tbuckley/cabot-search huggingface dataset:
Gastrointestinal Toxicity With Celecoxib vs Nonsteroidal Anti-inflammatory Drugs for Osteoarthritis and Rheumatoid Arthritis
Authors: F E Silverstein, G Faich, J L Goldstein, L S Simon, T Pincus, A Whelton, R Makuch, G Eisen, N M Agrawal, W F Stenson, A M Burr, W W Zhao, J D Kent, J B Lefkowith, K M Verburg, G S Geis
Journal: JAMA (2000)

ContextConventional nonsteroidal anti-inflammatory drugs (NSAIDs) are associated with a spectrum of toxic effects, notably gastrointestinal (GI) effects, because of inhibition of cyclooxygenase (COX)-1. Whether COX-2–specific inhibitors are associated with fewer clinical GI toxic effects is unknown.ObjectiveTo determine whether celecoxib, a COX-2–specific inhibitor, is associated with a lower incidence of significant upper GI toxic effects and other adverse effects compared with conventional NSAIDs.DesignThe Celecoxib Long-term Arthritis Safety Study (CLASS), a double-blind, randomized controlled trial conducted from September 1998 to March 2000.SettingThree hundred eighty-six clinical sites in the United States and Canada.ParticipantsA total of 8059 patients (≥18 years old) with osteoarthritis (OA) or rheumatoid arthritis (RA) were enrolled in the study, and 7968 received at least 1 dose of study drug. A total of 4573 patients (57%) received treatment for 6 months.InterventionsPatients were randomly assigned to receive celecoxib, 400 mg twice per day (2 and 4 times the maximum RA and OA dosages, respectively; n = 3987); ibuprofen, 800 mg 3 times per day (n = 1985); or diclofenac, 75 mg twice per day (n = 1996). Aspirin use for cardiovascular prophylaxis (≤325 mg/d) was permitted.Main Outcome MeasuresIncidence of prospectively defined symptomatic upper GI ulcers and ulcer complications (bleeding, perforation, and obstruction) and other adverse effects during the 6-month treatment period.ResultsFor all patients, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.76% vs 1.45% (P = .09) and 2.08% vs 3.54% (P = .02), respectively. For patients not taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 0.44% vs 1.27% (P = .04) and 1.40% vs 2.91% (P = .02). For patients taking aspirin, the annualized incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib vs NSAIDs were 2.01% vs 2.12% (P = .92) and 4.70% vs 6.00% (P = .49). Fewer celecoxib-treated patients than NSAID-treated patients experienced chronic GI blood loss, GI intolerance, hepatotoxicity, or renal toxicity. No difference was noted in the incidence of cardiovascular events between celecoxib and NSAIDs, irrespective of aspirin use.ConclusionsIn this study, celecoxib, at dosages greater than those indicated clinically, was associated with a lower incidence of symptomatic ulcers and ulcer complications combined, as well as other clinically important toxic effects, compared with NSAIDs at standard dosages. The decrease in upper GI toxicity was strongest among patients not taking aspirin concomitantly.
Nighttime Cross-Coverage Is Associated with Decreased Intensive Care Unit Mortality. A Single-Center Study
Authors: Andre Carlos Kajdacsy-Balla Amaral, Bernardo S. Barros, Camilla C. P. P. Barros, Cameron Innes, Ruxandra Pinto, Gordon D. Rubenfeld
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Cross-coverage is associated with medical errors caused by miscommunication during handoffs. However, no direct evidence links handoffs to outcomes, or explains the mechanisms leading to outcomes. Furthermore, the previous literature may overestimate the impact of handoffs because of hindsight bias.Objectives: To explore the effects of nighttime cross-coverage on mortality and decision making in critically ill patients.Methods: Observational cohort of 629 consecutive critically ill admissions, admitted for at least 48 hours, and critical care fellows in an academic hospital.Measurements and Main Results: Intensive care unit (ICU) mortality and nighttime decisions. Our exposure variable was cross-covering status of fellows. We observed a decrease in ICU mortality (odds ratio, 0.77 per 1 d; 0.60–0.99; P = 0.04), a higher number of nighttime decisions (19.3 vs. 10.4%; odds ratio, 2.02; 95% confidence interval [CI], 1.03–3.95; P = 0.04), an increase in fentanyl equivalents administered to patients at night (difference, +10.2 μg/h; 95% CI, +1.4 to +19.0; P = 0.02), and an increase in transfusions at night (difference, +465 ml; 95% CI, +98 to +832; P = 0.01) when fellows were cross-covering.Conclusions: In this single-center study exposure to cross-covering fellows was associated with a decrease in ICU mortality and with more nighttime decisions. Our findings contradict the dominant hypothesis that cross-coverage is associated with worse outcomes, and suggest that a "second look" by cross-covering fellows may mitigate cognitive errors. Future interventions to improve patient safety in ICUs should focus both on the quality of handoffs and on strategies to decrease cognitive errors.
An evolutionary recent neuroepithelial cell adhesion function of huntingtin implicates ADAM10-Ncadherin
Authors: Valentina Lo Sardo, Chiara Zuccato, Germano Gaudenzi, Barbara Vitali, Catarina Ramos, Marzia Tartari, Michael A Myre, James A Walker, Anna Pistocchi, Luciano Conti, Marta Valenza, Binia Drung, Boris Schmidt, James Gusella, Scott Zeitlin, Franco Cotelli, Elena Cattaneo
Journal: Nature Neuroscience (2012)
The Incidence and Course of Depression in Bereaved Youth 21 Months After the Loss of a Parent to Suicide, Accident, or Sudden Natural Death
Authors: David Brent, Nadine Melhem, M. Bertille Donohoe, Monica Walker
Journal: American Journal of Psychiatry (2009)

Objective: This study examined effects of bereavement 21 months after a parent’s death, particularly death by suicide. Method: The participants were 176 offspring, ages 7–25, of parents who died by suicide, accident, or sudden natural death. They were assessed 9 and 21 months after the death, along with 168 nonbereaved subjects. Results: Major depression and alcohol or substance abuse 21 months after the parent’s death were more common among bereaved youth than among comparison subjects. Offspring with parental suicide or accidental death had higher rates of depression than comparison subjects; those with parental suicide had higher rates of alcohol or substance abuse. Youth with parental suicide had a higher incidence of depression than those bereaved by sudden natural death. Bereavement and a past history of depression increased depression risk in the 9 months following the death, which increased depression risk between 9 and 21 months. Losing a mother, blaming others, low self-esteem, negative coping, and complicated grief were associated with depression in the second year. Conclusions: Youth who lose a parent, especially through suicide, are vulnerable to depression and alcohol or substance abuse during the second year after the loss. Depression risk in the second year is mediated by the increased incidence of depression within the first 9 months. The most propitious time to prevent or attenuate depressive episodes in bereaved youth may be shortly after the parent’s death. Interventions that target complicated grief and blaming of others may also improve outcomes in symptomatic youth with parental bereavement.
Quitting Drugs: Quantitative and Qualitative Features
Authors: Gene M. Heyman
Journal: Annual Review of Clinical Psychology (2013)

According to the idea that addiction is a chronic relapsing disease, remission is at most a temporary state. Either addicts never stop using drugs, or if they do stop, remission is short lived. However, research on remission reveals a more complex picture. In national epidemiological surveys that recruited representative drug users, remission rates varied widely and were markedly different for legal and illegal drugs and for different racial/ethnic groups. For instance, the half-life for cocaine dependence was four years, but for alcohol dependence it was 16 years, and although most dependent cocaine users remitted before age 30, about 5% remained heavy cocaine users well into their forties. Although varied, the remission results were orderly. An exponential growth curve closely approximated the cumulative frequency of remitting for different drugs and different ethnic/racial groups. Thus, each year a constant proportion of those still addicted remitted, independent of the number of years since the onset of dependence.
Overall survival for sorafenib plus interleukin-2 compared with sorafenib alone in metastatic renal cell carcinoma (mRCC): final results of the ROSORC trial
Authors: G. Procopio, E. Verzoni, S. Bracarda, S. Ricci, C. Sacco, L. Ridolfi, C. Porta, R. Miceli, N. Zilembo, E. Bajetta
Journal: Annals of Oncology (2013)
Risk factors for oligodendroglial tumors: A pooled international study
Authors: B. J. McCarthy, K. M. Rankin, K. Aldape, M. L. Bondy, T. Brannstrom, H. Broholm, M. Feychting, D. Il'yasova, P. D. Inskip, C. Johansen, B. S. Melin, A. M. Ruder, M. A. Butler, M. E. Scheurer, J. Schuz, J. A. Schwartzbaum, M. R. Wrensch, F. G. Davis
Journal: Neuro-Oncology (2010)

Oligodendroglial tumors are rare subtypes of brain tumors and are often combined with other glial tumors in epidemiological analyses. However, different demographic associations and clinical characteristics suggest potentially different risk factors. The purpose of this study was to investigate possible risk factors for oligodendroglial tumors (including oligodendroglioma, anaplastic oligodendroglioma, and mixed glioma). Data from 7 case-control studies (5 US and 2 Scandinavian) were pooled. Unconditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for age group, gender, and study site. Data on 617 cases and 1260 controls were available for analyses. Using data from all 7 studies, history of allergies and/or asthma was associated with a decreased risk of anaplastic oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9), and history of asthma only was associated with a decreased risk of oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) and anaplastic oligodendroglioma (OR = 0.3; 95% CI: 0.1-0.9). A family history of brain tumors was associated with an increased risk of anaplastic oligodendroglioma (OR = 2.2; 95% CI: 1.1-4.5). Having had chicken pox was associated with a decreased risk of oligodendroglioma (OR = 0.6; 95% CI: 0.4-0.9) and anaplastic oligodendroglioma (OR = 0.5; 95% CI: 0.3-0.9) in the US studies. Although there is some overlap in risk factors between oligodendroglial tumors and gliomas as a group, it is likely that additional factors specific to oligodendroglial tumors have yet to be identified. Large, multi-institution international studies will be necessary to better characterize these etiological risk factors.
Ethnicity and Sex Affect Diabetes Incidence and Outcomes
Authors: Nadia A. Khan, Hong Wang, Sonia Anand, Yan Jin, Norman R. C. Campbell, Louise Pilote, Hude Quan
Journal: Diabetes Care (2010)

OBJECTIVE Diabetes guidelines recommend aggressive screening for type 2 diabetes in Asian patients because they are considered to have a higher risk of developing diabetes and potentially worse prognosis. We determined incidence of diabetes and risk of death or macrovascular complications by sex among major Asian subgroups, South Asian and Chinese, and white patients with newly diagnosed diabetes. RESEARCH DESIGN AND METHODS Using population-based administrative data from British Columbia and Alberta, Canada (1997–1998 to 2006–2007), we identified patients with newly diagnosed diabetes aged ≥35 years and followed them for up to 10 years for death, acute myocardial infarction, stroke, or hospitalization for heart failure. Ethnicity was determined using validated surname algorithms. RESULTS There were 15,066 South Asian, 17,754 Chinese, and 244,017 white patients with newly diagnosed diabetes. Chinese women and men had the lowest incidence of diabetes relative to that of white or South Asian patients, who had the highest incidence. Mortality in those with newly diagnosed diabetes was lower in South Asian (hazard ratio 0.69 [95% CI 0.62–0.76], P &amp;lt; 0.001) and Chinese patients (0.69 [0.63–0.74], P &amp;lt; 0.001) then in white patients. Risk of acute myocardial infarction, stroke, or heart failure was similar or lower in the ethnic groups relative to that of white patients and varied by sex. CONCLUSIONS The incidence of diagnosed diabetes varies significantly among ethnic groups. Mortality was substantially lower in South Asian and Chinese patients with newly diagnosed diabetes than in white patients.
Rho Kinase Mediates Cold-Induced Constriction of Cutaneous Arteries
Authors: S.R. Bailey, A.H. Eid, S. Mitra, S. Flavahan, N.A. Flavahan
Journal: Circulation Research (2004)

Cold-induced vasoconstriction in cutaneous blood vessels is mediated in part by increased activity of vascular smooth muscle α2-adrenoceptors (VSM α2-ARs). In mouse cutaneous arteries, α2C-ARs are normally silent at 37°C but mediate cold-induced augmentation of α2-AR responsiveness. In transfected HEK293 cells, this functional rescue is mediated by cold-induced translocation of α2C-ARs from the Golgi to the plasma membrane. Experiments were performed to determine the role of Rho/Rho kinase signaling in this process. Inhibition of Rho kinase (fasudil, Y27632 or H-1152) did not affect constriction of isolated mouse tail arteries to the α2-AR agonist UK 14 304 at 37°C but dramatically reduced the augmented responses to the agonist at 28°C. After Rho kinase inhibition, cooling no longer increased constriction evoked by α2-AR stimulation. Cooling (to 28°C) activated Rho in VSM cells and increased the calcium sensitivity of constriction in α toxin-permeabilized arteries. Stimulation of α2-ARs in VSM cells had no effect on Rho activity or calcium sensitivity at 37°C or 28°C. In HEK293 cells transfected with α2C-ARs, cooling (to 28°C) stimulated the translocation of α2C-ARs to the plasma membrane and this effect was prevented by inhibition of Rho kinase, using fasudil or RNA interference. Consistent with inhibition of the spatial rescue of α2C-ARs, fasudil inhibited α2-AR–mediated mobilization of calcium in tail arteries at 28°C but not 37°C. Therefore, cold-induced activation of Rho/Rho kinase can mediate cold-induced constriction in cutaneous arteries by enabling translocation of α2C-ARs to the plasma membrane and by increasing the calcium sensitivity of the contractile process.
Transcriptional Characterization of a Prospective Series of Primary Plasma Cell Leukemia Revealed Signatures Associated with Tumor Progression and Poorer Outcome
Authors: Katia Todoerti, Luca Agnelli, Sonia Fabris, Marta Lionetti, Giacomo Tuana, Laura Mosca, Luigia Lombardi, Vitina Grieco, Gabriella Bianchino, Fiorella D'Auria, Teodora Statuto, Carmela Mazzoccoli, Luciana De Luca, Maria Teresa Petrucci, Fortunato Morabito, Massimo Offidani, Francesco Di Raimondo, Antonietta Falcone, Paola Omede', Pierfrancesco Tassone, Mario Boccadoro, Antonio Palumbo, Antonino Neri, Pellegrino Musto
Journal: Clinical Cancer Research (2013)

Abstract Purpose: Plasma cell leukemia (PCL) is a rare form of plasma cell dyscrasia that presents either as a progression of previously diagnosed multiple myeloma, namely secondary PCL, or as initial manifestation of disease, namely primary PCL (pPCL). Although the presenting signs and symptoms include those seen in multiple myeloma, pPCL is characterized by several aspects that define a more aggressive course. Here, we have investigated the transcriptome of pPCLs and correlated differential expression profiles with outcome to provide insights into the biology of the disease. Experimental Design: The expression profiles of 21 newly diagnosed pPCLs included in a multicenter prospective clinical trial were generated using high-density microarray, then evaluated in comparison with a representative series of patients with multiple myeloma and in association with clinical outcome. Results: All but one of the pPCLs had one of the main immunoglobulin heavy-chain locus translocations, whose associated transcriptional signatures resembled those observed in multiple myeloma. A 503-gene signature distinguished pPCL from multiple myeloma, from which emerged 26 genes whose expression trend was associated with progressive stages of plasma cells dyscrasia in a large dataset from multiple institutions, including samples from normal donors throughout PCL. Finally, 3 genes were identified as having expression levels that correlated with response to the first-line treatment with lenalidomide/dexamethasone, whereas a 27-gene signature was associated with overall survival independently of molecular alterations, hematologic parameters, and renal function. Conclusions: Overall, our data contribute to a fine dissection of pPCL and may provide novel insights into the molecular definition of patients with poorer prognosis. Clin Cancer Res; 19(12); 3247–58. ©2013 AACR.
Soluble RNA Methylase Activity of Transplantable Mouse Hepatomas&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: R. L. Hancock, J. Grunau
Journal: JNCI Journal of the National Cancer Institute (1970)

The soluble ribonucleic acid (sRNA) methylase activity and the histology of several transplantable mouse hepatomas were examined. Three hepatomas (H-1, H-4, and H-6) were relatively fast growing. H-1 and H-6 hepatomas had higher sRNA methylase activity, H-4 had amounts of activity similar to those of liver, and H-3 hepatoma had variable amounts. sRNA methylase activity did not seem to be correlated with rate of growth but may have been associated with the state of differentiation.
Anatomical and Functional Brain Abnormalities in Drug-Naive First-Episode Schizophrenia
Authors: Wenting Ren, Su Lui, Wei Deng, Fei Li, Mingli Li, Xiaoqi Huang, Yuqing Wang, Tao Li, John A. Sweeney, Qiyong Gong
Journal: American Journal of Psychiatry (2013)

The authors sought to explore whether anatomical and functional brain deficits are present in similar or different brain regions early in the course of schizophrenia, before antipsychotic treatment, and whether these deficits are more severe or otherwise different in patients with prominent negative symptoms. A total of 100 drug-naive first-episode schizophrenia patients and 100 matched healthy comparison subjects underwent structural and resting-state functional MRI scanning. Gray matter volume and amplitude of low-frequency fluctuations during resting-state functional studies were measured. Group comparisons of gray matter volume showed significant differences mainly in thalamo-cortical networks, while alterations in the amplitude of low-frequency fluctuations were observed in fronto-parietal and default mode networks. Thus, different brain regions had alterations in gray matter volume and resting state physiology. These changes did not correlate with the duration of untreated illness, nor with acute clinical symptom severity. Patients with prominent negative symptoms had greater regional alterations in brain anatomy, particularly in the left dorsolateral prefrontal cortex, while the pattern of functional alterations was unrelated to severity of negative symptoms. Anatomical and resting-state functional deficits were observed in different brain regions, indicating that anatomical and functional brain abnormalities are significantly dissociated in the early course of schizophrenia. The lack of association of these abnormalities with illness duration and episode severity suggests that these anatomical and functional changes may be early-evolving features of the illness that are relatively stable early in the course of illness. The different structural deficits of regional gray matter observed in patients with prominent negative symptoms may provide unique insight into the early regional neuropathology of this symptom dimension in schizophrenia.
Short- and Long-Term Antibiotic Treatment Reduces Airway and Systemic Inflammation in Non–Cystic Fibrosis Bronchiectasis
Authors: James D. Chalmers, Maeve P. Smith, Brian J. McHugh, Cathy Doherty, John R. Govan, Adam T. Hill
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Rationale: The vicious cycle hypothesis of bronchiectasis argues that bacterial colonization leads to airway inflammation and progressive lung damage. The logical extension of this hypothesis is that acute or chronic antibiotic therapy should improve airway inflammation and clinical outcome. There are little data to support this hypothesis in patients with non–cystic fibrosis (CF) bronchiectasis.Objectives: To determine whether acute or chronic antibiotic therapy improves airway inflammation and clinical outcome in non-CF bronchiectasis.Methods: The relationship between bacterial load and airway and systemic inflammation was investigated in 385 stable patients, 15 stable patients treated with intravenous antibiotics, and 34 patients with an exacerbation of bronchiectasis treated with intravenous antibiotics. Long-term antibiotic therapy was investigated using samples from a 12-month controlled trial of nebulized gentamicin.Measurements and Main Results: In stable patients, there was a direct relationship between airway bacterial load and markers of airway inflammation (P < 0.0001 for all analyses). High bacterial loads were associated with higher serum intercellular adhesion molecule-1, E-selectin, and vascular cell adhesion molecule-1 (P < 0.05 above bacterial load ≥1 × 107 cfu/ml). In stable patients, there was a direct relationship between bacterial load and the risk of subsequent exacerbations (odds ratio, 1.20; 95% confidence interval, 1.11–1.29; P < 0.0001) and severe exacerbations (odds ratio, 1.11; 95% confidence interval, 1.01–1.21; P = 0.02). Short- and long-term antibiotic treatments were associated with reductions in bacterial load, airways, and systemic inflammation.Conclusions: High airway bacterial loads in non-CF bronchiectasis are associated with airway and systemic inflammation and a greater risk of exacerbations. Short- and long-term antibiotic therapy reduce markers of airways and systemic inflammation.Clinical trial registered with www.clinicaltrials.gov (NCT 00749866).