tbuckley/cabot-search huggingface dataset:
Association Between Hospitalization for Heart Failure and Dipeptidyl Peptidase 4 Inhibitors in Patients With Type 2 Diabetes: An Observational Study
Authors: Alex Z. Fu, Stephen S. Johnston, Ameen Ghannam, Katherine Tsai, Katherine Cappell, Robert Fowler, Ellen Riehle, Ashley L. Cole, Iftekhar Kalsekar, John Sheehan
Journal: Diabetes Care (2016)

To examine, among patients with type 2 diabetes, the association between hospitalization for heart failure (hHF) and treatment with dipeptidyl peptidase 4 inhibitors (DPP-4is) versus sulfonylureas (SUs), and treatment with saxagliptin versus sitagliptin.This was a retrospective, observational study using a U.S. insurance claims database. Patients initiated treatment between 1 August 2010 and 30 August 2013, and had no use of the comparator treatments in the prior 12 months (baseline). Each comparison consisted of patients matched 1:1 on a propensity score. Time to each outcome was compared between matched groups using Cox models. Analyses were stratified by the presence of baseline cardiovascular disease (CVD). Secondary analyses examined associations between comparator treatments and other selected cardiovascular events.After matching, the study included 218,556 patients in comparisons of DPP-4i and SU, and 112,888 in comparisons of saxagliptin and sitagliptin. The hazard ratios (HRs) of hHF were as follows: DPP-4i versus SU (reference): HR 0.95 (95% CI 0.78-1.15), P = 0.580 for patients with baseline CVD; HR 0.59 (95% CI 0.38-0.89), P = 0.013 for patients without baseline CVD; saxagliptin versus sitagliptin (reference): HR 0.95 (95% CI 0.70-1.28), P = 0.712 for patients with baseline CVD; HR 0.99 (95% CI 0.56-1.75), P = 0.972 for patients without baseline CVD. Comparisons of the individual secondary and composite cardiovascular outcomes followed a similar pattern.In patients with type 2 diabetes, there was no association between hHF, or other selected cardiovascular outcomes, and treatment with a DPP-4i relative to SU or treatment with saxagliptin relative to sitagliptin.
Safety, pharmacokinetics, and efficacy of palonosetron in pediatric patients: A multicenter, stratified, double-blind, phase 3, randomized study
Authors: R. Kadota, V. Shen, Y. Messinger
Journal: Journal of Clinical Oncology (2007)

9570 Background: A single intravenous (IV) dose of palonosetron (PALO) 0.25 mg is used in the prevention of acute chemotherapy-induced nausea and vomiting (CINV) after highly (HEC) and moderately emetogenic chemotherapy (MEC) and in the prevention of delayed CINV after MEC. Since younger age is a risk factor that increases the likelihood of CINV, we conducted this study to explore the safety, pharmacokinetics (PK) and efficacy of PALO in pediatric patients receiving MEC (32% of patients) or HEC (68%). Methods: Sixty pediatric patients in 2 age strata, ages 2–11 and 12–17 years, were randomized to receive a single IV dose of PALO 3 mcg/kg (max total dose = 0.25 mg) or 10 mcg/kg (max total dose = 0.75 mg), with no concomitant antiemetics prior to MEC or HEC. The same doses were used in 12 additional younger patients (age range: 28 days - 23 months) treated in an open-label fashion. Safety, assessed as incidence of adverse events (AEs), was the primary between-group analysis endpoint. Plasma concentrations, PK parameters and efficacy (up to 24 hours after chemotherapy) were assessed descriptively for both PALO doses in each age group. Results: Only 3 AEs, 2 (pyrexia and pruritus) in the 3 mcg/kg dose group (5.7%) and 1 (pain) in the 10 mcg/kg group (2.7%), were judged possibly related to study medication by the investigators, and none of them were severe or led to study discontinuation. No cardiac safety issues were identified; vital signs and laboratory data did not raise any safety concerns for the administration of either dose of PALO. Systemic exposure (AUC) to PALO increased with increasing dose across all age groups (AUC 0–8 : 22.17–33.25 ng*h/mL at 3 mcg/kg dose; 49.85–75.1 ng*h/mL at 10 mcg/kg dose). Clearance and volume of distribution increased in correlation with age-related growth in body weight. T 1/2 ranged from 21–37 hours across groups, slightly shorter than adult T 1/2 of 40 hours. Complete Response (no emesis no rescue, 0–24 hours) rates showed overlapping Confidence Intervals in the two dose groups (37.1% [22.0%-55.1%] at 3 mcg/kg, n=35; and 54.1% [37.1%-70.2%] at 10 mcg/kg, n=37). Conclusions: PALO, dosed according to patient's weight at 3 and 10 mcg/kg, was effective and well tolerated in the pediatric population. No significant financial relationships to disclose.
Modified gemcitabine regime in advanced lung cancers
Authors: S. Agarwal, P. Agarwal
Journal: Journal of Clinical Oncology (2006)

17148 Background: Gemcitabine is established treatment modality for NSCLC. However it’s introduction on day 8 is sometimes delayed because of low counts or poor patient acceptance because of effects of d1 dose. Methods: We have used gemcitabine 10000 mg/m 2 as d1,d10 regimen in 32 patients of advanced lung cancer incombination with either cisplatin or carboplatin .Colony stimulating factors were required in 2 patients. Results: The patients tolerated the chemotherapy (4 to 6 cycles) satisfactorily and none of the patient required delaying of the d10 therapy. Complete regression was seen in 2 patients,partial regression in 22 patients.the median survival was 10.2 months. Conclusions: The d1–10 schedule of gemcitabine based chemotherapry is safe,effective and better tolerated then the d1-d8 schedule. No significant financial relationships to disclose.
Would you do it again? The perspectives of patients as they receive and recover from adjuvant therapy for stage II/III colon cancer.
Authors: N. Love, C. Bylund, L. M. Ellis, A. Grothey, N. J. Meropol, P. Ravdin, L. Saltz, M. Elder, K. A. Ziel, D. Paley
Journal: Journal of Clinical Oncology (2010)

e14029 Background: We previously reported that many survivors of colon cancer (CC) would elect to receive adjuvant chemotherapy (ACTX) again even for a modest absolute reduction in recurrence risk (ARRR). Limitations posed by the retrospective nature of that work led to this study, in which we prospectively assessed the experiences of patients (pts) with CC during and after ACTX. Methods: Pts with Stage II/III CC were recruited through advocacy groups and oncology practices to participate in a longitudinal survey regarding their experiences with ACTX. Pts were given an initial survey within 3 months of having started ACTX and then 3 follow-up surveys at 3-month intervals. Survey items addressed expectations, experiences, and decision-making regarding ACTX. Results: 94 pts completed the initial survey (70% female, median age 52 years, 78% Stage III, 81% received oxaliplatin). 74 pts completed all 4 surveys. After the discontinuation of treatment, as part of the follow-up surveys, pts were presented clinical scenarios in which ACTX would offer different ARRR and were asked, considering their overall experience with ACTX, if they would receive treatment again in each of the described situations. 26% of pts would choose to be treated again for a 1% ARRR, 43% for a 3% ARRR, 63% for a 5% ARRR and 78% for a 10% ARRR — findings similar to the previous retrospective study. Overall, more than 75% of pts reported that they would choose to receive ACTX again, regardless of whether the question was asked during or after completion of ACTX. Conclusions: The prospective data obtained in this convenience sample support prior observations that many pts with CC would elect to receive ACTX for modest potential absolute benefits. In spite of potential selection biases, these results support the clinical importance of shared decision-making in the context of adjuvant therapy for colon cancer, particularly when the absolute benefit is small and there is substantial variability in patient preferences. Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration LifeCell, Myriad Genetics Adolor/ GlaxoSmithKline, Genzyme
Person centred coordinated care: where does the QOF point us?
Authors: M. McShane, E. Mitchell
Journal: BMJ (2015)

Martin McShane and Edward Mitchell question the validity of the Quality and Outcomes Framework and suggest how it should change in the future

The Quality and Outcomes Framework (QOF) is a pay for performance programme that was introduced in 2004 to improve care in general practice. It now constitutes roughly 13% of practice income—QOF payments in 2013-14 were £1057m (€1451m; $1613m) (fig⇓).1 The arguments for and against the QOF (and pay for performance schemes in general) have been hotly debated over the past decade. Its seminal impact on UK general practice is undeniable, but its influence is such that it has affected our idea of what constitutes quality improvement. It has been suggested, for example, that we equate (or perhaps conflate) good care with the recording of disease specific biomedical or process markers.2



QOF payments per year. Source: Health and Social Care Information Centre



The QOF is facing change. The 2014-15 GP contract deal has seen a 30% reduction in QOF points.3 After eleven years, and billions of pounds in QOF payments, we take stock of the QOF and discuss three changes in the healthcare system that mean QOF must change. 

By the late 1990s, the increasing use of clinical audits and computerised records showed considerable variations in the management of chronic diseases. The government’s desire to increase healthcare funding (which as a proportion of gross domestic product lagged behind that of most other European countries) was complemented by a political drive for more systematic clinical governance.4

The origins of QOF lie in the 1997 Primary Care Clinical Evaluation Project, in which a group of GPs and colleagues in Kent designed indicators and standards in 13 clinical areas. By 2000 they had signed up 85% of local practices to participate in the scheme at …
Association between family history of affective disorder and the depressive syndrome of Alzheimer's disease
Authors: G D Pearlson, C A Ross, W D Lohr, B W Rovner, G A Chase, M F Folstein
Journal: American Journal of Psychiatry (1990)

For each of 41 index patients with probable Alzheimer's disease and a first episode of major depression and 71 nondepressed Alzheimer's disease patients, two first-degree relatives were interviewed by a rater blind to presence or absence of depression in the proband. The depressed patients had significantly more first- and second-degree relatives with depression than did control subjects. The lifetime risk for major depression, adjusted for differences in age distribution, was significantly greater in first-degree relatives of index patients, suggesting that depression in Alzheimer's disease is genetically related to primary affective disorder. Alzheimer's disease may be useful for studying aspects of depressive pathophysiology.
Pathologic characteristics and cell cycle regulatory protein expression as a prognosis marker after curative resection in gall bladder cancer
Authors: M. Lee, S. Hong, E. Chung, Y. Koh, J. Kang, Y. Hong, K. Lee, D. Kim, S. Kim
Journal: Journal of Clinical Oncology (2008)

15634 Background: We investigated pathologic characteristics, ERCCI, survivin, Thymidine phosphorylase (TP) and some cell cycle regulatory proteins to determine the prognostic and predictive value in gall bladder cancer after curative surgery. Methods: We reviewed the pathologic parameters, including tumor tissue differentiation, lymphatic, perineural, and venous invasion in formalin-fixed, paraffin-embedded block from 73 gall bladder cancer tissues after curative surgery. We also performed immunohistochemical staining for ERCC1, survivin, TP, p53, cyclin D1 and bcl-2 to determine the association with clinical course. Results: Male and was 33 and 40 cases(45.2% vs. 54.8%), respectively and the median age was 62 year old. Of the 73 cases, TP expression showed in 54.8%, p53 in 43.8%, survivin in 27.4%, ERCC1 in 24.7% and cyclin D1 in 23.3%. In correlated with prognosis and pathological parameters, lymphatic invasion had statistically significant association with recurrence (p=0.033), showing less in negative group. Histologically, the group of well differentiated tumor had better survival outcome than those of poor differentiated tumor (p<.001), and positive perineural invasion showed poorer survival than negative group (p=.027). However, no significant correlation was found between survivin, ERCC1, thymidine phosphorylase (TP), p53, cyclin D1 and bcl-2 expression and survival or recurrence. Conclusions: In gall bladder cancer after surgery, pathologic characteristics, such as lymphatic, perineural invasion or tissue differentiation can be a useful prognostic marker for survival or recurrence. No significant financial relationships to disclose.
Novel monoclonal antibodies for measuring 5-fluorouracil concentrations in biological fluids
Authors: S. J. Salamone, J. B. Courtney, D. Stocker, R. L. Harney
Journal: Journal of Clinical Oncology (2006)

2055 Background: Therapeutic drug monitoring of anticancer drugs has potential for improving treatment of individual patients. 5-Fluorouracil (5-FU) has been reported to exhibit high pharmacokinetic variability and in some cases severe toxicity. Pharmacokinetic guided dosing of 5-FU using physical methodologies has demonstrated clinical usefulness in decreasing toxicity while resulting in equivalent or improved outcomes. The current physical methods for measuring 5-FU require specially trained personnel, are expensive, time consuming and therefore not amenable for widespread use. However, an automated immunoassay would provide a rapid, simple and inexpensive method to routinely measure levels of 5-FU in patients. Methods: In order to develop monoclonal antibodies that were selective for 5-FU, immunogens were prepared by attaching the drug to keyhole limpet hemocyanin (KLH) or bovine thyroglobulin (BTG) via a hydrocarbon tether bound through the N-3 nitrogen. Mice were immunized and the resulting antibodies were screened by ELISA. The selection of antibodies was based on sensitivity and cross-reactivity characteristics. Results: These immunogens were successful in eliciting 20 highly selective monoclonal antibodies for 5-FU with immunoassay dose response curves in the clinical range of 10 ng/mL to 5000 ng/mL. The immunoassay was tested with a mixture of the various pyrimidine compounds at their respective endogenous levels and shown to have no impact on the measurement of 5-FU. The Table below lists typical cross-reactivity performance characteristics that are elicited by this type of immunogen. Conclusion: This library of monoclonal antibodies represents the first report of antibodies selective for 5-fluorouracil. These antibodies will be useful for the rapid and cost effective analysis of 5-FU in human samples, providing a tool for optimization of 5-FU levels by pharmacokinetic guided dosing. [Table: see text] [Table: see text]
Nucleotide Polymerase Inhibitor Sofosbuvir plus Ribavirin for Hepatitis C
Authors: Edward J. Gane, Catherine A. Stedman, Robert H. Hyland, Xiao Ding, Evguenia Svarovskaia, William T. Symonds, Robert G. Hindes, M. Michelle Berrey
Journal: New England Journal of Medicine (2013)

The standard treatment for hepatitis C virus (HCV) infection is interferon, which is administered subcutaneously and can have troublesome side effects. We evaluated sofosbuvir, an oral nucleotide inhibitor of HCV polymerase, in interferon-sparing and interferon-free regimens for the treatment of HCV infection.
Combination of nanogel polyethylene glycol-polyethylenimine and 6 (hydroxymethyl)-1,4-anthracenedione as an anti-pancreatic cancer nanomedicine
Authors: Chanran Ganta, Aibin Shi, Srinivas Battina, Marla Pyle, Sandeep Rana, Duy Hua, Masaaki Tamura, Deryl Troyer
Journal: Cancer Research (2008)

5625   Pancreatic cancer is generally the most lethal cancer and its five year survival is less than 5%. Development of new therapeutic agents and effective treatment procedures are urgently needed. In order to approach this problem we synthesized multiple anticancer drugs and tested their effect on the growth of pancreatic cancer cells and nanoparticle-based targeted delivery system. Although polyethylene glycol-polyethylenimine (PEG-PEI) nanogels have been used to deliver nucleic acids and oligonucleotides into cells, its potential ability to delivery anticancer drugs was evaluated. We first synthesized various nanogels with altering ratios of CH 2 O:CH 2 N (methylene protons) in PEG-PEI and tested their cytotoxicity using a rodent pancreatic adenocarcinoma cell line (Pan 02). Results indicate that the nanogel PEG-PEI with lower methylene protons ratio (4:1) exhibited a strong cytotoxicity over the higher methylene protons ratio (~6.8:1). We then incorporated a newly synthesized anti-cancer drug, 6-(hydroxymethyl)-1,4-anthracenedione (AQ) analogue (AQ10) into nanogel PEG-PEI with higher methylene protons ratio (~6.8:1) and tested the effect of AQ10 encapsulated nanogel PEG-PEI (AQ10-nanogel PEG-PEI) and AQ10 dissolved in DMSO on Pan 02 cell growth. Our results showed that, Pan 02 cells treated with AQ10-nanogel PEG-PEI was three to four times more effective in cell growth attenuation than the cells treated with AQ10 alone. Nanogel PEG-PEI apparently acts as a drug delivery agent by penetrating the cell membrane and carrying the anti-cancer drug AQ10 into the cells, so that they become more susceptible to the drug even at a lower dose. These results suggest that AQ10-nanogel PEG-PEI is a potentially effective anti-cancer agent in pancreatic cancer therapy. This work was supported by NIH grant R01AG025500, NSF grants CHE-0555341 and NSF43529, AHA Heartland Affiliate grant 0750115Z and Kansas State University (KSU) Terry C. Johnson Center for Basic Cancer Research, Kansas State Legislative Stem Cell Appropriation, KSU Targeted Excellence grant, and KSU College of Veterinary Medicine Dean’s and SMILE Funds.
Leukocyte interleukin, injection (LI) treatment in advanced primary squamous cell carcinoma of the head &amp; neck a phase II multi-center trial and pathology study
Authors: E. Talor, J. Timar, G. Repassy, G. Szabo, E. Remenar, Z. Balatoni, B. Zemplen
Journal: Journal of Clinical Oncology (2004)

2605 Background: Previously we reported that peritumoral administration 5/week, 2 weeks, cumulative doses 2400, 4800, 8000 IU [as IL-2] of LI [Multikine] increased cancer cells sensitivity to radiation in 27 oral squamous cell carcinoma (OSSC T2–3N0–2M0) patients (p<0.05) resulting in tumor cells entering cell cycle with no recurrence at 24 months in 8/27 LI-treated patients (data to date) as opposed to controls. Treatment regimen included LI (above) single low-dose cyclophosphamide (iv 300mg/m2) indomethacin (po 25mg tid) and Zinc Sulfate (po 50mg) [CIZ]. Methods: Paraffin embedded samples obtained at surgery from 19 LI-treated patients (different cohort of OSSC T2–3N0–2M0) receiving LI (800IU/mL) \(\frac{1}{2}\) peritumorally \(\frac{1}{2}\) perilymphatically (5/week for 3 weeks + CIZ) were compared to 20 disease-matched (non-LI treated) controls. All patients had surgery & radiation. Histology, necrosis, AJCC grading was scored from H&E. Immunohistochemistry evaluated three tumor regions (surface, center, tumor-stroma interface). Trichrome stain visualized connective tissue. Morphometry by ImagePro software. All by 3 pathologists blinded to Study. Results: LI treatment induced a shift from stromal T cells to tumor epithelia (p<0.05) increase in intraepithelial CD3+ CD25+ CD4+ T cells and decrease in CD8+ T cells (p<0.05) causing a shift from low (<1) to high (>2.5–3) intra-tumoral CD4/CD8 ratio. Stroma/cancer-nest ratio showed reduction of cancer cells (LI-treated, p<0.005) as compared to control. LI-treated had 2/19 complete responders, 2/19 partial responders (>50%), and 4/19 minor responders (>30% but <50%). Conclusions: Objective response 21% overall response 42%. The results may be highly beneficial to OSCC patients: LI treatment induced CD3+ CD25+ CD4+ T cell increase in cancer nests including significant (p<0.005) decrease in tumor epithelia compared to control. Non-cycling cancer cells entered cell cycle following LI treatment increasing tumor susceptibility to radiation (p<0.05). LI-treatment appears to cause an increase in the local control of OSSC. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration CEL-SCI Corp. CEL-SCIU Corp. CEL-SCIU Corp.
Multiplexed targeted sequencing of recurrent fusion genes in acute leukaemia
Authors: P Ruminy, V Marchand, N Buchbinder, T Larson, B Joly, D Penther, E Lemasle, S Lepretre, E Angot, S Mareschal, P-J Viailly, S Dubois, F Clatot, M Viennot, E Bohers, D Rizzo, M Cornic, P Bertrand, C Girod, V Camus, P Etancelin, G Buchonnet, P Schneider, J-M Picquenot, J-P Vannier, C Bastard, H Tilly, F Jardin
Journal: Leukemia (2015)
Maintenance chemotherapy after frontline therapy in patients with nonsquamous non-small cell lung cancer (NSCLC).
Authors: E. S. Santos, A. Belalcazar, J. E. Gomez, R. E. Ochoa, M. Karr, L. E. Raez
Journal: Journal of Clinical Oncology (2011)

e18061 Background: Maintenance therapy (MCX) has been accepted for non-squamous NSCLC patients (pts) due to OS advantage. However, the best MCX is not yet defined. To date, there is not enough data about the role of single agent pemetrexed (Pem) or combination with bevacizumab (B) as MCX after first-line chemotherapy (FCX) which includes Pem. The objective of this retrospective analysis was to evaluate the efficacy of Pem single agent or in combination as MCX for NSCLC pts who have received Pem as FCX. Methods: A retrospective chart review considered pts with stage IIIB/IV NSCLC treated with Pem alone or Pem/B combination as MCX. Results: 41 pts were treated, median age: 64 years (range, 34-84); gender: 23 males/18 females; ethnicity: 26 Hispanic, 10 White, 4 African-American, and 1 Asian; histology: 39 adenocarcinoma. All chemotherapy regimens were frontline unless otherwise specified: 32 Carbo/Pem/B (1 pt received it as second line), 3 Cis/Pem/B, 3 Carbo/Pem, 1 Cis/Pem, and 2 Pem/B (as second line). Treatment schema was 6 cycles of FCX followed by MCX. The best response after completion of at least 4 cycles of FCX (n=37) was: 15 (41%) PR and 22 (59%) SD; 2 pts progressed after 2 cycles, and 2 other pts are receiving FCX (<4 cycles). One of these early progressions had ALK-EML4 mutation. 30 pts had received at least 1 cycle of MCX (median number of MCX cycles: 8; range: 1-27). Five pts progressed prior to start MCX. 28 of 30 pts on MCX received Pem as FCX; 29 of these pt. received Pem/B combination and 1 Pem alone as MCX regimen. Most common grade 3/4 AEs during MCX were: fatigue (n=1), anemia and thrombocytopenia (n=1), hyperkalemia (n=1), and hyponatremia (n=1). One of them died with pneumonia during Pem MCX without disease progression. After a median follow up of 10 months (range: 2-24), 15 pts (50%) who received at least 1 cycle of MCX has progressed. There are 3 long-term responders to MCX (> 20 months). Conclusions: Carbo/Pem/B is becoming a common regimen used as FCX followed by MCX Pem/B in eligible patients with non-squamous NSCLC. As MCX, Pem/B is well tolerated with most related AEs being grade 1-2. In patients who are able to receive at least 4 cycles of triplet therapy, the chances to attain DCR is high.