bluuebunny/crossref_metadata_2025 huggingface dataset:
Global geologic expert system and database for predicting carbonate reservoirs from seismic: Application to the Upper Jurassic
Authors: Nacef Omar , Michel Julien , Borgomano Jean , Martin-Garin Bertrand
Published: June 2024

Carbonate systems are influenced by a great variety of physical and biological controlling factors that operate from global to local scales. The resulting intrinsic complexity of carbonate platforms makes them difficult to predict, especially when data are limited. Predicting geologic geometries and properties based on limited sampling or uncalibrated seismic data generally relies on a priori knowledge and equivocal interpretations that are marked by geologist perception and personal experience. To overcome these uncertain interpretations of such a complex natural system, which can become critical in frontier exploration, we developed an expert system that relies on a process-based method and a standardized data set using normalized information and parameters. The main innovation relies on the realization of knowledge- and process-based synthetic carbonate stratigraphic architectures that support seismo-stratigraphic interpretations. The workflow consists of four steps: (1) bibliographic compilation of a geologic database for each case study supported by quantitative parameters (e.g., sedimentation duration and thickness) and qualitative parameters (geodynamic context, seismic architecture, and facies model); (2) statistical analyses to establish consistent geologic classes and spatiotemporal trends; (3) process-based modeling to simulate stratigraphic architectures associated with carbonate sedimentation processes in a physically constrained numerical environment and testing different geologic hypotheses; and (4) realization of a predictive palaeogeographic map representing the global distribution of carbonate stratigraphic architectures, and estimation of controlling parameters for unconstrained case studies. The expert system is based on 77 case studies of Upper Jurassic carbonate platforms, which reveal the resemblance of these carbonate systems, in response to uniform global palaeoclimatic conditions and sea level. Significant local differences in stratigraphic architectures are related to specific geodynamic contexts and subsidence trends. The thickest carbonate platforms are developed in extensive/passive geodynamic settings such as the Central Atlantic Ocean margins, while thinner platforms form in intra- and peri-cratonic settings such as those of the Arabian region.
Childhood adversity and mental health admission patterns prior to young person suicide (CHASE): a case-control 36 year linked hospital data study, Scotland UK 1981–2017
Authors: Dougall Nadine , Savinc Jan , Maxwell Margaret , Karatzias Thanos , O'Connor Rory C. , Williams Brian , John Ann , Cheyne Helen , Fyvie Claire , Bisson Jonathan I. , Hibberd Carina , Abbott-Smith Susan , Nolan Liz , Murray Jennifer
Published: June 2024

Background

Childhood adversity is associated with increased later mental health problems and suicidal behaviour. Opportunities for earlier healthcare identification and intervention are needed.

Aim

To determine associations between hospital admissions for childhood adversity and mental health in children who later die by suicide.

Method

Population-based longitudinal case-control study. Scottish in-patient general and psychiatric records were summarised for individuals born 1981 or later who died by suicide between 1991 and 2017 (cases), and matched controls (1:10), for childhood adversity and mental health (broadly defined as psychiatric diagnoses and general hospital admissions for self-harm and substance use).

Results

Records were extracted for 2477 ‘cases’ and 24 777 ‘controls’; 2106 cases (85%) and 13 589 controls (55%) had lifespan hospitalisations. Mean age at death was 23.7; 75.9% were male. Maltreatment or violence-related childhood adversity codes were recorded for 7.6% cases aged 10–17 (160/2106) versus 2.7% controls (371/13 589), odds ratio = 2.9 (95% CI, 2.4–3.6); mental health-related admissions were recorded for 21.7% cases (458/2106), versus 4.1% controls (560/13 589), odds ratio = 6.5 (95% CI, 5.7–7.4); 80% of mental health admissions were in general hospitals. Using conditional logistic models, we found a dose-response effect of mental health admissions <18y, with highest adjusted odds ratio (aOR) for three or more mental health admissions: aORmale = 8.17 (95% CI, 5.02–13.29), aORfemale = 15.08 (95% CI, 8.07–28.17). We estimated that each type of childhood adversity multiplied odds of suicide by aORmale = 1.90 (95% CI, 1.64–2.21), aORfemale = 2.65 (95% CI, 1.94–3.62), and each mental health admission by aORmale = 2.06 (95% CI, 1.81–2.34), aORfemale = 1.78 (95% CI, 1.50–2.10).

Conclusions

Our lifespan study found that experiencing childhood adversity (primarily maltreatment or violence-related admissions) or mental health admissions increased odds of young person suicide, with highest odds for those experiencing both. Healthcare practitioners should identify and flag potential ‘at-risk’ adolescents to prevent future suicidal acts, especially those in general hospitals.
Efficacy and safety of a mineral and vitamin treatment on symptoms of antenatal depression: 12-week fully blinded randomised placebo-controlled trial (NUTRIMUM)
Authors: Bradley Hayley A. , Moltchanova Elena , Mulder Roger T. , Dixon Lesley , Henderson Jacki , Rucklidge Julia J.
Published: June 2024

Background

Broad-spectrum micronutrients (minerals and vitamins) have shown benefit for treatment of depressive symptoms.

Aims

To determine whether additional micronutrients reduce symptoms of antenatal depression.

Method

Eighty-eight medication-free pregnant women at 12–24 weeks gestation, who scored ≥13 on the Edinburgh Postnatal Depression Scale (EPDS), were randomised 1:1 to micronutrients or active placebo (containing iodine and riboflavin), for 12 weeks. Micronutrient doses were generally between recommended dietary allowance and tolerable upper level. Primary outcomes (EPDS and Clinical Global Impression – Improvement Scale (CGI-I)) were analysed with constrained longitudinal data analysis.

Results

Seventeen (19%) women dropped out, with no group differences, and four (4.5%) gave birth before trial completion. Both groups improved on the EPDS, with no group differences (P = 0.1018); 77.3% taking micronutrients and 72.7% taking placebos were considered recovered. However, the micronutrient group demonstrated significantly greater improvement, based on CGI-I clinician ratings, over time (P = 0.0196). The micronutrient group had significantly greater improvement on sleep and global assessment of functioning, and were more likely to identify themselves as ‘much’ to ‘very much’ improved (68.8%) compared with placebo (38.5%) (odds ratio 3.52, P = 0.011; number needed to treat: 3). There were no significant group differences on treatment-emergent adverse events, including suicidal ideation. Homocysteine decreased significantly more in the micronutrient group. Presence of personality difficulties, history of psychiatric medication use and higher social support tended to increase micronutrient response compared with placebo.

Conclusions

This study highlights the benefits of active monitoring on antenatal depression, with added efficacy for overall functioning when taking micronutrients, with no evidence of harm. Trial replication with larger samples and clinically diagnosed depression are needed.
Bridging the gap from medical to psychological safety assessment: consensus study in a digital mental health context
Authors: Taher Rayan , Bhanushali Palak , Allan Stephanie , Alvarez-Jimenez Mario , Bolton Heather , Dennison Laura , Wallace Brian E. , Hadjistavropoulos Heather D. , Hall Charlotte L. , Hardy Amy , Henry Alasdair L. , Lane Sam , Maguire Tess , Moreton Adam , Moukhtarian Talar R. , Vallejos Elvira Perez , Shergill Sukhi , Stahl Daniel , Thew Graham R. , Timulak Ladislav , van den Berg David , Viganò Noemi , Stock Ben Wensley , Young Katherine S. , Yiend Jenny
Published: June 2024

Background

Digital Mental Health Interventions (DMHIs) that meet the definition of a medical device are regulated by the Medicines and Healthcare products Regulatory Agency (MHRA) in the UK. The MHRA uses procedures that were originally developed for pharmaceuticals to assess the safety of DMHIs. There is recognition that this may not be ideal, as is evident by an ongoing consultation for reform led by the MHRA and the National Institute for Health and Care Excellence.

Aims

The aim of this study was to generate an experts’ consensus on how the medical regulatory method used for assessing safety could best be adapted for DMHIs.

Method

An online Delphi study containing three rounds was conducted with an international panel of 20 experts with experience/knowledge in the field of UK digital mental health.

Results

Sixty-four items were generated, of which 41 achieved consensus (64%). Consensus emerged around ten recommendations, falling into five main themes: Enhancing the quality of adverse events data in DMHIs; Re-defining serious adverse events for DMHIs; Reassessing short-term symptom deterioration in psychological interventions as a therapeutic risk; Maximising the benefit of the Yellow Card Scheme; and Developing a harmonised approach for assessing the safety of psychological interventions in general.

Conclusion

The implementation of the recommendations provided by this consensus could improve the assessment of safety of DMHIs, making them more effective in detecting and mitigating risk.
Preclinical efficacy of BRG1/BRM ATPase inhibitor in B lymphoblastic leukemia.
Authors: Garcia Isela , Sivandzade Farzane , Wither Matthew , Rau Rachel
Published: June 2024

10030

Background: Acute lymphoblastic leukemia (ALL) is the most common blood cancer in children and young adults. While ALL has a high cure rate, approximately 20% of patients who initially respond to treatment relapse and prognosis post relapse remains poor. New therapeutic treatments are needed to reduce relapse rates in B-ALL pediatric patients and to minimize the toxic side effects seen with current therapies. We and others have previously shown that BRG1/BRM ATPase inhibitors have efficacy in targeting acute myeloid leukemia (AML) and one, FHD-286, is currently being evaluated for its use in AML in an ongoing clinical trial (NCT04891757). BRG1 and BRM are the ATP-dependent catalytic subunits of the SWI/SNF chromatin remodeling complex which has a critical role in controlling gene expression, cell growth and survival of AML cells. Our prior work revealed that BRG1/BRM ATPase inhibition leads to selective transient reduction of normal B cells. Further, data from Depmap also nominates SMARCA4, the gene encoding BRG1, as a dependency in B-ALL cell lines, leading us to hypothesize that BRG1/BRM inhibition may be an effective therapy for B-ALL. Methods: We treated B-ALL cell lines with varying genetic lesions ( KMT2A-rearranged: RS4;11, KOPN-8, SEM; ETV6::RUNX1 fusion: REH and DUX4-rearranged: Nalm6) with dose titrations of FHD-286 and measured cell growth over the course of six days. In addition, at 48- and 72-hours post-treatment, we assayed cells for viability, cell cycle kinetics, and apoptosis induction via flow cytometry to provide insight into FHD-286’s mechanism of action in B-ALL. Results: We found that FHD-286 treatment resulted in decreased cell growth in a dose-dependent manner across all B-ALL cell lines. While all cell lines were displayed reduced proliferation at nanomolar doses, sensitivity varied. Nalm6, REH and SEM cells were the most sensitive with low nanomolar IC50s (2-7nM). In contrast, two of the KMT2Ar B-ALL lines, RS4;11 and KOPN-8, required higher doses to achieve growth inhibition (40-70nM). To better understand the mechanism by which FHD-286 is affecting cell growth, we evaluate whether FHD-286 is targeting cell growth through the apoptotic pathway or through cell cycle arrest. Our preliminary data indicates cell growth inhibition is only slightly attributable to cell cycle arrest and apoptosis induction, leading us to explore terminal differentiation as a mechanism of slowed proliferation. Conclusions: Our results show FHD-286 can strongly inhibit B-ALL cell growth in vitro, indicating FHD-286 as a potential therapeutic agent to treat B-ALL. In vivo validation is ongoing. Further directions include defining the effect of FHD-286 on chromatin remodeling, gene expression, and exploring efficacy in combination therapy, which has been shown to increase FHD-286 efficacy against AML. Our data may ultimately justify inclusion of B-ALL patients in clinical studies of BRG1/BRM inhibitors.
Naxitamab chemo-immunotherapy regimens other than with irinotecan/temozolomide for patients with relapsed/refractory high-risk neuroblastoma.
Authors: Larrosa Cristina , Rafael Margarida Simao , Muñoz Juan Pablo , Gorostegui Maite , Castaneda Heredia Alicia , Garraus Moira , Mora Jaume
Published: June 2024

10037

Background: Patients with relapsed/refractory (R/R) high-risk neuroblastoma (HR-NB) have dismal prognosis with chemotherapy-only salvage regimens. Naxitamab, a humanized anti-GD2 monoclonal antibody (mAb), when combined with Irinotecan and Temozolomide (I/T), has demonstrated clinically meaningful efficacy in R/R HR-NB patients (NCT03189706). We aimed to investigate the potential synergy of naxitamab with other cytotoxics. Methods: In this retrospective analysis, we examined patients treated at SJD with chemo-refractory disease, who received naxitamab in combination with chemotherapeutics other than I/T. Each cycle comprised naxitamab 2.25 mg/kg/day IV over 30 minutes, days 2, 4, 9 and 11 (total 9 mg/kg or 270 mg/m2 per cycle), and GM-CSF 250 mg/m2/day subcutaneously, days 6-10 combined with either a) cyclophosphamide (250mg/m2) and topotecan (0.75mg/m2) D1 to D5 (C/T), b) ifosfamide (1500mg/m2), etoposide (100mg/m2) D1-D3 and carboplatin (400mg/m2) D1 (ICE) or c) doxorubicin 37.5mg/m2 D1-D2 and cyclophosphamide (250mg/m2) D1-D3 (C/D). Toxicity was measured by CTCAE v4.0 and responses by INRC. Results: Twenty-nine patients received naxitamab plus GM-CSF with C/T (n=23), ICE (n=6) and C/D (n=1). One patient received both ICE and C/T. Seventeen patients had a variable number of prior relapses (1 n=14, 2 n=1, and 3 n=2). Twelve patients had refractory disease, most having received additional therapy post-induction. All but 4 patients had received naxitamab and I/T (n=20), and/or ICE (n=3/n=1), and dinutuximab-beta and I/T (n=1). Toxicities of the new regimens included myelosuppression expected with chemotherapy, and pain and hypertension expected with naxitamab. Hemorrhagic cystitis occurred in 2 patients treated with C/T, BK infection documented in one. A total of 113 cycles (median 2; 1-8) were administered, outpatient. Out of the 30 treatments, 5 achieved complete response (CR), 2 partial response (PR), and 2 mixed response (MR), providing an objective response (OR) of 30%. Eight patients achieved stable disease (SD) and 13 progressed on treatment. Disease control rate (DCR) (OR or SD) after 2 cycles was 56.6%. Patients who never responded with prior chemo-immunotherapy progressed through the new combinations. Contrary, patients who showed initial stabilization with I/T or ICE but ultimately progressed, switching drugs resulted in 60% DCR and 30% OR. Most favourable OR (75%) was seen in patients who achieved CR with prior chemoimmunotherapy and relapsed (3 out of 4). Conclusions: Naxitamab-based chemo-immunotherapy with regimens other than I/T exhibited similar and manageable toxicity profiles. Switching chemotherapeutics provided objective responses only to patients who had previously shown efficacy with I/T chemo-immunotherapy.
Burden of gastrointestinal luminal tract cancer (GLC) from 2000 to 2019 in low SDI countries.
Authors: Saowapa Sakditad , Polpichai Natchaya , Wannaphut Chalothorn , Tanariyakul Manasawee , Wattanachayakul Phuuwadith , Siladech Pharit , Olavarria Bernal Diego Alonso , Tijani Lukman Aderoju
Published: June 2024

10558

Background: In regions with low social and economic development, gastrointestinal luminal cancer (GLC) poses a significant burden, and disparities in care are prevalent, leading to adverse disease outcomes but remain poorly studied. This study aims to assess the epidemiology of GLC in low Socio-demographic Index (SDI) regions. Methods: We analyzed temporal trends in the burden of GLC (Colorectal cancer, Esophageal cancer, Stomach cancer) using data from 2000 to 2019 from the Global Burden of Disease Study 2019. We conducted a comprehensive analysis of annual frequencies, age-standardized rates (ASRs), age-specific death rate (ASDR), and annual percentage change (APC) of luminal GI cancer incidence, death, and disability-adjusted life-years (DALYs) by sex, country, and cancer type. Results: In 2019, the frequency of incident cases due to colon cancer, esophageal cancer, and stomach cancer was 39,045, 28,132, and 43,188 respectively, with a male predominance. The number of death cases and DALYs is highest in stomach cancer, with 43,876 deaths and 1,233,251 DALYs, respectively. During 2000 to 2019, the ASDRs increased significantly for colon cancer (APC: 0.78% (0.71 to 0.84), while they decreased significantly for esophageal cancer (APC: -0.57% (-0.65 to -0.48)) and stomach cancer (APC: -1.1% (-1.26 to -0.96)). The highest ASDRs in colorectal cancer were noted in 2019 in Uganda (11.55 (9.24 - 13.75)), while the highest increase in APC in colorectal cancer was noted in Burkina Faso (APC: 1.27% (1.12 to 1.42)). Conclusions: In the preceding decade, the epidemiological landscape of GLC in low SDI countries has undergone dynamic shifts, demonstrating a heavier shift towards colorectal cancer. These findings warrant heightened awareness and strategic interventions to combat the disease.
Adverse childhood experiences and cancer: A systematic review and meta-analysis.
Authors: Mavromanoli Anna , Sikorski Claudia , Behzad Danial , Manji Karishma , Kreatsoulas Catherine
Published: June 2024

10565

Background: Cancer is one of the leading causes of morbidity and mortality globally, with increasing incidence rates. The major governing cancer societies identify cancer risk factors into five broad groups (infectious disease, environmental/chemical pollutants, genetics, behavioral and ultraviolet radiation). However, little attention has been dedicated to understanding the potential primordial risk of the early psychosocial environment. Life course epidemiology is a framework that considers how the harmful effects of adverse childhood experiences (ACEs) contribute to the development of disease later in life. It is postulated that such stressful events that occur during a critical period of development likely trigger increased inflammatory responses, which could ultimately contribute to the manifestation of chronic diseases such as cancer. While there are studies that have reported an association between ACEs and cancer, this relationship has yet to be systematically analyzed. The objectives of this study are to a) meta-analyze the pooled association of the presence of at least one ACE, b) the burden of different ACEs, and c) specific ACE types, and their association with cancer in adulthood. Methods: This systematic review compiled studies from PubMed, EMBASE, Medline, Web of Science, Google Scholar, Biological Psychiatry, and grey literature up to Mar 16, 2023, and was registered on PROSPERO. Observational studies with a comparator group that assessed ACEs that occurred prior to age 18, and diagnosed cancer ≥21 years of age were included. Two review authors independently screened articles, extracted data, assessed risk of bias using QUIPS, and conducted GRADE assessment. Pooled odds ratios (ORs) were calculated using multilevel linear random-effects models. Results: Of the total 39,658 articles, our search identified 26 studies, of which 23 studies (356,519 participants, 9 countries) were eligible for meta-analysis. The occurrence of ≥1 ACE(s) was associated with cancer (OR=1.16, 95% CI: 1.08-1.24, I2 = 58.7%), compared to participants with no ACEs. As the number of ACEs increased, the odds of cancer increased (≥4 ACEs compared to no ACEs OR=1.30, 1.04-1.62, p-trend = 0.0003). Specific ACE types did explain a significant amount of heterogeneity (F = 2.02, p = 0.04). Parental or sibling death (OR=1.88, 1.29-2.73), household mental illness (OR=1.36, 1.14-1.61), sexual abuse (OR=1.20, 1.04-1.37), and physical abuse (OR=1.18, 1.05-1.34) had the largest associations with cancer. Conclusions: Our findings confirm ACEs as important risk factors for cancer in adulthood. These findings have important clinical and public health implications to develop primary and secondary prevention and treatment strategies. Also, further research is warranted to explore this relationship on the epigenetic level, and among specific cancers.
Early palliative care among patients diagnosed with advanced cancers in the US (2010-2019): Trends and contribution of provider variation.
Authors: Hu Xin , Kwon Youngmin , Jiang Changchuan , Fan Qinjin , Shi Sylvia Sylvia , Zheng Zhiyuan , Zhao Jingxuan , Warren Joan , Yabroff Robin , Han Xuesong
Published: June 2024

11017

Background: Early integration of palliative care (PC) is recommended for advanced cancers, but evidence of its use and the role of provider practice patterns and organizational characteristics in uptake is limited. This study examined recent trends of early PC among Medicare beneficiaries newly diagnosed with advanced cancers, and provider- and organization-variation in the receipt of early PC. Methods: We identified patients aged ≥65.5 years newly diagnosed with advanced stage breast, colorectal, non-small cell lung (NSCL), small cell lung (SCL), pancreas, and prostate cancers in 2010-2019 with ≥6 months survival and continuous fee-for-service coverage from the linked SEER-Medicare data. Early PC was identified by claims with corresponding diagnosis codes or hospice and palliative medicine provider specialty codes within 90 days post-diagnosis or up to first hospice admission date (whichever came earlier). Treating physicians and corresponding organizations (i.e., Tax Identification Number) were assigned based on the plurality of visits within 180 days after diagnosis. We described the percent of patients receiving early PC each year. Generalized linear models with physician- and organization-fixed effects evaluated variation in early PC receipt between and within physicians/organizations. Results: Among 103,045 patients treated by 25,736 unique providers and 11,163 organizations, the percent receiving early PC increased from 0.98% in 2010 to 10.64% in 2019. Although statistically significant increases were observed across cancer types, receipt in patients with prostate cancer was relatively lower compared to pancreas, SCL, NSCL, and breast cancers (Table). After adjusting for patients’ characteristics, variation in early PC use between treating providers and organizations explained 47.9% and 31.2% of the total variation, respectively. Conclusions: Despite considerable growth in early PC receipt, utilization remained low in 2019. The large variation between providers and organizations suggests important modifiable provider behaviors and organizational characteristics in early PC use, which warrant future research. [Table: see text]
Cost-utility analysis of a supervised exercise program for patients with metastatic breast cancer in the PREFERABLE-EFFECT randomized controlled trial (RCT).
Authors: Hiensch Anouk E. , Schouten Aniek , Monninkhof Evelyn M. , Schmidt Martina , Clauss Dorothea , Trevaskis Mark , Rundqvist Helene , Wiskemann Joachim , Mueller Jana , Van Der Wall Elsken , Aaronson Neil K , Senkus-Konefka Elzbieta , Urruticoechea Ander , Bloch Wilhelm , Zopf Eva , Stuiver Martijn M. , Wengstrom Yvonne , Steindorf Karen , van der Meulen Miriam , May Anne Maria ,   on behalf of the PREFERABLE Consortium
Published: June 2024

11121

Background: Exercise for patients with metastatic breast cancer (mBC) significantly reduced fatigue and improved quality of life (QoL) in the multinational PREFERABLE-EFFECT RCT (NCT04120298). Evidence on the cost-effectiveness of exercise for patients with mBC is lacking, albeit essential for implementation in clinical practice. In this study, we evaluated the cost-utility of an exercise program for patients with mBC in the EFFECT RCT. Methods: We conducted a cost-utility analysis using data from the 357 EFFECT trial participants (mean age 55 ± 11 yrs, 75% on 1st/2nd line treatment). These participants, from centers in NL, DE, SE, PL, ES, AU, were randomized to either a 9-month supervised exercise intervention (n=178) or a usual care control group (n=179). We used a societal perspective with a time-horizon of 9 months. Two different scenario analyses (SA) were used to determine intervention costs using a bottom-up micro-costing method: SA-1) 1-on-1 supervision; SA-2) 4-on-1 supervision. Data on healthcare resource use, productivity loss and QoL (converted to QALYs) were collected with country-adapted, self-report questionnaires, including the iMCQ, iPCQ and EQ-5D-5L, at 3-, 6- and 9-months post-baseline. Multiple imputation was performed, and bootstrapping was used to study uncertainty. Results: Compared to usual care, supervised exercise led to a QALY gain of 0.015 (95% CI: -0.02; 0.05) over a 9-month period, corresponding to an increase of 5.3 days in perfect health. The mean intervention costs were €1,696 in SA-1 and €609 in SA-2. The mean total cost differences (adjusted for center and line of treatment) were -€27 (SA-1), and -€1,112 (SA-2), in favor of the exercise group ( Table). The greatest cost-savings occurred in hospital costs, meaning that the exercise group had lower hospital costs compared to the control group (€4,430 vs €5,211). The probability of supervised exercise being cost effective at a willingness-to-pay threshold of €20.000 or €80.000 per QALY gained was 62% or 76% in SA-1, and 91% or 92% in SA-2, respectively. Conclusions: Exercise for patients with mBC is likely to be cost-effective when individually supervised and even dominant (greater cost-savings and more effective) when group-based. Based on our positive findings for both effectiveness and cost-effectiveness, we recommend supervised exercise to be reimbursed as supportive care during treatment for mBC. Clinical trial information: NCT04120298 . [Table: see text]
Linking an early access program (EAP) to the National Health Data System (NHDS) in France and assessing its performances and potential biases.
Authors: Luu Vinh-Phuc , Charkaoui Icherak , Licour Muriel , Narbeburu Marion , Le Bihan Christine , Ozan Nicolas
Published: June 2024

11137

Background: Early access programs (EAP) are a unique opportunity to document first use of innovative treatments in real-world settings. The French HTA body requires mandatory patients’ clinical data collection for EAP and since July 2021, has recommended anticipating linkage EAP to the National Health Data System (NHDS). Prior to drug initiation, the collected data is almost complete contrary to follow-up data. To the best of our knowledge, no other study has proposed a methodology to link EAP to the French Cancer cohort (FCC), an extract of the NHDS of over 8 million persons diagnosed or at high risk of cancer, and to assess its assets and downsides. Methods: This cohort study has reused data of informed French EAP patients treated with durvalumab from October 1st, 2017 to December 31st, 2018 (n=457) in locally advanced unresectable NSCLC and of patients who received durvalumab at the time of the EAP in the FCC (n=666). The linkage methodology consists in harmonizing available data across sources, defining matching, control and study variables, testing several indirect deterministic linkage algorithms and assessing their performances. Consistency and differences between data sources were described for the best performing algorithm. Results: Proposed linkage algorithms required matches on a combination of data among sex, birth year and month, treating hospital ID and department. Performance started at 80.9% (370/457) patients from the EAP cohort linked to eligible patients from FCC up to 85.3% (390/457) for the best performing algorithm. The consistency of linkage variables between the two sources was substantial (Cohen’s kappa > 0.8) or excellent (intraclass correlation > 0.9). It was the same for control variables. Comparisons between linked patients and unlinked patients from the EAP cohort showed no statistically significant difference on matching and control variables, except for few cases on history of chemotherapy and history of radiation therapy prior to durvalumab. Similarly, no statistically significant difference was found on matching and control variables between linked patients and unlinked patients from FCC, except for history of radiation therapy and treating hospital department. Median of time difference between foreseen date of first durvalumab administration in EAP versus the effective date in FCC was -1 (IQR = [-9 ; 0]) day. Lack of reported diagnosis related to prior radiation therapy administration in out-of-hospital settings refrained from using them as matching or control variables. Conclusions: The study illustrates the feasibility of matching EAP patients to the French NDHS with indirect deterministic linkage. Additional EAP linkages will be required to ensure the validation and reproducibility of such methodology. Further works in progress will document the adequacy of French NHDS data to address effectiveness.
Comparative effectiveness of the bivalent COVID-19 mRNA vaccines, mRNA1273-222 and BNT162b2, in immunocompromised adults in the US.
Authors: Kopel Hagit , Nguyen Van Hung , Bogdanov Alina , Winer Isabelle , Boileau Catherine , Ducruet Thierry , Zeng Ni , Bausch-Jurken Mary , Esposito Daina B. , Beck Ekkehard , Bonafede Mac , Mansi James A.
Published: June 2024

e23057

Background: Despite the decline in COVID-19–related hospitalizations and mortality during the period of omicron predominance, immunocompromised individuals, including those with cancer, remain at an increased risk for severe COVID-19 outcomes. A subanalysis of a retrospective observational cohort study assessed the relative vaccine effectiveness (rVE) of 2 previously approved bivalent vaccines targeting the ancestral SARS-CoV-2 and the omicron BA.4/BA.5 variant, mRNA-1273.222 (Moderna, Inc., Cambridge, MA, USA) and BNT162b2 bivalent (Pfizer Inc., New York, NY, USA; BioNTech GmbH, Mainz, Germany), in immunocompromised adults in the United States. Methods: The study used a US electronic health record dataset (Veradigm) linked with medical and pharmacy claims data of adults aged ≥18 years with at least 1 underlying medical condition associated with increased risk of severe COVID-19 who received a dose of mRNA-1273.222 or BNT162b2 bivalent vaccines between August 31, 2022, and February 28, 2023. A subgroup analysis was conducted among an immunocompromised population, encompassing cancer patients, organ or stem cell transplant recipients, individuals with primary immunodeficiency, individuals with HIV, and individuals receiving immunosuppressing medications. Comorbid conditions were based on prior medical encounters in the 365 days before vaccination. The outcomes measured were rVE of the two bivalent mRNA vaccines against COVID-19-related hospitalizations (primary outcome) and outpatient visits (secondary outcome). Follow-up started 7 days after vaccination until May 31, 2023 (end of available claims data). Propensity score weighting was used to adjust for baseline differences between groups. Results: The subanalysis included 427,260 immunocompromised individuals, of which 250,573 (58.6%) were identified as having cancer. In the overall weighted immunocompromised population, 169,509 individuals received mRNA-1273.222, and 257,751 received BNT162b2 bivalent. The adjusted rVEs of mRNA-1273.222 versus BNT162b2 bivalent vaccine against COVID-19–related hospitalizations and outpatient visits were 15.0% (95% CI, 7.2%-22.0%; P< 0.001) and 4.8% (95% CI, 1.8%-7.7%; P= 0.002), respectively. Conclusions: In this study, the mRNA-1273.222 vaccine offered greater protection against COVID-19–related hospitalization compared with the BNT162b2 bivalent vaccine among immunocompromised individuals. This study emphasizes the importance of assessing COVID-19 vaccine formulations and optimizing protection, especially in immunocompromised adults, including those with cancer.
Assessing the missions and visions of NCI-designated cancer centers and their affiliated hospitals.
Authors: Bouvette Max Joseph , Xing Jiazhang , Moore Vanessa Ann , Lam Anh B. , Jiang Changchuan , Choradia Nirmal , Nipp Ryan David
Published: June 2024

e23118

Background: Mission and vision statements (MVS) help convey an institution's identity and priorities. Missions describe objectives and responsibilities, while visions describe overarching directions for the future. Effectively communicating MVS is particularly important for cancer centers and hospitals seeking to inspire and reach patients and employees. We sought to assess the composition, readability, and topics addressed for MVS provided by NCI-designated cancer centers and their affiliated hospitals. Methods: We extracted MVS data from institutional websites for 65 NCI-designated cancer centers and 59 affiliated hospitals in 2023 (6 cancer centers did not have an affiliated hospital). We determined the composition of statements using word counts and time to read. We assessed the readability of statements using Flesch-Kincaid (FK) reading ease and grade level scores. We reviewed the MVS to determine the presence of four topics: equity, quality care, training, and research. We used descriptive statistics to compare these issues in MVS for cancer center versus the hospital. Results: Among the 65 cancer centers, we found mission statements for 93.9% (61/65) and vision statements for 63.1% (41/65). All affiliated hospitals provided a mission statement and 86.4% (51/59) had a vision statement. Data for composition, readability, and topics addressed for MVS are provided in the table. Overall, readability of MVS was difficult based on FK reading ease scores, with relatively high reading grade levels. Mission statements for cancer centers had a significantly lower reading ease and higher grade level compared with hospitals. In general, mission statements were slightly longer than vision statements, more frequently addressing the topics of quality care, training, and research. Compared with hospitals, cancer centers had a significantly lower frequency of mentioning the topic "training" in their MVS. Conclusions: We found that the majority of NCI-designated cancer centers report mission statements, but fewer provide vision statements. We demonstrated difficult readability for the MVS provided, highlighting a need to consider simpler diction and structure of language. Additionally, our work provides an overview of topics addressed for these statements including equity, quality care, training, and research. These topics underscore the values and priorities of an institution, and this review of MVS provides insights into the messaging that cancer centers communicate. [Table: see text]
Climate therapy: Developing a climate change charter for Cancer Trials Ireland (CTI).
Authors: O'Reilly Seamus , Weadick Catherine , Murphy Lucy , Kivlehan Patrick , Clayton-Lea Angela , Mulroe Eibhlin
Published: June 2024

e23214

Background: Climate change is a threat to human existence. Healthcare is the 5th leading cause of CO2 emissions globally, while clinical trials generate the equivalent of half the CO2 emissions of Denmark. Consequently, both enterprises represent significant, potentially modifiable, causes of climate change. In response to this climate toxicity (PMID 36773799), CTI launched the National Green Cancer Clinical Trials Initiative in 2022. A climate charter, which was to consist of a living document of actionable areas, was commissioned by the CTI board to implement them. Methods: Carbon footprint touch points of CTI’s activity on climate change were identified such as travel, procurement, energy use, financial management. An online scoping review of existing academic and non-academic sustainability initiatives, funding agency and national policy documents, peer reviewed and grey literature sources was conducted using the terms climate change and sustainability. Action points were categorised and collated. No exemplar climate charters for clinical trial organisations were identified in the search. Results: 5 pillars of interaction with sustainability initiatives were evident. These were education, engagement, empowerment, embedding, and emphasising. These pillars related to 8 themes for climate smart involvement by CTI staff and members. Personal commitment to sustainability at an individual level eg dietary choices, EU climate pact participation. Trial design and management eg sustainability assessment & integration into protocols Recycling and waste management at central office and sites. Energy and water use eg optimise computing infrastructure, prioritise low carbon sources. Procurement and contracts eg promote green purchasing, integrate environmental and social sustainability clauses in contracts, sustainability assessment of financial services including pensions Meetings and conferences eg prioritising virtual meetings, select conference venues and accommodation with environmental certs. Commuting and business travel. Outreach eg, to University partners, trainees, network with Green Trial groups. Conclusions: The climate charter provides a structure to facilitate sustainability integration at CTI. This living document registers existing activities, highlights areas for engagement, facilitates horizon scanning and outreach to emerging initiatives, empowers staff , and demonstrates an organisational commitment to climate smart, clinical trial conduct.
Independent validation of 30-day emergency department visit after initial chemotherapy A-PROACCT model.
Authors: Maroney Thomas T. , He Yusen , Dhannapuneni Srujankumar , Shah Nikita C. , Laughlin Amy Iarrobino , Dvorak Tomas
Published: June 2024

e23243

Background: This study assessed model performance and, more importantly, the clinical usefulness of the PROACCT model created by Grant et al. (JAMA, 2019), refined as A-PROACCT by Stein et al. (JOP, 2023) with data from Orlando Health. The predictive performance of models anticipating acute care events within thirty days (ACE30) of initial chemotherapy administration (ICA) were evaluated. Methods: Stein et al. models classified high-risk patients as those whose model output risk score was at or above the 90th percentile. They studied 5153 ICAs between July and November of 2021, of which 559 (10.8%) had an ACE30. Their first model used drug category, age group, ED visits and hospitalizations in the prior year, and cancer type, and had sensitivity (Sen), specificity, (Spec), C-Statistic (C-Stat), and positive predictive value (PPV) of 0.28, 0.93, 0.79 and 0.18 respectively. Their second model added insurance category, number of anti-cancer agents, race, and BMI category and reported Sen, Spec, C-Stat, and PPV of 0.30, 0.94, 0.80 and 0.23 respectively. Of the high-risk patients, 33.6% and 34.1% had an ACE30 respectively. Of the low-risk patients, 8.3% and 8.1% had an ACE30 respectively. Our data were propagated through the two models. Results: Between February of 2012 and April 2021, Orlando Health had 15,483 distinct patient visits with ICAs. Overall, 2046 (13.2%) had an ACE30. Model one had Sen, Spec, C-Stat, and PPV of 0.19, 0.92, 0.65 and 0.27 respectively. Model two had Sen, Spec, C-Stat, and PPV of 0.19, 0.91, 0.65 and 0.25 respectively. Both models had an accuracy of 0.82. This demonstrated our data fit the Stein model. Of the 1460 ICAs identified as high-risk by model one, 387 (26.5%) had an ACE30, and of the 14,023 ICAs identified as low-risk, 1659 (11.8%) had an ACE30. Of the 1549 ICAs identified as high-risk by model two, 393 (25.4%) had an ACE30, and of the 13,934 ICAs identified as low-risk, 1653 (11.9%) had an ACE30. The difference of ACE30 rates between high risk and low risk groups were statistically significant (p < 0.0001) in both models. This demonstrated both models were clinically useful in identifying chemotherapy patients at high risk of acute care events. Conclusions: These models allowed for clinically relevant stratification of patients into meaningful high-risk and low-risk groups (26.5% vs 11.8% with our data) for risk of acute care events within 30 days of initial chemotherapy administration. Nevertheless, only 26.5% of these high-risk patients actually had an acute care event within thirty days of initial chemotherapy administration. Further research is needed to improve the precision of identifying high-risk patients, by potentially adding more clinical variables, using alternative sampling methods, and employing nonlinear and more complex machine learning methodologies.
Breaking the bad news of cancer: Exploring patient-doctor communication among clinical oncologists in Nigeria.
Authors: Okoye Ifeoma , Otene Samuel , Aniarodo Agnes , Ejoh Denise Uzoma , Okwor Vitalis Chukwuemeka , Akin-Odanye Elizabeth Oluwatoyin , Sarimiye Foluke , Nnamani Amaka , Okwu Gloria C. , Onyemah Tobenna , Okolie Tochukwu J. , Odo Obinna , Udeh Kingsley , Agha Agha A. , Chidebe Runcie C. W.
Published: June 2024

e23251

Background: Nigeria ranks top on the incidence of cancer as well as on cancer-related deaths in Africa with an estimated 72,000 cancer-related deaths and 124,000 incidences annually. Cancer patients in this population, report some of the worst patient outcomes. Previous studies have explored several systems and patient-level factors responsible for the high cancer mortality, and poor outcomes. The process of breaking the ‘bad’ news of cancer to patients by the clinical oncologists in Nigeria has remained an understudied area. This study aims to explore the process of breaking the ‘bad’ news of cancer to patients by clinical oncologists (COs) in Nigeria. Methods: Participants ( N = 24) were clinical oncologists who treat and care for cancer patients in Nigeria. We used a semi-structured interview for the data collection. All the data were managed using Dedoose and used grounded theory for the data analysis. Results: Five themes were identified: (1) the process of breaking the ‘bad’ news is overwhelming, (2) COs need training on patient-doctor communication, (3) every process of breaking the bad news should be unique (4) patients should be the primary focus and (5) clinical workload is affecting the capacity of CO in breaking the ‘bad’ news. Conclusions: The findings show that there is a need for a more robust patient engagement and navigation program focused on empowering patients to ask the right questions. There is a need for the government to explore ways of reducing clinical workload among COs.
Refining the 30-day emergency department visit after initial chemotherapy administration A-PROACCT model.
Authors: He Yusen , Maroney Thomas T. , Dhannapuneni Srujankumar , Shah Nikita C. , Laughlin Amy Iarrobino , Dvorak Tomas
Published: June 2024

e23253

Background: This study attempted to address limitations in the A-PROACCT model developed by Stein et al. (JOP, 2023) to predict the rate of acute care events within 30 days (ACE30) of initial chemotherapy administration (ICA). The four most important predictors were drug category (immunotherapy), cancer type (gastrointestinal), age group ( < 40), and BMI category (underweight). Only linear relationships were considered. For patients for whom an ACE30 was predicted by their first and second models, only 0.18 and 0.23 actually had an ACE30, a low positive predictive value (PPV). We attempted to improve the PPV with advanced modeling techniques. Methods: Using Orlando Health data between February of 2012 and April 2021, random sampling was used to split the dataset into training (10,838) and validation (4645). For the training data, resampling was employed to obtain a balanced quota, equal observations followed by an ACE30 and not followed by an ACE30. We included only variables used in Stein (drug category, age group, ED visits and hospitalizations in the prior year, cancer type, insurance category, number of anti-cancer agents, race, and BMI category). Logistic regression with L1-penalty, XGBoost (a non-linear nonparametric tree-based algorithm to account for nonlinear relationships), and artificial neural networks were used to develop and evaluate predictive models. Different sampling methods (bootstrap and SMOTE) as well as cuff-off thresholds for high-risk groups were tested. Results: Based on evaluation with validation data set, the best performing approach was an XGBoost model with SMOTE resampling in the training data. The four most important predictors were ED visits in the prior year, payor category (self-insured), cancer type (genitourinary) and hospitalization in past year. This model reported a PPV of 0.27. Many other combinations of methodologies described above were performed, and the PPV varied between 0.19 to 0.27. Of the 282 ICAs identified as high-risk by the best model, 76 (27.0%) had an ACE30. Of the 4346 ICAs identified as low-risk, 533 (12.3%) had an ACE30. The differences between high risk and low risk ACE30 rates were statistically significant (p < 0.0001). In comparison, using Stein et al. models with our data reported a PPV of 0.27 and 0.25 which are basically at the same level of our best trained model. Conclusions: Using the variables included in A-PROACCT and a variety of machine learning models, advanced sampling methodologies and threshold cut-off limits, the best results were similar to those obtained using basic logistic regression. This suggests improvement in predicting acute care events following chemotherapy administration need to incorporate more extensive multimodal data, such as vital signs, performance status, patient reported outcomes, socioeconomic factors, laboratory and radiology results, remote patient monitoring and wearable device data.