tbuckley/cabot-search huggingface dataset:
Randomized, Double-Blind, Placebo-Controlled Study to Assess the Efficacy and Toxicity of Subcutaneous Ketamine in the Management of Cancer Pain
Authors: Janet Hardy, Stephen Quinn, Belinda Fazekas, John Plummer, Simon Eckermann, Meera Agar, Odette Spruyt, Debra Rowett, David C. Currow
Journal: Journal of Clinical Oncology (2012)

Purpose The anesthetic ketamine is widely used for pain related to cancer, but the evidence to support its use in this setting is weak. This study aimed to determine whether ketamine is more effective than placebo when used in conjunction with opioids and standard adjuvant therapy in the management of chronic uncontrolled cancer pain. Ketamine would be considered of net benefit if it provided clinically relevant improvement in pain with limited breakthrough analgesia and acceptable toxicity. Patients and Methods In this multisite, dose-escalation, double-blind, randomized, placebo-controlled phase III trial, ketamine or placebo was delivered subcutaneously over 3 to 5 days. Results In all, 185 participants were included in the primary analysis. There was no significant difference between the proportion of positive outcomes (0.04; 95% CI, −0.10 to 0.18; P = .55) in the placebo and intervention arms (response rates, 27% [25 of 92] and 31% [29 of 93]). Pain type (nociceptive v neuropathic) was not a predictor of response. There was almost twice the incidence of adverse events worse than baseline in the ketamine group after day 1 (incidence rate ratio, 1.95; 95% CI, 1.46 to 2.61; P &lt; .001) and throughout the study. Those receiving ketamine were more likely to experience a more severe grade of adverse event per day (odds ratio, 1.09; 95% CI, 1.00 to 1.18; P = .039). The number of patients needed to treat for one additional patient to have a positive outcome from ketamine was 25 (95% CI, six to ∞). The number needed to harm, because of toxicity-related withdrawal, was six (95% CI, four to 13). Conclusion Ketamine does not have net clinical benefit when used as an adjunct to opioids and standard coanalgesics in cancer pain.
Effects of cyclo-oxygenase inhibition on exhaled eicosanoids in patients with COPD
Authors: P Montuschi
Journal: Thorax (2005)

Leukotriene (LT) B4 concentrations are increased and prostaglandin (PG) E2 concentrations are decreased in exhaled breath condensate (EBC) in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to investigate the short term effects of cyclo-oxygenase (COX) inhibition on exhaled LTB4 and PGE2 concentrations in patients with COPD and to identify the COX isoform responsible for exhaled PGE2 production.Two studies were performed. A double blind, crossover, randomised, placebo controlled study with ibuprofen (400 mg qid for 2 days), a non-selective COX inhibitor, was undertaken in 14 patients with stable COPD, and an open label study with oral rofecoxib (25 mg once a day for 5 days), a selective COX-2 inhibitor, was undertaken in a different group of 16 COPD patients. EBC was collected before and after drug treatment. Exhaled LTB4 and PGE2 concentrations were measured with specific immunoassays.All patients complied with treatment as indicated by a reduction in ex vivo serum thromboxane B2 concentrations (ibuprofen) and a reduction in lipopolysaccharide induced increase in ex vivo plasma PGE2 values (rofecoxib) of more than 80%. Exhaled LTB4 was increased after ibuprofen (median 175.5 (interquartile range 128.8-231.5) pg/ml v 84.0 (70.0-98.5) pg/ml, p < 0.001) and exhaled PGE2 was reduced (93.5 (84.0-105-5) pg/ml v 22.0 (15.0-25.5) pg/ml, p < 0.0001). Rofecoxib had no effect on exhaled LTB4 (p = 0.53) or PGE2 (p = 0.23).Non-selective COX inhibition decreases PGE2 and increases LTB4 in EBC, whereas selective COX-2 inhibition has no effect on these eicosanoids. PGE2 in EBC is primarily derived from COX-1 activity, and COX inhibition may redirect arachidonic acid metabolism towards the 5-lipoxygenase pathway.
Forced oscillation measurements do not affect upper airway muscle tone or sleep in clinical studies
Authors: J.R. Badia, R. Farré, J. Rigau, M.E. Uribe, D. Navajas, J.M. Montserrat
Journal: European Respiratory Journal (2001)

Upper airway obstruction in the sleep apnoea/hypopnoea syndrome (SAHS) can be easily assessed by measuring respiratory impedance with the forced oscillation technique (FOT). This methodology has been proposed as a useful clinical tool both for the diagnosis of sleep breathing disorders and for continuous positive airway pressure (CPAP) titration. However, previous studies suggest that the application of high-frequency pressure oscillation to the upper airway may induce changes in the electroencephalogram (EEG) or upper airway muscle function. The effect of FOT measurements on upper airway muscle tone and EEG in clinical sleep studies was examined. Seven patients with moderate SAHS were included (age: 54±11 yrs; apnoea/hypopnoea index: 43±21 events·h −1 ; body mass index: 30±2 kg·m −2 ). Genioglossus surface electromyogram activity (EMGgg) and EEG signal were analysed with and without FOT application (frequency: 5 Hz and 30 Hz; peak-to-peak pressure oscillation: 1 cmH 2 O) during stable sleep. Measurements were carried out in two different situations. Step 1: applying FOT during episodes of obstructive events or flow limitation; and step 2: during prolonged periods of normal breathing at optimal CPAP. The root mean square of EMGgg activity and fast Fourier analysis (alpha and delta bands) of the EEG signal were performed. The application of FOT did not increase EMGgg activity in any of the situations studied. In addition, no evidence of the effects on EEG was found: alpha/delta relationship: awake:0.70, baseline sleep:0.13, FOT(5 Hz):0.18, FOT(30 Hz):0.11. The presented results suggest that the use of forced oscillation technique over the ranges of frequency and amplitude proposed for clinical sleep studies does not induce changes in upper airway muscle activity and neurological variables in patients with sleep apnoea/hypopnoea syndrome.
Nasal versus full face mask for noninvasive ventilation in chronic respiratory failure
Authors: G.N. Willson, A.J. Piper, M. Norman, W.G. Chaseling, M.A. Milross, E.R. Collins, R.R. Grunstein
Journal: European Respiratory Journal (2004)

This study was undertaken to determine the efficacy of nasal mask (NM) versus full face mask (FFM) for the delivery of noninvasive ventilation (NIV) in subjects with nocturnal hypoventilation. A total of 16 patients (11 males) were enrolled, all with nocturnal hypoventilation currently treated at home with NIV via pressure preset devices. Subjects underwent full polysomnography on three occasions; on the first night current therapy on NM was reviewed, followed by two experimental studies in randomised order using either NM or FFM. NIV settings and oxygen flow rate were the same under both conditions. Notably, 14 of the 16 subjects required the use of a chinstrap to minimise oral leak. Apnoea-hypopnoea indices were within normal limits under both conditions (1.7±3.4 NM versus 1.6±2.4 h FFM). The type of interface did not significantly affect gas exchange during sleep (minimum average arterial oxyhaemoglobin saturation total sleep time 93.4±2.1 NM versus 92.8±2.5% FFM, Delta transcutaneous carbon dioxide nonrapid eye movement sleep to rapid eye movement sleep (0.58±0.36 NM versus 0.50±0.40 kPa FFM). Sleep efficiency was significantly reduced on the FFM (78±9 NM versus 70±14% FFM), although arousal indices were comparable under both conditions (15.6±9.8 NM versus 15.8±8.8 h FFM). Full face masks appear to be as effective as nasal masks in the delivery of noninvasive ventilation to patients with nocturnal hypoventilation. However, a chinstrap was required to reduce oral leak in the majority of subjects using the nasal mask.
Serum screening for Down's syndrome.
Authors: P. Burton, J. J. Kurinczuk, H. Botha, A. Lowry, T. A. Sheldon
Journal: BMJ (1989)

Breach of this standard is ipso facto malpractice.Furthermore, responsibility for professional acts rests with the actUal treatihg physician and may not be trahsferted to leiployers, government pro- gramnmes, hospital officials or commnittees, chiefs of service, comftiiWs §onets, atid the like.We have no professional dMty to any such party; our obligatlon is solely t6 out patienits.
The Supreme Court and the Purposes of Medicine
Authors: M. Gregg Bloche
Journal: New England Journal of Medicine (2006)

What role should physicians have in defining the purposes of their profession — the functions that medicine should and should not serve? Many observers hold that medicine's aims are for doctors and patients to decide, without interference from the state. But in fact, government limits medicine's purposes in many ways. Doctors cannot prescribe mind-altering substances for recreational use or anabolic steroids to enhance athletic performance. Physicians were once barred from terminating pregnancies, and today, in 49 states, they are not allowed to assist the terminally ill in ending their lives. In some jurisdictions, psychiatrists cannot medicate condemned prisoners to make . . .
Evidence of cataplerosis in a patient with neonatal classical galactosemia presenting as citrin deficiency
Authors: François Feillet, Marc Merten, Shyue-Fang Battaglia-Hsu, Daniel Rabier, Keiko Kobayashi, Jean Straczek, Michèle Brivet, Elisabeth Favre, Jean-Louis Guéant
Journal: Journal of Hepatology (2008)
Antibody response to a T-dependent antigen requires B cell expression of complement receptors.
Authors: D A Croix, J M Ahearn, A M Rosengard, S Han, G Kelsoe, M Ma, M C Carroll
Journal: The Journal of Experimental Medicine (1996)

Several lines of evidence indicate that antibody responses to T-dependent antigens require complement receptors expressed on either B lymphocytes or follicular dendritic cells. We have used RAG-2 deficient blastocyst complementation to create mice specifically lacking B cell complement receptors. Despite normal expression of complement receptor 1 (CR1[CD35]) and CR2 (CD21) on follicular dendritic cells, these mice have a profound defect in their capacity to mount a T-dependent antibody response. This is the first direct demonstration in vivo that B cell expression of complement receptors is required for a humoral immune response. This is the first direct demonstration in vivo that B cell expression of complement receptors is required for a humoral immune response. This suggests that CD21 and/or CD35 on B lymphocytes may be required for cellular activation, adsorptive endocytosis of antigen, recruitment to germinal centers, and/or protection from apoptosis during the humoral response to T-dependent antigens.
Generation of Carcinoembryonic Antigen (CEA)-Specific T-Cell Responses in HLA-A*0201 and HLA-A*2402 Late-Stage Colorectal Cancer Patients after Vaccination with Dendritic Cells Loaded with CEA Peptides
Authors: Ko-Jiunn Liu, Chuan-Cheng Wang, Li-Tzong Chen, Ann-Lii Cheng, Dong-Tsamn Lin, Yu-Chen Wu, Wei-Lan Yu, Yi-Mei Hung, Hui-Yu Yang, Shin-Hun Juang, Jacqueline Whang-Peng
Journal: Clinical Cancer Research (2004)

Abstract Purpose: We intranodally immunized metastatic colorectal carcinoma patients, who had failed standard chemotherapy, with dendritic cells (DCs) pulsed with HLA-A*0201- or HLA-A*2402-restricted carcinoembryonic antigen (CEA) peptides to evaluate the safety of this treatment and the immune response against CEA peptides before and after the treatment. Experimental Design: Six patients with the HLA-A*2402 genotype and 4 patients with the HLA-A*0201 genotype were enrolled. A single CEA peptide (YLSGANLNL) or two CEA peptides (QYSWFVNGTF and TYACFVSNL) were used for patients with the HLA-A*0201 or HLA-A*2402 genotype, respectively. Autologous DCs were generated by culturing adherent mononuclear cells with interleukin 4 and granulocyte macrophage colony-stimulating factor for 6 days. Maturation of DCs was then induced with tumor necrosis factor α for 40 h. Mature DCs were pulsed with appropriate CEA peptides for 2 h. After washing, 1 million peptide-pulsed DCs were injected into one inguinal lymph node under sonographic guidance. Each patient received four injections. Results: No grade II/III toxicity or autoimmunity was observed. An increase in the number of CEA-specific T cells after DC vaccination could be detected in 7 of 10 (70%) patients. Two (20%) patients had stable disease for at least 12 weeks. One of these 2 patients experienced a transient decrease in CEA levels during the treatment period and also had the most significant T-cell response against the immunizing CEA peptides. Conclusions: These results suggest that our vaccination procedure can generate or boost specific T-cell responses and may provide clinical benefit in certain cancer patients.
Healthcare costs of inflammatory bowel disease have shifted from hospitalisation and surgery towards anti-TNFα therapy: results from the COIN study
Authors: Mirthe Emilie van der Valk, Marie-Josée J Mangen, Max Leenders, Gerard Dijkstra, Ad A van Bodegraven, Herma H Fidder, Dirk J de Jong, Marieke Pierik, C Janneke van der Woude, Mariëlle J L Romberg-Camps, Cees HM Clemens, Jeroen M Jansen, Nofel Mahmmod, Paul C van de Meeberg, Andrea E van der Meulen-de Jong, Cyriel Y Ponsioen, Clemens JM Bolwerk, J Reinoud Vermeijden, Peter D Siersema, Martijn GH van Oijen, Bas Oldenburg
Journal: Gut (2012)

<h3>Objective</h3> The introduction of anti tumour necrosis factor-α (anti-TNFα) therapy might impact healthcare expenditures, but there are limited data regarding the costs of inflammatory bowel diseases (IBD) following the introduction of these drugs. We aimed to assess the healthcare costs and productivity losses in a large cohort of IBD patients. <h3>Design</h3> Crohn9s disease (CD) and ulcerative colitis (UC) patients from seven university hospitals and seven general hospitals were invited to fill-out a web-based questionnaire. Cost items were derived from a 3 month follow-up questionnaire and categorised in outpatient clinic, diagnostics, medication, surgery and hospitalisation. Productivity losses included sick leave of paid and unpaid work. Costs were expressed as mean 3-month costs per patients with a 95% CI obtained using non-parametric bootstrapping. <h3>Results</h3> A total of 1315 CD patients and 937 UC patients were included. Healthcare costs were almost three times higher in CD as compared with UC, €1625 (95% CI €1476 to €1775) versus €595 (95% CI €505 to €685), respectively (p&lt;0.01). Anti-TNFα use was the main costs driver, accounting for 64% and 31% of the total cost in CD and UC. Hospitalisation and surgery together accounted for 19% and &lt;1% of the healthcare costs in CD and 23% and 1% in UC, respectively. Productivity losses accounted for 16% and 39% of the total costs in CD and UC. <h3>Conclusions</h3> We showed that healthcare costs are mainly driven by medication costs, most importantly by anti-TNFα therapy. Hospitalisation and surgery accounted only for a minor part of the healthcare costs.
Oregon Physicians' Attitudes About and Experiences With End-of-Life Care Since Passage of the Oregon Death with Dignity Act
Authors: Linda Ganzini
Journal: JAMA (2001)

The Oregon Death with Dignity Act, passed by ballot measure in 1994 and enacted in October 1997, legalized physician-assisted suicide for competent, terminally ill Oregonians, but little is known about the effects of the act on clinical practice or physician perspective.To examine Oregon physicians' attitudes toward and practices regarding care of dying patients since the passage of the Death with Dignity Act.A self-administered questionnaire was mailed in February 1999 to Oregon physicians eligible to prescribe under the act. Of 3981 eligible physicians, 2641 (66%) returned the questionnaire by August 1999.Physicians' reports of their efforts to improve care for dying patients since 1994, their attitudes, concerns, and sources of information about participating in the Death with Dignity Act, and their conversations with patients regarding assisted suicide.A total of 791 respondents (30%) reported that they had increased referrals to hospice. Of the 2094 respondents who cared for terminally ill patients, 76% reported that they made efforts to improve their knowledge of the use of pain medications in the terminally ill. Nine hundred forty-nine responding physicians (36%) had been asked by a patient if they were potentially willing to prescribe a lethal medication. Seven percent of all survey participants reported that 1 or more patients became upset after learning the physician's position on assisted suicide, and 2% reported that 1 or more patients left their care after learning the physician's position on assisted suicide. Of the 73 physicians who were willing to write a lethal prescription and who had received a request from a patient, 20 (27%) were not confident they could determine when a patient had less than 6 months to live.Most Oregon physicians who care for terminally ill patients report that since 1994 they have made efforts to improve their ability to care for these patients and many have had conversations with patients about assisted suicide.
The cost impact of in vivo diagnosis of diminutive polyps: experience from a screening endoscopy programme
Authors: G. Longcroft-Wheaton, P. Bhandari
Journal: Gut (2011)

<h3>Introduction</h3> The histological evaluation of diminutive polyps is time consuming and expensive. Recent developments in endoscopic techniques have enabled the prediction of histology in vivo using vascular enhancement techniques and dye sprays. This study aims to evaluate the cost effectiveness of in vivo histology prediction using white light (WLI) FICE and indigo carmine (IC) dye spray in the bowel cancer screening programme. <h3>Methods</h3> Patients undergoing screening on the national bowel cancer screening programme (BCSP) were prospectively evaluated. Polyps were examined using WLI, FICE and IC prior to removal and histological examination. The accuracy of the in vivo histology prediction was calculated. Using a histology cost of £58.90 per polyp the cost of histological analysis for the cohort was calculated. Cost savings for sending neoplastic polyps (Portsmouth protocol) or just polyp cancers (modified Portsmouth protocol) was then calculated. Finally the cost per missed adenoma was assessed for WLI, FICE and IC dye spray. <h3>Results</h3> 141 patients were examined, with 305 diminutive polyps &lt;10 mm found in 106 patients (mean 2.9 polyps per patient). When using HD endoscopes a sensitivity for adenomas of 76% with WLI, 93% with FICE and 94% with IC was achieved. This is in keeping with similar results from the DISCARD study using narrow band imaging. No polyp cancers were mis-diagnosed. Rescope interval as determined by BSG guidelines would have been correct in 97% of cases using either FICE or IC for in vivo histology prediction. The potential costs for each strategy are shown in table 1. Based on our data a potential cost saving of £109 per person undergoing screening colonoscopy could be made. Within the national BCSP 12153 colonoscopies are performed per annum with 11,619 benign polyps &lt;10 mm removed per year. Using this data we have calculated that in vivo diagnosis could represent a potential saving of £684,339.47 per annum for histology related costs. <h3>Conclusion</h3> (1) In vivo diagnosis of polyps and retrieving and sending only adenomas can lead to a 1.5–2-fold reduction in pathology costs. (2) In vivo diagnosis where only diminutive cancers are sent for histology can lead to an 75–113-fold reduction in pathology costs. (3) A simple change in practice (after appropriate training) with in vivo polyp diagnosis can significantly reduce the work load for extremely stretched and busy endoscopy and pathology departments.
<i>SLCO2B1</i> and <i>SLCO1B3</i> May Determine Time to Progression for Patients Receiving Androgen Deprivation Therapy for Prostate Cancer
Authors: Ming Yang, Wanling Xie, Elahe Mostaghel, Mari Nakabayashi, Lillian Werner, Tong Sun, Mark Pomerantz, Matthew Freedman, Robert Ross, Meredith Regan, Nima Sharifi, William Douglas Figg, Steven Balk, Myles Brown, Mary-Ellen Taplin, William K. Oh, Gwo-Shu Mary Lee, Philip W. Kantoff
Journal: Journal of Clinical Oncology (2011)

Purpose Androgen deprivation therapy (ADT), an important treatment for advanced prostate cancer, is highly variable in its effectiveness. We hypothesized that genetic variants of androgen transporter genes, SLCO2B1 and SLCO1B3, may determine time to progression on ADT. Patients and Methods A cohort of 538 patients with prostate cancer treated with ADT was genotyped for SLCO2B1 and SLCO1B3 single nucleotide polymorphisms (SNP). The biologic function of a SLCO2B1 coding SNP in transporting androgen was examined through biochemical assays. Results Three SNPs in SLCO2B1 were associated with time to progression (TTP) on ADT (P &lt; .05). The differences in median TTP for each of these polymorphisms were about 10 months. The SLCO2B1 genotype, which allows more efficient import of androgen, enhances cell growth and is associated with a shorter TTP on ADT. Patients carrying both SLCO2B1 and SLCO1B3 genotypes, which import androgens more efficiently, exhibited a median 2-year shorter TTP on ADT, demonstrating a gene-gene interaction (P interaction = .041). Conclusion Genetic variants of SLCO2B1 and SLCO1B3 may function as pharmacogenomic determinants of resistance to ADT in prostate cancer.
The effect of brief vagal stimulation on the isolated rabbit sinus node.
Authors: J F Spear, K D Kronhaus, E N Moore, R P Kline
Journal: Circulation Research (1979)

We developed an isolated rabbit atrial preparation which responds consistently and reproducibly to brief, submaximal stimulation of the autonomic nerves contained in it. In 6 of 11 preparations in the presence of propranolol (1 mg/liter), the time course of changes in the atrial rate following 120 msec vagal stimulation was bimodal. The maximal slowing occurred at 0.64 +/- 0.16 second, and the peak secondary slowing occurred at 2.3 +/- 1.0 seconds. An acceleratory component occurred between the first and second peaks between 0.8 and 1.6 seconds. The total time course of vagal effect lasted for 5.0 +/- 2.0 seconds. These changes in rate could not be explained by shifts in the location of the primary pacemaker. The acceleratory component was due to a 4.7 +/- 2.0 (SD) mV depolarization of the maximum diastolic membrane potential of the primary pacemaker of the sinus node which lasted for 1.8 +/- 0.3 seconds. Following vagal stimulation, there was an increase of 0.2 mM in the activity of potassium in the extracellular space recorded with a potassium-sensitive electrode; this peaked between 1.4 and 2.5 seconds and cleared with an exponential time course. The halftimes for recovery ranged between 2.8 and 4.6 seconds. The initial peak slowing of the bimodal time course and the acceleratory component therefore appear to be direct effects of acetylcholine. The secondary slowing occurs after acetylcholine presumably has been inactivated and occurs coincidently with the accumulation of potassium in the extracellular space.
An assessment of interactions between global health initiatives and country health systems
Authors: Badara Samb, Tim Evans, Mark Dybul, Rifat Atun, Jean-Paul Moatti, Sania Nishtar, Anna Wright, Francesca Celletti, Justine Hsu, Jim Yong Kim, Ruairi Brugha, Asia Russell, Carissa Etienne
Journal: The Lancet (2009)