent reliability with the Spanish version of the DIGS interview. The Spanish version of DIGS showed an acceptable to excellent concurrent validity. Giving the good reliability and validity of Spanish version of DIGS it should be considered to identify psychiatric phenotypes for genetics studies.
Revista de investigación y educación en ciencias de la salud, May 30, 2020
Resumen: El Juego Patológico se define como una conducta de juego recurrente y persistente que de... more Resumen: El Juego Patológico se define como una conducta de juego recurrente y persistente que deteriora todas las áreas de la vida. Está considerado un importante problema de salud pública. El objetivo del trabajo es describir las características sociodemográficas, conducta de juego e impulsividad de una muestra de pacientes que solicitó iniciar tratamiento en la Unidad de Ludopatía del Hospital Universitario Ramón y Cajal. La muestra estuvo compuesta por 19 pacientes (89.5% hombres) con diagnóstico de JP según criterios diagnósticos DSM-5. Los resultados muestran que la media de edad fue de 39.89 años, en su mayoría estaban solteros, tenían estudios secundarios o universitarios y se encontraban en situación laboral activa; la edad media de inicio al juego fue de 24.21 años y la evolución del problema de 5.16 años; la modalidad de juego online estaba presente en el 42.1% de los casos, siendo las apuestas deportivas la principal actividad de juego practicada (42.1%); tienen en su mayoría deudas (78.9%) que ascienden de media a 12263.16€; y puntúan elevado en todas la subescalas de impulsividad. Como conclusión, exponer que, si bien el paciente que solicita tratamiento sigue siendo un hombre soltero y laboralmente activo, cada vez más son más numerosos aquellos que tienen estudios universitarios, que comienzan a jugar a una edad cada vez más temprana y cuya principal actividad de juego ya no son las máquinas tragaperras, sino las apuestas deportivas, que estarían detrás de gran parte de los problemas relacionados con el juego en la actualidad.
Los estudios farmacogenéticos mejoran nuestros conocimientos sobre las consecuencias funcionales ... more Los estudios farmacogenéticos mejoran nuestros conocimientos sobre las consecuencias funcionales de las variantes genéticas, ayudándonos a identificar aquellos pacientes predispuestos a la aparición de determinados efectos secundarios o, por el contrario, ...
The International journal of social psychiatry, 2022
BACKGROUND Traumatic life events (TLEs) are one of the most robust environmental risk factors for... more BACKGROUND Traumatic life events (TLEs) are one of the most robust environmental risk factors for the onset of first-episode psychosis (FEP). AIMS To explore TLEs in FEP patients and healthy controls (HC), to analyze gender differences and to examine whether TLEs were associated with sociodemographic, clinical and psychofunctional variables in all FEP sample and split by age. METHODS Descriptive and cross-sectional study. Three hundred and thirty-five FEP and 253 HC were recruited at 16 Spanish mental health research centers. The Traumatic Experiences in Psychiatric Outpatients Questionnaire was administered. RESULTS We found a higher number of TLEs in FEP than in HC, and the proportion of individuals with three or more TLEs was significantly higher in the FEP group. No differences were found in terms of gender and age. There was no relationship between total number of TLEs and psychotic symptomatology and functional outcomes. CONCLUSIONS The number and cumulative TLEs should be tak...
Relapses are frequent in the first years following a first episode of schizophrenia (FES), being ... more Relapses are frequent in the first years following a first episode of schizophrenia (FES), being associated with a higher risk of developing a chronic psychotic disorder, and poor clinical and functional outcomes. The identification and intervention over factors associated with relapses in these early phases are timely and relevant. In this study, 119 patients in remission after a FES were closely followed over three years. Participants came from the 2EPS Project, a coordinated, naturalistic, longitudinal study of 15 tertiary centers in Spain. Sociodemographic, clinical, treatment and substance abuse data were analyzed. 49.6% of the participants relapsed during the 3-years follow-up. None of the baseline demographic and clinical characteristics analyzed showed a statistically significant association with relapses. 22% of patients that finished the follow-up without relapsing were not taking any antipsychotic. The group that relapsed presented higher mean antipsychotics doses (381.93 vs. 242.29 mg of chlorpromazine equivalent/day, p = 0.028) and higher rates of antipsychotic polytherapy (28.6% vs. 13%, p < 0.001), benzodiazepines use (30.8% vs. 8.5%, p < 0.001), side effects reports (39.2% vs. 25%, p = 0.022), psychological treatment (51.8% vs. 33.9%, p = 0.03), and cannabis consumption (93.2% vs. 56.7%, p < 0.001). Clozapine use was notably higher in the group that reminded in remission (21.7% vs. 8.2%, p < 0.019). These findings may guide clinicians to detect subgroups of patients with higher risk to present a second episode of psychosis, focusing on measures to ensure an adequate treatment or facilitating cannabis use cessation. This study supports future research to identify relapse prevention strategies for patients in early phases of schizophrenia.
The relationship between psychotic symptoms and global measures of functioning has been widely st... more The relationship between psychotic symptoms and global measures of functioning has been widely studied. No previous study has assessed so far the interplay between specific clinical symptoms and particular areas of functioning in first-episode psychosis (FEP) using network analysis methods. A total of 191 patients with FEP (age 24.45 ± 6.28 years, 64.9% male) participating in an observational and longitudinal study (AGES-CM) comprised the study sample. Functioning problems were assessed with the WHO Disability Assessment Schedule (WHODAS), whereas the Positive and Negative Syndrome Scale (PANSS) was used to assess symptom severity. Network analysis were conducted with the aim of analysing the patterns of relationships between the different dimensions of functioning and PANSS symptoms and factors at baseline. According to our results, the most important nodes were "conceptual disorganization", "emotional withdrawal", "lack of spontaneity and flow of conversation", "delusions", "unusual thought content", "dealing with strangers" and "poor rapport". Our findings suggest that these symptoms and functioning dimensions should be prioritized in the clinical assessment and management of patients with FEP. These areas may also become targets of future early intervention strategies, so as to improve quality of life in this population.
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Papers by Angela Ibáñez