bluuebunny/crossref_metadata_2025_split huggingface dataset:
Can mHealth bridge the digital divide in rheumatic and musculoskeletal conditions?
Authors: Schreurs L. , Steenhout I. , Bosmans J. , Buyl R. , De Cock D. 
Published: January 2023

Abstract
Background
The impact of rheumatic and musculoskeletal diseases is significant worldwide. Progress in disease management has put current care models under pressure. Mobile Health solutions may constitute a solution for these changes. However, vulnerable populations groups including people with a migration or ethnic background different from the host country, people with low socio-economic status and people with low (digital) literacy skills seem to be underrepresented in mHealth research and practice.

Main body
In this editorial, we propose tailored interventions with mobile health applications on three levels including patient-related strategies, healthcare provider-related strategies and healthcare system-related strategies to solve this unmet need for patients from vulnerable populations groups with rheumatic and musculoskeletal diseases. Patient-related mobile health strategies should focus on increasing self-efficacy and enabling peer-education. Gamification could be a solution to motivate patients to use mobile health. On the level of the healthcare provider, we propose strategies including technology-enhanced learning and adaptative communication strategies, to tailor mobile health towards vulnerable populations groups with rheumatic and musculoskeletal diseases. Regarding healthcare system-related strategies, the aim is to increase minority participation in research in a cost-effective manner by remote longitudinal data tracking, using teleconsultation or remote symptom monitoring devices to ensure quality care for all patients with rheumatic and musculoskeletal diseases, even in vulnerable populations groups that are normally hard to reach.

Conclusion
Vulnerable population groups in rheumatic and musculoskeletal diseases are underrepresented in mobile health research and practice. Evidence is sparce on the scale of the digital divide between patients using or not using mobile health. Interventions that directly attempt to reduce health disparities among vulnerable populations groups are needed to guarantee all patients with rheumatic and musculoskeletal diseases might be engaged in the rheumatology care of the future.
Association between polypharmacy and depression relapse in individuals with comorbid depression and type 2 diabetes: a UK electronic health record study
Authors: Jeffery Annie , Bhanu Cini , Walters Kate , Wong Ian C. K. , Osborn David , Hayes Joseph F. 
Published: January 2023

BackgroundIndividuals with physical comorbidities and polypharmacy may be at higher risk of depression relapse, however, they are not included in the ‘high risk of relapse’ group for whom longer antidepressant treatment durations are recommended.AimsIn individuals with comorbid depression and type 2 diabetes (T2DM), we aimed to investigate the association and interaction between depression relapse and (a) polypharmacy, (b) previous duration of antidepressant treatment.MethodThis was a cohort study using primary care data from the UK Clinical Practice Research Datalink (CPRD) from years 2000 to 2018. We used Cox regression models with penalised B-splines to describe the association between restarting antidepressants and our two exposures.ResultsWe identified 48 001 individuals with comorbid depression and T2DM, who started and discontinued antidepressant treatment during follow-up. Within 1 year of antidepressant discontinuation, 35% of participants restarted treatment indicating depression relapse. As polypharmacy increased, the rate of restarting antidepressants increased until a maximum of 18 concurrent medications, where individuals were more than twice as likely to restart antidepressants (hazard ratio (HR) = 2.15, 95% CI 1.32–3.51). As the duration of previous antidepressant treatment increased, the rate of restarting antidepressants increased – individuals with a previous duration of ≥25 months were more than twice as likely to restart antidepressants than those who previously discontinued in <7 months (HR = 2.36, 95% CI 2.25–2.48). We found no interaction between polypharmacy and previous antidepressant duration.ConclusionsPolypharmacy and longer durations of previous antidepressant treatment may be associated with depression relapse following the discontinuation of antidepressant treatment.
HCRN GI16-288: A phase II trial of perioperative CV301 vaccination in combination with nivolumab and systemic chemotherapy for resectable hepatic-limited metastatic colorectal cancer—Preliminary efficacy and correlative results.
Authors: Spencer Kristen Renee , Hochster Howard S. , Boland Patrick M , Berim Lyudmyla Derby , Kennedy Timothy , Grandhi Miral , Langan Russell C , Moore Dirk F. , Kane Michael P. , Krishnamurthi Smitha S. , Mayo Skye C. , Kasi Anup , Pimentel Agustin , Carpizo Darren R. 
Published: January 2023

103 Background: Novel strategies to improve the efficacy of immune checkpoint inhibitors in microsatellite stable (MSS) mCRC are needed. CV301 is a vector-based vaccine that expresses carcinoembryonic antigen (CEA) and mucin 1 (MUC1), and in a phase II study in resected hepatic limited mCRC significantly improved OS compared with unvaccinated contemporary controls. Methods: In this multi-center randomized phase II study, patients with previously untreated resectable hepatic-limited mCRC were randomized to perioperative nivolumab + mFOLFOX +/- CV301 (Arm B) with a primary endpoint of 3-year OS. Treatment included mFOLFOX-nivo (+/- CV) x 4 cycles followed by resection, then 8 more cycles of mFOLFOX-nivo followed by maintenance nivo monthly for two years in both arms, and CV boosters concurrently with mFOLFOX, and then every 3 months for two years in arm B. Secondary endpoints of ORR (following induction pre-resection), PRR, and safety were determined. Correlative analyses included immune cell quantification using Immunoscore and T-cell clonality. Results: 17 patients were enrolled prior to premature closure for slow accrual (8 arm A, 9 arm B). At the time of data cutoff, 5 patients remained on treatment and no deaths had occurred. One patient was removed from study due to protocol non-compliance. The median age was 61, majority were male (59% vs 41%), and ECOG PS 0-1 (71% 0, 17% 1). All patients had complete surgical resection. Four patients (24%) experienced a SAE related to drug. The TRAE rate was 40.3%,. No AEs delayed/prevented surgical resection. The ORR in arm A was 50% (including 4 CR) and 87.5% in arm B (including 7 CR) (p=0.129, NS). There was no significant difference in pathologic response (p=0.9047). Correlative analyses demonstrated the Immunoscore CD3/CD8 predicted response to mFOLFOX + nivolumab, but did not correlate with response to CV301, though CV301 may induce a shift to predominantly cytotoxic CD8+ T cells. While there was no significant difference in T cell repertoire, clonality, fraction (TCFr) or richness, patients in arm B had significant decreases in blood TCFr and increase in tumor TCFr with treatment; those with CR had higher TCFr and clonality. Conclusions: The addition of CV301 to perioperative nivolumab and mFOLFOX was safe, did not delay or prevent surgical resection, and gave a higher response (p=ns due to sample size). Changes in T cells suggest a vaccine response. Clinical trial information: NCT03547999 . [Table: see text]
Bleeding and thrombotic events in patients with colorectal cancer treated with bevacizumab and receiving novel oral anticoagulants and antiplatelet medications.
Authors: Rho Shinji , Wang Chris , Hosseini Dehkordi Seyed Hamed , Sears Jerod J , Hu Zishuo Ian 
Published: January 2023

104 Background: Bevacizumab is a humanized monoclonal VEGF antibody given in combination with fluorouracil-based chemotherapy for metastatic colorectal cancer (mCRC). Many patients with mCRC also have cardiovascular comorbidities requiring anticoagulation or antiplatelet therapy. The bleeding and thrombotic event rates in the setting of concurrent novel oral anticoagulants (NOACs) and bevacizumab treatment in patients with mCRC remain unclear. Methods: 462 patients with mCRC at Barnes-Jewish Hospital were identified between December 1, 2016 and December 1, 2021 and screened for concurrent treatment with bevacizumab and anticoagulant or antiplatelet therapy. Demographic and clinical information was extracted by electronic chart review. Results: 21 patients were identified who received bevacizumab and either apixaban or rivaroxaban for mCRC treatment. Aspirin was prescribed in some of these patients within 3 years of starting apixaban or rivaroxaban. Of the 13 patients who had no history of aspirin prescription, 9 were given apixaban, and 4 were given rivaroxaban while on bevacizumab. 44.4% of the patients who received apixaban experienced bleeding. All these events were epistaxis, and only 25% of the cases resulted in any treatment discontinuation. 75% of the patients who received rivaroxaban experienced bleeding events, which 33.3% of the time resulted in discontinuation of either rivaroxaban or bevacizumab. We also looked at 8 patients who had received aspirin in the last three years: 7 patients were on apixaban, and one was on rivaroxaban while on concomitant aspirin and bevacizumab. 28.6% of the patients who received apixaban with bevacizumab and aspirin experienced an adverse bleeding event that resulted in some form of treatment discontinuation. Meanwhile, the patient who received rivaroxaban with bevacizumab and aspirin experienced a bleeding event that resulted in discontinuation of a medication. No patient experienced any adverse thrombotic events. Conclusions: Patients with mCRC treated with bevacizumab and apixaban with no history of prior aspirin use within three years have a relatively low risk of developing bleeding events that warrant treatment discontinuation. The addition of NOAC to bevacizumab therapy does not appear to increase the risk of adverse thrombotic events.
Comparative study of prognosis of conversion therapy vs palliative therapy without surgery in colorectal cancer with synchronous liver metastasis according to risk classifications.
Authors: Nozawa Hiroaki , Tsushima Tatsuya , Suzuki Nobumi , Fujishiro Mitsuhiro , Kawaguchi Yoshikuni , Hasegawa Kiyoshi , Ishihara Soichiro 
Published: January 2023

107 Background: Recent progress in chemotherapy and targeting antibodies has brought an increased opportunity of conversion to curative resection in initially unresectable/metastatic colorectal cancer (CRC). Survival of CRC patients with liver metastasis who underwent conversion therapy was reported better than that of those who received palliative systemic therapy without surgery. However, it is largely unknown whether such patients who undergo conversion therapy can uniformly benefit from the surgical resections. Methods: We retrospectively reviewed 172 patients who received systemic therapy for unresectable CRC with synchronous liver metastasis in our hospital between 2010 and 2020. Patients were divided into ‘Conversion’ group (n = 45) and ‘Non-conversion’ group (n = 127) according to conversion to surgical resection with curative intent. Patients were also divided by pre-treatment Fong’s Clinical Risk Score (CRS), in addition to Grade A, B, or C group according to Japanese Grade Classification for colorectal liver metastasis. Overall survivals (OS) of Conversion and Palliation groups were compared according to these risk classifications. Results: Overall, 3-year OS rate was 76% for Conversion group and 25% for Non-conversion group (p < 0.001). Three-year OS rate for patients in Conversion group with CRS 1-3 was 73%, whereas that for those with CRS 4-5 was 77%. Both were higher than the rates for the counterparts in Non-conversion group (26% and 24%, respectively; both p < 0.001). When confined to Grade A and B of Japanese Grade Classification, 3-year OS rate was 68% for Conversion group and 25% for Non-conversion group (p = 0.002). The 3-year OS rate for the patient groups was 83% and 25% respectively in the analyses of patients classified into Grade C (p < 0.001). Conclusions: Conversion therapy provided a significant survival benefit in CRC patients with liver metastasis regardless of risk groups by the above classifications. Both classifications did not discriminate OS curves well between Conversion and Non-conversion groups in the era of conversion therapy.
A phase II study of CAPOXIRI as a neoadjuvant chemotherapy in patients with locally advanced rectal cancer (Colorectal Cancer Treatment Group, MSCSGO).
Authors: Kagawa Yoshinori , Matsuda Chu , Kudo Toshihiro , Morimoto Yoshihiro , Tei Mitsuyoshi , Ide Yoshihito , Miyoshi Norikatsu , Takahashi Hidekazu , Uemura Mamoru , Takemasa Ichiro , Satoh Taroh , Mizushima Tsunekazu , Murata Kohei , Doki Yuichiro , Eguchi Hidetoshi ,   Multicenter Clinical Study Group of Osaka, Colorectal Cancer Treatment Group (MSCSGO)
Published: January 2023

109 Background: Addition of perioperative multi-agent chemotherapy to the treatment strategy for locally advanced rectal cancer (LARC) may be a promising option. We conducted a multicenter single-arm phase II study to evaluate the safety and efficacy of capecitabine combined with oxaliplatin and irinotecan (CAPOXIRI) as triplet neoadjuvant chemotherapy in patients with LARC. Methods: The key eligibility criteria were as follows: (1) age over 20 years; (2) Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1; (3) resectable clinical stage II (T3 or T4 with N0) or III (any T and N1–3), with the primary tumor located within 12 cm of the anal verge. Patients received intravenous oxaliplatin (85 mg/m2) and intravenous irinotecan (150 mg/m2) on day 1 and oral capecitabine (1,000 mg/m2) twice daily on days 1–7 followed by 7 days of rest, repeated every 2 weeks for six cycles. Total mesothelial resection was performed 4–8 weeks after chemotherapy ended. In addition to the treatment protocol, patients received adjuvant chemotherapy for four cycles. The primary study endpoint was the pathological complete response (pCR) rate. We based the sample size of the study described herein on an expected pCR rate of 18% and a threshold pCR rate of 5% to detect differences at a two-sided alpha error of 0.05 and a statistical power of 0.2. Results: Between June 2013 and December 2016, 55 patients were enrolled in the study. Forty-five (83.3%) of the 54 patients who underwent NAC received the full six courses. Fifty-two (94.5%) patients underwent tumor resection. Laparoscopic surgery was performed in 47 (90.4%) patients, and lateral lymph node dissection was performed in 35 (67.3%) patients. Forty-nine (94.2%) patients underwent R0 resection. The pCR rate was 7.7% (95% CI 3.0% to 18.2%). The 3-year local recurrence rate was 3.9%, the 3-year disease-free survival (DFS) rate was 77.3, and the 3-year overall survival rate was 96.0%. NAC-related grade 3/4 adverse event rates were as follows: neutropenia (25.9%), anorexia (13.0%), diarrhea (11.1%) and anemia (7.4%). Conclusions: CAPOXIRI neoadjuvant chemotherapy appears to be feasible and efficacious for patients with LARC. Although neoadjuvant XELOXIRI alone did not yield our expected pCR rate, the local recurrence rate, 3-year DFS and measures of safety met current standards. Clinical trial information: UMIN000009974 .
Effectiveness and safety of encorafenib-cetuximab in BRAFV600E metastatic colorectal cancer: Confidence study.
Authors: Fernandez Montes Ana , Ros Javier , Graña Begoña , García-Alfonso Pilar , Brozos Elena , Melian Marcos , Jiménez-Gordo Ana M. , Martinez de Castro Eva , Busquier Isabel , Gallego Javier , Gravalos Cristina , Covela Marta , Ruiz-Casado Ana , González Flores Encarnación , Safont Mariajose , Cano Juana Maria , Alonso Lopez Carmen , Gomez-Reina Maria Jose , Donnay Olga , Aranda Enrique ,   Confidence Study Group
Published: January 2023

126 Background: BRAFV600E mutant metastatic colorectal cancer (mCRC) has a poor prognosis. The BEACON trial demonstrated an improvement in tumor response, overall survival (OS), and progression-free survival (PFS) when administering encorafenib-cetuximab (EC) to patients (pts) who progressed after 1 or 2 therapy lines. This study provides a retrospective analysis of the effectiveness and safety of EC in the real-world setting in Spain. Methods: This retrospective analysis included BRAFV600E mCRC pts treated with EC in 2nd line treatment, recruited from March to July 2022. The Co-primary study endpoints included effectiveness based on PFS and OS. Secondary endpoints included sociodemographic and clinical characteristics of patients before EC initiation, overall response rate (ORR), and safety. Results: From March to July 2022, 81 evaluable pts were included. Sociodemographic and clinical characteristics are displayed.A median (interquartile range [IQR]) of 6.0 (4.0-13.0) cycles of encorafenib and 6.0 (4.0-14.5) cycles of cetuximab were administered. Median treatment duration was 4.4 (2.6-7.8) months (m) and 4.4 m (2.8-7.6) respectively. The ORR and disease control rate was 33.8 % (CI 95% 23.4-45.5) and 68.8 (CI 95% 57.3 – 78.9) respectively. One (1.2%) pt achieved complete response At data cut-offwith a 9.7 median follow-up, 50 (61.7%) pts had died, all of them due to disease progression. Median (95% Confidence Interval, CI) OS was 12.6 m (8.0-17.3) and median PFS was 5.0 m (3.8-6.2). The 12-m OS and 12-m PFS rates were 54.6% (95% CI, 43.3-65.9) and 19.9% (10.5-29.3) respectively. Pts with neutrophils/lymphocyte ratio (NLR) ≥3 had worse OS (HR, 1.8 95% CI 1.0-3.2; p < 0.049) and worse PFS (HR, 2.3, 1.4-3.8; p < 0.002). Disease progression (86.7%) was the most frequent cause of treatment discontinuation, followed by unacceptable AEs (3.7%). Eleven pts (13.5%) experienced treatment-related graded 3 or 4 AEs, mainly acne (3.7%). Treatment-related deaths were not reported. Conclusions: This study provides real-world data of BRAFV600E mCRC pts treated with EC combination in routine clinical practice in Spain. EC effectiveness and safety were consistent with the results obtained in clinical trials. [Table: see text]
Racial disparities in tumor microbiome in young-onset and average-onset colorectal cancer.
Authors: Dave Heloni M , Sangwan Naseer , Nair Kanika G. , Barot Shimoli V , Liska David , Schmit Stephanie , Khorana Alok A. 
Published: January 2023

13 Background: The occurrence of young-onset colorectal cancer (yoCRC) is rising alarmingly, with a disproportionate incidence in Black patients as compared to White. We and others have previously shown differences in tumor microbiomes between yoCRC and average-onset colorectal cancer (aoCRC), but it is unknown if these differences contribute to racial disparities. We therefore analyzed racial differences in the intra-tumoral microbiome of CRC in young adults (<50 years). Methods: We analyzed 277 samples of histologically confirmed cases of stage I-IV CRC patients identified as either non-Hispanic Black or non-Hispanic White, who underwent surgical resection at Cleveland Clinic from year 2000-2020, who consented to a prospective biorepository. Fresh frozen specimens from the primary tumor with paired adjacent nonmalignant tissue were analyzed. The 16s rRNA gene was amplified and sequenced using V4 region primers and Illumina’s MiSeq system. Using DADA2, the quality filtered 16S rRNA amplicon reads were clustered and annotated as amplicon sequence variants (ASVs). The abundance count matrix was analyzed for alpha and beta diversity and differential abundance analysis (DAA) using Phyloseq package. Statistical tests included analysis of variance (ANOVA), permutational multivariate analysis (PERMANOVA), linear regression and Wilcoxon test. DAA and correlation analysis were controlled for false discovery rate using Benjamini Hochberg correction. Results: Differential abundance analysis highlighted key differences in the microbiome composition of Black and White patients with yoCRC. Amongst Black patients, the most prevalent taxa were Limosilactobacillus, Bacillus, Staphylococcus, Listeria and Akkermansia, whereas amongst White patients the most prevalent taxa were Enterococcus and Escherichia-Shigella (Table). Microbial profiles were also significantly different between Black patients with yoCRC and aoCRC and between White patients with yoCRC and aoCRC. At ASV level, the microbiome of Black yoCRC is more similar (R2 =0.87) to Black aoCRC, in comparison to white yoCRC (R2=0.57). Conclusions: We found significant differences between the intra-tumoral microbiome of yoCRC in the United States by race. Future epidemiologic studies and public health interventions need to account for these differences to reduce risk of yoCRC across various US populations. [Table: see text]
The impacts of initiating regorafenib with reduced dose on treatment outcomes in metastatic colorectal cancer.
Authors: Kawakami Takeshi , Harada Kazuaki , Ogata Takatsugu , Hu Qingjiang , Fushiki Kunihiro , Oshima Kotoe , Kadowaki Shigenori , Taniguchi Hiroya , Muro Kei , Nakanishi Ryota , Ando Koji , Nambara Sho , Yamamura Takahiro , Kawamoto Yasuyuki , Komatsu Yoshito , Oki Eiji , Masuishi Toshiki , Yamazaki Kentaro , Yuki Satoshi 
Published: January 2023

133 Background: Since the results of the ReDOS study were published, starting regorafenib (REG) at a reduced dose is now considered a treatment option for patients with metastatic colorectal cancer (mCRC). However, the impact of starting REG at a reduced dose on treatment outcomes in the real-world setting has not been fully investigated. Methods: We retrospectively analyzed patients who received REG for mCRC at 4 institutions between May 2013 and December 2020. These patients were divided into two groups: those who started REG before (Period A) and after (Period B) the ReDOS study publication (May 2018). The treatment outcomes between Period A and B were compared in this analysis. Results: A total of 573 patients were evaluated (385 in Period A and 188 in Period B, respectively). In Period B, significantly more patients started REG with reduced dose (34.3% vs. 75.5%, p< 0.001). The median time to first dose reduction was 32.0 days [95% CI: 29.1-34.9] in Period A and 61.0 days [95% CI: 33.7-88.9] in Period B, which was significantly longer in Period B (HR = 0.685, p= 0.003). Both any grades and ≥grade3 hand foot skin reaction (HFSR) were significantly less frequent in Period B than in Period A (any grades: 65.5% vs 54.8%, p= 0.017, ≥grade3: 21.3% vs 14.4%, p= 0.054). The median time to onset of any grades HFSR was 16.0 days [95% CI: 13.6-18.4] in Period A and 28.0 days [95% CI: 15.6-40.4] in Period B, which was significantly longer in Period B (HR = 0.738, p= 0.007). The median overall survival was 6.7 months [95% CI: 5.9-7.4] in Period A, and 5.4 month [95% CI: 4.3-6.5] in Period, respectively (HR = 1.105, p= 0.281). The median progression free survival was 2.0 months [95% CI: 1.9-2.1] in Period A and 2.1 months [95% CI: 1.8-2.4] in Period B, respectively (HR = 1.064, p= 0.498). Conclusions: Our results suggest that starting REG at a reduced dose may contribute to reducing the frequency and delaying the onset of HFSR, whereas it may not affect efficacy.