tbuckley/cabot-search huggingface dataset:
Efficacy of Blended Collaborative Care for Patients With Heart Failure and Comorbid Depression
Authors: Bruce L. Rollman, Amy M. Anderson, Scott D. Rothenberger, Kaleab Z. Abebe, Ravi Ramani, Matthew F. Muldoon, John M. Jakicic, Bea Herbeck Belnap, Jordan F. Karp
Journal: JAMA Internal Medicine (2021)

Depression is often comorbid in patients with heart failure (HF) and is associated with worse clinical outcomes. However, depression generally goes unrecognized and untreated in this population.To determine whether a blended collaborative care program for treating both HF and depression can improve clinical outcomes more than collaborative care for HF only and physicians' usual care (UC).This 3-arm, single-blind, randomized effectiveness trial recruited 756 participants with HF with reduced left ventricular ejection fraction (<45%) from 8 university-based and community hospitals in southwestern Pennsylvania between March 2014 and October 2017 and observed them until November 2018. Participants included 629 who screened positive for depression during hospitalization and 2 weeks postdischarge and 127 randomly sampled participants without depression to facilitate further comparisons. Key analyses were performed November 2018 to March 2019.Separate physician-supervised nurse teams provided either 12 months of collaborative care for HF and depression ("blended" care) or collaborative care for HF only (enhanced UC [eUC]).The primary outcome was mental health-related quality of life (mHRQOL) as measured by the Mental Component Summary of the 12-item Short Form Health Survey (MCS-12). Secondary outcomes included mood, physical function, HF pharmacotherapy use, rehospitalizations, and mortality.Of the 756 participants (mean [SD] age, 64.0 [13.0] years; 425 [56%] male), those with depression reported worse mHRQOL, mood, and physical function but were otherwise similar to those without depression (eg, mean left ventricular ejection fraction, 28%). At 12 months, blended care participants reported a 4.47-point improvement on the MCS-12 vs UC (95% CI, 1.65 to 7.28; P = .002), but similar scores as the eUC arm (1.12; 95% CI, -1.15 to 3.40; P = .33). Blended care participants also reported better mood than UC participants (Patient-Reported Outcomes Measurement Information System-Depression effect size, 0.47; 95% CI, 0.28 to 0.67) and eUC participants (0.24; 95% CI, 0.07 to 0.41), but physical function, HF pharmacotherapy use, rehospitalizations, and mortality were similar by both baseline depression and randomization status.In this randomized clinical trial of patients with HF and depression, telephone-delivered blended collaborative care produced modest improvements in mHRQOL, the primary outcome, on the MCS-12 vs UC but not eUC. Although blended care did not differentially affect rehospitalization and mortality, it improved mood better than eUC and UC and thus may enable organized health care systems to provide effective first-line depression care to medically complex patients.ClinicalTrials.gov Identifier: NCT02044211.
Diet quality and risk and severity of COVID-19: a prospective cohort study
Authors: Jordi Merino, Amit D Joshi, Long H Nguyen, Emily R Leeming, Mohsen Mazidi, David A Drew, Rachel Gibson, Mark S Graham, Chun-Han Lo, Joan Capdevila, Benjamin Murray, Christina Hu, Somesh Selvachandran, Alexander Hammers, Shilpa N Bhupathiraju, Shreela V Sharma, Carole Sudre, Christina M Astley, Jorge E Chavarro, Sohee Kwon, Wenjie Ma, Cristina Menni, Walter C Willett, Sebastien Ourselin, Claire J Steves, Jonathan Wolf, Paul W Franks, Timothy D Spector, Sarah Berry, Andrew T Chan
Journal: Gut (2021)

Poor metabolic health and unhealthy lifestyle factors have been associated with risk and severity of COVID-19, but data for diet are lacking. We aimed to investigate the association of diet quality with risk and severity of COVID-19 and its interaction with socioeconomic deprivation.
A commentary on “Robotic distal pancreatectomy reduces pancreatic fistula in patients without visceral obesity as compared to open distal pancreatectomy: A propensity score matching retrospective cohort study” (Int J Surg 2021 Jun; 90:105960)
Authors: Jhony Alejandro Díaz-Vallejo, María Manuela Rodríguez-Gutiérrez, Daniel Andrés Vergara Maestre, María Carolina Díaz-Rivera
Journal: International Journal of Surgery (2021)
Spotlight influenza: Estimation of influenza vaccine effectiveness in elderly people with assessment of residual confounding by negative control outcomes, Finland, 2012/13 to 2019/20
Authors: Ulrike Baum, Sangita Kulathinal, Kari Auranen
Journal: Eurosurveillance (2021)

Background Cohort studies on vaccine effectiveness are prone to confounding bias if the distribution of risk factors is unbalanced between vaccinated and unvaccinated study subjects. Aim We aimed to estimate influenza vaccine effectiveness in the elderly population in Finland by controlling for a sufficient set of confounders based on routinely available register data. Methods For each of the eight consecutive influenza seasons from 2012/13 through 2019/20, we conducted a cohort study comparing the hazards of laboratory-confirmed influenza in vaccinated and unvaccinated people aged 65–100 years using individual-level medical and demographic data. Vaccine effectiveness was estimated as 1 minus the hazard ratio adjusted for the confounders age, sex, vaccination history, nights hospitalised in the past and presence of underlying chronic conditions. To assess the adequacy of the selected set of confounders, we estimated hazard ratios of off-season hospitalisation for acute respiratory infection as a negative control outcome. Results Each analysed cohort comprised around 1 million subjects, of whom 37% to 49% were vaccinated. Vaccine effectiveness against laboratory-confirmed influenza ranged from 16% (95% confidence interval (CI): 12–19) to 48% (95% CI: 41–54). More than 80% of the laboratory-confirmed cases were hospitalised. The adjusted off-season hazard ratio estimates varied between 1.00 (95% CI: 0.94–1.05) and 1.08 (95% CI: 1.01–1.15), indicating that residual confounding was absent or negligible. Conclusion Seasonal influenza vaccination reduces the hazard of severe influenza disease in vaccinated elderly people. Data about age, sex, vaccination history and utilisation of hospital care proved sufficient to control confounding.
Consensus Report: Definition and Interpretation of Remission in Type 2 Diabetes
Authors: Matthew C. Riddle, William T. Cefalu, Philip H. Evans, Hertzel C. Gerstein, Michael A. Nauck, William K. Oh, Amy E. Rothberg, Carel W. le Roux, Francesco Rubino, Philip Schauer, Roy Taylor, Douglas Twenefour
Journal: Diabetes Care (2021)

Improvement of glucose levels into the normal range can occur in some people living with diabetes, either spontaneously or after medical interventions, and in some cases can persist after withdrawal of glucose-lowering pharmacotherapy. Such sustained improvement may now be occurring more often due to newer forms of treatment. However, terminology for describing this process and objective measures for defining it are not well established, and the long-term risks versus benefits of its attainment are not well understood. To update prior discussions of this issue, an international expert group was convened by the American Diabetes Association to propose nomenclature and principles for data collection and analysis, with the goal of establishing a base of information to support future clinical guidance. This group proposed "remission" as the most appropriate descriptive term, and HbA1c <6.5% (48 mmol/mol) measured at least 3 months after cessation of glucose-lowering pharmacotherapy as the usual diagnostic criterion. The group also made suggestions for active observation of individuals experiencing a remission and discussed further questions and unmet needs regarding predictors and outcomes of remission.
HRAS is a therapeutic target in malignant chemo-resistant adenomyoepithelioma of the breast
Authors: Ivan Bièche, Florence Coussy, Rania El-Botty, Sophie Vacher, Sophie Château-Joubert, Ahmed Dahmani, Elodie Montaudon, Cécile Reyes, David Gentien, Fabien Reyal, Francesco Ricci, André Nicolas, Caterina Marchio, Anne Vincent-Salomon, Marick Laé, Elisabetta Marangoni
Journal: Journal of Hematology & Oncology (2021)

Abstract Malignant adenomyoepithelioma (AME) of the breast is an exceptionally rare form of breast cancer, with a significant metastatic potential. Chemotherapy has been used in the management of advanced AME patients, however the majority of treatments are not effective. Recent studies report recurrent mutations in the HRAS Q61 hotspot in small series of AMEs, but there are no preclinical or clinical data showing H-Ras protein as a potential therapeutic target in malignant AMEs. We performed targeted sequencing of tumours’ samples from new series of 13 AMEs, including 9 benign and 4 malignant forms. Samples from the breast tumour and the matched axillary metastasis of one malignant HRAS mutated AME were engrafted and two patient-derived xenografts (PDX) were established that reproduced the typical AME morphology. The metastasis-derived PDX was treated in vivo by different chemotherapies and a combination of MEK and BRAF inhibitors (trametinib and dabrafenib). All malignant AMEs presented a recurrent mutation in the HRAS G13R or G12S hotspot. Mutation of PIK3CA were found in both benign and malignant AMEs, while AKT1 mutations were restricted to benign AMEs. Treatment of the PDX by the MEK inhibitor trametinib, resulted in a marked anti-tumor activity, in contrast to the BRAF inhibitor and the different chemotherapies that were ineffective. Overall, these findings further expand on the genetic features of AMEs and suggest that patients carrying advanced HRAS-mutated AMEs could potentially be treated with MEK inhibitors.
Clinical Significance of Natural Killer Cell-Mediated Alloreactivity in Unrelated Cord Blood Transplantation for Children with Acute Leukemia: A Japanese National Registry Study
Authors: Hirotoshi Sakaguchi, Nobuyoshi Arima, Atsushi Narita, Sae Ishimaru, Daisuke Tomizawa, Daiichiro Hasegawa, Motohiro Kato, Hiroyuki Ishida, Junya Kanda, Masami Inoue, Nao Yoshida, Katsuyoshi Koh, Jiro Inagaki, Atsushi Ogawa, Tsukasa Hori, Yoshiko Hashii, Koji Kato, Yoshiko Atsuta
Journal: Blood (2017)
Importance of the Assessment Time Window for Intravenous Tranexamic Acid and Thromboembolic Events—Reply
Authors: Isabel Taeuber, Suma Choorapoikayil, Patrick Meybohm
Journal: JAMA Surgery (2021)

In Reply We thank Sentilhes and colleagues for their comment on our systematic review and meta-analysis of the association of tranexamic acid (TXA) with thromboembolic events and mortality1 and their important perspective on a sufficient follow-up period.
Artificial intelligence sepsis prediction algorithm learns to say “I don’t know”
Authors: Supreeth P. Shashikumar, Gabriel Wardi, Atul Malhotra, Shamim Nemati
Journal: npj Digital Medicine (2021)

Abstract Sepsis is a leading cause of morbidity and mortality worldwide. Early identification of sepsis is important as it allows timely administration of potentially life-saving resuscitation and antimicrobial therapy. We present COMPOSER (COnformal Multidimensional Prediction Of SEpsis Risk), a deep learning model for the early prediction of sepsis, specifically designed to reduce false alarms by detecting unfamiliar patients/situations arising from erroneous data, missingness, distributional shift and data drifts. COMPOSER flags these unfamiliar cases as indeterminate rather than making spurious predictions. Six patient cohorts (515,720 patients) curated from two healthcare systems in the United States across intensive care units (ICU) and emergency departments (ED) were used to train and externally and temporally validate this model. In a sequential prediction setting, COMPOSER achieved a consistently high area under the curve (AUC) (ICU: 0.925–0.953; ED: 0.938–0.945). Out of over 6 million prediction windows roughly 20% and 8% were identified as indeterminate amongst non-septic and septic patients, respectively. COMPOSER provided early warning within a clinically actionable timeframe (ICU: 12.2 [3.2 22.8] and ED: 2.1 [0.8 4.5] hours prior to first antibiotics order) across all six cohorts, thus allowing for identification and prioritization of patients at high risk for sepsis.
Efficacy and safety of dupilumab in patients with uncontrolled severe chronic rhinosinusitis with nasal polyps and a clinical diagnosis of NSAID‐ERD: Results from two randomized placebo‐controlled phase 3 trials
Authors: Joaquim Mullol, Tanya M. Laidlaw, Claus Bachert, Leda P. Mannent, G. Walter Canonica, Joseph K. Han, Jorge F. Maspero, Cesar Picado, Nadia Daizadeh, Benjamin Ortiz, Yongtao Li, Marcella Ruddy, Elizabeth Laws, Nikhil Amin
Journal: Allergy (2021)

About one-tenth of patients with difficult-to-treat chronic rhinosinusitis with nasal polyps (CRSwNP) have comorbid non-steroidal anti-inflammatory drug-exacerbated respiratory disease (NSAID-ERD). Dupilumab, a fully human monoclonal antibody that blocks the shared interleukin (IL)-4/IL-13 receptor component, is an approved add-on treatment in severe CRSwNP. This post hoc analysis evaluated dupilumab efficacy and safety in patients with CRSwNP with/without NSAID-ERD.Data were pooled from the phase 3 SINUS-24 and SINUS-52 studies in adults with uncontrolled severe CRSwNP who received dupilumab 300 mg or placebo every 2 weeks. CRSwNP, nasal airflow, lung function, and asthma control outcomes at Week 24 were evaluated, and treatment-subgroup interactions were assessed for patients with and without NSAID-ERD.Of 724 patients, 204 (28.2%) had a diagnosis of NSAID-ERD. At Week 24, least squares mean treatment differences demonstrated significant improvements in nasal polyp score, nasal congestion (NC), Lund-Mackay computed tomography, 22-item Sinonasal Outcome Test (SNOT-22), Total Symptom Score (TSS), rhinosinusitis severity visual analog scale, peak nasal inspiratory flow (PNIF), six-item Asthma Control Questionnaire score, and improvement in smell with dupilumab versus placebo (all p < .0001) in patients with NSAID-ERD. Treatment comparisons demonstrated significantly greater improvements with dupilumab in patients with versus without NSAID-ERD for NC (p = .0044), SNOT-22 (p = .0313), TSS (p = .0425), and PNIF (p = .0123).In patients with uncontrolled severe CRSwNP, dupilumab significantly improved objective measures and patient-reported symptoms to a greater extent in the presence of comorbid NSAID-ERD than without. Dupilumab was well tolerated in patients with/without NSAID-ERD.
A third of ethnic minority staff working in mental health trusts have experienced harassment, bullying, or abuse at work
Authors: Abi Rimmer
Journal: BMJ (2021)

Thousands of ethnic minority staff working in mental health trusts are subjected to harassment, bullying, or abuse from the public or work colleagues, an analysis by the Royal College of Psychiatrists has found.

The college analysed the 2020 NHS annual staff survey results and found that a third (32.7%) of 16 165 ethnic minority staff working in mental health trusts experienced harassment, bullying, or abuse …
How to solve misplacement of a lumen-apposing metal stent during cholecystogastrostomy: immediately perform a second one!
Authors: Benedetto Mangiavillano, Francesco Auriemma, Danilo Paduano, Laura Lamonaca, Federica Spatola, Alessandro Repici
Journal: Endoscopy (2021)

A 66-year-old man was referred to our endoscopy unit because of a computed tomography (CT) scan diagnosis of a 4-cm pancreatic head neoplasia causing malignant biliary obstruction (MBO) with a 3-cm distal common bile duct (CBD) obstruction owing to neoplastic infiltration. The patient underwent endoscopic ultrasonography (EUS) plus fine needle biopsy with macroscopic on-site evaluation (MOSE) of the specimen [1]. Subsequently an attempt to approach the major papilla for CBD drainage was performed using endoscopic retrograde cholangiopancreatography (ERCP) but was unsuccessful because of infiltration in the duodenal and papillary area. Because of gallbladder distension, we therefore decided to perform a freehand cholecystogastrostomy under EUS guidance from the anterior wall of the gastric antrum with a new 10 × 20-mm electrocautery-enhanced lumen-apposing metal stent (EC-LAMS; Hot-Spaxus; Taewoong Medical Co., Gimpo, Korea) [2] [3]. During the EC-LAMS placement, after the device had entered the gallbladder, the distal flange was accidentally released inside the abdominal cavity, causing bile extravasation inside the peritoneum. We extracted the stent with a tooth-rat forceps and immediately performed a successful second cholecystogastrostomy ([Video 1]).
Extrinsic Macrophages Protect While Tendon Progenitors Degrade: Insights from a Tissue Engineered Model of Tendon Compartmental Crosstalk
Authors: Tino Stauber, Maja Wolleb, Anja Duss, Patrick K. Jaeger, Irina Heggli, Amro A. Hussien, Ulrich Blache, Jess G. Snedeker
Journal: Advanced Healthcare Materials (2021)

Abstract Tendons are among the most mechanically stressed tissues of the body, with a functional core of type‐I collagen fibers maintained by embedded stromal fibroblasts known as tenocytes. The intrinsic load‐bearing core compartment of tendon is surrounded, nourished, and repaired by the extrinsic peritendon, a synovial‐like tissue compartment with access to tendon stem/progenitor cells as well as blood monocytes. In vitro tendon model systems generally lack this important feature of tissue compartmentalization, while in vivo models are cumbersome when isolating multicellular mechanisms. To bridge this gap, an improved in vitro model of explanted tendon core stromal tissue (mouse tail tendon fascicles) surrounded by cell‐laden collagen hydrogels that mimic extrinsic tissue compartments is suggested. Using this model, CD146 + tendon stem/progenitor cell and CD45 + F4/80 + bone‐marrow derived macrophage activity within a tendon injury‐like niche are recapitulated. It is found that extrinsic stromal progenitors recruit to the damaged core, contribute to an overall increase in catabolic ECM gene expression, and accelerate the decrease in mechanical properties. Conversely, it is found that extrinsic bone‐marrow derived macrophages in these conditions adopt a proresolution phenotype that mitigates rapid tissue breakdown by outwardly migrated tenocytes and F4/80 + “tenophages” from the intrinsic tissue core.
Durable Responses and Low Toxicity After Fast Off-Rate CD19 Chimeric Antigen Receptor-T Therapy in Adults With Relapsed or Refractory B-Cell Acute Lymphoblastic Leukemia
Authors: Claire Roddie, Juliana Dias, Maeve A. O'Reilly, Mahnaz Abbasian, Amaia Cadinanos-Garai, Ketki Vispute, Leticia Bosshard-Carter, Marina Mitsikakou, Vedika Mehra, Harriet Roddy, John A. Hartley, Victoria Spanswick, Helen Lowe, Bilyana Popova, Laura Clifton-Hadley, Graham Wheeler, Joanna Olejnik, Adrian Bloor, David Irvine, Leigh Wood, Maria A. V. Marzolini, Sabine Domning, Farzin Farzaneh, Mark W. Lowdell, David C. Linch, Martin A. Pule, Karl S. Peggs
Journal: Journal of Clinical Oncology (2021)

Prognosis for adult B-cell acute lymphoblastic leukemia (B-ALL) is poor, and there are currently no licensed CD19 chimeric antigen receptor (CAR) therapeutics. We developed a novel second-generation CD19-CAR (CAT19-41BB-Z) with a fast off rate, designed for more physiologic T-cell activation to reduce toxicity and improve engraftment. We describe the multicenter phase I ALLCAR19 (NCT02935257) study of autologous CAT19-41BB-Z CAR T cells (AUTO1) in relapsed or refractory (r/r) adult B-ALL.Patients age ≥ 16 years with r/r B-ALL were eligible. Primary outcomes were toxicity and manufacturing feasibility. Secondary outcomes were depth of response at 1 and 3 months, persistence of CAR-T, incidence and duration of hypogammaglobulinemia and B-cell aplasia, and event-free survival and overall survival at 1 and 2 years.Twenty-five patients were leukapheresed, 24 products were manufactured, and 20 patients were infused with AUTO1. The median age was 41.5 years; 25% had prior blinatumomab, 50% prior inotuzumab ozogamicin, and 65% prior allogeneic stem-cell transplantation. At the time of preconditioning, 45% had ≥ 50% bone marrow blasts. No patients experienced ≥ grade 3 cytokine release syndrome; 3 of 20 (15%) experienced grade 3 neurotoxicity that resolved to ≤ grade 1 within 72 hours with steroids. Seventeen of 20 (85%) achieved minimal residual disease-negative complete response at month 1, and 3 of 17 underwent allogeneic stem-cell transplantation while in remission. The event-free survival at 6 and 12 months was 68.3% (42.4%-84.4%) and 48.3% (23.1%-69.7%), respectively. High-level expansion (Cmax 127,152 copies/µg genomic DNA) and durable CAR-T persistence were observed with B-cell aplasia ongoing in 15 of 20 patients at last follow-up.AUTO1 demonstrates a tolerable safety profile, high remission rates, and excellent persistence in r/r adult B-ALL. Preliminary data support further development of AUTO1 as a stand-alone treatment for r/r adult B-ALL.
Current allergy educational needs in primary care. Results of the EAACI working group on primary care survey exploring the confidence to manage and the opportunity to refer patients with allergy
Authors: Martha Cabrera, Dermot Ryan, Elisabeth Angier, Laura Losappio, Bertine M. J. Flokstra ‐ de Blok, Radoslaw Gawlik, Dan Purushotam, Sinthia Bosnic‐Anticevich
Journal: Allergy (2021)

The aim of this survey was to explore the specific educational needs of a cohort of European GPs with regards to allergy training so that future educational initiatives may better support the delivery of allergy services in primary care.This study took the form of a cross-sectional observational study in which a structured electronic questionnaire was distributed to primary care providers, in eight languages, across 8 European countries between September 2019 and November 2019. Data associated with demographic parameters, professional qualifications, type of employment, level of confidence regarding competencies for diagnosis and treatment of allergic diseases, referral of patients to allergist and preferred method of learning and assessment were collected. A 5-point Likert scale was used to assess level of confidence. Exploratory analysis was carried out.A total of 687 responses were available for analysis, with 99.3% of responders working within Europe. 70.1% of participants were female; and 48.0% and 48.0% of participants respectively had received some undergraduate and/or postgraduate allergy education. Confidence in dealing with different aspect of allergy management differed between countries. The main reason for specialist referral was a perceived need for tertiary assessment (54.3%), and the main barrier for referral was the consideration that the patient's condition could be appropriately diagnosed and treated in a primary care facility. Up to 44.7% and 55.3% of participants reported that they preferred e-Learning over traditional learning.This study identified the specific areas of skills training and educational needs of GPs in managing allergic conditions in primary care, and provided insights into possible strategies for more feasible and cost-effective approaches.
P-61 Relatlimab + nivolumab in patients with advanced hepatocellular carcinoma who are naive to immuno-oncology therapy but progressed on tyrosine kinase inhibitors, a phase 2, randomized, open-label study: RELATIVITY-073
Authors: B. Sangro, K. Numata, Y. Huang, C. Gomez-Martin, A. Hiraoka, M. Moriguchi, Y. Shen, A. Horvath, W. Feely, T. Young, J. Neely, M. Kudo
Journal: Annals of Oncology (2021)