tbuckley/cabot-search huggingface dataset:
Clinical Trials: Are They a Good Buy?
Authors: Charles L. Bennett, Jared R. Adams, Kirstin S. Knox, Andrew M. Kelahan, Samuel M. Silver, Joseph S. Bailes
Journal: Journal of Clinical Oncology (2001)

PURPOSE: Concern that clinical trials may be too costly has been used to justify traditionally restrictive insurer policies regarding clinical trials. Additionally, fear of insurer reimbursement denial can be a significant barrier to clinical trial participation. In this study, we reviewed the empirical data on costs of clinical trials versus standard care and summarized the current status of policy initiatives related to clinical trial insurance reimbursement. METHODS: Electronic and print data sources were searched for studies on the costs of oncology clinical trials. Information on policy initiatives for clinical trial reimbursement was obtained from the American Society of Clinical Oncology, the American Society of Hematology, and the Coalition of National Cancer Cooperative Groups and from searches of World Wide Web sites. RESULTS: Five pilot studies provided information for 377 patients on phase II/III clinical trials matched with controls on standard care. Cost estimates ranged from 10% lower to 23% higher costs/charges for clinical trials in comparison to standard medical care. Medicare, 14 states, and several private insurers now cover the costs of patient care in “qualifying” clinical trials. CONCLUSION: Findings from small pilot studies suggest that phase II and III clinical trials result in at most modest increases in cost over standard treatment costs. Also, an increasing number of policy makers have decided to support clinical trial reimbursement initiatives. It is hoped that economic data from large observational studies will facilitate widespread and permanent decisions that support reimbursement for phase I, II, and III clinical trial participation.
Value of routine funduscopy in patients with hypertension: systematic review
Authors: Bert-Jan H van den Born, Caroline A A Hulsman, Joost B L Hoekstra, Reinier O Schlingemann, Gert A van Montfrans
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objective</b> To evaluate the additional value of funduscopy in the routine management of patients with hypertension. <b>Design</b> Systematic review. <b>Participants</b> Adults aged 19 or more with hypertensive retinopathy. <b>Data sources</b> Medline, Embase, and the Cochrane Library from 1990. <b>Review methods</b> Studies were included that assessed hypertensive retinopathy with blinding for blood pressure and cardiovascular risk factors. Studies on observer agreement had to be assessed by two or more observers and expressed as a κ statistic. Studies on the association between hypertensive retinopathy and hypertensive organ damage were carried out in patients with hypertension. The association between hypertensive retinopathy and cardiovascular risk was carried out in unselected normotensive and hypertensive people without diabetes mellitus. <b>Results</b> The assessment of microvascular changes in the retina is limited by large variation between observers. The positive and negative predictive values for the association between hypertensive retinopathy and blood pressure were low (47% to 72% and 32% to 67%, respectively). Associations between retinal microvascular changes and cardiovascular risk were inconsistent, except for retinopathy and stroke. The increased risk of stroke, however, was also present in normotensive people with retinopathy. These studies did not adjust for other indicators of hypertensive organ damage. <b>Conclusion</b> Evidence is lacking that routine funduscopy is of additional value in the management of hypertensive patients.
Nasal CPAP or intubation at birth for preterm infants
Authors: Alex Shalshin
Journal: Thorax (2008)

Bronchopulmonary dysplasia, resulting from damage to the lungs caused by ventilation, remains a major cause of mortality in preterm infants. In this international multicentre study the investigators compared continuous positive airway pressure (CPAP) with intubation in preterm infants (infants born at 25–28 weeks’ gestation) to assess whether avoidance of ventilation reduced the incidence of bronchopulmonary dysplasia.

A total of 610 …
Endothelin-1-mediated contraction of mouse small airways is resistant to salbutamol, but sensitive to rosiglitazone
Authors: Jane Bourke, Chantal Donovan, Meaghan FitzPatrick
Journal: European Respiratory Journal (2013)

Introduction:  In vitro  investigations of bronchodilator efficacy routinely examine large airways and utilise methacholine (MCh) as a constrictor agent. However, small airway reactivity can be assessed  in situ  in lung slices, and increased levels of endothelin-1 (Et-1) detected in steroid-resistant asthma support its use as a clinically relevant alternative constrictor. We have identified rosiglitazone (RGZ) as a novel bronchodilator opposing small airway contraction to methacholine (MCh), but its efficacy against Et-1 is yet to be determined.  Methods: Changes in airway lumen area in response to Et-1, MCh, RGZ and the β 2 -adrenoceptor agonist salbutamol (SALB) were visualized in lung slices from Balb/C mice. The effects of ET A - and ET B -selective antagonists (BQ123, BQ788) on contractions to Et-1 were also assessed.  Results: Mouse small airways were >10-fold more sensitive to Et-1 than trachea or bronchi. Et-1 was ∼20-fold more potent than MCh in small airways (pEC 50  8.5±0.1, 7.1±0.1, p B -receptors. In reversing submaximal Et-1 contractions, RGZ had lower potency but greater efficacy than SALB (max %relaxation: RGZ 71±4%, SALB 51±14%). Relaxation to RGZ, but not SALB, was maintained in maximally contracted airways, and the development of Et-1-induced reductions in lumen area was inhibited by RGZ only.  Conclusion: Et-1 is a potent bronchoconstrictor of mouse small airways. Contraction to Et-1 is relatively resistant to β 2  -adrenoceptor-mediated relaxation. Characterisation of the mechanism underlying the greater efficacy of RGZ in this setting may identify novel approaches targetting small airways for asthma treatment.
Fate of Skin Homografts in X-Irradiated Mice Treated With Homologous Marrow
Authors: Joan M. Main, Richmond T. Prehn
Journal: JNCI Journal of the National Cancer Institute (1957)

Fate of Skin Homografts in X-Irradiated Mice Treated With Homologous Marrow Joan M. Main, Joan M. Main Laboratory of Biology, National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Richmond T. Prehn Richmond T. Prehn Laboratory of Biology, National Cancer Institute,3Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar 2Present address: U. S Public Health Service Hospital, Seattle, Washington. 3National Institutes of Health, Public Health Service, U. S. Department of Health, Education, and Welfare. Author Notes JNCI: Journal of the National Cancer Institute, Volume 19, Issue 6, December 1957, Pages 1053–1064, https://doi.org/10.1093/jnci/19.6.1053 Published: 01 December 1957 Article history Received: 04 June 1957 Published: 01 December 1957
Targeted Temperature Management after Cardiac Arrest
Authors: Niklas Nielsen, Jørn Wetterslev, Hans Friberg
Journal: New England Journal of Medicine (2014)

To the Editor: Nielsen and coauthors (Dec.5 issue) 1 show the importance of avoiding hyperthermia in patients who have had a cardiac arrest.However, if the clinical objective is to improve the neurologic outcome, it is important to define the expected neurologic outcome in individual patients.Studies have shown that the severity of neuronal lesions is dependent on the delay in initiation of cooling after reperfusion. 2 In the article by Nielsen et al., the studied patients had a median return of spontaneous circulation of 25 minutes, with a wide interquartile range of 18 to 40 in the hypothermic group and 16 to 40 in the normothermic group.In prolonged cardiac arrest, we do not expect that a reduction of neurologic metabolism by hypothermia will have a real effect on already damaged structures.We should not conclude, on the basis of this trial, that hypothermia is simply an antihyperthermic strategy.Not all cardiac arrests are equal in terms of the time to return of spontaneous circulation.We should identify the subgroups of patients who can benefit from this form of therapy.
Magnesium from bioresorbable implants: Distribution and impact on the nano- and mineral structure of bone
Authors: T.A. Grünewald, H. Rennhofer, B. Hesse, M. Burghammer, S.E. Stanzl-Tschegg, M. Cotte, J.F. Löffler, A.M. Weinberg, H.C. Lichtenegger
Journal: Biomaterials (2015)
Intensive care units have good reasons not to do it
Authors: A. Manara, C. Jewkes
Journal: BMJ (1995)

<h3>Introduction</h3> Anticoagulants are arguably the most important drug family of all, based on the frequency and duration of their use, and the clinical importance and frequency of benefits and harms. Several direct acting oral anticoagulants (DOACs) have recently joined warfarin for the treatment of atrial fibrillation, with a resultant significant expansion in use of oral anticoagulants (OACs). Our objectives are to compare safety and effectiveness of DOACs versus warfarin in a full population where anticoagulation management is good and to identify which types of patients do better with DOACs versus warfarin and vice versa. <h3>Methods and analysis</h3> This is a retrospective cohort study of all adults living in British Columbia who have a diagnosis of atrial fibrillation in hospital or medical service data, and a first prescription for an OAC. Coprimary outcomes are ischaemic stroke and systemic embolism (benefit) and major bleeding (harm). Secondary outcomes include net clinical benefit (composite of stroke, systemic embolism, major bleeds, myocardial infarction, pulmonary embolism and death), drug discontinuation and individual composite item occurrence. We will estimate the effects of treatment in a 2-year follow-up period, using time-to-event models with propensity score adjustment to control confounding. Secondary analyses will examine ‘as treated’ outcomes. <h3>Ethics and dissemination</h3> The protocol, data creation plan, privacy impact statement and data sharing agreements have been approved. Dissemination is planned via conferences and publications as well as directly to drug policy leaders. Information on the overall comparative effectiveness and safety of DOACs versus warfarin in a country with high quality anticoagulation management, as well as for vulnerable subgroups, will be an important addition to the literature.
Determinants of limitations in life-sustaining treatment in a Norwegian intensive care unit
Authors: Henrik Hoel, Stein Arve Skjaker, Rolf Haagensen, Vegard Dahl, Knut Stavem
Journal: European Respiratory Journal (2014)

Background:  To withhold or withdraw treatment are important decisions made in intensive care units (ICUs). Few studies have investigated the association between clinical variables available after 24 hours in the ICU and decisions to limit life-sustaining treatment.   Objectives:  To assess factors associated with limitations in life-sustaining treatment in a general ICU, from 2007 to 2009 in a university hospital in Norway.   Methods:  During the first 24 hours in the ICU patients had age, sex, Simplified Acute Physiology Score II (SAPS II), type of admission, and length of hospital stay prior to ICU admission registered. We retrospectively registered Charlson Comorbidity Index (CCI) for all patients, based on the medical records prior to the index stay. A multivariate logistic regression analysis was used to assess determinants of limitations in treatment (withholding or withdrawing treatment) during the ICU stay.   Results:  In total, 1035 patients were included; 766 (74%) medical, 221 (21%) unscheduled surgical, and 48 (5%) scheduled surgical patients. Overall, 256 patients (25%) had limitations in treatment during the ICU stay. In multivariate analysis (n=1035), older age (OR 1.68 per 10 years), higher SAPS II score (OR 1.05), and higher CCI (OR 1.19) were significantly associated with limitations in treatment (p   Conclusion:  In multivariate analysis, age, severity of illness, comorbidity and length of stay prior to ICU admission were associated with subsequent limitations in life-sustaining treatment during the ICU stay.
Gleason upgrading with time in a large, active surveillance cohort with long-term follow-up.
Authors: Suneil Jain, Danny Vesprini, Alexandre Mamedov, D. Andrew Loblaw, Laurence Klotz
Journal: Journal of Clinical Oncology (2013)

1 Background: Active surveillance (AS) is an accepted management strategy for localized prostate cancer. However, the rate of pathological upgrading has not been well described in mature study cohorts. Furthermore, concern exists over the possibility of prostate cancer dedifferentiation with time in patients on AS. Methods: Patients in our prospectively collected AS database with at least one repeat prostate biopsy were included. Linear regression analysis was used to estimate the proportion of patients upgraded (Gleason 6 to 3+4 or higher, Gleason 3+4 to 4+3 or higher) with time from diagnostic biopsy. Results: 593 of 862 patients in our cohort had at least one repeat biopsy. Median follow-up was 6.4 years (max. 20.2 years). The total number of biopsies ranged from 2 to 6. 20% of patients were intermediate risk, 0.3 % high risk, all others low risk. 31.2% of patients were upgraded during active surveillance. The proportion of patients upgraded increased with time, suggesting prostate cancer dedifferentiation occurred at a rate of 1.0%/year (95%CI -0.12 to 2.16%/year). The estimated rate of increase was 2.5 times higher in patients with intermediate risk disease at diagnosis (rate 1.9%/year, 95%CI -0.7-4.6) compared with those with low risk disease (rate 0.75%/year, 95%CI -0.5-2.0). Further analysis is underway. 62% of upgraded patients (n=114) went on to have active treatment. Patients who were upgraded and treated had significantly greater PSA velocities (median 1.2 ng/ml/y vs 0.42 ng/ml/y, p=0.01) and significantly higher Gleason scores when upgraded, than those who remained on surveillance (21.8% vs 2.8% Gleason 8-10, p&lt;0.01). Conclusions: This is the largest re-biopsy cohort, with long-term follow-up, described to date, enabling the first estimates of prostate cancer dedifferentiation in patients on AS. Dedifferentiation rates appear higher in patients with intermediate risk prostate cancer compared with those who are low risk at baseline.
Biochemical and functional characterization of lysyl oxidase like 2 (LOXL2) inhibitors
Authors: Ravi Rajagopalan, Shawn Misialek, Jin-Xing Huang, Lisa Hooi, Hemanth Ramesha, John Nicholas, John Ramphal, Kumar Emayan, Lin Pan, Sophia Yap, Lea Huang, Scott Seiwert, Brad Buckman
Journal: European Respiratory Journal (2014)

Introduction: A lysyl oxidase like 2 (LOXL2) directed monoclonal antibody (simtuzumab) is being clinically evaluated for the treatment of various fibrotic diseases including idiopathic pulmonary fibrosis (IPF).  Objective: To characterize small molecule LOXL2 inhibitors biochemically and in functional assays to assess anti-fibrotic activity.  Methods: High throughput screening was used to identify small molecule LOXL2 inhibitors. Screening hits were profiled for biochemical inhibition of LOXL2 and closely related amine oxidases (AOs). Binding to LOXL2 was confirmed by surface plasmon resonance (SPR) methods. Mechanistic experiments were used to judge substrate activity, reversibility, and allosteric and/or non-competitive LOXL2 inhibition. A novel collagen cross-linking assay was developed to evaluate the inhibitors.  Results: Both reversible and irreversible LOXL2 inhibitors from various chemotypes were identified with biochemical IC50s of  100-fold over monoamine oxidase A and B was achieved. Lead molecules demonstrated low micromolar inhibition of collagen cross-linking.  Conclusions: We have identified novel LOXL2 selective small molecule inhibitors, which demonstrate activity in functional assays relevant to fibrosis.
Inhibitory Effects of Ticagrelor Compared With Clopidogrel on Platelet Function in Patients With Acute Coronary Syndromes
Authors: Robert F. Storey, Dominick J. Angiolillo, Shankar B. Patil, Bhaloo Desai, Rosemary Ecob, Steen Husted, Hakan Emanuelsson, Christopher P. Cannon, Richard C. Becker, Lars Wallentin
Journal: Journal of the American College of Cardiology (2010)
Practical allergy (PRACTALL) report: risk assessment in anaphylaxis
Authors: F. E. R. Simons, A. J. Frew, I. J. Ansotegui, B. S. Bochner, D. B. K. Golden, F. D. Finkelman, D. Y. M. Leung, J. Lotvall, G. Marone, D. D. Metcalfe, U. Müller, L. J. Rosenwasser, H. A. Sampson, L. B. Schwartz, M. Van Hage, A. F. Walls
Journal: Allergy (2007)

Effector mechanisms in anaphylaxis were reviewed. Current approaches to confirmation of the clinical diagnosis were discussed. Improved methods for distinguishing between allergen sensitization (which is common in the general population) and clinical risk of anaphylaxis (which is uncommon) were deliberated. Innovative techniques that will improve risk assessment in anaphylaxis in the future were described.
Phase I Trial of the Combination of Irinotecan, Paclitaxel, and Carboplatin in Patients With Advanced Non–Small-Cell Lung Cancer
Authors: Mark A. Socinski, Alan B. Sandler, Langdon L. Miller, Paula K. Locker, Cristy K. Hanover, Gary L. Elfring, Valerie K. Israel, Nicoletta Pirotta, Ronald B. Natale
Journal: Journal of Clinical Oncology (2001)

PURPOSE: To determine the maximum-tolerated dose, toxicities, and dose suitable for phase II/III trials of irinotecan (CPT-11) combined with paclitaxel and carboplatin in patients with advanced non–small-cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients with stage IIIB/IV NSCLC were enrolled to this multicenter, phase I study. The initial regimen was paclitaxel 225 mg/m 2 /3 h, followed by carboplatin area under the curve (AUC) 6 over 30 minutes on day 1, and CPT-11 starting at 40 mg/m 2 over 90 minutes, days 1 and 8, every 3 weeks. Dose-limiting toxicity occurred in three of seven patients. The regimen was amended, with doses reduced to paclitaxel 175 mg/m 2 /3 h, carboplatin AUC 5 and CPT-11 at 40 mg/m 2 , all on day 1 every 3 weeks. Dose escalation of CPT-11 proceeded to 80 mg/m 2 then 125 mg/m 2 before dose-limiting toxicities were experienced. Subsequent patients received an intermediate CPT-11 dose of 100 mg/m 2 . RESULTS: Thirty-three patients were enrolled; 32 patients were assessable for safety, and 31 were assessable for tumor response. The primary first-cycle dose-limiting toxicities were neutropenia and diarrhea. The most common grade 3/4 toxicity observed during all cycles was neutropenia (16 patients [50%], with six [19%] developing neutropenic fever). Objective tumor response was observed in 39% (12/31, 95% confidence interval, 22% to 58%). The median time to tumor progression was 6.8 months, median survival 11.0 months, and 1-year survival probability 0.46. CONCLUSION: CPT-11 100 mg/m 2 , paclitaxel 175 mg/m 2 , and carboplatin AUC 5 given every 3 weeks can be safely administered in patients with advanced NSCLC. Neutropenia and diarrhea are the dose-limiting toxicities. The combination shows appreciable activity, and survival data are favorable.
224. Induced Pluripotent Stem Cells as a Model To Test Gene Augmentation Therapy for Choroideremia
Authors: Vidyullatha Vasireddy, Jason A. Mills, Rajashekhar Gaddameedi, Etiena Basner-Tschakarjan, Monica Kohnke, Aaron H. Black, Kirill Alexandrov, Albert M. Maguire, Daniel Chung, Helen Mac, Lisa Sullivan, Paul Gadue, Jeannette L. Bennicelli, Deborah L. French, Jean Bennett
Journal: Molecular Therapy (2013)

Choroideremia (CHM) is an X-linked, blinding, inherited retinal degeneration that is symptomatic in childhood and leads to total blindness in midlife. The disease is characterized by the degeneration of photoreceptors, retinal pigment epithelium (RPE) and choriocapillaris. The causative factor for CHM was identifi ed as a defect in the Rab Escort Protein 1 (REP1) which is involved in prenylation of Rab proteins. The nature and onset of the disease and the size of the gene makes CHM an excellent target for recombinant adeno-associated virus (rAAV) mediated gene therapy. However, the animal model of this disease is not an exact replica of the condition and is not readily available. Therefore, we generated and evaluated induced pluripotent stems cells (iPSCs) from CHM subjects as in vitro models to explore the potential of gene augmentation therapy. A recombinant adeno-associated virus (AAV2) was generated that delivers the wild-type human CHM cDNA driven by a constitutive promoter. Infection of iPSCs with AAV2-CHM resulted in the expression of the CHM protein and rescue of enzymatic function in the defective cells. The gene transfer is effi cient and appears to be safe in the short-term, as shown by studies in affected cells and in normalsighted animal models. These studies not only aid in deciphering the pathogenetic mechanisms of the disease, but also pave the way for a human gene therapy clinical trial for CHM.
List predatory journal publications separately from genuine scholarly publications as standard for CVs
Authors: M. S. Cappell
Journal: BMJ (2015)

I have several comments to make after reading Clark and Smith’s courageous editorial on predatory journals.1

Firstly, I worry that my 240 plus publications in peer reviewed journals indexed in PubMed,2 with zero publications in predatory journals, may be adulterated and devalued because pseudo-academics can pay for publication in predatory journals. This phenomenon could retard my academic advancement.

Secondly, the authors emphasise the damage from predatory publishing in lower income countries. I …