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1.
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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Split-dose administration of a dual-action, low-volume bowel cleanser for colonoscopy: the SEE CLEAR I study.
Rex, DK, Katz, PO, Bertiger, G, Vanner, S, Hookey, LC, Alderfer, V, Joseph, RE
Gastrointestinal endoscopy. 2013;(1):132-41
Abstract
BACKGROUND New bowel cleansers for colonoscopy that lead to improved efficacy, safety, and tolerability are needed. OBJECTIVE This study evaluated a nonphosphate, dual-action, low-volume, orange-flavored preparation containing sodium picosulfate and magnesium citrate (P/MC). DESIGN Multicenter, assessor-blinded, randomized, noninferiority study. SETTING University hospitals, academic medical centers, and private clinics across the United States. PATIENTS Adults preparing for colonoscopy. INTERVENTIONS P/MC versus 2 L of polyethylene glycol solution (2L PEG-3350) and two 5-mg bisacodyl tablets. MAIN OUTCOME MEASUREMENTS This phase 3 study investigated the efficacy, safety, and tolerability of split-dose administration of P/MC versus day-before dosing of 2L PEG-3350 and two 5-mg bisacodyl tablets (SEE CLEAR I study). Efficacy was evaluated by using the Aronchick and Ottawa scales; noninferiority and superiority analyses were performed. Safety was assessed by monitoring adverse events (AEs). Tolerability was measured via a patient questionnaire. RESULTS The intent-to-treat population consisted of 601 patients who self-administered P/MC (n = 304) or 2L PEG-3350 and bisacodyl tablets (n = 297). P/MC was superior to 2L PEG-3350 and bisacodyl tablets in overall colon cleansing (84.2% vs 74.4%; 1-sided 97.5% confidence interval [CI], 3.4) (Aronchick scores of excellent or good) and in cleansing of the ascending (89.5% vs 78.8%; 1-sided 97.5% CI, 4.9), mid (transverse and descending) (92.4% vs 85.9%; 1-sided 97.5% CI, 1.6), and rectosigmoid (92.4% vs 87.2%; 1-sided 97.5% CI, 0.4) segments of the colon (Ottawa scores of excellent, good, or fair). Commonly reported AEs related to the bowel preparations were nausea, vomiting, headache, and chills. Patient-reported tolerability, including ease of consumption and taste, was significantly higher for P/MC than 2L PEG-3350 and bisacodyl tablets (P < .0001). LIMITATIONS Because of differences in administration and volume of the bowel preparations, the study was designed to be a single-assessor, blinded study. CONCLUSIONS The bowel-cleansing effects and patient acceptability of split-dose P/MC were superior to day-before dosing with 2L PEG-3350 and bisacodyl tablets.
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[Preventive effect of polaprezinc suspension dispersed in sodium alginate solution (P-AG) for stomatitis induced by Docetaxel/Cisplatin/Fluorouracil (DCF) chemotherapy in patients with head and neck cancer].
Sugisaki, T, Kawakami, K, Nemoto, M, Kawata, K, Ishibashi, M, Fujiki, Y, Mishima, Y, Yokoyama, M, Takahashi, S, Hatake, K, et al
Gan to kagaku ryoho. Cancer & chemotherapy. 2011;(5):783-7
Abstract
We measured the effectiveness of the prophylactic administration of a polaprezinc suspension dispersed in sodium alginate solution (P-AG) by dividing it into two courses in the same patients, and measured the stomatitis induced by Docetaxel/Cisplatin/Fluorouracil (DCF) chemotherapy. We then evaluated the results. We defined the therapeutic course as the course where P-AG was given therapeutically for stomatitis induced after DCF chemotherapy. We defined the prophylactic course as when P-AG was prophylactically given before any incidences of stomatitis after the therapeutic course. We compared the incidences of stomatitis in the prophylactic courses with those of the therapeutic courses. The incidences of stomatitis that were higher than Grade 1 were 17 out of 17 patients (100%) in the therapeutic course. On the other hand, they were 15 out of 17 patients (88. 2%) in the prophylactic course. Compared with the mean of the Grade of Stomatitis by the Common Terminology Criteria for Adverse Events version 3. 0 (CTCAE v. 3. 0), the maximal Grade of stomatitis significantly decreased in the prophylactic courses compared to those of the therapeutic courses(p<0. 05). Therefore, these results suggested that we were able to decrease the severity of stomatitis by using P-AG prophylactically, as opposed to using P-AG therapeutically.
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An observational study of methionine-bound zinc with antioxidants for mild to moderate acne vulgaris.
Sardana, K, Garg, VK
Dermatologic therapy. 2010;(4):411-8
Abstract
APC is a novel methionine-based zinc complex with antioxidants that has been used in acne as a nutritional supplement. This is based on the proven role of zinc and antioxidants in improving acne, specially the inflammatory lesions. The objectives of this study are to explore the efficacy, safety, and tolerability of APC in acne patients with mild to moderate facial acne vulgaris. In this exploratory trial, 48 patients were treated with oral APC thrice a day for 3 months followed by a 4-week treatment-free period. At the end of treatment (Week 12), there was a statistically significant improvement in the global acne count (p < 0.05), which began after 8 weeks (p < 0.05). Almost 79% (38/48) of the patients had 80-100% improvement. There was a significant reduction in pustules (8 weeks (p < 0.05) and 12 weeks (p < 0.001)), and papules and closed comedones (8 weeks (p < 0.05) and 12 weeks (p < 0.001)). Only two patients had side effects. The current data indicate that treatment with oral APC thrice daily for 12 weeks in patients with mild to moderate facial acne vulgaris is efficacious and well tolerated. As the onset of action is late, concomitant topical therapy can enhance the results.
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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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A randomised controlled trial of a new 2 litre polyethylene glycol solution versus sodium picosulphate + magnesium citrate solution for bowel cleansing prior to colonoscopy.
Worthington, J, Thyssen, M, Chapman, G, Chapman, R, Geraint, M
Current medical research and opinion. 2008;(2):481-8
Abstract
BACKGROUND A new 2 L polyethylene glycol (PEG) solution containing ascorbic acid (Asc) and electrolytes (Moviprep) has been developed for bowel cleansing. OBJECTIVES To compare the efficacy, safety and acceptability of PEG + Asc versus sodium picosulphate + magnesium citrate in patients scheduled to undergo colonoscopy. DESIGN AND METHODS This single blind, parallel group pilot study included 65 adult male and female patients. A blinded assessment of cleansing was made for each bowel segment by the colonoscopist and the scores determined an overall grading of bowel cleansing. Patients completed a questionnaire on the acceptability of the preparation. RESULTS Successful bowel preparation was reported in 84.4% of patients who received PEG + Asc and 72.7% of patients who received sodium picosulphate + magnesium citrate (treatment difference +11.6, 95% CI -11.2, +34.5; p = 0.367). Patients were more likely to have a higher overall quality of bowel cleansing with PEG + Asc (p = 0.018), with specifically better cleansing in the ascending colon (p = 0.024) and caecum (p = 0.003) compared with patients who received sodium picosulphate + magnesium citrate. The adverse event profile of the two treatments was similar, with headache and gastrointestinal effects being the most commonly reported. Some patient acceptability results favoured sodium picosulphate + magnesium citrate for those patients who had experience of previous bowel preparation, but were similar for those patients who had not had a previous bowel preparation. CONCLUSIONS PEG + Asc provided effective bowel cleansing, which was equivalent to that of sodium picosulphate + magnesium citrate in terms of grading cleansing as overall success or failure. In the proximal colon (ascending colon and caecum) PEG + Asc provided significantly better cleansing to that achieved with sodium picosulphate + magnesium citrate.
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Dehydration induced by bowel preparation in older adults does not result in cognitive dysfunction.
Ackland, GL, Harrington, J, Downie, P, Holding, JW, Singh-Ranger, D, Griva, K, Mythen, MG, Newman, SP
Anesthesia and analgesia. 2008;(3):924-9, table of contents
Abstract
BACKGROUND Postoperative cognitive dysfunction occurs in a proportion of patients after noncardiac surgery. Older patients are particularly vulnerable. We hypothesized that dehydration, a common perioperative problem in the elderly, may provoke cognitive dysfunction. We used a clinical scenario free of surgical/anesthetic intervention to determine whether dehydration caused by bowel preparation results in cognitive changes. METHODS Thirty-eight patients of an age associated with a significant incidence of postoperative cognitive dysfunction were recruited in a prospective observational study. A further control group of 14 patients undergoing sigmoidoscopy, who did not receive any bowel preparation, were matched for age, education, and gender. RESULTS Loss of total body weight (1.5 kg [95% CI: 0.9-2.2]; P < 0.001) occurred in patients undergoing bowel preparation (2.0 [95% CI: 1.3-2.6] percent total body weight), whereas sigmoidoscopy patients' weight did not change (0.17 kg [95% CI: -0.2-0.6 kg]; P = 0.26). Total body water, derived from foot bioimpedance, indicated dehydration in the bowel preparation group only (mean impedance change 36 [Omega] [95% CI; 25-46], P < 0.001) with a calculated decrease of 2.6% in total body water (95% CI: 1.1-4.8; P < 0.001). Hematocrit increased after bowel preparation only (prebowel prep 0.41 [0.40-0.43] versus postbowel prep 0.43 [0.42-0.45]; P = 0.003). Despite this degree of dehydration, all cognitive tests were within 1 SD of the population mean of normal values. Repeated measures analysis of variance did not reveal significant changes for within group comparisons over time for motor speed (P = 0.51), executive function (P = 0.57), Trail Making Tests and recall (P = 0.88), other than a 3 s slowing in learning ability (Rey Auditory Verbal Learning Test; P = 0.04). Hydration status did not affect learning (P = 0.42), recall (P = 0.30) motor speed (P = 0.36), or executive function tests (P = 0.26). CONCLUSION Dehydration alone does not result in cognitive dysfunction.
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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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Comparative assessment of the bioavailability, efficacy and safety of a modified-release (MR) carbonyl iron tablet and oral conventional iron preparation in adult Indian patients with nutritional iron deficiency anaemia.
Adsul, BB, Desai, A, Gawde, A, Baliga, V
Journal of the Indian Medical Association. 2005;(6):338-42
Abstract
The objective of the study is to evaluate the bioavailability, efficacy and safety of a new modified-release (MR) formulation of carbonyl iron (45 mg) relative to a commercially available conventional formulation of ferrous fumarate (300 mg) in adult Indian patients with clinical and laboratory diagnosis of nutritional iron deficiency anaemia. This prospective, comparative, randomised, double-blind study was carried out among 60 patients received a single daily dose of either MR carbonyl iron or ferrous fumarate for 12 weeks. The effect of therapy on haematological parameters and iron status and estimation of bioavailability were the main efficacy outcomes. There was a significant (p<0.05) increase in mean haemoglobin levels, reticulocyte counts, haematocrit and mean corpuscular volume in MR carbonyl iron group compared to ferrous fumarate group. There was also an increase in mean serum iron and ferritin levels and a corresponding decrease in total iron binding capacity in MR carbonyl iron group compared to ferrous fumarate group at the end of 12 weeks therapy. The estimated overall bioavailability of MR carbonyl iron was about 147% that of ferrous fumarate. Both the formulations were equally well-tolerated and adverse events were mainly gastrointestinal in nature. The prevalence of adverse events was slightly more in the ferrous fumarate group. It can be concluded that the MR formulation of carbonyl iron was more efficacious than ferrous fumarate in correcting haematologic abnormalities and improving iron status in patients with nutritional iron deficiency anaemia. In conditions where efficacy is an important consideration, the higher bioavailability of MR carbonyl iron may make it the treatment of choice for nutritional iron deficiency anaemia.