Chronomodulated chemotherapy: clinical value and possibilities for dissemination in the United States

Modern medicine has been relatively slow to apply chronotherapeutic principles to standard oncologic practice. Despite the impressive body of evidence supporting the use of chronochemotherapy, with only a rare exception most oncology clinics in the United States lack the expertise and capability to implement it. At the same time, American medicine has increasingly come to recognize the importance of toxicity mitigation, cytoprotection, and quality of life for patients undergoing cancer treatment. However, toxicity mitigation strategies such as chronomodulated infusional chemotherapy and novel cytoprotective agents are not widely embraced by U.S. physicians. This article explores some reasons why this situation exists, including the influence of non-medical biases that may affect management decisions on the application of chemotherapy. The author conducted a survey of U.S. companies representing the three private insurance payers available (HMO, PPO, Indemnity) as well as representatives of Medicare and Medicaid. Responses to the survey confirmed that U.S. insurers do not at present officially reimburse for chronotherapy; however, changes will come about through educational efforts aimed at increasing awareness among insurers as to the clinical benefits and cost-effectiveness of this mode of treatment. At this juncture, the outlook for cancer chronotherapy as a first-line approach to the treatment of metastatic cancer in the United States remains uncertain. Under the current method of insurance reimbursement, the advancement of chronotherapy in the United States is threatened despite evidence that such treatment is both therapeutically sound and cost-effective.     

Contribution of the rest–activity circadian rhythm to quality of life in cancer patients

Quality of life (QoL) is estimated from patients scores to items related to everyday life, including rest and activity. The rest–activity rhythm reflects endogenous circadian clock function. The relation between the individual rhythm in activity and QoL was investigated in 200 patients with metastatic colorectal cancer. Patients wore a wrist actigraph (Ambulatory Monitoring Inc., New York, NY) for 3–5 d before chronotherapy, and completed a QoL questionnaire developed by the European Organization for Research and Treatment of Cancer (QLQ-C30) plus the Hospital Anxiety and Depression Scale. The rest–activity circadian rhythm was characterized by the mean activity level (m), autocorrelation coefficient at 24h (r24), and the dichotomy index (I<O), a ratio between the amount of activity while in and out of bed. The distribution of the rest–activity cycle parameters and that of QoL scores was independent of sex, age, primary tumor, number of metastatic sites, and prior treatment. Both the 24h rhythm indicators were positively correlated with global QoL score as well as physical, emotional, and social functioning. Negative correlations were found between m, r24, or I<O and fatigue, appetite loss, and nausea. The rest–activity circadian rhythm appeared to be an objective indicator of physical welfare and QoL. This analysis suggests that circadian function may be one of the biological determinants of QoL in cancer patients.     

先天性心脏病患儿术前营养不良的危险因素分析及其对术后临床结局、免疫功能和生存质量的影响

摘要 目的：分析先天性心脏病（CHD）患儿术前营养不良的危险因素,并观察术前营养不良对患儿术后临床结局、免疫功能和生存质量的影响。方法：选取2020年1月-2022年6月期间江苏省人民医院收治的65例CHD患儿,采用世界卫生组织（WHO）推荐的美国国家卫生统计中心制订的相关营养诊断标准评估CHD患儿的营养情况,统计CHD患儿术前营养不良发生率,采用单因素和多因素Logistic回归分析CHD患儿术前营养不良的危险因素,并观察术前营养不良对患儿术后临床结局、免疫功能和生存质量的影响。结果：本次研究入选的患儿中,有31例出现术前营养不良,34例无营养不良。根据患儿的营养状况将患儿分为营养不良组（n=31）和非营养不良组（n=34）。多因素Logistic回归分析结果显示：出生时体质量偏低、母亲有焦虑情况、母亲有抑郁情况是CHD患儿术前营养不良的危险因素,母亲主动获取疾病知识则是其保护因素（P<0.05）。两组并发症发生率组间对比无统计学差异（P>0.05）,营养不良组的住院时间长于非营养不良组,住院费高于非营养不良组（P<0.05）。两组术后3个月CD3⁺、CD4⁺、CD4⁺/CD8⁺升高,CD8⁺下降,且非营养不良组的改善效果优于营养不良组（P<0.05）。两组术后3个月术前沟通问题、心脏问题和症状、治疗焦虑、感知身体外貌、认知心理问题评分均升高,且非营养不良组的改善效果均优于营养不良组（P<0.05）。结论：出生时体质量偏低、母亲有焦虑情况、母亲有抑郁情况是CHD患儿术前营养不良的危险因素,而母亲主动获取疾病知识是CHD患儿术前营养不良的保护因素。术前营养不良会导致CHD患儿术后免疫功能下降,生存质量降低,临床结局相对偏差。