tbuckley/cabot-search huggingface dataset:
Storage, disposal, and utilization of opioids among cancer outpatients.
Authors: Akhila Sunkepally Reddy, Maxine Grace Jaucian De La Cruz, Eden Mae Rodriguez, Jessica Thames, Jimin Wu, Gary B. Chisholm, Diane Liu, Susan Frisbee-Hume, Hilda Cantu, Alejandra Marin, Vicki Gayle, Nancy Shinn, Angela Xu, Janet L. Williams, Sriram Yennurajalingam, David Hui, Eduardo Bruera
Journal: Journal of Clinical Oncology (2013)

222 Background: Prescription opioid abuse is an epidemic in the US. Of the abusers, 75% obtain the opioid from a friend or relative, which may be related to improper opioid storage and disposal practices. Our aim was to determine patients’ practices of opioid use, storage, and disposal. Methods: We surveyed 300 cancer outpatients presenting to our Supportive Care Center who were receiving opioids for at least 1 month and collected information regarding opioid use, storage, and disposal along with patient characteristics and scores on Cut-down, Annoyed, Guilty, Eye-opener (CAGE) questionnaire for alcoholism. Sharing or losing their opioids was defined as an unsafe use. Results: The median age of the patients was 57 years; 53% were female, 72% were white, and 63% were married. Most (89%) had advanced cancer, and lung cancer was the most common (22%). CAGE was positive in 19%, 9% had history of illicit drug use, and 36% lived with adult/young adult children. Of the 300 respondents, 19% stored opioids in the open, 69% kept opioids hidden but unlocked, and 9% locked their opioids. Patients with history of CAGE positivity (P=.007), illicit drug use (.0002), smoking (P=.03), and those living with adult children (P=.004) were more likely to keep their opioids locked. 66% were unaware of proper opioid disposal methods. 46% had unused opioids at home. 53% did not routinely dispose opioids, of whom 44% saved them for future use. 26% indulged in unsafe use by sharing (9%) or losing (17%) their opioids, and 44% informed their family and friends that they were on pain medications. 39% were unaware that their opioid could be fatal when taken by others. Compared with married patients, those who were never married [OR=2.92; 95% CI 1.48-5.77], separated [OR=11.38; 1.52-112.5], or divorced [OR=1.27; 0.55-2.91] had higher odds of unsafe use (P=.006). CAGE positivity (40% vs. 21%, P=.003) and illicit drug use (42% vs. 23%, P=.031) were also significant predictors of unsafe use. Conclusions: An alarming proportion of patients improperly and unsafely use, store, and dispose of opioids. Patient education by physicians/pharmacists and creation of more drug take back programs may reduce availability of prescription opioids for potential abuse. More research is needed in this area.
The clinical relevance of telomerase activity and telomere length in pediatric solid tumors
Authors: I. Yaniv, A. Ohali, S. Avigad, I. J. Cohen, Y. Goshen, S. Ash, D. Luria, M. Feinmesser, I. Meller, J. Issakov, R. Zaizov
Journal: Journal of Clinical Oncology (2005)

8547 Background: Maintenance of telomeres, in the majority of cases by reactivation of telomerase, is obligatory for the indefinite proliferation of tumor cells. In some tumors, telomeres are maintained by a telomerase independent mechanism known as alternative lengthening of telomeres (ALT). Telomerase activity (TA) has been already established as a prognostic marker in adult and pediatric malignancies, but the clinical significance of telomere length (TRF) has not been yet determined. Methods: TA (TRAP analysis) and TRF (southern blotting) were evaluated in pediatric solid tumors: neuroblastoma (NBL), Ewing sarcoma (ES) and rhabdomyosarcoma (RMS) and correlated to progression and prognosis. Results: High TA was detected in 52% (26/50) of NBL, 71% (15/21) ES and 40% (6/15) RMS primary tumors. In NBL a significant correlation between TA and outcome was detected (p=0.006) at diagnosis. In ES, 88 PBL samples were analyzed for minimal residual disease by TA during a long follow up (median 60 months). Highly significant association was observed between high TA and subsequent relapse (p>0.0001), predicting relapse before overt clinical progression. Shorter telomeres were detected in 46% (18/39) NBL and correlated with favorable prognosis (p=0.01). In the group of patients over one year of age, TA and TRF, each individually, defined two prognostic groups with favorable and adverse outcome. By multivariate analysis of known prognostic factors, TRF remained the only independent predictive variable. In RMS, preliminary results suggest that ALT is the predominant mechanism of telomere maintenance in embryonal RMS, while in alveolar RMS both telomerase dependent mechanism and ALT may be prevalent, reflecting the difference in prognosis in the two subgroups. Conclusions: Low and high TA were found to be of significant favorable and adverse prognosis, respectively, in NBL at diagnosis and in ES during follow up. Telomere length is a strong prognostic parameter in NBL patients, particularly in children older than one year. We recommend to include TA and TRF analyzes in the diagnostic investigations of NBL and ES. No significant financial relationships to disclose.
Abstract P068: Obstructive Sleep Apnea is Associated with an Increase Risk of Osteoporosis
Authors: Anawin Sanguankeo, Sikarin Upala
Journal: Circulation (2015)

Background: Obstructive sleep apnea (OSA) is thought to be a systemic disease and has been associated with many disorders such as metabolic, endocrine, and especially cardiovascular diseases. One of the consequences of OSA is hypoxia, which can lead to a reduction in growth of osteoblast and a stimulation of osteoclast. Our meta-analysis was conducted to determine the risk of osteoporosis in patients with OSA compared to controls. Objectives: Eligible studies assessing the effects of obstructive sleep apnea on osteoporosis risk were comprehensively searched in PubMed/MEDLINE, EMBASE, and CENTRAL from their inception to September 2014. Two authors independently assessed article quality and extracted the data. Primary outcome were number of participants, prevalence, or risk ratio of osteoporosis in OSA and controls. Results: From 40 full-text articles, 3 studies involving 113,090 participants were included in the meta-analysis that were based on the random effects model. Compared with controls, participants who were diagnosed with obstructive sleep apnea had increased risk of osteoporosis (pooled risks ratio, 1.85; 95% CI, 1.34, 2.56). Conclusion: Patients with OSA had a higher risk of developing osteoporosis. Further study is needed to evaluate the possible mechanisms between these two conditions and to find potential treatment for OSA that could prevent osteoporosis.
OC-008 A 3D primary tumour drug screen identifies hedgehog signalling as a key regulator of intestinal cancer stem cell quiescence and tumorigenesis
Authors: S Popova, E Burley, DJ Winton, SJA Buczacki
Journal: Gut (2015)

<h3>Introduction</h3> Tumour dormancy and cellular quiescence have recently been strongly implicated in disease recurrence after adjuvant therapy in colorectal cancer (CRC). CRC is increasingly recognised as a heterogeneous disease with significant implications for medical and surgical management. Little is known about the control of cellular quiescence and the molecular features of dormant cells in CRC. Here we present the molecular and functional features of dormant intestinal tumour cells and describe the paracrine signalling pathways that govern their behaviour. <h3>Method</h3> Transgenic Apc<sup>1322t</sup>/H2BYFP mice were generated to allow the characterisation, both functionally and molecularly of dormant tumour cells. A drug screen was performed on <i><i>ex vivo</i></i>3D matrigel-cultured tumour spheroids. Proliferation kinetics, growth characteristics and molecular alterations were correlated with known signalling pathways implicated in intestinal tumorigenesis. Selected compounds were then advanced to validation using six human colorectal cancer cell lines, that represent the three main subtypes of CRC, in 2D and 3D culture experiments. <h3>Results</h3> Dormant tumour cells represent a small population of tumour cells that are highly clonogenic, chemoresistant and share many features similar to reserve intestinal stem cells. The Hedgehog and BMP pathways play a dominant role in controlling the growth of tumour spheroids in culture. Antagonism of the Hedgehog pathway causes spheroid growth collapse, the activation of dormant tumour cells and yet no cytotoxicity. The effects of Hedgehog antagonism appears to be CRC sub-type specific; with the most marked effects in the commonest CCSN1 (CIN) subtype of CRC. <h3>Conclusion</h3> Here we provide the first molecular and functional characterisation of dormant tumour cells, showing them to represent the hypothesised quiescent cancer stem cell. Interestingly, our data confirms that of others, in demonstrating Wnt inactivation fails to effect the growth of Apc-mutant tumour cells. However we show that the Hedgehog pathway appears to control not only spheroid growth at a global level but also and uniquely the activation of dormant tumour cells. Manipulation of the Hedgehog pathway in combination with standard-of-care chemotherapy may provide significant benefits for patients with classical Apc-mutated and Wnt driven CRC. <h3>Disclosure of interest</h3> None Declared. <h3>References</h3> Buczacki SJ, Zecchini HI, Nicholson AM, <i>et al</i>. Intestinal label-retaining cells are secretory precursors expressing Lgr5. Nature 2013;495(7439):65–9 Buczacki SJA, Davies RJ. The confounding effects of tumour heterogeneity and cellular plasticity on personalized surgical management of colorectal cancer. Colorectal Dis. 2014;16(5):329–31
Dose-dense and sequential combination of epirubicin and cyclophosphamide followed by paclitaxel and gemcitabine ± trastuzumab as neoadjuvant chemotherapy in stage II and III breast cancer. A phase II and pharmacogenomic study
Authors: P. Sanchez-Rovira, B. Duenas, M. Cidraque, R. Duenas, A. Jaen, A. Sanchez, E. Martinez, B. Medina, E. Carrasco, A. Lozano
Journal: Journal of Clinical Oncology (2004)

608 Background: We conducted a phase II study to determine the efficacy in terms of clinical and pathologic response of a combination of epirubicin and cyclophosphamide followed by paclitaxel and gemcitabine in a sequential and dose dense schedule. In addition, patients with Her2-neu overexpression received trastuzumab during the second sequence. A pharmacogenomic study is ongoing to correlate gene clusters with the clinical and pathological response. Methods: Patients with histologically confirmed invasive breast cancer stages II and III were included. A biopsy was performed before treatment for the microarrays study. Treatment consisted of a first sequence with epirubicin 90 mg/m2 and cyclophosphamide 600 mg/m2 for 3 cycles, and a second sequence with paclitaxel 150 mg/m2 and gemcitabine 2500 mg/m2 for six cycles. All drugs were administered on day 1, every 2 weeks with prophylactic growth factors support. In addition, weekly trastuzumab was administered at a dose of 4 mg/kg in the first infusion and 2 mg/kg in the following ones, concomitantly with paclitaxel and gemcitabine in patients with Her2-neu overexpression. Results: Thirty patients have been included so far. Median age was 46. They were staged as T2: 14 patients, T3: 4 patients, and T4: 12 patients. 15 patients were clinically node negative before treatment. Main toxicities per patient were neutropenia grade III-IV (3%), nauseas and vomiting grade III 12%, myalgia grade II (6%) and skin grade II toxicity (3%). No cardiac toxicity was found confirmed by left ventricular ejection fraction. Clinical response was very high, with 9/26 (34,6%) and 15/26 (57,7%) complete and partial responders. Pathological data is available for 21 patients to date, with 6 patients achieving pCR (28,6%). Five patients were Her2-neu overexpresers (1 pCR and 1 microscopic residual disease were found within them). Conclusions: These preliminary results show a high response rate for a group of patients with predominantly advanced breast cancer, and low toxicity. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eli Lilly & Co. Eli Lilly & Co. Eli Lilly & Co. Eli Lilly & Co.
Four hour waiting time for acute psychiatric care urged
Authors: Anne Gulland
Journal: BMJ (2016)

A new waiting time target for admission to acute psychiatric care of four hours should be introduced, a commission convened by the Royal College of Psychiatrists has said.1

The commission warned that access to acute care for severely ill adult mental health patients was “inadequate nationally and, in some cases, potentially dangerous.” There were major problems both in admissions to psychiatric wards and in providing alternative care and treatment in the community, it added.

The commission asked for a new waiting time pledge to be included in the NHS Constitution from October 2017. It wants a maximum four hour wait for admission to an acute psychiatric ward or …
Genetics for the Human Race
Authors: Myles Axton, Francis Collins, Charles Rotimi, Charmaine Royal, Daniel Drell David Goldstein, Georgia Dunston, Rick Kittles, Lynn Jorde, Mildred Cho, Joanna Mountain, Ari Patrinos, Neil Risch, Shomarka Keita, Kenneth Kidd, Mark Shriver, Sarah Tishkoff
Journal: Nature Genetics (2004)
Vastus lateralis proteomic analysis in muscle wasted patients with COPD
Authors: Roberto Rabinovich, Lakhdar Ramzi, Ellen Drost, Ricardo Bastos, William MacNee
Journal: European Respiratory Journal (2013)

Muscle wasting, that is present in a subgroup of patients with COPD, is an independent predictor of health related quality of life and survival. The two-dimensional fluorescence difference in gel electrophoresis (2D-DIGE) technology is recognized as an accurate method to determine/quantify proteins.  With the aim of identifying proteins potentially involved in the process of muscle wasting, we performed 2D-DIGE protein expression profiling in the vastus lateralis of 10 patients with COPD and low fat free mass index (FFMI) (COPD L ) (FEV 1  33±4.3 %pred, FFMI 15±0.2 Kg.m -2 ) in comparison with both 8 patients with preserved FFMI (COPD N ) (FEV 1  47±7.3 %pred, FFMI 19±0.6 Kg.m -2 ) and 9 age and gender-matched healthy sedentary subjects (C) (FEV 1  96±4.0 %pred, FFMI 20±0.9 Kg.m -2 ). Data analysis was performed using DeCyder software and for protein identification MALDI_TOF mass spectrometry (MS).  Ten proteins, whose expression was significantly changed in COPD L , were identified; serum albumin (ALBU), heat shock protein beta-1 (HSPB1), peroxiredoxin-6 (PRDX6), Alpha-crystallin B chain (CRYAB) and Alpha-1-antitrypsin (A1AT) were increased while Histone-lysine N-methyltransferase (DOT1L), Troponin T (TNNT1), Myozenin-1 (MYOZ1), Myosin light chain 1 (MYL1) and mitochondrial ATP synthase subunit alpha (ATPA) were decreased.  Our results showed a down-regulation of structural muscle proteins, proteins involved in myofibrillogenesis, cell cycle arrest and energy production and up-regulation of proteins reacting to cell stress and proteins involved in oxidative stress protection.  Supported by Chief Scientist Office (CSO) Scotl06/S1103/5 and FIS PI08/0320.  Dr. Ramzi Lakhdar was supported by an ERS long term research fellowship.
Gestational trophoblastic disease in Nepalese women managed in B. P. Koirala Memorial Cancer Hospital
Authors: J. Pariyar
Journal: Journal of Clinical Oncology (2009)

e16570 Background: Gestational trophoblastic disease (GTD) is potentially curable disease. Its incidence varies in different countries with high incidence reported in Japan (2/1000 pregnancies) and Mexico (2.5/1000 pregnancies). No studies have been reported regarding epidemiology, management and outcome of GTD in Nepal. Methods: The study was a descriptive case series. Case records of GTD patients attending B.P. Koirala Memorial Cancer Hospital, Nepal from 2001 to 2007 were analyzed. The main outcomes were measured in terms of duration, antecedent pregnancy, investigations, treatment and follow-up. Results: A total of 45 cases of gestational trophoblastic disease (GTD) were received from 26 districts of Nepal. The age of the patients ranged from 16 to 50 years with a mean age of 29.1 years (SD 9.4 years). Out of 45 cases 19 (43%) were of Tibeto-Burmese ethnic group and 15 (33%) belonged to Indo-Aryan ethnic group. There were 17 cases (37.8%) of hydatidiform mole, 6 were invasive mole (13.35%), 4 of persistent gestational trophoblastic tumour (8.8%) and 22 patients (48.8%) of choriocarcinoma. In 7 cases (15.5%) molar pregnancy had occurred in the first conception, another 7 cases (15.5%) had previous molar pregnancy and in 16 (35.5%) cases GTD had occurred following abortion. The most common presenting symptom was vaginal bleeding and 26 (57.8%) patients had anaemia. Theca Leuteal cyst was present in 11 (24.5%), 17 (37.8%) cases had lung metastasis, 4 (8.9%) had brain metastasis and another 4 (8.9%) had disseminated disease detecteted radiologically. Among the 45 cases 6 (13.3%) were treated with suction evacuation only; 9 (20%) underwent hysterectomy for uterine perforation, excessive hemorrhage and invasive mole. 28 (62.2%) cases underwent adjuvant chemotherapy among which 12 (26.6%) received single agent chemotherapy and 15 (33.3%) received EMA-CO regimen. Brain irradiation was required in a case with brain metastasis. Five (11.1%) cases with disseminated disease and high WHO risk score left the hospital against medical advice. There were 3 (6.7%) mortalities. 37 (82.1%) cases are in remission and follow-up. Conclusions: Early diagnosis of disease and proper management strongly influences the outcome of GTD. Even in disseminated state GTD can be cured. No significant financial relationships to disclose.
Results of biopsies performed after breast conservation therapy for stage I-II breast cancer
Authors: E. E. Harris, J. Starzyk, L. J. Solin
Journal: Journal of Clinical Oncology (2004)

843 Background: This study was performed to identify the factors predictive of positive biopsy after breast conservation therapy with definitive breast irradiation (RT) for early stage breast cancer. Methods: The records of patients treated for stage I-II unilateral or bilateral invasive breast cancer between 1977 and 1996 were reviewed to identify patients who had undergone post-treatment ipsilateral breast biopsies. Results: There were 195 biopsies performed in 193 treated breasts. The median time to biopsy was 49 months (mos) after irradiation. Among all biopsies, 59% were positive and 41% were negative. Subsequent biopsies were performed in 28 breasts, of which 27% were positive, thus 12% of women with a negative first biopsy later developed local recurrence. Biopsies were positive in 41% of patients with physical exam (PE) findings only, in 69% with mammographic findings only and in 80% with physical exam and mammographic abnormalities (p=0.001). When analyzed by type of biopsy, core biopsies were positive in 85% (6 of 7), excisional biopsies in 58%, and fine needle aspirations were positive in 28% (p=0.025). When analayzed by age at diagnosis, positive biopsies were obtained in 54% of patients age 51 or older, in 59% of patients age 36 to 50 and in 83% of patients 35 years or younger (p=0.05). Positive biopsy rate also increased with the interval from completion of radiation, as follows: ≤ 60 months = 50%; 61–120 months = 67%; 121–180 months = 80%; ≥ 181 months = 100% positive biopsies (p=0.01). Positive biopsy rate was not correlated with location of recurrence, pathologic T or N stage, ER/PR status or final pathologic margins of excision (all p ≥ 0.15). Conclusions: Biopsy remains the standard for diagnosis of local recurrence after breast conservation therapy. In this study, we identified groups at high risk for a positive biopsy. No significant financial relationships to disclose.
Abstract 16107: Combined HbA1c and Systolic Blood Pressure Reduction With Dapagliflozin in Patients With Both Inadequately Controlled Type 2 Diabetes Mellitus and Hypertension
Authors: Michael A Weber, James List, Traci A Mansfield, Shamik J Parikh, Agata Ptaszynska
Journal: Circulation (2014)

Background: Hypertension is a common comorbidity in patients with type 2 diabetes mellitus (T2DM). Initial treatment is usually with an angiotensin-converting enzyme inhibitor (ACEi) or an angiotensin receptor blocker (ARB), with other antihypertensive therapies (AHTs) added if needed. Dapagliflozin (DAPA) increases urinary glucose excretion accompanied by diuresis and weight loss, which contributes to blood pressure (BP) reduction. Here we evaluate the proportions of patients achieving combined HbA1c and systolic blood pressure (SBP) reduction with DAPA in two studies of patients with both inadequately controlled T2DM and hypertension. Methods: Patients with both inadequately controlled T2DM (HbA1c 7.0-10.5%) and hypertension (seated SBP / diastolic BP: 140-164 / 85-104 mmHg) despite receiving glucose-lowering drugs and an ACEi or ARB (Study 1) plus a 2nd AHT agent (Study 2) were randomized to receive double-blind DAPA 10 mg or placebo for 12 weeks. Primary results have been presented previously; here we present proportions of patients achieving combined changes from baseline (Δ) in HbA1c and SBP. Results: In Study 2, additional AHT drugs were thiazide/thiazide-like diuretics (~44%), calcium channel blockers (~27%), and beta blockers (~27%). Across both studies, 520 and 522 patients had available paired ΔHbA1c and ΔSBP values in the DAPA and placebo groups, respectively. More patients achieved combined ΔHbA1c and ΔSBP reduction with DAPA (n=325; 62.5%) vs placebo (n=190; 36.4%) (Figure - dotted boxes). Considering more stringent thresholds, more patients achieved combined reductions in ΔHbA1c of ≥0.5% and ΔSBP of ≥5 mmHg with DAPA (n=194; 37.3%) vs placebo (n=86; 16.5%) (Figure - solid boxes). Conclusions: In T2DM patients with hypertension on glucose-lowering therapies and an ACEi or ARB ± 1 additional AHT, adding dapagliflozin achieved clinically significant combined HbA1c and SBP reductions over 12 weeks in greater numbers of patients than placebo.