Impact of Split Dosing the First Rituximab Infusion in Patients with High Lymphocyte Count

The most common adverse reactions to rituximab are infusion-related reactions (IRR). We evaluated the efficacy of split dosing the first rituximab infusion over two days to reduce IRR incidence in patients with hematological cancer and a high lymphocyte count. This is a retrospective observational study conducted in two healthcare centers in Quebec, Canada. The study enrolled patients with white blood cell counts ≥25.0 × 109/L who received their first rituximab dose for hematological cancer between December 2007 and May 2020. One healthcare center used asymmetrical split dosing, while the other used symmetrical split dosing. A total of 183 treatment episodes were collected from 143 patients. Among patients who received a fractionated dosing schedule, 42% developed an IRR from the first rituximab infusion compared with 50% for the standard protocol (adjusted relative risk, 0.89; p = 0.540). No significant difference was observed in IRR severity between either groups. However, 24% of patients who received the asymmetrical protocol developed an IRR compared to 68% for the symmetrical protocol (adjusted relative risk, 0.32; p = 0.003). These results suggest that an asymmetrical split dosing could be effective in reducing the incidence of IRR and is preferable to a symmetrical one.

Bowel preparation with 1L polyethylene glycol and ascorbate NER1006 doubles the chance to detect three or more adenomas in overweight or obese males

Background and study aims Men have more colon cleansing failures, colorectal adenomas, and colorectal cancers than women. We analyzed whether 1-liter (1 L) polyethylene glycol (PEG) NER1006 improves high-quality (HQ) colon cleansing and adenoma detection in males versus two mid-volume alternatives. Patients and methods The analysis of 1028 adult patients in two randomized clinical trials was performed. Adenoma detection and HQ cleansing were compared for overnight split dosing regimens with NER1006 (n = 513) versus combined oral sulfate solution or 2 L PEG + ascorbate (OSS/2 L PEG) (n = 515). Analyses included males versus females, overweight or obese (OO) males versus lean males, and NER1006 versus OSS/2 L PEG. In male patients, the adenoma detection rate of at least 3 (ADR3 +) was predicted with multiple logistic regression and statistical comparisons used the two-sided t-test. Results ADR3 + was greater in males versus females (10.7 % [56/524] versus 5.8 % [29/504]; P = 0.004) despite comparable adequate cleansing success rates (93.2 % [479/514] versus 93.0 % [466/501]; P = 0.912) and more HQ-scores in females (41.6 % [1069/2570] versus 45.3 % [1134/2505]; P = 0.008). ADR was almost twice as high in OO versus lean males (43.4 % [184/424] versus 23.1 % [21/91]; P < 0.001). Multivariate logistic regression predicted ADR3 + detection to be twice as likely in OO males using NER1006 versus OSS/2 L PEG (odds ratio (95 % confidence interval [CI]) = 2.049 (1.082–3.973); P = 0.030) and 90 % more likely in all males (1.902 (1.045–3.526); P = 0.037). In males, including OO males, NER1006 attained more HQ-scores per trial than OSS or 2 L PEG (P ≤ 0.017 for all comparisons). Conclusions NER1006 predicted the detection of more males for frequent surveillance than OSS/2 L PEG.

The importance of colonoscopy bowel preparation for the detection of colorectal lesions and colorectal cancer prevention

Background and study aims Colonoscopy for colorectal cancer (CRC) screening has reduced CRC incidence and mortality and improved prognosis. Optimal bowel preparation and high-quality endoscopic technique facilitate early CRC detection.This review provides a narrative on the clinical importance of bowel preparation for colonoscopy and highlights available bowel preparations. Methods A PubMed search was conducted through June 2019 to identify studies evaluating clinical outcomes, efficacy, safety, and tolerability associated with bowel preparation for CRC screening-related colonoscopy. Results Selecting the optimal bowel preparation regimen is based on considerations of efficacy, safety, and tolerability, in conjunction with individual patient characteristics and preferences. Available bowel preparations include high-volume (4 L) and low-volume (2 L and 1 L), polyethylene glycol (PEG) solutions, sodium sulfate, sodium picosulfate/magnesium oxide plus anhydrous citric acid, sodium phosphate tablets, and the over-the-counter preparations magnesium citrate and PEG-3350. These preparations may be administered as a single dose on the same day or evening before, or as two doses administered the same day or evening before/morning of colonoscopy. Ingesting at least half the bowel preparation on the day of colonoscopy (split-dosing) is associated with higher adequate bowel preparation quality versus evening-before dosing (odds ratio [OR], 2.5; 95 % confidence interval [CI], 1.9−3.4). Conclusions High-quality bowel preparation is integral for optimal CRC screening/surveillance by colonoscopy. Over the last 30 years, patients and providers have gained more options for bowel preparation, including low-volume agents with enhanced tolerability and cleansing quality that are equivalent to 4 L preparations. Split-dosing is preferred for achieving a high-quality preparation.

BCG shortage: Reassessing the clinical viability of Bacillus Calmette-Guerin (BCG) after reconstitution.

534 Background: To address the current worldwide shortage of BCG, the AUA and SUO recommend reducing the dose to 1/3rd vial and enabling 3 patients to be treated in one setting. The manufacturer states that BCG must be used immediately after reconstitution, despite literature in the bacteriological world suggesting that M. Bovis might be viable for longer than a few hours. Herein we sought to study the viability of BCG after re-constitution at time points relevant to clinical practice. Methods: TICE BCG from separate lots was reconstituted per the manufacturer’s guidance and stored at 4 °C without light exposure. At predetermined time points, BCG was inoculated on Selective Middlebrook 7H11 agar in triplicate and incubated at 37°C with 5% CO2. M. smegmatis served as a positive control and un-inoculated media was incubated for 2 weeks as a negative control. CFUs were assessed between 3 and 4 weeks from plating. Acid-fast staining confirmed the presence of BCG. Data was analyzed as the mean of replicated experiments and compared to the reference (Time 0) using Student’s T-tests. Results: No significant difference in CFUs was observed for BCG between 0 and 8 hours after reconstitution (Table). Colony forming units significantly declined starting 24 hours after reconstitution, though the magnitude of this difference was less than 10 fold (which falls within the range of CFUs listed for the vial by manufacturer). Viability remained constant for both lots analyzed. Conclusions: Given the recurrent shortages of BCG, split dosing may become a clinical necessity. This often presents logistic quandaries since the manufacturer recommends each vial must be used within 2 hours. We have shown that the viability of TICE BCG is unaltered at least 8 hours after reconstitution and only begins to decline at 24 hours after reconstitution. This should allow pharmacists and physicians administering BCG more leeway in scheduling patients for split dose therapy. [Table: see text]