tbuckley/cabot-search huggingface dataset:
Concerns Regarding Resource Use and Outcomes in Subsets of Clinicians—Reply
Authors: Jennifer P. Stevens, David J. Nyweide, Bruce E. Landon
Journal: JAMA Internal Medicine (2018)

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
Change in Overweight from Childhood to Early Adulthood and Risk of Type 2 Diabetes
Authors: Lise G. Bjerregaard, Britt W. Jensen, Lars Ängquist, Merete Osler, Thorkild I.A. Sørensen, Jennifer L. Baker
Journal: New England Journal of Medicine (2018)

Childhood overweight is associated with an increased risk of type 2 diabetes in adulthood. We investigated whether remission of overweight before early adulthood reduces this risk.We conducted a study involving 62,565 Danish men whose weights and heights had been measured at 7 and 13 years of age and in early adulthood (17 to 26 years of age). Overweight was defined in accordance with Centers for Disease Control and Prevention criteria. Data on type 2 diabetes status (at age ≥30 years, 6710 persons) were obtained from a national health registry.Overweight at 7 years of age (3373 of 62,565 men; 5.4%), 13 years of age (3418 of 62,565; 5.5%), or early adulthood (5108 of 62,565; 8.2%) was positively associated with the risk of type 2 diabetes; associations were stronger at older ages at overweight and at younger ages at diagnosis of type 2 diabetes. Men who had had remission of overweight before the age of 13 years had a risk of having type 2 diabetes diagnosed at 30 to 60 years of age that was similar to that among men who had never been overweight (hazard ratio, 0.96; 95% confidence interval [CI], 0.75 to 1.21). As compared with men who had never been overweight, men who had been overweight at 7 and 13 years of age but not during early adulthood had a higher risk of type 2 diabetes (hazard ratio, 1.47; 95% CI, 1.10 to 1.98), but their risk was lower than that among men with persistent overweight (hazard ratio [persistently overweight vs. never overweight], 4.14; 95% CI, 3.57 to 4.79). An increase in body-mass index between 7 years of age and early adulthood was associated with an increased risk of type 2 diabetes, even among men whose weight had been normal at 7 years of age.Childhood overweight at 7 years of age was associated with increased risks of adult type 2 diabetes only if it continued until puberty or later ages. (Funded by the European Union.).
Adding an invasive procedure will not necessarily change treatment or outcome of NSCLC patients with preoperative clinical N1 disease
Authors: Alfredo Addeo, Giuseppe Banna
Journal: European Respiratory Journal (2018)

We have read with great interest and welcome the publication of a prospective multicentre study regarding the role of mediastinal staging by video-assisted mediastinoscopy (VAM) in patients with clinical N1 (cN1) nonsmall cell lung cancer (NSCLC) [1]. The objective of the study was to assess the sensitivity, negative predictive value and accuracy of VAM in a well-defined group of patients with cN1. Video-assisted mediastinoscopy or VAM-lymphadenectomy is not a standard procedure in cN1 disease <http://ow.ly/dAZq30irs63>
Adjuvant FOLFOX-Nab-paclitaxel (FOLFOX-A) for pancreatic cancer: A phase II Brown University Oncology Research Group (BrUOG) trial.
Authors: Howard Safran, Kevin Charpentier, Kalyan C. Mantripragada, Rimini Breakstone, Thomas J. Miner, Thomas A. DiPetrillo, Eric I Marks, Kayla Rosati, Kristen Mitchell, Rachael Rossiter, Denise Luppe, Molly Rago, Andrew Schumacher, Lindsey Cavanagh
Journal: Journal of Clinical Oncology (2018)

TPS550 Background: The FOLFOX-A regimen was developed by BrUOG, in response to the activity of nab-paclitaxel (nP) in metastatic pancreatic cancer (mPC), by substituting nP for irinotecan in FOLFIRINOX. In a phase I/II study of FOLFOX-A in mPC, median overall survival (OS) was 15 months (Safran H, et al. Am J Clin Oncol, 2016 Dec;39(6):619-622), which motivated evaluation of the tolerability and efficacy of this aggressive regimen in the adjuvant setting. Therefore, a phase II study of FOLFOX-A was initiated for patients with resected pancreatic cancer. Methods: Eligibility criteria included potentially curative resection of pancreatic adenocarcinoma (positive margins allowed if all gross tumor was removed), pathologic stages T1-3/N0-1/M0, interval between surgery and registration of 21-70 days and post resection serum CA19-9 ≤ 180 units/mL. All patients received nab-paclitaxel 150mg/m2, oxaliplatin 85mg/m2 and leucovorin 400mg/m2, followed by fluorouracil 2400mg/m2 infused over 46 hours. Cycles were repeated every 2 weeks. The primary objective is to assess the feasibility of administering at least 10 of 12 planned cycles of FOLFOX-A without unacceptable toxicity in 25 patients. Secondary endpoints include progression-free survival and OS. Results: Between June 2014-August 2017, 19 patients have been enrolled, 8 male and 11 female. Median age is 63 (43-68). Fifteen patients had positive lymph nodes on pathology with stages T1N0(n = 2), T3N0(n = 2), T1N1(n = 1), T3N1(n = 14) [AJCC Cancer Staging Manual, 7th Edition (2010)]. Conclusions: This study is testing the tolerability of administering adjuvant FOLFOX-A to patients with resected pancreatic cancer. Accrual is expected to be complete by January 2018. Clinical trial information: NCT02022033.
Predicting risk of unplanned hospital readmission in survivors of critical illness: a population-level cohort study
Authors: Nazir I Lone, Robert Lee, Lisa Salisbury, Eddie Donaghy, Pamela Ramsay, Janice Rattray, Timothy S Walsh
Journal: Thorax (2018)

Intensive care unit (ICU) survivors experience high levels of morbidity after hospital discharge and are at high risk of unplanned hospital readmission. Identifying those at highest risk before hospital discharge may allow targeting of novel risk reduction strategies. We aimed to identify risk factors for unplanned 90-day readmission, develop a risk prediction model and assess its performance to screen for ICU survivors at highest readmission risk.Population cohort study linking registry data for patients discharged from general ICUs in Scotland (2005-2013). Independent risk factors for 90-day readmission and discriminant ability (c-index) of groups of variables were identified using multivariable logistic regression. Derivation and validation risk prediction models were constructed using a time-based split.Of 55 975 ICU survivors, 24.1% (95%CI 23.7% to 24.4%) had unplanned 90-day readmission. Pre-existing health factors were fair discriminators of readmission (c-index 0.63, 95% CI 0.63 to 0.64) but better than acute illness factors (0.60) or demographics (0.54). In a subgroup of those with no comorbidity, acute illness factors (0.62) were better discriminators than pre-existing health factors (0.56). Overall model performance and calibration in the validation cohort was fair (0.65, 95% CI 0.64 to 0.66) but did not perform sufficiently well as a screening tool, demonstrating high false-positive/false-negative rates at clinically relevant thresholds.Unplanned 90-day hospital readmission is common. Pre-existing illness indices are better predictors of readmission than acute illness factors. Identifying additional patient-centred drivers of readmission may improve risk prediction models. Improved understanding of risk factors that are amenable to intervention could improve the clinical and cost-effectiveness of post-ICU care and rehabilitation.
Abstract P373: Trends in Cardiovascular Risk Factors by Clinical Definitions of Prediabetes
Authors: Caroline Liu, Kathryn Foti, Elizabeth Selvin
Journal: Circulation (2018)

Introduction: There are five different definitions of prediabetes currently used in clinical practice. How cardiovascular risk may differ by these different definitions of prediabetes and whether trends in cardiovascular risk in persons with prediabetes have changed over time is largely uncharacterized. Hypothesis: We expect the prevalence of cardiovascular risk factors will vary by prediabetes definition and will be highest among those who meet clinical definitions with higher cutoff values. We hypothesize awareness, treatment and control of hypertension and hypercholesterolemia have increased over time among those with prediabetes. Methods: We analyzed data for adults ages ≥ 20 years from the 1999-2014 National Health and Nutrition Examination Survey (NHANES). We used calibrated HbA1c and FPG values to estimate prediabetes prevalence. We examined the prevalence and trends of hypertension and hypercholesterolemia among those who met each clinical definition of prediabetes, as well as awareness, treatment, and control. Results: The prevalence of prediabetes by each definitions remained stable across survey years. The prevalence, awareness, treatment, and control of hypertension and hypercholesterolemia by clinical definition modestly increased over time. Conclusion: The prevalence of hypertension and hypercholesterolemia was higher among individuals who met HbA1c-based definitions of prediabetes than other measures and was highest when more restrictive criteria for prediabetes were used. Awareness, treatment, and control of cardiovascular risk factors increased over time by any definition, but the high prevalence of cardiovascular risk factors highlights the need for improvement in risk factor management in people with prediabetes.
The influence of hospital and surgeon volume on survival and local control in rectal cancer: Long-term results of the CAO/ARO/AIO-94 trial.
Authors: Thilo Sprenger, Tim Beissbarth, Rolf Sauer, Emmanouil Fokas, Werner Hohenberger, Torsten Liersch, Claus Rödel, Michael Ghadimi
Journal: Journal of Clinical Oncology (2018)

738 Background: The association of hospital and surgeon volume with the outcome of rectal cancer patients is under debate. In this study the long-term influence of the hospital as well as the surgeon volume on overall survival and local recurrence were investigated. Methods: In a post-hoc analysis of the randomized phase III CAO/ARO/AIO-94 trial after a follow-up of more than 10 years, 799 patients with locally advanced rectal cancers were evaluated. Survival and local recurrence rates were stratified by the hospital recruitment volume (≤20 vs. 21-90 vs. &gt; 90 patients) and by the surgeon volume (≤10 vs. 11-50 vs. &gt; 50 procedures). Results: Patients treated in „high-volume“ hospitals had a longer overall survival than those treated in hospitals with medium or low treatment volume (p = 0.03). The surgeon volume was significantly associated with decreased local recurrences (p = 0.01) but had no influence on overall survival. The effect of neoadjuvant chemoradiation on local control was the strongest in patients being operated by medium-volume surgeons. Conclusions: Patients with locally advanced rectal cancers might benefit from treatment in in specialized high-volume hospitals. In particular, the surgeon volume had significant influence on local control.
Annals Story Slam - Despair to Hope
Authors: Michael S. Weinstein
Journal: Annals of Internal Medicine (2018)

Web Exclusives3 April 2018Annals Story Slam - Despair to HopeFREEMichael S. Weinstein, MDMichael S. Weinstein, MDThomas Jefferson University, Philadelphia, Pennsylvania (M.S.W.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W18-0001 SectionsAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Video. Annals Story Slam - Despair to Hope "Despair to Hope," by Dr. Michael Weinstein (Duration 7:40)Building on the popular Annals feature “On Being a Doctor,” storytellers share stories about the experience of doctoring on video.For more videos from and information on Annals Story Slam, visit go.annals.org/StorySlam. Comments0 CommentsSign In to Submit A Comment Author, Article, and Disclosure InformationAffiliations: Thomas Jefferson University, Philadelphia, Pennsylvania (M.S.W.)Corresponding Author: Michael S. Weinstein, MD; e-mail, michael.[email protected]edu. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics 3 April 2018Volume 168, Issue 7Page: SS1 ePublished: 3 April 2018 Issue Published: 3 April 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.Loading ...
Immunological and hematological effects of <scp>IL</scp> ‐5(Rα)‐targeted therapy: An overview
Authors: M. Hassani, L. Koenderman
Journal: Allergy (2018)

IL-5 is an important cytokine for priming and survival of mature eosinophils and for proliferation and maturation of their progenitors. Hence, IL-5(Rα) targeting will be increasingly used in diseases where eosinophils are the key immune effector cells such as eosinophilic asthma (EA), hypereosinophilic syndrome (HES), eosinophilic esophagitis (EE), and eosinophilic granulomatosis with polyangiitis (EGPA). Therefore, several neutralizing monoclonal antibodies directed against IL-5 (mepolizumab and reslizumab) and its receptor IL-5Rα (benralizumab) have found or will find their way to the clinic. While the clinical effect of these drugs has been extensively investigated and reviewed, the understanding of the underlying immunological and hematological mechanisms remains less clear. This review will discuss the translational outcomes of treatment with these monoclonal antibodies in humans to shed light on the mechanisms underlying the main immunological and hematological findings from these clinical trials in humans.
Number needed to treat (NNT) as a measure of drug benefit: Lenalidomide versus bortezomib for treatment of relapsed/refractory multiple myeloma (MM).
Authors: Satyin Kaura, George Dranitsaris
Journal: Journal of Clinical Oncology (2012)

e18562 Background: Lenalidomide(LEN) and bortezomib(BORT) are active agents in the treatment of refractory MM. The former is administered 25 mg/day orally on days 1-21 of repeated 28-day cycles. The latter as a 1.3 mg/m^2 intravenous dose on days 1, 4, 8 and 11 for eight, three week cycles. Both agents have demonstrated an improvement in disease response, progression free (PFS) and overall survival (OS) in the refractory MM setting. NNT represents the number of patients that need to be treated with a new intervention in order to have one additional patient deriving benefit, and is a powerful approach that can be used to make sense of numerical results from clinical trials. In this analysis, the NNT approach was used to compare LEN and BORT in patients with relapsed MM. Methods: The pivotal randomized trials for LEN (Weber, Dimopoulos, 2007) and BORT (Richardson, 2005) were reviewed. A key requirement for a NNT comparative analysis is that all outcomes be measured against a comparable control. The NNT was then calculated for both agents with respect to disease response and PFS at 12 months by taking the reciprocal of the absolute differences in treatment effect between the experimental therapies and the control group. Results: For a disease response, the NNT for LEN and BORT was 3 and 5 patients respectively; to have one additional patient achieving a disease response. A difference in the NNT was also noted for PFS at 12 months; only 3 patients would need to be treated with LEN for an additional patient remaining progression free compared to 9 with BORT. This is a relevant finding because it suggests a 3 fold relative increase in clinical benefit in patients treat with LEN compared to BORT. Conclusions: In situations of multiple numerical outcomes from randomized trials, NNT approach is a simple and effective method to express the findings in a clinically meaningful way. In this analysis, it appears that more patients treated with LEN are likely to respond and to achieve a 12 month PFS than comparable patients treated with BORT. Possible reasons for this effect include differences in the trial population, extent of disease, and/or true differences in efficacy.
Should This Patient Receive Prophylactic Medication to Prevent Delirium?
Authors: Anjala V. Tess, Melissa L.P. Mattison, Joshua R. Leo, Eileen E. Reynolds
Journal: Annals of Internal Medicine (2018)

In 2015, the American Geriatrics Society released recommendations for prevention and management of postoperative delirium, based on a systematic literature review and evaluation of nonpharmacologic and pharmacologic approaches by an expert panel. The guidelines recommend an interdisciplinary focus on nonpharmacologic measures (reorientation, medication management, early mobility, nutrition, and gastointestinal motility) for prevention and consideration of this strategy for acute management. They also recommend optimizing nonopioid medication as a means to manage pain and avoiding benzodiazepines other than to treat substance withdrawal. The authors concluded that evidence to recommend antipsychotics for prevention of delirium is insufficient but that these drugs may be considered for short-term treatment in the setting of imminent harm to the patient or caregivers or severe distress due to agitation. Patients should be given the lowest possible dose for the shortest duration when other nonpharmacologic measures have failed. In this Beyond the Guidelines, a psychiatrist and a geriatrician debate whether Mr. W, a 79-year-old man at high risk for postoperative delirium, should receive prophylactic antipsychotics with his next surgery. They review risk factors, appropriate evaluation, and potential benefits and harms of the various medications often used in this setting.
Abstract P060: Poorer Lung Function Associated With Higher Risk of Type II Diabetes (DM) Among Chinese Adults With Silicosis
Authors: Ho Yu Cheng, Sek Ying Chair, Janet Wing Hung Sit, Kai Chow Choi
Journal: Circulation (2018)

Background: Development of silicosis is a global occupational hazard, characterized by progressive and irreversible deterioration of lung function. Established associations between the decreased lung function and low-grade systemic inflammation place adults with silicosis at extreme risk of developing DM, but little is known about the prevalence of DM and potential risk factors of DM among adults with silicosis. Methods: We enrolled 390 Chinese adults (mean age=68.7±7.8, men=99.5%) with confirmed silicosis by the Pneumoconiosis Medical Board. The Compensation Ordinance determines the degree of incapacity (DOI), according to lung function loss based on the forced vital capacity. Diagnosed DM by a medical practitioner/physician. Occupational information included job type and duration of dust exposure. Validated questionnaires were used to measure respiratory symptoms, activity limitation and physical activity level. Insulin resistance, fasting glucose, high sensitivity C-reactive protein (hs-CRP), lipid profiles, and vitamin C were via 8-hour fasting venous sample. Body mass index, waist circumference, body fat mass percentage and blood pressure were measured. Logistic regression model was used to adjust covariates of DM. Results: The prevalence of DM among adults with silicosis was 18.5% (n=72), which is higher than the general Chinese male population (Hong Kong=11.4%; China=12.1%). Participant characteristics according to DOI are presented in Table 1. After adjusting for hs-CRP, age, education and physical activity level, body fat mass percentage, medication use for lipid and blood pressure control, higher DOI was significantly associated with higher odds of DM (OR=1.65, 95%CI=1.08-2.53). Conclusion: Adults with longer duration of silicosis have an intensifying risk of DM development. Rehabilitation programs for this vulnerable group with impaired lung function need to target cardiometabolic risk factors to reduce development of CVD.
Growth inhibition of synovial sarcoma cells by curcumin
Authors: Joanna M. Lubieniecka, Wanda Kwan, Jefferson Terry, Torsten O. Nielsen
Journal: Cancer Research (2005)

646  Synovial sarcoma (SS) is a soft tissue malignancy for which no effective systemic therapy currently exists. It represents 7-10% of primary soft tissue malignancies and most typically arises in the extremities of young adults. The results of expression profiling studies by our group and others indicate that Wnt/β-catenin signaling pathway may be particularly important to the biology of SS. In addition, our group’s analysis of β-catenin using tissue microarrays has revealed nuclear accumulation of this protein in patient SS samples, a strong evidence for its activation. Interaction of β-catenin with Tcf4, and thus expression of its target genes, has been recently shown to be regulated by acetylation of β-catenin by p300. Therefore, inhibitors of the p300/ β-catenin pathway may represent a novel targeted therapy for this disease. We examined the cytotoxic effect of curcumin, a reported p300 inhibitor, in SS cell lines. Two SS cell lines, Syo1 and Fuji, were treated with 1 - 100 uM of curcumin for 24, 48 and 72 hours. The effect of curcumin on cell growth was measured by MTT assay and apoptosis was measured by flow cytometry using Annexin V. Doxorubicin was used as positive and vehicle (dimethyl sulfoxide) as negative control drugs. Normal fibroblasts were used as control cells. Dose and time dependent cytotoxicity was observed in both SS cell lines, with doses above 10 μM (Figure). Syo-1 cells were slightly more sensitive to curcumin than Fuji cells, with cell death matched to that of doxorubicin at 25 μM curcumin for Syo-1 cells and 50 μM curcumin for Fuji cells. Much less cytotoxicity was seen in normal human foreskin fibroblasts (30% viable cells vs. less than 10% in both SS cell lines after 72 hours treatment with 100 μM curcumin). The results of Annexin V assay indicated that the observed cell death after curcumin treatment occurred through apoptosis in a dose dependent manner. Expression profiling and tissue microarray analysis of SS indicates that Wnt/β-catenin pathway plays an important role in the development of this tumor, and curcumin, an inhibitor of p300 involved in acetylation of β-catenin, is a potent inhibitor of SS cell growth.