Aspectos neurobiológicos en la toma de decisiones afectivas y sociales e influencia del estrés: posibles implicancias en la toma de decisiones clínicas / Neurobiological aspects in affective and social decision-making: possible implications on clinical decision-making

RESUMEN: La toma de decisiones está influenciada por múltiples factores muchas veces no conscientes. En este artículo se sintetizan algunos correlatos neurobiológicos del componente afectivo y social sobre la toma de decisiones, incluyendo el impacto del estrés agudo y crónico y la perspectiva cognitiva de las heurísticas y los sesgos en la práctica clínica. A nivel afectivo, la hipótesis del marcador somático ha asociado la respuesta corporal periférica con estructuras nerviosas centrales en la configuración de las decisiones; intervienen estructuras como la corteza orbitofrontal y el hipocampo. En la toma de decisiones sociales se involucran las dimensiones recompensa y motivación. En este tipo de decisiones es crucial la capacidad de mentalizar a otro e integrar su perspectiva en la toma de decisiones. Esta función se ha relacionado con el surco temporal posterosuperior, la unión temporoparietal, la corteza cingulada anterior y la corteza prefrontal medial. No obstante, en la toma de decisiones sociales también se integra el cumplimiento de normas socialmente establecidas. El estrés agudo o crónico puede afectar la toma de decisiones, positiva o negativamente. En estos procesos se han involucrado al eje hipotálamo-hipófiso-adrenal junto con circuitos corticoestriados, prefrontales, amigdalinos e hipocampales. En la toma de decisiones clínicas se conjugan factores "prerreflexivos" emocionales, sociales y cognitivos que influyen directamente en las conductas adoptadas con los pacientes. Recomendamos enfatizar la investigación en esta área y fortalecer su enseñanza para reconocerlos adecuadamente.

ABSTRACT Decision-making is influenced by multiple unaware factors. We synthesize some neurobiological correlates of the affective and social components on decision-making, including the impact of acute and chronic stress. We also address the impact of heuristics and biases on clinical practice from the cognitive perspective. At an affective level, the hypothesis of the somatic marker has associated the peripheral body response with central nervous structures in the configuration of decisions; structures such as the orbitofrontal cortex and the hippocampus intervene. The reward and motivation dimensions are involved in social decision-making. In these types of decisions, the ability to mentally engage others and integrate their perspective into decision making is crucial. This function has been related to the posterior superior temporal sulcus, the temporoparietal junction, the anterior cingulate cortex, and the medial prefrontal cortex. However, compliance with socially established norms is also integrated into social decision-making. Acute or chronic stress may affect decision-making, positively or negatively. The hypothalamic-pituitary-adrenal axis has been involved in these processes together with corticostriatal, prefrontal, amygdala and hippocampal circuits. In clinical decision-making, "pre-reflective" emotional, social and cognitive factors are combined, influencing the decisions towards patients. We recommend emphasizing research in this field and strengthening education in this area to recognize these aspects adequately.

Drug Induced Liver Injury in Geriatric Patients Detected by a Two-Hospital Prospective Pharmacovigilance Program: A Comprehensive Analysis Using the Roussel Uclaf Causality Assessment Method.

Background/aim: A prospective evaluation of drug-induced liver injury (DILI) in two tertiary hospitals was conducted through a pharmacovigilance program from laboratory signals at hospital (PPLSH) to determine the principal characteristics of DILI in patients older than 65 years, a growing age group worldwide, which is underrepresented in the literature on DILI. Methods: All DILI in patients older than 65 years detected by PPLSH in two hospitals were followed up for 8 years in the La Paz Hospital and 2 years in the Getafe Hospital. A descriptive analysis was conducted that determined the causality of DILI and suspected drugs, the incidence of DILI morbidities, DILI characteristics, laboratory patterns, evolution and outcomes. Results: 458 DILI cases in 441 patients were identified, 31.0% resulting in hospitalisation and 69.0% developing during hospitalisation. The mean age was 76.61 years old (SD, 7.9), and 54.4% were women. The DILI incidence was 76.33/10,000 admissions (95%CI 60.78-95.13). Polypharmacy (taking >4 drugs) was present in 86.84% of patients, 39.68% of whom took >10 drugs. The hepatocellular phenotype was the most frequent type of DILI (53.29%), a higher proportion (65%) had a mild severity index, and, in 55.2% of the evaluated drugs the RUCAM indicated that the causal relationship was highly probable. The most frequently employed drugs were paracetamol (50-cases), amoxicillin-clavulanate (42-cases) and atorvastatin (37-cases). The incidence rate of in-hospital DILI per 10,000 DDDs was highest for piperacillin-tazobactam (66.96/10,000 DDDs). A higher risk of in-hospital DILI was associated with the therapeutic chemical group-J (antiinfectives for systemic use) (OR, 2.65; 95%CI 1.58-4.46) and group-N (central nervous system drugs) (OR, 2.33; 95%CI 1.26-4.31). The patients taking >4 medications presented higher maximum creatinine level (OR, 2.01; 95%CI 1.28-3.15), and the patients taking >10 medications had a higher use of group J drugs (OR, 2.08; 95%IC 1.31-3.32). Conclusion: The incidence rate of DILI in the patients older than 65 years was higher than expected. DILI in elderly patients is mild, has a good outcome, has a hepatocellular pattern, develops during hospitalisation, and prolongs the hospital stay. Knowing the DILI incidence and explanatory factors will help improve the therapy of the elderly population.

[Thyroid hormone prescription patterns in a Colombian population]. / Patrones de prescripción de hormonas tiroideas en una población colombiana.

OBJECTIVE: Determine thyroid hormone prescription patterns in the population covered by the Colombian Social Security Health System. METHODS: Descriptive study using a database of 6.2 million people. The selected patients, men and women of all ages, received continuous thyroid hormone treatment from April to June 2013. A database on medication use was designed, using data obtained by the company that dispenses these drugs. RESULTS: It was found that 29 947 patients in 82 Colombian cities had been treated for hypothyroidism. The majority (79.1%) were women, with an average age of 63.2 ± 16.1 years. The most common prescription was for levothyroxine in 50 µg tablets (85.7%) at higher-than-recommended daily dosages, especially as monotherapy. Significant differences between age groups and cities of residence were found for the combined use of thyroid hormone and co-medication. The most frequently prescribed concomitant drugs were antiulcer agents (44%), hypoglycemics (17.4%), and iron salts (16.1%). CONCLUSIONS: There are significant differences in prescribing practices in the cities studied. Clinical management guidelines that standardize dosages and physicians' practices are needed, since a lack of guidelines has likely had an impact on patients' health. The clinical efficacy of the prescriptions studied should be explored.

Patrones de prescripción de hormonas tiroideas en una población colombiana / Thyroid hormone prescription patterns in a colombian population

OBJETIVO: Determinar los patrones de prescripción de hormonas tiroideas en personas afiliadas al Sistema General de Seguridad Social en Salud de Colombia. MÉTODOS: Estudio descriptivo a partir de una base de datos poblacional de 6,2 millones de personas. Se seleccionaron los pacientes medicados con hormonas tiroideas, de uno y otro sexo y todas las edades, con tratamiento continuo de abril a junio de 2013. Se diseñó una base de datos sobre consumo de medicamentos, obtenidos por la empresa que dispensa dichos fármacos. RESULTADOS: Se hallaron 29 947 pacientes tratados para hipotiroidismo en 82 ciudades colombianas. La mayoría (79,1%) eran mujeres, con una edad media de 63,2 ± 16,1 años. La presentación prescrita con mayor frecuencia fue levotiroxina en tabletas de 50 µg (85,7%) a dosis diarias definidas mayores de las recomendadas, sobre todo como monoterapia. Se detectaron diferencias significativas entre los grupos etarios y las ciudades de residencia para el uso combinado de hormona tiroidea y de comedicación. Los medicamentos prescritos de manera concomitante con mayor frecuencia fueron los antiulcerosos (44%), hipoglucemiantes (17,4%) y sales de hierro (16,1%). CONCLUSIONES: Existen diferencias significativas en las recetas de los médicos en las ciudades estudiadas. Hacen falta guías de manejo clínico que estandaricen las dosis y conductas médicas, pues es probable que su ausencia tenga impacto en la salud de los pacientes. Es necesario explorar la efectividad clínica de las prescripciones estudiadas.

OBJECTIVE: Determine thyroid hormone prescription patterns in the population covered by the Colombian Social Security Health System. METHODS: Descriptive study using a database of 6.2 million people. The selected patients, men and women of all ages, received continuous thyroid hormone treatment from April to June 2013. A database on medication use was designed, using data obtained by the company that dispenses these drugs. RESULTS: It was found that 29 947 patients in 82 Colombian cities had been treated for hypothyroidism. The majority (79.1%) were women, with an average age of 63.2 ± 16.1 years. The most common prescription was for levothyroxine in 50 µg tablets (85.7%) at higher-than-recommended daily dosages, especially as monotherapy. Significant differences between age groups and cities of residence were found for the combined use of thyroid hormone and co-medication. The most frequently prescribed concomitant drugs were antiulcer agents (44%), hypoglycemics (17.4%), and iron salts (16.1%). CONCLUSIONS: There are significant differences in prescribing practices in the cities studied. Clinical management guidelines that standardize dosages and physicians' practices are needed, since a lack of guidelines has likely had an impact on patients' health. The clinical efficacy of the prescriptions studied should be explored.

[Hereditary angioedema. Treatment of acute attacks in Argentina]. / Angioedema hereditario. Tratamiento del ataque agudo en la Argentina.

In the world, hereditary angioedema (HAE) affects 1 every 50000 persons. It is characterized by highly disabling and recurrent episodes of cutaneous, abdominal and laryngeal episodes of angioedema. Asphyxia related mortality ranges from 15 to 50%. In Argentina a plasma derived C1 inhibitor concentrate (pdC1INH) has been available for the treatment of acute attacks for many decades, however, only15 (26%) out of 58 patients had received pdC1INH at least once until 2008, and only2 (3.4%) had used it regularly. After worldwide approval of the new drugs for the treatment of acute HAE attacks, adding icatibant to pdC1INH in Argentina, and after publication of the therapeutic guide for the country, 42 (82%) out of 51 patients from the original group has pdC1INH available to treat their next attack. However, 16 (18%) patients continue without access to medication and other 15 (35.7%) obtain their therapy spuriously through some other affected relative in their environment. Only 12 (28.6%) patients of the group self-treated at home. Access to treatment has greatly improved, but needs to be extended to all patients and self-treatment at home should be encouraged.

Angioedema hereditario: Tratamiento del ataque agudo en la Argentina / Hereditary angioedema: Treatment of acute attacks in Argentina

En el mundo, el angioedema hereditario (HAE) afecta a 1 de cada 50 000 personas. Produce episodios de angioedema cutáneo, abdominal y laríngeos que generan gran incapacidad. La mortalidad por la enfermedad oscila entre 15 y 50%. Aunque en Argentina un concentrado plasmático de C1 inhibidor (pdC1INH) ha estado aprobado y disponible por décadas para el tratamiento del ataque agudo, solo 15 (26%) de 58 pacientes había recibido pdC1INH alguna vez hasta el año 2008, y solo 2(3.4%) lo usaban regularmente. Luego de la aprobación de los nuevos medicamentos para HAE, incluido el icatibant en Argentina y de la publicación de las guías terapéuticas, 42 (82%) de 51 pacientes del grupo original tienen pdC1INH para tratar el próximo ataque. Sin embargo, 16 (18%) de estos pacientes continúan sin acceso a la medicación y otros 15 (35.7%) acceden a través de otro enfermo en forma espuria. Solo 12 (28.6%) de los pacientes con el medicamento puede auto tratarse en su domicilio. La mejora en el acceso a la medicación es importante pero debe extenderse a todos los afectados y facilitarse el auto-tratamiento.

In the world, hereditary angioedema (HAE) affects 1every 50 000 persons. It is characterized by highly disabling and recurrent episodes of cutaneous, abdominal and laryngeal episodes of angioedema. Asphyxia related mortality ranges from 15 to 50%. In Argentina a plasma derived C1 inhibitor concentrate (pdC1INH) has been available for the treatment of acute attacks for many decades, however, only15 (26%) out of 58 patients had received pdC1INH at least once until 2008, and only2 (3.4%) had used it regularly. After worldwide approval of the new drugs for the treatment of acute HAE attacks, adding icatibant to pdC1INH in Argentina, and after publication of the therapeutic guide for the country, 42 (82%) out of 51 patients from the original group has pdC1INH available to treat their next attack. However, 16 (18%) patients continue without access to medication and other 15 (35.7%) obtain their therapy spuriously through some other affected relative in their environment. Only 12 (28.6%) patients of the group self-treated at home. Access to treatment has greatly improved, but needs to be extended to all patients and self-treatment at home should be encouraged.

Will biofilm disassembly agents make it to market?

Nearly 12 years after promising results suggested that antibiofilm agents might be developed into novel therapeutics, there are no such products on the market. In our opinion, the reasons for this have been predominantly economic. Recent developments, however, suggest that there could still be emerging opportunities for the developments of such products.