tbuckley/cabot-search huggingface dataset:
Biomarkers for Alzheimer Dementia in Diverse Racial and Ethnic Minorities—A Public Health Priority
Authors: Lisa L. Barnes
Journal: JAMA Neurology (2019)

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 Neurology 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 Neurology journal
Randomized controlled trials (RCTs) examining continuous (CS) versus intermittent strategies (IS) of delivering systemic treatment (Tx) for untreated metastatic colorectal cancer (mCRC): A meta-analysis from the Cancer Care Ontario program in evidence-based care.
Authors: Scott R. Berry, Roxanne Cosby, Timothy R. Asmis, Kelvin K. Chan, Nazik Hammad, Monika K. Krzyzanowska
Journal: Journal of Clinical Oncology (2013)

3534 Background: Given the varying impact on efficacy demonstrated in individual RCTs of CS vs IS of delivering systemic Tx for mCRC, a meta-analysis of the available RCTs was performed. Methods: RCTs that compared a CS versus IS of delivering systemic Tx were identified by a systematic search (MEDLINE, EMBASE and ASCO and ESMO proceedings) and review. The results of identified trials were clinically homogeneous (Table) so the data was pooled using Review Manager software (RevMan 5.2). Overall survival (OS) hazard ratios were extracted directly from the most recently reported trial results. A random effects model was used for all pooling. Results: 10 RCTs were identified (n= 4,296). After an induction period, the maintenance Tx patients received during the IS was: none (5 trials, n=2,562), fluoropyrimidine (F) (2 trials, n=759), biologic (B) (2 trials, n=852), F+B (1 trial, n=123). Results of the meta-analysis are summarized in the Table (HR&gt;1 favors CS). Sensitivity analyses performed demonstrate results are robust independent of the induction or maintenance Tx used. QOL (data from 2 trials) was either the same in both arms (single Tx induction trial with no maintenance Tx, n=354) or improved in the IS arm (combination tx induction trial with no maintenance Tx, n=1,630). Conclusions: IS of delivering systemic Tx for mCRC do not result in a statistically significant reduction in OS compared to a CS of delivery whether or not maintenance therapy is included. QOL is the same or better with an IS. [Table: see text]
An international survey of health care providers involved in the management of cancer patients exposed to cardiotoxic therapies.
Authors: Susan Faye Dent, Jeffrey Allen Sulpher, Christopher Johnson, Michele Turek, Nadine A. Graham, Franco Dattilo, Daniel John Lenihan
Journal: Journal of Clinical Oncology (2014)

6629 Background: Targeted agents used in cancer therapy may negatively impact cardiovascular health. There is increasing interest by health care providers (HCPs) in developing multidisciplinary approaches to manage these patients (pts). The objective of this international survey was to gain better understanding of current knowledge and practice patterns among HCPs involved in the management of cancer pts exposed to potentially cardiotoxic drugs. Methods: HCPs involved in the management of cardiac disease in cancer pts were surveyed using email lists from the Canadian Association of Medical Oncologists, Canadian Cardiovascular Society, Canadian Cardiac Oncology Network and International CardiOncology Society. The survey consisted of 14 questions related to cancer treatment-induced cardiotoxicity. Canadian HCP’s were asked to comment on treatment strategies for 3 case scenarios. Descriptive data was collected and summarized. Results: 393 survey responses were received (response rate of 25%). The majority of respondents were cardiologists (47%, 185/393), or medical oncologists (40%, 158/393). 55% of respondents were in academic practice (212/383). The majority agreed that cardiac issues are important to cancer pts (97%, 381/393); 94% felt that the diagnosis of cardiac disease had an impact on cancer prognosis (349/383), and 77% agreed that chemotherapy or radiation is an important risk factor for cardiac disease (301/393). Only 36% of respondents felt there is an accepted definition of cardiotoxicity (109/383). 78% of respondents felt cardiac medications are protective during active cancer treatment (307/393), however only 51% would consider prescribing these medications upfront in cancer pts (199/393). While the majority of Canadian HCP’s (n=77) agreed on pt care strategies, there was marked discrepancy in the cardiac management of metastatic breast cancer pts with asymptomatic heart failure. Conclusions: There is a high level of concern for cardiac safety among HCP’s regarding active cancer therapy for pts; however, there is a lack of consensus on the definition of cardiotoxicity and uncertainty remains for optimal management in this new field of cancer care.
Use of Targeted Next-Generation Sequencing to Identify Activating Hot Spot Mutations in Cherry Angiomas
Authors: Nikolai Klebanov, William M. Lin, Mykyta Artomov, Michael Shaughnessy, Ching-Ni Njauw, Romi Bloom, Agda Karina Eterovic, Ken Chen, Tae-Beom Kim, Sandy S. Tsao, Hensin Tsao
Journal: JAMA Dermatology (2019)

<h3>Importance</h3> Shared gene variants in benign-malignant process pairs, such as<i>BRAF</i>mutations common to benign nevi and melanoma, are associated with differing phenotypic manifestations. Study of gene mechanisms underlying cherry angioma may uncover previously unknown disease relationships. <h3>Objective</h3> To identify somatic mutations present in cherry angioma specimens by using targeted next-generation sequencing. <h3>Design, Setting, and Participants</h3> In a single-center case series, 10 formalin-fixed, paraffin-embedded cherry angioma specimens from biopsies performed at Massachusetts General Hospital in Boston from July 10, 2016, to January 23, 2018, were obtained and underwent sequencing across a panel of 323 genes most relevant to cancer. Somatic mutations were curated by excluding variants that were presumed to be germline or of low mapping quality. <h3>Main Outcomes and Measures</h3> Identification of somatic mutations associated with cherry angiomas. <h3>Results</h3> In 10 cherry angioma tissue samples originating from 6 female and 4 male patients with a median (range) age of 54 (26-79) years, 5 samples (50%) revealed somatic missense mutations in<i>GNAQ</i>(Q209H, Q209R, and R183G) and<i>GNA11</i>(Q209H). Individually, these mutational hot spots are known to be involved in entities that include congenital and anastomosing hemangiomas, hepatic small-vessel neoplasms (Q209), port-wine stains, and Sturge-Weber syndrome (R183). Both hot spots are associated with blue nevi, melanoma associated with blue nevus, and uveal melanoma. <h3>Conclusions and Relevance</h3> In this case series study, the high prevalence of 5 known genetic drivers within the benign cherry angioma entity appears to support the context-dependent role of gene alterations in both benign and malignant proliferations from various cellular origins.
Protein Phosphatase 2A Regulates Cardiac Na <sup>+</sup> Channels
Authors: Mona El Refaey, Hassan Musa, Nathaniel P. Murphy, Ellen R. Lubbers, Michel Skaf, Mei Han, Omer Cavus, Sara N. Koenig, Michael J. Wallace, Daniel Gratz, Elisa Bradley, Katherina M. Alsina, Xander H.T. Wehrens, Thomas J. Hund, Peter J. Mohler
Journal: Circulation Research (2019)

Voltage-gated Na
Lipid-rich Core Quantification in Carotid Atherosclerosis Using MRI T2 Mapping - Relation to Clinical Presentation and Plaque Macrophage Activation
Authors: Joshua T Chai, Luca Biasiolli, Linqing Li, Mohammad Alkhalil, Francesca Galassi, Chris Darby, Alison Halliday, Linda Hands, Timothy Magee, Jeremy Perkins, Ed Sideso, Ashok Handa, Peter Jezzard, Matthew D Robson, Robin P Choudhury
Journal: Circulation (2015)

Introduction: Non-invasive plaque lipid quantification is appealing both for treatment selection and as predictor of future plaque events. However, current MRI methods are insensitive, require a coalesced mass of lipid and rely on multicontrast acquisition. We sought to: (1) provide tissue validation of quantitative T2 maps to measure plaque lipid; and (2) investigate whether this technique could discern differences in plaque characteristics between symptomatic and asymptomatic plaques. We also hypothesised that plaque lipid content correlates with differential plaque macrophage activation. Methods: 40 patients scheduled for carotid endarterectomy were recruited for 3T carotid MRI. Lipid Area was derived from segmented T2 maps and compared directly to plaque lipid defined by histology. Plaque macrophages were procured using laser-capture microdissection from frozen tissue and subjected to microarray analysis. Results: Lipid Area (%) on T2 mapping and histology showed excellent correlation, both by individ...
Outcomes of invasive mechanical ventilation in elderly patients with metastatic cancer.
Authors: Achuta Kumar Guddati, Touqir Zahra, Guibenson Hyppolite, Parijat Saurav Joy, Creticus Petrov Marak, Gagan Kumar
Journal: Journal of Clinical Oncology (2014)

9554 Background: Aggressive management of elderly patients with metastatic cancer has helped prolong their survival. Respiratory failure in elderly patients with metastatic disease may significantly contribute to a decline in their functional status. However, the outcomes of the use of invasive mechanical ventilation (IMV) in patients with rapidly declining functional status have not been studied in detail. Methods: Using the Healthcare Cost and Utilization Project – Nationwide Inpatient Sample database 2000-2009, patients aged 65 and above undergoing IMV were identified using appropriate ICD-9-CM codes. The rates of prolonged IMV (≥96 hours) and use of tracheostomy were examined. Chi square test and Wilcoxon rank test were used to compare discrete and continuous variables respectively. Significance was defined as p value set at <0.05. Bonferroni’s correction as applied for multiple comparisons. Results: 4,256,372 patients aged 65 and above underwent IMV during the years 2000 to 2009. Of these, 192,852 (4.5%) had metastatic cancer. After adjusting for age, the odds of mortality were 1.86 times higher (95% CI 1.8-1.9) when compared to those without any cancer. The outcomes of patients undergoing IMV are shown below (see Table). Conclusions: The hospital LOS and hospital charges in patients undergoing IMV were higher in patients with cancer and in those with metastatic disease. The mortality was however significantly higher in patients with metastasis. Of the survivors, almost twice the number of patients are discharged to hospice facilities when compared to cancer patients with no metastatic disease. The use of prolonged IMV portends a higher mortality and worser outcomes in elderly patients with metastatic disease. No cancer Solid organ cancer Metastatic solid organ cancer Mortality (%) 39.4 42.4* 53* Prolonged IMV (> 96 hrs) 39.8 37.8 37.6 Tracheostomy (%) 8.8 10.3* 8.4 Disposition of survivors Home 21.6 25.2* 20.4 Home healthcare 14.1 19.7* 22.6* Skilled Nursing Facility 50.6 41.2* 37.3* Hospice 4.5 6.6 13.5* Others 9.2 7.3 8.2 Median LOS in survivors, days(IQR) 12 (7-20) 13(8-21)* 14(8-22)* Median time to death 6(2-14) 8(3-16)* 8(3-16)* Median hospital charges, USD 61,035 68,378* 67,181* * p<0.025 when compared with no cancer.
Serum Proteomics Reveals Distinct Subtypes Associated with Treatment Response in Idiopathic Multicentric Castleman Disease
Authors: Dustin Shilling, Jason R Ruth, Christopher Sheild Nabel, Sheila K Pierson, Mary Guilfoyle, Craig Tendler, Manjula P Reddy, Michael Weinblatt, Nancy Shadick, Mark Bower, Alessia Dalla Pria, Yasufumi Masaki, Philip Beineke, Sofija Miljovska, Laura Katz, Sushila Shenoy, Ana B Oromendia, Jason Mezey, Jeff Wiser, Jef Benbanaste, David Lee, Alexander Fosså, Frits van Rhee, David C Fajgenbaum
Journal: Blood (2018)
Voice of Cancer Patients (VoCP): Analysis of Patient Experiences and Use of Burton's Tyrosine Kinase (BTK) Inhibitors and Venetoclax in Hematological Malignancies
Authors: Sangeeta Aggarwal, Alok Aggarwal, Jyoti Bhowmick, Rishi Sharma, Rahul Gond, Siddhant Kapoor, Sujeet Kumar
Journal: Blood (2018)
Prognostic significance of membrane cofactor protein (CD46) on breast tumors.
Authors: Zahra Madjd, Ian Spendlove, Sarah E. Pinder, Neil K. Rushmere, B. Paul Morgan, Lindy G. Durrant
Journal: Cancer Research (2004)

2196  Introduction: To prevent complement –mediated autologous tissue damage, host cells express a number of membrane –bound complement regulatory proteins including CD59 , CD55 (DAF), and CD46. Membrane cofactor protein (MCP, CD46), a widely distributed regulator of complement activation, is a cofactor for the factor I-mediated degradation of C3b and C4b deposited on host cells. Aim and methods: Our previous immunohistochemical study showed that in breast carcinoma loss of CD59 and CD55 correlated with poor survival. This study aimed to investigate the prognostic significance of CD46 on breast tumors by rabbit polyclonal anti-CD46 antibody using a standard immunohistochemistry method. 510 breast tissues from patients with primary operable breast cancer diagnosed between 1987 and 1992 had previously been included in tissue microarrays. They include patients 70 years of age or less (mean: 54) with a long term follow up (mean: 7 years). Results: Immunohistochemical study revealed that 507/510 (99.4%)of breast tumors express CD46 on the cytoplasm and cell membrane.136/510(27%) of tumors exhibited strong immunoreactivity while moderate and weak staining was observed in 43% and 29% of tumors.Intensity of CD46 expression was significantly associated with tumor grade (p
Sociodemographic factors impacting clinical trial enrollment and outcomes in stage III non-small cell lung cancer (NSCLC).
Authors: Josephine Louella Feliciano, Andinet Woldemichael, C. Daniel Mullins
Journal: Journal of Clinical Oncology (2014)

e17563 Background: Determining sociodemographic factors associated with clinical trial enrollment is crucial to identify under-represented populations and barriers to enrollment. This may ultimately lead to interventions to improve the generalizability of clinical trials and reduce health disparities. Methods: 306 patients with stage III NSCLC were treated at our institution with curative intent from 2000 and 2010. We estimate a logit model of the probability of enrollment into clinical trials. We use a Cox Proportional Hazard model to estimate survival outcomes. In both models, we control for demographic and socioeconomic characteristics, exposure, chronic conditions, and clinical characteristics. Results: Patients received bimodal [chemo (C) and radiation (R)] or trimodal [C+R+surgery] therapy. 134 (44%) were AA and 92 (30%) of all patients were treated on clinical trials. Of those on clinical trial, 27% were AA. Increasing age, COPD, stage IIIB disease, male sex, and AA race decreased the probability of being enrolled on clinical trial (Table). Private insurance enrollment was associated with a higher probability of trial enrollment. Increasing age (HR=1.02; 95% CI 1.002,1.04; p=0.025), male gender (HR=1.44; 95% CI 1.03,2.01; p=0.032), unmarried status (HR=1.62; 95% CI 1.13,2.2; p=0.008), and stage IIIB (HR=1.66; 95% CI 1.23,2.23; p=0.001) were associated with inferior survival. Conclusions: We identified several important factors associated with decreased odds of clinical trial enrollment. Age, COPD, and stage were likely related to trial eligibility criteria. Gender and racial disparities in trial enrollment were identified. Compared to historic averages of AA clinical trial participation, AA enrollment at our institution has been relatively high (27% vs. 10% nationally). Although trial enrollment was not associated with survival at our institution, it is imperative that institutions with unique populations work to improve representation of minority patients in clinical trials. Factors impacting the probability of clinical trial enrollment. Odds ratio Age 0.97 Male 0.57 Race: Black 0.58 Dx COPD 0.52 Stage IIIB 0.63 Pvt. Insurance 1.98 * all p values < 0.1.
Internet‐delivered psychological treatments: from innovation to implementation
Authors: Gerhard Andersson, Nickolai Titov, Blake F. Dear, Alexander Rozental, Per Carlbring
Journal: World Psychiatry (2019)

Internet interventions, and in particular Internet-delivered cognitive behaviour therapy (ICBT), have existed for at least 20 years. Here we review the treatment approach and the evidence base, arguing that ICBT can be viewed as a vehicle for innovation. ICBT has been developed and tested for several psychiatric and somatic conditions, and direct comparative studies suggest that therapist-guided ICBT is more effective than a waiting list for anxiety disorders and depression, and tends to be as effective as face-to-face CBT. Studies on the possible harmful effects of ICBT are also reviewed: a significant minority of people do experience negative effects, although rates of deterioration appear similar to those reported for face-to-face treatments and lower than for control conditions. We further review studies on change mechanisms and conclude that few, if any, consistent moderators and mediators of change have been identified. A recent trend to focus on knowledge acquisition is considered, and a discussion on the possibilities and hurdles of implementing ICBT is presented. The latter includes findings suggesting that attitudes toward ICBT may not be as positive as when using modern information technology as an adjunct to face-to-face therapy (i.e., blended treatment). Finally, we discuss future directions, including the role played by technology and machine learning, blended treatment, adaptation of treatment for minorities and non-Western settings, other therapeutic approaches than ICBT (including Internet-delivered psychodynamic and interpersonal psychotherapy as well as acceptance and commitment therapy), emerging regulations, and the importance of reporting failed trials.
Immunotherapy with grass pollen tablets reduces medication dispensing for allergic rhinitis and asthma: A retrospective database study in France
Authors: Philippe Devillier, Mathieu Molimard, Xavier Ansolabehere, Isabelle Bardoulat, Nicolas Coulombel, Frédérique Maurel, Philippe Le Jeunne, Pascal Demoly
Journal: Allergy (2018)

Moderate-to-severe allergic rhinitis (AR) may increase the risk of developing or worsening asthma, whereas treatment of AR with subcutaneously or sublingual allergen immunotherapy (SLIT) may slow this progression.In a retrospective real-world analysis, prescription fulfilment data were gathered from French retail pharmacies between 1 March 2012 and 31 December 2016. Using linear regression analyses, patients having received at least two prescriptions of grass pollen SLIT tablets over at least 2 successive years were compared with control patients having received symptomatic medications only.A total of 1099 SLIT patients and 27 475 control patients were included in the main analysis. With regard to symptomatic AR medication dispensing, we observed a 50% decrease in the pre-index/follow-up ratio in the SLIT group, a 30% increase in the control group without age matching (P < 0.0001 vs SLIT) and a 20% increase in the control group with age matching (P < 0.0001 vs SLIT). During the follow-up, 11 (1.8%) and 782 (5.3%) patients initiated asthma treatment in the SLIT and control groups, respectively. The relative risk of medication dispensing for new asthma was lower in the SLIT group (by 62.5% [29.1%-80.1%] without age matching (P = 0.0025) and by 63.7% [31.5%-80.7%] with age matching; P = 0.0018). SLIT was also associated with slower progression of asthma medication dispensing during the follow-up period, relative to the control group (regression coefficient: -0.58 [-0.74 to 0.42] without age matching (P < 0.0001) and -0.61 [-0.76 to -0.46] with age matching; P < 0.0001).Prescription of grass pollen SLIT tablets reduced the dispensing of AR and asthma medications in real life.
Volume-based response evaluations with consensual lesion selection using cloud solutions in clinical trials: A pilot study.
Authors: Estanislao Oubel, Eric Bonnard, Naoko Sueoka-Aragane, Naomi Kobayashi, Colette Charbonnier, Junta Yamamichi, Hideaki Mizobe, Shinya Kimura
Journal: Journal of Clinical Oncology (2014)

e13538 Background: The use of lesion volume is considered as a promising alternative to RECIST (Response Evaluation Criteria in Solid Tumors) to make tumor measurements more accurate, consistent, and for earlier detection of changes. Herein, we report the results of a pilot study aiming at evaluating the effects of target (TL) and new lesions (NL) selection on volume-based response (VBR) assessments, thanks to cloud solutions intended to standardize evaluations in multi-center clinical trials. Methods: 11 lung cancer patients with CT scans acquired at 3 time points were retrospectively selected from RIDER (Reference Image Database to Evaluate Therapy Response) and proprietary databases. Images were analyzed according to RECIST and VBR criteria by two oncologists (Japan and Scotland) and one radiologist (France) by using cloud solutions (MEDIAN Technologies). They allowed carrying out a consensus process on the choice of the TL and NL used for computing response. As there are no accepted thresholds for assessing VBR, we have applied previously published values based on measurement variability (-35 %/+55 %) and 3D-extensions of RECIST thresholds (-67%/+73%). The benefits of VBR and consensus were measured in terms of multi-observer agreement by using Fleiss’ kappa (FK) and associated standard errors (SE). Results: VBR with -35%/+55% thresholds and a consensual selection of TL allowed to obtain FK=0.85 (SE=0.091), which increases to 0.95 (SE=0.092) with an extra consensus on NL. As a reference, the agreement for RECIST is FK=0.72 (SE=0.088). According to Landis and Koch’s table, an almost perfect agreement is achieved when the proposed protocol is applied. As expected, the response was shown to be dependent on the set of volumetric thresholds, but in a consistent way (FK is always higher for the -35 %/+55 % set). Conclusions: This study provides additional evidence about the benefit of using VBR over RECIST. The use of cloud solutions showed to be an interesting and feasible strategy for standardizing response evaluations and reducing variability in multi-center clinical trials. This type of initiative is of great importance for increasing consistency in the production of trial results.