Adverse Gastrointestinal Symptoms Research Articles

#1926 Persistence to first- and second- generation potassium binder treatment—an observational study based on the DEMONSTRATE database

Abstract Background and Aims Hyperkalemia (HK) is a common electrolyte abnormality mainly caused by reduced renal potassium excretion in patients with chronic kidney disease (CKD). Potassium binders, such as sodium polystyrene sulfonates (SPS) are widely used but may lead to adverse gastrointestinal (GI) symptoms, reducing their tolerability. Patiromer and sodium zirconium cyclosilicate (SZC) are newer ion exchange resins for treatment of HK which may cause fewer GI side-effects. This study aims to evaluate the persistence to first- (SPS) and second-generation potassium binder (patiromer and SZC) treatment and the related clinical characteristics. Method In this observational study based on the DEMONSTRATE database, a novel national and regional database comprising laboratory data from six regions in central Sweden (18% of the Swedish population), linked to the national health registry data, we selected all patients in Sweden having at least one pharmacy dispensation of either first (SPS) or second (patiromer or SZC) generation potassium binder between July 2005 and December 2022. By semi-automatically interpreting the prescribed dosages in combination with the amount of medical supply, duration for each dispensation was estimated and episodes of potassium binder treatments were established. For all potassium binder episodes, we described patient characteristics and persistence to treatment. Results are mainly presented by treatment episodes and by strata of (a) all, (b) first and (c) second generation potassium binders. Results Between July 2005 and December 2022, we identified 68 133 treatment episodes of potassium binders for 32 424 patients (Table 1). Of these, 31 730 individuals and 66 309 treatment episodes were attributed to first generation (throughout the study period), and 1,276 individuals and 1,824 treatment episodes to second-generation potassium binders (between 2018-2022) Mean (SD) age was slightly lower in patients initiating second compared to first generation potassium binders; 68.5 (15.6) vs 65.2 (16.6) years. Potassium binder treatment was more common in men compared to women (66.9% vs. 33.1%) with similar gender distribution between first- and second-generation potassium binders. Comorbidities were more common in patients initiating treatment with second than first generation potassium binders, notably for heart failure (40.0% vs. 29.7%) and dialysis (38.8% vs 29.2%). RAASi and MRA were more often prescribed to the second generation potassium binders vs first; 70.8% vs 62.9% for RAASi and 18.8% vs. 8.5% for MRA. Second generation potassium binders were more commonly initiated in cardiology/internal medicine units (41.7% vs. 34.8%) and dialysis (38.8% vs. 29.2%). Persistence was higher among patients treated with second generation potassium binders (Fig. 1). Conclusion Second generation potassium binders were more often prescribed to younger patients that had more co-morbidities being slightly more persistent to treatment when compared to patients on first generation potassium binders.

Effects of Modified Ramadan Fasting on Mental Well-Being and Biomarkers in Healthy Adult Muslims - A Randomised Controlled Trial.

Ramadan fasting has seen increased attention in research, often with inconsistent findings. This study aims to investigate whether dietary and lifestyle modifications during Ramadan can improve well-being and health in healthy adult Muslims. A randomised controlled trial with two parallel groups was conducted in an outpatient clinic of a university hospital in Essen, Germany, in 2016. Healthy adult Muslims (n = 114) aged 18-60years were randomised to a modified fasting group; i.e., they received educational material prompting dietary and lifestyle modifications pre-Ramadan, and a control group who undertook Ramadan fasting as usual. Primary outcome was quality of life (WHO-5 Well-Being Index). Secondary outcomes included sleep quality, spirituality, and mindfulness (all self-report), body weight, body mass index, body fat, waist circumference, hip circumference, blood pressure, and heart rate, as well as blood serum biomarkers. Safety was examined via adverse events. The modified fasting group reported significantly higher quality of life (WHO-5) compared to the control after Ramadan (MD 5.9; 95% CI, 0.02-11.8; p < 0.05). Group differences in favour of the modified fasting were also found for satisfaction with health (MD 5.9, 95% CI 0.19-11.67), ease of life (MD 4.1, 95% CI 0.38-7.80) and mindfulness (MD 7.6, 95% CI 2.68-12.52), reductions in weight (MD, - 0.9kg; 95% CI - 1.39 to - 0.42), BMI (MD - 0.3kg/m2, 95% CI - 0.50 to - 0.15), hip circumference (MD - 0.3kg/m2, 95% CI - 0.50 to - 0.15), and diastolic blood pressure (MD - 2.8mmHg, 95% CI - 5.15 to - 0.43). About 60% of participants reported adverse events, mostly headaches/migraines, dizziness/fatigue, common cold, and gastrointestinal symptoms, with no group differences. One serious non-related adverse event each occurred in both groups. Pre-Ramadan dietary and lifestyle advice can lead to short-term improvements in mental and physical well-being of adult Muslims observing Ramadan. As such, this study demonstrates the potential benefits of culturally appropriate health interventions in a religious context. ClinicalTrials.gov (Identifier NCT02775175).

Bacterial cellulose: A highly versatile nanomaterial.

Bacterial cellulose: A highly versatile nanomaterial.

Blenderized food tube feeding in very young pediatric patients with special healthcare needs.

Up to 85% of children with severe developmental disabilities have feeding disorders and require enteral tube feeding. Many caregivers desire blenderized tube feeding (BTF) instead of commercial formula (CF) for their child, citing a desire for a more physiologic feeding, to reduce gastrointestinal (GI) symptoms and/or promote oral intake. In this retrospective, single-center study, medical records (n = 34) of very young children (aged ≤36 months) with severe developmental disabilities were reviewed. Comparisons of growth parameters, GI symptoms, oral feeding, and GI medication use were made between the initial introduction of BTF and again at the last patient encounter when the children aged out of the program. Of the 34 charts reviewed (16 male and 18 female patients), comparisons between baseline BTF introduction and the last patient encounter indicated reductions in adverse GI symptoms, significant GI medication reduction (P = 0.000), increased oral food intake, and nonsignificant improvements in growth parameters. These positive outcomes were realized whether children received full or partial BTF or type of BTF formulation. Consistent with similar research studies, transitioning very young children with significant special healthcare needs from CF to BTF resulted in improvement in GI symptoms, reduced need for GI medications, supported growth goals, and contributed to improved oral feeding.

Microbial toxins in fermented foods: health implications and analytical techniques for detection.

Recently, demand for fermented foods has increased due to their improved nutritional value, taste, and health-promoting properties. Worldwide consumption of these products is increasing. Fermented foods are generally safe for human consumption. However, some toxins, primarily biogenic amines (putrescine, phenylethylamine, histamine, tyramine, and cadaverine), mycotoxins (fumonisins, aflatoxins, ochratoxin A, zearalenone, and trichothecenes), and bacterial toxins (endotoxins, enterotoxins, and emetic toxins) can be produced as a result of using an inappropriate starter culture, processing conditions, and improper storage. These toxins can cause a multitude of foodborne illnesses and can lead to cardiovascular aberration and adverse gastrointestinal symptoms. Analytical techniques are in use for the detection of toxins in fermented foods for monitoring and control purposes. These include culture, chromatographic, immunoassays, and nano sensor-based techniques. These detection techniques can be used during the production process and along the food chain. On an industrial scale, HPLC is widely used for sensitive quantification of toxins in fermented foods. Recently, biosensor and nano sensor-based techniques have gained popularity due to accuracy, time efficiency, and simultaneous detection of multiple toxins. Other strategic methods being investigated for the removal of toxins from fermented foods include the use of specific starter cultures for bio-preservation, aflatoxin-binding, and biogenic amine-degradation agents that may help to appropriately manage the food safety concerns associated with fermented foods.

Effect of Fructooligosaccharides Supplementation on the Gut Microbiota in Human: A Systematic Review and Meta-Analysis.

Background: Numerous studies have investigated the effects of the supplementation of fructooligosaccharides (FOS) on the number of bacteria in the gut that are good for health, but the results have been inconsistent. Additionally, due to its high fermentability, supplementation of FOS may be associated with adverse gastrointestinal symptoms such as bloating and flatulence. Therefore, we assessed the effects of FOS interventions on the composition of gut microbiota and gastrointestinal symptoms in a systematic review and meta-analysis. Design: All randomized controlled trials published before 10 July 2022 that investigated the effects of FOS supplementation on the human gut microbiota composition and gastrointestinal symptoms and met the selection criteria were included in this study. Using fixed or random-effects models, the means and standard deviations of the differences between the two groups before and after the intervention were combined into weighted mean differences using 95% confidence intervals (CIs). Results: Eight studies containing 213 FOS supplements and 175 controls remained in this meta-analysis. Bifidobacterium spp. counts significantly increased during FOS ingestion (0.579, 95% CI: 0.444–0.714) in comparison with that of the control group. Subgroup analysis showed greater variation in Bifidobacterium spp. in adults (0.861, 95% CI: 0.614–1.108) than in infants (0.458, 95% CI: 0.297–0.619). The increase in Bifidobacterium spp. counts were greater in the group with an intervention duration greater than 4 weeks (0.841, 95% CI: 0.436–1.247) than an intervention time less than or equal to four weeks (0.532, 95% CI: 0.370–0.694), and in the group with intervention doses > 5 g (1.116, 95% CI: 0.685–1.546) the counts were higher than those with doses ≤ 5 g (0.521, 95% CI: 0.379–0.663). No differences in effect were found between FOS intervention and comparators in regard to the abundance of other prespecified bacteria or adverse gastrointestinal symptoms. Conclusions: This is the first meta-analysis to explore the effect of FOS on gut microbiota and to evaluate the adverse effects of FOS intake on the gastrointestinal tract. FOS supplementation could increase the number of colonic Bifidobacterium spp. while higher dose (7.5–15 g/d) and longer duration (>4 weeks) showed more distinct effects and was well tolerated.

Gastrointestinal Bleeding Secondary to High-Dose Melphalan Pretreatment in Patients with Multiple Myeloma Was Associated with the Mode of Melphalan Administration.

Objective To analyze the characteristics of gastrointestinal bleeding secondary to high-dose melphalan pretreatment in patients with multiple myeloma. Methods Between 1 January 2016 and 31 October 2021, 26 patients with multiple myeloma after autologous peripheral blood hematopoietic stem cell transplantation with high-dose melphalan pretreatment were recruited. They were assigned to either the oral administration group or the intravenous administration group according to the administration modes, or to either the gastrointestinal bleeding group or the nongastrointestinal bleeding group. Analyses were performed based on the differences in general gastrointestinal symptoms and hemorrhage between different administration modes and on the differences in the general gastrointestinal symptoms, platelet alterations, and the intestinal microecology before pretreatment between patients with and without gastrointestinal bleeding. Results Of the 26 included patients, heavy secondary gastrointestinal bleeding was found in 6 patients with intravenous pretreatment. In patients given intravenous melphalan, those with gastrointestinal bleeding showed more pronounced general symptoms such as nausea and vomiting versus those without. There was no significant difference in platelet alterations between the two groups. Gastrointestinal bleeding was associated with more significant microecological disturbances than no bleeding. Conclusion Gastrointestinal bleeding secondary to high-dose melphalan pretreatment in patients with multiple myeloma was associated with the mode of melphalan administration, adverse symptoms at pretreatment, and the intestinal microecology prior to pretreatment. Thus, improvement of the intestinal microecology prior to pretreatment and mitigation of adverse gastrointestinal symptoms during pretreatment may contribute to a lower incidence of secondary gastrointestinal bleeding and enhanced transplantation safety.

Almonds and Their Impact on Gastrointestinal Physiology, Luminal Microbiology and Gastrointestinal Function: A Randomized Controlled Trial

ObjectivesThe objective of this study was to investigate the impact of almonds, and almond form (whole, ground) on fecal Bifidobacteria (primary outcome) and gut microbiology, physiology, and symptoms in healthy adults.MethodsEighty-seven healthy adults with moderate fiber intake (<22g/d) were randomized to receive whole almonds (56 g/d), ground almonds (56 g/d) or a control muffin (2/d) in place of their habitual snacks for 4 weeks. Fecal Bifidobacteria, gut microbiota composition and diversity (16S rRNA sequencing), short-chain fatty acids (SCFA; gas-chromatography), volatile organic compounds (gas-chromatography mass-spectrometry), gut transit time (wireless motility capsule), and stool output and symptoms (7-day diary) were measured at baseline and at end of intervention. Differences between groups were assessed by analysis of covariance (ANCOVA) or a non-parametric equivalent and corrected for multiple testing (Bonferroni (p) or Benjamini-Hochberg FDR (q)) where appropriate.ResultsThere were no differences in relative abundance of fecal bifidobacteria following 4-weeks consumption of whole almonds (8.7%, SD 7.7), ground almonds (7.8%, SD 6.9) or control (13.0%, SD 10.2; q = 0.613). There was no effect of almonds on gut microbiota at the phylum level or on diversity. At the genus level, almonds (whole and ground pooled) increased relative abundance of Lachnospiraceae_NK4A136_group, Phascolarctobacterium and decreased Tyzerella (all p < 0.05), however these were no longer significant following FDR adjustment. Pre-specified analysis comparing almonds (whole and ground pooled) demonstrated higher concentrations of butyrate (24.1 μmol/g, SD 15.0) versus control (18.2, SD 9.1; p = 0.046). There was no effect of almonds on gut transit time, stool consistency or gut symptoms. Almond form as either whole (low nutrient bioaccessibility) or ground (higher nutrient bioaccessibility) did not affect any outcome.ConclusionsAlmonds are a high fibre snack that can be incorporated into the diet of moderate fibre consumers with no adverse gastrointestinal symptoms. Almonds do not have major impact on global microbiota composition but may exert a prebiotic effect on microbial metabolism in healthy adults.Funding SourcesThe Almond Board of California.

Safety and Tolerability of SBD111 an Optimized Probiotic/Prebiotic Medical Food Combination Designed for the Dietary Management of Age-Related Bone Loss in Adults.

ObjectivesTo determine the effect of a daily administration of 6.1 × 1010 CFU/d of SBD111 (an optimized probiotic/prebiotic combination) on safety and tolerability in adults in a randomized trial. MethodsParticipants (n = 32) were randomized to either SBD111 or placebo. The primary outcomes were the number, frequency and severity of adverse Gastrointestinal (GI) symptoms over 28-d. Secondary outcomes were the number and severity of all adverse events (AEs). Stool samples were collected at baseline and after 28-d to determine the impact of SBD111 on gut microbial engraftment, diversity and function using shotgun metagenomics. Groups were compared using Incidence Rate Ratios (negative binomial regression), Odds Ratios (logistic regression) and 95%CI (P< 0.05) using intention-to-treat approach. ResultsAt baseline, the mean age was 45(SD:18)y in SBD111 users (n = 5M, 10F) vs 42(SD:14)y in placebo users (n = 5M, 12F). The two groups did not significantly differ in age, BMI, blood pressure and screening labs. After 28-d, the presence of GI symptoms tended to be higher with SBD111 use vs placebo (P = 0.08). The total number, frequency/severity of GI symptoms did not significantly differ between groups and only 1 person withdrew from the placebo group due to side effects. The number of AEs possibly related to the study were significantly higher with SBD111 use vs placebo (P = 0.05), there were no significant differences in the mean number or severity of AEs. The majority of reported AEs were mild, some were moderate, but none were severe. There were no significant differences in Shannon diversity/microbial richness between the two groups at baseline or after 28-d. After 28-d, participants receiving SBD111 but not placebo showed a significant enrichment in metabolic pathways of menaquinone (vitamin K2) production including the superpathway of menaquinol-10. Fragment recruitment analysis identified the genomic signal of the strains comprising SBD111 after 28-d of SBD111 use, but not placebo. SBD111 strains were undetectable at baseline in either group. ConclusionsThe relatively low frequency and mild severity of GI symptoms and AEs suggests that SBD111 at the level tested is safe for human consumption and that SBD111 microbes are able to pass through the intestinal tract, be identified in stool and enrich microbial gene pathways related to bone health. Funding SourcesSolarea Bio Inc.

Strongly increased risk of gastric and duodenal ulcers among new users of low-dose aspirin: results from two large cohorts with new-user design.

Low-dose aspirin is a risk factor for peptic ulcer disease but previous, population-based cohort studies may have underestimated the low-dose aspirin risk because they did not use a new-user design. Gastrointestinal bleeding occurs more frequently early after initiation of low-dose aspirin therapy than in later years. To assess the associations of low-dose aspirin with gastric and duodenal ulcer incidence in prevalent- and new-user design. Multivariate Cox regression models in the German ESTHER study (N=7737) and the UK Biobank (N=213,598) with more than 10 years of follow-up. In the prevalent-user design, there was no significant association between low-dose aspirin and gastric ulcer observed in both cohorts. Furthermore, low-dose aspirin was weakly, statistically significantly associated with prevalent duodenal ulcer in the UK Biobank (hazard ratio [95% confidence interval]: 1.27 [1.07-1.51]) but not in the ESTHER study (1.33 [0.54-3.29]). When restricting the exposure to only new users, the hazard ratios for incident gastric and duodenal ulcer disease were 1.82 [1.58-2.11] and 1.66 [1.36-2.04] in the UK Biobank, respectively, and 2.83 [1.40-5.71] and 3.89 [1.46-10.42] in the ESTHER study, respectively. This study shows that low-dose aspirin is an independent risk factor for both gastric and duodenal ulcers. The associations were not significant or weak in the prevalent-user design and strong and statistically significant in the new-user design in both cohorts. Thus, it is important to weigh risks against benefits when low-dose aspirin treatment shall be initiated and to monitor adverse gastrointestinal symptoms after the start of low-dose aspirin therapy.

29: INCIDENCE, DIAGNOSIS AND MANAGEMENT OF MALABSORPTION FOLLOWING OESOPHAGECTOMY: A SYSTEMATIC REVIEW

Abstract Background and aim Survival following oesophagectomy for oesophageal cancer is increasing. This has resulted in increased focus on quality-of-life and improved survivorship. Weight loss and malnutrition occurs in 25–46% of patients after three years, with associated adverse gastrointestinal symptoms. Malabsorption syndrome is multifactorial and includes exocrine pancreatic insufficiency (EPI), small intestinal bacterial overgrowth (SIBO) and bile acid malabsorption (BAM), however there is little literature available in patients following oesophagectomy. The aim of this study was to evaluate the reported incidence and management of malabsorption syndromes post-oesophagectomy. Methods A systematic search of PubMed, EMBASE, MEDLINE, Scopus and the Cochrane Library evaluating incidence, diagnosis and management of malabsorption was performed for studies published until March 2021. Results Of 461 identified studies, seven studies (6/7 non-randomised observational studies) were included, with a combined population of 344 (range 7–87). Incidence of malabsorption syndromes including EPI, SIBO and BAM were 10.2–100%, 37.8–100% and 3.33–100% respectively. There was no consensus definition for EPI, SIBO or BAM; and there was variation in diagnostic methods. Diagnostic criteria varied from clinical (gastrointestinal symptoms or weight loss), or biochemical (faecal elastase, hydrogen breath test and Selenium-75-labelled synthetic bile acid measurements). Treatment modalities using pancreatic enzyme replacement, rifaximin and colesevelam showed improvement in symptoms and weight in all studies. Conclusion Malabsorption syndromes following oesophagectomy are likely to be severely underestimated. The resultant gastrointestinal symptoms have a negative effect on post-operative quality of life. Current literature suggests benefit with outlined therapies, however greater understanding of these conditions, their diagnosis, and management is required to further understand which patients will benefit from treatment.

P-OGC33 Incidence, diagnosis and management of malabsorption following oesophagectomy: a systematic review

Abstract Background Survival following oesophagectomy for oesophageal cancer is increasing. This has resulted in increased focus on quality-of-life and improved survivorship. Weight loss and malnutrition occurs in 25-46% of patients after three years, with associated adverse gastrointestinal symptoms. Malabsorption syndrome is multifactorial and includes exocrine pancreatic insufficiency (EPI), small intestinal bacterial overgrowth (SIBO) and bile acid malabsorption (BAM), however there is little literature available in patients following oesophagectomy. The aim of this study was to evaluate the reported incidence and management of malabsorption syndromes post-oesophagectomy. Methods A systematic search of PubMed, EMBASE, MEDLINE, Scopus and the Cochrane Library evaluating incidence, diagnosis and management of malabsorption was performed for studies published until March 2021. Results Of 461 identified studies, seven studies (6/7 non-randomised observational studies) were included, with a combined population of 344 (range 7-87). Incidence of malabsorption syndromes including EPI, SIBO and BAM were 10.2-100%, 37.8-100% and 3.33-100% respectively. There was no consensus definition for EPI, SIBO or BAM; and there was variation in diagnostic methods. Diagnostic criteria varied from clinical (gastrointestinal symptoms or weight loss), or biochemical (faecal elastase, hydrogen breath test and Selenium-75-labelled synthetic bile acid measurements). Treatment modalities using pancreatic enzyme replacement, rifaximin and colesevelam showed improvement in symptoms and weight in all studies. Conclusions Malabsorption syndromes following oesophagectomy are likely to be severely underestimated. The resultant gastrointestinal symptoms have a negative effect on post-operative quality of life. Current literature suggests benefit with outlined therapies, however greater understanding of these conditions, their diagnosis, and management is required to further understand which patients will benefit from treatment.

Efficacy and safety of hydroxychloroquine as pre-and post-exposure prophylaxis and treatment of COVID-19: A systematic review and meta-analysis of blinded, placebo-controlled, randomized clinical trials.

BackgroundHydroxychloroquine (HCQ) is an anti-malarial and immunomodulatory drug considered a potential candidate for drug repurposing in COVID-19 due to their in vitro antiviral activity against SARS-CoV-2. Despite the potential antiviral effects and anti-inflammatory profile, the results based on clinical studies are contradictory. Therefore, the quality of the decision-making process from meta-analyses summarizing the available evidence selecting studies with different designs and unblinded trials is limited. The aim of this study was to synthesize the best evidence on the efficacy and safety of HCQ as pre-and post-exposure prophylaxis and treatment of non-hospitalized and hospitalized patients with COVID-19.MethodsSearches were performed in PubMed, Web of Science, Embase, Lilacs, the website ClinicalTrials.gov and the preprint server medRxiv from January 1, 2020 to May 17, 2021. The following elements were used to define eligibility criteria: (1) Population: individuals at high-risk of exposure to SARS-CoV-2 (pre-exposure), individuals who had close contact with a positive or probable case of COVID-19 (post-exposure), non-hospitalized patients with COVID-19 and hospitalized patients with COVID-19; (2) Intervention: HCQ; (3) Comparison: placebo; (4) Outcomes: incidence of SARS-CoV-2 infection, need for hospitalization, length of hospital stay, need for invasive mechanical ventilation (MV), death, and adverse events; and (5) Study type: blinded, placebo-controlled, randomized clinical trials (RCTs). Risk of bias was judged according to the Cochrane guidelines for RCTs. Treatment effects were reported as relative risk (RR) for dichotomous variables and mean difference (MD) for continuous variables with 95% confidence intervals (CI). We used either a fixed or random-effects model to pool the results of individual studies depending on the presence of heterogeneity. The GRADE system was used to evaluate the strength of evidence between use of HCQ and the outcomes of interest.FindingsFourteen blinded, placebo-controlled RCTs were included in this meta-analysis. Four trials (1942 patients: HCQ = 1271; placebo = 671) used HCQ as a prophylactic medication pre-exposure to COVID-19, two (1650 patients: HCQ = 821; placebo = 829) as a prophylactic medication post-exposure to COVID-19, three (1018 patients: HCQ = 497; placebo = 521) as treatment for non-hospitalized patients, and five (1138 patients: HCQ = 572; placebo = 566) as treatment for hospitalized patients with COVID-19. We found no decreased risk of SARS-CoV-2 infection among individuals receiving HCQ as pre-exposure (RR = 0.90; 95% CI 0.46 to 1.77) or post-exposure (RR = 0.96; 95% CI 0.72 to 1.29) prophylaxis to prevent COVID-19. There was no significant decreased risk of hospitalization for outpatients with SARS-CoV-2 infection (RR = 0.64; 95% CI 0.33 to 1.23) and no decreased risk of MV (RR = 0.81; 95% CI 0.49 to 1.34) and death (RR = 1.05; 95% CI 0.62 to 1.78) among hospitalized patients with COVID-19 receiving HCQ. The certainty of the results on the lack of clinical benefit for HCQ was rated as moderate. Moreover, our results demonstrated an increased risk for any adverse events and gastrointestinal symptoms among those using HCQ.InterpretationAvailable evidence based on the results of blinded, placebo-controlled RCTs showed no clinical benefits of HCQ as pre-and post-exposure prophylaxis and treatment of non-hospitalized and hospitalized patients with COVID-19.FundingThere was no funding source.

Timing of pancreatic enzyme replacement therapy (PERT) in cystic fibrosis.

Cystic fibrosis (CF) is an autosomal recessive, life-limiting, multisystem disease affecting over 70,000 individuals worldwide. Between 80% and 90% of people with CF suffer with pancreatic exocrine insufficiency, which if left untreated, leads to a poor nutritional status. Pancreatic enzyme replacement therapy (PERT) has been shown to be effective in improving nutritional status and subsequently associated with improved lung function. However, the timings of PERT administration in relation to a meal are subjective and not standardised, meaning that variations in the timing of PERT dosing persist. The primary objective of the review is to compare the efficacy (fat absorption) and effectiveness (nutritional status, lung function and quality of life)of different PERTdosing strategies in terms of timing of administration for treating dietary malabsorption in all individuals with CF. We searched the Cochrane Cystic Fibrosis Trials Register, compiled from electronic database searches and handsearching of journals and conference abstract books. We also searched the reference lists of relevant articles and reviews. Date of last search: 24 June 2021. We also searched ongoing trials registers on 09 July 2021. Randomised controlled trials (RCTs), including cross-over RCTs with a minimum washout period of two weeks, and quasi-RCTs of PERT dosing regimens in people (of any age) with CF. Two authors independently assessed and screened the studies identified from the searches. We planned to use GRADE to assess the certainty of evidence for our pre-specified critical outcomes, but we did not identify anyeligible studies. No studiesmet the eligibility criteria and therefore we did not include anyin this review. The excluded studieswere either cross-over in design (but lacking a sufficient washout period between treatments) or did not assess the timing of PERT. One study which was terminated early is awaiting assessment pending further information. We were unable to determine whether one dosing schedule for PERTis better than another since we identified no eligible RCTs. While the introduction of PERT to people with CF can improve their nutritional status, there are a limited number of studies which address this review question, and none met our eligibility criteria. Since malnutrition and adverse gastrointestinal symptoms remain a common feature in CF, the assessment of the relative performance of dosing schedules may provide evidence to improve outcomes in people with CF who are pancreatic insufficient. Further research is needed to fully evaluate the role of dosing schedules for PERT in fat absorption. Research should also establish reliable outcome measures and minimal clinically important differences. While RCTs with a cross-over design may have advantages over a parallel group design, an adequate washout period between intervention periods is essential.

Intolerability to postoperative early oral nutrition in older patients (≥70 years) undergoing gastrectomy for gastric cancer: A case-control study.

BackgroundPostoperative early oral nutrition has increasingly been adopted for patients undergoing gastrectomy. However, intolerability to early oral nutrition remains a major concern, especially in older patients. This study aimed to investigate early oral nutrition intolerability in older patients who had undergone gastrectomy.MethodsWe retrospectively reviewed 825 patients who had undergone gastrectomy for gastric carcinoma between 2017 and 2019. All patients received an oral diet on postoperative day 1. Patients were divided into older (≥70 years) and younger (<70 years) adult groups, and short-term outcomes and intolerability to oral nutrition were compared. Intolerability to early oral nutrition was defined as oral diet cessation due to adverse gastrointestinal symptoms.ResultsAmong the 825 patients (≥70 years, n = 286; <70 years, n = 539), 151 (18.3%) developed intolerability to early oral nutrition, of whom 100 patients were < 70 years old and 51 were ≥70 years old. The most common symptom causing intolerability was abdominal distension. The mean duration of fasting after developing intolerability was 2.8 ± 2.4 days. The incidence of intolerability in the older and younger adult groups was 17.8% and 18.6%, respectively (p = 0.799). In terms of sex, operative approach, gastric resection, lymph node dissection, reconstruction, and tumor stage subgroups, the older adult group did not exhibit a significant increase in intolerability. Postoperatively, the older adult group showed a higher incidence of systemic complications; however, anastomotic complications did not significantly differ between the two groups.ConclusionsPostoperative early oral nutrition can safely be adopted for older patients undergoing gastrectomy, with acceptable intolerability and surgical outcomes.

Low-dose colchicine in type 2 diabetes with microalbuminuria: A double-blind randomized clinical trial.

Neutrophil-related chronic inflammation (NRCI) may contribute to the pathogenesis of diabetic kidney disease (DKD). We evaluated whether blocking NRCI with low-dose colchicine prevents DKD. A double-blind, randomized, placebo-controlled study was conducted. A total of 160 patients with type 2 diabetes (T2D) and microalbuminuria (urinary albumin creatinine ratio [UACR] 30 to 300 mg/g Cr) who received angiotensin-converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) for at least 3 months were included. Subjects were 1:1 randomized to a placebo or colchicine group (0.5mg/day). The primary end point was the incidence of overt nephropathy (UACR > 300 mg/g Cr). During the 36 months, 38 patients (51.4%) in colchicine group and 39 (54.1%) in the control group developed overt nephropathy (hazard ratio,1.066; 95% confidence interval,0.679-1.673; P= .78). Compared with placebo, colchicine modestly lowered levels of NRCI parameters (P values <.05 for high-sensitivity C-reactive protein, white blood cell counts, neutrophil counts, and neutrophil-to-lymphocyte ratio), whereas the changes of UACR and estimated glomerular filtration rate (eGFR) were similar between the two groups. There were no significant differences between the two groups in drug-related adverse events, including infection, gastrointestinal symptoms, and limb numbness. In patients with T2D with microalbuminuria, low-dose colchicine effectively and safely lowered NRCI but did not prevent the incidence of overt nephropathy.

Efficacy and safety comparison of pharmacotherapies for interstitial cystitis and bladder pain syndrome: a systematic review and Bayesian network meta-analysis.

The objective was to compare the clinical efficacy and safety of pharmacological interventions for interstitial cystitis and bladder pain syndrome (IC/BPS) with direct and indirect evidence from randomized trials. We searched PubMed, the Cochrane library, and EMBASE for randomized controlled trials (RCTs) that assessed the pharmacological therapies for IC/BPS. Primary efficacy outcomes included ICSI (O'Leary Sant Interstitial Cystitis Symptom Index), ICPI (O'Leary Sant Interstitial Cystitis Problem Index), 24-h micturition frequency, visual analog scale (VAS), and Likert score for pain. Safety outcomes are total adverse events (AEs, intravesical instillation, and others), gastrointestinal symptoms, headache, pain, and urinary symptoms. A systematic review and Bayesian network meta-analysis were performed. A total of 23 RCTs with 1,871 participants were identified. The ICSI was significantly reduced in the amitriptyline group (MD = -4.9, 95% CI: -9.0 to -0.76), the cyclosporine A group (MD = -7.9, 95% CI: -13.0 to -3.0) and the certolizumab pegol group (MD = -3.6, 95% CI:-6.5 to -0.63) compared with placebo group. Moreover, for ICPI, cyclosporine A showed superior benefit compared to placebo (MD = -7.6, 95% CI: -13 to -2.3). VAS score improved significantly in cyclosporine A group than pentosan polysulfate sodium (MD = 3.09, 95% CI: 0.13 to 6.07). None of the agents revealed a significant alleviation of 24-h micturition frequency. In terms of safety outcomes, the incidence rate on urinary symptoms for botulinum toxin A was the only variate higher than chondroitin sulfate (MD = -2.02, 95% CI: -4.99 to 0.66) and placebo (MD = -1.60, 95% CI:-3.83 to 0.17). No significant difference was found among the other treatments. Cyclosporine A might be superior to other pharmacological treatments in efficacy. Amitriptyline and certolizumab pegol were capable of lowering the ICSI as well.

Improvement of bowel movements among people with a sedentary lifestyle after prebiotic snack supply - preliminary study.

IntroductionDietary fiber is one of the most important components of food. Fulfilling regulatory and nutritional functions for the intestinal microbiota, it appears to be an essential ingredient for people with a sedentary lifestyle.AimWe hypothesized that regular intake of a snack containing high amounts of soluble fibre in parallel to a regular diet may rapidly improve bowel habits with simultaneous elevation of synthesis of short-chain fatty acids (SCFA).Material and methodsA total of 20 healthy volunteers, with a stool frequency of less than 3 spontaneous bowel movements per week, completed a 14-day double-blind, parallel-arm, randomized clinical trial with the intervention comprising daily intake of 2 doses (9.99% per 100 g or 13.91% per 100 g) of fibre. Food consumption was evaluated via 72-hour recall diaries at baseline and after 14 days of intervention. Gastrointestinal symptoms (abdominal comfort, distension, bloating, flatulence, stomach rumbling, number of bowel movements) were monitored via the IBS/VAS scale every day.ResultsWe found that the elevated fibre intake improved bowel habits significantly (defecation frequency increased from 0.28 to 0.87 times/day; p = 0.0002) in both study arms. After 14 days of the trial, an increase in SCFA concentration (for whole study group: acetic p < 0.036, propionic p < 0.019, and butyric acid p < 0.0012 compared to baseline parameters) with no adverse gastrointestinal symptoms was reported.ConclusionsShort-term, regular intake of a snack containing soluble fibre improves the SCFA synthesis and bowel habits in healthy people living a sedentary lifestyle. The exact mechanism behind this observation requires further investigation.

MEDICAL MANAGEMENT OF THE COMPLICATIONS OF EARLY PREGNANCY WITH MISOPROSTOL

OBJECTIVE: The study’s goal was to ascertain if misoprostol is beneficial for people who have early pregnancycomplications. And to prevent these individuals from undergoing surgical evacuation.METHODOLOGY: Between 2015 and 2017, an experimental investigation was carried out at the MardanMedical Complex Hospital in Mardan at the Department of Obstetrics and Gynecology, Unit A. For misoprostoltherapy, 200 women with early pregnancy problems were included. Patients with early pregnancy problems who werehemodynamically stable and had a gestational age of fewer than 15 weeks met the inclusion criteria. Patients having ahistory of ectopic pregnancy, gestational trophoblastic illness, hemodynamic instability, uterine rupture, hypersensitivityto prostaglandin, and hemoglobin levels below 9 g were excluded. The ability to successfully resolve miscarriages withoutthe need for surgery was the primary outcome measure. Incidence of discomfort, vaginal bleeding, infection, pyrexia,and adverse gastrointestinal symptoms were secondary outcomes. The research included 200 women in total. They wereprimigravida to grand multigravida, ranging in age from 16 to 45. Thirty (15%) had an embryonic pregnancy, 88(44%) had an incomplete abortion, and 82 (41%) had an early fetal death. When misoprostol was the only medicationused for therapy, 140 (or 70%) women entirely expelled the conceptual products; nevertheless, 60 (30%) patients neededsurgery since their conceptual products had not been fully expelled and they were bleeding excessively. The average timebetween induction and expulsion was 16 hours. The most common adverse effects reported were diarrhea, vomiting,pyrexia, discomfort, and nausea. In 14 individuals, more than one side event was reported. For individuals with earlypregnancy difficulties, misoprostol is an appropriate and effective treatment for early pregnancy loss. It may be kept atroom temperature and is inexpensive and heat stable.RESULTS: The study concerned a diverse institution of women, starting from primigravida to grand multigravida,and spanning a while sixteen to 45. The distribution of pregnancy headaches covered 15% with embryonic pregnancy,44% with incomplete abortion, and 41% with early fetal demise. Out of the 2 hundred girls, one hundred forty (70%)effectively expelled the conceptual products solely through misoprostol therapy. However, 30% of sufferers requiredsurgical operation because of incomplete expulsion and excessive bleeding. The common time between misoprostolinduction and complete expulsion changed into reported as sixteen hours.The look at additionally referred to notunusual adverse consequences, such as diarrhea, vomiting, pyrexia, pain, and nausea. In some instances, a couple ofside impact became reported, affecting 14 people.CONCLUSION: The observe contributes treasured insights into the scientific management of early pregnancycomplications using misoprostol. It emphasizes the effectiveness of misoprostol in resolving miscarriages without theneed for surgery in a significant proportion of instances. The documented negative consequences, while present, shouldbe weighed towards the blessings of averting surgical processes.KEYWORDS: Misoprostol, medical treatment, miscarriage.

Is fasting still necessary prior to contrast-enhanced computed tomography? A randomized clinical study

There is very limited evidence to support the common practice of preparative fasting prior to contrast-enhanced computerized tomography (CT). This study examined the effect of withholding fasting orders, prior to contrast-enhanced CT, on the incidence of aspiration pneumonitis and adverse gastrointestinal symptoms. This randomized controlled trial enrolled hospitalized patients referred for non-emergency, contrast-enhanced CT scan to either at least 4h of fasting or to an unrestricted consumption of liquids and solids up to the time of CT. The primary outcome was incidence of aspiration pneumonitis and the secondary outcomes were rates of adverse gastrointestinal symptoms (nausea and/or vomiting). After excluding participants with incomplete follow-up, a total of 1080 participants were assigned to the fasting group and 1011 were assigned to the non-fasting group. Aspiration pneumonitis was not identified in either group. The mean time of fasting in the fasting group was 8.4±1.6h. Rates of nausea and vomiting were not statistically different between the fasting group compared with the non-fasting group, 6.6% vs. 7.6% (p = 0.37) and 2.6% vs. 3.0% (p = 0.58), respectively. A subgroup analysis of patients who were required to drink oral contrast agent (n = 1257) showed that rates of nausea and vomiting were not statistically different between the fasting and non-fasting groups, 6.8% vs. 8.0% (p = 0.42) and 2.6% vs. 3.6% (p = 0.3), respectively. Withholding fasting orders prior to contrast-enhanced CT was not associated with a greater risk of aspiration pneumonitis or a significant increase in rates of adverse gastrointestinal symptoms. ClinicalTrials.gov : NCT03533348 KEY POINTS: • Is fasting necessary prior to contrast-enhanced computed tomography (CT)? • In this randomized clinical study including 2091 participants referred to non-emergency contrast-enhanced CT scan, withholding preparative fasting was not associated with a greater risk of aspiration pneumonitis or clinically significant increase in rates of adverse gastrointestinal symptoms. • Eating and drinking prior to contrast-enhanced CT can be allowed and are not associated with an increased risk of aspiration pneumonitis.