Efectividad del tratamiento no farmacológico para el insomnio crónico de pacientes polimedicados / Effectiveness of non-pharmacological treatment for chronic insomnia in polypharmacy patients

Objetivo Analizar la efectividad de las medidas de higiene del sueño y la terapia conductual basada en el control de estímulos para el insomnio crónico de pacientes polimedicados. Diseño Estudio de intervención sin grupo control tipo antes-después. Emplazamiento Centro de Salud Molino de la Vega (Huelva). Participantes Se seleccionó una muestra aleatoria de 235 pacientes polimedicados. La intervención se realizó en 28 pacientes que cumplían los criterios de inclusión. Intervención Enseñar las medidas de higiene del sueño y la terapia de control de estímulos en sesiones semanales individuales de 30min de duración durante 6 semanas. Intervención Seguimiento con los diarios de sueño y el cuestionario de calidad del sueño de Pittsburg. Mediciones Variables dependientes: calidad del sueño, latencia y tiempo total de sueño, tiempo despierto después de iniciado el sueño. Resultados Se incluyeron 196 pacientes. 65,8% mujeres, edad media de 68,5 años (DE=9,3). El 68,9% duermen mal. Peor calidad del sueño en los que consumen hipnóticos (p=0,001) y en las mujeres (p=0,003). Resultados 28 pacientes iniciaron la intervención, hubo 3 pérdidas. Resultados Tras la misma mejoran todos los parámetros. La puntuación en el cuestionario de calidad del sueño de Pittsburg disminuye en promedio 4,8 puntos (IC95% 3,9–5,6); la latencia en 23,4min (IC95%: 15,2–31,5) y el tiempo despierto después de iniciado el sueño en 34,9 (IC95%: 18,1–51,8); el tiempo total de sueño se incrementa en 71,6min (IC95%: 42,6–100,5). Conclusiones Las medidas en higiene del sueño y el control de estímulos han sido efectivas en pacientes polimedicados con insomnio crónico (AU)

Objective To examine the effectiveness of sleep hygiene education and behavioral therapy based on stimulus control for chronic insomnia in patients using many drugs. Design Quasi-experimental study without before-after control group. Setting Molino de la Vega Health Care Center (Huelva). Participants A random sample of 235 patients using five or more drugs. A total of 28 participants fulfilled the conditions for intervention. Intervention Teaching sleep hygiene and stimulus control for six 30-minute sessions. Follow-up through sleep diaries and the Pittsburg Sleep Quality Index (PSQI) were used for monitoring. Measurements The main outcome measures were sleep quality, sleep-onset latency (SL), total sleep time (TST) and total wake time (TWT). Results 196 patients were included in the study (65.8% female, mean age 68.5 (SD 9.3) years. 68.9% of the patients reported sleep problems. Patients using hypnotic drugs (p=0.001) and women (p=0.003) had worse sleep quality. Of the 28 participants enrolled in the intervention, 3 dropped out. The intervention had improved all outcome measures. PSQI score decreased an average of 4.8 points (95% CI: 3.9–5.6); SL decreased 23.4 minutes (95% CI: 15.2–31.5) and TWT 34.9 (95% CI: 18.1–51.8); TST showed an increase in 71.6 minutes (95% CI: 42.6–100.5). Conclusions Sleep hygiene education and stimulus control have been effective in patients with chronic primary insomnia and polypharmacy (AU)

Efectividad del tratamiento no farmacológico para el insomnio crónico de pacientes polimedicados / Effectiveness of non-pharmacological treatment for chronic insomnia in polypharmacy patients

Objetivo: Analizar la efectividad de las medidas de higiene del sueño y la terapia conductual basada en el control de estímulos para el insomnio crónico de pacientes polimedicados. Diseño. Estudio de intervención sin grupo control tipo antes-después. Emplazamiento: Centro de Salud Molino de la Vega (Huelva). Participantes: Se seleccionó una muestra aleatoria de 235 pacientes polimedicados. La intervención se realizó en 28 pacientes que cumplían los criterios de inclusión. Intervención: Enseñar las medidas de higiene del sueño y la terapia de control de estímulos en sesiones semanales individuales de 30min de duración durante 6 semanas. Intervención: Seguimiento con los diarios de sueño y el cuestionario de calidad del sueño de Pittsburg. Mediciones Variables dependientes: calidad del sueño, latencia y tiempo total de sueño, tiempo despierto después de iniciado el sueño. Resultados: Se incluyeron 196 pacientes. 65,8% mujeres, edad media de 68,5 años (DE=9,3). El 68,9% duermen mal. Peor calidad del sueño en los que consumen hipnóticos (p=0,001) y en las mujeres (p=0,003). Resultados: 28 pacientes iniciaron la intervención, hubo 3 pérdidas. Resultados: Tras la misma mejoran todos los parámetros. La puntuación en el cuestionario de calidad del sueño de Pittsburg disminuye en promedio 4,8 puntos (IC95% 3,9–5,6); la latencia en 23,4min (IC95%: 15,2–31,5) y el tiempo despierto después de iniciado el sueño en 34,9 (IC95%: 18,1–51,8); el tiempo total de sueño se incrementa en 71,6min (IC95%: 42,6–100,5). Conclusiones: Las medidas en higiene del sueño y el control de estímulos han sido efectivas en pacientes polimedicados con insomnio crónico (AU)

Objective: To examine the effectiveness of sleep hygiene education and behavioral therapy based on stimulus control for chronic insomnia in patients using many drugs. DesignQuasi-experimental study without before-after control group. Setting Molino de la Vega Health Care Center (Huelva). Participants: A random sample of 235 patients using five or more drugs. A total of 28 participants fulfilled the conditions for intervention. Intervention Teaching sleep hygiene and stimulus control for six 30-minute sessions. Follow-up through sleep diaries and the Pittsburg Sleep Quality Index (PSQI) were used for monitoring. Measurements: The main outcome measures were sleep quality, sleep-onset latency (SL), total sleep time (TST) and total wake time (TWT).Results196 patients were included in the study (65.8% female, mean age 68.5 (SD 9.3) years. 68.9% of the patients reported sleep problems. Patients using hypnotic drugs (p=0.001) and women (p=0.003) had worse sleep quality. Of the 28 participants enrolled in the intervention, 3 dropped out. The intervention had improved all outcome measures. PSQI score decreased an average of 4.8 points (95% CI: 3.9–5.6); SL decreased 23.4 minutes (95% CI: 15.2–31.5) and TWT 34.9 (95% CI: 18.1–51.8); TST showed an increase in 71.6 minutes (95% CI: 42.6–100.5). Conclusions: Sleep hygiene education and stimulus control have been effective in patients with chronic primary insomnia and polypharmacy (AU)

NPY-Y1 receptor antisense injected centrally in rats causes hyperthermia and feeding.

The central actions of neuropeptide Y antisense oligodeoxynucleotide (aNPY) and NPY-Y1 receptor antisense (aNPY-Y1) on body temperature (Tb), feeding and body weight of unrestrained rats were determined by the repeated intracerebroventricular (i.c.v.) injection of 0.5 microgram doses. aNPY-Y1 caused intense phasic rises in Tb, lowered body weight and caused transient feeding. aNPY increased food intake paradoxically, accompanied by a gain in body weight but did not affect Tb. Circadian activity was unaffected by either antisense oligodeoxynucleotide, and the mismatched NPY (mNPY) was without effect. These results show that NPY-Y1 receptors underlie the central thermolytic action of NPY, since aNPY-Y1 induces hyperthermic responses. Overall, the functional reduction in NPY activity by aNPY might cause a compensatory de novo synthesis of NPY in structures remote from the ventricles to augment feeding behavior.

Antisense to NPY-Y1 demonstrates that Y1 receptors in the hypothalamus underlie NPY hypothermia and feeding in rats.

Neuropeptide Y (NPY) is a highly potent endogenous peptide which when injected into the medial hypothalamus causes spontaneous eating behaviour and an intense fall in body temperature (Tb). This study used antisense oligodeoxynucleotides (ODNs) to determine whether the Y1 subtype of NPY receptor could underlie these remarkable physiological responses. In the unrestrained rat, the ventromedial hypothalamus (VMH) which is highly reactive to NPY was injected with antisense for NPY (aNPY), Y1 receptors (aNPY-Y1) and mismatched controls (mNPY; mNPY-Y1). After cannulae were implanted bilaterally in the brain of 19 rats, 0.4 or 0.8 microgram per 0.8 microliter of the phosphorothioate synthesised ODNs were delivered to the VMH of the rats at 12 h intervals over 2 d. Only the lower dose of aNPY-Y1, but not aNPY, evoked an intense phasic rise in the Tb following each micro-injection. Simultaneously, 0.4 microgram per 0.8 microliter of aNPY-Y1, but not aNPY, suppressed feeding behaviour after a sequence of micro-injections and on the following day. Body weights and locomotor activity of the rats likewise declined concomitantly with the hyperthermia and hypophagia caused by the Y1 receptor antisense. Neither of the control ODNs for NPY or Y1 receptors injected similarly in the VMH of the rats exerted any effects on these measures. These results clearly provide convincing evidence that in the VMH the Y1 subtype of NPY receptor mediates, in part, the neuronal mechanisms responsible for spontaneous feeding and hypothermia produced by native NPY when applied directly to this structure. The concurrent decline in body weight and activity caused by aNPY-Y1 could be caused by the episodes of hyperthermia.

Role of interleukin-1 beta, interleukin-6 and macrophage inflammatory protein-1 beta in prostaglandin-E2-induced hyperthermia in rats.

The purpose of this study was to investigate the role of pyrogenic cytokines, such as IL-1 beta, IL-6 and MIP-1 beta, in the mechanisms underlying the hyperthermic response of rats to central injection of PGE2. Thus, specific murine neutralizing antibodies against these cytokines were micro-injected directly into the anterior hypothalamic, preoptic area (AH/POA) of unrestrained rats just before intracerebroventricular injection of PGE2. The significant hyperthermia induced by PGE2 was markedly suppressed by micro-injection of anti-IL-6 and partially attenuated by anti-IL-1 beta. However, the micro-injection of anti-MIP-1 beta failed to alter the hyperthermic response. The results indicate that PGE2-induced hyperthermia is presumably mediated through actions of IL-6 on the thermosensitive cells of the AH/POA and confirm that distinct and alternate pathways exist in the rat brain for the induction of fever.

Cytokines and thermoregulation: interleukin-9 injected in preoptic area fails to evoke fever in rats.

A number of the members of the family of cytokines including IL-1, IL-2, IL-6, and IL-11 act directly in the brain to induce a febrile response in the rat and other species. The purpose of this study was to examine the effect of interleukin-9 (IL-9) when this cytokine is applied directly to the thermosensitive and pyrogen reactive region of the anterior hypothalamic, preoptic area (AH/POA). In male Sprague-Dawley rats, guide cannulae for microinjection into the AH/POA were implanted stereotaxically, and radio transmitters for monitoring body temperature (Tb) were placed intraperitoneally. Following postoperative recovery, recombinant murine macrophage inflammatory protein (MIP)-1 beta was microinjected in the AH/POA of each rat in a dose of 28 pg/microliters to identify pyrogen reactive sites in the AH/POA. Then recombinant human IL-9 was suspended in pyrogen-free CSF vehicle and microinjected in the same sites in concentrations of 2.4, 24, and 240 U/microliters. In contrast to the pyrexic action of MIP-1 beta, IL-9 failed to elicit a significant alteration in the Tb of the rats at any of the doses tested. IL-9 was also without effect on the intakes of either water or food. These results demonstrate that IL-9 applied to the region of the diencephalon in which other cytokines act to evoke fever may not play a direct role in the thermogenic component underlying the acute phase response. However, as demonstrated in several different cell systems, IL-9 may require a cofactor related to pyrogen for a febrile response to develop.

Fever and feeding in the rat: actions of intrahypothalamic interleukin-6 compared to macrophage inflammatory protein-1 beta (MIP-1 beta).

The chemokines, macrophage inflammatory protein-1 (MIP-1) and its subunit MIP-1 beta, induce an intense fever in the rat when they are injected directly into the anterior hypothalamic, pre-optic area (AH/POA), a region containing thermosensitive neurons. The purpose of this study was to compare the central action on body temperature (Tb) of MIP-1 beta with that of interleukin-6 (IL-6), which also has been implicated in the cerebral mechanism underlying the pathogenesis of fever. Following the stereotaxic implantation in the AH/POA of guide cannulae for repeated micro-injections, radio transmitters which monitor Tb continuously were inserted intraperitoneally in each of 15 male Sprague-Dawley rats. Each micro-injection was made in a site in the AH/POA in a volume of 1.0 microliter of pyrogen-free artificial CSF, recombinant murine MIP-1 beta, or recombinant human IL-6. MIP-1 beta in a dose of 25 pg evoked an intense fever characterized by a short latency, a mean maximum rise in Tb of 2.4 +/- 0.21 degrees C reached by 3.7 +/- 0.42 hr, and a duration exceeding 6.5 hr. Injected into homologous sites in the AH/POA, IL-6 induced a dose dependent fever of similar latency and a mean maximal increase in Tb of 1.2 +/- 0.25 degrees C, 1.8 +/- 0.15 degrees C, and 2.1 +/- 0.22 degrees C and duration of 6.2 +/- 1.28 hr, 6.7 +/- 0.49 hr, and 6.8 +/- 0.65 hr when given in doses of 25, 50, and 100 ng, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Fever produced by interleukin-11 (IL-11) injected into the anterior hypothalamic pre-optic area of the rat is antagonized by indomethacin.

A number of cytokines including the family of interleukins and the macrophage inflammatory proteins act in the brain to produce fever. The purpose of this study was to determine whether the recently discovered hematopoietic progenitor cell stimulator, interleukin-11 (IL-11), alters the body temperature (Tb) of the rat when the cytokine is delivered directly to the thermosensitive and pyrogen reactive region of the hypothalamus. A guide cannula for micro-injection into the anterior hypothalamic pre-optic area (AH/POA) was implanted stereotaxically in each of 19 male Sprague-Dawley rats. A Mini-mitter transmitter for continuous monitoring of Tb of the animal was implanted i.p. Following postoperative recovery, recombinant human IL-11 was micro-injected in a volume of 1.0 microliter into the AH/POA in a dose of 2.7, 13.5, 27 or 250 ng. rhuIL-11 evoked a dose dependent fever with a mean rise in Tb of 0.91 +/- 0.06 degrees C, 1.68 +/- 0.11 degrees C and 0.99 +/- 0.08 degrees C following 13.5 ng, 27 ng and 250 ng, respectively. No significant change in Tb of the rats was produced by 2.7 ng IL-11 or the CSF control vehicle. A significant decline in the intake of food occurred also after the micro-injection of the 27 ng of IL-11. Prior treatment of the rat with 5.0 mg/kg of a prostaglandin synthesis inhibitor, indomethacin, administered intraperitoneally attenuated significantly the febrile response induced by the 250 ng dose of IL-11. These results demonstrate that IL-11 possesses potent thermogenic properties when acting within the ventral forebrain.(ABSTRACT TRUNCATED AT 250 WORDS)

[Pharmaceutical marketers: professional and informative aspects]. / Los visitadores médicos: aspectos profesionales y formativos.

This study tries to know the opinion of pharmaceutical detailers about their profession, as well as their pharmacological knowledge. 75 questionnaires were distributed to an equal number of detailers. The questionnaires were composed of two parts. In the first one, several questions about their profession were posed. In the second one, the questions were about Pharmacology. The main results were that most of them have got only lower degrees; however, they all have carried out training courses in their companies. With regard to pharmacological questions, percentage of success was 61%.

[Pharmacological knowledge among general physicians]. / Análisis de los conocimientos farmacológicos de médicos generales.

We inquired to 200 physicians about the 50 pharmaceutical products most dispensed in Seville during 1989. The most significative results were: 68.5% of the inquired answered the questionnaire. 98.5% knew the product, but only 80.3% prescribed it. The principal sources of information to know the drug were books and scientific journals (67.3%), followed by detailers (62%). 86.1% knew the composition of the product, and 94.9% knew its indications. 71.5% described the side effects, 66.4% the contraindications, and 25.5% the interactions with other drugs. Only 56.9% mentioned a therapeutic alternative.

[An analysis of drug advertising in non-specialty medical journals]. / Análisis de la publicidad medicamentosa en revistas médicas no especializadas.

It has been evaluated drug advertisement in four medical journals during 1989. A questionnaire allows us to evaluate pharmacological and advertising data. The main results obtained are the following: amoxicillin + clavulanic acid was the more advertising drug; the ratio publicity/pharmacological information was 3:1; 60% of the advertising products were new drugs, and only a 6% were essentials drugs according to WHO; slogans were acceptable; generally, aspects such as dosage and toxicology are referred. However, it is necessary to improve information about drug use in elderly patients, patients with impaired renal functional, as well as the necessary information in adverse drug reactions.

[The effects of ticlopidine and nifedipine on platelet aggregation in patients with obliterating arteriopathy of the lower limbs]. / Efectos de la ticlopidina y el nifedipino sobre la agregación plaquetaria en pacientes con arteriopatía obliterante de miembros inferiores (AOMI).

This paper evaluates the antiaggregant action of ticlopidine and nifedipine in patients with obliterate arteriopathy in inferior limbs of arteriosclerotic etiology (OAIL). They were established 4 study groups: control, with health volunteers without treatment (N = 10); patients treated with placebo (n = 11); patients treated with 500 mg/day of ticlopidine (n = 12) and treated with 30 mg/day of nifedipine (n = 12). The last 3 groups the treatment duration was 30 days. It was studied the platelet aggregatory activity against ADP and collagen, before drug administration and at 15 and 30 days post-treatment. Our results suggest that: Platelet aggregation is increased in patients with AOMI compared with that observed in the control group. Ticlopidine inhibits platelet aggregation induced by ADP, but not that induced by collagen. Nifedipine doesn't produce any effect on platelet aggregation.