Circadian rhythm in prostate cancer: time to take notice of the clock / 亚洲男科学杂志(英文版)

The circadian clock is an evolutionary molecular product that is associated with better adaptation to changes in the external environment. Disruption of the circadian rhythm plays a critical role in tumorigenesis of many kinds of cancers, including prostate cancer (PCa). Integrating circadian rhythm into PCa research not only brings a closer understanding of the mechanisms of PCa but also provides new and effective options for the precise treatment of patients with PCa. This review begins with patterns of the circadian clock, highlights the role of the disruption of circadian rhythms in PCa at the epidemiological and molecular levels, and discusses possible new approaches to PCa therapy that target the circadian clock.

Effects of breast milk intake ratio during hospitalization on antibiotic therapy duration in preterm infants less than 34 gestational weeks: a multicenter retrospective cohort study / 中华围产医学杂志

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d<DOT≤15.0 d), Q 3 (15.0 d<DOT≤27.0 d) and Q 4 (DOT>27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%<breast milk intake ratio≤50%), medium-ratio breastfeeding group (50%<breast milk intake ratio≤75%) and high-ratio breastfeeding group (breast milk intake ratio>75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.

A study of chronopharmacological relevance of antihypertensive drugs prescription

Background: Chronopharmacology is the 搒cience dealing with the optimization of drug effects and minimization of adverse effects by timing the medications in relation to the biological rhythm.� In patients with hypertension, it is important to maintain a steady blood pressure throughout the day, which necessitates to have knowledge of chronopharmacology and drugs following it. Better understanding of the circadian rhythm and its application for drug administration serves productive utilization of drug. Aims and Objectives: This study aims to study the chronopharmacological relevance to the time of drug administration in general medicine inpatients at Gulbarga Institute of Medical Sciences, Kalaburagi. Materials and Methods: It is a prospective, non-interventional, observational study which was conducted on patients admitted in General Medicine wards at GIMS, Kalaburagi. A special pro forma was designed, and data were obtained from medical case records of patients suffering from various disorders admitted in the wards of general medicine. Demographic data, disease data, data pertaining to drug therapy, data pertaining to other comorbid illness, and adverse effects of drugs, if any, were collected. Descriptive statistics and other suitable statistical test were applied for analyzing the data. Results: A total of 110 patients who were on antihypertensive drugs and who meet the inclusion and exclusion criteria of the study were included in the study. The average age of both male and female was found to be between 45 and 68 years. Among 110 patients, 72 (65.45%) were male and 38 (34.54%) were female. In the current study, a total of 124 wide variety of antihypertensive drugs were recorded. The study of ideal time of administration of all antihypertensive drugs showed that, most of the prescription was according to chronopharmacological relevance. Conclusion: Updating the knowledge of chronopharmacology and its application in clinical practice will provide better health care. The current study highlights the importance of timing of administration of antihypertensive drugs in human health care.

Papel del ritmo circadiano en el infarto agudo de miocardio / Role of circadian rhythm in acute myocardial infarction

Múltiples investigaciones evidencian una máxima incidencia del infarto agudo de miocardio en la mañana. El objetivo de este artículo es revisar la organización del sistema circadiano, su importancia en la fisiología del sistema cardiovascular y su relación con el desarrollo del infarto agudo de miocardio. Se realizó una búsqueda bibliográfica en diferentes bases de datos para identificar artículos publicados durante los últimos 20 años, centrados en la variación circadiana del infarto agudo de miocardio y en la cronoterapia cardiovascular. Se preseleccionaron 115 artículos, de los cuales se escogieron 60. Se concluyó que la mayor incidencia matutina del infarto agudo de miocardio se explica por la acción conjunta de factores endógenos (aumento matutino de cortisol, catecolaminas, presión arterial, frecuencia cardiaca, resistencias vasculares) y exógenos (alteración en el ciclo sueño-vigilia, bipedestación, e inicio de la actividad) que predispone a ruptura de la placa ateromatosa y aparición de episodios trombóticos durante la mañana.

Multiple investigations show a maximum incidence of acute myocardial infarction in the morning. The objective of this article is to review the organization of the circadian system, its importance in the physiology of the cardiovascular system and its relationship with the development of acute myocardial infarction. A bibliographic search was carried out in different databases to identify articles published during the last 20 years, focused on the circadian variation of acute myocardial infarction and on cardiovascular chronotherapy. 115 articles were preselected, of which 60 were chosen. It was concluded that the higher morning incidence of acute myocardial infarction is explained by the joint action of endogenous factors (morning increase in cortisol, catecholamines, blood pressure, heart rate, vascular resistance) and exogenous (alteration in the sleep-wake cycle, standing, and onset of activity) that predisposes to rupture of the atheromatous plaque and the appearance of thrombotic episodes during the morning.

Qual o melhor horário da tomada da medicação anti-hipertensiva? / What is the best time to take antihypertensive medication?

A hipertensão arterial é a principal causa de morte precoce no mundo. Existem diversos fatores que contribuem para sua variação dentro da fisiologia do ritmo circadiano, e que exercem forte impacto sobre o controle da pressão arterial (PA). Os valores da PA sofrem interferência de acordo com o horário da medida. Nas primeiras horas da manhã PAS aumenta rapidamente em 20 a 25 mmHg e a PAD em 10 a 15 mmHg. As drogas anti-hipertensivas, sofrem diversas influências na sua absorção, metabolização e excreção dependentes do ritmo circadiano e de suas propriedades físico-químicas. O ciclo circadiano exerce grande impacto no controle da PA, e apenas modificando o horário das prescrições, seguindo o ritmo circadiano, talvez seja possível obter melhor controle pressórico com menor dose da medicação, reduzindo assim, as possíveis reações adversas

Hypertension is the leading cause of early death worldwide. Several factors contribute to its variation within the physiology of circadian rhythm, and these factors have a strong impact on blood pressure (BP) control. BP values are influenced by the measurement time. In the early hours of the morning, SBP increases rapidly by 20 to 25 mmHg and DBP by 10 to 15 mmHg. Antihypertensive drugs suffer from a variety of influences on their absorption, metabolism and excretion, depending on the circadian rhythm and its physical-chemical properties. The circadian cycle has a great impact on BP control, and only by changing the schedule of prescriptions, following the circadian rhythm, it may be possible to obtain better pressure control with a lower dose of medication, thus reducing potential adverse reactions

Preparation and Drug Release Mechanism of Time Controlled Explosive Pulsatile Tablets with Ethylcellulose Coating

Background The time rhythm of human body is associated with the occurrence and development of manydiseases, and it also affects the efficacy and pharmacokinetic characteristics of the corresponding therapeuticdrugs. Therefore, the chronopharmacological drug delivery system has potential applications. Aim In this work, it is proposed to develop a kind of pulsatile release tablet of simple structure and preparingprocess, thus to provide an alternative drug delivery system for therapeutic agents used in treatment of diseasesof typical onset biorhythm at period inconvenient to take drug.Methods Metoprolol tartrate (MT), a drug widely used clinically to treat cardiovascular diseases was selected asa model drug for developing pulsatile tablets of time-controlled explosive system (TES). The MT pulsatile tabletswere ethyl cellulose (EC) coating tablets produced by pan coating process, and the core tablets were preparedby direct compression. The formulation and process was optimized by single factor test and orthogonal design.Also, the pulsatile release mechanism of the tablets was discussed through investigating the water absorptionand swelling capacity of tablets as well as the mechanical properties of EC free film.Results A kind of pulsatile tablets of MT were developed with a drug release lag time around 7 h and a fastrelease of drug after lag time. When the swelling force of core tablet caused by water uptake was high enoughover the tensile strength of EC coating film, the MT pulsatile tablets demonstrated a shell-type exploding rupturedue to the great rigidity and weak flexibility of EC film, and then a fast pulsatile release of drug was observed.Both the swelling capacity of core tablet and the thickness of coating film together controlled the lag time of drugrelease. The lag time showed a good linear relationship with the thickness of coating film (r = 0.9984, P < 0.01).The sort and amount of fillers and disintegrants dominated the release behaviour after lag time.Conclusion The developed MT pulsatile tablets can exert a timely release of drug before peak onset period ofhypertension and angina pectoris early in the morning after drug taking around 22:00 P.M the night before. Thegood linear relationship between lag time and coating thickness enabled the pulsatile tablets to be used fordelivery of other therapeutic agents of similar chronotherapy demand by adjusting the coating thickness toachieve the appropriate lag time of drug release to match the different high attack rhythm of the exact diseases.

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

RESUMEN 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 % 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 % de los casos presentó ritmo circadiano no dipper y la cronoterapia disminuyó hasta un 10 % 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.

ABSTRACT 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 % 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 % of the cases showed no dipper circadian rhythm and the chronotherpy diminished to 10 % 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.

Formulation And In Vivo Evaluation Of Chronomodulated Drug Delivery Of Nimodipine

Chronotherapy has been emerging as a novel technology in the field of pharmaceutical research. Delivery of drugs with respect to the circadian rhythm has gained greater importance in the diseases such as diabetes, asthma and hypertension in producing maximum therapeutic action. Present study focus on the formulation and evaluation of Nimodipine pulsatile release tablets with the incorporation of Eudragit pH sensitive polymers used for the chronotherapy of hypertension. Pharmacologically Nimodipine is an anti-hypertensive agent that acts by blocking the L and N-type calcium channels. Evaluation parameters for Nimodipine tablets included friability, drug content, bulk and tapped density, angle of repose and Carr’s index and drug release in vitro and in vivo.

Research progress and new ideas in circadian gene Bmal1 and oncotherapy / 中国肿瘤临床

Circadian rhythm plays a role in regulating life activities and contributes to periodicity, orderliness, and synergy in organ-isms . The Bmal1 gene is one of the core components of the circadian rhythm system; the level of Bmal1 expression differs between tu-mor and normal tissues. Studies have shown that Bmal1 plays different roles in different tumors. Therefore, understanding the role of Bmal1 in different tumorigenesis could provide a new theoretical basis for early detection or effective treatment of tumors. In recent years, with the in-depth studies on time-based approaches, chrono-chemotherapy, which combines pharmacokinetics and biotic rhythm, has become one of the important methods of tumor treatment. Radiotherapy at different times can lead to differences in ra-diosensitivity, which makes chrono-radiotherapy increasingly prominent in tumor treatment. In-depth studies on circadian rhythm in cancer biology could provide new perspectives for tumor treatment.

Clinical Significance and Therapeutic Implication of Nocturnal Hypertension: Relationship between Nighttime Blood Pressure and Quality of Sleep

Recent global hypertension guidelines recommend an early, strict and 24-hour blood pressure (BP) control for the prevention of target organ damage and cardiovascular events. Out-of-office BP measurement such as ambulatory BP monitoring and home BP monitoring is now widely utilized to rule out white-coat hypertension, to detect masked hypertension, to evaluate the effects of antihypertensive medication, to analyze diurnal BP variation, and to increase drug adherence. Nocturnal hypertension has been neglected in the management of hypertension despite of its clinical significance. Nighttime BP and non-dipping patterns of BP are stronger risk predictors for the future cardiovascular mortality and morbidity than clinic or daytime BP. In addition to ambulatory or home daytime BP and 24-hour mean BP, nocturnal BP should be a new therapeutic target for the optimal treatment of hypertension to improve prognosis in hypertensive patients. This review will provide an overview of epidemiology, characteristics, and pathophysiology of nocturnal hypertension and clinical significance, therapeutic implication and future perspectives of nocturnal hypertension will be discussed.

Development and evaluation of multiparticulate biphasic system for the treatment of circadian diseases

Multiparticulate systems have biopharmaceutical advantages when compared to the monolithic systems, once they allow different patterns of drug release and can be used in different treatments. The aim of the present work was to develop a biphasic controlled release delivery system, using propranolol hydrochloride (PROP) that can be used for the treatment of circadian diseases. This system was obtained by the combination of cellulosic polymers hydroxypropyl methylcellulose (HPMC) and ethylcellulose (EC) in a 2² factorial experimental design, which allowed the optimization of the development stage. The pellets produced and used in biphasic formulations were evaluated for physical and chemical characteristics and presented acceptable results. The immediate fraction obtained showed the complete release in 30 min while the others kept the release of the drug for 24 h. This study showed that the combination of beads with different releasing characteristics allowed to obtain different release profiles, which can be modulated according to the pathological needs, especially with regard to circadian diseases that suffer alterations throughout the day.

Los ritmos circadianos en cáncer y la cronoterapia / The circadian rhythms in cancer and chronotherapy / Os ritmos circadianos em câncer e a cronoterapia

Los ritmos circadianos, períodos fisiológicos de 24 horas aproximadamente, coordinan la actividad temporal de la mayoría, si no, de todos los seres vivos del planeta. Uno de los procesos más importantes del cuerpo, la proliferación celular, también está regulado por el reloj biológico cuya alteración puede tener repercusiones directas en el desarrollo del cáncer. El concepto de cronoterapia ha surgido a partir de la evidencia que tanto la proliferación de las células, como los mecanismos responsables de la farmacocinética y la farmacodinamia de los antineoplásicos ocurren a horas específicas del día. En esta revisión se presentan las generalidades del ciclo circadiano y su relación con el ciclo celular y el cáncer. Además, se expone evidencia del uso de la cronoterapia en pacientes con leucemia linfocítica aguda y en estudios clínicos de cáncer de colon, endometrio y ovario con asignación aleatoria. Se concluye que la hora de administración de la quimioterapia debe tener en cuenta los ritmos circadianos de los pacientes. Se enfatiza en la necesidad de hacer estudios clínicos enfocados en la quimioterapia cronomodulada, con el fin de aumentar la tolerancia y efectividad de los medicamentos con los protocolos existentes.

Circadian rhythms, physiological periods of about 24 hours, coordinate the temporal processes of most, or maybe all, living beings on the planet. Cell proliferation, one of the most important events in the body, is also regulated by the biological clock, whose alteration may have a direct impact on cancer development. The concept of chronotherapy comes from evidence showing that both cell proliferation and the mechanisms responsible for pharmacokinetics and pharmacodynamics of antineoplastic drugs occur at specific times of the day. This review presents an overview of the circadian cycle and its relation to cell cycle and cancer. Also, it presents evidence for the use of chronotherapy in patients with acute lymphocytic leukemia and in randomized clinical trials for colon, endometrial and ovarian cancer. As a conclusion, the time of chemotherapy administration should take into account the circadian rhythms of patients. We emphasize on the need to conduct clinical trials focused on chronomodulated chemotherapy, in order to increase the tolerance and effectiveness of drugs under the existing protocols.

Os ritmos circadianos, períodos fisiológicos de 24 horas aproximadamente, coordenam a atividade temporal da maioria, se não, de todos os seres vivos do planeta. Um dos processos mais importantes do corpo, a proliferação celular, também está regulada pelo relógio biológico cuja alteração pode ter repercussões diretas no desenvolvimento do câncer O conceito de cronoterapia há surgido a partir da evidência que tanto a proliferação das células, como os mecanismos responsáveis da farmacocinética e a farmacodinâmica dos antineoplásicos ocorrem a horas específicas do dia. Nesta revisão se apresentam as generalidades do ciclo circadiano e sua relação com o ciclo celular e o câncer. Ademais, se expõe evidência do uso da cronoterapia em pacientes com leucemia linfocítica aguda e em estudos clínicos de câncer de cólon, endométrio e ovário com designação aleatória. Se conclui que na hora de administração da quimioterapia deve ter em conta os ritmos circadianos dos pacientes. Se enfatiza na necessidade de fazer estudos clínicos enfocados na quimioterapia cronomodulada, com o fim de aumentar a tolerância e efetividade dos medicamentos com os protocolos existentes.

The study on methotrexate therapy in collagen induced arthritis rats / 中华风湿病学杂志

Objective To explore the circadian rhythm of interleukin (IL)-6 in collagen induced arthritis (CIA) rats and investigate the effectiveness and safety of methotrexate (MTX) administered according to IL-6 rhythm.Methods Serum IL-6 concentrations of CIA and normal rats at different time points were measured by enzyme-linked immunosorbent assay (ELISA).CIA rats were randomly divided into the experimental group A,experimental group B and control group.MTX (1/7 mg·kg-1 ·d-1) was administered once a day when the IL-6 level began to increase or decrease in the experimental group,while MTX (1 mg/kg) administered once a week in the control group.Arthritis scores and leukocyte counts were observed.The production of IL-6 and C reactive protein (CRP) levels in the serum were measured.Moreover,histological changes in the ankle joint were examined.One-way analysis of variance (ANOVA),two independent sample t test were used to evaluate the experimental data.Results The plasma IL-6 levels in CIA rats were different at different time points,which began to increase at 18:00 and decrease at 6:00.Arthritis score in the experimental group A (4.8±0.7)was lower than that in the control group (5.8±1.0,t=2.256,P=0.0406) and experimental group B (5.5±0.5,t=2.393,P=0.0313).The levels of TNF-α [(185±21) ng/L],IL-6 [(99±6) ng/L],IL-1β[(20.1±1.6) ng/L] and CRP[(1251±282) μg/L] in the experimental group A were significantly lower than those in control group [TNF-α:(207±10) ng/L,t=2.726,P=0.016 4;IL-6:(100±6) ng/L,t=2.669,P=0.0183;IL-1β:(22.0±1.3) ng/L,t=2.814,P=0.0138;CRP:(1 417±278) μg/L,t=2.369,P=0.0327].The level of IL-6 in the experimental group A[(93±6) ng/L] was lower than that in the experimental group B [(99±6) ng/L,t=2.323,P=0.0358].Compared with the control group [(9650±1062)/μl],the counts of leukocyte in the experimental group A [(4595±603)/μl,t=3.841,P=0.0064] and experimental group B [(3833±585)/μl,t=4.442,P=0.003] were significantly lower.Compared with the control group (9.1 ±2.0),histopathology scores in the experimental group A (6.6±1.3,t=2.606,P=0.015) and experimental group B (7.4±1.3,t=3.857,P=0.0007) were significantly lower.Conclusion The plasma IL-6 levels in CIA rats have shown evident circadian rhythm.There-fore,once a day administration is better than once a week.The therapeutic effect of RA may be improved by administering MTX at the time points according to the circadian rhythm of IL-6.

Circadian rhythms of myocardial ischemia and chronotherapy / 药学实践杂志

The occurrence of the clinical manifestations of myocardial ischemia shows clear circadian rhythmicity ,and they are unevenly distributed during the 24 h with higher morbidity during the initial hours of the daily activity span and in the late afternoon or early evening .Such temporal patterns result from circadian rhythms in pathophysiological mechanisms plus cyclic environmental stressors that trigger these clinical events .β‐receptor antagonist medications ,oral nitrate ,and calcium channel blocker have been shown to be influenced by the circadian time of their administration .Here we briefly review the char‐acteristics of circadian rhythmicity in MI ,the pathophysiological mechanisms as well as the current chronotherapy ,and then discuss the future treatment strategies .

Effects of chronotherapy on neutrophils in breast cancer patients / 中国实用护理杂志

Objective To investigate the effect of chronotherapy (chemotherapy plus timely medication) on neutrophils in breast cancer patients with neoadjuvant chemotherapy.Methods Fifty breast cancer patients with neoadjuvant chemotherapy were selected from 2011 to 2014 and divided into chronotherapy group and conventional treatment group (conventional group) by random number table method with 25 cases each.Conventional group received conventional neoadjuvant chemotherapy and conventional drug treatment.Chronotherapy group received neoadjuvant chemotherapy combined with chronochemotherapy and timely medication treatment,and applied clinical nursing care pathway.Both groups were conducted three cycles of chemotherapy,three weeks after the first and the second chemotherapy,the results of routine blood and liver function were compared in patients between two groups.The number of readmission and fever because of agranulocytosis were calculated.Results The two groups of patients were successfully completed three cycles of chemotherapy,after the first cycle of chemotherapy,the neutrophil was (4.40 ± 2.20)x109/L in chronotherapy group,and (3.18 ± 1.35) × 109/L in conventional group;after the second cycle of chemotherapy,the neutrophil was (3.95 ± 1.58) × 109/L,and (2.83 ± 1.49) x 109/L in conventional group,the two groups were statistically significant,t=2.375,2.563,P ＜0.05.Two cases needed readmission in chronotherapy group during chemotherapy,accounting for 8％(2/25),much lower than conventional group of 8 cases accounting for 32％(8/25).Conclusions The use of chronotherapy in breast cancer chemotherapy has less neutropenia,mild side effects of bone marrow suppression.It is an effective and safe viable option.

Clinical Experience with Low-dose Modified-release Prednisone Chronotherapy in Asian Patients with Rheumatoid Arthritis in Singapore

OBJECTIVE: To examine the demographic profile and treatment patterns in patients with rheumatoid arthritis (RA) prescribed low-dose modified-release prednisone (LODOTRA(R)) on a named patient basis in Singapore and to evaluate safety and clinical outcome of the treatment. METHODS: Medical records of adult patients with RA who had inadequate responses to prior RA treatment and were prescribed low-dose modified-release prednisone between January and December 2012 at a specialist clinic were reviewed retrospectively. Demographics, treatment information, relevant laboratory evaluations, and disease condition, prior to and after the start of treatment, were collected. RESULTS: Thirty-eight patients were enrolled. The mean age was 52.8 years and median disease duration was 1.3 years (0.04 to 8.2 years). Patients received a mean daily dose of 5.0+/-1.0 mg of modified-release prednisone for a median period of 4.4 months (0.2 to 11.8 months). Before treatment, the majority of patients received disease-modifying anti-rheumatic drugs (78.9%), glucocorticoids (71.0%), and non-steroidal anti-inflammatory drugs (NSAIDs) (68.4%). After the start of treatment, prescription of NSAIDs declined from 68.4% to 28.9%. Similar laboratory findings were observed before and after treatment. The median C-reactive protein level decreased substantially from 9.8 mg/L (0.2 to 77.7 mg/L) to 3.9 mg/L (0.4 to 27.6 mg/L). High proportions of patients reported improvement or recovery from morning stiffness (94.7%) or joint pain (70.0 to 100.0%) after treatment. The median number of painful joints decreased from 4 (1 to 8) to 0 (0 to 4) after treatment. CONCLUSION: Our clinical experience in Asian patients with RA suggests that low-dose modified-release prednisone chronotherapy is associated with similar treatment patterns, safety profile, and clinical outcomes as in Western populations.

Active surveillance of renal masses: an analysis of growth kinetics and clinical outcomes stratified by radiological characteristics at diagnosis

AIMS To determine the growth rate of renal masses (RMs) under active surveillance (AS), and to describe the clinical outcome of AS patients. Materials and Methods We conducted a retrospective review of an AS database to obtain demographics, radiological and pathologic characteristics and RM size of patients. RMs were followed at 6-12 month intervals for ≥1 year with computed tomography (CT), magnetic resonance imaging (MRI), or renal ultrasound. Kaplan-Meier analysis determined the annual likelihood of intervention. RMs were divided into 3 radiographic subcategories (solid, cystic, and angiomyolipoma). A linear regression model determined RM growth rates. Results 131 RMs in 114 patients were included. Median age, Charlson Comorbidity Index score and mean follow-up were 69.1 years, 4.0 and 4.2±2.6 years, respectively. Maximal tumor diameter (MTD) at diagnosis was 2.1±1.3 cm. 49 RMs exhibited negative or zero net growth. Mean MTD growth rate for all RMs was 0.72±3.2 (95% CI: 0.16-1.28) mm/year. When stratified by MTD at diagnosis, mean RM growth rates were 0.84, 0.84, 0.44, 0.74 and 0.71 mm/year for RMs <1 cm, 1-<2cm, 2-<3cm, 3-<4cm and ≥4cm, respectively (p<0.01). The 5 and 10-year freedom from intervention rates were 93.1% and 88.5%, respectively. There was a single case of suspected metastases, but no deaths related to kidney cancer. Conclusions RMs under AS grew slowly, and had a low incidence of requiring surgical intervention and progression. Solid enhancing masses grew slowly, and were more likely to trigger intervention. AS should be considered for selected patients with small RMs. .

Cronoterapia y psiquiatría: aspectos a considerar en la clínica / Chronotherapy and psychiatry: issues to consider clinic

Se ha demostrado que las funciones fisiológicas oscilan durante ciclos de 24 horas (circadianos), menos de 24 horas (ultradianos) y mayores de 24 horas (infradianos), lo que se denomina ritmos biológicos (cronobiología). El presente artículo hace énfasis en cómo los ritmos biológicos pueden incidir en la respuesta a los medicamentos y la terapéutica psiquiátrica (cronofarmacología, cronoterapia). Esta variable de estudio podría ofrecer nuevos márgenes en la eficacia y seguridad de los medicamentos y hacer su uso más racional.

It has been shown that physiological functions oscillate during cycles of 24 hours (circadian), of less than 24 (ultradian) and larger than 24 hours (infradian). These are called biological rhythms (chronobiology). This article emphasizes on how biological rhythms may influence response to drugs and psychiatric treatment (chronopharmacology, chronotherapy). The study of this variable could offer new perspectives on efficacy and safety of drugs in order to pursue a more rational use of them.

Clinical Significance of Nighttime Blood Pressure / 대한내과학회지

It was impossible to measure the nighttime blood pressure in patients with hypertension for more than one hundred years. The introduction of ambulatory blood pressure monitoring made it possible to evaluate the nighttime blood pressure and clinical significances in recent 40 years. There are tremendous evidences for proving that the nighttime blood pressure is the more powerful predictor in cardiovascular morbidity and mortality than conventional office and ambulatory daytime blood pressure. The cardiovascular mortality can be reduced when 5% of nighttime blood pressure decreased from Ohasama registry report. So investigators should reevaluate the antihypertensive drugs in the view points of nighttime blood pressure reduction. And changing the administration schedule of antihypertensive drugs, so called chronotherapy, is effective for controlling the nighttime blood pressure and modifying the blood pressure circadian rhythm. Korean Ambulatory Blood Pressure (KORABP), nationwide ambulatory blood pressure monitoring registry in Korea, may answer unproved questions for controlling nighttime blood pressure.

Study of community nursing intervention on medication compliance of hypertension patients / 中国实用护理杂志

Objective To discuss the effect of community nursing intervention on medication compliance and control rates of blood pressure in patients with essential hypertension.Methods Community nursing intervention was conducted to 73 community patients with essential hypertension. The patients' medication compliance was compared before and after intervention and their control of blood pressure was also observed. Results The difference was statistically significant in the comparison of patients' knowledge of antihypertension and the proper use of antihypertensive drugs before and after intervention. Blood pressure control rate was 80.82%.Conclusions Community nursing intervention can improve patients' medication compliance and effectively control the blood pressure of the patients.