tbuckley/cabot-search huggingface dataset:
New statistical strategy for monitoring safety and efficacy in single-arm clinical trials.
Authors: P F Thall, R M Simon, E H Estey
Journal: Journal of Clinical Oncology (1996)

PURPOSE Efficacy and toxicity are both important outcomes in cancer clinical trials. Nonetheless, most statistical designs for phase II trials only provide rules for evaluating treatment efficacy, and moreover only allow early stopping after fixed cohorts of patients have been treated. We illustrate a new statistical design strategy for monitoring both adverse and efficacy outcomes on a patient-by-patient basis in phase II and other single-arm clinical trials. DESIGN The new strategy is used to design a phase II trial of the experimental regimen idarubicin plus cytarabine (ara-C) plus cyclosporine for treatment of patients with intermediate-prognosis acute myelogenous leukemia (AML). The design requires a maximum of 56 patients and provides continuous monitoring boundaries to terminate the trial if the toxicity rate is unacceptably high or the complete remission (CR) rate is unacceptably low compared with the rates of these events with the standard regimen of anthracycline plus ara-C. RESULTS The design has an 88% to 91% probability of stopping the trial early with a median of 15 to 18 patients if the toxicity rate of the experimental regimen is .05 to .10 above that of the standard and there is no improvement in the CR rate. If there is a .15 improvement in the CR rate and the toxicity rate is no more than .05 above that of the standard, then there is at least an 83% probability that the trial will run to completion. CONCLUSION The proposed monitoring strategy provides a flexible, practical means to continuously monitor both safety and efficacy in single-arm cancer clinical trials. The design strategy can be implemented easily using a freely available menu-driven computer program, and provides a scientifically sound alternative to the use of ad hoc safety monitoring rules.
Rosuvastatin‐Induced Carotid Plaque Regression in Patients With Inflammatory Joint Diseases: The Rosuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and Other Inflammatory Joint Diseases Study
Authors: S. Rollefstad, E. Ikdahl, J. Hisdal, I. C. Olsen, I. Holme, H. B. Hammer, K. T. Smerud, G. D. Kitas, T. R. Pedersen, T. K. Kvien, A. G. Semb
Journal: Arthritis & Rheumatology (2015)

Patients with rheumatoid arthritis (RA) and carotid artery plaques have an increased risk of acute coronary syndromes. Statin treatment with the goal of achieving a low-density lipoprotein (LDL) cholesterol level of ≤1.8 mmoles/liter (≤70 mg/dl) is recommended for individuals in the general population who have carotid plaques. The aim of the ROsuvastatin in Rheumatoid Arthritis, Ankylosing Spondylitis and other inflammatory joint diseases (RORA-AS) study was to evaluate the effect of 18 months of intensive lipid-lowering treatment with rosuvastatin with regard to change in carotid plaque height.Eighty-six patients (60.5% of whom were female) with carotid plaques and inflammatory joint disease (55 with RA, 21 with AS, and 10 with psoriatic arthritis) were treated with rosuvastatin to obtain the LDL cholesterol goal. Carotid plaque height was evaluated by B-mode ultrasonography.The mean ± SD age of the patients was 60.8 ± 8.5 years, and the median compliance with rosuvastatin treatment was 97.9% (interquartile range [IQR] 96.0-99.4). At baseline, the median number and height of the carotid plaques were 1.0 (range 1-8) and 1.80 mm (IQR 1.60-2.10), respectively. The mean ± SD change in carotid plaque height after 18 months of treatment with rosuvastatin was -0.19 ± 0.35 mm (P < 0.0001). The mean ± SD baseline LDL cholesterol level was 4.0 ± 0.9 mmoles/liter (154.7 ± 34.8 mg/dl), and the mean reduction in the LDL cholesterol level was -2.3 mmoles/liter (95% confidence interval [95% CI] -2.48, -2.15) (-88.9 mg/dl [95% CI -95.9, -83.1]). The mean ± SD LDL cholesterol level during the 18 months of rosuvastatin treatment was 1.7 ± 0.4 mmoles/liter (area under the curve). After adjustment for age/sex/blood pressure, no linear relationship between a reduction in carotid plaque height and the level of LDL cholesterol exposure during the study period was observed. Attainment of the LDL cholesterol goal of ≤1.8 mmoles/liter (≤70 mg/dl) or the amount of change in the LDL cholesterol level during the study period did not influence the degree of carotid plaque height reduction.Intensive lipid-lowering treatment with rosuvastatin induced atherosclerotic regression and reduced the LDL cholesterol level significantly in patients with inflammatory joint disease.
Comparative effects of inspiratory muscle training and resistance training on respiratory and skeletal muscle strength in COPD: Responses of the a pulmonary rehabilitation program
Authors: Laura Neves, Adriana Chiappa, Vinicius da Silva, Paulo Vieira, Gerson Cipriano, Ross Arena, Alexandre Dias, Gaspar Chiappa
Journal: European Respiratory Journal (2014)

Background: We tested the hypothesis that inspiratory muscle training (IMT) is more effective than resistance training (RT) in improving exercise capacity, inspiratory fraction (IF), maximal respiratory muscle strength and lower limb muscle force production in Chronic Obstructive Pulmonary Disease (COPD) patients. Methods: Patients were assigned to a 6-month program of IMT (n=51), RT (n=53) or control (usual care, n=50). Pulmonary function, inspiratory and expiratory muscle strength (PImax and PEmax), exercise capacity by oxygen uptake (peak VO2) and 6-minute walk distance (6-MWT), and quadriceps muscle torque (QMT) and endurance (QME) were evaluated. Results: RT significantly increased forced vital capacity (65 ±10 vs. 71 ± 9 % pred), PEmax (63 ± 14 vs. 127± 31 cm H2O), peak QMT (1.71 ± 0.21 vs. 2.02 ± 0.32 N.m) and QME (127 ± 38 vs. 189 ± 39 kg.max rep) compared with IMT and controls. In contrast, IMT increased PImax (IMT, 53 ± 15 vs. 125 ± 24 cm H2O), and IF (28.4 ± 9.7 vs. 30.3 ± 9.1 % pred) compared with RT. Both IMT and RT similarly increased peak VO2 (IMT, before 18.5 ± 4.5; after, 21.1± 3.8 ml.kg-1.min-1; RT, before, 19.7 ± 5.6; after, 20.5± 4.3 ml.kg-1.min-1; p
Depression of Ventilation by Dopamine in Man
Authors: Michael J. Welsh, Donald D. Heistad, Francois M. Abboud
Journal: Journal of Clinical Investigation (1978)

Dopamine is present in the carotid body and has been postulated to be an inhibitory neurotransmitter. The purpose of this study was to determine the effects of dopamine on ventilation in man and to examine its mechanism of action. Dopamine (0.5-10 μg/kg per min) was infused in eight normal men at different levels of arterial chemoreceptor activity, produced by varying the inspired Po2. During normoxia dopamine produced a small decrease in minute ventilation (V̇e) and an increase in arterial Pco2. When arterial chemoreceptors were stimulated by hypoxia, infusion of dopamine produced a marked initial depression of V̇e followed by a sustained although less pronounced decrease in V̇e. An increase in Paco2 and a decrease in Pao2 were also observed. When arterial chemoreceptor activity was suppressed by hyperoxia, infusion of dopamine did not affect ventilation. Subjects also breathed a hypercarbic, hyperoxic gas mixture. The hypercarbia produces hyperventilation by stimulating central chemoreceptors, whereas the hyperoxia suppresses peripheral chemoreceptors. Dopamine did not alter ventilation while the subjects were breathing this gas mixture.
Stop hunting for zebras in Texas: end the diagnostic culture of “rule-out”
Authors: Saurabh Jha
Journal: British Journal of Sports Medicine (2015)

“The patient's skull was struck by a baseball bat. He has a perfectly legitimate reason for subarachnoid hemorrhage. He already had a CT [computed tomogram] of the head showing the bleed in good detail. Why another?” I remonstrated with Watson, the neurosurgeon.

“But you don't know that there is no intracranial aneurysm. You can't rule that out. He needs a CT angiogram of the brain immediately,” protested Watson.

Hit by a hard object (cause) and blood in brain (effect) is deductive reasoning at its simplest. But Watson was correct: I could not rule out cerebral artery aneurysm without a CT angiogram. I could not, for that matter, rule out bleeding brain metastases from lung cancer. Perhaps the patient needed a CT of the chest, I suggested facetiously.

The diagnostic permutations in medicine are innumerable, and what prevents doctors from descending into parody is the application of conditional probability: Bayes' theorem. Without clinical context we stare into the abyss.

The likelihood that someone with cerebral aneurysm hit by a bat develops subarachnoid hemorrhage (near certainty) is not the same as the likelihood that someone who develops subarachnoid hemorrhage after high impact trauma has an aneurysm, hitherto undisclosed …
Abstract 201: Specific Metabolic Pathways Involved in Outcome of Cardiopulmonary Resuscitation: A Pilot Plasma Metabolomic Study in a Rat Model of Cardiac Arrest and CPR
Authors: Laura Brunelli, Francesca Fumagalli, Renzo Bagnati, Roberta Pastorelli, Roberto Latini, Giuseppe Ristagno
Journal: Circulation (2011)

Introduction. The mechanisms responsible for postresuscitation myocardial and cerebral dysfunction are not well understood. We hypothesized that untargeted plasma metabolomic analyses would be a feasible approach to identify perturbations in circulating metabolites and thus potential mechanisms accounting for outcome of cardiac arrest (CA). Methods. Six male rats, 440 ± 50 g, were used. Ventricular fibrillation was induced in 3 rats and was untreated for 6 mins. CPR, including mechanical chest compressions, ventilations and epinephrine, was then initiated and continued for additional 6 mins prior to defibrillation. Two hrs following resuscitation, animals were sacrificed and plasma collected. The other 3 rats were not subjected to cardiac arrest and served as controls. Plasma metabolome was examined by liquid chromatography-tandem mass spectrometry. Differences in chromatogram profiles were then analyzed using SIEVE v1.3 analysis software. Chromatographic peaks, with accurate masses, retention time and tandem mass fragmentation patterns were then identified using mass-spectral libraries of metabolites. Results. A total of 523 chromatographic peaks showed significant differences after CA. Changes in metabolites participating in purine/pyrimidine metabolism, glycolisis, TCA cycle, pentose phosphate pathways, cholesterols and derivatives, lipids, and fatty acid oxidation, were observed. Changes in long-chain acylcarnitine and corticosterone/cortisol levels were also found, suggesting oxidative damages and deregulation of hypothalamic-pituitary-adrenal axis, respectively. More importantly, numerous metabolites along the kynurenine pathway from tryptophan oxidation, typically related to neurological degeneration, were identified (Figure). Conclusions. In this pilot study, plasma metabolomics allowed for identification of specific metabolic pathways, i.e. tryptophan pathway, that ultimately may contribute to CA outcome.
Smokers in England and Wales launch campaign for class action against tobacco companies
Authors: Susan Mayor
Journal: BMJ (2015)

<b>1687</b> <h3><b>Objectives</b></h3> Several reports showed the myocardial microvascular dysfunction in the patients with the end-stage renal disease (ESRD). However, it is still unknown that the difference of the influence on the myocardial microcirculation between the etiologies of ESRD. We investigated the myocardial microcirculation using 13N-ammonia PET myocardial perfusion imaging (MPI) in the ESRD patient with maintained dialysis. <h3><b>Methods</b></h3> Myocardial blood flow (MBF) at rest and during ATP induced hyperemia, and coronary flow reserve (CFR) in the ESRD patient were evaluated by 13N-ammonia PET MPI study. Twenty-seven diabetic ESRD patients and 50 non-diabetic ESRD patients without perfusion defect (SSS&lt;3) were investigated. The patients with abnormal myocardial microcirculation is defined as follows; CFR&lt;2.0: functional disorder of micro-vessels, stress MBF&lt;2.0: reduced density of micro-capillaries, and both of them: mixed impairment. <h3><b>Results</b></h3> No significant difference was observed between diabetic and non-diabetic ESED patients in rest MBF (0.98±0.25mL/g/min, 1.05±0.22mL/g/min, p=n.s.). Stress MBF was significantly reduced in diabetic ESRD patients than in non-diabetic ESRD patients (2.38±0.50mL/g/min, 2.98±0.75mL/g/min, p=0.0002). CFR was significantly reduced in diabetic ESRD patients than in non-diabetic ESRD patients (2.14±0.46, 2.74±0.58, p = 0.04). The severe microvascular dysfunction (MD) were more frequently observed in diabetic patients than in no-diabetic patients (CFR&lt;2.0: 25.9%, 10.0%, respectively, p&lt;0.05, Stress MBF&lt;2.0: 22.2%, 8.0%, restrictively, p&lt;0.01, both of them: 14.8%, 4.0%, restrictively, p&lt;0.01). The logistic regression analysis revealed that the diabetic-ESRD most related to the severe MD. <h3><b>Conclusions</b></h3> Reduced pharmacological-stress induced hyperemic MBF and reduced CFR were observed in the diabetic ESRD patients than in the non-diabetic ESRD patients evaluated by 13N-ammonia PET MPI study. It would reflect the myocardial microvascular dysfunction with poorer prognosis.
Cisplatin-etoposide and carboplatin-etoposide induction chemotherapy for good-risk patients with germ cell tumor
Authors: S.A. Tjulandin, A.M. Garin, A.A. Mescheryakov, N. I Perevodchikova, V.A. Gorbunova, A.V. Sokolov, N.V. Ljubimova, G.T. Mironova, G.V. Molchanov, R.F. Ozols, J.M. Hamilton
Journal: Annals of Oncology (1993)
Aclidinium bromide reduces extracellular matrix deposition by COPD-derived mesenchymal cells
Authors: Christopher Lambers, Ying Qi, Eleni Papakonstantinou, Elisabeth Schuller, Michael Roth, Lutz-Hening Block
Journal: European Respiratory Journal (2013)

Background:  Addition of muscarinic receptor inhibitors to COPD therapy showed beneficial effects on lung function.   Objective:  To evaluate the effect of aclidinium bromide and formoterol on deposition and  de novo  synthesis of extracellular matrix components by human airway smooth muscle cells and fibroblasts.   Methods : Primary cells from patients with stage III COPD (n=7) and non-COPD controls (n=7) were characterised for α-smooth muscle actin (muscle) and fibronectin (fibroblast) 24 and 48 hours after TGF-β1 stimulation. Deposition and mRNA levels for collagen type-I, III, IV and fibronectin were analysed by ELISA and real-time PCR.   Results:  TGF-β1 stimulated matrix deposition was significantly reduced by pre-treatment with the drugs for collagen type-I and -III as was fibronectin; but not for collagen type-IV. The reduced collagen and fibronectin deposition correlated with decreased mRNA levels. The reduction of collagen type-III was only observed at the protein level without reduced mRNA synthesis. TGF-β1 stimulated collagen type-I deposition was dose-dependently reduced by aclidinium bromide (10 -11 -10 -8  M; max. 32%) and formoterol (10 -8 -10 -10 M; max. 18%). When combined, the effect of the drugs was additive. The inhibitory effect of the drugs was similar in fibroblasts and smooth muscle cells. This effect was observed in cells from diseased and non-diseased subjects.   Conclusion:  The results suggest that aclidinium bromide and formoterol reduce remodelling in the two main mesenchymal cell types of the lung through gene inhibition.   Clinical implication:  This observation may contribute to the clinically observed improvement of lung function by reducing extracellular matrix deposition.
Pharmacokinetic/pharmacodynamic assessment of the in-vivo efficacy of imipenem alone or in combination with amikacin for the treatment of experimental multiresistant Acinetobacter baumannii pneumonia
Authors: M. Bernabeu-Wittel, C. Pichardo, A. García-Curiel, M.E. Pachón-Ibáñez, J. Ibáñez-Martínez, M.E. Jiménez-Mejías, J. Pachón
Journal: Clinical Microbiology and Infection (2005)
Human pentraxin 3 (PTX3) as a novel biomarker for the diagnosis of pulmonary arterial hypertension
Authors: Yuichi Tamura, Masataka Kuwana, Kenji Inoue, Tomohiko Ono, Makoto Takei, Tsunehisa Yamamoto, Masaharu Kataoka, Motoaki Sano, Toru Satoh, Keiichi Fukuda
Journal: European Respiratory Journal (2012)

Background  Although inflammation is an important feature of pulmonary arterial hypertension (PAH), the usefulness of local inflammatory markers as biomarkers for PAH is unknown. In this study, we tested plasma concentrations of human pentraxin 3 (PTX3), a local inflammatory marker, would be a useful biomarker for detecting PAH.  Methods  Plasma PTX3 concentrations were evaluated in 50 PAH patients (27 with idiopathic PAH, 17 with PAH associated with connective tissue disease (CTD-PAH), and six with congenital heart disease), 100 age and sex-matched healthy controls, and 34 disease-matched CTD patients without PAH. Plasma concentrations of B-type natriuretic peptide (BNP) and C-reactive protein (CRP) were also determined.  Results  Mean PTX3 levels were significantly higher in all PAH patients than in the healthy controls (4.40±0.37 vs. 1.94±0.09 ng/mL, respectively; P   Conclusion  Plasma concentrations of PTX3 are more excellent than BNP in the detection of PAH, especially in patients with CTD.
The Financial Effect of Value-Based Purchasing and the Hospital Readmissions Reduction Program on Safety-Net Hospitals in 2014
Authors: Matlin Gilman, Jason M. Hockenberry, E. Kathleen Adams, Arnold S. Milstein, Ira B. Wilson, Edmund R. Becker
Journal: Annals of Internal Medicine (2015)

Medicare's value-based purchasing (VBP) and the Hospital Readmissions Reduction Program (HRRP) could disproportionately affect safety-net hospitals.To determine whether safety-net hospitals incur larger financial penalties than other hospitals under VBP and HRRP.Cross-sectional analysis.United States in 2014.3022 acute care hospitals participating in VBP and the HRRP.Safety-net hospitals were defined as being in the top quartile of the Medicare disproportionate share hospital (DSH) patient percentage and Medicare uncompensated care (UCC) payments per bed. The differences in penalties in both total dollars and dollars per bed between safety-net hospitals and other hospitals were estimated with the use of bivariate and graphical regression methods.Safety-net hospitals in the top quartile of each measure were more likely to be penalized under VBP than other hospitals (62.9% vs. 51.0% under the DSH definition and 60.3% vs. 51.5% under the UCC per-bed definition). This was also the case under the HRRP (80.8% vs. 69.0% and 81.9% vs. 68.7%, respectively). Safety-net hospitals also had larger payment penalties ($115 900 vs. $66 600 and $150 100 vs. $54 900, respectively). On a per-bed basis, this translated to $436 versus $332 and $491 versus $314, respectively. Sensitivity analysis setting the cutoff at the top decile rather than the top quartile decile led to similar conclusions with somewhat larger differences between safety-net and other hospitals. The quadratic fit of the data indicated that the larger effect of these penalties is in the middle of the distribution of the DSH and UCC measures.Only 2 measures of safety-net status were included in the analyses.Safety-net hospitals were disproportionately likely to be affected under VBP and the HRRP, but most incurred relatively small payment penalties in 2014.Patient-Centered Outcomes Research Institute.
Respiratory Psychophysiology of Panic Disorder: Three Respiratory Challenges in 98 Subjects
Authors: Laszlo A. Papp, Jose M. Martinez, Donald F. Klein, Jeremy D. Coplan, Robert G. Norman, Randolph Cole, Marybeth J. de Jesus, Donald Ross, Raymond Goetz, Jack M. Gorman
Journal: American Journal of Psychiatry (1997)

Respiratory abnormalities may play a central role in the pathophysiology of panic disorder. The current study was undertaken to examine the respiratory response in the largest series of subjects to date during three respiratory challenges that used improved methodology.Fifty-nine patients with DSM-III-R panic disorder and 39 normal volunteers were challenged with 5% and 7% CO2 inhalation and room air hyperventilation separated by room air breathing with continuous spirometry.Patients with panic disorder were more sensitive to the anxiogenic effects of CO2 than were normal subjects, and CO2 was a more potent stimulus to panic than hyperventilation. Patients increased their respiratory rate more quickly during CO2 inhalation than did comparison subjects, and this increase preceded the panic attacks. Patients who panicked in response to 5% CO2 demonstrated continued rise in end-tidal CO2, while the end-tidal CO2 of the comparison groups stabilized. Low end-tidal CO2 and high variance in minute ventilation at baseline predicted panic attacks during CO2 inhalation. Following CO2 or hyperventilation challenges, respiratory rate dropped sharply, while tidal volume remained elevated longer in patients than in comparison subjects.The findings confirm the greater behavioral and physiological sensitivity of patients with panic disorder to CO2 inhalation and identify a series of respiratory abnormalities. Panic attacks in panic disorder may be explained by inefficient compensatory mechanisms, primarily of respiratory rate.
Telomere length predicts progression and overall survival in chronic lymphocytic leukemia: data from the UK LRF CLL4 trial
Authors: J C Strefford, L Kadalayil, J Forster, M J J Rose-Zerilli, A Parker, T T Lin, N Heppel, K Norris, A Gardiner, Z Davies, D Gonzalez de Castro, M Else, A J Steele, H Parker, T Stankovic, C Pepper, C Fegan, D Baird, A Collins, D Catovsky, D G Oscier
Journal: Leukemia (2015)
A survey of arterial blood gas use and analysis in respiratory inpatients
Authors: Kate Williams, Su Ann Leong, Alison Gill
Journal: European Respiratory Journal (2013)

Background: Doctors routinely request arterial blood gases (ABGs) to guide patient management. Interpretation can be complex and is often dependent on a number of factors including patients’ clinical status and inspired oxygen fraction (FiO2). ABGs are usually performed by junior doctors and printed on a thermal paper that fades with time. We were concerned that poor documentation was adversely affecting interpretation of ABG results and patient care.

Methods: A one day audit of all respiratory inpatients (n=80) was performed. Records were scrutinised for ABG reports from the current admission. FiO2, patient identification details, indication for ABG, interpretation of result, action taken after ABG, use of local anaesthetic and complications were recorded.

Results: 185 ABG reports were identified from 44 patients. Numbers of ABGs per patient varied from 1 to 20 (median 2.5). An indication was recorded in 70% of cases; 31% of patients were using NIV. Local anaesthetic was never used. Allen’s test was not carried out in any case. No complications were recorded. RCP standards for documentation were met in less than 70% of cases. The full result was only handwritten into the record in 58% of cases. FiO2 was recorded in 78% of cases. In only 33% of cases was a clinical judgement documented alongside the result and this more likely to occur on a medical ward than in A&E (50% vs 10%). A management plan was only documented in half of all cases.

Conclusions: Documentation of ABG results is variable with scope for improvement. There is evidence that junior doctors do not feel comfortable interpreting ABGs and acting on the results. Education of trainees is therefore essential as this is an invaluable test.
Sex Differences in Cardiac Risk Factors, Perceived Risk, and Health Care Provider Discussion of Risk and Risk Modification Among Young Patients With Acute Myocardial Infarction
Authors: Erica C Leifheit-Limson, Gail D'Onofrio, Mitra Daneshvar, Mary Geda, Héctor Bueno, John A Spertus, Harlan M Krumholz, Judith H Lichtman
Journal: Journal of the American College of Cardiology (2015)