Search

Background: Pre-clinical models demonstrate that platelet activation is involved in the spread of malignancy. Ongoing clinical trials are assessing whether aspirin, which inhibits platelet activation, can prevent or delay metastases., Methods: Urinary 11-dehydro-thromboxane B 2 (U-TXM), a biomarker of in vivo platelet activation, was measured after radical cancer therapy and correlated with patient demographics, tumour type, recent treatment, and aspirin use (100 mg, 300 mg or placebo daily) using multivariable linear regression models with log-transformed values., Results: In total, 716 patients (breast 260, colorectal 192, gastro-oesophageal 53, prostate 211) median age 61 years, 50% male were studied. Baseline median U-TXM were breast 782; colorectal 1060; gastro-oesophageal 1675 and prostate 826 pg/mg creatinine; higher than healthy individuals (~500 pg/mg creatinine). Higher levels were associated with raised body mass index, inflammatory markers, and in the colorectal and gastro-oesophageal participants compared to breast participants (P < 0.001) independent of other baseline characteristics. Aspirin 100 mg daily decreased U-TXM similarly across all tumour types (median reductions: 77-82%). Aspirin 300 mg daily provided no additional suppression of U-TXM compared with 100 mg., Conclusions: Persistently increased thromboxane biosynthesis was detected after radical cancer therapy, particularly in colorectal and gastro-oesophageal patients. Thromboxane biosynthesis should be explored further as a biomarker of active malignancy and may identify patients likely to benefit from aspirin., (© 2023. The Author(s).)

University students are twice as likely to self-harm than community controls but, unfortunately, help-seeking among this population is particularly low. Given the stigma around self-harm, the face-to-face nature of traditional support for self-harm can be a barrier to help-seeking. Smartphone applications (apps) are a possible alternative source of support, and research has shown that students are receptive to this option. This study sought to assess the acceptability of a smartphone app called BlueIce for university students who self-harm. Semi-structured interviews were conducted with 25 students with a history of self-harm. A qualitative content analysis was undertaken and five categories were identified: the content of BlueIce, the use of BlueIce with university students, the function of BlueIce, comparison with other support, and the implementation and uptake of BlueIce. Responses to BlueIce were very positive with students believing BlueIce to be a helpful resource that was perceived as more accessible than alternative support. Participants believed it could provide help in moments of distress as well as helping individuals learn longer-term coping skills. Others felt that BlueIce would not be adequate for some people and would be better used alongside other face-to-face support. Overall, it was clear that BlueIce was acceptable to the students in this study. Future research should seek to evaluate the feasibility and effectiveness of BlueIce within a university setting with students. HIGHLIGHTSStudents who self-harm found the BlueIce app to be an acceptable and appealing source of support for self-harm as well as other mental health difficulties.Participants felt that the app was more accessible than other forms of support, particularly for individuals who prefer not to discuss self-harm with a professional.Some felt that BlueIce could provide immediate support in moments of distress, while others believed it to be a longer-term solution that could help students learn more adaptive coping strategies.

Background: Inflammatory Bowel Diseases with its complexity and heterogeneity could benefit from the increased application of Artificial Intelligence in clinical management., Aim: To accurately predict adverse outcomes in patients with IBD using advanced computational models in a nationally representative dataset for potential use in clinical practice., Methods: We built a training model cohort and validated our result in a separate cohort. We used LASSO and Ridge regressions, Support Vector Machines, Random Forests and Neural Networks to balance between complexity and interpretability and analyzed their relative performances and reported the strongest predictors to the respective models. The participants in our study were patients with IBD selected from The OptumLabs® Data Warehouse (OLDW), a longitudinal, real-world data asset with de-identified administrative claims and electronic health record (EHR) data., Results: We included 72,178 and 69,165 patients in the training and validation set, respectively. In total, 4.1% of patients in the validation set were hospitalized, 2.9% needed IBD-related surgeries, 17% used long-term steroids and 13% of patients were initiated with biological therapy. Of the AI models we tested, the Random Forest and LASSO resulted in high accuracies (AUCs 0.70-0.92). Our artificial neural network performed similarly well in most of the models (AUCs 0.61-0.90)., Conclusions: This study demonstrates feasibility of accurately predicting adverse outcomes using complex and novel AI models on large longitudinal data sets of patients with IBD. These models could be applied for risk stratification and implementation of preemptive measures to avoid adverse outcomes in a clinical setting., (© 2022. The Author(s).)

Importance: Older and/or frail patients are underrepresented in landmark cancer trials. Tailored research is needed to address this evidence gap., Objective: The GO2 randomized clinical trial sought to optimize chemotherapy dosing in older and/or frail patients with advanced gastroesophageal cancer, and explored baseline geriatric assessment (GA) as a tool for treatment decision-making., Design, Setting, and Participants: This multicenter, noninferiority, open-label randomized trial took place at oncology clinics in the United Kingdom with nurse-led geriatric health assessment. Patients were recruited for whom full-dose combination chemotherapy was considered unsuitable because of advanced age and/or frailty., Interventions: There were 2 randomizations that were performed: CHEMO-INTENSITY compared oxaliplatin/capecitabine at Level A (oxaliplatin 130 mg/m2 on day 1, capecitabine 625 mg/m2 twice daily on days 1-21, on a 21-day cycle), Level B (doses 0.8 times A), or Level C (doses 0.6 times A). Alternatively, if the patient and clinician agreed the indication for chemotherapy was uncertain, the patient could instead enter CHEMO-BSC, comparing Level C vs best supportive care., Main Outcomes and Measures: First, broad noninferiority of the lower doses vs reference (Level A) was assessed using a permissive boundary of 34 days reduction in progression-free survival (PFS) (hazard ratio, HR = 1.34), selected as acceptable by a forum of patients and clinicians. Then, the patient experience was compared using Overall Treatment Utility (OTU), which combines efficacy, toxic effects, quality of life, and patient value/acceptability. For CHEMO-BSC, the main outcome measure was overall survival., Results: A total of 514 patients entered CHEMO-INTENSITY, of whom 385 (75%) were men and 299 (58%) were severely frail, with median age 76 years. Noninferior PFS was confirmed for Levels B vs A (HR = 1.09 [95% CI, 0.89-1.32]) and C vs A (HR = 1.10 [95% CI, 0.90-1.33]). Level C produced less toxic effects and better OTU than A or B. No subgroup benefited from higher doses: Level C produced better OTU even in younger or less frail patients. A total of 45 patients entered the CHEMO-BSC randomization: overall survival was nonsignificantly longer with chemotherapy: median 6.1 vs 3.0 months (HR = 0.69 [95% CI, 0.32-1.48], P = .34). In multivariate analysis in 522 patients with all variables available, baseline frailty, quality of life, and neutrophil to lymphocyte ratio were independently associated with OTU, and can be combined in a model to estimate the probability of different outcomes., Conclusions and Relevance: This phase 3 randomized clinical trial found that reduced-intensity chemotherapy provided a better patient experience without significantly compromising cancer control and should be considered for older and/or frail patients. Baseline geriatric assessment can help predict the utility of chemotherapy but did not identify a group benefiting from higher-dose treatment., Trial Registration: isrctn.org Identifier: ISRCTN44687907.

Background: Despite advancements in treatment for inflammatory bowel disease (IBD), surgery remains inevitable for patients and IBD management is costly. Introduction: Frequent postoperative monitoring is needed for early detection of both short-term complications and long-term disease recurrence. We developed a care pathway for postoperative home monitoring of IBD patients using telehealth applications. Materials and Methods: We performed a retrospective cohort study with a matched control group to assess the efficacy of the Tight Control Surgery Scenario (TCSS), a 4-week postoperative care pathway. IBD patients aged 18 or older who underwent an IBD-related intestinal operation between October 2013 and December 2015 were eligible. Enrolled participants submitted postsurgical questionnaires and wound photos through e-mail. We measured patient satisfaction with the care pathway and assessed its impact on 30-day postoperative hospital readmission rates, emergency department (ED) visits, and gastroenterologist (GI)-related office visits. Results: Sixty-four ( n ) cases were enrolled in TCSS and matched to 64 historic controls. Patients who completed the additional evaluation survey expressed overall satisfaction. Readmissions, 30-day ED rates, and GI visits were numerically higher in cases compared with controls, but this difference was not statistically significant. Discussion: TCSS demonstrates the feasibility of implementing a telehealth care coordination platform for postsurgery IBD management. Patients with more complications may have sent in more photos due to greater concern for maintaining their health. Conclusions: Implementation of TCSS for easy home monitoring is feasible. While we did not see reductions in ED visits, GI follow-up visits, or readmissions, patient satisfaction was high, thus demonstrating its feasibility for telehealth applications.

Background: Caregiver burden is the emotional, physical, practical, and/or financial burden associated with taking care of a patient with a chronic condition. Limited literature on caregiver burden in Inflammatory Bowel Diseases (IBD) has accounted for some predictors, but its effect on work productivity (absenteeism and presenteeism) is unknown., Methods: In a prospective study, patients and their respective caregivers were surveyed from November 2015 until July 2017. Data on demographics, work productivity, quality of life, disease activity, caregiver burden and productivity were collected. The burden on caregivers was assessed and associations between caregiver productivity and caregiver burden were analyzed. Additionally, predictors for caregiver burden were identified., Results: One hundred two IBD patients and their respective caregiver were included. In total, 39% of IBD caregivers experienced burden. Caregivers with burden experienced significantly more absenteeism and presenteeism (65 and 85% respectively). Furthermore, 51% of caregivers felt that they should be doing more for their care recipient and felt they could do a better job at caregiving. Predictors of burden included race/ethnicity, history of fistulas, diagnosis of ulcerative colitis, higher caregiver education, and hours spent caregiving., Conclusion: Caregivers with burden had significantly more productivity decrease compared to those without burden. Additionally, the majority of caregivers feel they should be providing more and better care for their recipients. The development of strategies to address caregiver's distress and perceived burden when caring for IBD patients is warranted.

Background: The emergence of chatbots in health care is fast approaching. Data on the feasibility of chatbots for chronic disease management are scarce., Objective: This study aimed to explore the feasibility of utilizing natural language processing (NLP) for the categorization of electronic dialog data of patients with inflammatory bowel diseases (IBD) for use in the development of a chatbot., Methods: Electronic dialog data collected between 2013 and 2018 from a care management platform (UCLA eIBD) at a tertiary referral center for IBD at the University of California, Los Angeles, were used. Part of the data was manually reviewed, and an algorithm for categorization was created. The algorithm categorized all relevant dialogs into a set number of categories using NLP. In addition, 3 independent physicians evaluated the appropriateness of the categorization., Results: A total of 16,453 lines of dialog were collected and analyzed. We categorized 8324 messages from 424 patients into seven categories. As there was an overlap in these categories, their frequencies were measured independently as symptoms (2033/6193, 32.83%), medications (2397/6193, 38.70%), appointments (1518/6193, 24.51%), laboratory investigations (2106/6193, 34.01%), finance or insurance (447/6193, 7.22%), communications (2161/6193, 34.89%), procedures (617/6193, 9.96%), and miscellaneous (624/6193, 10.08%). Furthermore, in 95.0% (285/300) of cases, there were minor or no differences in categorization between the algorithm and the three independent physicians., Conclusions: With increased adaptation of electronic health technologies, chatbots could have great potential in interacting with patients, collecting data, and increasing efficiency. Our categorization showcases the feasibility of using NLP in large amounts of electronic dialog for the development of a chatbot algorithm. Chatbots could allow for the monitoring of patients beyond consultations and potentially empower and educate patients and improve clinical outcomes., (©Aria Zand, Arjun Sharma, Zack Stokes, Courtney Reynolds, Alberto Montilla, Jenny Sauk, Daniel Hommes. Originally published in the Journal of Medical Internet Research (http://www.jmir.org), 26.05.2020.)

Differential Evolution (DE) has become one of the leading metaheuristics in the class of Evolutionary Algorithms, which consists of methods that operate off of survival-of-the-fittest principles. This general purpose optimization algorithm is viewed as an improvement over Genetic Algorithms, which are widely used to find solutions to chemometric problems. Using straightforward vector operations and random draws, DE can provide fast, efficient optimization of any real, vector-valued function. This article reviews the basic algorithm and a few of its modifications with various enhancements. We provide guidance for practitioners, discuss implementation issues and give illustrative applications of DE with the corresponding R codes to find different types of optimal designs for various statistical models in chemometrics that involve the Arrhenius equation, reaction rates, concentration measures and chemical mixtures., Competing Interests: Declaration of interests The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Objective: A dose escalation study was performed for patients with locally advanced squamous carcinoma of cervix to determine the maximum tolerated dose (MTD) of daily capecitabine when combined with weekly cisplatin and radiotherapy. MTD would be reached if at least 2 out of 6 at any particular dose level developed Grade 3 or 4 diarrhoea, mucositis, skin or bladder toxicity or Grade 4 neutropenia associated with fever lasting more than 7 days or Grade 3 or 4 thrombocytopenia. The secondary endpoints were to define the toxicity profile, compliance with treatment, late radiation effects and to determine the tumour responses., Methods: Thirteen patients were enrolled (7 Stage II(b), 6 Stage III(b)). Cisplatin was given weekly at 40 mg/m2 (maximum 70 mg) concurrently with radiotherapy. Two doses of capecitabine were studied 300 mg/m2 bid (cohort 1) and 450 mg bid (cohort 2)., Results: One patient in cohort 1 developed Grade 3 diarrhoea and 2 patients had Grade 3 leucopenia. Two patients in cohort 2 developed Grade 4 leucopenia and neutropenic fever; one of these patients also had Grade 3 diarrhoea and thrombocytopenia. Only 1 patient had Grade 1 palmar-plantar erysthrodysesthesia. Three patients have developed late (RTOG/ECOG) Grade 3 toxicity bladder or vaginal mucosa at 6, 9 and 15 months. The MDT of continuous capecitabine, when given with pelvic radiotherapy and weekly cisplatin, is 450 mg m2 bid., Conclusions: The recommended dose of capecitabine in this combination is 300 mg/m2 bid. The regimen was well tolerated and the compliance was high. Progression-free survival at 12 months was 69.2%, and at 24 months, it was 49.2% (SE 15.4%) with an overall survival of 57.7% (SE 15.0%) at 24 months. Further evaluation of this regimen in a phase II/III study is warranted.

Vancomycin has been reported to be an ototoxic drug in the clinical literature. At best, this literature is confusing. There are no reports of ototoxicity of vancomycin in experimental animals, even when it is administered concurrently with ethacrynic acid, a drug known to augment the ototoxic effect of most other ototoxic drugs. In most of the cases of permanent ototoxicity that have been reported, the patient was treated with an aminoglycoside antibiotic as well as vancomycin. This study found no evidence of vancomycin ototoxicity in guinea pigs, but found that vancomycin greatly enhanced the ototoxicity of gentamicin.