A 3-Year Retrospective Study of the Impact of Integrating an Addiction Liaison Team into an Outpatient Alcoholism Treatment Programme.

BACKGROUND: The number of inpatients with alcohol and other substance-related problems (ASRP) in the general hospital population at any time is vast. To meet the needs of those patients, most hospitals have an Addiction Liaison Team (ALT) that diagnoses and initiates the treatment of the addictive disorder. In our hospital, this team is part of a more extensive and intensive Outpatient Alcoholism Treatment Programme that facilitates the continuity of care. AIM: the main goal of this study is to evaluate the performance and effectiveness of our inpatient ALT. METHODOLOGY: we carried out an observational cohort study of patients with ASRP admitted to the hospital from 2015 to 2017. We evaluated the performance and effectiveness of our ALT: referrals to the programme, inpatients mortality, readmissions to hospital, hospital length of stay (LOS) and medical or surgical treatment adherence. RESULTS: out of 133,181 admissions, 17,387 (13.14%) were positive for ASRP, and 615 (3.54%) were referred to the ALT. Referred patients had less in-hospital mortality, shorter LOS and lower risk of readmissions during the first year of follow-up. Subjects treated in the programme had better therapeutic adherence. CONCLUSIONS: integrating the ALT into an outpatient programme facilitates an earlier detection and initiation of treatment during the hospital stay and the continuity of care. Alcohol misuse conditions affect the patient's prognosis and health outcomes, so appropriate care is needed. Inclusion in the programme was associated with less risk of hospital mortality, fewer readmissions and a lower LOS.

Molecular Changes Associated with Suicide.

Suicide is a serious global public health problem, with a worrying recent increase in suicide rates in both adolescent and adult populations. However, it is essential to recognize that suicide is preventable. A myriad of factors contributes to an individual's vulnerability to suicide. These factors include various potential causes, from psychiatric disorders to genetic and epigenetic alterations. These changes can induce dysfunctions in crucial systems such as the serotonergic, cannabinoid, and hypothalamic-pituitary-adrenal axes. In addition, early life experiences of abuse can profoundly impact an individual's ability to cope with stress, ultimately leading to changes in the inflammatory system, which is a significant risk factor for suicidal behavior. Thus, it is clear that suicidal behavior may result from a confluence of multiple factors. This review examines the primary risk factors associated with suicidal behavior, including psychiatric disorders, early life adversities, and epigenetic modifications. Our goal is to elucidate the molecular changes at the genetic, epigenetic, and molecular levels in the brains of individuals who have taken their own lives and in the plasma and peripheral mononuclear cells of suicide attempters and how these changes may serve as predisposing factors for suicidal tendencies.

Psychological recovery stages of alcohol dependent patients after an intensive outpatient treatment: A 4-year follow-up study. / Fases de la recuperación psicológica en pacientes dependientes del alcohol tras un tratamiento intensivo: Un seguimiento de 4 años.

The aim of this work is to determine if relapses can hinder the sequence of psychological recovery and to rebuild this sequence in patients with severe alcohol dependence that seek treatment. The sample was comprised of 159 patients seeking an intensive outpatient treatment of two years duration and who were subject to follow-up during four years after discharge. Patients were grouped according to the presence of relapse during follow-up, resulting in abstainers (n = 80) and relapsers (n = 79). Assessments were carried out in the following periods: baseline, at discharge, and at the second- and fourth-year follow-ups. The measurement variables were avoidance behavior, anxiety, depression, impulsivity and meaning in life (MiL). A control group (n = 74) was evaluated at the same periods as the patients. Results indicate a slower recovery in relapsers in comparison to abstainers in all psychological dimensions and periods assessed. At the second-year follow-up, the abstainers achieved similar scores in depression as the control participants, in addition to higher scores in Meaning in Life at the end of treatment. In patients with severe alcohol dependence, our data supports a sequence of recovery that could continue beyond the four years of follow-up after treatment. This sequence would begin with the avoidance of risk situations and continue with the rest of dimensions (anxiety, depression, impulsivity).

El objetivo de este trabajo es comprobar si las recaídas dificultan la secuencia de la recuperación psicológica y reconstruir la secuencia de la recuperación de pacientes graves que solicitan tratamiento. Los participantes fueron 159 pacientes tratados durante dos años en un programa ambulatorio intensivo y tras ser dados de alta fueron seguidos durante cuatro años. En función de la presencia o no de recaída durante el seguimiento se configuraron dos grupos, el de abstinentes (n = 80) y el de pacientes que recaen (n = 79). Las evaluaciones se realizaron: basal, al alta del tratamiento, al 2.º y 4.º año de seguimiento. Las variables fueron: conductas de evitación, ansiedad, depresión, impulsividad y sentido de la vida. Se incluyó un grupo de control (n = 74) que fue evaluado con la misma cadencia que los pacientes. Los resultados indican una recuperación más lenta en el grupo con recaídas frente a los abstinentes, en todas las dimensiones psicológicas y los períodos estudiados. A los dos años de seguimiento, los pacientes abstinentes obtuvieron puntuaciones en depresión similares a los controles, además de puntuaciones superiores en sentido de la vida (MiL) a partir del final del tratamiento. Al menos en pacientes con dependencia grave del alcohol, nuestros resultados apoyan una secuencia de recuperación que podría continuar más allá de los cuatro años de seguimiento. Se inicia con la evitación de situaciones de riesgo y continúa con el resto de las dimensiones (ansiedad, depresión, impulsividad).

Molecular Alterations of the Endocannabinoid System in Psychiatric Disorders.

The therapeutic benefits of the current medications for patients with psychiatric disorders contrast with a great variety of adverse effects. The endocannabinoid system (ECS) components have gained high interest as potential new targets for treating psychiatry diseases because of their neuromodulator role, which is essential to understanding the regulation of many brain functions. This article reviewed the molecular alterations in ECS occurring in different psychiatric conditions. The methods used to identify alterations in the ECS were also described. We used a translational approach. The animal models reproducing some behavioral and/or neurochemical aspects of psychiatric disorders and the molecular alterations in clinical studies in post-mortem brain tissue or peripheral tissues were analyzed. This article reviewed the most relevant ECS changes in prevalent psychiatric diseases such as mood disorders, schizophrenia, autism, attentional deficit, eating disorders (ED), and addiction. The review concludes that clinical research studies are urgently needed for two different purposes: (1) To identify alterations of the ECS components potentially useful as new biomarkers relating to a specific disease or condition, and (2) to design new therapeutic targets based on the specific alterations found to improve the pharmacological treatment in psychiatry.

Effects of the lockdown due to the COVID-19 pandemic on alcohol consumption in patients under treatment in an alcohol relapse prevention programme. / Efectos del confinamiento en el hogar debido a la pandemia por COVID-19 en el consumo en pacientes en tratamiento en un programa de deshabituación de alcohol.

During the COVID-19 pandemic, several exceptional measures were put in place in order to avoid virus propagation, such as lockdown and the discontinuation of usual health care assistance services. It was considered that these changes might be associated with an increase in alcohol consumption and a higher risk of relapse for patients under treatment. The aim of this study was to assess changes in alcohol consumption during the lockdown period (between March and May, 2020) in patients following treatment under the Alcohol Use Disorders Programme at the "Hospital 12 de Octubre" in Madrid. A total of 311 patients were assessed through interviews carried out by telephone in accordance with usual clinical practice during that period. 76% of the total number of patients did not experience changes in their alcohol consumption, 9.2% stopped drinking and some experienced severe withdrawal syndrome, while 7.5% relapsed. The risk factors found for worsening the prognosis of the patients were: being female, drinking alcohol alone or at home, binge drinking, concomitant substance misuse and failure to attend therapy groups or self-help groups online during the lockdown. 31.6% of the sample described psychopathological symptoms due to the lockdown, especially those who already had psychiatric comorbidities. For this reason, we can conclude that during the lockdown as a result of the pandemic, most of our alcohol dependent patients did not modify their drinking patterns, but specific factors enabled us to identify a more vulnerable subgroup.

Durante la pandemia producida por la infección por el Covid-19 se produjeron una serie de cambios sociosanitarios excepcionales para evitar su propagación como el confinamiento en el hogar y la supresión de los servicios asistenciales sanitarios habituales. Se consideró que estos cambios podrían implicar un incremento en el consumo de alcohol y un mayor riesgo de recaídas para los pacientes en tratamiento. El objetivo de este estudio fue valorar los cambios en el consumo durante el período de confinamiento (marzo a mayo de 2020) en los pacientes en tratamiento en el programa de alcohol del Hospital Doce de Octubre de Madrid. Fueron valorados 311 pacientes mediante entrevista telefónica dentro de la práctica clínica habitual durante ese período. Un 76 % de los pacientes no presentaron cambios en su situación de consumo, un 9,2% de estos cesaron en el consumo, algunos de ellos con cuadros de abstinencia graves, y un 7,5% recayeron. El sexo femenino, el consumo en solitario o en el hogar, en atracón, o el de otras drogas de forma concomitante y el no estar en terapia grupal o no asistir a grupos de las asociaciones de ayuda mutua por videoconferencia durante el confinamiento fueron factores predictores de mal pronóstico. Un 31,6% presentó alteraciones psicopatológicas debidas al confinamiento, sobre todo, aquellos pacientes con comorbilidad psiquiátrica. Por lo tanto, en situaciones similares a esta, la mayoría de los pacientes en tratamiento no modifican el patrón de consumo, pero, ciertas características identifican un subgrupo de sujetos más vulnerables.

Antidepressant effect r TMS during pregnancy in a case of Major Depression Resistant to Pharmacological Treatment.

Major depressive disorder (MDD) is a common complication of pregnancy and the postpartum period. Approximately 5% of women who have MDD during pregnancy or the postpartum period meet criteria for resistant depression, associated with increased morbidity in both the newborn and the pregnant woman. Currently we have different therapeutic options for the treatment of MDD during pregnancy, although in cases of resistance during that period the treatment criteria are not that well established.

Cannabis-induced psychosis: clinical characteristics and its differentiation from schizophrenia with and without cannabis use. / Psicosis inducida por cannabis: características clínicas y su diferenciación con la esquizofrenia con y sin consumo de cannabis asociado.

Cannabis use is considered an established risk factor for psychosis development. Differentiating between cannabis-induced disorders and schizophrenia is useful for prognostic and therapeutic purposes. Three inpatients groups were differentiated: cannabis-induced psychosis (CIP) (n = 69; mean age = 27.4, SD = 6.5; 82.6% males), schizophrenia with cannabis abuse or dependence (SZ + CB) (n = 57; mean age = 31.9, SD = 10.1; 94.7% males) and schizophrenia without cannabis abuse or dependence (SZ) (n = 181; mean age = 41.8, SD = 13.3; 54.1% males). The Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV) scale was used to differentiate induced psychosis. The CIP group presented lower mean scores on the negative PANSS subscale (M = 12.9, SD = 5.9; F = 32.24, p < 0.001), fewer auditory hallucinations (60.3%; X² = 6.60, p = 0.037) and greater presence of mania (26.1% vs. 12.3%; X² = 32.58, p < 0.001) than the SZ + CB group. There were few clinical differences between patients with schizophrenia, regardless of previous cannabis use. The age of first admission due to psychosis was lower in both psychotic inpatients groups with cannabis use (M = 26.1, SD = 6.4 in CIP and M = 25.3, SD = 6.2 in SZ + CB; X² = 20.02, p < 0,001). A clinical pattern characteristic of cannabis-induced psychosis was not observed, but the precipitating role of cannabis in the appearance of psychotic symptoms was demonstrated, given the lower age of first admission due to psychosis in cannabis user groups.

El consumo de cannabis se considera un factor de riesgo establecido para el desarrollo de psicosis. Diferenciar los trastornos inducidos por cannabis de la esquizofrenia resulta útil desde el punto de vista pronóstico y terapéutico. Se diferenciaron tres grupos de pacientes hospitalizados: psicosis inducida por cannabis (PIC) (n = 69; Media de edad = 27,4, DE = 6,5; 82,6 % varones), esquizofrenia con abuso o dependencia de cannabis (EZ + CB) (n = 57; Media de edad = 31,9, DE = 10,1; 94,7% varones) y esquizofrenia sin abuso o dependencia de cannabis (EZ) (n = 181; Media de edad = 41,8, DE = 13,3; 54,1% varones). Se utilizó la escala Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV) para la diferenciación de cuadros inducidos. El grupo PIC presentó puntaciones inferiores en la subescala PANSS negativa (M = 12,9, DE = 5,9; F = 32,24; p < 0,001), menos alucinaciones auditivas (60,3%; X²  = 6,60; p = 0,037) y mayor presencia de manía (26,1% vs. 12,3%; X² = 32,58; p < 0,001) en comparación con el grupo EZ + CB. Hubo pocas diferencias clínicas entre los pacientes con esquizofrenia, independientemente del consumo de cannabis. La edad del primer ingreso por psicosis fue menor en ambos grupos de psicóticos consumidores (M = 26,1, DE = 6,4 en PIC y M = 25,3, DE = 6,2 en EZ + CB; X² = 20,02; p < 0,001). No se observó un patrón clínico característico de las psicosis inducidas por cannabis, aunque sí se demostró el papel precipitante del cannabis en la aparición de psicosis, dada la menor edad de ingreso en los consumidores.

Allele-Specific Silencing Ameliorates Restrictive Cardiomyopathy Attributable to a Human Myosin Regulatory Light Chain Mutation.

BACKGROUND: Restrictive cardiomyopathy is a rare heart disease associated with mutations in sarcomeric genes and with phenotypic overlap with hypertrophic cardiomyopathy. There is no approved therapy directed at the underlying cause. Here, we explore the potential of an interfering RNA (RNAi) therapeutic for a human sarcomeric mutation in MYL2 causative of restrictive cardiomyopathy in a mouse model. METHODS: A short hairpin RNA (M7.8L) was selected from a pool for specificity and efficacy. Two groups of myosin regulatory light chain N47K transgenic mice were injected with M7.8L packaged in adeno-associated virus 9 at 3 days of age and 60 days of age. Mice were subjected to treadmill exercise and echocardiography after treatment to determine maximal oxygen uptake and left ventricular mass. At the end of treatment, heart, lung, liver, and kidney tissue was harvested to determine viral tropism and for transcriptomic and proteomic analysis. Cardiomyocytes were isolated for single-cell studies. RESULTS: A one-time injection of AAV9-M7.8L RNAi in 3-day-old humanized regulatory light chain mutant transgenic mice silenced the mutated allele (RLC-47K) with minimal effects on the normal allele (RLC-47N) assayed at 16 weeks postinjection. AAV9-M7.8L RNAi suppressed the expression of hypertrophic biomarkers, reduced heart weight, and attenuated a pathological increase in left ventricular mass. Single adult cardiac myocytes from mice treated with AAV9-M7.8L showed partial restoration of contraction, relaxation, and calcium kinetics. In addition, cardiac stress protein biomarkers, such as calmodulin-dependent protein kinase II and the transcription activator Brg1 were reduced, suggesting recovery toward a healthy myocardium. Transcriptome analyses further revealed no significant changes of argonaute (AGO1, AGO2) and endoribonuclease dicer (DICER1) transcripts, and endogenous microRNAs were preserved, suggesting that the RNAi pathway was not saturated. CONCLUSIONS: Our results show the feasibility, efficacy, and safety of RNAi therapeutics directed towards human restrictive cardiomyopathy. This is a promising step toward targeted therapy for a prevalent human disease.

Resting-state connectivity and network parameter analysis in alcohol-dependent males. A simultaneous EEG-MEG study.

There is supporting evidence of alcohol negative effects on the brain: neuroimaging and psychophysiological studies finding anatomical and functional connectivity (FC) changes associated with the dependence process. Thus, the aim of this work was to evaluate brain FC and network characteristics of alcohol-dependent individuals in resting state. For this study, we included males diagnosed with alcohol dependence (N = 25) and a group of healthy individuals (N = 23). Simultaneous EEG-MEG (electroencephalographic and magnetoencephalographic) activity was recorded in 5 min of eyes-closed resting state. EEG-MEG activity was preprocessed and FC was computed through the leakage-corrected version of phase locking value (ciPLV). Additionally, local (degree, efficiency, clustering) and global (efficiency, characteristic path length) network parameters were computed. Connectivity analysis showed an increase in phase-lagged synchronization, mainly between frontal and frontotemporal regions, in high beta band, and a decrease in interhemispheric gamma, for alcohol-dependent individuals. Network analysis revealed intergroup differences at the local level for high beta, indicating higher degree, clustering, and efficiency, mostly at frontal nodes, together with a decrease in these measures at more posterior sites for patients' group. The hyper-synchronization in beta, next to the hypo-synchronization in gamma, could indicate an alteration in communication between hemispheres, but also a possible functional compensation mechanism in neural circuits. This could be also supported by network characteristic data, where local alterations in communication are observed.

[Effects of including mutual aid groups in the adherence of a continuing care programme of alcohol dependent patients carried out in a Primary Care setting]. / Efectos de la integración de grupos de ayuda mutua sobre la adherencia al programa de continuidad en el cuidado a pacientes con dependencia del alcohol realizado en Atención Primaria.

OBJECTIVES: To demonstrate the effects of including mutual aid associations into a continuing care programme for patients with alcohol dependence carried out by Primary Care teams. SITE: Primary Care Teams belonging to the attendance area of the University Hospital 12 de Octubre at Madrid. PARTICIPANTS: 207 participants with alcohol dependence treated in an intensive hospital outpatient-setting programme were included in a continuing care programme carried out by a Primary Care team for a four-year period. INTERVENTIONS: Patients were randomised into two intervention modalities. The first group was followed up while receiving a treatment modality known as «monitoring recovery¼ (Group A, n = 97). The other group, in addition to the above-mentioned intervention, attended to a mutual aid association included in the Federation of Alcoholics of the Community of Madrid (FACOMA) in which the programme «Help Yourself-Help Us¼ was carried out (Group B, n = 112). MAIN OUTCOMES: Dropout rates on the sessions designed to monitor their recovery from their alcohol dependence and other comorbid medical conditions. RESULTS: Patients in Group B reached higher rates of therapeutic adherence to the programme (47.9% vs. 14.7%, p < 0.01), as well as for the comorbid medical issues when compared to Group A. CONCLUSIONS: Including mutual aid associations that carried out the «Help yourself-Help Us¼ programme for a four-year period improves outcomes related to therapeutic adherence in patients with alcohol dependence attending Primary Care teams.

DSM-5 in patients seeking their first treatment for alcohol use disorder. Sex differences in the multicenter CohRTA study. / DSM-5 en pacientes que solicitan el primer tratamiento del trastorno por uso de alcohol. Diferencias de sexo en el estudio multicéntrico CohRTA.

OBJECTIVE: We aimed to analyze sex differences in the DSM-5 criteria among patients admitted to  their first treatment of alcohol use disorder (AUD). METHODS: Assessment of AUD was carried out using DSM-5 diagnostic criteria in a multicenter study (CohRTA) within the Spanish Network on Addictive Disorders. Further, baseline questionnaires including socio-demographics, family history, lifetime alcohol consumption and other substance use, as well as clinical and laboratory parameters were obtained during admission. RESULTS: 313 patients (74.8%M) were eligible; mean age at first AUD treatment was 48.8 years (standard deviation (SD): 9.9 years). Age at onset of alcohol use was 15.9 years (SD: 3.3 years) and age at starting regular alcohol consumption was 25.6 years (SD: 9.6 years). Almost 69.3% of patients were tobacco smokers and 61% had family history of AUD. Regarding other substance use, 7.7% were current cocaine users and 18.2% were cannabis users. Women started regular alcohol consumption later than men (p<,001) and used benzodiazepines more frequently (p=.013). According to DSM-5, 89.5% of cases had severe AUD (≥6 criteria). In the adjusted analysis (logistic regression), men were more likely to neglect major rules (OR=1.92, 95%CI: 1.06-3.48) and to have hazardous alcohol use (OR=3.00, 95%CI: 1.65-5.46). DISCUSSION: DSM-5 detects sex differences in patients seeking their first AUD treatment. Social impairment and risky alcohol use are significantly more frequent in men.

Objetivo: Analizar las diferencias de sexo en los criterios diagnósticos del DSM-5 de los pacientes que solicitan un tratamiento para el trastorno por uso de alcohol (TUA) por primera vez. Métodos: Pacientes incluidos entre enero 2014 y marzo 2016 en el estudio multicéntrico CohRTA de la Red de Trastornos Adictivos. El diagnóstico del TUA se realizó mediante el DSM-5. Además, se recogieron datos sociodemográficos, sobre el consumo de alcohol y otras sustancias, variables clínicas y una analítica general. Resultados: se incluyeron 313 pacientes (74,8% hombres); la edad al inicio del primer tratamiento fue de 48,8 años (desviación estándar (DE): 9,9 años), la edad al inicio del consumo de alcohol de 15,9 años (DE: 3,3 años) y la de inicio del consumo regular de 25,6 años (DE: 9,6 años). Un 69,3% de los pacientes eran fumadores y un 61% tenían antecedentes familiares de TUA. Un 7,7% eran consumidores de cocaína y un 18,2% de cannabis. Las mujeres iniciaron el consumo regular de alcohol más tarde que los hombres (p<,001) y usaban benzodiacepinas con mayor frecuencia (p=,013). Según el DSM-5, el 89,5% de los pacientes presentaban un TUA grave (≥6 criterios). En el análisis ajustado (regresión logística), los hombres tenían mayor probabilidad de presentar el criterio diagnóstico relacionado con el incumplimiento de los deberes fundamentales en el trabajo o en el hogar (OR=1,92, IC95%: 1,06-3,48) y el criterio diagnóstico de consumir alcohol en situaciones de riesgo físico (OR=3,00, IC95%: 1,65-5,46). Discusión: El DSM-5 detecta diferencias de sexo en pacientes que solicitan el primer tratamiento del TUA. El deterioro social y el consumo de alcohol de riesgo son significativamente más frecuentes en hombres.

Alcohol-induced cognitive deficits are associated with decreased circulating levels of the neurotrophin BDNF in humans and rats.

Chronic alcohol consumption is associated with neurocognitive and memory deficits, dramatically affecting plasticity and connectivity, with maximal expression as dementia. Neurotrophic factors may contribute to alcohol-related cognitive decline. For further investigation, a cross-sectional study was performed to evaluate the association of cognitive impairment, by using frontal assessment battery, and memory loss, using memory failures everyday, with the circulating levels of the neurotrophin brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3) in abstinent subjects with alcohol use disorders (AUDs, N = 58, average of 17.9 years of problematic use and 4.3 months of abstinence) compared with healthy control subjects (N = 22). This association was also explored in a pre-clinical model of adolescent rats chronically exposed to alcohol up to adulthood (~77 days old) in a three-bottle free-choice (5-10-20 percent), repeated abstinence and relapse paradigm. AUD subjects had low educational level and cognitive impairment associated with teenage consumption and lower circulating levels of BDNF and NT-3. Only BDNF concentration showed a positive correlation with frontal assessment battery in AUD patients. In the ethanol-exposed rats, the plasma levels of BDNF and NT-3 were also decreased, and a negative correlation between hippocampal Bdnf mRNA levels and recognition memory was found. The ethanol-exposed rat hippocampus showed a decrease in the mRNA levels of neurotrophic (Bdnf and Ntf-3) and neurogenic (Mki67, Sox2, Dcx, Ncam1 and Calb1) factors, associated to a deactivation of the neurogenic regulator mitogen-activated protein kinase extracellular signal-regulated kinase. Results suggest a relevant role of BDNF/extracellular signal-regulated kinase 2 signaling in alcohol-induced cognitive impairment and suggest that early alcohol exposure-derived effects on cognition are associated with neurotrophin signaling deficits.

[Drug using risks screening in primary care patients using the ASSIST test: Cross sectional study]. / Cribado de riesgos derivados del consumo de drogas utilizando la herramienta ASSIST (Alcohol, smoking and substances involvement screening test) en pacientes de atención primaria: estudio transversal.

OBJECTIVE: The aim of this study is to estimate risky-drug use patterns of consumption of primary care patients. DESIGN: Multicentric descriptive cross-sectional study. SETTING: five primary health care centers of the South of Madrid. PARTICIPANTS: all patients between 16-100 year-old consulting with their family physician. MEASUREMENTS: Spanish-validated World Health Organization ASSIST test was use to screen risky drug use in primary care. Total points scored at the test were obtained. RESULTS: A sum of 441 screening test were collected. Mean age was 51,3 years and 51.6% of patients presented a moderate-severe risky drug use out of the nine drugs tested. The more frequent drug use screened were tobacco (41.7%) followed by alcohol (15.4%), hypnotics (13.7%) and cannabis (5.7%). Differences were found between genders in the patterns: men had higher risky drug uses compared to women regarding alcohol and cannabis. Women had higher sedatives/hypnotics consumption prevalence. A 16% of patients presented with polyconsumption drug use patterns. CONCLUSIONS: There is risk derived from drug misuse in primary care for tobacco, alcohol, hypnotics and cannabis as detected by the ASSIST test. There is a higher rate of hypnotics than expected.

Complexity analysis of spontaneous brain activity in mood disorders: A magnetoencephalography study of bipolar disorder and major depression.

BACKGROUND AND PURPOSE: The lack of a biomarker for Bipolar Disorder (BD) causes problems in the differential diagnosis with other mood disorders such as major depression (MD), and misdiagnosis frequently occurs. Bearing this in mind, we investigated non-linear magnetoencephalography (MEG) patterns in BD and MD. METHODS: Lempel-Ziv Complexity (LZC) was used to evaluate the resting-state MEG activity in a cross-sectional sample of 60 subjects, including 20 patients with MD, 16 patients with BD type-I, and 24 control (CON) subjects. Particular attention was paid to the role of age. The results were aggregated by scalp region. RESULTS: Overall, MD patients showed significantly higher LZC scores than BD patients and CONs. Linear regression analyses demonstrated distinct tendencies of complexity progression as a function of age, with BD patients showing a divergent tendency as compared with MD and CON groups. Logistic regressions confirmed such distinct relationship with age, which allowed the classification of diagnostic groups. CONCLUSIONS: The patterns of neural complexity in BD and MD showed not only quantitative differences in their non-linear MEG characteristics but also divergent trajectories of progression as a function of age. Moreover, neural complexity patterns in BD patients resembled those previously observed in schizophrenia, thus supporting preceding evidence of common neuropathological processes.

Inclusion of Alcoholic Associations Into a Public Treatment Programme for Alcoholism Improves Outcomes During the Treatment and Continuing Care Period: A 6-Year Experience.

AIMS: To investigate whether inclusion of self-help groups into the hospital treatment programme improves the prognosis of alcohol dependence through the treatment period; and to examine therapeutic adherence and prognosis during continuing care. METHOD: Patients attending the treatment programme at the 'Hospital 12 de Octubre' were randomized into two groups. In Group A (n = 123), patients received the usual treatment included in our programme, whereas in Group B (n = 126), patients also attended self-help groups. Patients were assessed with psychological scales at baseline, at the end of the treatment period and after completing the continuing care visits. Data were collected over a total of 6 years. RESULTS: During the treatment period, patients in Group B accumulated more months of abstinence and dropped out less. During continuing care, patients in Group B accumulated more months of abstinence and therapeutic adherence was higher. Variables that were associated with these results during the continuing care period were: visits to the GP, scores on anxiety, impulsivity and meaning of life scales, and belonging to the group that attended the alcoholic associations. CONCLUSIONS: Mutual help groups incorporated into a public treatment programme appear to improve outcomes during treatment and on into continuing care. This experience supports cooperation between public health centres and alcoholic associations in treating alcoholism. SHORT SUMMARY: Including alcoholic associations into the public treatment programme for alcoholism of the 'Hospital 12 de Octubre' in Madrid was shown to be associated with better outcomes in terms of months of accumulated abstinence, dropout rates and therapeutic adherence, during the treatment and continuing care periods.

Patients with alcohol use disorder: initial results from a prospective multicenter registry in the Spanish Network on Addiction Disorders. CohRTA Study. / Pacientes con trastorno por uso de alcohol: resultados iniciales de un registro multicéntrico en la Red de Trastornos Adictivos-RTA. Estudio CohRTA.

The Alcohol Program of the Spanish Network on Addictive Disorders-RTA requires a longitudinal study to address different research questions related to alcoholism. The cohort study (CohRTA) focuses on patients seeking treatment for alcohol use disorder, as a multicentre, collaborative research project aimed to improve secondary prevention and early diagnosis of pathological processes associated with the disorder. Methods: multicentre cohort study in adults (>18 years) seeking their first treatment of the disorder. Patients sign an informed consent and data is collected in an online platform specifically designed for the study; patients are also requested to provide biological samples that are stored in a biobank. Baseline and prospective, socio-demographic, epidemiological, clinical and treatment data are collected. Currently there are 10 participating centres that expect to recruit more than 1,000 patients. Results: As of December 2015, 344 patients (77% men) were included. Median age at admission was 50 years (IQR: 43-55 years). Median age at the start of alcohol consumption was 15 years (IQR: 14-18 years) and 61% of cases reported antecedents of alcohol use disorder in the family. During the 30 days prior to admission, alcohol consumption amounted to 12.5 SDU/day (IQR: 7.1-20 SDU/day), 72% of the patients were tobacco smokers and 30% currently used cocaine. Organising an open cohort of patients with alcohol use disorder may be crucial to better understand the clinical consequences of alcoholism in Spain. This cohort may potentiate quantitative and qualitative research within the Spanish Network on Addictive Disorders-RTA/RETICS. Having a well-established, representative cohort of patients will increase translational research on consequences of alcoholism in our country.

El Programa Alcohol de la Red de Trastornos Adictivos (RTA) requiere de un estudio clínico longitudinal para dar respuesta a preguntas de investigación en el trastorno por uso de alcohol. El proyecto CohRTA es un estudio multicéntrico de investigación cooperativa que se pone en marcha para mejorar la prevención secundaria y el diagnóstico precoz de los procesos patológicos asociados al trastorno por uso de alcohol. Método: estudio observacional en cohorte multicéntrica de pacientes mayores de 18 años que solicitan tratamiento del trastorno por primera vez y autorizan su participación. La información clínica se recoge en una plataforma online diseñada para el estudio y puede ir acompañada de una muestra biológica que se deposita en un biobanco. Se recogen datos basales y prospectivos, sociodemográficos, epidemiológicos, clínicos y de tratamiento. A diciembre de 2015 son 10 los centros proveedores de pacientes y se espera reclutar más de 1.000 pacientes en los próximos años. Resultados: se dispone de 344 pacientes (77% hombres) que cumplen los criterios de inclusión en el estudio y con una edad de 50 años (RIQ: 43-55 años). La edad de inicio de consumo de alcohol fue de 15 años (RIQ: 14-18 años) y un 61% tenían antecedente familiar de trastorno por uso de alcohol. Durante los 30 días previos al inicio del tratamiento los pacientes bebían 12.5 UBE/día (RIQ: 7.1-20 UBE/día), el 72% fumaba tabaco y el 30% consumía cocaína. Conclusiones: Disponer de una cohorte abierta y multicéntrica de pacientes con trastorno por uso de alcohol será útil para analizar las consecuencias del abuso de alcohol, potenciar la investigación traslacional y añadir valor a la investigación clínica y básica del Programa Alcohol dentro de RTA/RETICS. Con una cohorte bien establecida y representativa se espera aumentar la cantidad y calidad científica en relación a las complicaciones del trastorno por uso de alcohol y sus consecuencias clínicas y sociales en España.

A Bibliometric Analysis of Scientific Production on Second-Generation Anti-Psychotic Drugs in Malaysia.

OBJECTIVE: We carried out a bibliometric study on the scientific papers related to second-generation antipsychotic drugs (SGAs) in Malaysia. METHODS: With the SCOPUS database, we selected those documents made in Malaysia whose title included descriptors related to SGAs. We applied bibliometric indicators of production and dispersion, as Price's law and Bradford's law, respectively. We also calculated the participation index of the different countries. The bibliometric data were also been correlated with some social and health data from Malaysia (total per capita expenditure on health and gross domestic expenditure on R&D). RESULTS: We found 105 original documents published between 2004 and 2016. Our results fulfilled Price's law, with scientific production on SGAs showing exponential growth (r = 0.401, vs. r = 0.260 after linear adjustment). The drugs most studied are olanzapine (9 documents), clozapine (7), and risperidone (7). Division into Bradford zones yields a nucleus occupied by the Medical Journal of Malaysia, Singapore Medical Journal, Australian and New Zealand Journal of Psychiatry, and Pharmacogenomics. Totally, 63 different journals were used, but only one in the top four journals had an impact factor being greater than 3. CONCLUSION: The publications on SGAs in Malaysia have undergone exponential growth, without evidence a saturation point.

In Vivo Post-Cardiac Arrest Myocardial Dysfunction Is Supported by Ca2+/Calmodulin-Dependent Protein Kinase II-Mediated Calcium Long-Term Potentiation and Mitigated by Alda-1, an Agonist of Aldehyde Dehydrogenase Type 2.

BACKGROUND: Survival after sudden cardiac arrest is limited by postarrest myocardial dysfunction, but understanding of this phenomenon is constrained by a lack of data from a physiological model of disease. In this study, we established an in vivo model of cardiac arrest and resuscitation, characterized the biology of the associated myocardial dysfunction, and tested novel therapeutic strategies. METHODS: We developed rodent models of in vivo postarrest myocardial dysfunction using extracorporeal membrane oxygenation resuscitation followed by invasive hemodynamics measurement. In postarrest isolated cardiomyocytes, we assessed mechanical load and Ca(2) (+)-induced Ca(2+) release (CICR) simultaneously using the microcarbon fiber technique and observed reduced function and myofilament calcium sensitivity. We used a novel fiberoptic catheter imaging system and a genetically encoded calcium sensor, GCaMP6f, to image CICR in vivo. RESULTS: We found potentiation of CICR in isolated cells from this extracorporeal membrane oxygenation model and in cells isolated from an ischemia/reperfusion Langendorff model perfused with oxygenated blood from an arrested animal but not when reperfused in saline. We established that CICR potentiation begins in vivo. The augmented CICR observed after arrest was mediated by the activation of Ca(2+)/calmodulin-dependent protein kinase II (CaMKII). Increased phosphorylation of CaMKII, phospholamban, and ryanodine receptor 2 was detected in the postarrest period. Exogenous adrenergic activation in vivo recapitulated Ca(2+) potentiation but was associated with lesser CaMKII activation. Because oxidative stress and aldehydic adduct formation were high after arrest, we tested a small-molecule activator of aldehyde dehydrogenase type 2, Alda-1, which reduced oxidative stress, restored calcium and CaMKII homeostasis, and improved cardiac function and postarrest outcome in vivo. CONCLUSIONS: Cardiac arrest and reperfusion lead to CaMKII activation and calcium long-term potentiation, which support cardiomyocyte contractility in the face of impaired postarrest myofilament calcium sensitivity. Alda-1 mitigates these effects, normalizes calcium cycling, and improves outcome.

The Modulation of the Startle Reflex as Predictor of Alcohol Use Disorders in a Sample of Heavy Drinkers: A 4-Year Follow-Up Study.

BACKGROUND: Previous studies demonstrated that patients with alcohol use disorders (AUDs) show altered startle reflex responses to alcohol-related stimuli. However, there is little information about the role of these altered responses in the development of AUDs. This study examined the startle reflex response to different visual stimuli and the role of these patterns in the development of AUDs in a 4-year follow-up. METHODS: Two hundred and thirty-nine (nondependent) heavy-drinking participants were selected. In the baseline period, the startle reflex responses to alcohol-related, aversive, appetitive, and neutral pictures were assessed. Startle reflex responses to these pictures were used as predictive variables. Status drinking (alcohol dependence and nondependence) assessed at 4-year follow-up was used as outcome measure. RESULTS: At the 4-year follow-up assessment, 46% of participants fulfilled DSM-IV alcohol abuse or dependence criteria. Alcohol dependence status was predicted by an attenuated startle reflex response to alcohol-related and aversive pictures. CONCLUSIONS: This study revealed that an attenuated modulation of startle reflex response to alcohol-related and aversive stimuli could be used as a clinical marker to predict the development of AUDs in participants with previous alcohol consumption.