306 research outputs found
Local governmental audit and accounting manual, as of March 1, 1991: a nonauthoritative practice aid
https://egrove.olemiss.edu/aicpa_guides/1211/thumbnail.jp
Local governmental audit and accounting manual, as of March 1, 1990 : a nonauthoritative practice aid
https://egrove.olemiss.edu/aicpa_guides/1210/thumbnail.jp
Local governmental audit and accounting manual, as of March 1, 1991: a nonauthoritative practice aid;Notes to the illustrative combined financial statements;
https://egrove.olemiss.edu/aicpa_guides/1005/thumbnail.jp
Phase I and pharmacokinetic study of brostallicin (PNU-166196), a new DNA minor-groove binder, administered intravenously every 3 weeks to adult patients with metastatic cancer
PURPOSE: Brostallicin (PNU-166196) is a cytotoxic agent that binds to the
minor groove of DNA with significant antitumor activity in preclinical
studies. This trial was designed to determine the maximum tolerated dose,
the toxicity profile, and the pharmacokinetics of Brostallicin in cancer
patients. Experimental Design: Patients were treated with escalating doses
of Brostallicin ranging from 0.85 to 15 mg/m(2) administered as a 10-min
i.v. infusion every 3 weeks. Blood samples for pharmacokinetic analysis
were collected during the first and second course, and analyzed by
liquid-chromatography with tandem-mass spectrometric detection. RESULTS:
Twenty-seven evaluable patients received a total of 73 courses. Grade 4
neutropenia was the only dose-limiting toxicity at 12.5 mg/m(2), whereas
grade 4 thrombocytopenia (1 patient) and grade 4 neutropenia (2 patients)
were the dose-limiting toxicities at 15 mg/m(2). Other side effects,
including thrombocytopenia and nausea, were generally mild. The maximum
tolerated dose was defined at 10 mg/m(2). The clearance and terminal
half-life of Brostallicin were dose-independent, with mean (+/-SD) values
of 9.33 +/- 2.38 liters/h/m(2) and 4.69 +/- 1.88 h, respectively. There
was no significant accumulation of Brostallicin with repeated
administration. Significant relationships were observed between systemic
exposure to Brostallicin and neutrophil counts at nadir. One partial
response was observed in a patient with a gastrointestinal stromal tumor.
CONCLUSION: Brostallicin was found to be well tolerated, with neutropenia
being the principal toxicity. The recommended dose for additional
evaluation in this schedule is 10 mg/m(2)
A multicenter randomized clinical trial investigating the cost-effectiveness of treatment strategies with or without antibiotics for uncomplicated acute diverticulitis (DIABOLO trial)
Background. Conservative treatment of uncomplicated or mild diverticulitis usually includes antibiotic therapy. It is, however, uncertain whether patients with acute diverticulitis indeed benefit from antibiotics. In most guidelines issued by professional organizations antibiotics are considered mandatory in the treatment of mild diverticulitis. This advice lacks evidence and is merely based on experts' opinion. Adverse effects of the use of antibiotics are well known, including allergic reactions, development of bacterial resistance to antibiotics and other side-effects. Methods. A randomized multicenter pragmatic clinical trial comparin
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MARTIN THURNER, Gott als das offenbare Geheimnis nach Nikolaus von Kues, NICOLĂS DE CUSA, Acerca de la docta ignorancia, trad. J. M. MACHETTA / C. DâAMICO. THILO OFFERGELD, Reges pueri. Das Königtum MinderjĂ€hriger im FrĂŒhen Mittelalter. W. EFFERT (ed), Monumenta Germaniae Historica, Constitutiones et acta publica imperatorum et regum. THOMAS EBENDORFER, Chronica regum Romanorum, ed. H. ZIMMERMANN. MARTIN THURNER (ed), Nicolaus Cusanus zwischen Deutschland und Italien. PEDRO ABELARDO, DiĂĄlogo entre un filĂłsofo, un judĂo y un Cristiano, trad. SILVIA MAGNAVACCA. M. ĂLVAREZ GĂMEZ / J. MARĂA ANDRĂ, Coincidencia de opuestos y concordia. Los caminos del pensamiento en NicolĂĄs de Cusa. J. IGNASI SARANYANA, La filosofĂa medieval. Desde sus orĂgenes patrĂsticos hasta la EscolĂĄstica barroca. TOMĂS DE AQUINO-PEDRO DE ALVERNIA, Comentario a la PolĂtica de AristĂłteles, trad. A. MALLEA. G. FERNĂNDEZ DE OVIEDO, Claribalte, ed. M. J. RODILLA LEĂN. RICCARDO QUINTO, Scholastica. Storia di un concetto. LUIS ALBERTO DE BONI, De Abelardo a Lutero. Estudos sobre filosofia prĂĄtica na Idade Media. O. B. Rader (ed), âTurbata per aequora mundiâ
Gluten sensitivity enteropathy in patients with recurrent aphthous stomatitis
<p>Abstract</p> <p>Background</p> <p>Gluten sensitive enteropathy (GSE) is an autoimmune enteropathy triggered by the ingestion of gluten-containing grains in susceptible individuals. Recurrent aphthous stomatitis (RAS) may be the sole manifestation of GSE. The aim of this study was to determine the prevalence of gluten sensitivity enteropathy (GSE) in a large group of patients with RAS and assess the efficacy of gluten free diet (GFD) on the improvement of aphthous lesions in those who were diagnosed with GSE.</p> <p>Methods</p> <p>Two hundred and forty seven patients with RAS were included. The patients had at least three aphthous attacks per year. Patients were screened by IgA anti-endomysial antibody (EMA), IgA anti tissue transglutaminase (TTG) and serum IgA level. Those with a positive serology underwent endoscopic biopsies of the duodenal mucosa and patients with negative serology were excluded. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histology. For patients with GSE, gluten free diet was recommended.</p> <p>Results</p> <p>Six out of 247 RAS patients had positive TTG test alone, and one had positive EMA and TTG. All 7 patients with positive serologic tests underwent duodenal biopsies. Histological findings were compatible with GSE in all of them (Marsh I in four patients, Marsh II in two patients and Marsh IIIB in one another.). The mean age of GSE patients was 27.42 ± 10.56 (range, 13 to 40) years old. They were suffering from RAS for an average duration of 4.5 years. All of the 7 GSE patients had not responded to the routine anti-aphthae medications, including topical corticosteroids, tetracycline and colchicine. Four patients who adhered to a strict gluten-free diet showed noticeable improvement in their aphthous lesions over a period of 6 months.</p> <p>Conclusion</p> <p>A significant minority (e.g. 2.83%) of RAS patients have GSE. This could be compared with the 0.9% prevalence of GSE in the general population of Iran. This study suggests that evaluation for celiac disease is appropriate in patients with RAS. Additionally, the unresponsiveness to conventional anti-aphthae treatment could be an additional risk indicator.</p
Post-progression outcomes of NSCLC patients with PD-L1 expression â„ 50% receiving first-line single-agent pembrolizumab in a large multicentre real-world study
Effect of concomitant medications with immune-modulatory properties on the outcomes of patients with advanced cancer treated with immune checkpoint inhibitors: development and validation of a novel prognostic index
Background: Concomitant medications are known to impact on clinical outcomes of patients treated with immune checkpoint inhibitors (ICIs). We aimed weighing the role of different concomitant baseline medications to create a drug-based prognostic score. Methods: We evaluated concomitant baseline medications at immunotherapy initiation for their impact on objective response rate (ORR), progression-free survival (PFS) and overall survival (OS) in a single-institution cohort of patients with advanced cancer treated with ICIs (training cohort, N = 217), and a drug-based prognostic score with the drugs resulting significantly impacting the OS was computed. Secondly, we externally validated the score in a large multicenter external cohort (n = 1012). Results: In the training cohort (n = 217), the median age was 69 years (range: 32â89), and the primary tumours were nonâsmall-cell lung cancer (70%), melanoma (14.7%), renal cell carcinoma (9.2%) and others (6%). Among baseline medications, corticosteroids (hazard ratio [HR] = 2.3; 95% confidence interval [CI]: 1.60â3.30), systemic antibiotics (HR = 2.07; 95% CI: 1.31â3.25) and proton-pump inhibitors (PPIs) (HR = 1.57; 95% CI: 1.13â2.18) were significantly associated with OS. The prognostic score was calculated using these three drug classes, defining good, intermediate and poor prognosis patients. Within the training cohort, OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0297) were significantly distinguished by the score stratification. The prognostic value of the score was also demonstrated in terms of OS (p < 0.0001), PFS (p < 0.0001) and ORR (p = 0.0006) within the external cohort. Conclusion: Cumulative exposure to corticosteroids, antibiotics and PPIs (three likely microbiota-modulating drugs) leads to progressively worse outcomes after ICI therapy. We propose a simple score that can help stratifying patients in routine practice and clinical trials of ICIs
Predictive ability of a drug-based score in patients with advanced nonâsmall-cell lung cancer receiving first-line immunotherapy
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