Clinical features and outcomes at discharge of outborn very preterm infants of different ages after interhospital transfer / 中华围产医学杂志

Objective:To analyze the distribution of ages at the interhospital transfer of outborn very preterm infants in China and to compare their perinatal characteristics and outcomes at discharge and neonatal intensive care unit (NICU) treatment.Methods:A total of 3 405 outborn very premature infants with a gestational age of 24-31 +6 weeks who were transferred to the NICUs of the Chinese Neonatal Network (CHNN) in 2019 were included in this retrospective study. According to the age at transfer, they were divided into three groups: early transfer (≤1 d), delayed transfer (>1-7 d) and late transfer (>7 d) groups. Analysis of variance, t-test, Chi-square test (Bonferroni correction), Kruskal-Wallis test and Wilcoxon rank-sum test were used to compare the general clinical condition, treatment, and outcomes at discharge among the three groups. Results:The median gestational age was 29.7 weeks (28.3-31.0 weeks) and the average birth weight was (1 321.0 ± 316.5) g for these 3 405 infants. There were 2 031 patients (59.6%) in the early transfer group, 406 (11.9%) in the delayed transfer group and 968 (28.4%) in the late transfer group. Infants who received continuous positive airway pressure ventilation and tracheal intubation in the delivery room accounted for 8.4% (237/2 806) and 32.9% (924/2 805), respectively. A total of 62.7% (1 569/2 504) of the mothers received antenatal glucocorticoid therapy and the ratio in the early transfer group was 68.7% (1 121/1 631), which was higher than that in the delayed transfer group [56.1% (152/271), χ2=16.78, P<0.017] and the late transfer group [49.2% (296/602), χ2=72.56, P<0.017]. The total mortality rate of very premature infants was 12.7% (431/3 405), and the mortality rates in the early, delayed and late transfer groups were 12.4% (252/2 031), 16.3% (66/406) and 11.7% (113/968), respectively ( χ2=5.72, P=0.057). The incidences of severe intraventricular hemorrhage, late-onset sepsis, necrotizing enterocolitis, and bronchopulmonary dysplasia at the corrected gestational age of 36 weeks or discharge were all higher in the delayed and late transfer groups than in the early transfer group, respectively. The incidences of retinopathy of prematurity, retinopathy of prematurity requiring treatment and bronchopulmonary dysplasia at the corrected gestational age of 36 weeks or discharge in the late transfer group were significantly higher than that in the delayed transfer group (Bonferroni correction, all P<0.017). In the late transfer group, the median age of very premature infants at discharge was 66.0 d (51.0-86.0 d), and the corrected gestational age at discharge was 38.9 weeks (37.1-41.2 weeks), and both were greater than those in the early transfer [48.0 d (37.0-64.0 d), Z=260.83; 36.9 weeks (35.7-38.3 weeks), Z=294.32] and delayed transfer groups [52.0 d (41.0-64.0 d), Z=81.49; 37.4 weeks (36.1-38.7 weeks), Z=75.97] (all P<0.017). Conclusions:Many very premature infants need to be transferred to higher-level hospitals after birth. The later the very premature infants are transferred, the higher the incidence of complications will be. It is suggested that intrauterine or early postnatal transport may improve the prognosis of very premature infants.

Design and optimization of self-microemulsifying drug delivery system (SMEDDS) of felodipine for chronotherapeutic application

The objective of this research work was to design, develop and optimize the self micro-emulsifying drug delivery system (SMEDDS) of Felodipine (FL) filled in hard gelatine capsule coated with polymer in order to achieve rapid drug release after a desired time lag in the management of hypertension. Microemulsion is composed of a FL, Lauroglycol FCC, Transcutol P and Cremophor EL. The optimum surfactant to co-surfactant ratio was found to be 2:1. The resultant microemulsions have a particle size in the range of 65-85 nm and zeta potential value of -13.71 mV. FL release was adequately adjusted by using pH independent polymer i.e. ethyl cellulose along with dibutyl phthalate as plasticizer. Influence of formulation variables like viscosity of polymer, type of plasticizer and percent coating weight gain was investigated to characterize the time lag. The developed formulation of FL SMEDDS capsules coated with ethyl cellulose showed time lag of 5-7 h which is desirable for chronotherapeutic application.

O objetivo desse trabalho de pesquisa foi planejar, desenvolver e otimizar sistema de liberação de fármaco auto-microemulsificante(SMEDDS) de felodipino (FL) em cápsulas de gelatina dura revestidas com polímero, a fim de obter liberação rápida após tempo desejado no manejo da hipertensão. A microemulsão é composta de FL, lauroglilcol FCC, Transcutol P e Cremophor EL. A proporção ótima de tensoativo e de co-tensoativo foi de 2:1. As microemulsões resultantes têm tamanho de partícula na faixa de 65-85 nm com potencial zeta de -13,71 mV. A liberação de FL foi ajustada adequadamente, utilizando-se polímero independente de pH, como etilcelulose com ftalato de dibutila como plastificante. A influência das variáveis da formulação, como viscosidade do polímero, tipo de plastificante e ganho percentual de peso do revestimento foi investigada para caracterizar o intervalo de tempo de liberação. A formulação de cápsulas de FL SMEDDS revestidas com etilcelulose mostrou intervalo de tempo de liberação de 5 a 7 horas, o que é desejável para uma aplicação cronoterapêutica.

The effects of chronotherapy on non-dipper patients with refractory hypertension / 中国基层医药

Objective To investigate whether switching anti-hypertensive medication to bedtime could improve blood pressure control in non-dipper patients with refractory arterial hypertension.Methods 30 patients (as observation group) with refractory arterial hypertension and non-dipper pattern on ambulatory blood pressure monitoring were shifted all non-diuretic anti-hypertensive drugs from morning to evening.22 patients with similar characteristics and no changes in the therapeutic regimen formed the control group.Results After 12 weeks treatment,the changes of 24h average systolic/diastolic blood pressure,average diastolic blood pressure during the day and the average diastolic blood pressure at day/nigh were-(2.8 ± 4.2)/-(2.1 ± 3.4)mm Hg,(-1.1 ± 3.1)mm Hg and (-6.3 ±5.9)/(-4.3 ±5.7)mm Hg,respectively.The decrease of mean systolic blood pressure and mean diastolic blood pressure in the observation group were significantly larger than those in the control group(all P ＜0.05).The circadian blood pressure profile changed from non-dipper to dipper in 6 cases in the observation group and no changes were observed in the control group(x2 =4.974,P =0.0263).There was also no difference between two group in terms of untoward reaction.Conclusion In non-dipper patients with refractory arterial hypertension,changing the timing of anti-hypertensive medication to the evening could improve blood pressure control aud help the abnormal circadian blood pressure profile recover to the normal.

Pulsatile Drug Delivery System: an Approach of Medication according to Circadian Rhythm.

Pulsatile drug delivery systems are developed to deliver drug according to circadian behavior of diseases. This means that these systems will deliver drug at time when disease display it’s most morbid and mortal state within a circadian cycle (24 hrs.). The product follow a sigmoidal drug release profile characterized by a time period of no release (lag time) followed by a rapid and complete drug release. Thus drug can be delivered at right time, in right amount and at right site of action by use of such approach. The potential benefits of chronotherapeutics have been investigated and established for number of diseases like asthma, arthritis, cancer, diabetes, epilepsy, hypertension, ulcer, hypercholesterolemia etc. Various capsular, osmotic, single and multiple unit systems that are modulated by soluble or erodible polymer coatings, rupturable membranes are available in market. These systems are beneficial for diseases showing chronopharmacological behavior where night time dosing is required or for the drugs having high first pass effect or having site specific absorption in GIT, or for drugs with high risk of toxicity or tolerance. These systems also improve patient compliance by decreasing dosing frequency.

Antimicrobial activity assessment of time-dependent release bilayer tablets of amoxicillin trihydrate

The aim of present study was the assessment of antimicrobial activity of prepared time-dependent release bilayer tablets of amoxicillin trihydrate and in vitro evaluation of drug release by antimicrobial assay using agar plate diffusion method. The bilayer tablets comprised of a delayed and sustained release layer. Direct compression method was used for the preparation of bilayer tablets containing Eudragit-L100 D55 as delayed release polymer, and HPMCK4M and HPMCK15 as sustained release polymers. The prepared bilayer tablets containing amoxicillin trihydrate were evaluated for hardness, thickness, friability, weight variation and drug content. Further, in vitro drug release was assessed by antimicrobial assay using S. aureus and E. coli as test microorganisms. The aliquot samples of in vitro drug release study were found to be effective against both microorganisms for 16 hours due to sustained action. The in vitro drug release study and antimicrobial assay showed that bilayer tablets have sustained release profile of drug delivery with time-dependent burst release after a lag-time of 2 hours. The lower MIC value (2 µg/mL) of prepared bilayer tablets vis-à-vis marketed preparation (5 µg/mL) represented its good antimicrobial activity.

O objetivo do presente estudo foi avaliar a atividade antimicrobiana de formulações de comprimidos de dupla camada contendo amoxicilina triidratada para liberação tempo dependente e avaliação da liberação in vitro do fármaco pelo ensaio de atividade antimicrobiana utilizando o método de difusão em placa de ágar. Os comprimidos de dupla camada consistem em uma camada para liberação retardada e outra sustentada. O método de compressão direta foi usado para a preparação dos comprimidos de dupla camada contendo Eudragit-L 100 D55 como polímero para liberação retardada e HPMCK4M ou HPMCK15 como polímeros para liberação sustentada. As formulações de comprimidos de dupla camada contendo amoxicilina triidratada foram avaliadas quanto a dureza, espessura, friabilidade, variação de peso e conteúdo de fármaco. Além disso, a liberação do fármaco in vitro foi avaliada por ensaio de atividade antimicrobiana usando S. aureus e E. coli como microrganismos teste. A alíquota das amostras do estudo de liberação do fármaco in vitro demonstrou ser efetiva contra ambos os microrganismos por um período de 16 horas devido à ação sustentada. O estudo de liberação do fármaco in vitro e o ensaio de atividade antimicrobiana mostraram que os comprimidos de dupla camada tiveram um perfil de liberação sustentada do fármaco com um pico de liberação após 2 horas de ensaio. O menor valor de MIC (2 ug/mL) dos comprimidos de dupla camada quando comparados à formulação comercial (5 ug/mL) representa uma boa atividade antimicrobiana.

Chronotherapeutics: A range of newer drug delivery approaches for better patient compliance.

A major objective of chronotherapy in the treatment of several diseases is to deliver the drug in higher concentration during the time of greatest need according to the circadian onset of the disease or syndrome. The physiology and biochemistry of a human being is not constant during the 24 hours, but it shows some variability in a predictable manner as defined by the timing of peak and trough of each of the body circadian processes and functions in relation to the time. There are quite a few approaches are in progress to control the drug to the desired degree to the clinical physiology of diseases with the aid of single unit and multiparticulate systems. The chronotherapy of a medication may be accomplished by the judicious timing of conventionally formulated tablets and capsules are of current interest.

Promotion of Tissue Regeneration with Acupuncture / 针灸推拿医学（英文版）

Acupuncture can promote the regeneration of tissues. That acupuncture therapy can be called Regenerative Acupuncture, which is based upon the idea that by the unlimited and universal power of qi the process of creation can be triggered again, disabled or destroyed physiological functions of organs and tissues can be restored, and even the reconstruction and renewal of a physically disabled or destroyed organ or tissue might be possible. Regenerative Acupuncture, its point selection and its rationale are based on the ancient and modern Chinese acupuncture literature and clinical experiences of the authors. Now this acupuncture method was introduced by one case report.

Extraordinary Vessels Needling for Vascular Dementia / 针灸推拿医学（英文版）

Purpose To observe the clinical efficacy of extraordinary vessels needling in treating vascular dementia. Method 39 cases vascular dementia were treated by acupoints selected from the eight extraordinary meridians and the time needling techniques such as eight methods of spiritual turtle, in accordance with time period and pattern identifition. Results 2 cases were cured, 30 cases improved and 7 cases failed; the total effective rate was 82.1%. Conclusion Extraordinary vessels needling has positive effects in treating vascular dementia.