Split-dose Regimen Research Articles

Effectiveness and safety of polyethylene-glycol-4000 versus sodium picosulphate plus magnesium oxide and citric acid for bowel cleansing before colonoscopy in children: A systematic review with meta-analysis.

Colonoscopy is performed for diagnostic and therapeutic purposes. The quality of colonoscopy depends on adequate bowel cleansing. However, there is no standardized protocol for bowel preparation in children. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) to estimate the effectiveness, safety, and tolerability profile of polyethylene glycol (PEG) compared with those of sodium picosulfate (SPMC) in children. The primary sources of the reviewed studies were Scopus, PubMed, and Cochrane Library. The databases were systematically searched for RCTs comparing PEG 4000 to SPMC as a bowel cleansing solution. Six studies were included. The analysis showed that both PEG and SPMC are effective for bowel cleansing, while a split-dose regimen may be preferable to a day-before one. There were no differences between the two groups regarding adverse events such as abdominal pain, nausea, vomiting, bloating, and anal discomfort. Additionally, preparation with SPMC was preferred in terms of acceptability and compliance. Still, the need to place a nasogastric tube was significantly lower in the SPMC group compared to the PEG group and in the split dose regimen compared to the day before. In conclusion, PEG and SPMC are equally effective in obtaining an adequate bowel cleansing with a comparable adverse event rate; moreover, split-dose administration may be preferable to day-before one in terms of effective bowel cleansing. However, SPMC preparation is more acceptable seems to result in higher compliance, and to reduce the use of a nasogastric tube, that we encounter daily in clinical practice, is perceived as a stressful experience for children and their families.

The effect of a split-dose intravenous dexamethasone and a single high-dose on postoperative blood glucose after total joint arthroplasty: a randomized double-blind placebo-controlled trial

BackgroundIn patients undergoing total joint arthroplasty (TJA), the administration of dexamethasone may contribute to perioperative blood glucose (BG) disturbances, potentially resulting in complications, even in patients without diabetes. This study aimed to demonstrate the impact of different administration regimens of dexamethasone in postoperative BG levels.MethodsIn this randomized, controlled, double-blind trial, 136 patients without diabetes scheduled for TJA were randomly assigned to three groups: two perioperative saline injections (Group A, placebo); a single preoperative injection of 20 mg dexamethasone and a postoperative saline injection (Group B), and two perioperative injections of 10 mg dexamethasone (Group C). Primary outcomes were the postoperative fasting blood glucose (FBG) levels. Secondary outcome parameters were the postoperative postprandial blood glucose (PBG) levels. Postoperative complications within 90 days were also recorded. Risk factors for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl were investigated.ResultsCompared to Group A, there were transient increases in FBG and PBG on postoperative days (PODs) 0 and 1 in Groups B and C. Statistical differences in FBG and PBG among the three groups were nearly absent from POD 1 onward. Both dexamethasone regimens did not increase the risk for postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl. Elevated preoperative HbA1c levels may increase the risk of postoperative FBG ≥ 140 mg/dl or PBG ≥ 180 mg/dl, respectively.ConclusionPerioperative intravenous high-dose dexamethasone to patients without diabetes has transient effects on increasing BG levels after TJA. However, no differences were found between the split-dose and single high-dose regimens. The elevated preoperative HbA1c, but not the dexamethasone regimens were the risk factor for FBG ≥ 140 mg/dl and PBG ≥ 180 mg/dl.Trial registrationChinese Clinical Trail Registry, ChiCTR2300069473. Registered 17 March 2023, https://www.chictr.org.cn/showproj.html?proj=186760.

Online Educational Module Improves Knowledge of Nurses on Bowel Preparation for Colonoscopy.

The effectiveness of colonoscopy is limited by the adequacy of bowel preparation. Nurses are essential in providing bowel cleansing agents and instructions for hospitalized patients before colonoscopy. This study aims to assess and improve the knowledge of nurses on bowel preparation for inpatient colonoscopy. Participants were asked to complete the survey before and after completing an educational module. The module and survey questions were placed in the NetLearning environment of the hospital intranet. A minimum post-test score of 80% was required to pass the course. A total of 1,107 nurses participated in the survey. Overall, the average score improved from 87% to 93% after the module (p < .0495). Knowledge of the different ways of consuming bowel cleansing agents improved from 54.3% to 83.6% (p = .0001). Only 56.2% of nurses knew how to carry out a split-dose bowel preparation regimen, which increased to 80.1% after the educational module (p = .0001). Nurses' knowledge about the different ways of consuming bowel cleansing agents before colonoscopy and the split-dose regimen is inadequate. A simple online educational module significantly improved the knowledge of nurses on bowel preparation for colonoscopy.

Adenoma detection rate and tolerability of 2 ultra-low-volume bowel preparations in screening: a noninferiority randomized controlled trial

The adenoma detection rate (ADR), recognized as a surrogate marker for colorectal cancer incidence and mortality reduction, is closely linked to the efficacy of bowel cleansing. However, there is a dearth of evidence examining the impact on ADR when employing two distinct very low-dose bowel cleansing products. This study sought to compare ADR in a fecal immunochemical occult blood testing (iFOBT) based organized screening program by utilizing 1L polyethylene glycol plus ascorbate (1L-PEGA) versus magnesium citrate plus picosulphate (SPMC), both administered in a split-dose regimen. We conducted a comparative, parallel, randomized, noninferiority, and low-intervention clinical trial, the study targeted individuals from a population colorectal cancer screening program aged 50-69 with a positive iFOBT result scheduled for a work-up colonoscopy in the morning. Participants were randomized to either 1L-PEGA or SPMC for bowel cleansing. Main outcome was ADR. Secondary outcomes were bowel preparation quality, individuals' safety, tolerability and satisfaction. A total of 1,002 subjects were included, 501 in each group. There were no differences between groups with respect to pooled ADR (SPMC, 56.5% [52.1-60.8]; 1L-PEGA, 53.7% [49.3-58.0]; RR 0.95 [0.85-1.06]); therefore, SPMC demonstrated noninferiority in ADR compared to 1L-PEGA (difference, 2.8%; 2-sided 95% lower confidence limit (LCL), -3.4). In addition, there were no significant differences in mean lesions regardless of size and location between arms. Bowel preparation favored 1L-PEGA (96.2% vs. 89.2%; p<0.001) whereas SPMC exhibited significantly higher safety and tolerability, as evidenced by fewer non-serious treatment-emergent adverse events CONCLUSIONS: SPMC emerged as a noninferior laxative compared to 1L-PEGA concerning ADR. Despite the superior bowel preparation quality associated with 1L-PEGA, the safety, tolerability and overall satisfaction of participants were higher with SPMC. This trial was registered at ClinicalTrials.gov (EudraCT: 2019-003186-18) on March 18, 2019.

Split Dose of Prednisolone in the Treatment for Erythema Nodosum Leprosum: A Case Series.

Background Erythema nodosum leprosum (ENL) is an immune complex-mediated reaction that clinically presents as tender erythematous evanescent nodules, mostly associated with systemic symptoms. Oral prednisolone is the drug of choice, with doses ranging from 0.5 to 1 mg/kg. Some cases may develop new lesions and systemic symptoms despite 1 mg/kg prednisolone, and in ideal practice, physicians escalate the prednisolone dose for immediate arrest of inflammation to prevent complications. However, a high dose of prednisolone has more side effects in the long term and causes more immunosuppression. Methods In cases of ENL, those not responding to a conventional once-daily regimen were given a split dose of oral prednisolone instead of increasing the dose. They were followed up for response, and serum cortisol was measured to see for hypothalamic-pituitary-adrenal (HPA) axis suppression. Results Eight cases of ENL (three nodular, three necrotic, one pustular, and one nodulcerative) had a dramatic response to split-dose therapy without any relapse and HPA axis suppression. Conclusion A split-dosing regimen can be a good treatment option in ENL with better control, less steroid dependency, and a lower relapse rate.

Evaluation of parameters influencing the quality of colon preparation with a split-dose regimen of sulfate salts.

Bowel cleansing is an important factor for the quality of colonoscopy. We aimed to evaluate the efficacy of split-dose oral sulfate salts on bowel preparation and to determine parameters influencing the quality of bowel cleaning. Consecutive adults who completed their preparation for colonoscopy with a regimen of sulfate salts were enrolled. Of the 446 patients, 11 were excluded from the analysis. Among the 435 patients, 257 (59.1%) were female, mean age was 62.0±11.6 years and median body mass index (BMI) 26.1 kg/m2 (interquartile range [IQR] 23.8-29.4). Indications for colonoscopy were screening 155 (35.6%), surveillance 102 (23.5%), or other 178 (40.9%). The median time between the end of second dose of the preparation regimen and colonoscopy initiation was 5:15 h (IQR 4:30-6:00, min: 2:20, max: 12:20). Minor adverse events were reported in 62 (14.3%) patients. BBPS=9 was observed in 279 (64.14%) patients. Segmental BBPS=3 was achieved in 387 (88.97%), 346 (79.54%) and 289 (66.44%) patients (P<0.001) in the descending, transverse and ascending colon, respectively. Multivariate analysis revealed that BMI (odds ratio [OR] 1.05, 95% confidence interval [CI] 1-1.1) and time between the end of the second laxative dose and colonoscopy initiation (OR 1.25, 95%CI 1.08-1.45) were associated with poorer bowel preparation. A split dose of oral sulfate salts is an efficacious and well tolerated regimen. Obesity and a longer time interval between the end of the second dose and colonoscopy initiation negatively influence bowel cleanliness.

Effectiveness and safety of a 1L polyethylene glycol and ascorbic acid preparation for colonoscopy in routine clinical practice in Spain.

Large clinical trials and small real-world studies show that a 1L polyethylene glycol and ascorbic acid solution (1L PEG-ASC) is an effective and safe bowel preparation for colonoscopy. Here, the effectiveness and safety of 1L PEG-ASC was evaluated in a large cohort of patients in routine clinical practice in Spain. A sub-analysis was performed in an observational, multicenter, retrospective study assessing the effectiveness and safety of 1L PEG-ASC in adult patients undergoing a colonoscopy at 10 centers in Spain. Cleansing quality was assessed with the Boston Bowel Preparation Scale, scores ≥6 with all segmental scores ≥2 was considered adequate colon cleansing, high-quality was considered as cleansing ≥8 or =3 in the right colon. Polyp and adenoma detection rates, and adverse events were also assessed. Data was collected from 7160 patients: 48.3% males; mean age 58.0, 33.6% ≥65 years old. Adequate overall bowel cleansing was achieved in 95.6% of patients (95% CI 95.1%-96.0%), high quality cleansing in 74.4% (95% CI 73.4%-75.4%) and high-quality right colon cleansing in 66.0% (95% CI 64.9-67.1). The adequate overall cleansing rate was 97.0% with a split-dose and 94.0% with same-day regimen (P<0.0001), and high-quality right colon cleansing was 69.0% and 62.5% (P<0.0001), respectively. Colonoscopy was completed in 97.2% of cases. A multivariate regression analysis revealed that an overnight split-dose regimen and age <65 years were independent predictors of adequate bowel cleansing of the overall colon, age <65 years and female gender were independent predictors of HQ cleansing of the overall colon, and the three covariates were independent predictors of HQ cleansing of the right colon. At least one adverse event was experienced by 3.3% of participants, with nausea (1.5%) and vomiting (1.2%) being the most frequent. This sub-analysis confirmed 1L PEG-ASC to be an effective and safe bowel cleansing preparation in a real world setting in Spain.

Belantamab Mafodotin in Combination with Lenalidomide Plus Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma: Safety and Efficacy Analysis of DREAMM-6 Trial Arm-a

Introduction: Belantamab mafodotin (belamaf) is a first-in-class, antibody-drug conjugate that targets B-cell maturation antigen. In the recent ALGONQUIN study, clinical activity associated with belamaf in combination with the immunomodulatory drug pomalidomide were increased in triple-class exposed/refractory multiple myeloma (MM) patients, highlighting the potential for belamaf-based combinations in this population (Trudel, et al. Blood. 2022;140 (Suppl 1):7306-07). Preclinical data indicate that belamaf combined with other immunomodulatory agents, such as lenalidomide (Len) may also provide additional benefit. Arm A of the Phase I/II DREAMM-6 (NCT03544281) study aimed to assess the safety and clinical activity of belamaf doses/schedules in combination with the standard of care (SOC) of Len plus dexamethasone (Dex) in patients with relapsed/refractory MM (RRMM). Methods: Patients were eligible to participate if they had received ≥1 prior line of therapy (LOT). In Part 1 (dose escalation), up to two dose levels of belamaf (1.9 mg/kg [dose level -1 Q4W]; 2.5 mg/kg Q4W [dose level 1]) and alternative dosing schedules were administered in combination with the fixed SOC dose. In Part 2 (dose expansion), patients received belamaf at the following doses/schedules: 1.9 mg/kg Q8W, 1.9 mg/kg Q4W, 2.5 mg/kg Q4W, or 2.5 mg/kg Q4W split dose (50% on Days 1 and 8 of a given cycle). For this study, Len 25 mg was administered orally (10 mg if estimated glomerular filtration rate &amp;lt;60 mL/min/1.73m 2) on days 1-21 and Dex 40 mg was administered (20 mg for patients &amp;gt;75 years old, patients with BMI &amp;lt;18.5, or patients with prior tolerability issues to Dex) on Days 1, 8, 15, and 22 of every 28-day cycle. The primary outcome of Part 1 was the number/percent of subjects with adverse events (AE) or dose-limiting toxicity (as reported previously). The primary outcome of Part 2 wassafety profile (AEs and serious AEs) and efficacy (overall response rate [ORR]). Pharmacokinetics (PK) and anti-drug antibodies were secondary outcomes. Duration of response (DOR), progression-free survival (PFS) and overall survival (OS) were exploratory endpoints. Results: Overall, 45 patients were enrolled across Parts 1 and 2. At the final analysis cutoff date (Feb 28, 2023), the median (range) age was 68 (36-80) years; patients had received a median (range) of 3 (1-10) prior LOTs, and 26/45 (57.8%) patients were Len-exposed (Table). The median (range) follow-up was 23.7 (0.5- 51.3) months. Incidence of AEs resulting in permanent discontinuation and dose reduction/delays of any study treatment were similar across groups; however, interpretation is limited due to the small sample size. The most common drug-related Grade 3+ AEs were keratopathy, visual acuity decline, and neutropenia. Safety and efficacy data are presented in the Table below. The ORR ranged from 58% to 75% across groups. The greatest depth of response (≥very good partial response [VGPR] 56%, ≥complete response 44%) was observed in the 2.5 mg/kg Q4W cohort. Interpretation of DOR, PFS, and OS was limited due to the small sample size in each cohort (Table). PK characteristics of belamaf were consistent with those previously reported for belamaf monotherapy considering baseline patient characteristics. Higher Cycle 1 peak and average concentrations (C ave) were observed with higher doses, with large overlap among cohorts; lower peak concentrations were seen with the split dosing regimen. Len PK were consistent with historical data. PK data indicated no drug-drug interaction between belamaf and Len. A positive trend was observed between belamaf Cycle 1 C ave and the probability of achieving PR or better. Conclusion: Belamaf in combination with SOC (Len/Dex) demonstrated deep and durable responses with a manageable safety profile in patients with RRMM. As anticipated, there was no drug-drug interaction between belamaf and Len. These findings support the use of belamaf in combination with SOC for patients with RRMM.

PK-PD integration of enrofloxacin and cefquinome alone and in combination against Klebsiella pneumoniae using an in vitro dynamic model.

Introduction: Klebsiella pneumoniae is classified as a critical pathogen in both animals and humans and infections can be fatal in chickens resulting in substantial economic losses. However, the misuse of antibiotics can also lead to drug resistance and a potential transmission chain between animals and humans. Three K. pneumoniae strains with different susceptibility phenotypes were chosen to study the pharmacokinetic/pharmacodynamic (PK/PD) integration of enrofloxacin (ENR) and cefquinome (CEQ) alone and in combination. Results: Checkerboard assay results indicated that the combination treatment for type strain ATCC 700603 was synergistic effect with a fractional inhibitory concentration index (FICI) of ≤0.5. The other two clinical strains demonstrated an additive effect (FICI >0.5 to ≤1). Furthermore, static time-kill curves indicated that enrofloxacin and cefquinome added singly were effective in killing K. pneumoniae at concentrations of >2 MIC and ≥1 MIC, respectively. Additionally, the combination of enrofloxacin and cefquinome led to an enhanced antibacterial activity of cefquinome. The dynamic time-kill curves indicated that enrofloxacin and cefquinome had bactericidal and bacteriostatic activities, respectively at ≥1.5mg/L (single-dose) and 4mg/L (8h split-dose) causing a decrease in bacterial counts of ≥4.45 and >2log10CFU/mL. Enrofloxacin possessed no bacteriostatic effects against K. pneumoniae at a constant concentration of 1× MIC. Cefquinome used in combination with 1× MIC enrofloxacin exhibited bactericidal activity at ≥4mg/L (12h split-dose) with reductions of ≥3.65log10CFU/mL. The PK/PD parameters were also analyzed to determine the concentration and duration of the drugs needed to reduce bacteria by 3log10CFU/mL. For enrofloxacin alone, the AUC24h/MIC was 23.29h and the Cmax/MIC was 3.18. For cefquinome alone, the %T > MIC was 48.66 and when used in combination with enrofloxacin was 18.04. The combined use of cefquinome and enrofloxacin can increase the antibacterial activity of cefquinome against K. pneumoniae under a 12-h split-dose regimen regardless of individual drug susceptibility. Discussion: The static and dynamic time-kill curves indicated that enrofloxacin exhibited concentration-dependent activity, while cefquinome exhibited time-dependent activity. In the in vitro dynamic model, enrofloxacin alone exhibited better antimicrobial effects against K. pneumoniae compared to cefquinome alone. However, the antibacterial effect of cefquinome can be enhanced by combining it with enrofloxacin. These findings suggest a potentially effective approach for combating K. pneumoniae infections.

Optimal timing of simethicone administration prior to upper endoscopy: A multicenter, single-blind, randomized controlled trial.

Background and study aims Simethicone is useful as premedication for upper endoscopy because of its antifoaming effects. We aimed to evaluate the effect of timing of simethicone administration on mucosal visibility. Patients and methods In this multicenter, randomized, endoscopist-blinded study, patients scheduled for upper endoscopy were randomized to receive 40 mg simethicone at the following time points prior to the procedure: 20 to 30 minutes (early group), 0 to 10 minutes (late group) or 20 mg simethicone at both time points (split-dose group). Images were taken from nine predefined locations in the esophagus, stomach, and duodenum before endoscopic flushing. Each image was scored on mucosal visibility by three independent endoscopists on a 4-point scale (lower scores indicating better visibility), with adequate mucosal visibility defined as a score ≤ 2. Primary outcome was the percentage of patients with adequate total mucosal visibility (TMV), reached if all median subscores for each location were ≤ 2. Results A total of 386 patients were included (early group: 132; late group: 128; split-dose group: 126). Percentages of adequate TMV were 55%, 42%, and 61% in the early, late, and split-dose group, respectively ( P < 0.01). Adequate TMV was significantly higher in the split-dose group compared to the late group ( P < 0.01), but not compared to the early group ( P = 0.29). Differences between groups were largest in the stomach, where percentages of adequate mucosal visibility were higher in the early (68% vs 53%, P = 0.03) and split-dose group (69% vs 53%, P = 0.02) compared to the late group. Conclusions Mucosal visibility can be optimized with early simethicone administration, either as a single administration or in a split-dose regimen.

Bowel cleansing effectiveness and safety of 1L PEG + Asc in the real-world setting: Observational, retrospective, multicenter study of over 13000 patients.

Background and study aims Effective bowel cleansing is critical for detecting lesions during colonoscopy, highlighting the importance of bowel preparations. 1L polyethylene glycol (PEG) + ascorbate (Asc) is the only recommended 1L PEG product in Europe and the United States. Its efficacy was demonstrated in large-scale controlled trials and confirmed in smaller-scale real-world studies. However, no large-scale real-world data exist. Patients and methods This observational, retrospective, multicenter study, used outpatient follow-up data from medical records from 10 centers in Spain and two in Portugal. Outpatients aged ≥18 years using 1L PEG + Asc as bowel preparation were included. The main outcome measures were overall adequate colon cleansing (Boston Bowel Preparation Scale [BBPS] score ≥6 with BBPS score ≥2 in each segment) and high-quality cleansing of the right colon (BBPS score=3). Results Data from 13169 eligible patients were included. Overall cleansing success was achieved in 89.3% (95%CI 88.7%-89.8%) and high-quality cleansing in the right colon in 49.3% (95%CI 48.4%-50.2%) of patients. For the overnight split-dose and same-day regimens, overall adequate quality cleansing success rate was 94.7% and 86.7% ( P <0.0001) and high-quality cleansing of the right colon rate was 65.4% and 41.4% ( P <0.0001), respectively. Colonoscopy was completed in 97.3% of patients, with non-completion due to poor preparation in only 0.8%; 2.3% of patients experienced at least one adverse event (AE). Conclusions This large-scale, real-world study demonstrates the effectiveness of 1L PEG + Asc in the total and right colon, with a low percentage of patients with AEs in routine clinical practice.

Effectiveness and safety of 1-L PEG-ASC versus other bowel preparations for colonoscopy: A meta-analysis of nine randomized clinical trials.

A 1-L polyethylene glycol plus ascorbate (PEG-ASC) preparation has been recently developed to improve patients' experience in colonoscopy. This meta-analysis aimed to evaluate the effectiveness and safety of 1-L PEG-ASC compared with those of other bowel preparations for colonoscopy. MEDLINE, Embase, Scopus, and the Cochrane Library were systematically searched for randomized controlled trials comparing 1-L PEG-ASC with other bowel preparations published through July 2022. A random-effects model was applied for pooling the results; heterogeneity was expressed as I2. Nine studies met the inclusion criteria and were included. The analysis showed significantly higher cleansing success (CS) (OR=1.50; 95% CI=1.25-1.81; p<0.01, I2=0%) and right-colon high-quality cleansing (HQC) (OR=1.67; 95% CI=1.21-2.31; p<0.01, I2=43%) with 1-L PEG-ASC compared to the other preparations. The pooled estimate of the adenoma detection rate (ADR) did not significantly differ between the two groups either in the overall (OR=1.02; 95% CI=0.87-1.20; p=0.79, I2=0%) or split-dosing regimen subgroup analysis (OR=0.99; 95% CI=0.84-1.18; p=0.94, I2=0%). A significantly higher pooled estimate of the number of patients with adverse events (AEs) (OR=1.51; 95% CI=1.23-1.84; p<0.01, I2=0%) and incidence of AEs (IRR=1.33; 95% CI=1.11-1.58; p<0.01, I2=71%) was observed with 1-L PEG-ASC than with the other preparations. No serious AEs or deaths occurred. Compared to other preparations, 1-L PEG-ASC yielded higher overall CS, higher right-colon HQC rates, and similar ADR. The number of patients with AEs and incidence of the total AEs were significantly higher with 1-L PEG-ASC in the absence of serious AEs.

Comparison of the efficacy and safety of an oral sulfate solution and 3-L polyethylene glycol on bowel preparation before colonoscopy: a phase III multicenter randomized controlled trial

Adequate bowel preparation is crucial for clear mucosal visualization during colonoscopy. We aimed to comprehensively compare oral sulfate solution (OSS) and 3-L split-dose polyethylene glycol (PEG) for bowel preparation before colonoscopy. This randomized, active-controlled, noninferiority study was performed in 10 medical centers. Eligible subjects were enrolled to receive OSS or 3-L PEG in a split-dose regimen. The quality of bowel preparation, adverse reactions, and acceptability were evaluated. The quality of bowel preparation was evaluated using the Boston Bowel Preparation Scale. Safety was evaluated by adverse reactions. The study population was divided into the full analysis set (FAS), the safety set, the modified FAS (mFAS), and the per-protocol set (PPS). Three hundred forty-eight potentially eligible subjects were enrolled. Three hundred forty-four subjects were included in the FAS and safety set, 340 subjects were included in the mFAS, and 328 subjects were included in the PPS. Adequate bowel preparation of the OSS was not inferior to 3-L PEG in the mFAS (98.22% vs 97.66%) and the PPS (98.17% vs 98.78%). There was no significant difference in acceptability between the 2 groups (94.74% vs 94.80%, P= .9798). Overall adverse reactions were similar (50.88% vs 44.51%, P= .2370) between the 2 groups. The split-dose OSS regimen was not inferior to the split-dose 3-L PEG regimen for the quality of bowel preparation in a Chinese adult population. The safety and acceptability of the 2 groups were similar. (Clinical trial registration number: NCT05465889.).

Factors affecting the quality of bowel preparation for colonoscopy in hard-to-prepare patients: Evidence from the literature

Adequate bowel cleansing is critical for a high-quality colonoscopy because it affects diagnostic accuracy and adenoma detection. Nevertheless, almost a quarter of procedures are still carried out with suboptimal preparation, resulting in longer procedure times, higher risk of complications, and higher likelihood of missing lesions. Current guidelines recommend high-volume or low-volume polyethylene glycol (PEG)/non-PEG-based split-dose regimens. In patients who have had insufficient bowel cleansing, the colonoscopy should be repeated the same day or the next day with additional bowel cleansing as a salvage option. A strategy that includes a prolonged low-fiber diet, a split preparation regimen, and a colonoscopy within 5 h of the end of preparation may increase cleansing success rates in the elderly. Furthermore, even though no specific product is specifically recommended in the other cases for difficult-to-prepare patients, clinical evidence suggests that 1-L PEG plus ascorbic acid preparation are associated with higher cleansing success in hospitalized and inflammatory bowel disease patients. Patients with severe renal insufficiency (creatinine clearance < 30 mL/min) should be prepared with isotonic high volume PEG solutions. Few data on cirrhotic patients are currently available, and no trials have been conducted in this population. An accurate characterization of procedural and patient variables may lead to a more personalized approach to bowel preparation, especially in patients undergoing resection of left colon lesions, where intestinal preparation has a poor outcome. The purpose of this review was to summarize the evidence on the risk factors influencing the quality of bowel cleansing in difficult-to-prepare patients, as well as strategies to improve colonoscopy preparation in these patients.

Efficacy of morning-only dose compared with split-dose polyethylene glycol electrolyte solution in bowel cleansing for afternoon colonoscopy

Introduction: The efficacy of colonoscopy in detecting abnormalities within the colon is highly dependent on the adequacy of the bowel preparation. The objective of this study was to compare the efficacy and tolerability of morning only dose vs split-dose administration of polyethylene glycol (PEG) solution for colon cleansing in patients undergoing afternoon colonoscopy.&#x0D; Method: This was a comparative study conducted in Department of Medicine, Patan Academy of Health Sciences (PAHS), Patan Hospital, Nepal from November 2021 to June 2022. The ethical clearance was obtained from the Institutional Review Committee. Informed consent was taken from the patients. Patients aged &gt;18 y undergoing elective colonoscopy were randomly assigned to one of the two bowel preparation regimens- morning only or split-dose of PEG. The adequacy of bowel preparation was assessed by the endoscopist using Boston Bowel Preparation scale. Preparation to colonoscopy (PC) interval, adverse events and risk factors for poor bowel preparations were noted.&#x0D; Result: In this study, 110 patients were included in the final analysis- 55 received morning only regimen and 55 received split-dose. Mean Boston bowel preparation scales of Morning only and Split-dose regimen were 7.60 and 7.09 respectively (p= 0.019). Split-dose group had significant sleep disturbances compared to Morning only regimen (p&lt; 0.001), whereas nausea occurred significantly more often in Morning only regimen (p=0.012). Preparation to colonoscopy interval between 4-6 hours resulted in better bowel cleansing compared to PC interval of greater than 6 hours.&#x0D; Conclusion: Morning-only bowel preparation is more effective than Split-dose for achieving adequate colon cleansing for afternoon colonoscopy.

Efficacy Studies against PCV-2 of a New Trivalent Vaccine including PCV-2a and PCV-2b Genotypes and Mycoplasma hyopneumoniae When Administered at 3 Weeks of Age.

This study aimed to evaluate the efficacy of a new trivalent vaccine containing inactivated Porcine Circovirus 1-2a and 1-2b chimeras and a Mycoplasma hyopneumoniae bacterin administered to pigs around 3 weeks of age. This trivalent vaccine has already been proved as efficacious in a split-dose regimen but has not been tested in a single-dose scenario. For this purpose, a total of four studies including two pre-clinical and two clinical studies were performed. Globally, a significant reduction in PCV-2 viraemia and faecal excretion was detected in vaccinated pigs compared to non-vaccinated animals, as well as lower histopathological lymphoid lesion plus PCV-2 immunohistochemistry scorings, and incidence of PCV-2-subclinical infection. Moreover, in field trial B, a significant increase in body weight and in average daily weight gain were detected in vaccinated animals compared to the non-vaccinated ones. Circulation of PCV-2b in field trial A and PCV-2a plus PCV-2d in field trial B was confirmed by virus sequencing. Hence, the efficacy of this new trivalent vaccine against a natural PCV-2a, PCV-2b or PCV-2d challenge was demonstrated in terms of reduction of histopathological lymphoid lesions and PCV-2 detection in tissues, serum and faeces, as well as improvement of production parameters.

Safety and Efficacy of Split-Dose Thiopurine vs Low-Dose Thiopurine-Allopurinol Cotherapy in Pediatric Inflammatory Bowel Disease.

Split-dose thiopurine and allopurinol-thiopurine cotherapy strategies have been suggested as rescue therapeutic options for children with inflammatory bowel disease (IBD) and impaired thiopurine metabolism. We compared the efficacy and safety of these regimens in patients who previously failed conventional thiopurine treatment. Children with IBD treated with split-dose thiopurine or low-dose thiopurine-allopurinol cotherapy were retrospectively identified. Medical records were reviewed for demographics, treatment regimen, reason for thiopurine failure, side effects, and discontinuation of treatment. Laboratory findings were evaluated at different time points. After prior therapeutic failure, 42 patients were on split-dose regimen (group A) and 20 patients were on thiopurine-allopurinol cotherapy (group B). Twelve patients crossed from group A to group B because of treatment failure, 1 patient was lost at follow-up, and 1 patient discontinued the treatment. The final cotherapy group comprised 29 children (group C), while the split-dose group (group D) included 31 children. Intention-to-treat analysis showed significant differences between split-dose regimen and thiopurine-allopurinol cotherapy for 6-thioguanine nucleotide (6-TGN)/6-methyl mercaptopurine (6-MeMP) ratio ( P < 0.001), 6-TGN ( P < 0.05), and 6-MeMP ( P < 0.001) at 1-3 months. As per protocol analysis, there was a significant difference between group C and group D at 6 months for 6-MeMP ( P < 0.05) and 6-TGN/6-MeMP ratio ( P < 0.05) and at 12 months for 6-MeMP ( P < 0.05) and 6-TGN/6-MeMP ratio ( P < 0.001). Side effects were more frequent in allopurinol-thiopurine cotherapy ( P < 0.05). In children with IBD and impaired thiopurine metabolism, split-dose thiopurine and low-dose thiopurine-allopurinol cotherapy are both effective therapeutic strategies. The latter shows higher efficacy but a higher side effect rate, suggesting the use of split-dose regimen as the first-line approach.

Risk factors for inadequate bowel preparation in patients using high- and low-volume cleansing products.

Bowel preparation is crucial for colonoscopy completeness and lesions detection. Today, several cleansing products are equally recommended by guidelines, irrespective of patients' characteristics. Identification of preparation-specific risk factors for inadequate bowel preparation may lead to a personalized prescription of cleansing products to refine patients' tolerance and improve endoscopic outcomes. We prospectively enrolled consecutive outpatients referred for colonoscopy using either a high-volume [HV: 4 l polyethylene glycol (PEG)] or a low-volume (LV: 2 l PEG + bisacodyl) preparation. Day-before regimen or split-dose regimen was used for morning or afternoon colonoscopies, respectively. Univariate and multivariate analyses were conducted to identify risk factors related to inadequate bowel preparation, according to the Boston bowel preparation scale for HV and LV preparations. We enrolled 2040 patients, of which 1815 were included in the final analysis (average age 60.6 years, 50.2% men). Half of them (52%) used LV preparation. Adequate preparation was achieved by 87.6% without differences between the HV and LV groups (89.2% vs. 86.6%; P = 0.098). The use of day-before regimen and incomplete assumption of PEG were independent predictors of poor visibility for either HV or LV preparation. However, different specific risk factors for HV [diabetes: odds ratio (OR), 3.81; 95% confidence interval (CI), 1.91-7.58; low level of instruction: OR, 1.95; 95% CI, 1.11-3.44; and previous abdominal surgery: OR, 2.27; 95% CI, 1.20-4.30] and for LV (heart disease: OR, 2.06; 95% CI, 1.09-3.88; age > 65 years: OR, 1.51; 95% CI, 1.01-2.27) preparations were identified. Day-before preparation and incomplete assumption of the purgative agents affect bowel visibility irrespective of the preparation volume. LV should be preferred to HV preparations in patients with diabetes, low level of instruction, and previous abdominal surgery, whereas an HV preparation should be preferred in patients with heart disease and in older patients.

Split-Dose Administration Enhances Immune Responses Elicited by a mRNA/Lipid Nanoparticle Vaccine Expressing Respiratory Syncytial Virus F Protein.

mRNA vaccines have recently received significant attention due to their role in combating the SARS-CoV-2 pandemic. As a platform, mRNA vaccines have been shown to elicit strong humoral and cellular immune responses with acceptable safety profiles for prophylactic use. Despite their potential, industrial challenges have limited realization of the vaccine platform on a global scale. Critical among these challenges are supply chain considerations, including mRNA production, cost of goods, and vaccine frozen-chain distribution. Here, we assess the delivery of lipid nanoparticle-encapsulated mRNA (mRNA/LNP) vaccines using a split-dose immunization regimen as an approach to develop mRNA dose-sparing vaccine regimens with potential to mitigate mRNA supply chain challenges. Our data demonstrate that immunization by a mRNA/LNP vaccine encoding respiratory syncytial virus pre-F (RSV pre-F) over a 9 day period elicits comparable or superior magnitude of antibodies when compared to traditional bolus immunization of the vaccine. The split-dose immunization regimens evaluated in our studies were designed to mimic reported drug or antigen release profiles from microneedle patches, highlighting the potential benefit of pairing mRNA vaccines with patch-based delivery technologies to enable sustained release and solid-state stabilization. Overall, our findings provide a proof of concept to support further investigations into the development of sustained delivery approaches for mRNA/LNP vaccines.

S631 Overnight Split Dosing With 1L Polyethylene Glycol + Ascorbic Acid Bowel Preparation Delivers High Levels of High-Quality Cleansing for Colonoscopy: A Sub-Analysis of a Large Real-World Study

Introduction: Clinical guidelines recommend evening/morning split dosing for routine colonoscopy procedures. Overnight split dosing with 1 liter polyethylene glycol + ascorbic acid (1L PEG+ASC) has demonstrated strong cleansing performance in clinical trials. Here we report a sub-analysis from the largest real-world study to date of 1L PEG+ASC, evaluating patients who received this split dosing regimen. Methods: An observational, multicenter, retrospective study evaluated the medical records of colonoscopy outpatients between July 2019 and September 2021 at 12 centers in Spain and Portugal. Eligible adults (aged ≥18 years) had a screening, surveillance, or diagnostic colonoscopy after an evening/morning (split dose) or same-day regimen of 1L PEG+ASC. Bowel cleansing was assessed by site endoscopists using the Boston Bowel Preparation Scale (BBPS). Segmental BBPS scores of 3 defined high-quality cleansing. High adherence was defined as consumption of ≥75% of each dose and safety was assessed based on registered adverse events (AEs). BBPS scores were compared between time to colonoscopy groups with the Wilcoxon rank-sum test. Results: A total of 13,169 patients from the 12 centers were enrolled in the study, of which 4,316 received a split-dosing regimen and were included in this analysis. In the split-dose group, 48.0% of patients were male, mean (SD) age was 58.1 ± 13.4 years, and 33.4% were ≥65 years old. An overall BBPS score of 9 was attained in 58.3% of patients (Figure A). High rates of BBPS 3 were observed in all segments (Figure B). There was no effect of time lapse to colonoscopy on segmental cleansing in the transversal and left colon (Figure C). Only 1.6% of colonoscopies were incomplete, 0.39% due to poor preparation. Overall, 3.9% (95% CI: 3.4%–4.6%) of patients experienced an AE. The main AEs were nausea (2.4%), vomiting (1.2%), and abdominal pain (0.4%). Adherence was high at 97.6% of those 1,834 patients who reported volume intake. Conclusion: Results from this analysis show that overnight split dosing with 1L PEG+ASC delivered an excellent overall and segmental bowel cleansing quality in real-world settings.Figure 1.: Bowel cleansing performance of split dose 1L PEG+ASC: (A) Rates of overall colon high-quality cleansing (BBPS score >6); (B) Rates of segmental high-quality cleansing (BBPS score 3); (C) Effect of time to colonoscopy on mean segmental BBPS scores.