Pharmacokinetics,safety and metabolite profiling of minesapride,a novel 5-HT4 receptor partial agonist,in healthy elderly and young subjects

Minesapride is a novel 5-hydroxytryptamine 4 (5-HT₄) receptor partial agonist that is expected to show efficacy in patients with irritable bowel syndrome with predominant constipation and functional constipation. An open-label study was conducted to evaluate pharmacokinetics (PK) and safety of minesapride. Japanese subjects, 12 elderly and 12 young, received a single oral dose of minesapride 40 mg/day in the fasted state. Metabolite profiles were also investigated in this clinical study and in an in vitro study using cryopreserved hepatocytes. Clinical results showed that minesapride was rapidly absorbed (C_max: 2302.1 ng/mL in the elderly group, 2117.5 ng/mL in the young group), and the plasma concentration then decreased with half-life of approximately 7 h. There were no notable PK differences between elderly and young groups. No serious adverse events (AEs) were observed. The only AE that occurred in 2 or more subjects was diarrhea. Metabolite profiles in plasma and urine were similar between elderly and young groups. No major metabolites exceeded 10% of unchanged minesapride, and results of the in vitro study suggested that there were no human-specific metabolites. From the viewpoints of PK and metabolite profiling, no dose adjustment of minesapride is warranted in elderly population without renal or hepatic impairment.     

Pain Trajectories and Predictors: A 7-Year Longitudinal Study of Women With Vulvodynia

IntroductionA significant proportion of women report a reduction of symptoms over time—even without treatment—yet the natural progression of vulvodynia and which factors may explain decrease vs persistence of pain remain unclear.AimTo identify subgroups of pain trajectories in women with vulvodynia and to predict these different trajectories by treatments undertaken, pain characteristics, and psychosocial factors.MethodsData on pain intensity, treatments undertaken, pain characteristics, and psychosocial factors were collected 3 times over a 7-year period from 173 women who screened positive for vulvodynia. Latent class growth analysis was conducted to identify homogeneous subgroups with distinct pain trajectories. A multivariate binomial logistic regression was used to examine whether treatments, pain characteristics, and psychosocial factors predicted these trajectories.Main Outcome MeasureThe main outcome was pain intensity (0–10), measured at 3 time points with the numerical rating scale.Results2 pain trajectories were identified: 1 where pain persisted (28.9%), and 1 where pain decreased over time (71.1%). Whether a treatment had been undertaken was not predictive of the course of pain over time. Women who were older at first pain onset, had pain at another location than the entrance of the vagina, and reported more anxiety were more likely to have a persistent pain trajectory relative to the decreased pain trajectory.Clinical ImplicationsFindings suggest that the evolution of pain differs among women with vulvodynia depending on pain characteristics and anxiety.Strengths & LimitationsStrengths of the study include the 7-year longitudinal design to examine the natural history of provoked vestibulodynia and the inclusion of biopsychosocial factors as predictors of pain trajectories. However, women with major medical and psychiatric illnesses or deep dyspareunia were not included, and, thus, these factors could not be examined as predictors.ConclusionAssessing baseline characteristics associated with different pain trajectories during medical visits could have positive implications for the management of vulvodynia.Pâquet M, Vaillancourt-Morel M-P, Jodouin J-F, et al. Pain Trajectories and Predictors: A 7-Year Longitudinal Study of Women With Vulvodynia. J Sex Med 2019;16:1606–1614.     

实时校验本年盈余与预算结余差异调整法探讨

正确编制“本年盈余与预算结余差异调节表”是公立医院执行《政府会计制度》的一大难点,现有的几种差异调节方法存在诸多不足,核算正确与否依赖会计人员的基本素质,而且工作量巨大。以财务会计与预算会计差异产生的基本原理为基础,利用计算机软件实时校验并自动登记差异,是简便、高效、准确编制“本年盈余与预算结余差异调节表”的方法,本文对此进行了举例说明。     

Peak C-reactive protein levels do not predict 30-day mortality for bacteremia: A retrospective cohort study

IntroductionAlthough peak C-reactive protein (CRP) levels are correlated with the prognosis of some diseases, there have been no reports regarding the association between peak CRP levels and mortality in patients with bacteremia. The present study aimed to determine the association between peak CRP levels and prognosis in patients with bacteremia.MethodsThis retrospective cohort study was conducted in a single tertiary hospital and included patients with bacteremia admitted to the emergency department from November 2012 to March 2017. Cox regression analysis was performed to examine the association between peak CRP levels and 30-day mortality. We also performed propensity score adjustment using potential confounding factors.ResultsOne hundred fifty-nine patients were included in the study. Peak CRP levels were significantly higher in the β-hemolytic streptococci (P = 0.001) and Streptococcus pneumoniae (P = 0.003) groups. The C-statistic of the multivariate logistic regression model for the propensity score was 0.88. For 30-day mortality, peak CRP levels >20 mg/dL did not show significance in the Cox regression analysis (hazard ratio, 0.866; 95% confidence interval, 0.489–1.537; P = 0.62). Even after propensity score adjustment, no significance was noted (hazard ratio, 0.865; 95% confidence interval, 0.399–1.876; P = 0.71).ConclusionsPeak CRP levels were not an independent predictor of mortality in patients with bacteremia in the emergency department. Clinicians should consider that patients with extremely high peak CRP levels do not necessarily have high mortality and vice versa.     

Real‐time RF pulse adjustment for B0 drift correction

Although the magnetic field of an MR scanner is very stable under little or no load, it can become less stable under heavy‐duty cycle conditions, such as in diffusion tensor imaging (DTI). Uncorrected, such field drifts lead to an apparent image shift along the phase‐encoding direction and decreasing effectiveness of fat saturation pulses. A method is presented to adjust the center frequency of all RF pulses and the receiver in real time during the acquisition. No data postprocessing or changes to the sequence timing are necessary. In vivo acquisitions were performed to assess the prolonged effectiveness of fat saturation. Field drifts of approximately 2.5 Hz/min were measured and corrected during DTI acquisitions at b‐values of up to 3000 s/mm². The effectiveness of fat saturation diminished over the duration of an 18‐min acquisition when the drift was left uncorrected. The proposed method corrects for apparent image shift and ensures continuously effective fat saturation over the duration of an acquisition. Magn Reson Med, 2006. © 2006 Wiley‐Liss, Inc.     

MEAW技术在固定矫治末期精细调整中的应用

目的：探讨MEAW技术在错He畸形固定矫治末期进行精细调整中的应用效果。方法：选取处于方丝弓固定矫治后期遗留局部小开He，上下颌牙齿尖窝交错关系未建立，中线未对齐等缺陷的病例7例，年龄14～24岁，平均年龄17．6岁，采用MEAW技术加颌间弹力牵引，进行咬合关系的精细调整。结果：经过MEAW技术3～6个月的调整，全部病例均达到预期的矫治效果，上下牙列建立了正常的覆He覆盖关系和良好的尖窝咬合关系。结论：对于固定矫治末期出现的小缺陷，通过MEAW技术加各种不同方向和力值的颌间弹力牵引，进行牙列的精细调整，能很好地恢复咬合关系，提高矫治效果。     

Early parental adjustment to visible congenital disfigurement

Summary When a baby is born with a visible disfigurement, then parents need to adjust to the loss of the anticipated 'perfect' child and thus accept their baby. The impact of the birth on the parents is described in the context of a measure which identifies areas of potential difficulty. The two groups studied were parents of children with cleft palates and parents of children with congenital hand deficit. A wide range of adjustment was found. There was no significant difference between the two groups in terms of their overall adjustment, but there were individual differences in adjustment which did not relate to the severity or type of anomaly. The only significant variable found to relate to parental adjustment was perceived family support.     

The Relative Contribution of Domains of Quality of Life to Overall Quality of Life for Different Chronic Diseases

This study examined the contribution of the quality of life (QoL) domains physical, social and psychological functioning to the explanation of overall QoL. Various disorders may differentially affect QoL domains due to disease-specific factors and, consequently, the relationship between QoL domains and overall QoL may vary between diseases. We therefore studied this relationship for several diseases as well as the differential impact of these diseases on QoL. The present study had a cross-sectional design. We selected patients (aged 57 years and older) with one of the following eight chronic medical conditions: lung disorder, heart condition, hypertension, diabetes mellitus, back problems, rheumatoid arthritis, migraine, or dermatological disorders. The total group of respondents included 1457 patients and 1851 healthy subjects. Regression analyses showed that the domain of psychological functioning contributed to overall QoL for all disorders, whereas physical and social functioning contributed to overall QoL for some disorders. Differences were found between most patient groups and healthy subjects with respect to physical functioning; with respect to social and psychological functioning some groups differed from the healthy group. Explanations for the findings and implications for clinical practice are discussed.     

Subjective bias in reports of poor work adjustment in depressed patients

Twenty-five depressed inpatients were asked to report their adjustment at work during the 4-month period preceding their hospitalization. Two separate reports were given: the first during the acute illness phase and the second one 10-28 days later, after symptomatic remission following standardized pharmacotherapy. Thirty-two percent more patient ratings showed absence of adjustment problems on the second report compared with the first. Significant differences between the 2 reports were found in 7 of the 9 items on the Structured and Scaled Interview to Assess Maladjustment, which is designed to assess specific aspects of maladjustment at work. The changes in the scores of maladjustment correlated with the changes in the scores of depressive symptoms, and 40% of the variation in maladjustment scores was accounted for by the pessimism item of the Montgomery-Asberg Depression Rating Scale. Much of the poor work adjustment reported by the acutely depressed patients thus seems to be caused by symptom-related subjective bias.