Monitoreo ambulatorio de presión arterial y respuesta a la cronoterapia en pacientes diabéticos hipertensos / Ambulatory blood pressure monitoring and chronotherapy response in a diabetic hypertensive population

Fundamento: múltiples estudios avalan las aplicaciones del monitoreo ambulatorio de presión arterial en el seguimiento y evaluación de los paciente diabéticos hipertensos, es Regla de Oro en el control de estos enfermos y predice daño orgánico. Objetivo: caracterizar pacientes diabéticos hipertensos mediante los parámetros del monitoreo de tensión arterial (ritmo circadiano, presión del pulso, carga hipertensiva, hipertensión al despertar, índice de masa corporal y respuesta a cronoterapia). Métodos: se realizó un estudio descriptivo longitudinal para caracterizar los pacientes diabéticos hipertensos mediante el monitoreo ambulatorio de presión arterial de 24 horas y su respuesta a la cronoterapia, en el laboratorio del Hospital Universitario Manuel Ascunce Domenech de Camagüey, en los años 2017-2018. El universo del trabajo estuvo constituido por 179 casos que cumplieron con el criterio diagnóstico de hipertensión arterial no controlada y diabetes asociada por más de 12 meses, con 70 porciento de las mediciones de tensión arterial válidas. Resultados: predominó el sexo femenino en el estudio la edad mayor a 60 años constituyó un factor de riesgo de comorbilidades (obesidad, hipertrofia ventricular, enfermedad renal y cardiopatía isquémica crónica). El 50 porciento de los casos presentó ritmo circadiano no dipper y la cronoterapia disminuyó hasta un 10 porciento la carga hipertensiva sistólica y la presión del pulso. Conclusiones: el monitoreo ambulatorio de presión arterial demostró ser un valioso instrumento para facilitar información precisa del perfil de presión arterial de 24 horas, posibilitó individualizar el tratamiento y determinar daño vascular. La respuesta a la cronoterapia facilitó el control del diabético hipertenso (AU)

Background: multiples studies support the use of ambulatory blood pressure monitoring, the follow up procedure and evaluation of the diabetic patient with hypertension; it is considered a golden rule in the control of these sick people and predict target organ. Objective: to characterize the diabetic hypertensive patients by means of the monitoring parameters of blood pressure (circadian rhythm, pulse pressure, hypertensive charge, hypertension at wake up time, body mass index, and the response to chronotherapy) Methods: an descriptive longitudinal study was conducted in order to characterize the diabetic hypertensive patients by means of a 24 hour blood pressure ambulatory monitoring and its response to the chronotherapy, at Manuel Ascunce Domenech Universitary Hospital laboratory from 2017 to 2018. The target universe was composed of 179 cases with criteria of high blood pressure and diabetes diagnostics associated for over 12 months, accounting 70 percent of the blood pressure valid measurements in 24 hours. Results: in the research, the female gender prevailed; over 60 years the comorbidity increased (obesity, left ventricular hypertrophy, kidney disease and chronic ischemic cardiopathy). The 50 percent of the cases showed no dipper circadian rhythm and the chronotherpy diminished to 10 percent the night systolic hypertensive charge and the pulse pressure. Conclusions: the ambulatory blood pressure monitoring proved to be a valuable tool to facilitate accurate information about the 24-hour blood pressure profile, it made possible to individualize the treatment and determine the vascular damage. The response to the chronotherapy facilitated the hypertensive diabetic patient control (AU)

Cronoterapia con fármacos antihipertensivos y glaucoma / Chronotherapy with anti-hypertensive drugs and glaucoma

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Effectiveness of evening phototherapy for insomnia is reduced by bright daytime light exposure.

OBJECTIVE: To examine the effect of ambulatory daytime light exposure on phase delays and on the advances produced by timed exposure to bright evening or morning light. METHODS: As a subset of a larger study, 32 older (63.0 ± 6.43 years) adults with primary insomnia were randomized to an at-home, single-blind, 12-week, parallel-group study entailing daily exposure to 45 min of scheduled evening or morning bright (∼4000 lux) light. Light exposure patterns during the baseline and the last week of treatment were monitored using actigraphs with built-in illuminance detectors. Circadian phase was determined through analysis of in-laboratory collected plasma melatonin. RESULTS: Less daytime light exposure during the last week of treatment was significantly associated with larger phase delays in response to evening light (r's>0.78). Less daytime light exposure during the last week of treatment was also associated with a significant delay in wake time (r's>-0.75). There were no such relationships between light exposure history and phase advances in response to morning light. CONCLUSIONS: Greater light exposure during the daytime may decrease the ability of evening light, but not morning light, exposure to engender meaningful changes of circadian phase.

Biological rhythms, medication safety, and women's health.

Biological processes and functions in women are well organized in time, as evidenced by the expression of ultradian (high frequency), circadian ( approximately 24-hour), circamensual ( approximately monthly), and circannual ( approximately yearly) rhythms and by the changes that occur with menarche, reproduction, and menopause. Attributes of women's circamensual structure have been explored in depth, particularly with regard to fertility/infertility and birth control. However, the role of 24-hour and other rhythms in health, disease, and treatment has been little studied. The symptom intensity of a variety of chronic medical conditions is rhythmic, as is the risk of severe events, such as stroke and myocardial infarct (MI). Improving the safety, efficacy, and preventive qualities of medications requires the understanding of how rhythms impact drug pharmacokinetics and pharmacodynamics. The therapeutic and adverse effects of prescription and nonprescription medications widely used by women can vary markedly with the (circadian) time of administration. Circadian rhythm-dependent differences in the safety of medications are particularly relevant to pregnant women; laboratory animal studies show that the fetal toxicity of various treatments varies not only with developmental stage but also with circadian time. Rhythm-dependent differences in the actions of medications are also of great importance to perimenopausal and postmenopausal women, who are advised to ingest prescribed pharmacotherapy for osteopenia and osteoporosis in the morning to minimize the risk of adverse effects and, as a consequence, may elect to take other medications at times not recommended in the instructions for their use. Medication trials must be comprehensive and representative of women and men of different life stages, ethnicities, and likely times (morning vs. evening) of drug use.

Intrinsically long-acting agents compared with long-acting chronoformulations.

Intrinsically long-acting antihypertensive drugs may be characterized by long elimination half-lives with high trough: peak ratios for decreasing blood pressure. These agents are usually administered once daily in the morning, and at steady-state they provide 24 h blood pressure control, attenuate the early-morning surge in blood pressure, and maintain a normal circadian blood pressure pattern. In comparison, chronoformulations incorporate shorter-acting antihypertensive drugs into a delivery system that is delayed-onset or extended-release, or both. These agents, which are often designed to be given once daily at bedtime, deliver peak drug concentrations that coincide with the early-morning surge in blood pressure. Chronoformulations also provide 24 h blood pressure control. In highly compliant patients, both intrinsically long-acting drugs and chronoformulations are likely to provide comparable blood pressure control. However, in poorly compliant patients who miss doses of medication, intrinsically long-acting drugs are likely to be superior, because they sustain blood pressure control beyond the dosing interval.

A chronopharmacodynamic study on standard heparin, a low molecular weight heparin (nadroparin) and danaproid: establishing and comparing the daily variations of these drugs in rats.

The effects of dosing time on the anticoagulant activity of unfractionated heparin, low molecular weight heparin (nadroparin) and danaproid were investigated. The chronopharmacological comparisons of the drugs were done on the anti-Xa, anti-IIa activities and activated partial thromboplastin time assays. Several dosing times were considered and an analysis based on a population approach was adopted. Under unfractionated heparin, the pharmacological activities did not exhibit significant daily variations. In contrast, significant daily profiles were observed in all the biological assays performed with low molecular weight heparin. Anti-Xa and anti-IIa activities showed some fluctuations over a 24-hour period with a peak at noon. As for the variations of the activated partial thromboplastin time, two peaks were noted early in the morning and at the beginning of nightfall. As for danaproid, only a daytime maximum of anti-Xa activity could be found.

Circadian rhythm sleep disorders in adolescents: clinical trials of combined treatments based on chronobiology.

Delayed sleep phase syndrome (DSPS) and non-24-h sleep-wake rhythm are circadian rhythm sleep disorders that are common in adolescents. Most patients have difficulty adjusting to school life, poor class attendance or refuse to go to school. Since a treatment has not been established, the present paper is presented to propose a strategy for treating circadian rhythm sleep disorders in adolescents, based on our clinical studies. Twenty subjects (12 males and eight females, mean age 16.2+/-1.7 years) participated in the study. The onset of sleep disorder occurred between the ages of 11 and 17. The most common factors affecting the onset of disorders were changes in social environment. The subjects kept a sleep-log for the periods before and during treatments. The treatments were based on chronobiology: resetting the daily life schedule, chronotherapy, regulation of the lighting environment, methylcobalamin, and/or melatonin. Bright light exposure was successful in 10 patients, of whom four were treated with methylcobalamin. Melatonin treatment was successful in two patients (one with and one without chronotherapy). Thirteen of the 20 patients were successfully, treated with therapies based on chronobiology. After consideration of these results, a step-by-step procedure of combined treatments for the circadian rhythm sleep disorders is proposed.

Use of 2% propofol to produce diurnal sedation in critically ill patients.

OBJECTIVE: The assessment of propofol to produce diurnal sedation in critically ill patients. DESIGN: Prospective clinical study. SETTING: Intensive Care Unit, University Hospital. PATIENTS AND PARTICIPANTS: Thirty consecutive patients admitted to the Intensive Care Unit older than 18 years who were expected to be sedated for more than 50 h. INTERVENTIONS: The patients were randomised into two groups. All received sedation with a constant background infusion of morphine and a variable infusion rate of propofol, which was altered hourly to maintain the intended sedation score. The first group received constant light sedation (CLS) over 50 h aiming for a Ramsay score of 2-3. The second group received CLS between 0600 h and 2200 h and additional night sedation (ANS) with propofol between 2200 h and 0600 h, aiming for a sedation score of 4-5. MEASUREMENTS AND RESULTS: Patients were studied for 50 h from 1800 h on the first day of admission. Recordings of heart rate, blood pressure, sedation scores and propofol and morphine infusion rates were made hourly. An APACHE II score was recorded for each patient. Sedation scores were analysed by blind visual assessment and cosinor analysis, which is used in chronobiology to examine the correlation of data with a cosine curve. Patients in the ANS group had significantly better rhythmicity of sedation levels using cosinor analysis (r = 26% v 8%) p < 0.01. There was no difference between the CLS and ANS groups with respect to age, sex or APACHE II scores. Nine out of 15 patients in the ANS group achieved diurnal sedation. Three patients in the CLS group showed diurnal rhythmicity of sedation, which can be attributed to natural sleep, and had a median APACHE II score of 12. Five patients in the CLS group and three in the ANS group showed a deep constant sedation pattern. They had high APACHE II scores (median 21.5) and an obtunded conscious level on admission due to severe sepsis. CONCLUSION: Propofol can safely provide diurnal sedation in the critically ill when titrated against the Ramsay score. Sedation levels cannot be manipulated in some severely ill patients.