tbuckley/cabot-search huggingface dataset:
The legal implications of sexual activity between psychiatrist and patient
Authors: A A Stone
Journal: American Journal of Psychiatry (1976)

The author examines the legal and professional sanctions against sex between therapist and patient. The relevant literature of criminal law suggests that charges of rape or related sexual offenses against psychotherapists who exploit their patients are a remote possibility. Although sexual activity between therapist and patient may form the basis of a malpractice claim, the existing case law is complicated, and the legal distinctions are not always consistent with good psychiatric practice. Professional associations lack the legal expertise and indemnification to act in these situations, but medical boards in some states have the power to revoke licenses. In the end, patients must depend on the decent moral character of their therapists.
Predicting bacteraemia following chemotherapy administration in patients with hematological cancer (HC)
Authors: M. Moreau, A. Schwarzbold, J. Klastersky, A. Georgala, F. Muanza, M. Aoun, A. Ferrant, D. Bron, M. Paesmans
Journal: Journal of Clinical Oncology (2007)

19543 Background: Infections cause important morbidity and mortality in patients undergoing treatment for cancer. The type and the intensity of chemotherapy play an important role in the risk of infection which manifests itself most often as febrile neutropenia (FN) but regimen-specific risks are not well defined. Since bacteraemia is associated with increased mortality, we tried to determine predictors of it and to validate a classification of aggressiveness of a given chemotherapy regimen (CR) to be used in a risk prediction model in patients with HC. Methods: Patients older than 16 years, diagnosed with HC of any type were prospectively enrolled and followed at the “Institut Jules Bordet” and at the “Cliniques Universitaires Saint-Luc (UCL)” between 2001–2005. Out of the 266 patients, 22.9%, 43.6% and 33.5% were followed respectively during one cycle, 2 to 4 cycles and more than 4 cycles, totalizing 1053 cycles. Relevant patient’s information were collected at the beginning of the first cycle. Before each cycle, the CR score was computed, a blood examination performed and the temperature measured. Bacteraemia was defined according to IDSA criteria. FN was defined as a neutrophil count &lt; 500/μl and fever. Generalized Estimating Equations (GEE) was used for the analysis. Results: Among 1017 evaluable cycles, 148 (14.5%) were followed by an episode of bacteraemia. Among the cycles with FN, 35.5% had bacteraemia. In the final model, adjusted for antimibrobial prophylaxis (R 2 =0.22), the CR score was the most important predictor of bacteraemia (OR 4.2 [95% CI, 2.3–7.6]), for patients given an aggressive regimen compared to the others. The other predictors associated with bacteraemia were: underlying disease (3.2 [1.9–5.2]), a baseline monocytopenia (&lt;150/μL) (2.7 [1.6–4.3]), a baseline CRP &gt;10 mg/L (2.1 [1.2–3.7]), the first cycle of patient’s treatment (0.3 [0.2–0.7]) and the administration of immunosuppressive agents (2.2 [1.2–4.0]). Conclusions: Bacteraemia was frequent in patients with HC undergoing myelosuppressive chemotherapy, especially in patients with FN. The CR plays an important role but further studies are needed to investigate yet unidentified additional risk factors. Grant given by the FNRS in Belgium (“Fonds National pour la Recherche Scientifique”) No significant financial relationships to disclose.
Final results of the randomized phase III trial of sorafenib in advanced renal cell carcinoma: Survival and biomarker analysis
Authors: R. M. Bukowski, T. Eisen, C. Szczylik, W. M. Stadler, R. Simantov, M. Shan, J. Elting, C. Pena, B. Escudier
Journal: Journal of Clinical Oncology (2007)

5023 Background: Based on the significant PFS benefit of sorafenib (SOR) vs placebo (P) in a Phase III advanced RCC trial, P patients were unblinded and crossed over to SOR in May 2005. Final OS and biomarker data are reported. Methods: Final OS analysis was planned at ∼540 events (a=0.037 after adjusting for previous analyses). To minimize effect of crossover on OS, a secondary analysis was planned censoring P data on June 30, 2005 (a=0.037). Plasma VEGF and sVEGFR2 were measured by ELISA at baseline (BL), cycle (C) 1 day (D) 21, and C3D1. pERK was assayed by IHC. Results: 903 patients were randomized (SOR, 451; P, 452). The only OS analysis before crossover (May 2005) showed an estimated 39% OS improvement for SOR vs P (HR=0.72; p=0.018) (ECCO 2005); 216 P patients had crossed to SOR. OS analysis 6 months after crossover (Nov 2005) showed a 30% improvement in OS for SOR vs P (HR=0.77, p=0.015) (ASCO 2006). These OS differences did not reach prespecified O’Brien-Fleming statistical boundaries. Final OS (Sep 2006) at 561 deaths showed an improvement of 13.5% for SOR vs P and was not significant (median 17.8 vs 15.2 months; HR=0.88; p=0.146; a=0.037). Secondary analysis censoring P data (June 2005) showed a significant OS benefit for SOR vs P (HR=0.78, 95% CI: 0.62, 0.97; p=0.0287; a=0.037), suggesting crossover had confounded OS. Changes in VEGF (n=712) and sVEGFR2 (n=717) were observed after SOR treatment (AACR 2006); VEGF increased 32% (n=279) at C1D21 and 47% (n=203) at C3D1, and sVEGFR2 decreased 18% (n=282) and 24% (n=206). Using a COX proportional hazards model, BL VEGF was an independent prognostic factor (p=0.014); patients with high BL VEGF (&gt;131 pg/ml) had poorer prognosis and a trend towards greater PFS benefit with SOR (SOR vs P, HR=0.48 vs 0.64 for high vs low VEGF, p=0.096). BL sVEGFR2, changes in VEGF or sVEGFR2 at C1D21, and pERK levels in limited diagnostic tumor biopsies were not predictive of SOR response. Conclusion: SOR demonstrated a PFS benefit in advanced RCC, although ITT final OS analysis showed a confounding effect of crossover. Significant OS benefit of SOR was seen in a planned secondary analysis adjusting for crossover. VEGF levels have prognostic importance, and SOR-associated changes in VEGF and sVEGFR2 are consistent with inhibition of VEGF signaling. No significant financial relationships to disclose.
Abstract 12751: Activation of Stat-3 Mitochondria Translocation and Ameliorating Complex I Damage under Hypothermia Treatment for Post-cardiac Arrest Myocardial Dysfunction
Authors: Chien-Hua Huang, Min-Shan Tsai, Huei-Wen Chen, Wei-Tien Chang, Wen-Jone Chen
Journal: Circulation (2013)

Background: Myocardial dysfunction is one of the major causes leading mortality in the post-cardiac arrest period. Hypothermia treatment can ameliorate the myocardial injuries and improve myocardia...
The safety of vedolizumab for ulcerative colitis and Crohn's disease
Authors: Jean-Frédéric Colombel, Bruce E Sands, Paul Rutgeerts, William Sandborn, Silvio Danese, Geert D'Haens, Remo Panaccione, Edward V Loftus, Serap Sankoh, Irving Fox, Asit Parikh, Catherine Milch, Brihad Abhyankar, Brian G Feagan
Journal: Gut (2016)

<h3>Objective</h3> Vedolizumab is a gut-selective antibody to α<sub>4</sub>β<sub>7</sub> integrin for the treatment of ulcerative colitis (UC) and Crohn9s disease (CD). We report an integrated summary of the safety of vedolizumab. <h3>Design</h3> Safety data (May 2009–June 2013) from six trials of vedolizumab were integrated. Adverse events were evaluated in patients who received ≥1 dose of vedolizumab or placebo and were reported as exposure-adjusted incidence rates as the number of patients experiencing the event per 100 person-years (PYs) of exposure. Predictors of serious infection were assessed using a Cox proportional hazards model. <h3>Results</h3> In total, 2830 patients had 4811 PYs of vedolizumab exposure (median exposure range, 1–1977 days). No increased risk of any infection or serious infection was associated with vedolizumab exposure. Serious clostridial infections, sepsis and tuberculosis were reported infrequently (≤0.6% of patients). No cases of progressive multifocal leucoencephalopathy were observed. Independent risk factors for serious infection in UC were prior failure of a tumour necrosis factor α antagonist (HR, 1.99; 95% CIs 1.16 to 3.42; p=0.0122) and narcotic analgesic use (HR, 2.68; 95% CI 1.57 to 4.58; p=0.0003), and in CD were younger age (HR, 0.97; 95% CI 0.95 to 0.98; p&lt;0.0001), corticosteroid (HR, 1.88; 95% CI 1.35 to 2.63; p=0.0002) or narcotic analgesic use (HR, 2.72; 95% CI 1.90 to 3.89; p&lt;0.0001). Investigator-defined infusion-related reactions were reported for ≤5% of patients in each study. Eighteen vedolizumab-exposed patients (&lt;1%) were diagnosed with a malignancy. <h3>Conclusions</h3> Vedolizumab has a favourable safety profile with low incidence rates of serious infections, infusion-related reactions and malignancies over an extended treatment period. <h3>Trial registration number</h3> NCT01177228, NCT00619489, NCT00783718, NCT00783692, NCT01224171, NCT00790933.
Molecular monitoring of the myl/retinoic acid receptor-alpha fusion gene in acute promyelocytic leukemia by polymerase chain reaction
Authors: A Biondi, A Rambaldi, PP Pandolfi, V Rossi, G Giudici, M Alcalay, F Lo Coco, D Diverio, EM Pogliani, EM Lanzi
Journal: Blood (1992)
Use of a proliferation-based mRNA signature to predict outcome in early-stage non-small cell lung adenocarcinoma.
Authors: Carmen Behrens, Francesca Lombardi, Susanne Wagner, Junya Fujimoto, Maria G Raso, Lorenzo Spaggiari, Domenico Galetta, Elisha Huges, Julia E. Reid, Zaina Sangale, Stephen Swisher, Neda Kalhor, Cesar Moran, Alexander Gutin, Jerry S. Lanchbury, Edward S. Kim, Massimo Barberis, Ignacio I. Wistuba
Journal: Journal of Clinical Oncology (2012)

7023 Background: Adjuvant treatment of patients with early-stage lung adenocarcinoma is based on post-surgical pathological staging and patient performance status. Disparate outcomes within each staging group suggest that additional prognostic markers could improve our understanding of risk-benefit and potentially lead to better treatment decisions. A proliferation-based, mRNA expression profile was applied to public microarray data of surgically treated lung adenocarcinomas and a cohort of FFPE samples to test its potential prognostic utility. Methods: Public expression data (Director’s Consortium, DC) were derived from Affymetrix HG-U133A arrays. Clinical FFPE samples were assayed by quantitative PCR. A cell cycle progression (CCP) score was calculated from the expression average of 31 cell cycle genes normalized by 15 housekeeper genes. The prognostic value of the CCP score to predict stage I and II patient outcomes was evaluated by Cox proportional hazards analysis with disease-related death as the primary outcome measure. Results: In 256 DC cases, the CCP score was a significant predictor of death in univariate (p=0.0001) and multivariate analysis (p=0.001, HR 1.57, 95%CI 1.20-2.05) using age, stage, gender, smoking status and treatment as covariates. Similarly, in a second data set (GSE31210, n=204) the CCP score was highly associated with death (univariate, p=0.001; multivariate analysis, p=0.003, HR 1.81, 95% CI 1.24-2.66). Using quantitative PCR, the signature was applied to 381 FFPE samples with a median follow-up of 5 years collected at the MD Anderson Cancer Center and the European Institute for Oncology. In the presence of clinical covariates (as above and tumor size and pleural invasion), the CCP score remained the most significant predictor of death in univariate (p=0.0003) and multivariate analysis (p=0.007, HR 1.50, 95% CI 1.11-2.02). Conclusions: A 46 gene mRNA signature is a significant predictor of disease-related death in early-stage lung adenocarcinoma, providing independent prognostic value in the presence of clinical variables. This molecular predictor of cancer survival will be studied in additional cohorts for its ability to impact clinical treatment decisions.
Randomized pharmacokinetic evaluation of subcutaneous versus intravenous palonosetron in cancer patients treated with platinum-based chemotherapy.
Authors: A. Del Barrio, B. Sadaba, A. Gurpide, M. A. Campanero, M. Zudaire, J. M. López-Picazo, J. R. Azanza, A. Manubens, A. Gomez-Guiu, J. L. Perez-Gracia
Journal: Journal of Clinical Oncology (2010)

e19514 Background: 5-HT3 antagonists are one of the mainstays of antiemetic treatment and they are available for intravenous (IV) or oral use. However, these routes cannot be used in patients with emesis managed in an outpatient setting, such as palliative care. We have shown bioequivalence of subcutaneous (SC) and IV granisetron in cancer patients (Gurpide et al, The Oncologist 2007). Palonosetron is a novel and more potent 5-HT3 antagonist. We compared pharmacokinetics of palonosetron delivered by SC and IV route. Methods: Patients receiving platinum-based chemotherapy were randomized to receive SC or IV palonosetron 250 mcg during the first cycle and by the other route during the second one. The main endpoint was Area Under the Curve between 0-12 hours (AUC0–12h). Blood samples were drawn at 10, 15, 30, 45, 60, 90 m and 2, 3, 4, 8, 12 h after palonosetron. Drug levels were determined by HPLC with fluorescence detection after liquid-liquid extraction of the samples, with a quantitation limit of 0.1 ng/ml. A planned interim analysis was performed after the first 6 patients were included, to confirm safety and efficacy of the SC route. Results: From October 2009 to January 2010, 14 patients were included. Planned interim analysis showed that maximum concentration (Cmax) was reached 37.5 minutes after SC delivery and was higher and was reached faster by IV route. Ratio between SC-IV routes was 25% for Cmax and 84.1 for AUC0-12h. Palonosetron concentration at 4 h was the same for both routes. Emetic symptoms were equivalent with both alternatives. Conclusions: SC administration of palonosetron achieves similar AUC0–12h than IV administration, resulting in the same exposition to the drug. This administration route can benefit cancer patients managed in an outpatient setting. IV SC Ratio SC/IV 90% IC ratio Tmax (h) 0.03 ± 0.011 0.625 ± 0.137 Cmax (ng/ml) 5.57 ± 3.52 1.13 ± 0.32 25 15.15-41.34 AUC0-12h (ngxh/ml) 5.058 ± 2.8 4.5 ± 2.73 84.1 69.28-93.36 C4h (ng/ml) 0.53 ± 0.11 0.49 ± 0.12 90.3 81.6-99.94 No significant financial relationships to disclose.
Couple screening should be preferred for medical reasons
Authors: J. Morris
Journal: BMJ (1996)

EDITOR,—Oppenheimer and I recently concluded that the cost per detected fetus with cystic fibrosis was about £143000 for couple screening and £147000 for sequential (two step) screening,1 whereas H S Cuckle and colleagues conclude that the cost is about £46000-104000 for couple screening and £40000-90000 for sequential screening.2 Our costs are higher as we assumed that each person or couple would be retested for each pregnancy. Cuckle and colleagues assume that results would be reliably retained from previous pregnancies, and, if this was so, retesting would be unnecessary. …
A probabilistic generative model for quantification of DNA modifications enables analysis of demethylation pathways
Authors: Tarmo Äijö, Yun Huang, Henrik Mannerström, Lukas Chavez, Ageliki Tsagaratou, Anjana Rao, Harri Lähdesmäki
Journal: Genome biology (2016)

We present a generative model, Lux, to quantify DNA methylation modifications from any combination of bisulfite sequencing approaches, including reduced, oxidative, TET-assisted, chemical-modification assisted, and methylase-assisted bisulfite sequencing data. Lux models all cytosine modifications (C, 5mC, 5hmC, 5fC, and 5caC) simultaneously together with experimental parameters, including bisulfite conversion and oxidation efficiencies, as well as various chemical labeling and protection steps. We show that Lux improves the quantification and comparison of cytosine modification levels and that Lux can process any oxidized methylcytosine sequencing data sets to quantify all cytosine modifications. Analysis of targeted data from Tet2-knockdown embryonic stem cells and T cells during development demonstrates DNA modification quantification at unprecedented detail, quantifies active demethylation pathways and reveals 5hmC localization in putative regulatory regions.
A phase Ib/II study of cancer stem cell inhibitor BBI608 administered with panitumumab in KRAS wild-type (wt) patients (pts) with metastatic colorectal cancer (mCRC) following progression on anti-EGFR therapy.
Authors: Kristen Keon Ciombor, William Jeffery Edenfield, Joleen Marie Hubbard, Peter J. O'Dwyer, Carlos Becerra, Tim Larson, Alexander I. Spira, Axel Grothey, Divya Manoharan, Wei Li, Youzhi Li, Laura Borodyansky, Chiang Li, Tanios S. Bekaii-Saab
Journal: Journal of Clinical Oncology (2015)

3617 Background: BBI608 is an oral first-in-class cancer stemness inhibitor that works by targeting Stat3. Potent preclinical anti-tumor activity was observed in vitro and in vivo, in mono- and combination therapy. In a phase I study, BBI608 was well tolerated with encouraging signs of activity and a RP2D of 500 mg BID with additional ongoing studies showing that BBI608 can be safely combined with multiple chemotherapeutics. Methods: A phase Ib/II open-label, multi-center study in pts with advanced K-Raswt mCRC was performed to determine safety and preliminary activity of BBI608 administered orally at 480-500 mg BID with panitumumab (6 mg/kg bi-weekly) until disease progression, unacceptable toxicity, or other discontinuation criterion was met. Following clearance of the DLT period in 6 pts, 18 more pts were enrolled. Results: All of the 24 pts enrolled were pre-treated with ≥2 lines of therapy and 12/24 with ≥3 lines of therapy. An MTD was not determined and BBI608 could be given in combination with full dose panitumumab. The safety profile was consistent with that of each agent as monotherapy and most common adverse events included grade 1-2 diarrhea, abdominal cramps, nausea and vomiting. Grade 3 hypokalemia and dehydration occurred in 2 pts. No significant pharmacokinetic interactions were observed. Disease control (SD+PR) was observed in 4 of 9 (44.4%) anti-EGFR naïve pts. Of those, 2 of 9 (22%) had PR (35.5% and 33.3% regressions), and 2 had SD. Disease control (only SD) was observed in 8/15 (53.3%) pts who had failed anti-EGFR (cetuximab) therapy, 2 of which had SD with regression (12.9% and 6.8%). The median progression free survival was 9 and 16.4 weeks in anti-EGFR naive and previously exposed pts, respectively. Conclusions: This phase Ib/II study demonstrated that BBI608 and bi-weekly panitumumab can be safely combined at full dose. The response rate in anti-EGFR naïve pts was notably greater than that of anti-EGFR monotherapy. Moreover, encouraging preliminary activity was observed in K-Ras wt mCRC regardless of prior anti-EGFR exposure, suggesting that BBI608 may sensitize pts to repeat anti-EGFR therapy. Clinical trial information: NCT01776307.
To<i>JAMA</i>Peer Reviewers, Authors, and Readers—Thank You
Authors: Howard Bauchner, Phil B. Fontanarosa, Robert M. Golub
Journal: JAMA (2016)

1 Peer review remains an essential aspect of scientific publication in helping ensure that the manuscripts published in JAMA represent important and valid studies.The comments, suggestions, and insights from the peer reviewers are carefully considered in editorial decision making and are instrumental in improving the quality of published reports.We extend our sincere thanks to all peer reviewers who provided thoughtful and scholarly evaluations of manuscripts.The integrity and quality of JAMA are a reflection of our peer review process.We also
A Phase I Trial of Irinotecan (Iri) and Buparlisib in Previously Treated Patients (Pts) with Metastatic Colorectal Cancer (Mcrc): Final Results
Authors: J.C. Baranda, G. Reed, S. Williamson, M. Stoltz, R. Perez, C. Mackay, R. Madan, J. Scott, A. Godwin
Journal: Annals of Oncology (2014)
Symptom control during the terminal phase of malignancies
Authors: F. G. Foerster, E. Moebius, I. Wagner, E. Schlegel
Journal: Journal of Clinical Oncology (2004)

8236 Introduction & objective There is no doubt that palliative care plays an important role in improving the quality of living of patients suffering from tumors. The present study was designed to analyse our symptom management for moribund patients. Patients & methods The combined prospective/retrospective survey (significance test: χ2 ) of random samples from the years 2000 and 2003 covered a total of 144 patients (pts.), 75 female (52.1 %) and 69 male (47.9 %), with a mean age of 67.4 (36 –96) years. All pts. suffered from far advanced malignant tumors: brain tumors 3.5 %, head and neck tumors 11.1 %, lung cancer 14.6 %, oesophagogastrointestinal tumors 26.4 %, brest cancer 7.6 %, gynaecological tumors 11.8 %, urological tumors 13.2 %, skin tumors 0.7 %, soft-tissue tumors 0.7 %, CUP 2.8 %, hemoblastoses 7.6 %. 70.1 % of the pts. had metastases, 84.7 % major concomitant diseases, and 7.6 % further malignant tumors. Results 13 different symptoms were diagnosed in the moribund pts. The symptoms most frequently encountered included restlessness 63.9 %, pain 46.5 %, death rattle 29.2 %, dyspnoea 28.5 %, fever 24.3 %, anxiety 19.4 %. No (coma) symptoms were found in 6 %, 1 symptom in 19 %, 2 symptoms in 36 %, 3 symptoms in 24 %, and 4+ symptoms in 15 %. The analysis showed a significant (p < .001) reduction in symptom frequency as well as a significant (p < .01/< .001) control/palliation of complaints. Symptom evaluation was performed via an analysis of verbal utterances 20 % (speaking, crying, moaning) as well as through an appraisal of facial expressions 35 %, gestures 29 %, motoric expressions 20 % as well as of the respiratory rate and respiratory murmur 58 %. A range of different medicines were used for symptom control: opioids 65 %, peripheral analgetics 14 %, antipyretics 21 %, parasympatholics 20 %, psychotropics 21 %, hypnotics/sedatives 15 %, corticosteroids 10 %. Conclusion An effective symptom management is necessary and feasible during the final phase. It allows pts. to die in dignity. No significant financial relationships to disclose.
Levels of Allergy Cluster with Asthma Severity in Inner-City Children.
Authors: Edward M. Zoratti, Rebecca A. Zabel, Denise C. Babineau, Jacqueline A. Pongracic, George T. O'Connor, Robert A. Wood, Gurjit K. Khurana Hershey, Carolyn Kercsmar, Rebecca S. Gruchalla, Meyer Kattan, Stephen J. Teach, Samuel J. Arbes, Cynthia Visness, William W. Busse, Peter J. Gergen, Alkis Togias, Andrew H. Liu
Journal: Journal of Allergy and Clinical Immunology (2016)
Dangerousness and civil commitment of the mentally ill: some public policy considerations
Authors: S A Shah
Journal: American Journal of Psychiatry (1975)

The author discusses "dangerousness to others" as a ground for involuntary civil commitment of the mentally ill, suggesting that there is often a confounding of legal/public-policy concerns and mental health concerns in issues related to this concept. The questionable nature of the presumption of dangerousness in mental patients and the overprediction of dangerous behavior for this group indicate that such commitment processes may circumvent legal safeguards designed to ensure due process. The author recommends that psychiatrists and other mental health professionals assume greater responsibility for the ways in which their services are used in these proceedings.