tbuckley/cabot-search huggingface dataset:
Quality matters: Patterns of palliative interventions in metastatic colorectal cancer (mCRC) patients.
Authors: Rebecca M. Prince, Shuyin Liang, Mantaj Brar, Stephanie Ramkumar, Adena Scheer, Rebecca Wong, Julie I. Hallet, Camilla Zimmermann, Alexandra Maria Easson
Journal: Journal of Clinical Oncology (2017)

83 Background: Increasing recognition that high-quality end of life care is essential has resulted in internationally endorsed metrics allowing assessment of interventions at the end of life. Median survival for mCRC patients has improved to more than 24 months resulting in increased opportunity to undergo interventions for symptom relief at the end of life. We explored patterns of palliative interventions (chemotherapy, radiotherapy, surgery, endoscopy, drainage procedures) and outcomes in mCRC patients. Methods: A retrospective review was undertaken of all mCRC patients referred to the palliative care service from 2000 to 2010 at a tertiary cancer center in Toronto, Canada. Descriptive statistics, survival analysis and regression were employed. Results: A total of 542 patients were included of whom 52.8% were male, mean age was 62.8 years and 44.6% had stage 4 disease at diagnosis. Over the course of their disease 93.9% had an intervention at any time after their diagnosis including 27.5% of patients undergoing palliative surgery, 77% of patients had an intervention in the last year of life and 19.1% had an intervention in the last 30 days of life. The percentage of patients receiving interventions within the last 14 days of life were 1.23% for chemotherapy, 4.6% for radiotherapy, 0.5% for surgery, 10.4% for endoscopy and 23% drainage procedures. The mean time between referral to palliative care and death was 7 months (SD 10.4). For patients who received chemotherapy, the mean time between last chemotherapy and death was 9.5 months (SD 14.9). Overall survival for patients who did not receive chemotherapy was 28 months (SD 33) compared with 40 months (SD 32) for those who received chemotherapy. Regression analysis for risks of dying within 30 days of chemotherapy was limited by a low event rate. Increasing age was significantly associated with a lower risk of dying within 30 days of chemotherapy. Conclusions: In their final months of life, palliative mCRC patients undergo a significant number of interventions aiming to improve quality of life. These require considerable multi-disciplinary input with ramifications for quality care, planning for service provision and funding.
C/EBPα‐dependent preneoplastic tumor foci are the origin of hepatocellular carcinoma and aggressive pediatric liver cancer
Authors: Ashley Cast, Leila Valanejad, Mary Wright, Phuong Nguyen, Anita Gupta, Liqin Zhu, Soona Shin, Nikolai Timchenko
Journal: Hepatology (2017)

Recent publications show that classic hepatoblastoma (HBL) is the result of failure of hepatic stem cells to differentiate into hepatocytes, while hepatocellular carcinoma (HCC) is caused by the dedifferentiation of hepatocytes into cancer stem cells. However, the mechanisms of aggressive HBL and the mechanisms that cause dedifferentiation of hepatocytes into cancer stem cells are unknown. We found that, similar to HCC but opposite to classic HBL, aggressive HBL is the result of dedifferentiation of hepatocytes into cancer stem cells. In both cases of liver cancer, the dephosphorylation of tumor suppressor protein CCAAT/enhancer binding protein α (C/EBPα) at Ser193 (Ser190 in human protein) or mutation of Ser193 to Ala results in a modified protein with oncogenic activities. We have investigated liver cancer in a mouse model C/EBPα‐S193A, in a large cohort of human HBL samples, and in Pten/p53 double knockout mice and found that these cancers are characterized by elevation of C/EBPα that is dephosphorylated at Ser190/193. We found that dephosphorylated C/EBPα creates preneoplastic foci with cancer stem cells that give rise to HCC and aggressive HBL. C/EBPα‐dependent dedifferentiation of hepatocytes into cancer stem cells includes increased proliferation of hepatocytes, followed by generation of multinucleated hepatocytes and subsequent appearance of hepatocytes with delta‐like 1 homolog–positive intranuclear inclusions. We further isolated C/EBPα‐dependent multinucleated hepatocytes and found that they possess characteristics of tumor‐initiating cells, including elevation of stem cell markers. C/EBPα‐dependent cancer stem cells are observed in patients with aggressive HBL and in patients with a predisposition for liver cancer. Conclusion: The earliest steps of adult HCC and aggressive pediatric liver cancer have identical features that include conversion of the tumor suppressor C/EBPα into an oncogenic isoform, which further creates preneoplastic foci where hepatocytes dedifferentiate into cancer cells, giving rise to liver cancer. (H epatology 2018;67:1857‐1871).
Urgent versus elective inpatient anticancer therapy in patients with metastatic solid tumors: Analysis of admission characteristics and posthospitalization clinical outcomes.
Authors: Jordan P. McPherson, Halee R. Namanny, Jamie L. Brant, Paige A. Patterson, Julie A. Howell, Brighton A. Loveday, Rachel M. Montague, Jaclyn J. Piper-Williams, Jennifer S. Shaw, Jill E. Sindt, Paul D. Thielking, Joseph E. Biskupiak, Anna Catherine Beck, David D. Stenehjem
Journal: Journal of Clinical Oncology (2017)

12 Background: Palliative chemotherapy is used urgently in the hospital due to rapid disease progression, risk of toxicity, or other cancer-related acute medical diagnoses. Our primary objective was to characterize the utilization of urgent anticancer therapy (antiCT) in metastatic solid tumor patients. Secondary objectives were to compare time to next treatment (TTNT) and overall survival (OS) between those who received antiCT during urgent and elective admissions, and to further characterize if goals of care (GOC) or prognosis discussions were included in the decision process. Methods: This was a single-center observational cohort study of patients with advanced solid tumors treated with antiCT during urgent versus elective inpatient admissions at Huntsman Cancer Institute from June 1, 2014 to June 30, 2016. Line of therapy, ICU utilization, readmission rate, palliative care (PC) consultation, and documentation of GOC and prognosis discussions were evaluated for patients who received urgent antiCT. Results: 265 patients were included. The majority were treated during urgent admissions (63.7%). Patients receiving urgent antiCT were older (57.6 ± 14.2 vs 54.9 ± 14.9 years, p &lt; 0.001) with more advanced cancer at diagnosis (56.8% vs 37.5%, p = 0.009). Urgent antiCT was associated with both decreased median TTNT (3.5 vs 15.7 months; p &lt; 0.001) and median OS (4.7 vs 31.4 months; p &lt; 0.001) as compared to elective antiCT. Of those who received urgent antiCT, 47.9% were started on a new antiCT during admission. First-line therapy accounted for 58% of urgent antiCT, and 27.2% was third-line or higher. ICU care was utilized for 20.7% of these patients, and 23.1% were readmitted ≤30 days after discharge. PC was consulted for 37.9% during admission. Less than half (41.4%) had a documented GOC discussion; only 32.5% had a documented prognosis discussion. Conclusions: Urgent inpatient antiCT is associated with suboptimal advance care planning despite high risk of mortality in the 5 months following admission. Efforts to identify predictors of early mortality after urgent antiCT and incorporate earlier GOC and prognosis discussions are warranted.
Loss of control is not necessary to induce behavioral consequences of deprivation: The case of religious fasting during Ramadan
Authors: Mostafa Salari Rad, Jeremy Ginges
Journal: Behavioral and Brain Sciences (2017)

Abstract Pepper &amp; Nettle argue that the more present-oriented behavior associated with a low socioeconomic status is an adaptive response to having relatively little control over the future. However, a study of fasters during Ramadan shows that self-imposed deprivation, which carries no implications regarding the ability to realize deferred rewards, is associated with loss and risk aversion.
Undernutrition and severe acute malnutrition in children
Authors: Suparna Ghosh-Jerath, Archna Singh, Nameet Jerath, Suruchi Gupta, Elizabeth F Racine
Journal: BMJ (2017)

#### What you need to know

Undernutrition contributes to nearly 45% of all deaths in children under 5 years old globally.1 Low and middle income countries are worst affected.2 Treatment services are estimated to reach less than 15% of undernourished children.3 Healthcare providers can play a crucial role in identifying undernutrition in children and ensuring appropriate care and referral.

We provide an overview of assessment and initial management of undernutrition in children under 5 years of age. For the purpose of this paper, we focus on severe acute malnutrition, when children are at increased risk of medical complications unless diagnosed and managed promptly.

Undernutrition results from insufficient intake of energy foods (carbohydrates, fats), proteins, and micronutrients (vitamins and minerals).4 Energy and protein malnutrition can manifest clinically as marasmus, kwashiorkor, and marasmic-kwashiorkor (see fig 1⇓ and fig 2⇓). The current World Health Organization guidelines subsume these entities into the blanket term “severe acute malnutrition,” and its variants with or without medical complications.5 Acute malnutrition results from hunger or disease, or both, and is associated with rapid weight loss or failure to gain weight. Box 1 outlines the subclinical and clinical forms of undernutrition. Iron, iodine, vitamin …
The Role of Peers for Diabetes Management in Adolescents and Emerging Adults With Type 1 Diabetes: A Longitudinal Study
Authors: Koen Raymaekers, Leen Oris, Sofie Prikken, Philip Moons, Eva Goossens, Ilse Weets, Koen Luyckx
Journal: Diabetes Care (2017)

OBJECTIVE The increasing importance of peers in adolescence and emerging adulthood has been widely acknowledged. However, longitudinal research linking the peer context to diabetes management and outcomes is scarce. The present longitudinal study in a large sample of youths with type 1 diabetes related both positive and negative peer variables to diabetes outcomes over a time interval of 1 year. RESEARCH DESIGN AND METHODS Our sample consisted of 467 adolescents (14–17 years of age) and emerging adults (18–25 years of age) with type 1 diabetes who participated in a two-wave longitudinal study. Questionnaires tapped into peer support, extreme peer orientation, parental responsiveness, diabetes-related distress, and treatment adherence. HbA1c values were obtained from the treating physicians of patients. Cross-lagged analysis from a structural equation modeling approach was performed to assess the directionality of effects. RESULTS Peer support negatively predicted diabetes-related distress over time. Extreme peer orientation positively predicted treatment distress over time. Parental responsiveness negatively predicted food distress over time. Treatment adherence negatively predicted extreme peer orientation, treatment distress, and HbA1c values over time. For emerging adults specifically, there was a reciprocal relationship between HbA1c values and extreme peer orientation because they positively predicted each other. CONCLUSIONS This study highlights the importance of peers in predicting the functioning of youths with type 1 diabetes. Additionally, treatment adherence at baseline was found to negatively predict extreme peer orientation, treatment distress, and worse glycemic control over time. In sum, the current study underscores the importance of the peer context for adolescents and emerging adults with type 1 diabetes.
Vigilancia de la listeriosis en Europa
Authors: H de Valk, C Jacquet, V Goulet, V Vaillant, A Perra, F Simon, J C Desenclos, P Martin
Journal: Eurosurveillance (2005)

Ademas del impacto economico y de la amenaza asociada con los brotes, la listeriosis representa un problema importante de salud publica, debido a su tasa de letalidad entre las mas altas de todas las infecciones transmitidas por alimentos (20-30%), y a su alto potencial epidemico. La evolucion de los metodos de produccion de los alimentos, asi como la distribucion y el abastecimiento, facilitaron la ocurrencia de brotes afectando a numerosos paises. 
En 2002, se llevo a cabo un estudio para evaluar la necesidad y viabilidad de una red europea sobre infecciones humanas por Listeria. Los datos sobre los sistemas de vigilancia y los metodos de laboratorio se recogieron mediante dos cuestionarios enviados a los Centros Nacionales de vigilancia de enfermedades transmisibles y a los laboratorios de referencia de Listeria. En 16 paises entre los 17 entrevistados, existian sistemas de vigilancia de la listeriosis y 16 paises tenian un laboratorio nacional de referencia (LNR). En todos los paises, la definicion de caso estaba basada en el aislamiento de Listeria monocytogenes. Catorce LNR realizaban al menos un metodo de tipado de las cepas humanas. Trece paises por lo menos ya llevaban a cabo, o estaban por hacerlo, la caracterizacion de los aislamientos de las cepas humanas por electroforesis en gel de campo pulsado (PFGE) segun un protocolo estandardizado. Para los paises participantes, la existencia de una red de vigilancia europea de la listeriosis supondria un valor anadido, especialmente para la deteccion e investigacion de brotes. Tambien confirmaron la viabilidad de una red de vigilancia basada en los programas nacionales existentes.
Change over time in the rates of adverse events in patients receiving systemic therapy for psoriasis: A cohort study
Authors: Miguel Angel Descalzo, Gregorio Carretero, Carlos Ferrándiz, Raquel Rivera, Esteban Daudén, Fran J. Gómez-García, Pablo de la Cueva, Enrique Herrera-Ceballos, Isabel Belinchón, José Luis López-Estebaranz, Mercè Alsina, José Luis Sánchez-Carazo, Marta Ferrán, Ofelia Baniandrés, José Manuel Carrascosa, Mar Llamas-Velasco, Diana Ruiz-Genao, Enrique Herrera-Acosta, Carlos Muñoz-Santos, Ignacio García-Doval
Journal: Journal of the American Academy of Dermatology (2017)
Development of high specific activity 68Ga-labeled DOTA-rhenium cyclized alpha-MSH peptide analog to target MC1 receptors over-expressed by melanoma tumors
Authors: Melchor Cantorias, Thomas Quinn, John Lever, Timothy Hoffman, Lisa Watkinson, Terry Carmack, Said Figueroa, Cathy Cutler
Journal: Cancer Research (2008)

3165   MC1 receptors, known to be over-expressed in melanoma cells, are attractive targets for diagnosis and therapy of metastatic melanoma, a form of skin cancer with an increasing incidence and the third most commonly diagnosed cancer in the United States. Studies have shown that  68 Ga-DOTA-Re(Arg 11 )CCMSH has potential for targeting MC1 receptors to achieve early detection of malignant melanoma by PET. Because the half-life of  68 Ga is very short (68 min), the conventional method for labeling bioactive peptides through water-bath incubation for 30 - 60 min becomes a limiting factor in labeling, purification, and characterization of  68 Ga melanoma agent within an acceptable time. Currently, our laboratory is equipped with a remote monomodal microwave that allows us to perform labeling in mere seconds. We labeled a metal-cyclized α-MSH peptide analog, DOTA-Re(Arg 11 )CCMSH, with  68 Ga in 0.4 M NH 4 OAc (pH 5) using the remote microwave at 100 W for 60 s, followed by reversed-phase HPLC purification for 20 min. The treatment of B16/F1 melanoma-bearing C57 mice with  68 Ga-DOTA-Re(Arg 11 )CCMSH afforded favorable results from our biodistribution study :  % ID/g values for tumor uptake at 30 min, 1 h, and 4 h p.i. were 6.93 ± 1.11, 6.27 ± 1.60, and 5.85 ± 1.32, respectively. The peak tumor to kidney uptake ratio was 1.13 at 4 h p.i.. The kidneys were the main excretion pathway of  68 Ga-DOTA-Re(Arg 11 )CCMSH. A blocking study resulted in 84 % lower uptake in the tumor at 1 hr showing evidence of receptor-mediated process. Clearance rate of radioactivity was fast in normal organs (e.g. blood uptake: 2.41 ± 2.66 %ID/g at 30 min p.i. vs. 0.44 ± 0.03 %ID/g at 1 h p.i.). Tumor to non-target organ ratios were also favorable (e.g. tumor : blood = 14.25 at 1 h p.i.; tumor : muscle = 89.57 at 1 h p.i.). Consequently, microPET study produced superb tumor images due to the high tumor/background ratios and high tumor retention. In conclusion, we have demonstrated that  68 Ga-DOTA-Re(Arg 11 )CCMSH is readily prepared, and has promise as a PET imaging agent for early detection and staging of metastatic melanoma.
The behavioural constellation of deprivation: Compelling framework, messy reality
Authors: Martin Daly, Dandara Ramos, Gretchen Perry
Journal: Behavioral and Brain Sciences (2017)

Abstract Pepper &amp; Nettle's (P&amp;N's) argument is compelling, but apparently contradictory data are easily found. Associations between socioeconomic status (SES) and substance abuse are sometimes positive, the poor are sometimes eager to educate their children, and perceptions of local mortality risk can be so distorted as to constitute an implausible basis for contextually appropriate responding. These anomalies highlight the need for more psychological work.
Cultural consonance, deprivation, and psychological responses for niche construction
Authors: Robert J Quinlan
Journal: Behavioral and Brain Sciences (2017)

Cultural consonance is a measure of culturally encoded goals relevant to psychological, behavioral, and health responses to deprivation. Similar to extrinsic mortality, low cultural consonance and an associated inability to predict adaptive outcomes may activate impulsivity, delay discounting, and reward seeking. Low cultural consonance could promote "fast life history" in low-quality environments and motivate cultural niche construction for local adaptation.
Osimertinib vs standard of care (SoC) EGFR-TKI as first-line treatment in patients with EGFR-TKI sensitising mutation (EGFRm) positive advanced non-small cell lung cancer (NSCLC): FLAURA Asian subset
Authors: B.C. Cho, B. Chewaskulyong, K.H. Lee, A. Dechaphunkul, V. Sriuranpong, F. Imamura, Y. Ohe, N. Nogami, T. Kurata, I. Okamoto, C. Zhou, Y. Cheng, E.K. Cho, V.P. Jye, J.-S. Lee, H. Mann, M. Saggese, T. Reungwetwattana
Journal: Annals of Oncology (2017)
Serum Activity of Macrophage-Derived Adenosine Deaminase 2 Is Associated With Liver Fibrosis in Nonalcoholic Fatty Liver Disease
Authors: Z. Gordon Jiang, Bynvant Sandhu, Linda Feldbrügge, Eric U. Yee, Eva Csizmadia, Shuji Mitsuhashi, Jinhe Huang, Nezam H. Afdhal, Simon C. Robson, Michelle Lai
Journal: Clinical Gastroenterology and Hepatology (2017)
Time to ask patients about drugs for macular degeneration
Authors: John W Mackenzie
Journal: BMJ (2017)

Two of the three treatments we have for wet adult onset macular degeneration are manufactured by the same company—Roche/Novartis. As Cohen explains, now that non-inferiority of outcomes is known, the extreme difference in price continues to cause consternation.1

European law, which exists to protect the public from inferior imports and to promote production of high quality drugs, stipulates that when a drug with marketing …
Abstract 20397: Linking Improved Processes of Care With Timeliness of Intravenous Diuresis for Acute Heart Failure
Authors: Alisa Maznytsya, Caitlin Chang, Sara Brade, Natalia Persad, Talal Al-Jabbary, Chaim Bell, Douglas S Lee, Andrew Wyllie, Susanna Mak
Journal: Circulation (2016)

Background:  Intravenous administration of loop diuretics is a cornerstone of therapy for acute heart failure. We developed the MSH La6 Protocol, a tool to standardize practices for administration, monitoring and dose adjustment of IV furosemide over a 48-hour period. The tool also delegated autonomy to the nurse at the point of care to conduct all actions associated with the La6 Protocol, with the intent of minimizing delays arising from frequent consultation with ordering physicians. The safety and impact of this initiative on markers of quality heart failure care and timeliness of furosemide administration were evaluated.   Methods:  A pre- and post-implementation time series study analysis was performed. The primary process measure was adherence to daily monitoring of patients receiving IV loop diuretics and was evaluated using composite opportunity and all-or-none scores as well as Shewhart control charts. Outcome measures consisted of the doses of furosemide administered in the first 48 hours of admission to hospital, separated into two 24-hour blocks. Incidence of hypokalemia and increase in serum creatinine as evidence of AKI were evaluated as markers of safety.   Results:  Between the pre (32 months, n=338) and post (8 months, n=121) implementation period, a significant and stable improvement was observed in the opportunity-based composite score from a mean of 82% to 90% and the all-or-none score from 30% to 57% using Shewhart control charts. Within the pre-implementation cohort, the mean furosemide dose significantly decreased between the 0-24 and 24-48h time block, while no such change was observed within the post-implementation cohort. A significantly larger proportion of patients treated using the La6 Protocol had a dose increase in the 24-48 hour block versus patients treated with usual care. There were no serious adverse events and no deaths. There was no increase in the incidence of hypokalemia or evidence of AKI in the post-implementation cohort.   Conclusions:  An intervention that resulted in improved adherence to practices for monitoring was also associated with the observation that furosemide dosage was up titrated more frequently early during hospital admission.
Incretin-Based Therapies and the Short-term Risk of Pancreatic Cancer: Results From Two Retrospective Cohort Studies
Authors: Mathieu Boniol, Matteo Franchi, Maria Bota, Agnès Leclercq, Joeri Guillaume, Nancy van Damme, Giovanni Corrao, Philippe Autier, Peter Boyle
Journal: Diabetes Care (2017)

OBJECTIVE Concerns have been raised about a possible increased risk of pancreatic cancer associated with incretin-based therapies. We examined the risk of pancreatic cancer among patients with diabetes prescribed incretin drugs. RESEARCH DESIGN AND METHODS With the use of public health insurance databases of Belgium and the Lombardy Region, Italy, we created two retrospective cohorts that included adult patients who were first prescribed an incretin drug or another noninsulin antidiabetic drug (NIAD) from 1 July 2008 to 31 December 2013 in Belgium and from 1 January 2008 to 31 December 2012 in the Lombardy Region. The risk of pancreatic cancer was evaluated by multivariate-adjusted Cox models that included time-dependent variables. Adjusted hazard ratios (aHRs) from Belgium and Italy were pooled by using fixed-effects meta-analyses. RESULTS The cohorts included 525,733 patients with diabetes treated with NIADs and 33,292 with incretin drugs. Results in both cohorts were similar. Eighty-five and 1,589 subjects who developed pancreatic cancer were registered among the incretin and NIAD new users, respectively, which represented an aHR of pancreatic cancer of 2.14 (95% CI 1.71–2.67) among those prescribed an incretin compared with an NIAD. The aHR with a drug use lag exposure of 6 months was 1.69 (1.24–2.32). The aHR decreased from 3.35 (2.32–4.84) in the first 3 months after the first incretin prescription to 2.12 (1.22–3.66) in months 3–5.9, 1.95 (1.20–3.16) in months 6–11.9, and 1.69 (1.12–2.55) after 12 months. Among those prescribed an NIAD, pancreatic cancer occurred mostly within the year after the first prescription. The risk of pancreatic cancer among patients subsequently prescribed insulin was 6.89 (6.05–7.85). CONCLUSIONS The recent prescription of incretin therapy is associated with an increased risk of pancreatic cancer. The reason for such an increase is likely the consequence of an occult pancreatic cancer that provokes or aggravates diabetes. Studies are warranted for assessing the risk of pancreatic cancer associated with long-term use of incretin drugs.