Unveiling Anthraquinones: Diverse Health Benefits of an Essential Secondary Metabolite.

Since ancient times, plants have been used as a remedy for numerous diseases. The pharmacological properties of plants are due to the presence of secondary metabolites like terpenoids, flavonoids, alkaloids, etc. Anthraquinones represent a group of naturally occurring quinones found generously across various plant species. Anthraquinones attract a significant amount of attention due to their reported efficacy in treating a wide range of diseases. Their complex chemical structures, combined with inherent medicinal properties, underscore their potential as agents for therapy. They demonstrate several therapeutic properties such as laxative, antitumor, antimalarial, antibacterial, antifungal, antioxidant, etc. Anthraquinones are found in different forms (derivatives) in plants, and they exhibit various medicinal properties due to their structure and chemical nature. The precursors for the biosynthesis of anthraquinones in higher plants are provided by different pathways such as plastidic hemiterpenoid 2-C-methyl-D-erthriol4-phosphate (MEP), mevalonate (MVA), isochorismate synthase and polyketide. By conducting a thorough analysis of scientific literature, this review provides insights into the intricate interplay between anthraquinone biosynthesis and its broad-ranging contributions to human health.

Recent advances in treating constipation in children.

INTRODUCTION: Functional constipation (FC) is a common childhood condition, diagnosed via the Rome IV criteria. Standard therapy includes lifestyle and dietary modification followed by initiation of osmotic laxative therapy. About 30% of children continue to experience symptoms related to FC despite appropriate management. New pharmacologic, surgical, and neuromodulatory therapies for FC are now available for use in adult and pediatric populations. In 2023, the first pharmacologic agent, linaclotide, obtained FDA approval for treatment of FC in children 6-17 years old. AREAS COVERED: This article reviews current and emerging pharmacologic, surgical, and neuromodulation therapies for the management of FC in pediatric patients. Efficacy and safety data regarding each of these modalities was reviewed and discussed. EXPERT OPINION: Advancements in therapeutics available for the management of FC necessitate further investigation on safety and efficacy in pediatric populations. Careful consideration should be taken in choosing an available treatment with limited pediatric evidence as adult and pediatric FC have different underlying pathophysiology and require a different therapeutic approach. Standardization of methodology and pediatric endpoints are needed to optimize ability to compare efficacy of different treatments. We predict the future of pediatric FC management will include a personalized approach to care, resulting in improved outcomes.

Management of functional constipation-associated halitosis: a retrospective study.

The features of functional constipation (FC)-associated halitosis were identified in the author's previous report. In this report, the author aimed to further investigate its treatment and efficacy. This retrospective study reviewed 100 FC patients, including 82 (82%) halitosis patients and 18 (18%) non-halitosis patients. They underwent the organoleptic test (OLT) to diagnose halitosis, and the organoleptic score (OLS) (0-5) was used to evaluated halitosis severity. The Cleveland Clinical Constipation Score (CCCS) (0-30) was used to evaluate FC severity. Patients were treated with the laxative polyethylene glycol electrolyte powder (PGEP) for four weeks. These tests were performed before and after treatment. The author found that, before treatment, the CCCS was 20.00 (18.00-23.00) for all patients, 21.00 (19.00-24.00) for halitosis patients, and 18.00 (17.00-18.25) for non-halitosis patients. A significant difference was observed between halitosis patients and non-halitosis patients (P< 0.001). The OLS for halitosis patients was 3.00 (3.00-4.00). A positive correlation (r= 0.814, 95% CI: 0.732-0.872,P< 0.001) was found between OLS and CCCS. A CCCS ⩾18 predicted over 50% probability of halitosis. After treatment, the CCCS significantly decreased to 11.50 (6.00-14.75) (P< 0.001), and OLS significantly decreased to 1.00 (0.00-2.00) (P< 0.001). A positive correlation (r= 0.770, 95% CI: 0.673-0.841,P< 0.001) persisted between OLS and CCCS. A pre-treatment CCCS ⩾21 predicted over 50% probability of post-treatment halitosis, while a post-treatment CCCS ⩾12 predicted over 50% probability of post-treatment halitosis. The author concludes that the severity of FC parallels the severity of FC-associated halitosis, and can predict the probability of halitosis. Laxative treatment with PGEP is effective in improving FC-associated halitosis.

Phytochemical profile and pharmacological potential of Withania somnifera whole plant extracts.

Withania somnifera belongs to the family Solanaceae, commonly called ashwagandha, and is traditionally used as an astringent, hepatoprotective and antioxidant, and as a treatment for rheumatism. Therefore the current study aimed to explore the dichloromethane fraction of W. somnifera whole plant (DCFWS) and ethyl acetate fraction of W. somnifera (EAFWS) using gas chromatoghraphy-mass spectrometry (GC-MS) analysis and to find the acetylcholinesterase inhibition potential along with spasmolytic activity. The GC-MS-detected phytochemicals were 2,4-bis(1,1-dimethylethyl), hexadecanoic acid, 1-nonadecene and 11-octadecenoic acid. The DCFWS and EAFWS exhibited acetylcholinesterase inhibitory potential with significant inhibitory concentration values. The acute toxicity results of both fractions showed high toxicity, causing emesis at 0.5 g and both emesis and diarrhea at 1 g/kg. Both fractions exhibited significant (p ≤ 0.01) laxative activity against metronidazole (7 mg/kg) and loperamide hydrochloride (4 mg/kg) induced constipation. Both DCFWS (66.8 ± 3.85%) and EAFWS (58.58 ± 3.28%) significantly (p ≤ 0.05) increased charcoal movement compared with distal water (43.93 ± 4.34%). Similarly the effect of DCFWS on KCl-induced (80 mm) contraction was more significant as compared with EAFWS. It was concluded that the plant can be used in the treatment of gastrointestinal tract diseases such as constipation. Furthermore, additional work is required in the future to determine the bioactive compounds that act as therapeutic agents in W. somnifera.

A study on the related influencing factors of the quality of bowel preparation and the compliance of middle-aged and elderly patients for colonoscopy.

OBJECTIVE: Quality of bowel preparation and patient compliance are among the most important indicators to assess the quality of colonoscopy. To investigate the independent factors associated with the quality of bowel preparation in subjects undergoing colonoscopy and its impact on compliance. METHODS: A total of 329 patient records were collected and were divided into an adequate bowel preparation group (272 cases) and an inadequate bowel preparation group (57 cases), or a compliant group (260 cases) and a non-compliant group (69 cases), based on bowel preparation quality or compliance. The quality of bowel preparation is evaluated using the Boston Bowel Preparation Scale. The comfort level of subjects during bowel preparation is assessed using the Kolcaba General Comfort Questionnaire (GCQ). Subjects' compliance was assessed according to a self-developed compliance questionnaire. Prediction analyses were conducted to identify factors associated with the quality of bowel preparation and compliance. RESULTS: Age, bowel preparation duration, history of bowel inadequacy, and laxative dosage showed statistical differences between the adequate and inadequate bowel preparation groups (P < 0.05). Age, bowel preparation duration, and laxative dosage were independent influencing factors of bowel preparation quality. Correlation analysis showed that GCQ scores was significantly negatively correlated with age, bowel preparation duration, laxative dose, defecation frequency, and colonoscopy duration (r < 0, P < 0.05), and positively correlated with sleep duration (r > 0, P < 0.05). In addition, age, gender, bowel preparation duration, and laxative dosage showed statistical differences between the compliant and non-compliant groups (P < 0.05). Logistic regression analysis revealed that age, bowel preparation duration, and laxative dosage were independent influencing factors of bowel preparation compliance. Age and bowel preparation duration were independent influencing factors for bowel preparation adequacy and compliance. CONCLUSIONS: Age, bowel preparation duration, and laxative dosage are independent influencing factors for bowel preparation adequacy and compliance among patients undergoing colonoscopy at the First Affiliated Hospital, School of Medicine, Zhejiang University. It is recommended that a one-day low-residue diet combined with a 2000 mL laxative dosage be used as the bowel preparation protocol for the general colonoscopy population.

Factors Associated with Defecation Satisfaction among Japanese Adults with Chronic Constipation.

Background: Constipation causes substantial morbidity worldwide. Methods: This survey assessed constipation-related factors in Japan using the Japanese version of the Irritable Bowel Syndrome Quality of Life (IBS-QOL-J) instrument. We also examined the relationship among laxative type, Bristol Stool Form Scale (BSFS) scores, and treatment cost. Finally, we examined differences in satisfaction scores according to laxative type, treatment type, treatment cost, and BSFS score. Results: IBS-QOL-J was higher among those taking salt and/or irritation laxatives. Those paying >JPY 5000 (USD 50.00) had the lowest IBS-QOL-J. IBS-QOL-J was significantly lower among those with a BSFS score of 1 or 2 (severe constipation). Conclusions: This study's findings suggest that a variety of factors, including treatment type and cost, are associated with defecation satisfaction. Those who had hard stools, used multiple laxatives, or spent more on treatment were less satisfied. Future strategies should target therapies that do not require multiple laxatives with lower treatment costs. Adequate defecation with a small number of appropriate laxatives at minimal cost appears to improve defecation satisfaction. It is desirable to identify appropriate laxatives and improve dietary habits and exercise routines. It is also necessary to stop blindly increasing laxative usage and properly diagnose constipation disorders such as anatomical abnormalities other than functional constipation.

The phytochemistry and pharmacology of three Rheum species: A comprehensive review with future perspectives.

BACKGROUND: Rheum palmatum, R. tanguticum, and R. officinale, integral species of the genus Rheum, are widely used across global temperate and subtropical regions. These species are incorporated in functional foods, medicines, and cosmetics, recognized for their substantial bioactive components. PURPOSE: This review aims to synthesize developments from 2014 to 2023 concerning the botanical characteristics, ethnopharmacology, nutritional values, chemical compositions, pharmacological activities, mechanisms of action, and toxicity of these species. METHODS: Data on the three Rheum species were gathered from a comprehensive review of peer-reviewed articles, patents, and clinical trials accessed through PubMed, Google Scholar, Web of Science, and CNKI. RESULTS: The aerial parts are nutritionally rich, providing essential amino acids, fatty acids, and minerals, suitable for use as health foods or supplements. Studies have identified 143 chemical compounds, including anthraquinones, anthrones, flavonoids, and chromones, which contribute to their broad pharmacological properties such as laxative, anti-diarrheal, neuroprotective, hepatoprotective, cardiovascular, antidiabetic, antitumor, anti-inflammatory, antiviral, and antibacterial effects. Notably, the materials science approach has enhanced understanding of their medicinal capabilities through the evaluation of bioactive compounds in different therapeutic contexts. CONCLUSION: As medicinal and economically significant herb species, Rheum species provide both edible aerial parts and medicinal underground components that offer substantial health benefits. These characteristics present new opportunities for developing nutritional ingredients and therapeutic products, bolstering the food and pharmaceutical industries.

Chronic California herbal tea use causing biopsy-proven Melanosis coli.

Melanosis coli is a dark to brown pigmentation of the colon due to lipofuscin deposition within the cytoplasm of cells. It is a benign condition associated with excessive use of laxatives, particularly those that are anthracene derivatives and common herbal remedies like Cassia Angustifolla (senna). It is usually asymptomatic and diagnosed incidentally during colonoscopy or histopathologic evaluation. We present a case of a 56-year-old male patient who presented with diarrhea of 3 months duration, which started after he began to use California herbal tea for his constipation. Colonoscopic evaluation revealed an intense pigmentation throughout the colon suggestive of Melanosis coli, which was confirmed on histopathology. In patients with prolonged use of California herbal tea and dark to brown pigmentations of colonic mucosa on colonoscopy, there should be a high index of suspicion for Melanosis coli. And patients should be aware of the risk of developing Melanosis coli following prolonged herbal tea use. The findings presented in our case are in support of few previous literature that showed relations between chronic herbal tea use and Melanosis coli.

Opioids and Immunosuppression: Clinical Evidence, Mechanisms of Action, and Potential Therapies.

Background: In addition to the more well-known adverse effects of opioids, such as constipation, mounting evidence supports underlying immunosuppressive effects as well. Methods: In this study, we provide a narrative review of preclinical and clinical evidence of opioid suppression of the immune system as well as possible considerations for therapies. Results: In vitro and animal studies have shown clear effects of opioids on inflammatory cytokine expression, immune cell activity, and pathogen susceptibility. Observational data in humans have so far supported preclinical findings, with multiple reports of increased rates of infections in various settings of opioid use. However, the extent to which this risk is due to the impact of opioids on the immune system compared with other risk factors associated with opioid use remains uncertain. Considering the data showing immunosuppression and increased risk of infection with opioid use, measures are needed to mitigate this risk in patients who require ongoing treatment with opioids. In preclinical studies, administration of opioid receptor antagonists blocked the immunomodulatory effects of opioids. Conclusions: As selective antagonists of peripheral opioid receptors, peripherally acting mu-opioid receptor (MOR) antagonists may be able to protect against immune impairment while still allowing for opioid analgesia. Future research is warranted to further investigate the relationship between opioids and infection risk as well as the potential application of peripherally acting MOR antagonists to counteract these risks.

Evaluations of the in vivo Laxative Effects of Aqueous Leaf and Stem Extracts of Artemisia Abyssinica in Mice.

Background: People frequently complain of long-term constipation. The cost associated with using modern medications to treat constipation is significant, and the probability of encountering side effects is notably high. These limitations restrict their effectiveness in therapy, remain unresolved, and underscore the need for research on alternative therapeutic approaches. Plants of the genus Artemisia have been used to treat constipation. Therefore, the aim of this study was to evaluate the laxative effects of aqueous A. abyssinica leaf and stem extracts of Artemisia abyssinica in mice. Methods: The laxative activity of A. abyssinica leaf and stem extracts was evaluated using three models: laxative activity, gastrointestinal motility, and gastrointestinal secretion. In this study, bisacodyl was used as a standard laxative and loperamide was used to induce constipation. Results: In the laxative test, 200 (P<0.05) and 400 mg/kg (p<0.01) doses of plant extract significantly increased the percentage of fecal water content. Moreover, the highest dose of extract increased the frequency of defecation after 12 h (p<0.05). In the remaining two models, the experimental plans also showed significantly higher gastrointestinal motility and noticeable accumulation of intestinal fluid. Conclusion: The results of this study indicate that aqueous leaf and stem extracts of A. abyssinica have laxative effects.

Potential drug-induced constipation: A retrospective study using a Japanese claims database.

Background and Aim: Detailed clinical information regarding drug-induced constipation (DIC) is limited. This study aimed to investigate the real-world situation of DIC. Methods: This retrospective study used data from a Japanese claims database registered from 2014 to 2021. The constipation cohort included subjects with at least one record of treated constipation, while the non-constipation cohort was selected through random stratified sampling method, to match the constipation cohort by gender. The study population and control with at least one history of a known causative drug (CD) were matched 1:1 using propensity scores. The proportion of potential DIC (pDIC), the timing of diagnosis for pDIC, and the proportion of prescriptions by drug class for both the CDs and the laxatives were calculated, while logistic regression analysis was performed to explore additional associated factors. Results: Of the 4 533 905 subjects, 178 852 were eligible in both the study population and the control. The pDIC group comprised of 19 485 patients, which accounted for 10.9% of all treated constipation subjects, while the non-constipation with CD group had 10 430 subjects. The median duration between the recorded CD prescription and treated constipation was 38.0 days. The most frequently prescribed CD was cardiovascular drugs (47.9%). All CD classes, being male, and some comorbidities were associated with the occurrence of pDIC. Conclusion: The pDIC subjects accounted for about 11% of all treated constipation cases. Since DIC requires different treatment regimens compared to other constipation types, physicians should be cognizant to provide patients with optimized treatments.

The Potential Application of Aloe Barbadensis Mill. as Chinese Medicine for Constipation: Mini-Review.

Aloe barbadensis Mill. has a long history of medicinal use in the annals of traditional Chinese medicine, wherein it has garnered considerable renown. Its multifaceted therapeutic properties, characterized by its anti-inflammatory and antibacterial attributes, alongside its established efficacy as a laxative agent, have been extensively documented. This review commences with an exploration of the nomenclature, fundamental characteristics, and principal constituents of Aloe barbadensis Mill. responsible for its laxative effects. Subsequently, we delve into an extensive examination of the molecular mechanisms underlying Aloe barbadensis Mill.'s laxative properties, types of constipation treatments, commercially available preparations, considerations pertaining to toxicity, and its clinical applications. This review aims to serve as a comprehensive reference point for healthcare professionals and researchers, fostering an enhanced understanding of the optimal utilization of Aloe barbadensis Mill. in the treatment of constipation.

A case of pseudo-Bartter/Gitelman syndrome caused by long-term laxative abuse, leading to end-stage kidney disease.

Pseudo-Bartter/Gitelman syndrome (PBS/PGS) is a disorder that presents with hypokalemia and metabolic alkalosis resembling Gitelman syndrome (GS) due to secondary factors, such as lifestyle and /or medicines. Notably, PBS/PGS is more likely to cause renal dysfunction than GS. We report the first case of PBS/PGS due to long-term laxative abuse leading to end-stage kidney disease (ESKD). The patient was a 49-year-old woman with a history of constipation since school, who had used excessive doses of laxatives on her own judgment for nine years at least from 22 years of age. Two years later, blood tests revealed hypokalemia (serum K 3.1 mEq/L), and nine years later, the patient's renal function began to deteriorate (Cr-eGFR 48.7 mL/min/1.73 m2). Since abuse of laxatives was suspected as the cause, it was changed to the proper dosage of laxatives. At 33 years, the patient developed acute kidney injury (AKI), due to a urinary tract infection, and required intensive treatment, including hemodialysis. Although the patient was eventually weaned off dialysis, the renal function did not recover to pre-AKI levels. In suspected GS, comprehensive genetic testing for renal disease-related genes was performed; however, no obvious pathogenic variants were identified. Thereafter, despite decreasing the laxative doses and potassium supplementation, her renal function continued to decline. At 49 years, the patient developed ESKD and was started on maintenance hemodialysis. PBS/PGS is a disease that can lead to ESKD. An early diagnosis of PBS/PGS is crucial to prevent renal function deterioration, and the underlying causes should be removed immediately.

Factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20-year period: Retrospective cohort study.

BACKGROUND: Constipation is a common adverse effect of antipsychotics, but little investigation has been conducted. We aimed to address the factors associated with the initiation of laxative use in the same patients with schizophrenia over a 20-year period. METHODS: We enrolled patients with schizophrenia attending each hospital (n = 14) from April 1, 2021, and retrospectively examined all prescriptions as of April 1, 2016, 2011, 2006, and 2001, every 5 years starting in 2021, for this population. 716 participants with complete data were included in the analysis. The Cochran Q test followed by Bonferroni correction and the Cochran-Armitage trend test were used to determine the differences and trends of the frequency of each laxative. Multivariate logistic regression analysis was performed to assess the factors on the initiation of laxative use over a 20-year period. RESULTS: Of the patients, 25.1% were treated with laxatives in 2001, and 34.1% were treated in 2021. The numbers of patients treated with any laxatives significantly differed over the 20-year period, with a significant increasing trend. In all laxatives, the numbers of patients treated with magnesium oxide, lubiprostone and elobixibat differed with a significant increasing trend. Female sex, age, the total DZP equivalent dose, and the doses of levomepromazine maleate, olanzapine, quetiapine, zotepine, lithium, and carbamazepine in 2021 were significant factors associated with the initiation of laxative use over the 20-year period. CONCLUSIONS: Careful monitoring is needed for patients treated with levomepromazine maleate, olanzapine, quetiapine and zotepine. Optimizing prescriptions according to treatment guidelines could reduce antipsychotic-induced constipation.

Pharmacological, toxicological and phytochemical analysis of Spondias dulcis parkinson.

Spondias dulcis Parkinson have been used in traditional medicine in Asia, Oceania, and South America, for different diseases conditions and as a functional food. The scientific literature described as different potential pharmacology such as antioxidant, anti-inflammatory, antimicrobial, thrombolytic and enzymatic inhibitor. This study aimed to: (1) establish the pharmacological activity in intestinal motility in vivo and antioxidant activity in vitro; (2) perform the acute toxicology test in mouse; (3) characterize the phytochemical profile based on counter-current chromatography (CCC) and NMR analysis. The results revealed a laxative effect of S. dulcis extract and a high antioxidant activity (IC50 = 5.10 for DPPH assay and 14.14 for hydrogen peroxide scavenging test). No side effects were observed in the oral acute toxicity test for a dose up to 2000 mg/kg. The chemical profile was identified by CCC and NMR, and the comparison of the data obtained with previous literature revealed the presence of the flavonoid rutin (Quercetin-3-O-rutinoside) in the extract.

An observational post-authorization safety study (PASS) of naloxegol drug utilization in four European countries.

PURPOSE: Naloxegol has been shown to be an efficient alternative to treat opioid-induced constipation (OIC). This study aimed at describing the characteristics of naloxegol users and assessing patterns of naloxegol use and associated factors. METHODS: This drug utilization cohort study used observational registry data on patients newly prescribed naloxegol in four European countries. Patient characteristics and patterns of naloxegol use and associated factors were described. RESULTS: A total of 17 254 naloxegol users were identified across the countries. Their median age was 56-71 years, and each country had a majority of women (ranging 57.5%-62.9%). Multiple comorbidities, including cancer, were common. Natural opium alkaloids and osmotically acting laxatives (excluding saline) were the most frequently used opioids and laxatives. Overall prior use of opioids ranged from 91.9% to 99.6% and overall prior use of laxatives ranged from 69.9% to 92.4%. Up to 77.7% had prior use of medications with interaction potential, and up to 44.5% used them concurrently with naloxegol. Naloxegol was discontinued by 55.1%-90.9% of users, typically during the first 30 days. Approximately 10%-30% switched to or augmented the treatment with another constipation medication or restarted naloxegol after discontinuation. Augmentation with another constipation medication was relatively common, suggesting that naloxegol was used for multifactorial constipation. CONCLUSION: The present study reflects real-world clinical use of naloxegol, including in vulnerable patient groups. Some naloxegol users lacked laxative or regular opioid use within six months before index date or used naloxegol concomitantly with medications presenting an interaction potential.

The rhizomes of Atractylodes macrocephala relieve loperamide-induced constipation in rats by regulation of tryptophan metabolism.

ETHNOPHARMACOLOGICAL RELEVANCE: Constipation is one of the most prevalent gastrointestinal tract diseases that seriously affects health-related quality of human life and requires effective treatments without side effect. The rhizome of Atractylodes macrocephala Koidz. (Compositae), called Atractylodes Macrocephala Rhizome (AMR), a commonly used traditional Chinese medicine, has been used to relieve the clinical symptoms of patients with constipation. AIM OF THE STUDY: To reveal the dose-dependent laxative effect and potential mechanism of AMR on loperamide-induced slow transit constipation (STC) rats. MATERIALS AND METHODS: Loperamide-induced constipation rat model was established and the dose-dependent laxative effect of AMR was investigated. Untargeted metabolomics based on an UPLC-Q/TOF-MS technique combined with western blot analysis was used to explain the potential mechanism of AMR relieve loperamide-induced constipation in rats. RESULTS: The results showed that medium dose of AMR (AMR-M, 4.32 g raw herb/kg) and high dose of AMR (AMR-H, 8.64 g raw herb/kg) treatments significantly increased the fecal water content, Bristol score, gastrointestinal transit rate, and recovered the damaged colon tissues of constipated rats, but low dose of AMR (AMR-L, 2.16 g raw herb/kg) did not show laxative effect. Both AMR-M and AMR-H treatments also remarkably reduced the serum levels of vasoactive intestinal peptide (VIP), somatostatin (SS) and dopamine (DA), and increased the levels of motilin (MTL), gastrin (GAS) and 5-hydroxytryptamine (5-HT). Urine metabolomics revealed that constipation development was mainly ascribed to the perturbed tryptophan metabolism, and AMR-M and AMR-H markedly corrected the abnormal levels of five urine tryptophan metabolites, namely 4,6-dihydroxyquinoline, indole, 4,8-dihydroxyquinoline, 5-hydroxytryptamine, and kynurenic acid. Additionally, western blot analysis confirmed that the abnormal expression of rate-limiting enzyme involving in tryptophan metabolism, including tryptophan hydroxylase (TPH), monoamine oxidase (MAO) and indoleamine-2,3-dioxygenase (IDO) in the colon of constipated rats, were mediated by AMR-M and AMR-H. CONCLUSIONS: The findings provide insight into the mechanisms of STC and AMR could be developed as new therapeutic agent for prevention or healing of constipation.

A Phase 2 evaluation of a new flavored peg and sulfate solution compared to an over-the-counter laxative, peg and sports drink bowel preparation combination.

BACKGROUND: Acceptability and tolerance of bowel preparation is critical to overcome patient hesitancy in undergoing colon cancer screening and surveillance colonoscopy. To improve patient experience, a new sports drink-flavored bowel preparation containing polyethylene glycol (PEG) and sulfate salts (FPSS) was developed to provide a similar experience to a commonly used but not United States Food and Drug Administration (FDA) approved PEG and sports drink bowel preparation (PEG-SD), while also achieving improved cleansing efficacy. METHODS: This FPSS preparation, approved by the FDA in June 2023, was evaluated in a non-randomized Phase 2 study in which 40 patients requiring colonoscopy were prepared with FPSS and 20 with PEG-SD. RESULTS: Overall cleansing success was high with FPSS based on unblinded local endoscopist assessment (93%) and blinded central reading (97%), exceeding PEG-SD which achieved success rates of 84% (local read), 74% and 68% (blinded central reads). Similar differences favoring FPSS were seen for excellent preparations and cleansing success by colon segment as rated by local endoscopists. Both preparations were well-tolerated, with 93% of FPSS patients rating their preparation as Tolerable to Very Easy to consume, compared to 100% of PEG-SD. Patients who had previously taken a preparation for colonoscopy found FPSS and PEG-SD better than their prior preparation (73% and 70%, respectively) and nearly all would request their assigned study preparation again in the future. About two thirds of FPSS patients agreed that the preparation tasted similar to a sports drink. CONCLUSION: The new sports drink-like flavored preparation compares favorably to PEG-SD for bowel cleansing efficacy while achieving similar patient satisfaction. The study was registered at www. CLINICALTRIALS: gov (NCT03328507) on 01/11/2017.

A Retrospective Observational Study of Factors Affecting the Efficacy of Concurrent Prescription of Naldemedine for Opioid-Induced Constipation Caused by Oxycodone Tablets.

Naldemedine is indicated for the treatment of opioid-induced constipation (OIC), but reports on its efficacy in preventing OIC are few. Therefore, we retrospectively investigated factors affecting the efficacy of concurrent prescription of naldemedine on OIC. Outpatients with cancer who were started on oxycodone 10 mg/d were included in the study. The eligible patients were classified by their physicians into the following three groups: Group A used regular laxatives before the introduction of oxycodone and initiated naldemedine treatment simultaneously with oxycodone administration, Group B did not take laxatives before the introduction of oxycodone and started naldemedine simultaneously with oxycodone administration, and Group C had been administering regular laxatives before the introduction of oxycodone and were not prescribed naldemedine simultaneously with oxycodone treatment. The Support Team Assessment Schedule Japanese edition score for constipation, frequency of defecation, Bristol Stool Form Scale, sense of incomplete rectal evacuation, and development or worsening of straining to pass bowel movements were compared among the three groups before and after oxycodone administration. In Group B, there was significant worsening of the four parameters except for the sense of incomplete rectal evacuation, whereas Groups A and C did not present any changes. In logistic regression analysis, body weight ≥51.8 kg was a factor significantly decreasing the preventive effect of naldemedine on OIC, and regular use of laxatives was a factor significantly increasing the preventive effect of naldemedine on OIC. Thus, the initiation of naldemedine should be considered depending on the body weight and regular laxative use.

Re-evaluation of erythritol (E 968) as a food additive.

This opinion addresses the re-evaluation of erythritol (E 968) as food additive and an application for its exemption from the laxative warning label requirement as established under Regulation (EU) No 1169/2011. Erythritol is a polyol obtained by fermentation with Moniliella pollinis BC or Moniliella megachiliensis KW3-6, followed by purifications and drying. Erythritol is readily and dose-dependently absorbed in humans and can be metabolised to erythronate to a small extent. Erythritol is then excreted unchanged in the urine. It does not raise concerns regarding genotoxicity. The dataset evaluated consisted of human interventional studies. The Panel considered that erythritol has the potential to cause diarrhoea in humans, which was considered adverse because its potential association with electrolyte and water imbalance. The lower bound of the range of no observed adverse effect levels (NOAELs) for diarrhoea of 0.5 g/kg body weight (bw) was identified as reference point. The Panel considered appropriate to set a numerical acceptable daily intake (ADI) at the level of the reference point. An ADI of 0.5 g/kg bw per day was considered by the Panel to be protective for the immediate laxative effect as well as potential chronic effects, secondary to diarrhoea. The highest mean and 95th percentile chronic exposure was in children (742 mg/kg bw per day) and adolescents (1532 mg/kg bw per day). Acute exposure was maximally 3531 mg/kg bw per meal for children at the 99th percentile. Overall, the Panel considered both dietary exposure assessments an overestimation. The Panel concluded that the exposure estimates for both acute and chronic dietary exposure to erythritol (E 968) were above the ADI, indicating that individuals with high intake may be at risk of experiencing adverse effects after single and repeated exposure. Concerning the new application, the Panel concluded that the available data do not support the proposal for exemption.