tbuckley/cabot-search huggingface dataset:
Effect of Direct-to-Consumer Advertising on Asthma Medication Sales and Healthcare Use
Authors: Matthew Daubresse, Susan Hutfless, Yoonsang Kim, Rachel Kornfield, Dima M. Qato, Jidong Huang, Kay Miller, Sherry L. Emery, G. Caleb Alexander
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

The United States is one of only two countries that permit direct-to-consumer advertising (DTCA) of prescription drugs, and many questions remain regarding its effects.To quantify the association between asthma-related DTCA, pharmacy sales, and healthcare use.This was an ecological study from 2005 through 2009 using linked data from Nielsen (DTCA television ratings), the IMS Health National Prescription Audit (pharmacy sales), and the MarketScan Commercial Claims data (healthcare use) for 75 designated market areas in the United States. We used multilevel Poisson regression to model the relationship between DTCA and rates of prescriptions and use within and across designated market areas. Main outcome measures include (1) volume of total, new, and refilled prescriptions for advertised products based on pharmacy sales; (2) prescription claims for asthma medications; and asthma-related (3) emergency department use, (4) hospitalizations, and (5) outpatient encounters among the commercially insured.Four Food and Drug Administration-approved asthma medicines were advertised during the period examined: (1) fluticasone/salmeterol (Advair), (2) mometasone furoate (Asmanex), (3) montelukast (Singulair), and (4) budesonide/formoterol (Symbicort). After adjustment, each additional televised advertisement was associated with 2% (incident rate ratio, 1.02; 95% confidence interval, 1.01-1.03) higher pharmacy sales rate from 2005 through 2009, although this effect varied across the three consistently advertised therapies examined. Among the commercially insured, DTCA was positively and significantly associated with emergency room visits related to asthma (incident rate ratio, 1.02; 95% confidence interval, 1.01-1.04), but there was no relationship with hospitalizations or outpatient encounters.Among this population, DTCA was associated with higher prescription sales and asthma-related emergency department use.
Identification and function of the high affinity binding sites for Ca2+ on the surface of platelets.
Authors: L F Brass, S J Shattil
Journal: Journal of Clinical Investigation (1984)

Extracellular Ca2+ is required for platelet aggregation and secretion in response to ADP or epinephrine. Recently, we reported that the platelet surface contains two classes of high affinity binding sites for extracellular Ca2+. To identify these sites and clarify their role in platelet function, we have now (a) studied platelets congenitally deficient in surface membrane glycoproteins and (b) examined the effect of removing surface-bound Ca2+ on platelet responses to ADP and epinephrine. Unstimulated normal platelets contained 86,000 Ca2+-binding sites/platelet with a dissociation constant (Kd) of 9 nM and 389,000 sites with a Kd of 400 nM. In contrast, thrombasthenic platelets, which lack glycoproteins IIb and IIIa, exhibited a 92% reduction in the number of higher affinity Ca2+-binding sites and a 63% reduction in the number of lower affinity sites. Bernard-Soulier platelets, which lack glycoprotein Ib, were not deficient in Ca2+-binding sites. After stimulation with ADP, both normal and thrombasthenic platelets developed approximately 138,000 new Ca2+-binding sites/platelet (Kd = 400 nM), while the larger Bernard-Soulier platelets developed 216,000 new sites. These data suggest that IIb and IIIa represent the major Ca2+-binding glycoproteins on unstimulated platelets, while neither these glycoproteins nor Ib represent the new Ca2+-binding sites on stimulated platelets. Removal of Ca2+ from the platelet surface inhibited platelet function. Despite the presence of 1 mM Mg2+, ADP- and epinephrine-induced aggregation and [14C]serotonin release were markedly decreased at free Ca2+ concentrations less than 7 nM, a value similar to the Kd of the higher affinity Ca2+-binding sites. Moreover, gadolinium, a lanthanide that competed for these Ca2+-binding sites, also inhibited aggregation and serotonin release. These studies demonstrate, therefore, that the binding of extracellular Ca2+ to glycoproteins IIb/IIIa on unstimulated platelets or to additional membrane proteins on stimulated platelets is necessary for maximal platelet responses to ADP and epinephrine. Thus, the requirement for extracellular Ca2+ during platelet activation by these agonists may actually represent a requirement for surface-bound Ca2+.
Pallidal neurostimulation in patients with medication-refractory cervical dystonia: a randomised, sham-controlled trial
Authors: Jens Volkmann, Joerg Mueller, Günther Deuschl, Andrea A Kühn, Joachim K Krauss, Werner Poewe, Lars Timmermann, Daniela Falk, Andreas Kupsch, Anatol Kivi, Gerd-Helge Schneider, Alfons Schnitzler, Martin Südmeyer, Jürgen Voges, Alexander Wolters, Matthias Wittstock, Jan-Uwe Müller, Sascha Hering, Wilhelm Eisner, Jan Vesper, Thomas Prokop, Marcus Pinsker, Christoph Schrader, Manja Kloss, Karl Kiening, Kai Boetzel, Jan Mehrkens, Inger Marie Skogseid, Jon Ramm-Pettersen, Georg Kemmler, Kailash P Bhatia, Jerrold L Vitek, Reiner Benecke
Journal: The Lancet Neurology (2014)
Effects of obesity upon genioglossus structure and function in obstructive sleep apnoea
Authors: M. Carrera, F. Barbé, J. Sauleda, M. Tomás, C. Gómez, C. Santos, A.G.N. Agustí
Journal: European Respiratory Journal (2004)

Obesity is a common feature of the obstructive sleep apnoea syndrome. It can influence the structure and function of skeletal muscles. However, its effects upon the upper airway muscles have not been explored directly. This study assessed the structure and function of the genioglossus in patients with obstructive sleep apnoea syndrome and in healthy subjects (with and without obesity, defined by a body mass index &gt;30 kg·m −2 ). Further, to investigate the effects of continuous positive airway pressure (CPAP) treatment, patients with obstructive sleep apnoea syndrome after at least 1 yr under CPAP were also studied. The study found that obese and nonobese patients showed different in vitro geniglossus endurance properties. In obese patients, geniglossus endurance was indistinguishable from normal while, nonobese patients, at diagnosis, showed increased genioglossus fatigability; this was not observed in patients treated with CPAP. By contrast, patients with obstructive sleep apnoea syndrome showed at diagnosis a higher percentage of type II fibres than controls and patients under CPAP treatment independently of obesity. This difference is mainly due to a predominance of subtype IIb fibre. This difference was not observed in the group of patients treated with CPAP. Genioglossus twitch force was normal in all patients. These results suggest that different pathogenic mechanisms may underlie the development of obstructive sleep apnoea syndrome in obese and nonobese patients. This observation may have potential clinical implications.
Multicenter Prospective Study of Ventilator-Associated Pneumonia During Acute Respiratory Distress Syndrome
Authors: PHILIPPE MARKOWICZ, MICHEL WOLFF, KAMEL DJEDAÏNI, YVES COHEN, JEAN CHASTRE, CHRISTOPHE DELCLAUX, JACQUES MERRER, BERNARD HERMAN, BENOIT VEBER, ALAIN FONTAINE, DIDIER DREYFUSS
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

We investigated the incidence, risk factors for, and outcome of ventilator-associated pneumonia (VAP) in patients with acute respiratory distress syndrome (ARDS). We compared 134 patients with ARDS with 744 patients without ARDS on mechanical ventilation. Fiberoptic bronchoscopic examination and quantitative bacterial cultures (protected brush or catheter sampling [threshold: 103 cfu/ml], or bronchoalveolar lavage [threshold: 104 cfu/ml]) were used to diagnose pneumonia. VAP occurred in 49 patients (36.5%). The incidence of pneumonia was 23% (173 of 744 patients) among patients without ARDS (p < 0.002). Nonfermenting gram-negative rods caused significantly more pneumonia in ARDS patients. Mortality rates were identical in ARDS patients with (28 of 49 patients, 57%) and without (50 of 85 patients, 59%) pulmonary infection (p = 0.8). VAP resulted in a considerable increase in attributable time on mechanical ventilation of both the overall population of ARDS patients and of survivors. Both the use of sucralfate (adjusted odds ratio [OR]: 4.42; 95% confidence interval [CI]: 2.01 to 9.7, p = 0.0002) and the duration of exposure to sucralfate (adjusted OR: 1.206; 95% CI: 1.095 to 1.328, p = 0.0002) were associated with an increased risk of VAP during ARDS. VAP considerably prolongs the time on mechanical ventilation without affecting survival. Patients given sucralfate may be at greater risk of developing pulmonary infection during ARDS.
Electronic Implementation of a Novel Surveillance Paradigm for Ventilator-associated Events. Feasibility and Validation
Authors: Peter M. C. Klein Klouwenberg, Maaike S. M. van Mourik, David S. Y. Ong, Janneke Horn, Marcus J. Schultz, Olaf L. Cremer, Marc J. M. Bonten
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Accurate surveillance of ventilator-associated pneumonia (VAP) is hampered by subjective diagnostic criteria. A novel surveillance paradigm for ventilator-associated events (VAEs) was introduced.Objectives: To determine the validity of surveillance using the new VAE algorithm.Methods: Prospective cohort study in two Dutch academic medical centers (2011–2012). VAE surveillance was electronically implemented and included assessment of (infection-related) ventilator-associated conditions (VAC, IVAC) and VAP. Concordance with ongoing prospective VAP surveillance was assessed, along with clinical diagnoses underlying VAEs and associated mortality of all conditions. Consequences of minor differences in electronic VAE implementation were evaluated.Measurements and Main Results: The study included 2,080 patients with 2,296 admissions. Incidences of VAC, IVAC, VAE-VAP, and VAP according to prospective surveillance were 10.0, 4.2, 3.2, and 8.0 per 1000 ventilation days, respectively. The VAE algorithm detected at most 32% of the patients with VAP identified by prospective surveillance. VAC signals were most often caused by volume overload and infections, but not necessarily VAP. Subdistribution hazards for mortality were 3.9 (95% confidence interval, 2.9–5.3) for VAC, 2.5 (1.5–4.1) for IVAC, 2.0 (1.1–3.6) for VAE-VAP, and 7.2 (5.1–10.3) for VAP identified by prospective surveillance. In sensitivity analyses, mortality estimates varied considerably after minor differences in electronic algorithm implementation.Conclusions: Concordance between the novel VAE algorithm and VAP was poor. Incidence and associated mortality of VAE were susceptible to small differences in electronic implementation. More studies are needed to characterize the clinical entities underlying VAE and to ensure comparability of rates from different institutions.
A Colour Handbook of Gastroenterology
Authors: S P PEREIRA
Journal: Gut (2000)

A Colour Handbook of Gastroenterology . Edited by Hodgson HJF, Boulton R, Cousins C, et al . (Pp 208; illustrated; £29.95). London: Manson Publishing Ltd, 2000. ISBN 1 87454 555 3.

To paraphrase Mark Twain, reports of the impending demise of the print media have been greatly exaggerated—a trainee can still spend hours browsing new editions in a medical bookshop and, usually during frantic preparation for higher exams while fulfilling DSM-IV criteria for anxiety disorder, part with large sums of money on illustrated texts. …
Methylation study of a population environmentally exposed to arsenic in drinking water.
Authors: C Hopenhayn-Rich, M L Biggs, A H Smith, D A Kalman, L E Moore
Journal: Environmental Health Perspectives (1996)

Methylation is considered the detoxification pathway for inorganic arsenic (InAs), an established human carcinogen. Urinary speciation analysis is used to assess the distribution of metabolites [monomethylarsonate (MMA), dimethylarsinate (DMA), and unmethylated arsenic (InAs)], as indicators of methylation capacity. We conducted a large biomarker study in northern Chile of a population chronically exposed to high levels of arsenic in drinking water. We report the results of the methylation study, which focused on the effects of exposure and other variables on the percent InAs, MMA, DMA, and the ratio of MMA to DMA in urine. The study consisted of 122 people in a town with arsenic water levels around 600 micrograms/l and 98 participants in a neighboring town with arsenic levels in water of about 15 micrograms/l. The corresponding mean urinary arsenic levels were 580 micrograms/l and 60 micrograms/l, of which 18.4% and 14.9% were InAs, respectively. The main differences were found for MMA:DMA; exposure, smoking, and being male were associated with higher MMA:DMA, while longer residence, Atacameño ethnicity, and being female were associated with lower MMA:DMA. Together, these variables explained about 30% of the variability in MMA:DMA. Overall, there was no evidence of a threshold for methylation capacity, even at very high exposures, and the interindividual differences were within a much wider range than those attributed to the variables investigated. The differences in percent InAs were small and within the ranges of other studies of background exposure levels. The biological significance of MMA:DMA, which was more than 1.5 times greater in the exposed group, and its relationship to sex, length of exposure, and ethnicity need further investigation because its relevance to health risk is not clear.
Metallurgical analysis of failed Bjork-Shiley cardiac valve prostheses.
Authors: S H Sacks, M Harrison, P J Bischler, J W Martin, J Watkins, A Gunning
Journal: Thorax (1986)

An investigation into the mechanisms of failure of current Björk-Shiley cardiac valve prostheses is reported. Two failed valves, one apparently unfailed but defective valve, and one unused valve, were examined by scanning electron microscopy and metallographic section. In the first two valves (removed 12 and 23 months after implantation) fracture was associated with the welds joining the short strut to the valve ring. The fracture surfaces in all cases were heavily faceted and showed branching cracks. Extensive wear had occurred on one fracture surface in the first case, suggesting that one leg of the short strut had failed before the other, though this had been clinically undetectable. The third valve was removed owing to failure of the suturing (24 months after implantation) but one leg of the short strut was found to be completely fractured. The other leg showed extensive cracking and porosity in the weld region. A metallographic section taken through the weld region of the fourth (unused) valve illustrated several sizable defects directly attributable to the welding process. It is suggested that the valves failed by fatigue and that these problems could be overcome if the complete valve cage were machined as a single piece.
The sensitivity to change for lower disease activity is greater than for higher disease activity in rheumatoid arthritis trials
Authors: B Zhang, M Lavalley, D T Felson
Journal: Annals of the Rheumatic Diseases (2008)

<h3>Objective:</h3> To test whether rheumatoid arthritis (RA) trials treatment efficacy versus control is better detected for patients with lower tender joint counts (TJC) or swollen joint counts (SJC) than for higher counts. <h3>Methods:</h3> Using data from six large multicentre trials (N = 2002) and an intent-to-treat approach at 6 months, two subtrials were created within each trial, the lower disease activity group (defined by TJC less than overall median) and the higher disease activity group. The same approach was used for SJC. Active treatment was tested for treatment control differences using several RA trial outcome measures: ACR20, EULAR response, ACRHybrid. Sample sizes needed for higher TJC and SJC RA trials versus lower TJC and SJC trials were compared. <h3>Results:</h3> Subtrials of subjects with lower TJC were found to have much higher sensitivity to change than those of subjects with higher TJC across all trials and outcome measures. A trial with lower TJC patients would require a smaller sample size than those with higher TJC patients. Results were not consistent for SJC subgroups. Three reasons were found for sensitivity to change of lower TJC: compared with higher TJC, those with lower TJC showed greater response to active treatment. Subjects with higher TJC on control treatment had greater percentage improvement and more variable responses than those in the lower TJC group. <h3>Conclusions:</h3> In RA trials, patients with lower disease activity within the range of current trial eligibility are more likely to show treatment efficacy than patients with higher disease activity. Lowering thresholds especially for TJC in trials may make it easier to detect treatment effects in RA.
The developmental mechanisms and the signal functions of early infant crying
Authors: Joseph Soltis
Journal: Behavioral and Brain Sciences (2004)

The majority of the commentaries focused on excessive crying and colic and included two major themes: the consideration of proximate physiological mechanisms, and challenges to my interpretation of the signal functions of early infant crying amount. I initially concluded that none of the competing signaling hypotheses enjoyed strong support, but I nevertheless favored the signaling vigor hypothesis above the signaling need and manipulation hypotheses. Consideration of the neurobiological causation of the n-shaped crying curve and further evidence and argumentation concerning the potential signal functions, however, do not allow for the elevation of any one of these hypotheses above the others, and it remains the case that none are strongly supported. Taken together, however, the target article and commentary do provide a solid foundation for further research. In the target article, I also proposed a model of how infant cry acoustics can influence patterns of care and abuse. Commentary has enriched this model by including the consideration of developmental changes in cry acoustics across early infancy, and by further integrating the cry signal with other modalities of communication and with later development. I trust that the foregoing will show that the joint pursuit of the proximate mechanisms and the potential signal functions of early infant cry amount and cry acoustics should prove fruitful. Before embarking on my reevaluation, however, I begin this response by addressing the issue of consciousness in evolutionary accounts of signaling.
Effects of Intensive Blood-Pressure Control in Type 2 Diabetes Mellitus
Authors: C. Cushman, Gregory W. Evans, Robert P. Byington, Jeffrey A. Cutler, Denise G. Simons-Morton, Jan N. Basile, Jeffrey L. Probstfield, Lois Katz, Kevin A. Peterson, William T. Friedewald, John B. Buse, J. Thomas Bigger, Hertzel C. Gerstein
Journal: New England Journal of Medicine (2010)

There is no evidence from randomized trials to support a strategy of lowering systolic blood pressure below 135 to 140 mm Hg in persons with type 2 diabetes mellitus. We investigated whether therapy targeting normal systolic pressure (i.e., <120 mm Hg) reduces major cardiovascular events in participants with type 2 diabetes at high risk for cardiovascular events.
Relationship Between Gastric Tumorigenesis and Intestinal Metaplasia in Rats Given X-Radiation and/or &lt;italic&gt;N&lt;/italic&gt;-Methyl-&lt;italic&gt;N′&lt;/italic&gt;-Nitro-&lt;italic&gt;N&lt;/italic&gt;-Nitrosoguanidine&lt;xref ref-type="fn" rid="FN1"&gt;2&lt;/xref&gt;&lt;xref ref-type="fn" rid="FN2"&gt;3&lt;/xref&gt;
Authors: H Watanabe, A Ito
Journal: JNCI Journal of the National Cancer Institute (1986)

The influence of x-radiation and N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7] on intestinal metaplasia and gastric tumorigenesis was examined in 5-week-old male Crj:CD(SD) rats. The animals were treated either with two 10-Gy fractions of x-rays separated by 3 days for a total of 20 Gy to the gastric region and/or with MNNG orally for 4 months. Simultaneous treatment with x-rays and MNNG (group II) and MNNG only (group IV) induced gastric tumors in the majority of the animals. Sequential treatment with x-radiation and MNNG, either x-ray 2 months prior to MNNG (group I) or MNNG 2 months prior to x-ray (group III), resulted in a lower incidence of gastric tumors as compared with the incidence after treatment with MNNG alone. The frequencies of intestinal metaplasia in the x-irradiated groups (groups I and V) were significantly higher than those in group II, III, or IV. The incidence of intestinal metaplasia and of gastric tumor was inversely proportional. These results indicate that intestinal metaplasia does not play a role in the induction of gastric tumors by MNNG.
Srf-Dependent Paracrine Signals Produced by Myofibers Control Satellite Cell-Mediated Skeletal Muscle Hypertrophy
Authors: Aline Guerci, Charlotte Lahoute, Sophie Hébrard, Laura Collard, Dany Graindorge, Maryline Favier, Nicolas Cagnard, Sabrina Batonnet-Pichon, Guillaume Précigout, Luis Garcia, David Tuil, Dominique Daegelen, Athanassia Sotiropoulos
Journal: Cell Metabolism (2012)
ULCER. OF THE LEGS MISCALLED VARICOSE: A CLINICAL REVIEW.
Authors: R. PROSSE. WHITE
Journal: British Journal of Dermatology (1918)

Journal Article ULCER. OF THE LEGS MISCALLED VARICOSE: A CLINICAL REVIEW. Get access R. PROSSE. WHITE, M.D., M.R.C.S. R. PROSSE. WHITE, M.D., M.R.C.S. Consulting Physician and Dermatologist, R.A.E. Infirmary, Wigan Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology and Syphilis, Volume 30, Issue 3, 1 July 1918, Pages 138–155, https://doi.org/10.1111/j.1365-2133.1918.tb13142.x Published: 01 July 1918
Expression Levels of <i>TEL</i>, <i>AML1</i>, and the Fusion Products <i>TEL-AML1</i> and <i>AML1-TEL</i> versus Drug Sensitivity and Clinical Outcome in t(12;21)-Positive Pediatric Acute Lymphoblastic Leukemia
Authors: Wendy A.G. Stams, Monique L. den Boer, H. Berna Beverloo, Jules P.P. Meijerink, Elisabeth R. van Wering, Gritta E. Janka-Schaub, Rob Pieters
Journal: Clinical Cancer Research (2005)

t(12;21)(p13; q22), present in approximately 25% of pediatric precursor B-ALL, is highly sensitivity to L-asparaginase and the prognosis depends on the intensity of the treatment protocol. This study analyzes the relationship between the mRNA expression of the genes and fusion products involved in t(12;21), in vitro sensitivity to prednisolone, vincristine, and L-asparaginase, and long-term clinical outcome in t(12;21)+ acute lymphoblastic leukemia (ALL) patients.Long-term clinical outcome in 45 t(12;21)+ ALL patients was related to mRNA expression of TEL, AML1, TEL-AML1, and AML1-TEL, determined by real-time quantitative PCR, and the in vitro sensitivity to prednisolone, vincristine, and L-asparaginase, using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays.A significant approximately 3.5-fold lower TEL expression in t(12;21)+ compared with t(12;21)- ALL samples (P = 0.006) and normal controls (P = 0.004) was found. Expression of AML1 did not differ between t(12;21)+ and t(12;21)- ALL. However, AML1 expression in the leukemic cells was 2-fold higher compared with normal controls (P = 0.02). The TEL-AML1 fusion product was expressed in all t(12;21)+ cases, whereas the reciprocal fusion product AML1-TEL was expressed in only 76%. High expression levels of TEL-AML1 [hazard ratio (HR), 1.3; 95% confidence interval (95% CI), 1.10-1.57; P = 0.003], AML1-TEL (HR, 4.9; 95% CI, 1.99-12.40; P = 0.001) and AML1 (HR, 1.1; 95% CI, 1.03-1.22; P = 0.006) were associated with a poor long-term clinical outcome within t(12;21)+ ALL. Cellular drug resistance towards prednisolone, vincristine, and L-asparaginase could not explain this predictive value. Multivariate analysis including age and WBC showed that only high AML1-TEL expression is an independent poor prognostic factor in t(12;21)+ childhood ALL.High AML1-TEL expression is an independent poor prognostic factor in t(12;21)+ childhood ALL.