tbuckley/cabot-search huggingface dataset:
Impact of timing of antibiotic bundle therapy on outcomes in septic shock patients: a multicenter retrospective investigation
Authors: Xiaoyan Wu, Lei Bao, Weili Liu, Jilu Ye, Ruiqiang Zheng
Journal: BMJ (2018)

The clinical data of 372 patients with septic shock admitted in departments of critical care medicine of three Grade A tertiary hospitals from January 2013 to December 2015 were retrospectively reviewed, including 211 survival cases and 161 fatal cases. According to septic shock early goal-directed therapy implementation, 117 patients received bundle therapy (bundle group), including 30 cases with bundle goal-fully achieved, and 87 cases with bundle goal-partly achieved; and 255 cases received conventional treatment (non-bundle group). Multiple logistic regression analysis showed that the multiple organ dysfunction syndrome score, length of ICU stay and first time using of antibiotics were independent risk factors for prognosis of septic shock (P 0.05), while the fatality in bundle goal-fully achieved group(20.0%)was significantly lower than that of goal-partly achieved group (55.2%) and non-bundle group (42.0%) (P<0.05). Survival curve analysis showed that the medial survival time in bundle goal-fully achieved group was significantly higher than that in non-bundle group(19.4 vs. 10.5 days, P<0.05) and that in control group plus goal-partly achieved group(19.4 vs. 12.9 days, P<0.05). Multiple Logistic regression analysis showed that central venous oxygen saturation and antibiotics using within one hour were protective factors for prognosis of septic shock (P<0.05). The results indicate that antibiotic bundle treatment of all indicators up to standards could significantly reduce the mortality of septic patients and early antibiotics is important in bundle treatment.


Key words: 
Shock, septic; Combined modality therapy; Anti-bacterial agents; Hospital mortality
Effect of Suvorexant vs Placebo on Total Daytime Sleep Hours in Shift Workers
Authors: Jamie M. Zeitzer, Daniel S. Joyce, Amanda McBean, Yvonne L. Quevedo, Beatriz Hernandez, Jon-Erik Holty
Journal: JAMA Network Open (2020)

<h3>Importance</h3> Many shift workers have difficulty sleeping during the daytime owing to an inappropriately timed circadian drive for wakefulness. <h3>Objective</h3> To determine whether a dual hypocretin receptor antagonist would enable shift workers to have more daytime sleep. <h3>Design, Setting, and Participants</h3> This double-blind, placebo-controlled randomized clinical trial included 2 weeks of baseline data and 3 weeks of intervention data, from March 2016 to December 2018. Individuals were recruited through poster advertisements in the broader San Francisco Bay area in California. From an initial voluntary recruitment cohort of 38 shift workers, 19 individuals with self-reported difficulty sleeping during the daytime following night work shift were included. Data were analyzed from Janaury to March 2019. <h3>Interventions</h3> 1 week of 10 mg suvorexant or placebo, titrated upward to 20 mg suvorexant or placebo for 2 additional weeks. <h3>Main Outcomes and Measures</h3> Objective (ie, actigraphy) and subjective (ie, sleep logs) measures of sleep. <h3>Results</h3> Among 19 participants who completed the study (mean [SD] age, 37.7 [11.1] years; 13 [68%] men), 8 participants (42%) were assigned to the suvorexant group and 11 participants (58%) were assigned to the placebo group. Compared with individuals in the placebo group, individuals in the suvorexant group increased their objective total sleep time by a mean (SE) of 1.04 (0.53) hours (<i>P</i> = .05) at the end of 1 week of 10-mg doses and by 2.16 (0.75) hours (<i>P</i> = .004) by the end of the 2 weeks of 20-mg doses. Subjective sleep was similarly improved as, compared with the placebo group, individuals in the suvorexant group increased their subjective total sleep time by a mean (SE) of 2.08 (0.47) hours (<i>P</i> &lt; .001) at the end of 1 week of 10-mg doses and by 2.97 (0.56) hours (<i>P</i> &lt; .001) by the end of the 2 weeks of 20-mg doses. Physician ratings of daytime sleep aligned with these measures, as there was no change in the placebo group and a much improved change in the suvorexant group. No adverse events were reported in the suvorexant group. <h3>Conclusions and Relevance</h3> This pilot study found that the use of a dual hypocretin receptor antagonist in shift workers under real-world conditions resulted in more than 2 extra hours of daytime sleep per episode. Future research should confirm this pilot finding in a larger sample size and examine whether, over the long term, use of this medication has a concomitant improvement in medical and psychiatric health as well as workplace performance and safety. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:NCT02491788
The effect of chronic diseases on the clinical effect and survival period of patients with solid tumor treated with UMIPIC.
Authors: Shanshan Cui, Yanping Liu, Yanfei Wu, Wei Shang, Wei Han, Xingyou Xu, Baofa Yu
Journal: Journal of Clinical Oncology (2020)

e16532 Background: To observe the effect of chronic disease condition on the therapeutic effect and survival period of cancer patients treated with UMIPIC. Methods: 2594 cancer patients in our hospital from January 2011 to December 2015 who received UMIPIC for the study objects. 576 cases with chronic diseases, 2018 without chronic disease, 840 with lung cancer, 712 with esophageal cancer, 254 with liver cancer, 108 with pancreatic cancer, 93 with gastric cancer, 587 with other cancers. They signed the consent for treatment, evaluated the efficacy, followed up to the clinical effect, adverse reactions, survival data of patients. Results: The side effects of the chronic disease patients with cancer after UMIPIC therapy is fever at 26.56%, pain at 15.10%, the second was hemoglobin reduction 16.48%, leucopenia 5.27%, liver function damage 2.67%, thrombocytopenia 2.45%, nausea 2.26%, vomiting 1.39%, neurotoxicity and hair loss of less than 0.20%, while cancer patients without chronic disease after UMIPIC therapy, side effect is fever at 32.37%, pain at14.87%, hemoglobin reduction 13.26%, leucopenia 6.09%, nausea 2.73%, thrombocytopenia 2.6% 3%, liver function damage 1.77%, vomiting 1.73%, kidney function damage 0.89%, neurotoxicity and hair loss were lower than 0.20%; there is only fever difference in the two groups (P &lt; 0.05).There was no significant difference in other adverse reactions. This may be due to the immunity of normal patients was stronger than that of chronic patients. It was found that the clinical benefit rate of 90.91% in patients with chronic diseases was significantly lower than 93.44% in patients without chronic diseases (P = 0.021); after follow-up, we found that the mean survival time of patients with chronic diseases was 22.149 months, median survival time was 10.300 months, while median survival time of patients without chronic diseases was 22.940 months, median survival time was 11.200 months, and the survival rates of patients without chronic diseases for 1, 2, 3 and 5-year were 48.94%, 29.97%, 25.19%, and 25.18% respectively, it is significantly higher than those of patients with chronic diseases (43.19%, 22.33%, 18.37% and 16.04%) (P&lt;0.05). Conclusions: The survival time and survival rate of the patients without chronic diseases are higher than those of the patients with chronic diseases. The side effects of chronic diseases on the patients with cancer treated with UMIPIC are not significant different except for fever. The patients with chronic diseases can safely receive UMIPIC treatment.
The genes CNV and expression as a factors of HT-29 cells radioresistance.
Authors: Natalia G Kosheleva, Marina A. Gusareva, Gennady V. Balitsky, Natalia A. Lyman, Peter N. Gabrichidze, Umar Muhmadovich Gaziev, Anna A. Solntseva, Elena A. Karnauhova, Julia N. Krokhmal, Ekaterina O. Vasilyeva, Liubov Yu Vladimirova, Mikhail S. Zinkovich, Denis S. Kutilin
Journal: Journal of Clinical Oncology (2020)

e15590 Background: The initial radioresistance of tumor cells associated with certain molecular genetic features has a great influence on the effectiveness of radiation therapy (RD). These features include the transcriptional activity of genes that regulate DNA repair, cell cycle and apoptosis, and their copy number variation (CNV). The aim of the study was to analyze the expression and CNV of genes that regulate DNA repair, cell cycle and apoptosis in HT-29 cells subjected to RD. Methods: HT-29 cell culture was used in the study. For the model experiment, doses of 5 and 7 Gy were used (irradiation was performed 5 times every 24 hours on a Novalis TX linear accelerator). Cell counting was carried out in Goryaev chamber (0.4% trypan blue solution). On the 5th day of irradiation, HT-29 was removed from the substrate with Trypsin / Versen solution. RNA was isolated according to the method of Chomczynski&amp;Sacchi. For cDNA synthesis was used a "REVERTA-L". reagent. The phenol-chloroform method was used to DNA isolate. The RT-qPCR method was used to determine the CNV and expression of 32 genes: AKT, ATM, BRIP, BRCA1, BRCA2, CDK1, CDKN1B, CCND1, CCND3, EXO1, FGFR2, HIST1, H2AX, KU70, PTEN, RAD50, RAP80, RIF1, RNF8 TOPB1, TP53, XRCC4, BAX, CASP8, CASP3, CASP9, MDM2, BCL2, RBBP8, EP300, LIG4, C-FLIP. Statistical analysis was performed using ANOVA and Spearman's rank correlation coefficient (r). Results: After irradiation, only a specific pool of HT-29 cells remained viable: 32% for 5 Gy and 20% for 7 Gy of the initial number of cells. In HT-29 cells irradiated with 7 Gy, the CNV of the BRCA2, H2AX, CASP9 and RBBP8 genes was increased (p &lt; 0.05) and the CNV of BCL2 gene was reduced (p &lt; 0.05) relative to intact cells. In cells irradiated with 5 Gy only CASP9 and RBBP8 CNV was statistically significantly (p &lt; 0.05) increased. In cells irradiated with 5 and 7 Gy, expression of BRCA2, H2AX, CASP9 and RBBP8 genes was statistically significantly (p &lt; 0.05) increased and the expression of the BCL2 gene was reduced relative to intact cells. A strong positive correlation was observed between CNV and expression of the studied genes: r = 0.998 for control, r = 0.989 for cells irradiated at 5 Gy, and r = 0.993 for cells irradiated at 7 Gy. Conclusions: The study showed that 5 day RD at 5 and 7 Gy leads to selective survival of 32% and 20% of cells, respectively, with increased CNV and expression of BRCA2, H2AX, RBBP8 CASP9 genes and reduced CNV and expression of BCL2 gene.
The adoption of immune checkpoint inhibitors and patterns of care at the end of life.
Authors: Fauzia Riaz, Geliang Gan, Fangyong Li, Amy J. Davidoff, Kerin B. Adelson, Carolyn J Presley, Blythe J.S. Adamson, Pooja Shaw, Ravi Bharat Parikh, Ronac Mamtani, Cary Philip Gross
Journal: Journal of Clinical Oncology (2020)

12027 Background: As immune checkpoint inhibitors (ICIs) have transformed the care of patients with cancer, it is unclear whether treatment at end of life (EOL) has changed. Because aggressive therapy at EOL is associated with increased costs and patient distress, we explored the association between the FDA approvals of ICIs and treatment patterns at EOL. Methods: We conducted a retrospective, observational study using patient-level data from the Flatiron health EHR-derived de-identified database. Patients had advanced melanoma, non-small cell lung cancer (NSCLC) (cancer types with an ICI indication) or microsatellite stable (MSS) colon cancer (a cancer type without an ICI indication) and died between 2013 and 2017. We calculated annual proportions of decedents who received systemic cancer therapy in the final 30 days of life and used logistic regression to model the association between the post-ICI Federal Drug Administration (FDA) approval time period and use of systemic therapy at EOL, adjusting for patient characteristics. We also assessed the use of chemotherapy or targeted/biologic therapies at EOL, before and after FDA approval of ICIs using Pearson Chi Square test. Results: There was an increase in use of EOL systemic cancer therapy in the post-ICI approval period for both melanoma (33.9% to 43.2%, p-value &lt; 0.001) and NSCLC (37.4% to 40.3%, p-value &lt; 0.001). In contrast, the control group of decedents with MSS colon cancer demonstrated no significant increase in use of systemic therapy at EOL. After controlling for patient characteristics, there was a significantly higher odds of receiving systemic treatment at EOL in the post-ICI time period compared to the pre-ICI time period in melanoma (OR 1.42, 95% CI 1.09-1.86, p-value &lt; 0.001) and NSCLC (OR 1.13, 95% CI 1.06-1.20, p value &lt; 0.001), with no significant difference in receipt of systemic therapy in patients with MSS colon cancer. After FDA approval of ICIs, patients with NSCLC and melanoma had a decrease in the use of chemotherapy, with a concomitant increase in use of ICIs at EOL. Decedents with MSS colon cancer did not have a statistically significant change in use of chemotherapy or targeted/biologic therapies during the study period. Conclusions: The adoption of ICIs was associated with a substantive increase in the use of systemic therapy at EOL in melanoma, and a smaller yet significant increase in NSCLC.
Clinicopathological and molecular biological characteristics of early-onset stage II/III colorectal adenocarcinoma: An analysis of 25 studies with 47,184 patients (pts) in the adjuvant colon cancer end points (ACCENT) database.
Authors: Zhaohui Jin, Jesse G. Dixon, Hiral D. Parekh, Steven R Alberts, Greg Yothers, Carmen Joseph Allegra, Rachel Kerr, Daniel G. Haller, Aimery De Gramont, Takayuki Yoshino, Eric Van Cutsem, Chris Twelves, Julien Taieb, Leonard B. Saltz, Jean-François Seitz, Thierry Andre, Amit Mahipal, Richard M. Goldberg, Qian Shi, Thomas J. George
Journal: Journal of Clinical Oncology (2020)

4099 Background: Colorectal cancer (CRC) incidence and mortality has decreased since the 1970s but the incidence is increasing in young adults (age 20-49). The incidence of early onset CRC (eoCRC) will keep increasing significantly based on the trends of the SEER CRC registry data. There is limited data suggesting eoCRC may have different behaviors compared to traditional CRC (tCRC, age ≥ 50). Methods: Individual pt data of 47184 stage II/III CRC pts from 25 randomized studies in the ACCENT database were pooled. The distributions of demographics, clinicopathological features, biomarker status, and treatment-related data were summarized by age group. Overall survival (OS), disease-free survival (DFS), recurrence-free rate (RFR), and survival after recurrence (SAR) were assessed by Kaplan-Meier curves and Cox models stratified by treatment arms within studies, adjusting for stage, performance status (PS), BMI and grade. Results: Using 5% difference between age groups as clinically meaningful cutoff, eoCRC had similar gender, race, ethnicity, PS, risk group, disease sidedness and T stage as tCRC. eoCRC were less likely overweight (30 vs 36%) and more pts had ≥ 12 lymph nodes resected (63 vs 51%). eoCRC had more frequent dMMR status (18 vs 12%), less BRAF mutations (5 vs 13%), and more dMMR/BRAF wild type (WT) status (17 vs 7%). Overall, eoCRC had better OS, DFS, and SAR, with the most significant differences between the &lt; 30 and &gt; = 70 age groups. Similar results were observed within pMMR pts. eoCRC experienced less hematological side effects, diarrhea, and stomatitis, but had more nausea and/or vomiting. Conclusions: eoCRC have unique characteristics; although statistically significant, the clinical differences in outcomes between eoCRC and tCRC are potentially due to the difference seen in extremely young and old pts. eoCRC have a different adverse events panel compared to tCRC. [Table: see text]
Sodium aescinate gel alleviates hand swelling in elderly patients with distal radius fracture
Authors: Liyou Wei, Hongwei Zhang
Journal: BMJ (2016)

Sixty-two elderly patients with distal radius fractures after fixation with small splints were enrolled in the study from January to December 2014. Patients were randomly divided into intervention and control groups with 31 cases in each group. Patients in both groups received comprehensive prevention for hand swelling, those in intervention group were given additional external administration of sodium aescinate gel (SAG), 1 g, t. i.d for 7 d. Swelling score and visual analogue scale (VAS) were documented before and 3, 7 d after intervention. At the time of fracture healing, the wrist functions, including motions of flexion-extension, motions of radial-ulnar and motions of pronation-supination were examined. At 3 and 7 d after intervention, the swelling score(1.22±0.69 vs. 1.65±0.75 and 0.64±0.42 vs. 0.96±0.71)and VAS(1.96±1.27 vs. 2.85±1.40 and 1.11±0.65 vs. 1.86±1.09)of intervention group were lower than those of control group (all P<0.05). At the time of fracture healing, the wrist motions of flexion-extension [(83.7±8.6) vs. (77.6±7.1)%], motions of radial-ulnar [(83.0±7.6) vs. (78.2±8.7)%] and motions of pronation-supination [(81.0±7.0) vs. (76.2±7.5)%] of intervention group were higher than those of control group (P<0.05). The results indicate that SAG can reduce swelling, relief pain and promote the recovery of wrist function in elderly patients with distal radius fractures.


Key words: 
Radius fractures; Sudium aescinate gel; Administration, topical
Final results of a phase III randomized trial of comparison of three paclitaxel-based regimens concurrent with radiotherapy for patients with local advanced esophageal squamous cell carcinoma.
Authors: Dashan Ai, Jinjun Ye, Yun Chen, Qi Liu, Xiangpeng Zheng, Yunhai Li, Shihong Wei, Jiancheng Li, Qin Lin, Hui Luo, Jianzhong Cao, Jialiang Zhou, Guang Huang, Min Fan, Kailiang Wu, Huanjun Yang, Zhengfei Zhu, Weixin Zhao, Ling Li, Kuaile Zhao
Journal: Journal of Clinical Oncology (2020)

4564 Background: Paclitaxel (PTX) is effective in concurrent chemoradiation (CCR) against esophageal squamous cell carcinoma (ESCC). Which regimen, among cisplatin (DDP) (TP), carboplatin (CBP) (TC) or 5-Fu (TF) in combination with PTX concurrent with radiotherapy, provides best prognosis with minimum adverse events (AEs) is still unknown. Methods: The study compared two pairs of regimens: TF vs. TP and TF vs. TC concurrent with radiotherapy. Patients with histologically confirmed ESCC (clinical stage II, III or IVa) 20 were randomized into the three groups. Patients in TP group were treated with 2 cycles of CCR followed by 2 cycles of consolidation chemotherapy with TP (DDP 25 mg/m2/d, d1-3, PTX 175 mg/m2, d1, q28d). Patients in TF group were treated with 6 cycles of TF (5-Fu 300 mg/m2, civ 96h, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TF (5-FU 1800 mg/m2, civ 72h, PTX 175 mg/m2, d1, q28d) in consolidation chemotherapy. Patients in TC group were treated with 6 cycles of TC (CBP AUC = 2, d1, PTX 50 mg/m2, d1, qw) in CCR followed by 2 cycles of TC (CBP AUC = 5, d1, PTX 175 mg/m2 d1, q28d) in consolidation chemotherapy. The radiotherapy dose in all groups was 61.2 Gy delivered in 34 fractions. The primary endpoint was overall survival (OS) and the secondary endpoints were progression-free survival (PFS) and adverse events. Results: Between July 2015 and January 2018, 321 ESCC patients in 11 centers were enrolled. Median follow-up of patients who survived was 36.3 months (IQR 27.9–45.2). The 3-yr OS was 58.2% in TF group and 59.5% in both TP and TC group. (TF vs. TP, HR 0.935, 95% CI 0.627-1.417; TF vs. TC, HR 0.881, 95% CI 0.578-1.342; P = 0.839). No significant differences were found in 3-yr PFS between TF, TP and TC groups [48.3% vs. 45.5%(TP) or 48.3% (TC). P = 0.820]. TP group had a significant higher incidence of acute Grade 3/4 neutropenia [60.7% vs. 16.8%(TF) or 32.7%(TC)], thrombocytopenia [13.1% vs. 2.8%(TF) or 4.7%(TC)], anemia [5.6% vs. 1.9%(TF) or 3.7% (TC)], fatigue [10.3% vs. 1.9%(TF) or 0.9%(TC)] and vomiting [5.6% vs. 0%(TF) or 0.9%(TC))]than other two groups ( P&lt; 0.05). TF group had a significant higher incidence of Grade 3/4/5 esophagitis [11.2% vs. 0.9%(TP) or 4.7%(TC))]and pneumonitis [4.6% vs. 0%(TP) or 1.9% (TC)]than other two groups ( P&lt; 0.05). Conclusions: No statistical differences were found in OS and PFS among TF, TP and TC groups. TC might be an option used in CCR in ESCC patients with mild of side effects compared with other two groups, although it did not significantly prolong OS. Clinical trial information: NCT02459457 .
Influencing factors of choosing community health centers among Shanghai urban residents
Authors: Hong-xia Xu, Rui Song
Journal: BMJ (2012)

Random clustering was conducted among a total of 1068 residents aged 18 years or older at a certain Shanghai community.And they completed a questionnaire survey.Logistic data processing and model building were performed.The respondents were willing to go to a community health center for the following reasons:close proximity (88.4％),excellent service attitudes (40.4％) and low drug prices (37.8％).No statistically significant differences existed in terms of first choices of community health service,occupation,monthly income and-walking distance (P ＞ 0.05).However,statistically significant differences existed in education level,age and chronic diseases (P ＜ 0.05).

Key words: 
Community health services; Factorial analysis,statistical
Observation of clinical efficacy and survival of lung cancer patients with UMIPIC combined with low-dose chemotherapy.
Authors: Jianbin Feng, Peng Jing, Feng Gao, Jian Liu, Wei Han, Xingyou Xu, Xiaomin Zhang, Peicheng Zhang, Wei Shang, Ye Teng, Yanfei Wu, Baofa Yu
Journal: Journal of Clinical Oncology (2020)

e21605 Background: To observe the clinical efficacy and survival of UMIPIC combined with low-dose chemotherapy in patients with lung cancer. Methods: 840 patients with lung cancer underwent UMIPIC treatment from January 2011 to December 2015 were selected as the study subjects, 341 cases combined with low-dose chemotherapy in group A and 499 cases not combined with chemotherapy in group B. All patients were diagnosed with lung cancer and signed a consent form for treatment. The patients were treated according to the UMIPIC treatment guidelines. This study was mainly to observe the adverse reactions, clinical efficacy, survival time and survival rate of lung cancer patients after receiving UMIPIC combined with or without low dose chemotherapy. Results: The common adverse reactions in group A were fever 38.12%, followed by pain 9.38%, hemoglobin 7.94%, white blood cells 5.01%, nausea 2.35%, liver function damage 1.19%, vomiting 1.17%, and kidney function damage 0.30%; Common adverse reactions in group B were fever 38.68%, followed by pain 13.23%, hemoglobin reduction 12.87%, white blood cell reduction 5.29%, nausea 2.00%, vomiting 2.00%, liver function damage 1.92%. The hemoglobin reduction in group A was significantly lower than that in group B (P &lt; 0.05), and there was no difference in the other adverse reactions (P &gt; 0.05). Clinical efficacy of the two groups revealed that the benefit rate of group A was 95.45% higher than that of group B 93.47% (P &gt; 0.05). After follow-up, it was found that the average survival time and median survival time of patients in group A were 20.744 and 13.270 months, respectively, which were significantly higher than those of group B at 19.514 and 10.070 months (P &lt; 0.05). The survival rates of the two groups of patients, The 1-year, 2-year, and 5-year survival rates of group A patients are 52.48%, 23.60%, and 16.95%, and the 1-year, 2-year, and 5-year survival rates of group B patients are 42.96% and 17.07 % And 10.26%, the one-year survival rate of group A was significantly higher than that of group B (P &lt; 0.05). Conclusions: UMIPIC combined with low-dose chemotherapy has a good clinical effect in treating lung cancer without increasing the incidence of adverse reactions, and a significant effect on extending survival time and improving survival rate of lung cancer patients.