tbuckley/cabot-search huggingface dataset:
P14.11 Severe treatment-induced myelosuppression is more frequent in female malignant glioma patients and associated with reduced overall survival
Authors: P S Zeiner, K Filipski, M Forster, M Voss, E Fokas, U Herrlinger, P N Harter, J P Steinbach, M W Ronellenfitsch
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND An association of treatment-related myelotoxicity with female gender has been previously suggested. However, a systematic analysis of the prognostic relevance of radiochemotherapy-related cytopenia involving the different blood cell lineages is lacking. MATERIAL AND METHODS We retrospectively analyzed cytopenia during temozolomide-based concomitant radiochemotherapy (RCT) in 493 glioma patients. Histological grading, molecular pathology, surgical procedures and median overall survival (OS) were recorded. The extent of cytopenia was correlated with gender and outcome. RESULTS Treatment-induced severe cytopenia (leuko-, lympho-, neutro- and thrombocytopenia) occurred much more often in female than in male glioma patients (40.8 vs. 13.9%, p-value &amp;lt;0.0001). In female patients with IDH-wildtype high-grade astrocytomas there was a negative correlation of severe leuko-, lympho- and thrombocytopenia during temozolomide RCT with OS (36 vs. 54, 37 vs. 54 and 36 vs. 57 weeks, respectively; all p-values &amp;lt;0.05). In male patients there was also a trend for this unfavorable effect. Additionally, severe cytopenia correlated with reduced temozolomide dose exposure during RCT (all p-values &amp;lt;0.05 in total cohort) and reduced dose exposure was independently associated with worse OS (p-values &amp;lt;0.05 in the total and female cohort). CONCLUSION Our data confirm that women are at higher risk for treatment-induced cytopenia during RCT which is associated with a significant decrease in OS. From our data, it appears plausible that reduced temozolomide dose exposure during RCT is at least in part responsible for this finding. Immunosuppression of patients with severe cytopenia may be an independent contributor to adverse outcome.
Evaluation of drug cost avoidance resulting from conduct of cancer clinical trials in a community-based oncology practice.
Authors: Amit Sanyal, James M. Heun, Brittany Glynn, Ryan Porter, Daniel Wellner
Journal: Journal of Clinical Oncology (2021)

66 Background: Aim: To prospectively evaluate cost avoidance during routine conduct of cancer clinical trials in a community based integrated delivery network (IDN) consisting of a health services provider group, a health insurance plan and a hospital system. Only 2%–7% of adult cancer patients participate in clinical trials nationwide [1]. Inadequate funding and concerns about financial viability have been identified as factors that impede clinical trial accrual in the community oncology setting. ‘Cost-avoidance’, defined as dollars that would have been spent to purchase medications but were not spent because of study-related interventions [3] has been proposed as one mechanism to overcome this. Methods: Anti-cancer and hematology drugs provided by intergroup as well as pharmaceutical industry-based trial sponsors to patients enrolled in oncology clinical research were tabulated. Analysis of cost avoidance was restricted to patients covered by the IDNs health plan. Additionally, drugs provided by the trial sponsor were included in the analysis only if they represented a normal standard of care for the disease state. Cost avoidance was defined as the net ingredient cost of the drugs that would have been spent by the health plan for patient care if drugs provided by trial sponsors were not available. Results: Between January 2020 and April 2021, 25 patients covered by the IDN were recruited into clinical trials. Cost savings resulted from 7 targeted and immuno-oncology medications. Net cost avoidance in 2020 was $1,229,798 while that in 2021 till date has been $892,783. The realized cost savings has allowed recruitment of additional clinical research staff as well as expansion of clinical research to rural regional sites served by the IDN. Conclusions: Anticancer drugs provided free of charge by clinical trial sponsors render significant cost savings, ensuring viability and even expansion of oncology clinical research in community based IDNs. References: National Health Expenditure Data. 2018, U.S. Centers for Medicare &amp; Medicaid Services: Baltimore, MD 21244. McDonagh MS, M.S., Naden E., Costs and savings of investigational drug services. American Journal of Health-Systems Pharmacy, 2000. 57: p. 40-43.[Table: see text]
Public health monitoring of cannabis use in Europe: prevalence of use, cannabis potency, and treatment rates
Authors: Jakob Manthey, Tom P Freeman, Carolin Kilian, Hugo López-Pelayo, Jürgen Rehm
Journal: The Lancet Regional Health - Europe (2021)

Cannabis is one of the most widely used substances worldwide. Heavy use is associated with an increased risk of cannabis use disorders, psychotic disorders, acute cognitive impairment, traffic injuries, respiratory problems, worse pregnancy outcomes, and there are indications for genotoxic and epigenotoxic adverse effects. International regulation of medical and non-medical cannabis use is changing rapidly and substantially, highlighting the importance of robust public health monitoring. This study aimed to describe the trends of key public health indicators in European Union (27 member states + UK, Norway and Turkey) for the period 2010 to 2019, their public health implications, and to identify the steps required to improve current practice in monitoring of cannabis use and harm in Europe.Data on four key cannabis indicators (prevalence of use, prevalence of cannabis use disorder [CUD], treatment rates, and potency of cannabis products) in Europe were extracted from the United Nations Office on Drugs and Crime, European Monitoring Centre for Drugs and Drug Addiction and the Global Burden of Disease study. For prevalence of use and CUD, the first and last available estimate in each country were compared. For treatment rates and cannabis potency, linear regression models were conducted.Between 2010 and 2019, past-month prevalence of cannabis use increased by 27% in European adults (from 3·1 to 3·9%), with most pronounced relative increases observed among 35-64 year-olds. In 13 out of 26 countries, over 20% of all past-month users reported high-risk use patterns. The rate of treatment entry for cannabis problems per 100,000 adults increased from 27·0 (95% CI: 17·2 to 36·8) to 35·1 (95% CI: 23·6 to 46·7) and has mostly plateaued since 2015. Modest increases in potency were found in herbal cannabis (from 6·9% to 10·6% THC) while median THC values tripled in cannabis resin (from 7·6% to 24·1% THC).In the past decade, cannabis use, treatment rates and potency levels have increased in Europe highlighting major concerns about the public health impact of cannabis use. Continued monitoring and efforts to improve data quality and reporting, including indicators of high-risk use and cannabis-attributable harm, will be necessary to evaluate the health impact of international changes in cannabis regulation.This study received no specific funding.
LOSS OF EARLY GAINS IN LOW-DENSITY LIPOPROTEIN CHOLESTEROL GOAL ATTAINMENT AMONG HIGH RISK PATIENTS
Authors: Joanne M. Foody, Shiva Sajjan, Henry Hu, Dena R. Ramey, David Neff, Andrew M. Tershakovec, Joanne E. Tomassini, Kaan Tunceli
Journal: Journal of the American College of Cardiology (2010)
Tailored approaches facilitate high completion of tuberculosis infection treatment among migrants
Authors: Ineke Spruijt, Chantal Joren, Susan van den Hof, Connie Erkens
Journal: European Respiratory Journal (2021)

<b>Verbal education, higher self-perceived severity and risk of tuberculosis (TB), in combination with committed and supportive TB care staff and the use of professional interpreters facilitate high completion TB preventive treatment</b> https://bit.ly/3AugpTs
P11.02 Long-term impact of primary brain tumour diagnosis on health-related quality of life: a systematic review
Authors: S Frances, G Velikova, M Klein, S Short, L Murray, J Wright, F Boele
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND A primary brain tumour (PrBT) diagnosis can be devastating, and results in a wide range of symptoms. Relatively little is known about the long-term challenges these symptoms pose on HRQOL. The aim of this review is to identify the long-term HRQOL issues reported at least two years following diagnosis of a PrBT. MATERIAL AND METHODS Systematic literature searches were carried out using Medline, EMBASE, CINAHL, PsycINFO and Web of Science Core Collection. Searches were designed to identify a range of reported HRQOL aspects defined as physical, mental or social issues, in adult WHO grade II or III patients. To capture the full extent of patients’ experience, studies of any design reporting on primary data where patients had at least two years follow-up from diagnosis were included. WHO grade I and grade IV tumours were excluded due to their different prognoses and the expected nature of their disease trajectories. Quality assessment was conducted using the Mixed Methods Appraisal Tool (MMAT). Narrative synthesis was used to collate findings. RESULTS The search returned 8438 articles. 477 titles remained after title and abstract screening, with eighteen full text articles included in the final analysis. The majority of studies used quantitative methods, with only two articles reporting qualitative or mixed methodology. Articles were predominantly cross-sectional studies (n = 10), along with cohort studies (n = 3), clinical trials (n = 3) and pilot studies (n = 2). Results indicated that patients reported a variety of issues influencing their HRQOL, with emotional/psychological/cognitive changes being the most commonly reported. Physical complaints included problems with fatigue, seizures and maintaining daily activity. Social challenges included strained social relationships and issues managing finances. Patient coping strategies were found to significantly influence wellbeing and subsequent HRQOL. CONCLUSION PrBT patients’ long-term HRQOL and daily functioning can be impacted by their physical, mental and social wellbeing. Findings from this review lay the groundwork for efforts to improve patient HRQOL in long-term survivorship.
Covid-19: Unvaccinated face 11 times risk of death from delta variant, CDC data show
Authors: Owen Dyer
Journal: BMJ (2021)

Bronchiectasis in adults is a chronic disorder associated with poor quality of life and frequent exacerbations in many patients. There have been no previous international guidelines. The European Respiratory Society guidelines for the management of adult bronchiectasis describe the appropriate investigation and treatment strategies determined by a systematic review of the literature. A multidisciplinary group representing respiratory medicine, microbiology, physiotherapy, thoracic surgery, primary care, methodology and patients considered the most relevant clinical questions (for both clinicians and patients) related to management of bronchiectasis. Nine key clinical questions were generated and a systematic review was conducted to identify published systematic reviews, randomised clinical trials and observational studies that answered these questions. We used the GRADE approach to define the quality of the evidence and the level of recommendations. The resulting guideline addresses the investigation of underlying causes of bronchiectasis, treatment of exacerbations, pathogen eradication, long term antibiotic treatment, anti-inflammatories, mucoactive drugs, bronchodilators, surgical treatment and respiratory physiotherapy. These recommendations can be used to benchmark quality of care for people with bronchiectasis across Europe and to improve outcomes.
P14.41 Cost-effectiveness of FET PET for early treatment response assessment in glioma patients following adjuvant temozolomide chemotherapy
Authors: J Rosen, G Ceccon, E K Bauer, J M Werner, C Kabbasch, G R Fink, K J Langen, N Galldiks
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND In light of increasing healthcare costs, higher medical expenses should be justified socio-economically. Therefore, we calculated the effectiveness and cost-effectiveness of PET using the radiolabeled amino acid O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) compared to conventional MRI for early identification of responders to adjuvant temozolomide chemotherapy. A recent study in IDH-wildtype glioma patients suggested that after two cycles, FET-PET parameter changes predicted a significantly longer survival while MRI changes were not significant. MATERIALS AND METHODS To determine the effectiveness and cost-effectiveness of serial FET-PET imaging, we analyzed published clinical data and calculated the associated costs in the context of the German healthcare system.Based on a decision-tree model, FET-PET and MRI’s effectiveness was calculated, i.e., the probability to correctly identify a responder as defined by an overall survival ≥15 months. To determine the cost-effectiveness, the incremental cost-effectiveness ratio (ICER) was calculated, i.e., the cost for each additionally identified responder by FET-PET who would have remained undetected by MRI. The robustness of the results was tested by deterministic and probabilistic (Monte Carlo simulation) sensitivity analyses. RESULTS Compared to MRI, FET-PET increases the rate of correctly identified responders to chemotherapy by 26%; thus, four patients need to be examined by FET-PET to identify one additional responder. Considering the respective cost for serial FET-PET and MRI, the ICER resulted in €4,396.83 for each additional correctly identified responder by FET-PET. The sensitivity analyses confirmed the robustness of the results. CONCLUSION In contrast to conventional MRI, the model suggests that FET PET is cost-effective in terms of ICER values. Concerning the high cost of temozolomide, the integration of FET-PET has the potential to avoid premature chemotherapy discontinuation at a reasonable cost.
Mice lacking bi-1 gene demonstrate accelerated liver regeneration
Authors: Beatrice Bailly-Maitre, Emilie Chapeau, Frederic Luciano, Nathalie Droin, Jean-Marie Bruey, Juan M. Zapata, Jean-Ehrland Ricci, John Reed
Journal: Cancer Research (2005)

2582  Bax Inhibitor-1 (BI-1) is an evolutionarily conserved ER protein that was identified as a suppressor of Bax-induced cell death in a yeast-based screen (Xu & Reed, Mol Cell 1: 337, 1998) and that has the ability to suppress cell death in both animal and plant cells. Interestingly, the BI-1 protein has been shown to regulate Ca2+ handling by the ER, as described for several Bcl-2-family proteins which also reside at least in part in ER membranes, where they appear to control levels of releasable Ca2+ in this organelle. Moreover, an effect on cell cycle entry by Bcl-2/Bcl-xL family proteins has been described. These observations with Bcl-2/Bax family proteins therefore prompted us to explore whether bi-1-deficient mice display alterations in liver regeneration. Accordingly, we compared bi-1 (+/+) and bi-1 (−/−) mice subjected to partial hepatectomy (PH) with respect to the kinetics of liver regeneration, and associated events of hepatocyte proliferation, induction of cyclins, phosphorylation of Rb, and other molecular events. We report here that bi-1 regulates hepatocyte proliferation in vivo following PH. We demonstrated that bi-1-deficiency accelerates liver regeneration after PH. Regenerating hepatocytes of bi-1-deficient mice enter cell cycle faster, as documented by more rapid accumulation of BrdU-incorporating cells, associated with earlier increases in Cyclin D1, Cyclin D3, Cdk-2 and Cdk-4 protein levels, more rapid hyperphosphorylation of RB, and faster degradation of p27kip1. Ablation of bi-1 however does not disturb the homeostatic mechanisms that signal for cessation of hepatocyte proliferation once liver size has been restored, as liver weights of bi-1−/− mice did not exceed normal values after completion of regeneration. Altogether therefore this study of the effects of bi-1 deficiency on liver regeneration reveals additional similarities between BI-1 and Bcl-2/Bax-family proteins, showing a role for BI-1 in regulating cell proliferation in vivo, in addition to its previously described actions as a regulator of apoptosis. While much remains to be learned about the molecular mechanisms involved, elucidation of the signaling pathways modulated by BI-1 may provide new insights for improved understanding and possibly treatment of proliferative and degenerative diseases.
P14.66 Re-operation for recurrent meningioma - are we helping patients?
Authors: G E Richardson, M A Mustafa, C S Gillespie, S M Keshwara, B A Taweel, C P Millward, A I Islim, M D Jenkinson
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Meningioma is the commonest primary brain tumour. Despite surgery, meningiomas can recur. Surgery is usually the first line treatment for recurrent meningioma. The aim was to determine the risk factors associated with clinical outcomes (performance status, morbidity, mortality, recurrence) following re-operation for recurrence of intracranial meningioma. MATERIAL AND METHODS Retrospective cohort study (1998–2018). Eligible patients had reoperation for local recurrence of a previously operated meningioma. Collected data included baseline clinical and imaging characteristic. Primary outcome measure was performance status after each reoperation. Secondary outcome measures were medical and surgical morbidity, recurrence-free survival (RFS) and overall survival (OS). RESULTS Fifty-eight patients were eligible (37 female, mean age at 1st re-operation 56.1 years (SD=11.6)). Eleven patients (19.6%) had 2 re-operations and 3 patients (5.4%) had 3 re-operations. Median follow up was 128.5 months (IQR=73–194.5). Median time to 1st recurrence and 1st re-operation were 36.5 (IQR=24.3–81.0) and 43.8 months (IQR=20.3–103.4), respectively. Fifteen patients (26.8%) had worse performance status after 1st reoperation, compared to 5.4% (n=3) after the primary operation. Complication rate was 32.1% (n=18) after the primary operation compared to 48.2% (n=27) after 1st reoperation. At primary operation, there were 29 (51.8%) grade 1, 24 (42.9%) grade 2, and 1 (1.8%) grade 3 tumours. Median RFS after first re-operation was 36.5 months (95% CI 29.3–43.9). Median OS was 312 months (95 % CI 257.8–366.2). Increased number of post-operative complications were a risk factor for worsened performance status following reoperation (OR 2.2 [95% CI 1.1–4.6], P=0.029). CONCLUSION Re-operation is associated with a worse performance status and increased risk of complications. Re-operating meningiomas for radiological recurrence without symptoms increases patient morbidity. Shared-care management decision should be made with patients when considering operating for radiological recurrence only.
Considerations in boosting COVID-19 vaccine immune responses
Authors: Philip R Krause, Thomas R Fleming, Richard Peto, Ira M Longini, J Peter Figueroa, Jonathan A C Sterne, Alejandro Cravioto, Helen Rees, Julian P T Higgins, Isabelle Boutron, Hongchao Pan, Marion F Gruber, Narendra Arora, Fatema Kazi, Rogerio Gaspar, Soumya Swaminathan, Michael J Ryan, Ana-Maria Henao-Restrepo
Journal: The Lancet (2021)
Assessing the Prognostic Significance of Tumor-Infiltrating Lymphocytes in Patients With Melanoma Using Pathologic Features Identified by Natural Language Processing
Authors: Jie Yang, John W. Lian, Yen-Po (Harvey) Chin, Liqin Wang, Anna Lian, George F. Murphy, Li Zhou
Journal: JAMA Network Open (2021)

Although tumor-infiltrating lymphocytes (TILs) are an important histopathologic characteristic reflecting host immune response in patients with melanoma, their prognostic value remains controversial. Because manual review of medical records is labor intensive, a survival analysis using a large patient cohort with comprehensive clinical and histopathologic characteristics is lacking.To assess the prognostic significance of TILs among patients with cutaneous melanoma using a large cohort established through natural language processing (NLP) algorithms.This retrospective cohort study analyzed the medical records of 14 436 patients with cutaneous melanoma at Brigham and Women's Hospital between June 1, 2004, and December 31, 2019. Patients were followed up to death or censored at their last clinical visit.The primary outcome was overall survival (OS). Survival analysis was conducted using Kaplan-Meier curves, the log-rank test, and Cox proportional hazards regression analysis.A total of 14 436 patients with cutaneous melanoma were identified in the institution's pathology information system. Using NLP, we established a study cohort of 2624 patients (1462 men [55.7%]; median age, 61 years [interquartile range, 50-72 years]) who had vertical growth phase melanoma with TIL status scored. Absent TILs were identified in 434 patients (16.5%), nonbrisk TILs in 1916 patients (73.0%), and brisk TILs in 274 patients (10.4%). The 5-year survival rate was 71.0% (95% CI, 65.5%-76.9%) among patients with an absence of TILs, 73.8% (95% CI, 71.1%-76.5%) among patients with nonbrisk TILs, and 85.2% (95% CI, 80.0%-90.7%) among patients with brisk TILs. Brisk TILs were significantly associated with improved OS (adjusted hazard ratio, 0.63; 95% CI, 0.42-0.95; P = .03; 14.2% OS advantage at 5 years), and nonbrisk TILs were not associated with improved OS (adjusted hazard ratio, 0.87; 95% CI, 0.68-1.11; P = .25), compared with the absence of TILs.This study provides evidence based on a large patient cohort from a single institution that suggests that brisk TILs represent an independent prognostic factor for OS among patients with primary cutaneous melanoma. The study also suggests that NLP is a highly efficient tool to facilitate large-scale analyses that involve free-text clinical data.