bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparing the mental health trajectories of four different types of keyworkers with non-keyworkers: 12-month follow-up observational study of 21 874 adults in England during the COVID-19 pandemic
Authors: Bu Feifei , Mak Hei Wan , Fancourt Daisy , Paul Elise 
Published: January 2022

BackgroundThere are concerns that keyworkers may be at a greater risk for psychological distress than non-keyworkers during the COVID-19 pandemic. However, little research has included keyworkers outside of the healthcare sector or has disaggregated keyworkers into different subgroups.AimsTo examine longitudinal changes in mental health over 12 months during the COVID-19 pandemic comparing four different groups of keyworkers with non-keyworkers.MethodLongitudinal data were from 21 874 adults living in England (21 March 2020 to 22 February 2021). Latent growth modelling was utilised to compare growth trajectories of depressive and anxiety symptoms in non-keyworkers and four types of keyworkers: (a) health and social care workers, (b) teachers and child care workers, (c) public service workers, and (d) essential services keyworkers (such as food chain or utility workers).ResultsWhen accounting for both time-invariant and time-varying covariates, keyworkers in the essential services category had consistently higher levels of depressive and anxiety symptoms than non-keyworkers across the whole of the study period. There was little difference in the mental health trajectories between health/social care, teachers/child care and public service worker categories and non-keyworkers.ConclusionsOur findings suggest that the risk for poorer mental health during the COVID-19 pandemic varies within the broad category of keyworkers generally, and that those working in utility, food chain and transport roles are especially at risk. Future research should focus on identifying which aspects of working conditions may be contributing to occupational stress in these groups.
Robotic versus laparoscopic surgery for middle and low rectal cancer (REAL): Short-term outcomes of a multicenter randomized controlled trial.
Authors: Xu Jianmin , Yuan Weitang , Li Taiyuan , Tang Bo , Jia Baoqing , Zhou Yanbing , Zhang Wei , Zhao Ren , Zhang Cheng , Cheng Longwei , Zhang Xiaoqiao , Liang Fei , He Guodong , Wei Ye , Feng Qingyang 
Published: January 2022

14 Background: Robotic surgery for rectal cancer is gaining popularity, but persuasive evidence on long-term oncological outcomes is lacking. This multicenter randomized controlled trial compared robotic and conventional laparoscopic surgery regarding surgical quality and long-term oncological outcomes among patients with middle and low rectal cancer. Methods: This superiority trial was undertaken at 11 hospitals in 8 Chinese provinces. Patients with middle (> 7–12 cm from anal verge) or low (0–7 cm from anal verge) rectal adenocarcinoma, cT1–T3 N0–1 or ycT1–T3 Nx after preoperative radio-/chemoradiotherapy, and no evidence of distant metastasis were enrolled and randomly assigned in a 1:1 ratio to receive robotic or conventional laparoscopic surgery. Secondary (short-term) end points (surgical quality, pathological radicality, and postoperative recovery) were compared using modified intention-to-treat (mITT) analysis. Three-year locoregional recurrence rate as the primary endpoint is expected by the end of 2023. This trial was registered with ClinicalTrials.gov (NCT02817126). Results: Between July 2016 and December 2020, 1240 patients were enrolled; 1180 were included in the mITT analysis (591 in robotic and 589 in laparoscopic group). There were significantly more sphincter-preserving surgeries (low anterior resections) performed in the robotic group (83.1% vs. 76.9%, p = 0.008). With more macroscopic complete resections (95.4% vs. 91.9%, p = 0.012), robotic surgery had better integrity of the mesorectal fascia, and had lower circumferential resection margin positivity rate (4.0% vs. 7.1%, difference = -3.1%, 95% confidence interval = -6.0% to -0.5%, p = 0.023) and more lymph nodes harvested (median, 15.0 vs. 14.0, p = 0.004). Robotic surgery also reduced the open conversion rate (1.7% vs. 3.9%, p = 0.021), estimated blood loss (median, 40.0 ml vs. 50.0 ml, p < 0.001), intraoperative complication rate (5.4% vs. 8.7%, p = 0.029), and 30-day postoperative complication rate (Clavien-Dindo grade II or higher, 16.1% vs. 22.9%, p = 0.003), leading to better postoperative recovery and shorter postoperative hospital stay (median, 7.0 days vs. 8.0 days, p < 0.001). The 30-day postoperative mortality was similar between the two groups (0.2% vs. 0.2%, p > 0.999). Conclusions: Robotic surgery for middle and low rectal cancer significantly reduced surgical injury, improved oncological radicality, and promoted postoperative recovery compared with conventional laparoscopic surgery. Clinical trial information: NCT02817126.
Association between tumor mutation profile and clinical outcomes among Hispanic-Latino patients with metastatic colorectal cancer.
Authors: Ghafouri Sayed Reshad , Philipovskiy Alexander , Dwivedi Alok Kumar , McCallum Richard , Konstantinidis Ioannis , Maegava Felipe , Gaur Sumit , Corral Javier Chavez 
Published: January 2022

17 Background: According to the World Health Organization GLOBOCAN database, in 2019, approximately 1.8 million new colorectal cancer cases were diagnosed, and almost 861,000 deaths were reported. In the United States, CRC is the third most frequent type of cancer and the second leading cause of cancer-related death. Although the overall incidence of CRC among the Hispanic population has been declining over the last decades, recently, a dramatic increase in CRC incidents among Hispanics younger than 50 years of age (early-onset CRC) has been reported. The increase in the incidence of early-onset CRC is markedly more significant in Hispanic-Latino (HL) patients population (45%) than in non-Hispanic Whites (NHW) (27%) and African-Americans (AA) (15%). Additionally, in contrast to NHW, Hispanics have a worse survival rate. The exact reason for these racial disparities and the biology of CRC in the HL population are not well understood. Therefore, we performed this study to better understand the biology of the disease in HL patients, which might help to identify new directions for targeted therapy. Methods: For the study, 52 formalin-fixed paraffin-embedded (FFPE) tumor tissue samples were collected and analyzed. We compared the results with individual patient clinical histories and outcomes. Of 52 patients with mCRC, 52 (100%) were identified as HL. We identified several commonly altered genes in HL patients ( APC, TP53, KRAS, GNAS, PICK3CA, and NOTCH). Compared to those in other studies. Results: Mutation frequencies in the APC gene were significantly higher among HL patients with mCRC. Moreover, the prevalence of the APC mutation was significantly higher among male HL patients compared to female patients. The combination of mutations in the APC, NOTCH, and KRAS genes in the same tumors was associated with a higher risk of progression after the first-line of chemotherapy and worse overall survival. In addition, mutations in the combination of GNAS and AURKA genes were associated with a significantly higher risk of progression after the first-line of chemotherapy. Conclusions: The data support the notion that the molecular drivers of colon cancer might be different in HL patients compared to other racial/ethnic groups.
Chemotherapy delivery in early-onset colorectal cancer is impacted by urban versus rural settings in Colorado.
Authors: Sheneman David , Hu Junxiao , Das Santi , Lieu Christopher Hanyoung 
Published: January 2022

19 Background: While colorectal cancer (CRC) incidence has been decreasing overall, incidence in adults under age 50 has been rising both nationally and across Colorado. National guidelines have adapted to recognize this trend, but knowledge gaps regarding early-onset CRC remain. This group has previously established rising early-onset CRC incidence in Colorado, as well as later stage at diagnosis and worse prognosis. This study examines demographics, treatment, survival, and concomitant disease among patients < 50 and diagnosed with CRC across a multicenter healthcare system in Colorado in order to better understand early-onset CRC. Methods: We analyzed 1,192 CRC cases in patients < 50 from the Colorado Health Data Compass database and cross-referenced these cases with the Colorado Central Cancer Registry to examine for association of gender, race/ethnicity, BMI, zip code, insurance type, stage, and concomitant medical conditions with overall survival and oncologic treatment modality. Logistic regressions were used to evaluate the relationships between chemotherapy and the important variables while adjusting for covariates, with 95% confidence intervals reported. Cox proportional hazard regressions were used to evaluate the relationships between overall survival and the important variables while adjusting for covariates, with 95% confidence intervals reported. Results: Overall, early-onset CRC in our population was 2.8% stage I, 6.3% stage II, 12.7% stage III, 18.5% stage IV, and 59.8% were unstageable or no stage recorded. Surgical treatment was associated with a 52% improvement in overall survival. Chemotherapy treatment was not associated with any survival changes in stage II disease. Radiation treatment, insurance type, number of concomitant conditions, geographic location, and race/ethnicity were not associated with overall survival. Upon exploring chemotherapy relationships, patients from urban areas were significantly more likely to receive chemotherapy than patients from rural areas, while adjusting for ethnicity, inpatient encounters, and stage (OR 5.55, p = 0.001). Conclusions: While less is known about CRC in patients < 50, trends are emerging that are not as well described in a traditional CRC population. The difference between urban and rural patients and their rates of chemotherapy points to a potential disparity in access to care, particularly when considering advanced stage CRC. This persisted through insurance type, indicating that distance from an infusion center, rather than ability to pay, is more likely to be driving this relationship. Further research is needed to determine if these findings are generalizable to the larger early-onset CRC population, and how access may be affecting care for this population.
Colorectal cancer biomarker, AABH (Aspartyl [Asparaginyl] β- hydroxylase), a companion imaging and treatment strategy.
Authors: Moshiri Mahmood , Moshiri Kiarash , Nazari Reza , Pishrochi Mohammad , Moshiri Arsha , Monhemi Hassan 
Published: January 2022

25 Background: Colorectal cancer (CRC) is the third most common type of cancer diagnosed in the US and Canada. WHO, Canadian Cancer Society (CCS), the National Comprehensive Cancer Network (NCCN) and American Cancer Society (ACS) recommend that men and women begin CRC screening at age 50 or younger if at high risk. Recommended screening procedures: Annual occult fecal blood test (OFBT), a colonoscopy every 5 years, OFBT and colonoscopy every 5 years, or a colonoscopy every 10 years. According to The Surveillance, Epidemiology, and End Results (SEER) Program, only 39% of CRC are diagnosed in stage I, 36% are diagnosed in stage II, 19% are diagnosed with metastasis. The corresponding 5-year survival rates are 89.8%, 67.7%, and 10.3%. Neither the CCS nor the ACS recommends a blood test to be done as part of screening. This is due to the fact that, until now, there has not been a blood test with adequate sensitivity or specificity for screening. Methods: In this study we discovered that aspartyl (asparaginyl) β-Hydroxylase (AABH) measurement in serum can be used as a screening test for CRC. AABH has been detected by immunohistochemical staining (IHC) on the cell surface of different cancers including CRC. It has been detected by IHC in > 97% of tumor specimens tested (n > 210) but has not been found in tissue samples from normal individuals. Results: This observation and the observation that AABH is found in the serum of patients with cancer, but not in non cancer patients, led us to develop a Sandwich ELISA Assay to measure AABH in serum. In the current study we have quantified AABH levels in CRC patients and compared it with normal individual. Increased levels of AABH were found in the serum of 99% of patients with CRC in all different stages of Cancer (n = 277). In normal individuals, AABH was essentially undetectable in serum (n = 195). AABH was identified in serum from patients with CRC irrespective of cancer stage. All serum AABH levels for stages I, II, III and IV were more than 3.0 ng/mL. Conclusions: Thus, our data indicate that by measuring AABH in the serum, we should be able to detect CC at an earlier stage than it is currently detected, resulting to a much better 5-year survival for colon cancer.
Combining the quantitative fecal immunochemical test and full blood count to rule out colorectal cancer in a symptomatic patient referral pathway.
Authors: Johnstone Mark , Burton Paul , Kourounis Georgios , Winter Jack , Crighton Emilia M. , Mansouri David , Witherspoon Paul , Smith Karen , McSorley Stephen Thomas 
Published: January 2022

28 Background: The faecal immunochemical test (FIT) has proven utility for colorectal cancer (CRC) detection in symptomatic patients. Most studies have examined FIT in symptomatic patients subsequently referred from primary care. We investigated associations between CRC and FIT in both referred and non-referred symptomatic patients. Methods: A retrospective, observational study of all patients with a FIT submitted Aug’18-Jan’19 in NHS GG&C was performed. Referral to colorectal/gastroenterology and decision to perform colonoscopy were recorded. FIT results were grouped as f-Hb<10/10-149/150-399/≥400ug/g. The MCN cancer registry identified new cases of CRC. Covariables were compared using the χ2 test. Multivariate binary logistic regression identified independent predictors of CRC. Results: 4968 patients were included. Raised FIT correlated with decision to refer (p<0.001) and scope (p<0.001). With 23-month median follow-up, 61 patients were diagnosed with CRC. These patients were older (median 69 vs. 59 years, cancer and no cancer respectively, p=0.001), more likely to be male (55.7% vs. 42.1%, p=0.033) and to report rectal bleeding (51.7% vs. 36.1%, p=0.013). FIT (<10 µg/g 8.2% vs. 76.7% and ≥400 µg/g 55.7% vs. 3.8%, p<0.001) and anaemia (45.9% vs. 19.7%, p<0.001) were associated with CRC. On multivariate analysis, age (p=0.023), male sex (p=0.04), FIT (≥400 OR 54.256 (95% CI: 20.683-142.325; p<0.001)) and anaemia (OR 1.956 (1.071-3.574;p=0.029)) independently predicted CRC. 1 patient (0.04%) with a negative FIT and normal haemoglobin had CRC. Conclusions: Referral from primary care and secondary care investigation patterns were influenced by FIT. The combination of normal Hb and f-Hb excluded CRC in 99.96% of cases, providing excellent reassurance to those prioritising access to endoscopy services.
COVID-19 impact on diagnosis and staging of colorectal cancer: A single tertiary Canadian oncology center experience.
Authors: Castonguay Mathias , Richard Corentin , Vachon Marie-France , Nassabein Rami Mohamad , Charpentier Danielle , Tehfe Mustapha 
Published: January 2022

33 Background: COVID-19 pandemic urged public health to imposed drastic reduction on endoscopic activities and surgery, leading to delays that still not have been caught up today. The Ministry of Health and Social Services (MSSS) of Quebec conducted a study of the impact of those measures and reported a 66% reduction of colonoscopy and a 30% reduction of colorectal cancer (CRC) surgery activities during the first wave (March to May 2020). Whether those reduction had an impact on diagnosis and staging of CRC remains unknown. Methods: Demographic information of CRC diagnosed at Centre Hospitalier de l’Université de Montréal (CHUM) between January 1 2018 and March 12 2020 (pre-pandemic period), and March 13 2020 and June 30 2021 (pandemic period) were obtained from the SARDO registry and data regarding colonoscopy, surgery and staging at diagnosis (clinical or pathological as appropriate) were collected. Priority of elective colonoscopy was defined using the MSSS grading system ranging from P1 to P5. We compared delays to colonoscopy, delays to surgery and CRC staging of the pandemic period to the pre-pandemic period using one-way ANOVA, t tests and Chi-square tests as appropriate. Only delays in elective surgeries intended as first and curative treatment were analyzed. Results: 280 CRC diagnosis were made at the pre-pandemic period compared to 127 CRC diagnosis during the pandemic period. Mean diagnosis rates of the pandemic period tend to be lower (8.3 vs. 10.5 diagnosis/month, p=0.03) compared to the pre-pandemic period. 37.6% of patient in the pandemic period had a diagnosis of CRC during a hospitalization compared to 25.9% at the pre-pandemic period (p=0.048). 51.7% of elective colonoscopy leading to a diagnostic of CRC during the pandemic period did not meet required delays according to priority compared to 38.3% (p=0.049) during the pre-pandemic period. P3 colonoscopies (mostly indicated for a positive FIT and iron deficiency anemia) were the most affected (58.9 vs. 106.5 days, p˂0.001). P2 colonoscopy (indicated for suspected colorectal cancer) did not experienced an augmentation in delays (20.9 vs. 25.2 days, p=0.39). A mean of 3.5 elective curative surgeries per month were performed during the pandemic period compared to 3.4 at the pre-pandemic period (p=0.96), and mean delays for surgery were not affected (60.4 vs. 57 days, p=0.59). Stages at diagnosis did not differ (p=0.2). Most of the delayed colonoscopies led to a stage 0 or I CRC and did not lead to a higher stage at diagnosis (p=0.2). Conclusions: In our center, the COVID-19 pandemic led to overall less CRC diagnosis and increased diagnostic endoscopic delays without a higher rate of advanced stage disease. Delays for elective surgeries were quite similar once the CRC diagnostic established.
The potential long-term comparative effectiveness of larotrectinib versus entrectinib for treatment of metastatic TRK fusion colorectal cancer.
Authors: Suh Kangho , Carlson Josh John , Xia Fang , Williamson Todd E. , Sullivan Sean D 
Published: January 2022

40 Background: Commonly used systemic therapies in metastatic colorectal cancer (CRC) for patients who have progressed through available first- and second-line regimens are regorafenib or trifluridine/tipiracil. For the subset of metastatic CRC patients with neurotrophic receptor tyrosine kinase ( NTRK) gene fusions, there are two additional approved options, larotrectinib or entrectinib. Our objective was to estimate and compare expected life-years (LYs) and quality-adjusted life-years (QALYs) for metastatic TRK fusion CRC patients receiving larotrectinib versus entrectinib. Methods: We developed a partitioned survival model to project long-term comparative effectiveness of larotrectinib vs. entrectinib. Extrapolation was necessary as follow-up for both drugs was less than three years at the time of data reporting. Survival data for larotrectininb, assessed by independent review committee, were derived from a July 2020 analysis of 8 adult (≥18 years of age) TRK fusion CRC patients from the larotrectinib clinical trials program (NCT02122913, NCT02637687, and NCT02576431). Survival inputs for entrectinib were derived from 7 TRK fusion CRC patients from an October 2018 integrated analysis of three single arm trials (EudraCT 2012-000148-88, NCT02097810, and NCT02568267). Progression-free survival (PFS) and overall survival (OS) for both treatments were estimated using parametric survival distributions (Exponential, Weibull, Log-logistic, and Log-normal) fit to the available data. Exponential curves were used based on goodness-of-fit and clinical plausibility. QALYs were estimated by adjusting the time spent in the pre-progression and post-progression health states by health state utilities derived from publicly available literature. A constant discount rate of 3% was applied to LYs and QALYs. Model uncertainty was evaluated using one-way sensitivity analysis and probabilistic sensitivity analysis with 10,000 simulations. Results: Larotrectinib resulted in 2.11 LYs and 1.60 QALYs compared to 0.53 LYs and 0.41 QALYs for entrectinib. These estimates yielded additional gains for larotrectinib of 1.58 LYs and 1.19 QALYs against entrectinib. Conclusions: In metastatic TRK fusion CRC, larotrectinib may produce substantial life expectancy and quality-adjusted life-year gains compared to entrectinib. Additional data with longer follow-up times will further inform this comparison.
The potential long-term comparative effectiveness of larotrectinib versus regorafenib or trifluridine/tipiracil for treatment of metastatic TRK fusion colorectal cancer.
Authors: Suh Kangho , Carlson Josh John , Xia Fang , Williamson Todd E. , Sullivan Sean D. 
Published: January 2022

41 Background: Colorectal cancer (CRC) is the third leading cause of cancer-related mortality in the US, driven primarily by those with metastatic disease. For patients with metastatic disease who have progressed through available first- and second-line options, the standard of care systemic therapies are regorafenib or trifluridine/tipiracil. Larotrectinib is approved for patients with TRK fusion advanced solid tumors including metastatic CRC. Our objective was to compare expected life-years (LYs) and quality-adjusted life-years (QALYs) for metastatic CRC patients eligible to receive larotrectinib, regorafenib or trifluridine/tipiracil. Methods: We developed a partitioned survival model to project long-term comparative effectiveness of larotrectinib vs. regorafenib or trifluridine/tipiracil. Larotrectinib survival data, assessed by independent review committee, were derived from a July 2020 analysis of 8 adult (≥18 years of age) metastatic TRK fusion CRC patients from the larotrectinib clinical trials program (NCT02122913, NCT02637687, and NCT02576431). Survival inputs for regorafenib and trifluridine/tipiracil were derived from the CORRECT trial (NCT01103323) and the RECOURSE trial (NCT01607957), respectively. Progression-free (PFS) and overall survival (OS) for larotrectinib, regorafenib, and trifluridine/tipiracil were estimated using survival distributions (Exponential, Weibull, Log-logistic, and Log-normal) fit to the available data. Exponential fits were used based on goodness-of-fit and clinical plausibility. QALYs were estimated by adjusting the time spent in the pre-progression and post-progression health states by health state utilities derived from publicly available literature. In accordance with standard practice in health economics and outcomes research on future health benefits, a constant discount rate of 3% was applied to the LYs and QALYs. Model uncertainty was evaluated using one-way sensitivity analysis and probabilistic sensitivity analysis with 10,000 simulations. Results: Larotrectinib resulted in 2.11 LYs and 1.60 QALYs compared to 0.83 LYs and 0.59 QALYs for regorafenib and 0.85 LYs and 0.60 QALYs for trifluridine/tipiracil. These estimates yielded additional gains for larotrectinib of 1.28 LYs (1.01 QALYs) and 1.26 LYs (0.99 QALYs) against regorafenib and trifluridine/tipiracil, respectively. Conclusions: In metastatic CRC, larotrectinib may produce substantial life expectancy and quality-adjusted life-year gains compared to regorafenib or trifluridine/tipiracil. Additional data with longer follow-up times will further inform this comparison.