Magnesium hydroxide versus macrogol/electrolytes in the prevention of opioid-induced constipation in incurable cancer patients: study protocol for an open-label, randomized controlled trial (the OMAMA study).

BACKGROUND: Opioid-induced constipation (OIC) is a common symptom in cancer patients treated with opioids with a prevalence of up to 59%. International guidelines recommend standard laxatives such as macrogol/electrolytes and magnesium hydroxide to prevent OIC, although evidence from randomized controlled trials is largely lacking. The aim of our study is to compare magnesium hydroxide with macrogol /electrolytes in the prevention of OIC in patients with incurable cancer and to compare side-effects, tolerability and cost-effectiveness. METHODS: Our study is an open-label, randomized, multicenter study to examine if magnesium hydroxide is non-inferior to macrogol/electrolytes in the prevention of OIC. In total, 330 patients with incurable cancer, starting with opioids for pain management, will be randomized to treatment with either macrogol/electrolytes or magnesium hydroxide. The primary outcome measure is the proportion of patients with a score of < 30 on the Bowel Function Index (BFI), measured on day 14. The Rome IV criteria for constipation, side effects of and satisfaction with laxatives, pain scores, quality of life (using the EQ-5D-5L), daily use of laxatives and escape medication, and cost-effectiveness will also be assessed. DISCUSSION: In this study we aim to examine if magnesium hydroxide is non-inferior to macrogol/electrolytes in the prevention of OIC. The outcome of our study will contribute to prevention of OIC and scientific evidence of guidelines on (opioid-induced) constipation. TRIAL REGISTRATION: This trial is registered at clinicaltrials.gov: NCT05216328 and in the Dutch trial register: NTR80508. EudraCT number 2022-000408-36.

Optimizing investigation of suspected allergy to polyethylene glycols.

BACKGROUND: Polyethylene glycols (PEGs) are polymers of varying molecular weight (MW) used widely as excipients in drugs and other products, including the mRNA vaccines against coronavirus disease 2019. Allergy to PEGs is rare. Skin testing and graded challenge carries a high risk of inducing systemic reactions. OBJECTIVE: We evaluated skin prick test (SPT) results and in vitro reactivity over time to different MW PEGs and assessed cross-sensitization patterns in PEG allergy. METHODS: Ten patients with previously diagnosed PEG allergy underwent SPT twice with PEGs 26 months apart. Lower MW (PEG 300, 3000, 6000) were tested, followed by PEG 20,000, in stepwise, increasing concentrations. Cross-sensitization to polysorbate 80 and poloxamer 407 was assessed. SPT was performed in 16 healthy controls. In vitro basophil histamine release (HR) test and passive sensitization HR test were performed in patients and controls. RESULTS: Patients previously testing positive on SPT to PEG 3000 and/or 6000 also tested positive to PEG 20,000. Patients with a longer interval since diagnosis tested negative to lower MW PEGs and positive mainly to higher concentrations of PEG 20,000. Three patients developed systemic urticaria during SPT. Eight patients showed cross-sensitization to poloxamer 407 and 3 to polysorbate 80. All controls tested negative. In vitro tests showed limited usefulness. CONCLUSIONS: Skin test reactivity to PEG can decrease over time, but titrated SPT with increasing concentrations of PEG 20,000 can be diagnostic when lower MW PEGs test negative. To avoid systemic reactions, stepwise SPT is mandatory.

Whole-bowel irrigation in cases of poisoning: A retrospective multicentre study of feasibility, tolerability, and effectiveness.

BACKGROUND: Whole-bowel irrigation (WBI) is a strategy of gastrointestinal decontamination, recommended by several European and American learned societies, which may be used in the management of the poisoned patients. OBJECTIVES: The objectives of this study were to describe the feasibility and tolerability of this technique and to compare the clinical outcome of a group of poisoned patients treated with WBI versus that of an untreated group. METHODS: This was a retrospective and observational study of data recorded by the Angers Poison Control Centre (PCC) between 2012 and 2018. All cases for which the PCC advised WBI were included. The association between outcomes (clinical deterioration after WBI advised by a PCC, length of hospitalisation), WBI treatment, and relevant associated risk factors was determined using univariate and multivariate logistic regression. RESULTS: A total of 257 patients were included. One hundred forty-one patients were treated with WBI with clearly successful induction of diarrhoea in 47 cases (31%). WBI was not initiated in 89 patients. WBI was initiated but unsuccessful (no diarrhoea) in nine cases. The median age is 46 years (interquartile range: 32-55 years), with a sex ratio (M/F) of 1.3. A total of 27 of 150 patients (18%) who underwent WBI had adverse effects possibly linked to WBI, mainly vomiting (n=23). The patients with clinical deterioration (n=49) were irrigated significantly less often (95% confidence interval: 0.13-0.52; p<0.001). After adjustment for sex, age, time to implementation of WBI, type of substance ingested, and admission to intensive care, patients who were treated with WBI were less likely to deteriorate clinically than patients who were not treated with WBI (p<0.001). CONCLUSION: Despite a low rate of completion of this procedure, WBI appeared to provide clinical benefits in patients treated in comparison of an untreated group and is associated with an acceptably low risk of direct complications.

Clinical manifestations and impact on daily life of allergy to polyethylene glycol (PEG) in ten patients.

BACKGROUND: Polyethylene glycols (PEGs) are widely used as excipients in drugs, cosmetics and household products. Immediate-type allergy to PEGs including anaphylaxis is rare. The recent introduction of the mRNA-based COVID-19 vaccines has led to an increased focus on PEG as a possible culprit of allergic reactions to the vaccines. A low awareness of the allergenic potential of PEG among consumers, manufacturers and doctors leads to under-diagnosis and under-reporting of allergy to PEGs, putting patients at risk of repeated severe reactions. OBJECTIVES: To investigate clinical manifestations, time to diagnosis and impact of a PEG allergy diagnosis on the daily life of patients diagnosed with allergy to PEG from 2010 to 2019. METHOD: Ten patients diagnosed with allergy to PEG were included. Detailed clinical history was obtained, and allergy investigations had been performed at the time of diagnosis. All patients were contacted and asked to retrospectively complete a questionnaire about causes and impact on daily life of an allergy to PEG, scored on a likert scale (0-10) before and after diagnosis. RESULTS: Eight patients had experienced at least one anaphylactic reaction requiring adrenaline treatment. Anaphylaxis was primarily caused by antibiotic/analgesic tablets, depot-steroids, antacids and laxatives. Seven patients reported repeated reactions before diagnosis (median 3, range 2-6). Median time from first reaction to diagnosis was 20 months (range 2-120). None of the patients experienced severe allergic reactions after the diagnosis. Median likert score of the impact on daily life before diagnosis was 7 compared with 4 after diagnosis. CONCLUSION AND CLINICAL RELEVANCE: The clinical manifestations of PEG allergy are often dramatic. Improved awareness about the clinical presentation and common culprits, clear product labelling and a standardized nomenclature is needed to ensure the timely diagnosis of PEG allergy to prevent repeated anaphylactic reactions with severe impact on patients' lives.

Efficacy of macrogol 4000 plus electrolytes in bowel preparation for colonoscopy in patients with chronic constipation.

BACKGROUND: Chronic constipation is a significant factor in poor bowel preparation for colonoscopy. Macrogol 4000 plus electrolytes (Movicol, EA Pharma, Tokyo, Japan), containing polyethylene glycol (PEG) and electrolytes, have been used recently to treat patients with constipation. However, prospective studies on the use of macrogol 4000 for bowel cleansing for colonoscopy are lacking. This study aimed to investigate the efficacy and safety of macrogol 4000 in addition to PEG administered in patients with chronic constipation. METHODS: This single-center, single-arm prospective study enrolled patients with chronic constipation who were scheduled to undergo colonoscopy. The primary endpoint was the proportion of good bowel preparation assessed using the Boston bowel preparation scale (BBPS) (6 or more points). The secondary endpoints were the time from when pPEG (MoviPrep, EA Pharma, Tokyo, Japan) was taken until colonoscopy could be started, amount of PEG taken, number of defecations, whether additional PEG doses were taken, and adverse events. Endoscopy-related endpoints included cecal intubation rate, insertion time, observation time, adenoma detection rate (ADR), and polyp detection rate (PDR). The tolerability of PEG and macrogol 4000 was assessed using a questionnaire. RESULTS: Forty patients were included in the analysis. The median BBPS was 7 (range 3-9) and ≥ 6 points in 37 cases (92.5%). The median time until colonoscopy can be started was 210 min (90-360 min), the median volume of PEG taken was 1500 mL (1000-2000 mL), and the median number of defecations was 7 (3-20). No adverse events were observed. Fourteen patients required an additional dose of PEG. Cecal intubation was achieved in all cases, the median insertion time was 6.0 min (range 2.3-22 min), and the median observation time was 8.8 min (range 4.0-16.0 min). The ADR and PDR were 60.0% and 75.0%, respectively. A proportion of patients rated the tolerability of macrogol 4000 and PEG as 95.0% and 50.0%, respectively. CONCLUSIONS: Intake of macrogol 4000 in addition to PEG is effective and safe for colonoscopy in patients with chronic constipation. Clinical trial registration statement This study was registered in the UMIN-CTR database (UMIN-ID000038315).

Antifungal Effectiveness of Various Intracanal Medicaments against Candida albicans: An In Vitro Study.

AIM AND OBJECTIVE: To evaluate the antifungal efficiency of various intracanal medicaments against Candida albicans. MATERIALS AND METHODS: One-hundred and forty extracted human mandibular premolar teeth were decoronated, and the biomechanical preparation was done in crown-down technique. 10 µL culture suspension of C. albicans was placed into the prepared root canal space of all the teeth. After 21 days of incubation, all the teeth were randomly divided into 7 groups with 20 teeth per each group. Group I: triple antibiotic powder (TAP) mixed with 3% chitosan solution; group II: TAP mixed with macrogol-propylene (MP) glycol; group III: chlorhexidine-guttapercha (CHX-GP); group IV: Vitapex; group V: 2% chlorhexidine gel; group VI: calcium hydroxide paste; group VII: normal saline with cotton (positive control) were used as intracanal medicaments, and the samples were incubated for 14 days. Intracanal medicaments were then completely removed using the canal brush. Dentinal chips were harvested from the walls of the root canal space in all samples using Gates-Glidden drills, were transferred into test tubes containing saline, and were serially diluted and placed in 140 Sabouraud dextrose agar plates, incubated at 37°C for 48 hours. Colony forming units (CFUs) of C. albicans were then counted using the digital colony counter. RESULTS: One-way ANOVA test showed statistically significant difference among the seven groups, as the p value was < 0.001. Tukey's post hoc test showed intergroup comparison between group I and group V; group II and group III were statistically nonsignificant as p value was >0.05. CONCLUSION: 2% chlorhexidine gel and TAP mixed with 3% chitosan solution showed superior antifungal efficiency against C. albicans. CLINICAL SIGNIFICANCE: Chitosan solution's inherent antifungal efficiency and slow and controlled drug release make it as an effective alternate carrier in mixing it with TAP instead of mixing TAP with MP.

A comparison of different surfactants on foam stability in foam sclerotherapy in vitro.

OBJECTIVE: This article compares the effect of different surfactants on foam stability and determines the foam decay relationship, so that the suitability of surfactants in a clinical setting can be evaluated. METHODS: Five different surfactants were used to prepare sclerosing foam at room temperature using a liquid:gas ratio of 1:4 in vitro. Foam decay experiments were performed for each sample using a laboratory-made foaming apparatus, and the process was recorded using a video camera. The stability indices used included the drainage time, drainage rate, half-life, foam half-life volume, surfactant stability index, and foaming index. RESULTS: The sodium morrhuate foam was relatively more stable than the polidocanol foam, but exhibited weak foaming. After the addition of the surfactants, the foam half-life was less than 300 seconds. The effect of the surfactants on the stability of the sodium morrhuate foam was more pronounced. The surfactant stability indices could be arranged as follows: poloxamer 188 > Tween 80 > macrogol 4000 > propanediol > lecithin. However, the differences in the foaming indices were small. CONCLUSIONS: Of the five surfactants tested, poloxamer 188 has best performance to enhance sclerosing foam stability. The addition of the surfactants improved the stability of the sclerosing foams. It was observed that the relationships between the foam half-life and the surfactant stability index and the surfactant concentration follow the power law.

Comparison of the effectiveness of polyethylene glycol with and without electrolytes in constipation: a systematic review and network meta-analysis.

BACKGROUND: Polyethylene glycol is commonly used to manage constipation and is available with or without electrolytes. The addition of electrolytes dates back to its initial development as lavage solutions in preparation for gastrointestinal interventions. The clinical utility of the addition of electrolytes to polyethylene glycol for the management of constipation is not established. The objective of this systematic review and network meta-analysis (NMA) was to assess the relative effectiveness of polyethylene glycol with (PEG + E) or without electrolytes (PEG) in the management of functional constipation in adults. METHODS: A systematic review was conducted to identify randomised controlled clinical trials that assessed the use of polyethylene glycol in functional constipation. The primary outcome was the mean number of bowel movements per week. RESULTS: Nineteen studies were included in the NMA (PEG N = 9, PEG + E N = 8, PEG versus PEG + E N = 2; involving 2247 patients). PEG and PEG + E are both effective, increasing the number of bowel movements per week by 1.8 (95 % Crl 1.0, 2.8) and 1.9 (95 % Crl 0.9, 3.0) respectively versus placebo and by 1.8 (95 % Crl 0.0, 3.5) and 1.9 (95 % Crl 0.2, 3.6) respectively versus lactulose. There was no efficacy difference between PEG + E and PEG (0.1, 95 % Crl -1.1, 1.2) and there were no differences in safety or tolerability. CONCLUSIONS: Polyethylene glycol with and without electrolytes are effective and safe treatments for constipation in adults. The addition of electrolytes to polyethylene glycol does not appear to offer any clinical benefits over polyethylene glycol alone in the management of constipation.

Preparation and evaluation of valsartan by a novel semi-solid self-microemulsifying delivery system using Gelucire 44/14.

The aim of the present study was to develop a novel semi-solid self-microemulsifying drug delivery system (SMEDDS) using Gelucire(®) 44/14 as oil with strong solid character to improve the oral bioavailability of poorly soluble drug valsartan. The solubility of valsartan in various excipients was determined, the pseudo-ternary phase diagram was constructed in order to screen the optimal excipients, and DSC analysis was performed to evaluate the melting point of SMEDDS. The optimal drug-loaded SMEDDS formulation was consisted of 30% Gelucire(®) 44/14 (oil), 40% Solutol(®) HS 15 (surfactant), and 30% Transcutol(®) P (cosurfactant) (w/w) with 80 mg valsartan/g excipients. The average droplet sizes of the optimized blank and drug-loaded SMEDDS formulations were 26.20 ± 1.43 and 33.34 ± 2.15 nm, and the melting points of them were 35.6 and 36.8 °C, respectively. The in vitro dissolution rate of optimal semi-solid SMEDDS was increased compared with commercial capsules, resulting in the 2.72-fold and 2.97-fold enhancement of Cmax and AUC0-t after oral administration in rats, respectively. These results indicated that the novel semi-solid SMEDDS formulation could potentially improve the oral bioavailability of valsartan, and the semi-solid SMEDDS was a desirable system than the traditional liquid SMEDDS because it was convenient for preparation, storage and transportation due to semi-solid state at room temperature and melted state at body temperature.

Polyethylene glycol compared to lactulose for constipation in pregnancy: A randomized controlled trial.

OBJECTIVE: To compare polyethylene glycol 4000 versus lactulose in chronic constipation during pregnancy. METHODS: Women at 28-32 weeks' gestation attending antenatal clinic for routine care were screened using the Rome IV chronic constipation criterion. Eligible women were approached and consented. Participants were randomized to oral polyethylene glycol (10 g/day) or lactulose (10 g/day) for 4 weeks. A bowel movement diary was kept and outcomes using the Patient Assessment of Constipation Symptoms questionnaire (PAC-SYM), Patient Assessment of Constipation Quality of Life questionnaire (PAC-QoL) and Bristol Stool Form Scale (BSFS), which were evaluated at the start and end of the four-week period. Relative risks (RR) were determined for the coprimary outcomes of complete spontaneous bowel movement (CSBM) and PAC-SYM mean score improvement (decrease in score of >1 from the baseline). RESULTS: A total of 4323 women underwent screening, of which 780 fulfilled the Rome IV criterion, and 360 consented to participate (180 randomized to PEG and lactulose, respectively). Data from 247 women who completed the study were analyzed. CSBM was achieved in 107/124 (86.3%) versus 102/123 (82.9%) (RR 1.04, 95% CI: 0.93-1.16, P = 0.464) for PEG and lactulose trial arms, respectively. PAC-SYM mean score improvement was 62/118 (52.5%) in the PEG arm versus 44/118 (37.3%) in the lactulose arm (RR 1.40, 95% CI: 1.05-1.88). Of secondary outcomes, a significant difference was found in favor of PEG, with respect to PAC-SYM abdominal symptoms subscale, normal stool versus loose stool consistency and side effects of vomiting and diarrhea. After controlling for parity, baseline PAC-SYM, PAC-QoL scores, characteristics different at baseline, only diarrhea and loose stools remained significant. CONCLUSION: Both PEG 4000 and lactulose are effective laxatives in pregnancy with similar performance after adjusted analysis. Diarrhea and loose stools are less frequently reported with PEG.

Development of a novel squalene/α-tocopherol-based self-emulsified nanoemulsion incorporating Leishmania peptides for induction of antigen-specific immune responses.

Vaccination has emerged as the most effective strategy to confront infectious diseases, among which is leishmaniasis, that threat public health. Despite laborious efforts there is still no vaccine for humans to confront leishmaniasis. Multi-epitope protein/peptide vaccines present a number of advantages, however their use along with appropriate adjuvants that may also act as antigen carriers is considered essential to overcome subunit vaccines' low immunogenicity. In the present study, a stable self-emulsified nanoemulsion was developed and double-adjuvanted with squalene and α-tocopherol. The prepared nanoemulsion droplets exhibited low cytotoxicity in a certain range of concentrations, while they were efficiently taken up by macrophages and dendritic cells in vitro as well as in vivo in secondary lymphoid organs. To further characterize nanoformulation's potent antigen delivery capability, three multi-epitope Leishmania peptides were incorporated into the nanoemulsion. Peptide encapsulation resulted in dendritic cells' functional differentiation characterized by elevated levels of maturation markers and intracellular cytokine production. Intramuscular administration of the nanoemulsion incorporating Leishmania peptides induced antigen-specific spleen cell proliferation as well as elicitation of CD4+ central memory cells, supporting the potential of the developed nanoformulation to successfully act also as an antigen delivery vehicle and thus encouraging further preclinical studies on its vaccine candidate potency.

Multicentre Study Into the Use of Polyethylene Glycol With Electrolytes Over at Least 6 Months to Treat Constipation in Paediatric Populations.

Background: Constipation is a common clinical problem in children, for which the first-line therapeutic options are osmotic laxatives, mainly polyethylene glycol (PEG). These treatments are often prescribed for short or limited periods, with progressive treatment withdrawal often resulting in relapses. However, there are a few studies into the long-term use (≥6 months) of PEG 3350 with electrolytes (PEG+E) in terms of the patients' clinical evolution. Objectives: To assess bowel movement and other relevant symptoms in children with constipation receiving PEG+E (≥6 months), as well as parent/caregiver satisfaction with this treatment. Methods: A retrospective, observational, descriptive, longitudinal, and multicentre study was carried out on 74 children diagnosed with functional constipation (ROME IV criteria) who had received PEG+E (≥6 months). Bowel control was assessed using the Bristol stool scale, and the parent's/caregiver's perception of the treatment was also evaluated employing a nonvalidated questionnaire. Results: Children with an average duration of constipation >1 year experienced a significant improvement in bowel movements and stool consistency when using PEG+E. The mean duration of use was 18.6 (±13.4) months, without the need to adjust the dose for weight. All clinical symptoms improved significantly except bloating, and all the parents/caregivers confirmed these clinical improvements. Conclusions: Children treated with PEG+E (≥6 months) normalised their bowel movements, improving the clinical symptoms related to constipation in the absence of serious advert events or the need for dosage adjustments due to weight gain. Parents/caregivers reported good satisfaction with PEG+E treatment.

Protocol for treatment of constipation with polyethylene glycol 3350 plus electrolytes in critically ill children.

INTRODUCTION AND OBJECTIVES: No studies have analysed the effectiveness of treatment for constipation in critically ill children. The aim of this study was to assess the implementation, efficacy and safety of a treatment protocol using polyethylene glycol 3350 with electrolytes (PEG 3350 + E) for constipation in critically ill children. METHODS: We conducted a single-centre prospective study in children admitted to the paediatric intensive care unit for a minimum of 72 h and who developed constipation. Children with previous gastrointestinal disorders or diseases were excluded. The patients were treated with rectal enemas or with the oral PEG 3350 + E protocol at the discretion of the treating physician. We compared clinical and demographic variables as well as adverse events (diarrhoea, abdominal distension and electrolyte imbalances). RESULTS: The sample included 56 patients with a mean age of 48.2 ±â€¯11.9 months, of who 55.4% were male. Forty-four patients (78.6%) were treated with PEG 3350 + E and 12 (21.4%) with rectal enemas. The proportion of patients that responded well to treatment was greater in the PEG 3350 + E group (79.5%) compared to the enema group (58.3%), but the difference was not statistically significant (P = .151). There were no significant differences between the groups in any of the adverse effects. Treatment with PEG 3350 + E was more effective in children aged less than 2 years (100%) compared to older children (100% vs 65.4%; P < .01), with no significant differences in the development of adverse events. CONCLUSIONS: The PEG 3350 + E treatment protocol for constipation in critically ill children was effective and associated with few adverse events, even in children aged less than 2 years.

Comparative Study of Ozonated Glycerol and Macrogol Ointment on Bone Matrix Production by Human Osteosarcoma Cell Line Saos-2.

Ozonated glycerol is glycerol containing ozone, has no unpleasant odor, and has a long half-life. To apply ozonated glycerol for clinical use, ozonated macrogol ointment has been developed by adding macrogol ointment to ozonated glycerol to increase the retention in the affected area. However, the effects of ozone on this macrogol ointment were unclear. The viscosity of the ozonated macrogol ointment was approximately two times higher than that of ozonated glycerol. The effect of the ozonated macrogol ointment on the human osteosarcoma cell line Saos-2 (Saos-2 cells) proliferation, type 1 collagen production, and alkaline phosphatase (ALP) activity were studied. The proliferation of Saos-2 cells was assessed using MTT and DNA synthesis assays. Type 1 collagen production and ALP activity were studied using ELISA and ALP assays. Cells were treated for 24 h with or without 0.05, 0.5, or 5 ppm ozonated macrogol ointment. The 0.5 ppm ozonated macrogol ointment significantly elevated Saos-2 cell proliferation, type 1 collagen production, and ALP activity. These results also showed almost the same trend as for ozonated glycerol.

The BNT162b2 mRNA COVID-19 Vaccine Increases the Contractile Sensitivity to Histamine and Parasympathetic Activation in a Human Ex Vivo Model of Severe Eosinophilic Asthma.

The BNT162b2 COVID-19 vaccine is composed of lipid-nanoparticles (LNP) containing the mRNA that encodes for SARS-CoV-2 spike glycoprotein. Bronchospasm has been reported as an early reaction after COVID-19 mRNA vaccines in asthmatic patients. The aim of this study was to investigate the acute impact of BNT162b2 in a human ex vivo model of severe eosinophilic asthma. Passively sensitized human isolated bronchi were challenged with the platelet-activating factor to reproduce ex vivo the hyperresponsiveness of airways of patients suffering from severe eosinophilic asthma. BNT162b2 was tested on the contractile sensitivity to histamine and parasympathetic activation via electrical field stimulation (EFS); some experiments were performed after mRNA denaturation. BNT162b2 increased the resting tone (+11.82 ± 2.27%) and response to histamine in partially contracted tissue (+42.97 ± 9.64%) vs. the control (p < 0.001); it also shifted the concentration-response curve to histamine leftward (0.76 ± 0.09 logarithm) and enhanced the response to EFS (+28.46 ± 4.40%) vs. the control. Denaturation did not significantly modify (p > 0.05) the effect of BNT162b2. BNT162b2 increases the contractile sensitivity to histamine and parasympathetic activation in hyperresponsive airways, a detrimental effect not related to the active component but to some excipient. A possible candidate for the bronchospasm elicited by BNT162b2 could be the polyethylene glycol/macrogol used to produce LNP.

Bowel cleansing efficacy of 1 L NER1006versus macrogol and 3 L polyethylene glycol using split-dose administration.

Background and Aim: Colonoscopies are an important diagnostic technique in the detection of colorectal cancer and colonic disease. Adequate examination is dependent on the degree of mucosal visibility, with poor cleansing impeding the detection of neoplasms. These patients require shorter colonoscopy surveillance intervals, longer hospital stays, and increased healthcare costs-rendering a screening colonoscopy cost-ineffective. In Australia and the Gold Coast Hospital and Health Service (GCHHS), macrogol and 3 L of polyethylene glycol are the preferred regimen given its safety profile and efficacy. Yet, little is known locally about the use of the new low-volume bowel preparation NER1006 (Plenvu) given its recent registration with the Therapeutic Goods of Australia (TGA). The primary outcome assessed the bowel cleansing efficacy of NER1006 compared with 7 days of macrogol and 3 L of polyethylene glycol using the Boston Bowel Preparation Scale (BBPS), while also assessing the influence of notable patient characteristics such as age, gender, body mass index (BMI), and the patients Charlson comorbidity index (CCI). Secondary outcomes assessed the polyp detection rate and procedural factors including cecal intubation, scope withdrawal time, and rebooking rates. Methods: Data from all patients who underwent an outpatient colonoscopy procedure at GCHHS between 1 July 2020 and 30 September 2020 were analyzed. Patients were aged 50-74 years of age and were referred for a screening colonoscopy due to a positive fecal occult blood test (FOBT) result from the National Bowel Cancer Screening Program. Results: Of the 238 patients who met the inclusion criteria, 108 patients received NER1006 and 130 patients received macrogol and 3 L polyethylene glycol. NER1006 achieved superior overall (P < 0.001) and right-sided colon cleansing (P = 0.016). There was an even distribution of males and females (P = 0.118), the mean age of both cohorts was <65 years of age. The macrogol and 3 L polyethylene glycol group had a statistically higher BMI (P < 0.001) and CCI (P < 0.001). Cecal intubation success was achieved in both cohorts (≥95%) and scope withdrawal time was ≥6 min, polyp detection was non-superior (P = 0.824), but superior in NER1006 when BBPS ≥6 (P = 0.002). Rebooking rates were significantly lower in the NER1006 group (P = 0.013). Conclusion: This study demonstrated that NER1006 was superior in terms of overall and right-sided bowel cleansing as a primary endpoint. Patient factors demonstrated to be independent predictors of inadequate bowel preparation. Future studies should aim to explore the safety and tolerability of NER1006 while also assessing the bowel cleansing effectiveness in patients with a high BMI and comorbidity index.

PEG That Reaction: A Case Series of Allergy to Polyethylene Glycol.

Polyethylene glycol (PEG), also known as macrogol, is an excipient in numerous medications, health care products, cosmetics, and foods. It acts as an inert bulking, or stabilizing, agent. Despite its ubiquity, including in 2 of the newly launched vaccines against SARS-CoV-2, awareness of PEG allergy remains low. We present 6 cases of acute hypersensitivity to PEG. Accurate diagnoses in these cases posed a challenge, and although the triggering agents differed, PEG was demonstrated as the common culprit. All cases were female, with a mean age of 36.4 years. Four patients were originally suspected to have nonsteroid anti-inflammatory drug allergy, and 2 had a history of chronic spontaneous urticaria and angioedema. Biphasic allergic reactions featured prominently in this case series. Diagnosis relies on a high index of suspicion leading to a focused clinical history, supported by skin tests with PEG solutions to demonstrate sensitization. This case series highlights important clinical features of this rare, potentially serious, and increasingly recognized excipient allergy.

May polyethylene glycol be the cause of anaphylaxis to mRNA COVID-19 vaccines?

Vaccination against coronavirus is essential to minimize the impact of the COVID-19 pandemic. Rare cases of anaphylaxis associated with the mRNA COVID-19 vaccines are being described, and the mechanisms involved in these reactions are poorly understood. A potential culprit agent of these vaccine-induced anaphylaxis events is polyethylene glycol, which has been reported as a cause of anaphylaxis. However, a cause-effect association has not been demonstrated, and the cases of anaphylaxis to mRNA COVID-19 vaccines should be further investigated. In this scenario, the recommendations are inaccurate and can lead to misinterpretation. At the moment, a more accurate recommendation would be the contraindication of mRNA COVID-19 vaccines in patients with immediate hypersensitivity reaction to polyethylene glycol or polysorbate. Patients with history of anaphylaxis to other or unknown causes should be referred to an allergist-immunologist for further orientation.