tbuckley/cabot-search huggingface dataset:
Guanidine derivative inhibits C. albicans biofilm growth on denture liner without promote loss of materials’ resistance
Authors: Isadora Martini Garcia, Stéfani Becker Rodrigues, Maria Eduarda Rodrigues Gama, Vicente Castelo Branco Leitune, Mary Anne Melo, Fabrício Mezzomo Collares
Journal: Bioactive Materials (2020)

To reduce the burden of denture stomatitis and oral candidiasis, an aqueous solution containing polyhexamethylene guanidine hydrochloride (PHMGH) was investigated as an antifungal disinfectant against the leading cause of these oral conditions, Candida albicans. The solutions formulated with concentrations ranging from 0.125 to 0.50 wt% enabled increasing disinfection at the initial 5min-contact with 72h-mature candida biofilms formed on denture liner specimens. After 10 min-contact, the solution at lower concentration has reached total fungal elimination. The results also indicated that the denture liners preserved their mechanical property after the maximum contact time with the solution at the highest tested concentration. The PHMGH aqueous solutions at 0.125 wt% could be applied to promote interim denture liner disinfection without promoting the loss of materials' mechanical property.
Vefora, GETUG-AFU V06 study: Randomized multicenter phase II/III trial of fractionated cisplatin (CI)/gemcitabine (G) or carboplatin (CA)/g in patients (pts) with advanced urothelial cancer (UC) with impaired renal function (IRF)—Results of a planned interim analysis.
Authors: Loic Mourey, Aude Flechon, Diego Tosi, Sophie Abadie Lacourtoisie, Florence Joly, Aline Guillot, Yohann Loriot, Jerome Dauba, Guilhem Roubaud, Frederic Rolland, Christine Abraham, Hélène Gauthier, Philippe Barthelemy, Gwenaelle Gravis, Soazig Nénan-Le Ficher, Bastien Cabarrou, Thomas Filleron
Journal: Journal of Clinical Oncology (2020)

461 Background: Standard treatment for advanced UC is chemotherapy (CT) combining CI and G. 70% of pts with UC are over 65 and 40% of them are unfit for CI because of IRF or comorbidities. CA replaces frequently CI, when creatinine clearance (Cr Cl) is &lt; 60 ml/min according to Cockroft and Gault formula (CGF). However, CA tends to show a lower efficacy than CI, due to decreased dose intensity of CT. Methods: We performed a multicentre randomized phase II/III study in order to compare the activity and safety of a CT regimen with fractionated CI or CA for advanced UC in 1st line setting among pts unfit for standard CT because of IRF (40 ≤ Cr Cl ≤ 60ml/min) according to CGF. We report here the results of the interim analysis of phase II. Treatment: Arm A: CA AUC4,5 D1+ G 1000 mg/m² D1, [D1 = D21]; Arm B: fractionated CI 35 mg/m² D1D8 + G 1000 mg/m² D1D8, [D1 = D21] The co-primary objectives of the phase II were to evaluate activity (non-progression (RECIST V1.1) at (D21 C6)) and safety defined by the absence during treatment of: IRF: Cr Cl &lt;35 mL/min or deterioration of Cr Cl &gt;20%; delayed CT (≥ 2 weeks); decrease twice G dose on day 1 for: NCI CTC grade III or IV non-hematologic toxicity; hematologic toxicity; A two-stage Bryant and Day design was used. Results: A planned first step analysis was performed after randomization of 25 and 21 pts from April 2015 to January 2018. 23 and 19 of them were evaluable (resp. Arm A/B). 8 failures were reported for safety reason in experimental arm B, 7 for renal toxicity. Conclusions: According to our pre planned first step analysis, the trial met criteria for excessive toxicity in experimental arm (fractionated CI), predominantly renal toxicity. The study was therefore definitely stopped. Survival results will be available at the meeting. Clinical trial information: NCT02240017 . [Table: see text]
Microsatellite instability (MSI-H) in metastatic urothelial carcinoma (mUC): A biomarker of divergent responses to systemic therapy.
Authors: Michal Sarfaty, Min Yuen Teo, Hikmat Al-Ahmadie, Samuel Aaron Funt, Chung-Han Lee, David Henry Aggen, David B. Solit, Neha Ratna, Ashley Marie Regazzi, Jaclyn Frances Hechtman, Ahmet Zehir, Jonathan E. Rosenberg, Dean F. Bajorin, Gopa Iyer
Journal: Journal of Clinical Oncology (2020)

566 Background: MSI frequently arises from deficiencies in mismatch repair mechanisms (dMMR) and are associated with higher response rates to anti-PD1/PDL1 checkpoint inhibitors (CPI) in different cancer types, including mUC (Iyer et al, ASCO 2017). Here, we sought to (1) assess the platinum-based chemotherapy response in MSI-H mUC, and (2) present an updated analysis of CPI response in MSI-H mUC from a database of &gt; 1000 sequenced UC. Methods: From an institutional database of UC tumors genomically characterized using the MSK-IMPACT assay, we identified tumors with high MSIsensor score &gt; 10 (MSI-H) for in-depth analysis. MSIsensor has been shown to correlate strongly with MSI status (Middha et al, JCO Precis Oncol 2017). Patient and disease characteristics, as well as response to (1) platinum-based chemotherapy and (2) CPI were analyzed. Results: A total of 1,333 UC from 1,194 pts were sequenced. 26 pts (2%) had an MSI score &gt; 10. Of these, 20 (77%) were male, 17 (65%) were current or former smokers, and 20 (77%) had upper tract UC. 23/26 pts had alterations in MMR genes (MSH2, n = 15; MLH1, n = 6; MSH6 and PMS2, n = 1), 18 of which underwent germline testing which was positive in 14 cases (78%). 10/26 MSI-H patients developed metastatic UC. Six received first-line platinum-based chemotherapy with median PFS of 2.6 months, four with primary progressive disease. Ten patients received CPI in the mUC setting, two of them in combination with non-CTLA4 agents, six as second or third-line therapies, two following recurrence of disease within 12 months of peri-operative chemotherapy, and two as first line therapy. With a median follow-up of 24.3 months, PFS rate was 90% and 77% at 12 and 24 months, respectively, with near-complete or complete response in 9 patients. Conclusions: MSI-H status in UC predicts deep and durable responses to CPI and is associated with inferior chemotherapy responses. CPI should be considered for first-line treatment in this subset of patients. Pts with somatic MSI-H bladder or upper tract UC should be offered genetic testing for Lynch syndrome.
NHS trusts are given new powers to bar racist patients
Authors: Abi Rimmer
Journal: BMJ (2020)

From April NHS services in England will be able to bar non-emergency patients or visitors who inflict discriminatory or harassing behaviour on staff.1

Previously, individual NHS organisations could refuse services to patients only if they were aggressive or violent.

The news comes as results of the NHS staff survey in England show that more than a quarter of members of staff (28.5%) said they had experienced harassment, bullying, or abuse from patients, relatives, or members of the public. The 2019 survey was completed by 569 000 NHS employees (excluding those working in primary care) across 300 separate organisations in England.

It found that overall almost one in seven staff members (14.9%) had experienced physical violence. While 16.4% of ethnic minority staff said that …
A systematic review and network meta-analysis of first-line treatment options in patients metastatic renal cell carcinoma.
Authors: Irbaz Bin Riaz, Alexander J. Ryu, Yuan Yao, Rabbia Siddiqi, Jessey Mathew, Qurat Ul Ain Riaz Sipra, Haris Zahoor, Zhen Wang, M. Hassan Murad, Lance C. Pagliaro, Brian Addis Costello
Journal: Journal of Clinical Oncology (2020)

709 Background: Several immunotherapy (IMT) combinations either as an IMT doublet or IMT in combination with TKIs are now available for first-line therapy of metastatic renal cell carcinoma (mRCC). In the absence of head-to-head clinical trials, we performed an indirect comparison of frontline treatment options to provide clinical guidance. Methods: Medline, Embase and Cochrane Library were searched to identify relevant trials. Hazard ratios (HR) and confidence interval (CI) for primary outcome of progression-free survival (PFS) and secondary outcome of overall survival (OS) were abstracted. Network meta-analysis was performed using a multivariate, consistency model, random-effects meta-regression. Data on Grade 3 or higher AEs was abstracted and meta-analyzed. Pre-specified subgroup analyses were performed based on risk categories (high risk vs low and intermediate vs), history of prior nephrectomy, PD-L1 positivity, age and sex. Risk for bias(RoB) was assessed using the Cochrane Collaboration’s tool. Results: Nine studies were included for PFS analysis, and 6 studies for OS analysis. Avelumab-axitinib (AA) (HR 0.69, 0.48-0.96), and Pembrolizumab-Axitinib (PA) (HR 0.89, 0.50-0.96) significantly improved PFS, while there was no significant PFS benefit with atezolizumab-bevacizumab (AB) (HR 0.83, 0.62-1.13) and nivolumab-ipilimumab (NI) (HR 0.85, 0.63-1.15) as compared to Sunitinib. PA (HR 0.53, 0.38-0.75) and NI (HR 0.63, 0.44-0.90) significantly improved OS, while AB (HR 0.93, 0.75-1.12) showed no significant OS benefit as compared to Sunitinib. NI and AB had significantly fewer grade ≥3 AE than sunitinib. No significant interaction was found by risk group, age, sex or prior nephrectomy. Significant interaction was found by PD-L1 expression(p&lt;0.001), with significant PFS improvement in PD-L1 positive (HR 0.62, 0.53-0.73) but not in PD-L1 negative patients (HR 0.92, 0.81-1.05). Overall, RoB was low amongst included studies. Conclusions: AA improved PFS, NI improved OS, whereas PA improve both PFS and OS as compared to sunitinib monotherapy. However, no IMT combination was superior to other combinations. Cost effectiveness analysis will be reported separately.
What the HEC-C? An Analysis of the Healthcare Ethics Consultant-Certified Program: One Year in
Authors: Claire Horner, Andrew Childress, Sophia Fantus, Janet Malek
Journal: The American Journal of Bioethics (2020)

Efforts to professionalize the field of bioethics have led to the development of the Healthcare Ethics Consultant-Certified (HEC-C) Program intended to credential practicing healthcare ethics consultants (HCECs). Our team of professional ethicists participated in the inaugural process to support the professionalization efforts and inform our views on the value of this credential from the perspective of ethics consultants. In this paper, we explore the history that has led to this certification process, and evaluate the ability of the HEC-C Program to meet the goals it has set forth for HCECs. We describe the benefits and weaknesses of the program and offer constructive feedback on how the process might be strengthened, as well as share our team's experience in preparing for the exam.
Abstract P5-07-12: Prediction and clinical utility of a contralateral breast cancer risk model
Authors: Daniele Giardiello, Ewout W Steyerberg, Michael Hauptmann, Muriel A Adank, Agnes Jager, Hester OA Oldenburg, Maartje J Hooning, Marjanka K Schmidt
Journal: Cancer Research (2020)

Abstract Background: Breast cancer survivors are at risk for contralateral breast cancer (CBC), with the consequent burden of further treatment and potentially less favorable prognosis. We aimed to develop and validate a CBC risk prediction model, and evaluate its applicability for clinical decision-making. Methods: We included data of 132,756 invasive non-metastatic breast cancer patients from 20 studies with 4,682 CBC events and a median follow-up of 8.8 years. We developed a multivariable Fine and Gray prediction model (PredictCBC-1A) including patient, primary tumor, and treatment characteristics, and BRCA1/2 germline mutation status, accounting for the competing risks of death and distant metastasis. We also developed a model without BRCA1/2 mutation status (PredictCBC-1B). Prediction performance was evaluated using calibration and discrimination, calculated by a time-dependent Area-Under-the-Curve (AUC) at 5 and 10 years after diagnosis of primary breast cancer, and an internal-external cross-validation procedure. Decision curve analysis was performed to evaluate the net benefit of the model to quantify clinical utility. Results: In the multivariable model, BRCA1/2 germline mutation status, family history and systemic adjuvant treatment showed the strongest associations with CBC risk. The AUC of PredictCBC-1A was 0.63 (95% prediction interval (PI) at 5 years: 0.52–0.74; at 10 years: 0.53–0.72). Calibration in-the-large was -0.13 (95%PI: -1.62–1.37) and the calibration slope was 0.90 (95%PI: 0.73–1.08). The AUC of Predict-1B at 10 years was 0.59 (95% PI: 0.52–0.66); calibration was slightly lower. Decision curve analysis for preventive contralateral mastectomy showed potential clinical utility of PredictCBC-1A between thresholds of 4-10% 10-year CBC risk for BRCA1/2 mutation carriers and non-carriers. Conclusions: We developed a reasonably calibrated model to predict the risk of CBC in women of European-descent, however, prediction accuracy was moderate. Our model shows potential for improved risk counseling, but decision regarding contralateral preventive mastectomy, especially in the general breast cancer population, remains challenging. Citation Format: Daniele Giardiello, Ewout W Steyerberg, Michael Hauptmann, Muriel A Adank, Agnes Jager, Hester OA Oldenburg, Maartje J Hooning, Marjanka K Schmidt, Breast Cancer Association Consortium. Prediction and clinical utility of a contralateral breast cancer risk model [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P5-07-12.
Deprescribing Proton Pump Inhibitors
Authors: Todd C. Lee, Emily G. McDonald
Journal: JAMA Internal Medicine (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
HFWM: Sera from myocarditis patients caused iron depletion in culturedhuman cardiomyocytes
Authors: Kamil Kobak, Justyna Schubert, Magdalena Dzięgała, Monika Kasztura, Paweł Franczuk, M. Drozd, Katarzyna Kulej-Łyko, Jacek Bania, P. Ponikowski, Ewa Anita Jankowska
Journal: European Journal of Heart Failure (2019)
Incidence of Death From Unintentional Injury Among Patients With Cancer in the United States
Authors: Kunyu Yang, Yongqiang Zheng, Jiangtong Peng, Jiayuan Chen, Huayi Feng, Kaixu Yu, Ying Chen, Wenjing Luo, Pengcheng Yang, Yun Yang, Bian Wu
Journal: JAMA Network Open (2020)

Previous studies have suggested that patients with cancer may be at an increased risk of death from unintentional injury, but to our knowledge, no large studies have examined the rates of death from unintentional injury among patients with cancer.To characterize the incidence of death from unintentional injury among patients with cancer in the United States.This retrospective cohort study included patients diagnosed with a first primary cancer between January 1, 1973, and December 31, 2015, identified from the Surveillance, Epidemiology, and End Results (SEER) program data. Comparisons with the general US population were based on mortality data collected by the National Center for Health Statistics. Analyses were performed from February 1, 2019, to August 15, 2019.Rates and standardized mortality ratios (SMRs) of death from unintentional injury among patients with cancer.A total of 8 271 020 patients with cancer were included in this study (50.2% female; mean [SD] age, 63.0 [15.7] years). Among them, 40 599 deaths from unintentional injury were identified. The rates of death from unintentional injury were 81.90 per 100 000 person-years among patients with cancer and 51.21 per 100 000 person-years in the corresponding US general population. The SMR of death from unintentional injury was 1.60 (95% CI, 1.58-1.61). Higher rates of death from unintentional injury were associated with increasing age at diagnosis (≥80 years; rate ratio [RR], 2.91; 95% CI, 2.84-2.98; P < .001), male sex (RR, 1.69; 95% CI, 1.66-1.73; P < .001), American Indian or Alaskan Native population (RR, 1.48; 95% CI, 1.30-1.68; P < .001), and being unmarried (RR, 1.23; 95% CI, 1.18-1.28; P < .001). Rates of death from unintentional injury were the highest in patients with cancers of the liver (200.37 per 100 000 person-years), brain (175.04 per 100 000 person-years), larynx (148.78 per 100 000 person-years), and esophagus (144.98 per 100 000 person-years). The SMRs were the highest in the first month after cancer diagnosis.This study found that the incidence of death from unintentional injury among patients with cancer was significantly higher than that in the general population in the United States. The rates of death from unintentional injury varied by age, sex, race/ethnicity, marital status, cancer site, disease stage, and time since diagnosis. The findings suggest that death from unintentional injury among patients with cancer requires further attention and that initiatives to identify patients at risk and to develop targeted prevention strategies should be prioritized.
Pneumonia Risk in Asthmatic Children Using Inhaled Corticosteroids: A Nested Case-Control Study in a Birth Cohort
Authors: Pragya Shrestha, Chung-Il Wi, Katherine King, Euijung Ryu, Jungwon Yoon, Jung Hyun Kwon, Sunghwan Sohn, Hongfang Liu, Young Juhn
Journal: Journal of Allergy and Clinical Immunology (2020)
Dose-escalation results of a phase I study of 225Ac-J591 for progressive metastatic castration resistant prostate cancer (mCRPC).
Authors: Scott T. Tagawa, Joseph Osborne, Muhammad Junaid Niaz, Shankar Vallabhajosula, Panagiotis J. Vlachostergios, Charlene Thomas, Ana M. Molina, Cora N. Sternberg, Sharon Singh, Escarleth Fernandez, John Babich, David M. Nanus, Karla V. Ballman, Neil Harrison Bander
Journal: Journal of Clinical Oncology (2020)

114 Background: Prostate-specific membrane antigen (PSMA) can be targeted by antibodies (Ab) or small molecule ligands labeled with potent α emitters (e.g. 225 Ac). Unlike ligands, Ab biodistribution does not include non-tumor organs such as the salivary glands, kidneys and small bowel. We performed a phase I single ascending dose Ab study. Methods: Eligibility: progressive mCRPC following at least 1 potent AR pathway inhibitor (ARPI; e.g. abi/enza) and docetaxel (or unfit/refuse chemo) without limit of # prior therapies provided adequate organ function. Baseline 68 Ga-PSMA11 PET was performed but not used for eligibility. Single-subject cohorts received a single infusion of 225 Ac-J591 until grade (Gr) &gt; 1 attributable toxicity or dose level 5, then transition to 3+3 design. Cohort 1 = 13.3 KBq/kg with planned escalation up to dose level 7 (93.3 KBq/kg). Dose-limiting toxicity (DLT) defined as attributable Gr 4 heme or Gr 3/4 non-heme toxicity. Results: 22 men were treated on 7 dose levels; median age 72.5 (range 58-89), PSA 146.5 (4.8-7168.4); 82% with &gt;2 prior ARPI, 64% chemo, 45% sipuleucel-T, 23% radium-223, 55% prior 177 Lu-PSMA. By standard imaging 82% bone, 36% lymph node, 9% liver mets. At the time of data cutoff, 1 of 6 men in cohort 6 (80 KBq/kg) had DLT (Gr 4 anemia and platelets); he had 4 prior cycles of 177 Lu-PSMA. No other attributable Gr &gt;2 non-hematologic or Gr &gt;3 heme AE (including 0 of 6 at the highest dose level). Low Gr temporary AE’s include: 16 (73%) with fatigue, 11 (50%) pain, 11 (50%) nausea, 6 (27%) with xerostomia (5 of 6 with prior 177 Lu-PSMA), 3 (14%) AST elevation. With follow-up ongoing, 60% with any PSA decline, 35% with &gt;50% PSA decline. Of 10 with detectable baseline and 12-week CTC counts (CellSearch), 8 declined (45-100% decline); 5 (50%) with CTC count conversion. While PSMA uptake was not a prerequisite for treatment, all had some PSMA uptake on 68 Ga-PSMA11 PET/CT; 64% with SUV max &gt;5x liver SUV, 14% 2.5x – 5x liver, and 23% with SUV max 0-2.5x liver SUV. Conclusions: PSMA-targeted alpha-emitter 225 Ac utilizing intact Ab J591 is well tolerated with early evidence of clinical activity in a pre-treated population, including the majority with prior 177 Lu-PSMA. Clinical trial information: NCT03276572.
Specialty training application deadline is extended after Oriel recruitment portal collapses
Authors: Abi Rimmer
Journal: BMJ (2020)

The deadline for higher specialty training applications has been extended after the application website went down just as submissions were due.

Health Education England (HEE) said that the round 2 application deadline had been extended to 10 am on Monday 24 February in response to the Oriel website being down overnight on 18 February.

Applications for round 2 recruitment—which covers specialty training year 3 (ST3) posts, as well as some medical academic fellowship posts and core training year 1 (CT1) posts—was due to close on 19 February. …
Joint American Academy of Dermatology–National Psoriasis Foundation guidelines of care for the management of psoriasis with systemic nonbiologic therapies
Authors: Alan Menter, Joel M. Gelfand, Cody Connor, April W. Armstrong, Kelly M. Cordoro, Dawn M.R. Davis, Boni E. Elewski, Kenneth B. Gordon, Alice B. Gottlieb, Daniel H. Kaplan, Arthur Kavanaugh, Matthew Kiselica, Dario Kivelevitch, Neil J. Korman, Daniela Kroshinsky, Mark Lebwohl, Craig L. Leonardi, Jason Lichten, Henry W. Lim, Nehal N. Mehta, Amy S. Paller, Sylvia L. Parra, Arun L. Pathy, Elizabeth Farley Prater, Robert S. Rahimi, Reena N. Rupani, Michael Siegel, Benjamin Stoff, Bruce E. Strober, Elliot B. Tapper, Emily B. Wong, Jashin J. Wu, Vidhya Hariharan, Craig A. Elmets
Journal: Journal of the American Academy of Dermatology (2020)