Literature review to identify standardized scales for assessing adult suicide risk in the primary health care setting. / Revisión de literatura para identificar escalas estandarizadas de evaluación del riesgo suicida en adultos usuarios de atención primaria de salud.

According to the World Health Organization, suicide has become a public health problem of global dimensions. Forty-five percent of suicide fatalities had consulted with a primary care doctor in the month preceding the event, but no suicide risk assessment had been conducted. Although suicide is an avoidable event, there is no standardized scale for assessment of suicide risk in the primary health care setting, where mental health care competencies vary and decisions are often guided by clinical judgment. A search and review of the best available evidence was carried out to identify scales for assessment of suicide risk for the nonspecialist doctor (i.e., ideally, brief, predictive, and validated). We searched PubMed/MEDLINE, Cochrane, Epistemonikos, and Scholar Google. We also contacted national and international experts on the subject. We retrieved 3 092 documents, of which 2 097 were screened by abstract, resulting in 70 eligible articles. After screening by full text, 20 articles were selected from which four scales were ultimately extracted and analyzed. Our review concludes that there are no suicide risk assessment scales accurate and predictive enough to justify interventions based on their results. Positive predictive values range from 1 to 19%. Of the patients classified as "high risk," only 5% will die by suicide. Half of the patients who commit suicide come from "low-risk" groups. We also discuss 1) the importance of evaluating a patient with suicidal behavior according to socio-demographic variables, history of mental health problems, and stratification within a scale, and 2) possible initial actions in the challenging context of primary care.

Según la Organización Mundial de la Salud, el suicidio se ha convertido en un problema de salud pública de dimensiones globales. El 45% de los fallecidos por suicidio consultaron con un médico de atención primaria dentro del mes antes de consumar el hecho, sin evidenciarse una evaluación exhaustiva del riesgo suicida. Pese a ser un evento prevenible, no existe una evaluación estandarizada del riesgo suicida atingente al contexto de atención primaria de salud, donde las competencias en salud mental son variadas y muchas veces las decisiones guiadas por el juicio clínico. Se realizó una búsqueda y revisión de la mejor evidencia disponible sobre escalas de evaluación del riesgo suicida para el médico no especialista; idealmente breves, predictivas y validadas. Se buscó en las bases de datos PubMed/MEDLINE, Cochrane, Epistemonikos, Google Académico. Además, se contactó a referentes nacionales e internacionales en el tema. Se encontraron 3092 artículos en la literatura, de los cuales se tamizaron 2971 mediante lectura de sus abstracts, siendo 73 artículos elegibles. De ellos, mediante lectura del artículo completo, se seleccionaron 20 artículos de donde se extrajeron finalmente cuatro escalas a las que se les realizó análisis comparativo. La revisión mostró que no existen escalas para la evaluación del riesgo suicida suficientemente precisas y predictivas que justifiquen intervenciones según sus resultados. Sus valores predictivos positivos varían desde uno a 19%. De los pacientes que se cataloguen como de "alto riesgo", sólo el 5% fallecerá por suicidio. Más aún, la mitad de los pacientes que se suicidan provienen de grupos de "bajo riesgo". Se reflexiona finalmente en torno a una evaluación del paciente con conducta suicida que logre integrar variables sociodemográficas, antecedentes de problemas de salud mental, su estratificación dentro de una escala y posibles acciones iniciales en el difícil contexto de la incertidumbre inherente a la atención primaria.

How to face a patient with benzodiazepine dependence in primary health care? Strategies for withdrawal. / ¿Cómo afrontar un paciente con dependencia a benzodiacepinas en atención primaria? Estrategias para la deshabituación.

Benzodiazepines are widely used in primary health care, and their prolonged use is an important problem given the medical consequences particularly in older adults, such as dependence, cognitive impairment, and risk of falls, among others. Primary care doctors generally have few tools to help with managing withdrawal from benzodiazepines. We conducted a review of the best available evidence on practical strategies to avoid dependence at the time of the initial prescription, and to help the patient with prolonged and probably dependent use. We found ten relevant systematic reviews showing evidence in favor of the use of multifaceted prescription strategies, gradual dose reduction, standardized letters, standardized counseling, pharmacotherapy and cognitive behavioral psychotherapy. For benzodiazepine withdrawal, a simple strategy that can be effective and long-lasting is to inform patients of the need to reduce consumption, giving them in writing the withdrawal guideline, indicating the possible effects of withdrawal and its solution. Given the available evidence, an integrated and step-by-step model is proposed for the management of the benzodiazepine user, from prescription to withdrawal.

Las benzodiacepinas son fármacos ampliamente utilizados en atención primaria de salud. Su uso prolongado se ha convertido en un problema relevante dadas las consecuencias médicas que ocasionan, especialmente en adultos mayores. Entre otras, estas son: dependencia, deterioro cognitivo y riesgo de caídas. Además, los médicos que trabajan en atención primaria cuentan con pocas herramientas para ayudar al paciente en su deshabituación. Se realizó una búsqueda y revisión de la mejor evidencia disponible sobre estrategias prácticas para el médico no especialista en adicciones, para evitar la dependencia al momento de la prescripción inicial y en el paciente con uso prolongado y probablemente dependiente. Se encontraron 10 revisiones sistemáticas relevantes que mostraron evidencia a favor del uso de estrategias multifacéticas en la prescripción, disminución progresiva, cartas y consejería estandarizadas, farmacoterapia y psicoterapia cognitiva conductual. Una estrategia sencilla, eficaz y duradera para prescribir benzodiacepinas es informar al paciente de la necesidad de reducir su consumo, dándole por escrito la pauta de retirada, señalando sus posibles efectos y su solución. Debido a la evidencia disponible, se propone un modelo integrado y escalonado para el manejo del paciente usuario de benzodiacepinas, desde su prescripción hasta su descontinuación.

Ethanol self-administration and reinstatement of ethanol-seeking behavior in Per1(Brdm1) mutant mice.

RATIONALE: Alcohol consumption shows circadian rhythmicity, i.e., alcohol preference and intake change with circadian time. Circadian rhythmicity is controlled by a biological clock, which has been shown to govern behavioral, physiological, and hormonal processes in synchronization with internal as well as external cues. Molecular components of the clock include circadian clock genes such as period (Per) 1, 2, and 3. Previously, our lab demonstrated the involvement of mouse Per1 (mPer1) and Per2 (mPer2) in modulating cocaine sensitization and reward. What is more, we investigated voluntary alcohol consumption in Per2 ( Brdm1 ) mice with the results suggesting a relationship between this circadian clock gene and ethanol consumption. Objective To further complement the mPer2 study, our lab proceeded to assess mPer1's possible role on alcohol intake using operant and free choice two bottle paradigms. METHODS: Using operant conditions, Per1 ( Brdm1 ) and wild type mice were trained to self-administer ethanol (10%) under a fixed ratio 1 (FR1) paradigm. This was ensued by a progressive ratio (PR) schedule. Furthermore, extinction sessions were introduced, followed by reinstatement measures of ethanol-seeking behavior. In another set of animals, the mice were exposed to voluntary long-term alcohol consumption, ensued by a 2-month deprivation phase, after which the alcohol deprivation effect (ADE) was measured. RESULTS: Mutant mice did not display a significantly divergent number of reinforced lever presses (FR1 and PR) than wild type animals. Furthermore, no significant differences between groups were obtained regarding reinstatement of ethanol-seeking behavior. Similar results were obtained in the two bottle free choice paradigm. Specifically, no genotype differences concerning consumption and preference were observed over a broad range of different ethanol concentrations. Moreover, after the deprivation phase, both groups exhibited significant ADEs, yet no genotype differences. CONCLUSIONS: Contrary to the mPer2 data, the present findings do not suggest a relationship between the circadian clock gene mPer1 and ethanol reinforcement, seeking, and relapse behavior.

The clock gene Per2 influences the glutamatergic system and modulates alcohol consumption.

Period (Per) genes are involved in regulation of the circadian clock and are thought to modulate several brain functions. We demonstrate that Per2(Brdm1) mutant mice, which have a deletion in the PAS domain of the Per2 protein, show alterations in the glutamatergic system. Lowered expression of the glutamate transporter Eaat1 is observed in these animals, leading to reduced uptake of glutamate by astrocytes. As a consequence, glutamate levels increase in the extracellular space of Per2(Brdm1) mutant mouse brains. This is accompanied by increased alcohol intake in these animals. In humans, variations of the PER2 gene are associated with regulation of alcohol consumption. Acamprosate, a drug used to prevent craving and relapse in alcoholic patients is thought to act by dampening a hyper-glutamatergic state. This drug reduced augmented glutamate levels and normalized increased alcohol consumption in Per2(Brdm1) mutant mice. Collectively, these data establish glutamate as a link between dysfunction of the circadian clock gene Per2 and enhanced alcohol intake.

A toxic fraction from scolopendra venom increases the basal release of neurotransmitters in the ventral ganglia of crustaceans.

A toxic fraction from centipede (Scolopendra sp.) venom was tested in neurotransmitter release experiments. The venom was fractionated by DEAE-cellulose with a linear gradient from 20 mM to 1.0 M of ammonium acetate pH 4.7. Lethality tests were performed by injections into the third abdominal dorsolateral segment of sweet water crayfishes of the species Cambarellus cambarellus. Only fraction V (TF) was toxic. Analysis by SDS-PAGE showed that this fraction contains at least seven proteins. It induces an increase of basal gamma-amino butyric acid (GABA) and glutamate release from ventral abdominal ganglia of C. cambarellus. Assays conducted with this fraction in the presence of several drugs that affect ion channel function suggested that TF modifies membrane permeability by increasing basal release of neurotransmitters was very likely through sodium channels.

Cocaine sensitization and reward are under the influence of circadian genes and rhythm.

Investigations using the fruit fly Drosophila melanogaster have shown that the circadian clock gene period (Per) can influence behavioral responses to cocaine. Here we show that the mouse homologues of the Drosophila Per gene, mPer1 and mPer2, modulate cocaine sensitization and reward, two phenomena extensively studied in humans and animals because of their importance for drug abuse. In response to an acute cocaine injection mPer1 and mPer2 mutant mice as well as wild-type mice exhibited an approximately 5-fold increase in activity compared with saline control levels, showing that there is no initial difference in sensitivity to acute cocaine administration in Per mutants. After repeated cocaine injections wild-type mice exhibited a sensitized behavioral response that was absent in mPer1 knockout mice. In contrast, mPer2 mutant mice exhibited a hypersensitized response to cocaine. Conditioned place preference experiments revealed similar behavioral reactions: mPer1 knockout mice showed a complete lack of cocaine reward whereas mPer2 mutants showed a strong cocaine-induced place preference. In another set of experiments, we tested C57/BL6J mice at different Zeitgeber times and found that cocaine-induced behavioral sensitization and place preference are under the control of the circadian clock. In conclusion, we demonstrate that processes involved in cocaine addiction depend on the circadian rhythm and are modulated in an opposing manner by mPer1 and mPer2 genes.