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A Randomized Trial Comparing the Bowel Cleansing Efficacy of Sodium Picosulfate/Magnesium Citrate and Polyethylene Glycol/Bisacodyl (The Bowklean Study).
Hung, SY, Chen, HC, Chen, WT
Scientific reports. 2020;(1):5604
Abstract
Bowel cleansing is essential for a successful colonoscopy, but the ideal clearing agent and the volume have yet to be determined. A small-volume cleanser is important for patient compliance. This study aimed to compare the bowel cleansing efficacy, safety, tolerability, and acceptability of a 300-mL small-volume sodium picosulfate/magnesium citrate (PSMC) preparation-Bowklean with one 2-L polyethylene glycol (PEG)/bisacodyl-Klean-Prep/Dulcolax preparation under identical dietary recommendations. This multicenter, randomized, parallel-group, pre-specified noninferiority study enrolled 631 outpatients scheduled to undergo colonoscopy (Bowklean = 316 and Klean-Prep/Dulcolax = 315). After bowel preparation, an independent evaluator blinded to the subject's treatment allocation rated the quality of the colon cleansing. Efficacy was evaluated using the Aronchick Scale and Ottawa Bowel Preparation Scale (OPBS). Safety was assessed by monitoring adverse events. Tolerability and acceptability were measured via a patient questionnaire. Bowklean was non-interior to Klean-Prep/Dulcolax in overall colon cleansing but was associated with significantly better preparation quality. Notably, Bowklean was associated with significantly greater tolerability and acceptability of bowel preparations than Klean-Prep/Dulcolax. Safety profiles did not differ significantly between the groups. Our data indicate that Bowklean is a more effective and better-tolerated bowel cleansing preparation before colonoscopy than Klean-Prep/Dulcolax. Bowklean may therefore increase positive attitudes toward colonoscopies and participation rates.
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Phase IIb, Randomized, Double-Blind Trial of GC4419 Versus Placebo to Reduce Severe Oral Mucositis Due to Concurrent Radiotherapy and Cisplatin For Head and Neck Cancer.
Anderson, CM, Lee, CM, Saunders, DP, Curtis, A, Dunlap, N, Nangia, C, Lee, AS, Gordon, SM, Kovoor, P, Arevalo-Araujo, R, et al
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019;(34):3256-3265
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Abstract
PURPOSE Oral mucositis (OM) remains a common, debilitating toxicity of radiation therapy (RT) for head and neck cancer. The goal of this phase IIb, multi-institutional, randomized, double-blind trial was to compare the efficacy and safety of GC4419, a superoxide dismutase mimetic, with placebo to reduce the duration, incidence, and severity of severe OM (SOM). PATIENTS AND METHODS A total of 223 patients (from 44 institutions) with locally advanced oral cavity or oropharynx cancer planned to be treated with definitive or postoperative intensity-modulated RT (IMRT; 60 to 72 Gy [≥ 50 Gy to two or more oral sites]) plus cisplatin (weekly or every 3 weeks) were randomly assigned to receive 30 mg (n = 73) or 90 mg (n = 76) of GC4419 or to receive placebo (n = 74) by 60-minute intravenous administration before each IMRT fraction. WHO grade of OM was assessed biweekly during IMRT and then weekly for up to 8 weeks after IMRT. The primary endpoint was duration of SOM tested for each active dose level versus placebo (intent-to-treat population, two-sided α of .05). The National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.03, was used for adverse event grading. RESULTS Baseline patient and tumor characteristics as well as treatment delivery were balanced. With 90 mg GC4419 versus placebo, SOM duration was significantly reduced (P = .024; median, 1.5 v 19 days). SOM incidence (43% v 65%; P = .009) and severity (grade 4 incidence, 16% v 30%; P = .045) also were improved. Intermediate improvements were seen with the 30-mg dose. Safety was comparable across arms, with no significant GC4419-specific toxicity nor increase of known toxicities of IMRT plus cisplatin. The 2-year follow-up for tumor outcomes is ongoing. CONCLUSION GC4419 at a dose of 90 mg produced a significant, clinically meaningful reduction of SOM duration, incidence, and severity with acceptable safety. A phase III trial (ROMAN; ClinicalTrials.gov identifier: NCT03689712) has begun.
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Acute suppression of bone turnover with calcium infusion in persons with spinal cord injury.
Bauman, WA, Zhang, RL, Morrison, N, Spungen, AM
The journal of spinal cord medicine. 2009;(4):398-403
Abstract
BACKGROUND Some people with chronic spinal cord injury (SCI) have low vitamin D levels and secondary hyperparathyroidism. OBJECTIVE To determine whether, and to what extent, an acute calcium infusion decreased levels of N-telopeptide (NTx), a marker of osteoclastic activity, in individuals with chronic SCI. STUDY DESIGN Case series. SUBJECTS Eight men with chronic SCI. A relatively low serum 25 hydroxyvitamin D concentration (25[OH]D < or =20 ng/mL) and/or a high parathyroid hormone (PTH) (>55 pg/mL) was a prerequisite for study inclusion. METHODS Calcium gluconate bolus 0.025 mmol elemental calcium/kg over 20 minutes followed by a constant infusion of 0.025 mmol/kg per hour for 6 hours was infused; blood samples were collected every 2 hours for measurement of serum total calcium, creatinine, NTx, and PTH. RESULTS All results are expressed as means (+/- SDs). Baseline serum 25-hydroxyvitamin D level was 14.5 +/- 3.5 ng/mL (range: 10.2-19.6 ng/mL); PTH, 70 +/- 25 pg/mL (range: 37-100 pg/mL); and NTx, 21 +/- 7 nM bone collagen equivalents (BCE) (range: 14-34 nM). At 2, 4, and 6 hours after the calcium infusion, serum calcium rose from 9.3 +/- 0.2 to 10.8 +/- 0.9, 10.5 +/- 0.8, and 10.6 +/- 0.6 mg/d; PTH was suppressed from 70 +/- 25 pg/mL to 18 +/- 12, 16 +/- 9, and 15 +/- 9 pg/mL, respectively; NTx fell from 21 +/- 8 nM BCE to 17 +/- 5, 12 +/- 4, and 12 +/- 3 nM BCE, respectively. CONCLUSIONS Serum NTx is a marker for bone collagen catabolism, and its reduction suggests that bone turnover was decreased. A relative deficiency of vitamin D associated with chronically elevated levels of PTH would be expected to increase bone turnover and to worsen the bone loss associated with immobilization.
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186Re-HEDP in the treatment of patients with inoperable osteosarcoma.
Syed, R, Bomanji, J, Nagabhushan, N, Kayani, I, Groves, A, Waddington, W, Cassoni, A, Ell, PJ
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2006;(12):1927-35
Abstract
UNLABELLED The aim of this study was to examine the safety and efficacy of (186)Re-hydroxyethylidene diphosphonate (HEDP) as an adjuvant to external-beam radiotherapy (EBRT) in the treatment of patients with osteosarcoma. METHODS Thirteen patients (9 male, 4 female; age range, 12-42 y) were treated with combination chemotherapy (standard U.K. protocol) and (186)Re-HEDP therapy (18.5 MBq/kg, intravenously), followed by EBRT. A full blood count; liver function test; and measurements of urea and electrolytes, glomerular filtration rate, and left ventricular function were performed on all patients before and after therapy. Tumor volume and composition were obtained from CT or MRI data. Dosimetric calculations were performed using the MIRD formalism. RESULTS Of the 13 patients, 1 is still under follow-up. The median survival time was 36 mo (range, 12-216 mo) from diagnosis and 5 mo (range, 1-60 mo) from the last (186)Re-HEDP treatment. The mean tumor dose delivered with (186)Re-HEDP was calculated to be 5.8 Gy (range, 0.5-16 Gy). CT and MRI revealed the tumors to have a complex structure, comprising "ossified," "partially calcified," and "soft-tissue" components. Posttherapy scans showed a heterogeneous distribution of (186)Re-HEDP in the tumor mass: Although the "soft-tissue" component showed minimal uptake of the therapeutic dose, the "ossified component" showed intense uptake. The 3 long-term survivors in whom tumor sterilization was achieved received calculated mean tumor doses in the range of 2.0-3.1 Gy, which was believed to be an underestimate of the actual tumor doses delivered. CONCLUSION This study indicates that a simple approach to tumor dosimetry based on mean tumor dose is inappropriate because it may underestimate the dose delivered to these heterogeneous tumors. The data also indicate that EBRT combined with a standard dose of 18.5 MBq/kg of (186)Re-HEDP does not provide a sufficient dose to achieve tumor sterilization. A dose estimation technique is required that is based on the determination of tumor dose at the individual voxel level and that is able to represent the heterogeneous uptake observed in these complex tumor structures with highly nonuniform composition. This, coupled with individualized dose escalation, may then achieve the goal of tumor sterilization.
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Efficacy of bowel preparation with the use of a prepackaged, low fibre diet with a low sodium, magnesium citrate cathartic vs. a clear liquid diet with a standard sodium phosphate cathartic.
Delegge, M, Kaplan, R
Alimentary pharmacology & therapeutics. 2005;(12):1491-5
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BACKGROUND A colon free of faecal residue is required for accurate diagnostic colonoscopy. Patient tolerance of his/her colonoscopy cathartic regimen affects patient compliance and willingness to undergo repeated examinations. AIM: To determine whether a meal could be consumed during standard bowel preparation. METHODS This was a randomized, endoscopists' blinded comparison of the tolerability and efficacy of a prepackaged, low-residue diet (NutraPrep) combined with the LoSo Prep bowel cleansing system, which contains magnesium citrate, bisocodyl tablets and a bisocodyl suppository (NP-LS regimen), compared with a clear liquid diet and a double-dose sodium phosphate (Fleet Phospho-soda) regimen (2F regimen). Outcome measures included efficacy of bowel preparation, patient preparation tolerability, side-effects and patient safety. RESULTS A total of 506 patients completed the study, 222 randomized to 2F and 284 to NP-LS. The NP-LS regimen resulted in significantly better colon cleansing in terms of the proportion with good or excellent results (P = 0.025) and in significantly better patient tolerance and willingness to repeat the cathartic preparation (P < 0.01). CONCLUSION The NP-LS regimen proved superior to the 2F regimen.
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Peptide receptor radionuclide therapy for non-radioiodine-avid differentiated thyroid carcinoma.
Teunissen, JJ, Kwekkeboom, DJ, Kooij, PP, Bakker, WH, Krenning, EP
Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 2005;:107S-14S
Abstract
UNLABELLED In patients with progressive metastatic (or recurrent) differentiated thyroid carcinoma (DTC) who do not respond to radioiodine therapy or do not show uptake on radioiodine scintigraphy, treatment options are few. Because these tumors may express somatostatin receptors, peptide receptor radionuclide therapy might be effective. We evaluated the therapeutic efficacy of the radiolabeled somatostatin analog (177)Lu-1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid(0) (DOTA), Tyr(3)-octreotate ((177)Lu-DOTATATE) in patients with DTC. The uptake of radioactivity in tumors was also studied in relation to treatment outcome. METHODS Five patients with DTC (3 with Hurthle cell thyroid carcinoma [HCTC], 1 with papillary thyroid carcinoma [PTC], and 1 with follicular thyroid carcinoma [FTC]) were treated with 22.4-30.1 GBq of (177)Lu-DOTATATE. Response to therapy was evaluated with CT. Uptake on (177)Lu-DOTATATE scintigraphy (24 h after treatment), expressed as percentage of injected dose, was compared with uptake on pretherapy (111)In-octreotide scintigraphy (24 h after injection). RESULTS After the last treatment with (177)Lu-DOTATATE, 1 patient with HCTC had stable disease as a maximum response, 1 patient with HCTC had minor remission (tumor shrinkage between 25% and 50%), and 1 patient with HCTC had partial remission (shrinkage > or =50%). The responses in PTC and FTC were stable disease and progressive disease, respectively. A decrease in serum thyroglobulin level was found in patients with HCTC. Patients with minor and partial remissions had the highest (177)Lu-DOTATATE-to-(111)In-diethylenetriamine pentaacetic acid(0)-octreotide ((111)In-octreotide) uptake ratios (3.2 and 2.4, respectively) whereas the other patients had uptake ratios smaller than 1.5. CONCLUSION (177)Lu-DOTATATE therapy can be effective in patients with progressive DTC who have no therapeutic options and sufficient uptake of (111)In-octreotide in tumor lesions as shown on (111)In-octreotide scintigraphy. This finding is especially important in patients with HCTC, because they cannot benefit from radioiodine therapy because of non-iodine-avid lesions at diagnosis.
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Antimonial therapy induces circulating proinflammatory cytokines in patients with cutaneous leishmaniasis.
Kocyigit, A, Gur, S, Gurel, MS, Bulut, V, Ulukanligil, M
Infection and immunity. 2002;(12):6589-91
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The objective of this study was to evaluate the association between antimonial therapy and circulating levels of proinflammatory cytokines in patients with cutaneous leishmaniasis (CL). Patients were treated with conventional chemotherapy by using pentavalent antimonium salts (Glucantime) for 3 weeks. Circulating plasma levels of the proinflammatory cytokines interleukin-1beta (IL-1beta), IL-6, IL-8, and tumor necrosis factor alpha (TNF-alpha) were determined for CL patients and healthy subjects before and 3 weeks after the treatment was started. Plasma IL-1beta, IL-6, IL-8, and TNF-alpha levels were significantly higher for pretreatment CL patients than for healthy subjects. Proinflammatory cytokines significantly increased after 21 days postinfection compared to levels for the pretreatment patients. These increments were approximately 3-fold for IL-1beta and TNF-alpha levels, 10-fold for IL-6 levels, and 20-fold for IL-8 levels in patients with CL. Taken together these results indicate that circulating proinflammatory cytokine levels were increased in patients with CL as a consequence of host defense strategies, and antimonial therapy may induce these cytokines by affecting the macrophage or other components of the host defense system.
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Effects of meal consistency and ingested fluid volume on the intragastric distribution of a drug model in humans--a magnetic resonance imaging study.
Faas, H, Steingoetter, A, Feinle, C, Rades, T, Lengsfeld, H, Boesiger, P, Fried, M, Schwizer, W
Alimentary pharmacology & therapeutics. 2002;(2):217-24
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BACKGROUND Controlled delivery of drugs to the small intestine in relation to emptying of an ingested meal is important in various pathophysiological conditions. We investigated the effects of different food consistencies and the amount of co-ingested liquid on the intragastric distribution of a contrast marker. METHODS Five healthy subjects received four meals (each 650 kcal: A, mashed potato with 100 mL water; B, rice with 100 mL water; C, hamburger meal with 100 mL water; D, hamburger meal with 300 mL water). A capsule filled with gadolinium tetra-azacyclododecane tetra-acetic acid solution (as contrast marker) was ingested following meal termination, and its intragastric distribution was assessed by magnetic resonance imaging. RESULTS Initially, marker distribution was confined to the fundus, and subsequently extended along the inner curvature of the stomach. The maximum distribution volume of the marker was lower in meal A than in meal B (P < 0.05). No differences in marker distribution were observed when the hamburger meal was given with 100 or 300 mL water. CONCLUSIONS The intragastric distribution kinetics of the marker gadolinium tetra-azacyclododecane tetra-acetic acid appeared to depend on meal consistency, but not on the amount of water co-ingested. Three-dimensional magnetic resonance imaging allows detailed analysis of the intragastric distribution of a drug model in relation to meal emptying and intragastric meal distribution.