Risk of Positive Nonsentinel Nodes in Women with 1–2 Positive Sentinel Nodes Related to Age and Molecular Subtype Approximated by Receptor Status

We examine risk of positive nonsentinel axillary nodes (NSN) and ≥4 positive nodes in patients with 1–2 positive sentinel nodes (SN) by age and tumor subtype approximated by ER, PR, and Her2 receptor status. Review of two institutional databases demonstrated 284 women undergoing breast conservation between 1997 and 2008 for T1‐2 tumors and 1 (229) or 2 (55) positive SN followed by completion dissection. The median number of SN and total axillary nodes removed were 2 (range 1–10) and 14 (range 6–37), respectively. The rate of positive NSNs (p = 0.5) or ≥4 positive nodes (p = 0.6) was not associated with age. NSN were positive in 36% of luminal A, 26% of luminal B, 21% of TN and 38% of Her2+ (p = 0.4). Four or more nodes were present in 17% of luminal A, 13% luminal of B, 0% of TN and 29% of Her2+ (p = 0.1). Microscopic extracapsular extension was significantly associated with having NSNs positive (55% versus 24%, p < 0.0001) and with having total ≥4 nodes positive (33% versus 7%, p < 0.0001). In a population that was largely eligible for ACOSOG Z0011, the risk of positive NSN or ≥4 positive nodes did not vary significantly by age. The TN subgroup had the lowest risk of both positive NSN or ≥4 positive nodes. Several high risk groups with >15% risk for having ≥4 positive nodes were identified. Further data is needed to confirm that ACOSOG Z0011 results are equally applicable to all molecular phenotypes.     

200例慢性肾脏疾病患者营养状况与病程进展的关系

目的探讨主观综合营养评估法（subjective global assessment of nutrition,SGA）评价慢性肾脏疾病（chronic kidney disease,CKD）2～4期患者营养状态并分析其与病程进展的关系。方法对200例CKD患者进行分组：①根据肾小球滤过率（estimated glomerular filtration rate,eG-FR）分为CKD2期组、3期组、4期组;②根据SGA评估分为营养正常组、轻一中度营养不良组和重度营养不良组;③根据病程进展分为进展1组、进展2组、进展3组。于随访第1天、第12个月、第24个月分别检测血红蛋白（hemoglobin,Hb）,白蛋白（albumin,Alb）,前白蛋白（prealbumin,PA）,血清钙（Ca）,血清磷（P）,分析CKD患者的营养状况与病程进展的关系。结果在随访第1天、第12个月、第24个月,CKD4期组与2期组Hb比较有显著性差异;4期组与3期组比较,差异有统计学意义（P〈0．05）,但2期组与3期组比较无统计学差异;CKD2期组第1天与12个月Hb比较差异有统计学意义（P〈O．05）。CKD4期组随访第1天、第12个月、第24个月PA比较,均有统计学差异（P〈0．05）。在第1天、12个月,营养正常组、轻一中度营养不良组、重度营养不良组Alb组间比较,差异有统计学意义;轻一中度营养不良组随访第1天、第12个月、第24个月比较,均有统计学差异（P〈0．05）。重度营养不良组随访第1天、第12个月、第24个月PA比较,均有统计学差异（P〈0．05）。CKD患者不同营养状况与病程进展发生率差异有统计学意义（P〈0．05）,且重度营养不良患者进展3组发生率为92．6％。结论Alb可作为营养状况的评价指标之一。CKD患者PA随着肾功能下降及病程的延长而升高。重度营养不良对CKD患者病程进展影响较大,SGA评估CKD患者的营养状态具有一定临床参考价值。     

A Theory-Based Newsletter Nutrition Education Program Reduces Nutritional Risk and Improves Dietary Intake for Congregate Meal Participants

At-risk older adults need community-based nutrition programs that improve nutritional status and practices. This 6-month study assessed the impact of the traditional Chef Charles (CC) program (Control) compared to a theory-based CC program (Treatment) on nutritional risk (NR), dietary intakes, self-efficacy (SE), food security (FS), and program satisfaction for congregate meal participants. Participants were mostly educated, single, “food secure” White females. NR change for the treatment group was significantly higher (P = 0.042) than the control group. No differences were noted for SE or FS change and program satisfaction between groups. The overall distribution classification levels of FS changed significantly (P &#60; .001) from pre to post. Over half (n = 46, 76.7%) reported making dietary changes and the majority (n = 52, 86.7%) rated CC as good to excellent. Results suggest the theory-based CC program (treatment) is more effective in reducing NR and dietary practices than the traditional CC program (control).     

Cannabidiol inhibits paclitaxel-induced neuropathic pain through 5-HT1A receptors without diminishing nervous system function or chemotherapy efficacy

Background and Purpose

Paclitaxel (PAC) is associated with chemotherapy-induced neuropathic pain (CIPN) that can lead to the cessation of treatment in cancer patients even in the absence of alternate therapies. We previously reported that chronic administration of the non-psychoactive cannabinoid cannabidiol (CBD) prevents PAC-induced mechanical and thermal sensitivity in mice. Hence, we sought to determine receptor mechanisms by which CBD inhibits CIPN and whether CBD negatively effects nervous system function or chemotherapy efficacy.

Experimental Approach

The ability of acute CBD pretreatment to prevent PAC-induced mechanical sensitivity was assessed, as was the effect of CBD on place conditioning and on an operant-conditioned learning and memory task. The potential interaction of CBD and PAC on breast cancer cell viability was determined using the MTT assay.

Key Results

PAC-induced mechanical sensitivity was prevented by administration of CBD (2.5 – 10 mg·kg⁻¹) in female C57Bl/6 mice. This effect was reversed by co-administration of the 5-HT_1A antagonist WAY 100635, but not the CB₁ antagonist SR141716 or the CB₂ antagonist SR144528. CBD produced no conditioned rewarding effects and did not affect conditioned learning and memory. Also, CBD + PAC combinations produce additive to synergistic inhibition of breast cancer cell viability.

Conclusions and Implications

Our data suggest that CBD is protective against PAC-induced neurotoxicity mediated in part by the 5-HT_1A receptor system. Furthermore, CBD treatment was devoid of conditioned rewarding effects or cognitive impairment and did not attenuate PAC-induced inhibition of breast cancer cell viability. Hence, adjunct treatment with CBD during PAC chemotherapy may be safe and effective in the prevention or attenuation of CIPN.     

Do Incest,Depression, Parental Drinking,Serious Romantic Relationships,and Living with Parents Influence Patterns of Substance Use During Emerging Adulthood?

This study examined how incest, depression, parental drinking, relationship status, and living with parents affect patterns of substance use among emerging adults, 18 to 25 years old. The study sample included (n = 11,546) individuals who participated in Waves I, II, and III of the National Longitudinal Study of Adolescent Health (Add Health). The study used separate latent class analysis for males and females to determine how patterns of substance use clustered together. The study identified the following three classes of substance use: heavy, moderate, and normative substance use patterns. Multinomial logistic regression indicated that, for females only, incest histories also nearly doubled the risk of heavy-use class membership. In addition, experiencing depression, being single, and not living with parents serve as risk factors for males and females in the heavy-use group. Conversely, being Black, Hispanic, or living with parents lowered the likelihood of being in the group with the most substance use behaviors (i.e., heavy use). Findings highlight the need for interventions that target depression and female survivors of incest among emerging adults.     

Population pharmacokinetic analysis of axitinib in healthy volunteers

AIMS

Axitinib is a potent and selective second generation inhibitor of vascular endothelial growth factor receptors 1, 2 and 3 approved for second line treatment of advanced renal cell carcinoma. The objectives of this analysis were to assess plasma pharmacokinetics and identify covariates that may explain variability in axitinib disposition following single dose administration in healthy volunteers.

METHODS

Plasma concentration–time data from 337 healthy volunteers in 10 phase I studies were analyzed, using non-linear mixed effects modelling (nonmem) to estimate population pharmacokinetic parameters and evaluate relationships between parameters and food, formulation, demographic factors, measures of renal and hepatic function and metabolic genotypes (UGT1A1*28 and CYP2C19).

RESULTS

A two compartment structural model with first order absorption and lag time best described axitinib pharmacokinetics. Population estimates for systemic clearance (CL), central volume of distribution (V_c), absorption rate constant (k_a) and absolute bioavailability (F) were 17.0 l h⁻¹, 45.3 l, 0.523 h⁻¹ and 46.5%, respectively. With axitinib Form IV, k_a and F increased in the fasted state by 207% and 33.8%, respectively. For Form XLI (marketed formulation), F was 15% lower compared with Form IV. CL was not significantly influenced by any of the covariates studied. Body weight significantly affected V_c, but the effect was within the estimated interindividual variability for V_c.

CONCLUSIONS

The analysis established a model that adequately characterizes axitinib pharmacokinetics in healthy volunteers. V_c was found to increase with body weight. However, no change in plasma exposures is expected with change in body weight; hence no dose adjustment is warranted.     

Family income trajectory during childhood is associated with adolescent cigarette smoking and alcohol use

Background

Although childhood socioeconomic disadvantage has been linked with adolescent tobacco and alcohol use in cross-sectional research, less is known about the influence of changes in socioeconomic status during childhood. Upward socioeconomic mobility may attenuate the negative influence of earlier socioeconomic disadvantage on health, while downward mobility may counter the health benefits of earlier socioeconomic advantage. This study evaluated the influence of common trajectories of family income during childhood on smoking and alcohol use during adolescence.

Methods

Data utilized were part of the 15-year longitudinal Study of Early Child Care and Youth Development. A 5-class trajectory model (two stable, one downward, and two upward income trajectories) was developed previously with this sample (N = 1356). Logistic regression analyses were conducted to determine whether children of the more disadvantaged income trajectories were more likely to engage in tobacco and alcohol use at age 15 relative to those of the most advantaged trajectory.

Results

Family income trajectory was significantly associated with ever-smoking (p = .02) and past-year alcohol use at age 15 years (p = .008). Children from the less advantaged trajectories were more likely to have ever-smoked than children of the most advantaged trajectory (all p's < .05). Children of the downwardly mobile trajectory were more likely to have used alcohol within the past year than children of the most advantaged trajectories as well as the most disadvantaged trajectory (all p's < .05).

Conclusions

Findings indicate that childhood socioeconomic disadvantage influences adolescent smoking, while downward socioeconomic mobility influences adolescent alcohol use.     

北京市城区与郊区高中毕业生体质健康状况评价分析

目的 采用综合评价法,比较2012年北京市城区与郊区高中毕业生的体质健康状况,探讨其是否存在差异.方法 从身体形态、生理机能和健康缺陷等3方面,采用Wilcoxon秩和检验、Ridit分析以及模糊数学法对2012年北京市39 982名高中毕业生中城区与郊区学生的体质健康状况进行评价并对其总体情况进行比较.结果 男生中城区组9 117名,郊区组9 299名,女生中城区组10 380名,郊区组11 186名.男生中身体形态指标（R城区=0.518,R郊区=0.482,P＜0.05）和生理机能指标（R城区=0.520,R郊区=0.480,P＜0.05）方面城区优于郊区,健康缺陷（R城区=0.501,R郊区=0.554,P＜0.05）及综合指标（R城区=0.484,R郊区=0.516,P＜0.05）方面城区劣于郊区.女生中生理机能指标（R城区=0.562,R郊区=0.442,P＜0.05）方面城区优于郊区,健康缺陷（R城区=0.473,R郊区=0.523,P＜0.05）方面城区劣于郊区,身体形态指标（U女=5.79,P＞0.05）和综合指标（U女=5.73,P＞0.05）方面差别无统计学意义.使用模糊数学法对三项指标综合量化得出分数,男生中城区68.37分,郊区69.13分,女生中城区69.83分,郊区69.79分.结论 2012年北京市高中毕业生城区与郊区学生在身体形态、生理机能和健康缺陷三项指标方面还存在一定的差异,但在综合体质健康状况方面差异并不显著.