tbuckley/cabot-search huggingface dataset:
Predictors of fatigue and quality of life in a prospective palliative care cohort
Authors: M. G. Martin, D. C. Currow, A. P. Abernethy
Journal: Journal of Clinical Oncology (2006)

8571 Background: Palliative care seeks to minimize distress at the end of life. Fatigue significantly diminishes quality of life (QOL) in this population. Are there potentially modifiable factors that influence fatigue and QOL? Methods: This analysis focuses on a subset of 198 patients from a larger 2×2×2 factorial randomized trial of pain education and care coordination conducted in South Australia. Selected participants were adults referred to a community palliative care service with pain in the preceding 3 months and a hemoglobin assessment within 14 days of enrollment. Pain, other symptoms, and Australia-modified Karnofsky Performance Status (AKPS) were recorded at enrollment. Predictors considered were anxiety, depression, dyspnea, constipation, pain, AKPS, hemoglobin, age, and gender. Dependent variables were global QOL from the McGill QOL Questionnaire and fatigue. Using forward stepwise linear regression, multivariate models predicting fatigue and QOL were constructed from significant univariate variables. Results: Mean age was 69 (standard deviation (SD) 13); 97% had cancer. Most frequent diagnoses were lung (18%), hematological (15%), and colorectal (15%) malignancies. Mean hemoglobin was 11.4 gm/dL (SD 1.9); median AKPS 60%; mean worst pain 4.0 (SD 3.4; 0–10 scale). Distressing symptoms (3–4 on 0–4 scales) included dyspnea (22%), constipation (13%), anxiety (11%), and depression (6%). Mean QOL was 5.9 (SD 2.0) on a 0–10 scale; mean fatigue was 2.3 (SD 1.0) on a 0–4 scale. The final multivariate model predicting fatigue included AKPS (p&lt;0.01), constipation (p=0.02), and dyspnea (p=0.06). Hemoglobin was not predictive of fatigue (univariate p=0.7069). QOL was significantly influenced by fatigue (p=0.03), anxiety (p&lt; 0.01), and AKPS (p= 0.01). Conclusions: Fatigue was driven by performance status, constipation, and dyspnea. In contrast to an oncology population, hemoglobin was not a significant contributor to fatigue in this population, consistent with other palliative care cohorts. QOL was driven by fatigue, anxiety, and performance status. This analysis of a prospectively collected population suggests that performance status, constipation, dyspnea, and anxiety are potentially modifiable variables impacting fatigue and QOL in the palliative care setting. No significant financial relationships to disclose.
Cardiovascular risk in long-term testicular cancer survivors.
Authors: H. S. Haugnes, T. Wethal, N. Aass, O. Dahl, O. H. Klepp, C. Langberg, T. Wilsgaard, R. M. Bremnes, S. D. Fossa
Journal: Journal of Clinical Oncology (2010)

4533 Background: The aim was to evaluate the incidence of non-fatal cardiovascular disease (CVD) and risk profile in testicular cancer (TC) survivors (TCS). Methods: 990 men treated for unilateral TC (1980-1994) were included in this national follow-up study (2007-2008) including physical examination, blood samples and a questionnaire. Patients were categorized into four treatment groups: Surgery (n=206), radiotherapy only (RT, n=386), cisplatin-based chemotherapy only (chemo, n=364) and combined RT/chemotherapy (RT/chemo, n=34). Age-matched male controls from the general population (NORMs) were recruited from the Tromsø Study (n=990). Men diagnosed with CVD before or within two years after the TC diagnosis were excluded from analyses of CVD endpoints (age-adjusted Cox regression). CVD endpoints were 1) coronary heart disease (CHD) and 2) total CVD. All CVD diagnoses were validated by medical records (TCS). For comparisons to NORMs, the combination of stroke/myocardial infarction (MI) was the endpoint as only these diagnoses were validated. Results: Median observation time was 19 years (range 13-28). Overall 92 TCS (9.9%) experienced CVD events during follow-up. Compared with surgery group, the chemo (HR 2.6, 95% CI 1.0-6.9) and the RT/chemo group (HR 5.3, 95% CI 1.5-18.5) had increased risks for CHD. Increased risks for total CVD were observed after any cytotoxic treatment (RT: HR 2.3, 95% CI 1.1-4.7; chemo: HR 2.4, 95% CI 1.1-5.0; RT/chemo: HR 5.2, 95% CI 2.0-13.5). Compared with NORMs, TCS had 1.7 times higher risk (95% CI 1.0-2.8) for stroke/MI, with the highest risks for the RT (HR 2.0, 95% CI 1.2-3.5) and the RT/chemo group (HR 4.5, 95% CI 1.6-12.8). All treatment groups except surgery group had increased prevalence of antihypertensive medication compared to NORMS (22% vs. 13%), highest for the chemo (OR 3.3, 95% CI 2.4-4.5) and the RT/chemo group (OR 4.1, 95% CI 1.9-8.8). Survivors in the RT and RT/chemo group had higher levels of micro CRP (RT: β=0.38 mg/l, p<.001, RT/chemo: β=0.63 mg/l, p=0.014), and a higher prevalence of diabetes (RT: OR 2.3, 95% CI 1.5-3.6; RT/chemo: OR 3.9, 95% CI 1.4-10.9). Conclusions: Treatment with infradiaphragmatic RT and/or cisplatin-based chemotherapy, particularly when combined, increases the long-term risk for CVD. No significant financial relationships to disclose.
Abstract 12518: The Association of Electronic Health Record Use With Acute MI Quality of Care and Outcomes: Results From the NCDR®
Authors: Jonathan R Enriquez, James A de Lemos, Shailja V Parikh, DaJuanicia Holmes, Tracy Y Wang, Paul S Chan, John A Spertus, Sandeep R Das
Journal: Circulation (2013)

Introduction:  In 2009, national legislation promoted wide adoption of the electronic health record (EHR) across US hospitals; however ,  the association of EHR use with acute MI quality of care is unknown.   Methods:  Data regarding EHR use were collected from the American Hospital Association Annual Surveys (2007-2010), and data regarding acute MI processes of care and outcomes from the NCDR ACTION  Registry-GWTG. We compared patients treated at hospitals with self-reported fully-implemented EHR (n=43,527), partially-implemented EHR (n=72,029), and no EHR (n=9,270). Multivariable models were used to adjust for patient and hospital characteristics to determine associations between EHR implementation and process of care measures and in hospital outcomes.   Results:  Overall EHR use increased from 183/223 hospitals (82.1%) in 2007 to 275/277 hospitals (99.3%) in 2010. Hospitals with fully-implemented (n=49) or partially-implemented (n=101) EHRs in 2008 did not differ in size, teaching status, for-profit status, or patient insurance status compared to hospitals without EHRs (n= 19) at that time. After adjustment, patients treated at hospitals with fully-implemented EHRs were significantly more likely to receive defect-free care. In NSTEMI, fully-implemented EHR use was associated with significantly lower risk of in-hospital mortality and major bleeding compared to no EHR use. In STEMI, risk of mortality and major bleeding did not significantly differ by EMR status (Figure).   Conclusion:  EHR use has increased to very high levels among hospitals participating in ACTION Registry-GWTG. EHR use is associated with better adherence to guidelines-recommended therapies in acute MI and with an approximately 20% lower risk of in-hospital mortality or major bleeding in patients with NSTEMI; however, these differences were not seen among STEMI patients. Further studies are needed to elucidate the relationship between EHR use and acute MI quality of care and outcomes.
The cholesteryl ester transfer protein (CETP) TaqIB polymorphism in the cholesterol and recurrent events study: no interaction with the response to pravastatin therapy and no effects on cardiovascular outcome
Authors: Greetje J. de Grooth, Kim E. Zerba, Shu-Pang Huang, Zenta Tsuchihashi, Todd Kirchgessner, René Belder, Priya Vishnupad, Beihong Hu, Anke H.E.M. Klerkx, Aeilko H. Zwinderman, J.Wouter Jukema, Frank M. Sacks, John J.P. Kastelein, Jan Albert Kuivenhoven
Journal: Journal of the American College of Cardiology (2004)
Surface Charge Characteristics of Cells From Malignant Cell Lines and Normal Cell Lines of the Human Hematopoietic System
Authors: Y Marikovsky, H Ben-Bassat, S J Leibovich, L Cividalli, H Fischler, D Danon
Journal: JNCI Journal of the National Cancer Institute (1979)

Cells from malignant and normal lines of human hematopoietic origin were studied for their surface charge characteristics with the use of the following criteria: 1) the electron microscopic appearance of cell membranes after labeling with cationized ferritin (CF) either before or after glutaraldehyde fixation, 2) electrophoretic mobility, 3) total sialic acid content, and 4) agglutinability with poly-l-Iysine (PLL). CF induced a timedependent redistribution of surface receptors in unfixed malignant cells but not in unfixed normal cells. After 10 seconds of labeling with CF, both normal and malignant unfixed cells showed a uniform and even labeling pattern. After 5 minutes of labeling, malignant cells exhibited a highly pronounced pattern of clusters and patches, as distinct from a random and even pattern exhibited by normal cells. Both normal and malignant cells after fixation exhibited an equivalent random and even labeling pattern with CF, independent of the duration of labeling. The malignant cells studied possessed less sialic acid, had a lower electric mobility, and were agglutinated more readily with PLL than were the normal cells.
The global prevalence of IBS in adults remains elusive due to the heterogeneity of studies: a Rome Foundation working team literature review
Authors: Ami D Sperber, Dan Dumitrascu, Shin Fukudo, Charles Gerson, Uday C Ghoshal, Kok Ann Gwee, A Pali S Hungin, Jin-Yong Kang, Chen Minhu, Max Schmulson, Arkady Bolotin, Michael Friger, Tamar Freud, William Whitehead
Journal: Gut (2016)

<h3>Objectives</h3> The global prevalence of IBS is difficult to ascertain, particularly in light of the heterogeneity of published epidemiological studies. The aim was to conduct a literature review, by experts from around the world, of community-based studies on IBS prevalence. <h3>Design</h3> Searches were conducted using predetermined search terms and eligibility criteria, including papers in all languages. Pooled prevalence rates were calculated by combining separate population survey prevalence estimates to generate an overall combined meta-prevalence estimate. The heterogeneity of studies was assessed. <h3>Results</h3> 1451 papers were returned and 83, including 288 103 participants in 41 countries, met inclusion criteria. The mean prevalence among individual countries ranged from 1.1% in France and Iran to 35.5% in Mexico. There was significant variance in pooled regional prevalence rates ranging from 17.5% (95% CI 16.9% to 18.2%) in Latin America, 9.6% (9.5% to 9.8%) in Asia, 7.1% (8.0% to 8.3%) in North America/Europe/Australia/New Zealand, to 5.8% (5.6% to 6.0%) in the Middle East and Africa. There was a significant degree of heterogeneity with the percentage of residual variation due to heterogeneity at 99.9%. <h3>Conclusions</h3> The main finding is the extent of methodological variance in the studies reviewed and the degree of heterogeneity among them. Based on this, we concluded that publication of a single pooled global prevalence rate, which is easily calculated, would not be appropriate or contributory. Furthermore, we believe that future studies should focus on regional and cross-cultural differences that are more likely to shed light on pathophysiology.
African-American men, high cholesterol &amp; hs-CRP &amp; alternative medicine use documented at a prostate cancer screening: A unique opportunity for a complete men’s health intervention
Authors: M. A. Moyad, D. Giacherio, J. Montie
Journal: Journal of Clinical Oncology (2005)

4623 Background: The potential impact of prostate cancer on African-American (A.A.) men is well-known. However, a comprehensive men’s health screening that includes the risk of cardiovascular disease (CVD) has not been researched in the past in this same population of men that are traditionally just offered a PSA test. Therefore, we attempted to determine the prevalence of CVD risk at a traditional annual PSA screening of A.A. men in the Chicago, IL and Baltmore, MD areas. Methods: A total of 114 A.A. men (57 from each site) were offered PSA, cholesterol, and hs-CRP screening. In addition, men were asked about their use of alternative medicine for prostate cancer prevention, and their comments were recorded and verified by the men that participated. Results: A total of 114 men agreed to participate in the comprehensive screening. Approximately 50% of the men screened had a total cholesterol that was high (>200 mg/dL), 25% had abnormally low (<40mg/dL) high-density lipoprotein (HDL) levels, 20% had abnormally high (>130 mg/dL) low density lipoprotein (LDL) levels, 30% had abnormally high (>3 mg/L) levels of high sensitivity C-reactive protein levels (hs-CRP), more than 25% of men reported alternative medicine use, and less than 10% of the men had a high PSA level (>4 ng/ml). Conclusions: The high prevalence of dyslipidemia, hs-CRP, and alternative medicine use by A.A. men at a PSA screening is concerning. This is one of the first studies to document the high prevalence of such markers at an A.A. PSA screening. This represents a unique men’s health intervention potential for identifying men at high risk for CVD and prostate cancer. A.A. men and other men should be offered a combined health screening and asked about their alternative medicine use when also offered PSA screening. CVD is the number 1 cause of mortality in men, and future screenings that offer comprehensive health screening may be more appropriate than just PSA screening by itself. Source of funding: No outside source of funding. No significant financial relationships to disclose.
Histogenetic Behavior of Tumors. III. Possible Relationships to Patterns of Glycolysis&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: Nelly Auersperg
Journal: JNCI Journal of the National Cancer Institute (1972)

The ultrastructure and growth patterns of 2 human cervical squamous carcinoma cell lines of common origin suggest a difference in malignant progression as well as the retention of different tissue-specific properties by each of the 2 cell lines. In the present study, aerobic and anaerobic glycolysis in standard culture and with nutritional deprivation was compared in these lines. Under all conditions tested, the rates of glucose uptake and lactic acid accumulation were higher in the line (C-4 I) that appeared more malignant by previous criteria. Cells of line C-4 I also showed a reduced ability to modify patterns of aerobic glycolysis in response to environmental variables, and indirect evidence of anaerobic glycogen-olysis—characteristics which, like those found in the previous studies, suggest the spinous stage in squamous differentiation. The glycolytic properties of the other line (C-4 II) were more in keeping with less progressive malignancy and with the basal cell stage of squamous differentiation. Possible effects of retained traits of normal differentiation on the phenotype of malignant cells and resultant influences on the growth and invasion of tumors are discussed.
Impact of the Number of Treatment Courses on the Clinical Response of Patients Who Receive High-Dose Bolus Interleukin-2
Authors: Kimberly R. Lindsey, Steven A. Rosenberg, Richard M. Sherry
Journal: Journal of Clinical Oncology (2000)

To determine the impact of treatment with successive courses of high-dose bolus interleukin-2 (IL-2) on the incidence of clinical responses in patients with metastatic melanoma or renal cell cancer.A consecutive series of 350 patients with either metastatic melanoma or renal cell cancer who were treated with high-dose bolus IL-2 in the Surgery Branch, National Cancer Institute, between September 1985 and November 1996 was analyzed, with a median potential follow-up of 7.1 years. All patients were treated with 720,000 IU/kg of IL-2 administered by a 15-minute intravenous infusion every 8 hours for up to 5 days, as clinically tolerated per cycle. Patients were retreated according to clinical response and tolerance to the IL-2 therapy.Of the 149 patients with melanoma, 10 achieved complete responses (CRs) and 13 partial responses (PRs), for an overall response rate of 15.4%. Of the 201 patients with renal cell cancer, 18 achieved CRs and 20 PRs, for an overall response rate of 19.0%. Among responding patients, 21 of 23 with melanoma and 34 of 38 with renal cell cancer developed at least PRs after the first course of IL-2.Most patients with metastatic melanoma and renal cell cancer who achieved PRs or CRs to intravenous high-dose bolus IL-2 were identified after the first course of therapy. Those who demonstrated no response after two treatment courses failed to respond to additional IL-2 therapy. Based on this retrospective analysis, we recommend that patients who exhibit objective responses to treatment with high-dose bolus IL-2 receive additional treatment courses until either CR or IL-2 intolerance develops. Patients who do not achieve objective responses after two courses of IL-2 should receive no further treatment with this regimen.
Recent Trends in the Prevalence of Marijuana Use and Associated Disorders in the United States
Authors: Richard A. Grucza, Arpana Agrawal, Melissa J. Krauss, Patricia A. Cavazos-Rehg, Laura J. Bierut
Journal: JAMA Psychiatry (2016)

This study compares prevalence and trends in marijuana use and marijuana use disorder from the National Epidemiologic Survey of Alcohol and Related Conditions with those from the National Survey on Drug Use and Health.
Phase I pharmacokinetic (PK) and biodistribution study of radium-223 chloride in patients with castration resistant prostate cancer (CRPC) metastatic to bone.
Authors: J. A. Carrasquillo, J. A. O' Donoghue, N. Pandit-Taskar, D. E. Rathkopf, A. Aksnes, C. L. Viner, C. T. Hong, S. M. Larson, H. I. Scher, M. J. Morris
Journal: Journal of Clinical Oncology (2010)

4680 Background: Radium-223 chloride (Alpharadin) is a first-in-class alpha-pharmaceutical with a potent and highly targeted antitumor effect on bone metastases and a favorable safety profile in prior studies. This study was conducted to further define the PK, biodistribution, and safety profile of radium-223. Methods: Patients (pts) with progressive CRPC and ≥2 bone metastases were treated in cohorts of 3-6 pts with a single dose of: 50, 100, 200 kBq/kg followed by 1 optional dose of 50 kBq/kg 6 wks later. Blood and whole body radiation counts were determined and serial gamma camera images were acquired post injection: immediately, post first void (within 0-6 hrs of treatment), and on days 1, 2, 3, 5 and 7. DLT was defined as Grade (Gr) 3-4 non-hematologic toxicity, prolonged Gr 3-4 neutropenia (>14 days) or Gr 4 thrombocytopenia (>7 days), within 4 weeks of the first dose. Results: 10 pts were treated, 3 in cohorts 1 and 2 each, and 4 in cohort 3. 6 pts received a 2nd injection. 4 pts did not receive a 2nd dose due to disease progression (2 pts), Gr 3 anemia (1 pt), or an unrelated adverse event (1 pt). Within 10 mins of injection radium-223 accumulated in bone metastases and was also seen in the small bowel with subsequent fecal transit to the colon. Total body clearance was largely determined by transit through gut (mean biological t1/2=59hr). Blood clearance was rapid and bi-exponential with respective partition coefficients and t1/2 of 1.7%ID/L, 0.3 hr and 0.8%ID/L, 6.3 hr. The fraction of counts in the G.I. tract relative to the total body counts at 24hr ranged from 17.4 to 43.9% (mean 30.2%). Significant drug-related adverse events were: 1 pt with Gr 3 hemoglobin; 1 pt with Gr 3 platelets; and 1 pt with Gr 4 WBC, Gr 3 ANC, Gr 3 diarrhea, and Gr 3 nausea. Toxicities were unrelated to dose level. Conclusions: Radium-223 chloride was well tolerated, and no MTD was reached up to 200 kBq/kg. The agent was rapidly cleared from blood, accumulated in bone and excreted through small bowel with sequential transit through the large bowel. A phase I/IIa trial in combination with docetaxel is planned and a phase III survival study is ongoing (the ALSYMPCA study). Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Algeta ASA Algeta ASA Algeta ASA Algeta ASA
Phase I study of suramin given by intermittent infusion without adaptive control in patients with advanced cancer.
Authors: K Kobayashi, E E Vokes, N J Vogelzang, L Janish, B Soliven, M J Ratain
Journal: Journal of Clinical Oncology (1995)

PURPOSE Suramin is a promising agent for the treatment of hormone-refractory metastatic prostate cancer. However, questions about the relationship of severe neurotoxicity to sustained peak plasma concentrations greater than 300 micrograms/mL raised concerns that this drug could not be safely administered without adaptive control. To test the adaptive-control hypothesis, we designed a phase I study that relied on clinical end points, using a fixed dosing scheme that did not rely on adaptive control. PATIENTS AND METHODS In a phase I dose-escalation study using fixed dosing without adaptive control, gradually decreasing doses of suramin were administered to 63 patients on days 1 (loading dose), 2, 8, and 9 of a 28-day cycle. Fifty-four patients with hormone-refractory metastatic prostate cancer and nine patients with other solid tumors have been treated. RESULTS Doses of 400 mg/m2 to 2,080 mg/m2 on the first day have been administered. The mean peak plasma concentration following the loading dose at a dose level of 1,730 mg/m2 was 933 micrograms/mL (26% coefficient of variation), and the mean trough concentration was 139 micrograms/mL (40% CV) on day 1 of cycle 2 [corrected]. At 1,730 mg/m2, five of 13 patients experienced dose-limiting toxicity (DLT), including malaise, neurotoxicity, pericardial effusion, and coagulopathy. At 2,080 mg/m2, three of five patients experienced DLT. Two patients treated at this dose level died while on study. One of these patients died of a subdural hematoma sustained after a fall and had a prolonged prothrombin time at the time of his death. One patient developed classic suramin neurotoxicity, which led to respiratory failure, for which the patient refused intubation. No significant associations were noted between peak or trough concentrations during either cycles 1 or 2 and the occurrence of neurotoxicity. CONCLUSION (1) Suramin can be safely administered without adaptive control, (2) suramin on this schedule may exhibit significant activity against hormone-refractory metastatic prostate cancer, and (3) based strictly on toxicity considerations, we recommended that a day-1 dose of 1,440 mg/m2 be used in subsequent clinical trials, with a maximum of three cycles. Further studies to establish the optimal empiric dosing regimen are needed.