A graph model of combination therapies

The simultaneous use of multiple medications causes drug–drug interactions (DDI) that impact therapeutic efficacy. Here, we argue that graph theory, in conjunction with game theory and ecosystem theory, can address this issue. We treat the coexistence of multiple drugs as a system in which DDI is modeled by game theory. We develop an ordinary differential equation model to characterize how the concentration of a drug changes as a result of its independent capacity and the dependent influence of other drugs through the metabolic response of the host. We coalesce all drugs into personalized and context-specific networks, which can reveal key DDI determinants of therapeutical efficacy. Our model can quantify drug synergy and antagonism and test the translational success of combination therapies to the clinic.     

Diabetes is associated with high risk of severe adverse events during chemotherapy for cancer patients: A single-center study

Diabetes mellitus (DM) is a common comorbidity among cancer patients, but its impact on chemotherapy tolerance has not been widely studied. We aimed to compare the occurrence of severe grade 3/4 adverse events (G3/4 AEs) within 90 days of starting chemotherapy between patients with and without diabetes. We conducted a retrospective single-center study in Lille University Hospital Oncology Department, France. Patients who received the first cycle of chemotherapy for gastrointestinal, gynecological or cancer of unknown primary source between 1 May 2013 and 1 May 2016, were included. Overall, 609 patients were enrolled: 490 patients without diabetes (80.5%) and 119 patients with diabetes (19.5%). Within 90 days of starting chemotherapy, patients with diabetes had a significantly higher occurrence of AEs G3/4 compared to those with no diabetes (multivariate odds ratio [OR]: 1.57 [1.02-2.42], P = .04). More frequent G3/4 AEs in patients with diabetes were infection (26%), hematological disorders (13%), endocrine disorders (13%) and deterioration of the general condition (13%). In the year following the beginning of chemotherapy, patients with diabetes were twice as likely to be hospitalized as those without diabetes (univariate OR: 2.1 [1.40-3.15], P = .0003). After multivariate adjustment, diabetes was no longer significantly associated with the risk of hospitalization (P = .051). There were no differences between patients with and without diabetes regarding dose reduction and chemotherapy treatment delays (P = .61 and P = .30, respectively). Our study suggests the need for better consideration of DM in the personalized care plan to improve chemotherapy tolerance and quality of life of patients with DM.     

SHEL模式下基层医院护理人员高警示药品安全管理培训的效果

目的:探究SHEL模式下基层医院护理人员高警示药品安全管理培训的效果。方法:选取2020年7月—2021年6月在医院从事临床护理工作的80名护理人员,随机将其分为观察组与对照组各40人。对照组实施常规培训模式,观察组实施SHEL模式培训,比较两组护理人员高警示药品相关知识及技能掌握程度、意外事件发生率及核心能力。结果:培训后观察组护理人员理论及操作得分分别为(86.75±6.18)分及(93.19±4.28)分,核心能力得分为(228.98±8.37)分,均明显高于对照组(P<0.05),同时观察组护理人员在护理过程中出现给药前未双人核对、药品分类不清及交接记录不全的概率分别为0.95%、0.95%及1.90%,明显低于对照组(P<0.05),且未出现药物外渗及滴速有误等情况。结论:对基层医院护理人员实施SHEL模式下高警示药品安全管理培训,能够有效提高护理人员高警示药品理论、技能掌握程度及核心能力,同时有助于降低护理工作中意外事件的发生概率。     

Top advances of the year: Precision oncology

The advent of precision medicine has changed the landscape of oncologic biomarkers, drug discovery, drug development, and, more importantly, outcomes for patients with cancer. Precision oncology entails the genomic profiling of tumors to detect actionable aberrations. The advances in clinical next-generation sequencing from both tumor tissue and liquid biopsy and availability of targeted therapies has rapidly entered mainstream clinical practice. In this review, recent major developments in precision oncology that have affected outcomes for patients with cancer are discussed. Rapid clinical development was seen of targeted agents across various mutational profiles such as KRASG12C (which was considered “undruggable” for almost 4 decades), Exon 20 insertions, and RET mutations. Approaches to precision chemotherapy delivery by the introduction of antibody drug conjugates in the armamentarium against lung cancer has been appreciated.     

电针联合右美托咪定对骨科老年患者术中应激的影响研究

目的：探讨电针联合右美托咪定对老年骨科患者术中应激的影响。方法：选取拟行手术治疗的老年下肢骨折患者56例为研究对象，采用随机数字表法分为单纯全麻组、电针复合全麻组（简称复合电针组）、右美托咪定复合全麻组（简称复合右美组）及电针联合右美托咪定复合全麻组（简称针药复合组），各14例。记录各组各时间点血压、心率、血氧饱和度等各项监护指标，术前、术后神经心理学指标（简易智力检查评分和疼痛视觉模拟评分）及各时间点血糖水平，术中心血管活性药物使用情况及患者住院天数。结果：术后各时间点针药复合组简易智力检查评分高于单纯全麻组（P＜0.05）；术后72 h内，针药复合组疼痛评分低于其他三组（P＜0.05）；针药复合组术中循环系统指标及血糖水平更稳定；针药复合组术后意识恢复时间最短（P＜0.05）；四组术后呼吸恢复时间与住院天数比较，差异无统计学意义（P＞0.05）；四组心血管活性药物使用率比较，差异无统计学意义（P＞0.05）。结论：老年骨科患者手术中采用电针联合右美托咪定治疗，能够稳定围术期血糖、术中循环系统指标水平，减少术后认知功能障碍发生率，显著降低术中应激水平。     

Effectiveness of typhoid conjugate vaccine against culture-confirmed typhoid in a peri-urban setting in Karachi: A case-control study

BackgroundEnteric fever, caused by Salmonella Typhi and S. Paratyphi, is a cause of high morbidity and mortality among children in South Asia. Rising antimicrobial resistance presents an additional challenge. Typhoid Conjugate Vaccines (TCV) are recommended by the World Health Organization for use among people 6 months to 45 years old living in endemic settings. This study aimed to assess the effectiveness of TCV against culture-confirmed S. Typhi in Lyari Town, Karachi, Pakistan. This peri-urban town was one of the worst affected by the outbreak of extensively drug resistant (XDR) typhoid that started in November 2016.MethodsA matched case-control study was conducted following a mass immunization campaign with TCV at three key hospitals in Lyari Town Karachi, Pakistan. Children aged 6 months to 15 years presenting with culture-confirmed S. Typhi were enrolled as cases. For each case, at least 1 age-matched hospital control and two age-matched community controls were enrolled. Adjusted odds ratios with 95% confidence intervals (CIs) were calculated using conditional logistic regression.ResultsOf 82 typhoid fever patients enrolled from August 2019 through December 2019, 8 (9·8%) had received vaccine for typhoid. Of the 164 community controls and 82 hospital controls enrolled, 38 (23·2%) community controls and 27 (32·9%) hospital controls were vaccinated for typhoid. The age and sex-adjusted vaccine effectiveness was found to be 72% (95% CI: 34% − 88%). The consumption of meals prepared outside home more than once per month (adjusted odds ratio: 3·72, 95% CI: 1·55- 8·94; p-value: 0·003) was associated with the development of culture-confirmed typhoid.ConclusionA single dose of TCV is effective against culture confirmed typhoid among children aged 6 months to 15 years old in an XDR typhoid outbreak setting of a peri-urban community in Karachi, Pakistan.