Population pharmacokinetics of oxycodone in plasma and cerebrospinal fluid after epidural and intravenous administration

Objectives: To establish the first plasma and cerebrospinal fluid (CSF) oxycodone population pharmacokinetic (PopPK) model after epidural (EPI) and intravenous (IV) oxycodone administration.

Methods: The study was conducted with 30 female subjects undergoing elective gynecological surgery with epidural analgesia. A parallel single dose of EPI oxycodone with IV placebo (EPI group; n = 18) or IV oxycodone with EPI placebo (IV group; n = 12) was administered. An epidural catheter for drug administration was placed at T12/L1 and a spinal catheter for CSF sampling at L3/4. Plasma and CSF for oxycodone analysis were frequently collected. A PopPK model was built using the NONMEM software package.

Results: Plasma and CSF oxycodone concentrations were evaluated using separate central plasma and CSF compartments and separate peripheral plasma and CSF compartments. Epidural space served as a depot compartment with transfer to both the plasma and CSF central compartments. The population parameters for plasma clearance and apparent distribution volumes for central and peripheral compartments for plasma and CSF were 37.4 L/h, 90.2 L, 68.9 L, 0.035 L (fixed based on literature), and 0.039 L, respectively.

Conclusion: A PopPK model was developed and found to precisely and accurately describe oxycodone time-concentration data in plasma and CSF.     

他克莫司群体药动学在儿童肝移植中的研究进展

他克莫司治疗窗窄，药动学个体差异大，临床难以建立儿童受者的个体化治疗方案。群体药动学（PPK）在个体化给药研究方面有巨大优势。为了实现他克莫司在儿童肝移植受者中的个体化治疗，国内外学者致力于儿童肝移植受者的PPK研究，但各研究的结果存在差异。本文通过检索PubMed、Web of Science及Scopus数据库中的相关文献，着重分析了既往他克莫司PPK在儿童肝移植受者中的研究，总结影响他克莫司PPK参数的主要因素，期望应用PPK方法为构建儿童肝移植受者的个体化治疗方案奠定基础。     

Estudio de la obesidad en una población infantil rural y su relación con variables antropométricas

GoalsTo know the prevalence of obesity in primary and secondary school students, and to evaluate the diagnostic accuracy of anthropometric variables for its detection.DesignCross-sectional study.LocationRural area of Córdoba. In the year 2014.ParticipantsStudent population. A stratified sampling was performed according to age, gender and educational centers. A total of 323 students from 6 to 16 years were included in the study, all parents had signed informed consent.Main measurementsThe prevalence of obesity was determined and sociodemographic, anthropometric, physical condition and dietary predictor variables were collected. A binary logistic regression was performed determining crude and adjusted Odds Ratio (OR) values, ROC curves were obtained and cut-off values were determined, calculating the sensitivity, specificity and Youden index.ResultsThe prevalence of overweight and obesity was 26.2% and 22.3%, respectively. Only 15.2% of school children had an optimal Mediterranean diet. The waist-height ratio (WtHR) was the predictive variable with the highest adjusted OR 7.1 (4.3-11.6) and the largest area under the curve 0.954 (0.928-0.979), from a global cut-off value to discriminate obesity of 0.507. This gave a sensitivity of 90% and specificity of 87.2%.ConclusionsThe high prevalence of obesity, the low-medium adherence to the Mediterranean diet and the low physical fitness make this population a priority target for the prevention of future cardiovascular events. The WtHR has been the best anthropometric predictor of obesity, recommending its use for the diagnosis of obesity in children at the expense of body mass index.     

locStra: Fast analysis of regional/global stratification in whole‐genome sequencing studies

locStra is an ‐package for the analysis of regional and global population stratification in whole‐genome sequencing (WGS) studies, where regional stratification refers to the substructure defined by the loci in a particular region on the genome. Population substructure can be assessed based on the genetic covariance matrix, the genomic relationship matrix, and the unweighted/weighted genetic Jaccard similarity matrix. Using a sliding window approach, the regional similarity matrices are compared with the global ones, based on user‐defined window sizes and metrics, for example, the correlation between regional and global eigenvectors. An algorithm for the specification of the window size is provided. As the implementation fully exploits sparse matrix algebra and is written in C++, the analysis is highly efficient. Even on single cores, for realistic study sizes (several thousand subjects, several million rare variants per subject), the runtime for the genome‐wide computation of all regional similarity matrices does typically not exceed one hour, enabling an unprecedented investigation of regional stratification across the entire genome. The package is applied to three WGS studies, illustrating the varying patterns of regional substructure across the genome and its beneficial effects on association testing.     

The association of sleep quality and night sleep duration with coronary heart disease in a large-scale rural population

ObjectiveThe purposes of the present study were to explore independent and interactive associations between night sleep duration, night sleep quality and coronary heart disease (CHD) based on a rural population in China.MethodsA total of 27,935 participants (11,177 men and 16,758 women) were investigated from the Henan Rural Cohort. Information about sleep was assessed by using the Pittsburgh Sleep Quality Index (PSQI). Restricted cubic splines and logistic regression were used to estimate the relationship between night sleep duration and quality with CHD.ResultAmong the 27,935 participants, 1506 participants with CHD were identified. Compared with participants with scores lower than 3, the odds ratios (ORs) and 95% confidence intervals (95% CIs) of participants with score of 3–5, 6–8, ≥9 were respectively 1.42 (1.24–1.63), 1.99 (1.70–2.33), and 2.56 (2.13–3.08) with full adjustment of covariates. Compared with night sleep duration of 7 h, men and women who slept less than 5 h were 1.55 (1.11–2.17), 1.12 (0.59–2.12) and 1.80 (1.20–2.68), after being adjusted ORs (95% CIs) of the total. Moreover, the ORs and 95% CIs of CHD increased with the shortening of sleep duration at PSQI score above the highlighted levels.ConclusionPoor sleep quality and short night sleep duration were all associated with CHD in Chinese rural areas. Moreover, the association was more obvious in women. In addition, the strongest prevalence of CHD was found in short sleepers with poor sleep quality.     

Patterns of patient reluctance to receive complementary-medicine treatments in a hospital setting: A cross-sectional study

ObjectiveWe aim to characterize the patient population that exhibits reluctance to undergo complementary medicine (CM) treatments in a hospital setting.MethodsWe conducted a cross-sectional prospective study among patients prior to hospitalization using structured questionnaires in a single center in Israel. Participants were asked to rate their degree of consent to receiving CM treatments during hospitalization.ResultsThe CM-reluctant group was 7.1 % of the study cohort. The CM modalities most commonly refused were spiritual guidance, acupuncture, and energy and healing therapies. The CM-reluctant population showed a weaker relation to spiritual content and tended to value complementary medicine's effectiveness less in comparison to the CM-consenting group. The main reason for reluctance was skepticism of the perceived effectiveness of CM.ConclusionsWith skepticism playing a major role in decision making, we should question whether the Stakeholders in the field of CM and public health services are succeeding in explaining the benefits and risks of CM treatments.