Mirtazapine as Appetite Stimulant in Patients With Non-Small Cell Lung Cancer and Anorexia: A Randomized Clinical Trial.

Importance: Currently there is no standard therapy to improve cancer-related anorexia, hampering survival. Mirtazapine has been suggested as a feasible option in this context. Objectives: To assess the effect of mirtazapine on appetite and energy consumption in patients with advanced non-small cell lung cancer (NSCLC). Design, Setting, and Participants: This randomized, double-blind, placebo-controlled clinical trial including adults was performed in a tertiary cancer care center from August 2018 to May 2022 with a follow-up of 8 weeks. Overall, 134 patients were screened; 114 were assessed for eligibility and 28 were excluded. Interventions: Patients were randomized in a 1:1 ratio to receive mirtazapine, 15 mg, or placebo for 2 weeks followed by a dose escalation to 30 mg until week 8 or placebo. Both groups received nutritional assessment and dietary advice. Main outcomes and measures: Appetite was assessed by the Anorexia Cachexia Scale and energy intake. Dietary parameters were evaluated at baseline, 4 weeks, and 8 weeks, with a 24-hour dietary recall, and energy quantification based on the Mexican system of nutritional equivalents. Results: A total of 86 patients met the inclusion criteria and were randomized to the placebo (n = 43) or the mirtazapine group (n = 43). The mean (SD) age was 63.5 (11.2) years, 41 were women (57.7%) and had adenocarcinoma, Eastern Cooperative Oncology Group performance status scale score of 1, stage IV NSCLC, and were receiving first-line treatment. Baseline characteristics were similar between groups. There was no difference in appetite scores in patients who received mirtazapine or placebo after 4 and 8 weeks. After 4 weeks, mirtazapine significantly increased energy intake (379.3 kcal; 95% CI, 1382.6-576.1; P < .001) including proteins (22.5 g; 95% CI, 11.5-33.4; P = .001), carbohydrates (43.4 g; 95% CI, 13.1-73.8; P = .006), and fats (13.2 g; 95% CI, 6.0-20.4; P = .006). Fats intake was significantly higher in patients in the mirtazapine group (14.5 g vs 0.7 g; P = .02) after 8 weeks. The mirtazapine group significantly decreased the proportion of patients with sarcopenia (82.8% vs 57.1%, P = .03) at 8 weeks. Patients on mirtazapine tolerated the treatment well, but reported a higher perception of nightmares at 2 weeks based on a 10 cm VAS score (0 [25th-75th percentile, 0-1] vs 0 [25th-75th percentile, 0-0] in the control group; P = .009) but this finding was nonsignificant after 4 and 8 weeks. Conclusion and Relevance: In this randomized clinical trial of patients with advanced NSCLC, there was no difference in appetite scores in all patients who received mirtazapine or placebo, but the mirtazapine group had a significant increase in energy intake through the 4- and 8-week follow-up, mainly in fat intake, which is a better and crucial source of energy. The addition of mirtazapine in the treatment of patients with advanced NSCLC and anorexia may help these patients achieve their energy requirements and improve health-related quality of life, specifically emotional and cognitive functioning. Trial Registration: ClinicalTrials.gov Identifier: NCT04748523.

Medical cannabis: Critical points for clinical application / Cannabis medicinal: puntos críticos para su uso clínico.

Since ancient times cannabis has been used for recreational and medicinal purposes. It is a significant source of chemical compounds, most of them called phytocannabinoids. These compounds have several physiological effects and produce their effects primarily by binding to endogenous cannabinoid receptors such as CB1 and CB2, among others. Cannabis has potential therapeutic properties and its preparations have been used as traditional remedies to treat pain and emesis. Synthetic cannabinoids are used clinically as analgesics, antispastics, antiemetics, and appetite stimulants. Significant cannabis toxicity is rare in adults; however, it can produce countless acute and chronic side effects. The quality of the evidence in this field is limited by the short duration of the trials, poor sample sizes, lack of a control group, and the existence of bias in most of the reviewed studies. Therefore, a larger number of studies with better methodological quality is required to support the safe use of this therapy. The decision to include cannabinoids as a treatment for any of the conditions described will depend on the evidence, the use of previous therapies, and the type of patient.

El cannabis se ha utilizado desde la antigüedad con fines recreativos y medicinales. Es una fuente muy rica de compuestos químicos, la mayoría denominados fitocannabinoides, que tienen una variedad de efectos fisiológicos, principalmente por su unión a receptores cannabinoides endógenos como el CB1 y CB2, entre otros. El cannabis tiene propiedades terapéuticas potenciales y sus preparaciones se han utilizado como remedios tradicionales para tratar el dolor y la emesis. Los cannabinoides sintéticos se utilizan clínicamente como analgésicos, antiespasmódico, antieméticos y estimulantes del apetito. La toxicidad significativa del cannabis es poco común en los adultos, sin embargo, puede tener múltiples efectos adversos agudos y crónicos. La calidad de la evidencia en este campo se ha visto limitada por la corta duración de los estudios, los reducidos tamaños de las muestras, la falta de grupos de control y la existencia de sesgos en la mayoría de los estudios revisados. En este contexto, son necesarios más estudios de mejor calidad metodológica para apoyar el uso seguro de esta terapia en otras enfermedades. La decisión de incorporar los cannabinoides como terapia en alguna de las condiciones descritas depende de la evidencia, el uso de terapias previas y el tipo de paciente.

Appetite stimulants for patients with cancer: current evidence for clinical practice.

The incidence of neoplastic diseases has increased worldwide, with an estimated global burden of 19.3 million incident cases and 10 million deaths in 2020-a considerable increase compared with 9.6 million deaths in 2018. One of the most prevalent problems faced by patients with cancer and their physicians is malnutrition. It is estimated that patients with cancer have important nutritional alterations in 25% to 70% of cases, which directly affects many spheres of patient care and well-being, including quality of life, treatment toxicity, and survival outcomes. Despite the overwhelming need to address this pressing issue, current evidence in terms of pharmacologic interventions for cancer-related anorexia remains inconclusive, and there is no current standard of care for patients with cancer-related anorexia. Nonetheless, international guidelines recommend promoting anabolism through nutritional, physical, and pharmacologic therapies. In this review, the available information is summarized regarding pharmacologic therapies to treat cancer-related anorexia and findings are highlighted from a clinical stance.

[Avoidant/Restrictive Food Intake Disorder (ARFID): What the pediatrician should know]. / Trastorno de Evitación y Restricción de la Ingesta de Alimentos (ARFID): Lo que el pediatra debe saber.

Feeding problems during childhood have been described over time by various authors. In 2013, Avoi dant/Restrictive Food Intake Disorder (ARFID) was included in the Diagnostic and Statistical Ma nual of Mental Disorders, 5th Edition (DSM-5), as a new diagnosis within the Feeding and Eating di sorders, to describe a group of patients with avoidant or restrictive eating behaviors unrelated to body image disorder or weight loss desire. ARFID may appear as significant weight loss and/or nutritional deficiency and/or a marked interference in psychosocial functioning. There are three forms of pre sentation, which can co-occur or occur independently. The first one includes children with sensory aversions (selective), who reject certain foods due to their taste, texture, smell, or shape; the second one includes those children with poor appetite or limited intake (limited intake); and the third one includes those children who reject certain foods or stop eating as a result of a traumatic event (aversi- ve). Due to the recent incorporation of ARFID into the DSM-5, there is a lack of information regar ding its treatment. The purpose of this review is to clarify diagnostic criteria and to describe targeted management and treatment interventions with a multidisciplinary approach, without deepening on the treatment of organic medical causes.

Representação social de mães sobre alimentação e uso de estimulantes do apetite em crianças: satisfação, normalidade e poder / Social representation of mothers about feeding and use of appetite stimulants in children: satisfaction, normality and power

Resumo: Este estudo teve como objetivo identificar as representações sociais elaboradas por mães sobre o apetite dos filhos e os medicamentos utilizados para modificá-lo. A abordagem qualitativa desta pesquisa empregou como suporte a teoria das representações sociais. Por meio de entrevistas realizadas com 15 mães que administraram em seus filhos medicamentos para estimular o apetite, foi possível identificar uma insatisfação materna com o volume habitual e seletividade de alimentos ingeridos por seus filhos. Essas foram as principais razões para o uso de medicamentos. Outras razões que encontram espaço são o desenvolvimento da criança, com ganho de massa corpórea, além da vontade de regular as horas em que a criança deveria comer. Esses resultados apontam para a importância das representações sociais maternas sobre a percepção corporal, papel dos alimentos e medicamentos nas práticas do cuidado alimentar infantil.

Abstract: Social representation of mothers about feeding and use of appetite stimulants in children: satisfaction, normality and power This study aimed to identify the social representations elaborated by mothers about the appetite of children and the drugs used to modify this appetite. The qualitative approach used in this study employed as theoretical support the theory of social representations. Through interviews with 15 mothers who administered their children drugs to stimulate appetite, it was possible to identify a maternal dissatisfaction with the usual volume and selectivity of food eaten by their children. These were the main reasons for using drugs. Other related reasons were the growth of the children, with a body mass gain, beyond the desire to regulate the times which the child should eat. These results point to the importance of maternal social representations of body perception , and the role of food and medicine in child care practices.

Usos terapéuticos de los cannabinoides / Therapeutic uses of cannabinoids

INTRODUCCIÓN: Este informe presenta los resultados obtenidos, respecto a la eficacia y seguridad del uso medicinal de los cannabinoides para el tratamiento del dolor crónico, náuseas y vómitos debido a quimioterapia, estimulación del apetito en infección HIV / SIDA, espasticidad debido a esclerosis múltiple o paraplejía, síndrome de Tourette y epilepsia refractaria a los tratamientos convencionales; en pacientes de cualquier edad. MÉTODO: Se seleccionaron 16 revisiones sistemáticas / metanálisis y 2 estudios observacionales. Muchos de los estudios que se incluyeron son de baja calidad metodológica, relativamente corto período de observación- con respecto a las patologías- y escaso número de pacientes para cada punto final aislado. Por lo tanto las conclusiones tienen significado clínico en cuanto a la dirección y tamaño del efecto benéfico pero nula significación estadística en algunas de las condiciones observadas. DOLOR: los canabinoides muestran beneficios leves a moderados para el tratamiento del dolor cuando se los compara con placebo. El THC fumado ha demostrado ser la intervención con mayor efectividad. El nivel de efectividad de los cannabinoides es dosis dependiente y resultan ser opciones muy útiles cuando se asocian a otras alternativas terapéuticas. EPILEPSIA REFRACTARIA: se observó una reducción mayor o igual al 50% en la frecuencia de las convulsiones en el 47% de los pacientes tratados con CBD o su asociación con THC. Puede ser considerada como una alternativa adyuvante en el tratamiento de estos pacientes. ESPASTICIDAD Y ESPASMOS DOLOROSOS EN EM: especialmente el nabiximols, podría tener un rol importante en el manejo de la espasticidad no controlada con las terapéuticas habituales. REDUCCIÓN DE NÁUSEAS Y VÓMITOS: fueron 4 veces más efectivos que el placebo para el control de nauseas y vómitos en pacientes bajo tratamiento quimioterápico. ESTIMULACIÓN DEL APETITO: el acetato de megestrol ha demostrado ser superior a los cannabinoides. REDUCCIÓN DE TICS EN EL SÍNDROME TOURETTE: sin conclusión. CONSIDERACIONES FINALES: Otros puntos finales: depresión, trastornos de ansiedad, trastornos del sueño, glaucoma, trastorno del humor, calidad de vida, ingesta calórica, aumento de peso; no existen evidencias sustentables para su aplicación en estas patologías. Los dos principales fitocannabinoides son: Delta-9-tetrahidrocannabinol (THC) el principal constituyente psicoactivo de la planta de marihuana y el cannabidiol (CBD) que tienen muy pocas propiedades psicoactivas y de interés creciente con respecto a su potencial terapéutico. Los sintéticos más usados son: nabilona; dronabinol; ácido ajulémico; nabiximols; levonantradol. CONCLUSIÓN: Los eventos adversos (EA) para todos los puntos finales demostraron un rango de intensidad leve a moderada. Los más frecuentes fueron: mareos, boca seca, náuseas, fatiga, somnolencia, respiratorios y gastrointestinales. No se demostró diferencias de EA entre los distintos tipos de cannabinoides. Todas las conclusiones son débiles en cuanto a la fuerza de la recomendación. Es muy importante la realización de estudios que cumplimenten todos los recaudos metodológicos y un adecuado tamaño muestral para avanzar en el conocimiento sobre el uso medicinal de los cannabinoides.

Efficacy of PHENODRAL® product (sodium methylarsinate +ammonium ferric citrate +epinephrine) in bovines / Eficácia da formulação PHENODRAL® (metilarsinato de sódio + citrato de ferro amoniacal + adrenalina) em bovinos

We evaluated the efficacy of PHENODRAL® product on debilitated cattle, body condition (BC=2) and the influence of this product in clinical and laboratory parameters and weight gain. The experiment was performed using 20 young cattle aged 8 to 12 months, divided into two groups of 10 animals each, five males and five females/group (untreated Control Group - GI and Drug-treated group - Group - GII). The animals of GII received three doses of 15 mL of d PHENODRAL® product administered every six days (D0, D + 6 and D + 12), via IV, and the GI group received 0.9% IV saline administration. The experimental animals were monitored until D+35 The results showed that the weight gain in the GII group was higher in comparison to the control group GI, mainly at the moments before and after the product application, and a significant difference were observed at D + 28 in comparison to GI group. The results for the weekly parameters evaluated: feed intake, weekly weight gain and weekly feed conversion, were statistically different in moments D0 to D + 7, D + 7 to D + 14, D + 14 to D + 21 and D +21 to D + 28 between GI and GII emphasizing that the treated animals ingested greater amount of feed resulting in a higher weight gain due to better feed conversion compared to the control group animals. There were no statistical differences between GI and GII for the clinical, hematological and biochemical parameters evaluated throughout the trial period, however, the serum cortisol levels assessed in the GI group were above the reference values for the bovine species. On the other hand, the cortisol values found in GII decreased after the PHENODRAL® product administration, as well as the glucose concentrations when compared to the GI, thus demonstrating the efficacy of PHENODRAL® product in improving the treated animals performance.(AU)

Avaliou-se a eficácia do produto PHENODRAL® em bovinos debilitados com escore corporal 2 e a influencia deste produto nos parâmetros clínicos, laboratoriais e ganho de peso. O experimento foi realizado no município de Abadia dos Dourados/MG, com 20 bovinos jovens com idade entre 8 a 12 meses, divididos em dois grupos de 10 animais cada, sendo cinco machos e cinco fêmeas/grupo (Grupo Controle GI e Grupo Tratado GII). Os animais do grupo GII receberam três doses de 15 mL do produto PHENODRAL® administrado, a cada seis dias (D0, D+6 e D+12), via I.V., e o grupo GI recebeu administração de solução fisiológica 0,9%, via I.V. Os animais experimentais foram observados até o período D+35 Os resultados mostraram que o ganho de peso no grupo GII foi superior ao grupo controle GI, principalmente, nos momentos antes e após aplicação do produto, e uma diferença estatística mais evidente no momento D+28 em comparação ao GI. Os resultados encontrados para os parâmetros avaliados semanalmente: consumo de ração, ganho de peso semanal e conversão alimentar semanal, foram estatisticamente diferentes nos momentos D0 ao D+7, D+7 ao D+14, D+14 a D+21 e D+21 a D+28 entre os grupos GI e GII ressaltando-se que, os animais tratados ingeriram maior quantidade de ração resultando em um ganho de peso maior em função de melhor conversão alimentar em comparação aos animais do grupo controle. Não foram encontradas diferenças estatísticas entre os grupos GI E GII para os parâmetros clínicos, hematológicos e bioquímicos avaliados durante todo o período experimental, porém, os valores de cortisol sérico avaliados no grupo GI estavam acima dos valores de referencia para a espécie bovina. Por outro lado, os valores de cortisol no grupo GII diminuíram após a aplicação do produto PHENODRAL®assim como as concentrações de glicose em comparação ao GI, demonstrando assim a eficiência do produto PHENODRAL® na melhoria do desempenho dos animais tratados. (AU)

Efficacy of PHENODRAL® product (sodium methylarsinate +ammonium ferric citrate +epinephrine) in bovines / Eficácia da formulação PHENODRAL® (metilarsinato de sódio + citrato de ferro amoniacal + adrenalina) em bovinos

We evaluated the efficacy of PHENODRAL® product on debilitated cattle, body condition (BC=2) and the influence of this product in clinical and laboratory parameters and weight gain. The experiment was performed using 20 young cattle aged 8 to 12 months, divided into two groups of 10 animals each, five males and five females/group (untreated Control Group - GI and Drug-treated group - Group - GII). The animals of GII received three doses of 15 mL of d PHENODRAL® product administered every six days (D0, D + 6 and D + 12), via IV, and the GI group received 0.9% IV saline administration. The experimental animals were monitored until D+35 The results showed that the weight gain in the GII group was higher in comparison to the control group GI, mainly at the moments before and after the product application, and a significant difference were observed at D + 28 in comparison to GI group. The results for the weekly parameters evaluated: feed intake, weekly weight gain and weekly feed conversion, were statistically different in moments D0 to D + 7, D + 7 to D + 14, D + 14 to D + 21 and D +21 to D + 28 between GI and GII emphasizing that the treated animals ingested greater amount of feed resulting in a higher weight gain due to better feed conversion compared to the control group animals. There were no statistical differences between GI and GII for the clinical, hematological and biochemical parameters evaluated throughout the trial period, however, the serum cortisol levels assessed in the GI group were above the reference values for the bovine species. On the other hand, the cortisol values found in GII decreased after the PHENODRAL® product administration, as well as the glucose concentrations when compared to the GI, thus demonstrating the efficacy of PHENODRAL® product in improving the treated animals performance.

Avaliou-se a eficácia do produto PHENODRAL® em bovinos debilitados com escore corporal 2 e a influencia deste produto nos parâmetros clínicos, laboratoriais e ganho de peso. O experimento foi realizado no município de Abadia dos Dourados/MG, com 20 bovinos jovens com idade entre 8 a 12 meses, divididos em dois grupos de 10 animais cada, sendo cinco machos e cinco fêmeas/grupo (Grupo Controle GI e Grupo Tratado GII). Os animais do grupo GII receberam três doses de 15 mL do produto PHENODRAL® administrado, a cada seis dias (D0, D+6 e D+12), via I.V., e o grupo GI recebeu administração de solução fisiológica 0,9%, via I.V. Os animais experimentais foram observados até o período D+35 Os resultados mostraram que o ganho de peso no grupo GII foi superior ao grupo controle GI, principalmente, nos momentos antes e após aplicação do produto, e uma diferença estatística mais evidente no momento D+28 em comparação ao GI. Os resultados encontrados para os parâmetros avaliados semanalmente: consumo de ração, ganho de peso semanal e conversão alimentar semanal, foram estatisticamente diferentes nos momentos D0 ao D+7, D+7 ao D+14, D+14 a D+21 e D+21 a D+28 entre os grupos GI e GII ressaltando-se que, os animais tratados ingeriram maior quantidade de ração resultando em um ganho de peso maior em função de melhor conversão alimentar em comparação aos animais do grupo controle. Não foram encontradas diferenças estatísticas entre os grupos GI E GII para os parâmetros clínicos, hematológicos e bioquímicos avaliados durante todo o período experimental, porém, os valores de cortisol sérico avaliados no grupo GI estavam acima dos valores de referencia para a espécie bovina. Por outro lado, os valores de cortisol no grupo GII diminuíram após a aplicação do produto PHENODRAL®assim como as concentrações de glicose em comparação ao GI, demonstrando assim a eficiência do produto PHENODRAL® na melhoria do desempenho dos animais tratados.

A randomized, double-blind, placebo-controlled trial of cyproheptadine for appetite stimulation in cystic fibrosis.

OBJECTIVE: To determine whether the administration of cyproheptadine was able to induce weight gain in patients with cystic fibrosis. METHODS: We performed a double-blind, placebo-controlled trial in two centers in Brazil. Twenty-five patients with cystic fibrosis between 5 and 18 years completed the study. Patients were randomized into two groups, to receive either cyproheptadine 4 mg three times per day for 12 weeks or placebo. All data were collected at the beginning and at the end of the study period and included weight, height and spirometry. RESULTS: Average weight gain was 0.67 kg in the placebo group and 1.61 kg in the cyproheptadine group (p = 0.036). Body mass index (BMI) decreased 0.07 kg/m(2); in the placebo group and increased 0.46 kg/m(2); in the intervention group (p = 0.027). The change in BMI for age (z score) was -0.19 in the placebo group and +0.20 in the cyproheptadine group (p = 0.003). BMI z score decreased 0.19 in the placebo group and increased 0.2 in the cyproheptadine group (p = 0.003). Changes in pulmonary function were not statistically different. CONCLUSION: Use of cyproheptadine in cystic fibrosis patients was well tolerated, showing a significant weight gain and a significant increase in BMI after 12 weeks. A clinically relevant effect size for weight/age (z score) and body mass index for age (z score) was found. Such findings suggest that the prescription of cyproheptadine can be an alternative approach for patients who need nutritional support for a short period of time.

Ensaio clínico randomizado, duplo-cego e controlado por placebo de ciproheptadina para estímulo do apetite na fibrose cística / A randomized, double-blind, placebo-controlled trial of cyproheptadine for appetite stimulation in cystic fibrosis

OBJETIVO: O objetivo deste estudo foi determinar se a administração de ciproheptadina é capaz de induzir ganho de peso em pacientes com fibrose cística. MÉTODOS: Foi realizado um estudo duplo-cego, controlado com placebo em dois centros no Brasil. Vinte e cinco pacientes com fibrose cística entre 5 e 18 anos completaram o estudo. Os pacientes foram randomizados em dois grupos, para receber ciproheptadina 4 mg três vezes por dia durante 12 semanas ou placebo. Todos os dados foram coletados no início e no final do período de estudo e incluíram peso, altura e espirometria. RESULTADOS: O ganho de peso médio foi de 0,67 kg e 1,61 kg nos grupos placebo e ciproheptadina, respectivamente (p = 0,036). O índice de massa corporal (IMC) diminuiu 0,07 kg/m² no grupo placebo e aumentou 0,46 kg/m² no grupo intervenção (p = 0,027). A mudança no IMC para a idade (escore z) foi de -0,19 no grupo placebo e 0,20 no grupo ciproheptadina (p = 0,003). O IMC escore z diminuiu 0,19 no grupo placebo e aumentou 0,2 no grupo ciproheptadina (p = 0,003). Alterações na função pulmonar não foram estatisticamente diferentes. CONCLUSÃO: O uso de ciproheptadina em pacientes com fibrose cística foi bem tolerado, apresentando um ganho de peso significativo e um aumento no IMC após 12 semanas. Foi encontrado um tamanho de efeito clinicamente relevante para o peso/idade (escore z) e IMC para idade (escore z). Tais achados sugerem que a prescrição de ciproheptadina pode ser uma abordagem alternativa para pacientes que precisam de suporte nutricional por um curto período de tempo.

OBJECTIVE: To determine whether the administration of cyproheptadine was able to induce weight gain in patients with cystic fibrosis. METHODS: We performed a double-blind, placebo-controlled trial in two centers in Brazil. Twenty-five patients with cystic fibrosis between 5 and 18 years completed the study. Patients were randomized into two groups, to receive either cyproheptadine 4 mg three times per day for 12 weeks or placebo. All data were collected at the beginning and at the end of the study period and included weight, height and spirometry. RESULTS: Average weight gain was 0.67 kg in the placebo group and 1.61 kg in the cyproheptadine group (p = 0.036). Body mass index (BMI) decreased 0.07 kg/m² in the placebo group and increased 0.46 kg/m² in the intervention group (p = 0,027). The change in BMI for age (z score) was -0.19 in the placebo group and +0.20 in the cyproheptadine group (p = 0.003). BMI z score decreased 0.19 in the placebo group and increased 0.2 in the cyproheptadine group (p = 0.003). Changes in pulmonary function were not statistically different. CONCLUSION: Use of cyproheptadine in cystic fibrosis patients was well tolerated, showing a significant weight gain and a significant increase in BMI after 12 weeks. A clinically relevant effect size for weight/age (z score) and body mass index for age (z score) was found. Such findings suggest that the prescription of cyproheptadine can be an alternative approach for patients who need nutritional support for a short period of time.

Nutrition in the last days of life.

PURPOSE OF REVIEW: To summarize current knowledge about nutritional aspects in the final stage of life, with emphasis on mechanisms and clinical diagnosis, ethical aspects and management. RECENT FINDINGS: The most recent advances on the subject include new mechanisms involved in the pathophysiology, use of therapeutic approach combined with n-3 fatty acids and the active intervention of the patient in decision making. SUMMARY: The nutritional deterioration in a patient who passes the last stages of his life constitutes a subject area to varied analysis and considerations. For this reason, there exist an increasing number of investigations, particularly in the areas of pathophysiology and of therapeutics. The aspects related to quality of life, cultural context and bioethics, add more complexity to the subject.

Inhibition of tumor progression and paraneoplastic syndrome development in a murine lung adenocarcinoma by medroxyprogesterone acetate and indomethacin.

Mice bearing LP07 lung adenocarcinoma present some characteristics similar to those shown in patients with several malignant diseases. LP07 tumor bearers develop paraneoplastic syndromes such as cachexia, leukocytosis, and hypercalcemia, partly due to a systemic inflammatory response. We analyzed some of the mechanisms involved in the effectiveness of the association of the appetite-stimulant medroxiprogesterone acetate (MPA) and the nonselective cyclooxigenase (COX) inhibitor indomethacin (INDO) in LP07 tumor bearing mice. INDO and INDO plus MPA treatments significantly inhibited tumor growth, which was not inhibited by MPA. The number of lung metastatic nodules was decreased with all treatments, being most effective INDO alone and INDO plus MPA. A significant decrease of plasmatic levels of the matrix metalloproteinases MMP-9 and MMP-2 correlated with these results. Paraneoplastic syndromes, leukocytosis, and cachexia were abolished by all treatments. We determined effects of the treatments on circulating cytokines shown to regulate cachexia and inflammation. Both treatments alone, and INDO plus MPA, reduced circulating IL-6 throughout tumor evolution. A pronounced increase in serum IL-1ss levels was detected in untreated tumor bearers. These levels decreased and were closer to normal serum values when LP07 mice were treated with INDO plus MPA. The combination of a nonsteroidal antiinflammatory drug as INDO and MPA showed to be effective in inhibiting tumor and metastatic growth and diminishing paraneoplastic symptoms and SIR. A variety of specific molecules are implicated as playing a role in cancer-induced cachexia and hematological alterations.

Megestrol acetate for the treatment of anorexia-cachexia syndrome.

BACKGROUND: Megestrol acetate (MA) is currently used to improve appetite and to increase weight in cancer-associated anorexia. In 1993 MA was approved by the USA's Federal Drug Administration for the treatment of anorexia, cachexia, or unexplained weight loss in patients with AIDS. The mechanism by which MA increases appetite is unknown, and its effectiveness for anorexia and cachexia in neoplastic and AIDS patients is under investigation. OBJECTIVES: To evaluate the efficacy, effectiveness and safety of MA in palliating anorexia-cachexia syndrome in patients with cancer, AIDS and other underlying pathologies. SEARCH STRATEGY: Studies were sought thorough an extensive search of the electronic databases, journals, reference lists, contact with investigators and other search strategies outlined in the methods. The most recent search was carried out on October 2002. SELECTION CRITERIA: Studies were included in the review if they assessed megestrol acetate compared to placebo or other drug treatments in randomized controlled trials of patients with a clinical diagnosis of anorexia-cachexia related to cancer, AIDS or another underlying pathology. DATA COLLECTION AND ANALYSIS: Data extraction was conducted by two independent authors, and methodological quality evaluated. Quantitative analyses were performed using appetite and quality of life as a dichotomous variable, and weight gain was analysed as continuous and dichotomous variables. Studies with more than 50% of patients lost to follow-up were excluded from the analysis. MAIN RESULTS: Thirty trials met the inclusion criteria (4123 patients). Twenty-one trials compared MA at different doses with placebo; four compared different doses of MA versus other drugs; two compared MA with other drugs and placebo; and three compared different doses of MA. For all patient conditions, meta-analysis showed a benefit of MA compared with placebo, particularly with regard to appetite improvement and weight gain in cancer patients. Analysing quality of life, clinical and statistical heterogeneity was found and discussed. There was insufficient information to define the optimal dose of MA. AUTHORS' CONCLUSIONS: This review demonstrates that MA improves appetite and weight gain in patients with cancer. No overall conclusion about quality of life (QOL) could be drawn due to heterogeneity. The small number of patients, methodological shortcomings and poor reporting have not allowed us to recommend megestrol acetate in AIDS patients or with other underlying pathologies.

Desarrollo de la conducta alimentaria en la infancia y sus alteraciones / Development of feeding behavior in childhood and its alterations

El desarrollo de la conducta alimentaria es un proceso complejo en el que participan componentes fisiológicos de regulación de la ingesta alimentaria, del crecimiento y peso corporal; componentes psicológicos del niño, de los padres y de la familia y además componentes culturales y sociales. Son frecuentes sus alteraciones en los primeros años de vida, las que se pueden traducir en un retraso del crecimiento, aversiones alimentarias y dificultades secundarias en la convivencia familiar. El manejo de estas alteraciones debiera estar basado principalmente en una educación preventiva en los primeros dos años de vida a la madre, en la modificación conductual del ambiente familiar (madre, hijo, otros miembros de ella) y sólo secundariamente considerar el manejo con fármacos

Intoxicación por ciproheptadina / Intoxication by cyproheptadine

La intoxicación por ciproheptadina, principal componente de los estimulantes del apetito, se ha transformado en un importante motivo de consulta en los servicios de urgencia a lo largo del país. Estos fármacos, utilizados muchas veces sin prescripción médica, dado su agradable sabor resultan atractivos para los preescolares quienes los ingieren en dosis que sobrepasan el nivel terapéutico, desencadenando cuadros muy variados, que van desde excitación psicomotora hasta la muerte