tbuckley/cabot-search huggingface dataset:
Palliative Care Early and Systematic (PaCES): A survey of colorectal cancer clinicians of barriers and facilitators to early palliative care integration.
Authors: Sharon Watanabe, Aynharan Sinnarajah, Madalene Earp, Patricia A. Tang, Marc Kerba, Jessica Simon
Journal: Journal of Clinical Oncology (2017)

128 Background: Health systems struggle to systematically provide early and integrated palliative care (PC) to cancer patients. In Alberta, Canada, the PaCES (Palliative Care Early and Systematic) project is addressing this need by building an early PC pathway for advanced colorectal cancer (CRC) patients. As part of this work, we aimed to characterize barriers and facilitators to: a) providing primary palliative care to CRC patients; b) referring CRC patients for PC specialist consults; and c) working with specialist PC and home care services. Methods: This observational, knowledge translation questionnaire study collected both quantitative and open-ended responses from physicians, nurses and other allied health care professionals (HCP) working with advanced CRC patients in Alberta, Canada. Survey questions and format were informed by Michie’s Theoretical Domains Framework. The strength of this framework is that, in addition to identifying specific barriers to delivering early PC, it also maps out suggested solutions to addressing these barriers. Results: The survey response rate was 43% (65/150). 89% of the respondents were physicians or nurses with Medical Oncology as the primary discipline. Time and competing priorities were the biggest barriers to HCPs addressing patients PC needs (65%). Next, role confusion when working with PC teams, and lack of clear process for executing new orders when patients are at home, were identified by over 55% of HCPs as a barrier. Other aspects of working with PC teams, including, lack of standardized communication processes and inadequate documentation processes, were barriers as perceived by over 45% of HCPs. Over 90% of HCPs surveyed believe earlier PC is likely to benefit their patients, and would recommend an earlier PC pathway to their patients. Conclusions: In Alberta, the main barriers to early PC integration are no longer attitudinal, with over 90% believing that early PC is beneficial for their patients. Time needed to address PC needs in a busy oncology clinic is a barrier. A pathway to improve clarity around referral processes and role confusion when working with PC teams will be developed to address these barriers.
CPAP promotes HCC malignancy via the TNF-alpha/NF-kappa B and IL-6/STAT3 pathways
Authors: P-H Huang, R-Y Chen, S-T Yang, C-G Guo, M-H Lee, Y-J Lin, C-J Yen, H-W Tsai, L-Y Hung
Journal: Annals of Oncology (2017)
Comorbidity, metastases, and survival in women with metastatic breast cancer (mBC) receiving HER2-targeted agents (H2Ts).
Authors: Nicole Meyer, Yanni Hao, Xue Song, William M. Johnson, Nianwen Shi, Jaqueline Willemann Rogerio, Denise A. Yardley
Journal: Journal of Clinical Oncology (2014)

e11574 Background: Little information on survival is available for subgroups of HER2+ mBC patients. Study objectives were to compare clinical histories, progression, and survival of mBC patients treated with H2Ts, by de novo vs recurrent status , ER+ status, and age. Methods: Women ≥ 18 years with Stage IV mBC (index) during 2008-2012 and treated with H2Ts were selected from a large claims database and followed until death or end of data. Patients were stratified by ER+ status, de novo (≤90 days between initial BC diagnosis and index) vs recurrent (>90 days between initial BC diagnosis and index), and ages 18-44, 45-64, or 65+. Relative risk of progression and death were evaluated among the subset of patients with mortality data. Results: Of 2,629 eligible patients, 52% were ER+, 37% de novo, 15% 18-44, 69% 45-64 and 16% 65+. Median follow-up was longer for ER+ vs ER-, de novo vs recurrent, and decreased with age. Baseline comorbid conditions were lower for ER+ vs ER-, higher for de novo vs recurrent and increased with age. ER+ patient had fewer index metastases, were less likely to have liver, lung and brain but more likely to have bone metastases vs ER-. De novo had more index metastases sites, but lower rates of brain and lung metastases vs recurrent. Among the 32% of patient with mortality information, progression was similar by ER+ status, lower in de novo vs recurrent, and lowest for ages 45-64, while mortality rates were higher for ER- vs ER+ (33% vs 19%), recurrent vs de novo (29% vs 18%) and increased with age (18% 18-44, 23% 45-64, 40% 65+). Multivariate analysis suggested the risk of progression was 30% lower among ER+ patients vs ER- , 32% lower for de novo vs recurrent, and similar across age groups. The risk of death was 52% lower for ER+ vs ER-, 35% lower for de novo vs recurrent, and increased with age. Conclusions: Among mBC patients treated with H2Ts, ER+ status and younger age were associated with lower comorbidity, fewer sites of metastases at index and decreased risk of death during follow-up. De novo patients presented with more comorbid conditions and sites of metastases at index, but had lower risk of progression or death during follow-up vs. recurrent patients.
P1.04-014 Diagnostic Yield in Patients Undergoing Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration for Diagnosis of Lung Cancer
Authors: Sunkaru Touray, Rahul Sood, Carlos Martinez-Balzano, Jonathan Holdorf, Anne Lim, Andres Sosa, Paulo Oliveira, Scott Kopec
Journal: Journal of Thoracic Oncology (2017)
La tuberculosis pulmonar en dos centros de prisión preventiva en San Petersburgo, Rusia
Authors: T Lobacheva, V Sazhin, E Vdovichenko, J Giesecke
Journal: Eurosurveillance (2005)

La situacion de la tuberculosis (TB) en el sistema penitenciario ruso ha recibido mucha atencion. Se llevo a cabo un estudio epidemiologico descriptivo de la TB en dos centros de prision preventiva (SIZO) de San Petersburgo. Se buscaron en las bases de datos medicas de estos dos centros los casos de TB diagnosticados entre el 1 de enero 2000 y el 31 diciembre 2002. El metodo de diagnostico mas frecuente fue la radiologia de torax. 
En total, 876 casos de TB fueron notificados en estos dos centros durante este periodo de tres anos. En 432 de estos, el diagnostico se hizo al entrar en prision, y en 444 casos, la enfermedad se declaro durante el encarcelamiento, aumentando la proporcion de casos diagnosticados durante el encarcelamiento con el transcurso del tiempo. La mayor parte de los casos tenian menos de 30 anos. 
La incidencia de la TB en los centros de detencion preventiva en Rusia es todavia muy alta y necesita una vigilancia estricta.
Time to review the provision of addiction treatment for codeine dependence
Authors: Michelle Foley, Paolo Deluca, Andreas Kimergård
Journal: BMJ (2017)

Letter to the editors: .....People who take codeine for valid reasons may require higher doses over time, and this can develop into dependence. Once dependent, people are likely to start doctor and pharmacy â?oshoppingâ? or stealing to consume high doses and avoid withdrawal. Tighter regulation and closer monitoring of over-the-counter sales may be part of the solution, but we also need to examine the service provision for patients with codeine dependence, as current treatment services may not be adequate or appropriate. Timely access to addiction treatment is necessary to tackle the consequences of codeine dependence.
Chcapter XIII: Serum Triglyceride Changes
Journal: Circulation (1968)

Serum triglycerides were determined for Oakland, Twin Cities, and Faribault participants as an ancillary study (for methods, cf. Chapter V). There was considerable variation in average per cent change from center to center and after different periods on diet. After 12 weeks in the First Study, average decreases occurred in all diet groups in the three centers. Those with higher baseline levels tended to show larger average decreases. Mean levels for each diet continued to fall between 12 and 28 weeks on assigned diet in Faribault and the Twin Cities, but returned to baseline in Oakland. Between 28 and 44 weeks triglyceride levels rose in all three centers; they were still well below baseline in Faribault and the Twin Cities, above baseline in Oakland. This variation in response from center to center over time is not easy to interpret. It may be related to inter-center differences in technical methods (cf. Chapter V). It is clear, however, that the main effect of the hypocholesterolemic diets was to lower serum triglycerides, particularly in men with elevated baseline levels.
Corticotropin-Releasing Factor*
Authors: NAOKI YASUDA, MONTE A. GREER, TORU AIZAWA
Journal: Endocrine Reviews (1982)

IN 1948 Geoffrey Harris (1) hypothesized that stress-induced activation of the central nervous system is transduced from a neural into a humoral signal in the hypothalamus. Resultant chemical transmitter substances elaborated are transported to the adenohypophysis via the hypophyseal portal circulation to stimulate the secretion of ACTH from the corticotrophs. Despite intensive studies by many investigators throughout the world in the intervening years, identification of this putative neurotransmitter has been extremely difficult. Slusher and Roberts (2) were the first to describe ACTH-releasing activity in a hypothalamic extract. Unfortunately, the assay using intact, untreated rats employed in their experiments was inadequately refined (2, 3) since such animals will secrete ACTH in response to a variety of nonspecific stresses. In 1955 more specific experimental evidence for the existence of a brain extract that stimulated ACTH secretion was independently presented by Saffran and Serially (4) and Guillemin and Rosenberg (5). The former group named the putative material corticotropin-releasing factor (CRF). Although this appellation may be unfortunate in some respects, especially since CRF probably stimulates both formation and secretion of ACTH, it is “catchy” and provides a useful mnemonic handle. It has not only survived to the present but has spawned the generic term of “releasing factor” or “releasing hormone” for many hypothalamic materials with hypophysiotrophic activity.
Comparison of hydration events in patients (pts) receiving highly (HEC) or moderately (MEC) emetogenic chemotherapy treated with granisetron extended-release subcutaneous (GERSC) or palonosetron (PALO).
Authors: Jeffrey Vacirca, Dennis Caruana, George Calcanes, Michael Mosier, Ralph V. Boccia, Ali McBride
Journal: Journal of Clinical Oncology (2017)

108 Background: Breakthrough CT-induced nausea and vomiting (CINV) may increase resource needs, eg, hydration. GERSC (SUSTOL) + other antiemetics prevent CINV associated with MEC or anthracycline + cyclophosphamide–based therapy. This retrospective analysis evaluated CINV-related hydration in pts treated with PALO or GERSC antiemetic therapy. Methods: Pts at a multisite community practice had MEC or HEC and a 3-drug antiemetic regimen: NK-1 receptor antagonist (RA), dexamethasone, and 5-HT 3 RA (PALO only, GERSC only, or PALO then GERSC). CT emetogenicity (HEC, MEC), number of cycles, and CINV-related hydration were extracted from medical records. Hydration rate (events per cycle) was analyzed for pts who had PALO vs GERSC (group 1; nonparametric 2-sided Wilcoxon rank sum test) and pts who had PALO then GERSC (group 2; paired t-test). Results: There were 93 PALO, 91 GERSC, and 48 PALO-then-GERSC pts. Group 1 had mean (SD) CT cycles of 5.4 (2.8) on PALO vs 4.1 (2.2) on GERSC. The whole group ( P&lt;.0001) and HEC subgroup ( P&lt;.0001) had significantly higher hydration rates with PALO vs GERSC (Table). Overall, 22% (PALO) vs 58% (GERSC) of pts had no hydration. In HEC/MEC subgroups, respectively, 19%/33% (PALO) vs 60%/56% (GERSC) of pts had no hydration. Group 2 switched pts had mean (SD) 3.5 (3.2) cycles on PALO vs 3.1 (2.2) on GERSC. All pts and MEC subgroup had no differences in hydration rate with PALO vs GERSC. HEC subgroup hydration rates were significantly higher for PALO vs GERSC ( P=.028; Table). Conclusions: In a multisite practice, CINV-related hydration was ~3 times less per CT cycle for pts receiving GERSC vs PALO as part of a 3-drug antiemetic regimen. Pts on HEC and treated with PALO then GERSC had significantly reduced hydration needs with GERSC. Reduced hydration needs may improve quality of life and simplify pt management. [Table: see text]
Rash, neutrophil-lymphocyte ratio (NLR) and survival in the REAL3 trial
Authors: E.C. Smyth, K. Kouvelakis, C. Peckitt, T. Waddell, D. Watkins, S. Rao, N. Starling, C. Saffery, A.F. Okines, I. Chau, D. Cunningham
Journal: Annals of Oncology (2017)
Abstract 15199: L-Citrulline Supplementation Reduces Plasma Arginase Activity in Type 2 Diabetes Patients
Authors: Alia Shatanawi, Munther S Momani, Ruaa Aqtash, Mohammad H Hamdan, Ruth B Caldwell, R. William Caldwell
Journal: Circulation (2015)

Vascular dysfunction is a major cause of morbidity and mortality in diabetic patients. Diabetes has been linked to elevated arginase and associated with vascular endothelial dysfunction. The pathological process is characterized by impaired endothelial cell production of nitric oxide (NO) and/or decreased NO bioavailability. NO is produced by activity of endothelial NO synthase (eNOS) on its substrate L-arginine. Reduced availability of L-arginine to eNOS has been implicated in vascular dysfunction in diabetes. Arginase, which metabolizes L-arginine to urea and ornithine, competes directly with NOS for L-arginine. Hence increases in arginase activity can decrease arginine levels, reducing its availability to eNOS and decreasing NO production. We aimed to determine levels of plasma arginase activity in type 2 diabetic (T2DM) patients and the effects of L-citrulline, a natural arginase inhibitor, on inhibiting arginase activity in T2DM patients. We determined arginase activity levels in 62 T2DM patients and compared it to age matched healthy volunteers (ages 45-65). Our results show that arginase activity is 1.7 fold higher in T2DM patient’s plasma than healthy controls. Levels of arginase correlated with H1AC levels in diabetic patients r=0.81. Twenty five patients received L-citrulline supplements (2000 mg/day) for 1 month. Arginase activity was decreased 30% in T2DM patients after taking L- citrulline supplements. There was a modest improvement on H1Ac levels in these patients. The effect on L-citrulline on arginase activity was also measure in bovine aortic endothelial cells (BAECs) grown in high glucose (HG) conditions. HG (25mM, 72 hrs) caused a 2 fold increase in arginase activity in BAECs and decreased NO production by 40%. L-citrulline 100μM completely prevented the increase in arginase activity and restored NO production levels. These data indicate that inhibiting arginase activity can have therapeutic benefits in diabetic patients by preventing vascular dysfunction and maintaining NO levels.
Opioid utilization patterns among patients with cancer and noncancer pain.
Authors: Catherine J. Datto, Yiqun Hu, Eric Wittbrodt, Perry G. Fine
Journal: Journal of Clinical Oncology (2017)

194 Background: Opioids are used to manage moderate to severe pain in patients with cancer and non-cancer pain. Limited data exist comparing opioid utilization patterns between these two patient populations. Methods: This retrospective, commercial administrative claims database analysis (HealthCore Integrated Research Environment) investigated opioid use patterns, including opioid dose escalation, in adult patients with cancer-related (CP) and non-cancer-related pain (NCP). Adults (age ≥18 years) with at least one pharmacy claim for an opioid between July 1, 2006, and September 30, 2014, were identified (index date). Patients selected for analysis had to have continuous plan eligibility for 6 months pre- and 12 months post-index date and opioid use for at least 4 weeks. Patients with opioid use related to cancer pain were identified by a medical claim for a cancer diagnosis coded within 30 days prior to the index opioid date. Results: A total of 9,209 patients with CP and 409,703 patients with NCP were analyzed. Patients with CP were older than patients with NCP (mean [SD]: 62.6 [12.9] yrs vs. 49.3 [15.3] yrs); other demographics were similar between cohorts. The most common cancer diagnoses were breast, lung, and prostate. Hydrocodone was the most common opioid prescribed for both cohorts. Total mean (SD) days of opioid therapy were 167.1 (341.8) for CP and 196.6 (421.1) for NCP, with similar rates of opioid use for ≥1 year (10.6% for CP; 13.6% for NCP). Median index opioid doses were consistent between the cohorts (CP: 51.7 morphine-equivalent units (MEU); NCP: 45.0 MEU). Median post-index (after the first 30 days) opioid doses were also similar (CP: 55.8 MEU; NCP: 45.3 MEU). Post-index opioid dose reductions occurred in approximately one-third of both cohorts. Opioid dose escalations (up to dose doubling) occurred in 31.8% of CP and 28.3% of NCP patients. More patients died during the follow-up period in the CP cohort (24.1%) compared with the NCP cohort (0.02%). Conclusions: The use of opioids bears many similarities between patients with cancer pain and non-cancer pain, including clinically similar rates of chronic opioid utilization and dose escalation. This study was supported by AstraZeneca.
How do late-stage cancer patients join an early phase clinical trial? A qualitative investigation of the process.
Authors: Sarah Bracey Garrett, Christopher J Koenig, Daniel Paul Dohan
Journal: Journal of Clinical Oncology (2017)

60 Background: Late-stage cancer patients (LSCPs) face complex choices as they exhaust standard treatment options, including whether to seek enrollment in an early phase (EP) clinical trial and how they may engage palliative care. Existing research describes patient-level decisional motivations, but less is known about the process by which patients arrive at decisions and the institutional barriers or facilitators that shape it. We investigate this process and the key barriers and facilitators for initiating an EP trial. Methods: We collected longitudinal, ethnographic data on 96 LSCPs from breast, genitourinary, gastrointestinal, lung, gynecology, and melanoma clinics at two large academic medical centers. We used constant comparative analysis to inductively identify factors that shaped patients’ paths towards or away from EP trial initiation. Results: Four key factors shaped patients’ pathways and help explain why most patients did not join a trial. These arose during two distinct periods. The first, “Setting the Stage,” concerned achieving both (a) patient and (b) physician interest in and support for the patient’s involvement in an EP trial. These achievements depended on the patient’s knowledge and opinions of experimental research, the physician’s awareness of relevant EP trials, and whether the physician considered the patient a good EP candidate, among other influences. The second period, “Securing an Experimental Seat,” concerned aligning (c) the availability of a specific EP trial with (d) the patient meeting the trial’s eligibility requirements. Disease progression, type and timing of past treatments, and dynamic trial enrollment windows all complicated this alignment. Despite the complexity of Securing a Seat, our data suggest that Setting the Stage was the more consequential period in terms of when patients exited the EP trial pathway. Conclusions: Patients’ priorities and decision-making are only one part of a multi-level process. LSCPs’ paths onto an EP trial depend not only on their making a particular decision, but also on relational, clinical and system-level conditions. This suggests that boosting EP trials participation requires interventions on multiple levels.
N-Glycan Profile and Kidney Disease in Type 1 Diabetes
Authors: Mairead L. Bermingham, Marco Colombo, Stuart J. McGurnaghan, Luke A.K. Blackbourn, Frano Vučković, Maja Pučić Baković, Irena Trbojević-Akmačić, Gordan Lauc, Felix Agakov, Anna S. Agakova, Caroline Hayward, Lucija Klarić, Colin N.A. Palmer, John R. Petrie, John Chalmers, Andrew Collier, Fiona Green, Robert S. Lindsay, Sandra Macrury, John A. McKnight, Alan W. Patrick, Sandeep Thekkepat, Olga Gornik, Paul M. McKeigue, Helen M. Colhoun
Journal: Diabetes Care (2017)

Poorer glycemic control in type 1 diabetes may alter N-glycosylation patterns on circulating glycoproteins, and these alterations may be linked with diabetic kidney disease (DKD). We investigated associations between N-glycans and glycemic control and renal function in type 1 diabetes.Using serum samples from 818 adults who were considered to have extreme annual loss in estimated glomerular filtration rate (eGFR; i.e., slope) based on retrospective clinical records, from among 6,127 adults in the Scottish Diabetes Research Network Type 1 Bioresource Study, we measured total and IgG-specific N-glycan profiles. This yielded a relative abundance of 39 total (GP) and 24 IgG (IGP) N-glycans. Linear regression models were used to investigate associations between N-glycan structures and HbA1c, albumin-to-creatinine ratio (ACR), and eGFR slope. Models were adjusted for age, sex, duration of type 1 diabetes, and total serum IgG.Higher HbA1c was associated with a lower relative abundance of simple biantennary N-glycans and a higher relative abundance of more complex structures with more branching, galactosylation, and sialylation (GP12, 26, 31, 32, and 34, and IGP19 and 23; all P < 3.79 × 10-4). Similar patterns were seen for ACR and greater mean annual loss of eGFR, which were also associated with fewer of the simpler N-glycans (all P < 3.79 × 10-4).Higher HbA1c in type 1 diabetes is associated with changes in the serum N-glycome that have elsewhere been shown to regulate the epidermal growth factor receptor and transforming growth factor-β pathways that are implicated in DKD. Furthermore, N-glycans are associated with ACR and eGFR slope. These data suggest that the role of altered N-glycans in DKD warrants further investigation.
Darwin's charm
Authors: Peter Hayward
Journal: The Lancet (2008)

Think Darwin, think finches. That's the way it is. Charles Darwin left Cambridge University, set sail on HMS Beagle, headed straight for the Galapagos archipelago in the Pacific, and while pondering the improbable life residing there he saw the little brown and black birds with their differently shaped bills and "Eureka!"—the theory of evolution hatched right there. Darwin winged it home, wrote On the Origin of Species, and the rest is history. Had it not been for those 14 species of unprepossessing birds, humankind would still be languishing in some intellectual dark age.