The prevalence and severity of upper gastrointestinal complications among patients with chronic diseases: a cross-sectional study from Palestine.

BACKGROUND: Many old people have at least one chronic disease. As a result, multiple drugs should be used. Gastrointestinal complications may occur because of the harmful effects of these chronic drugs on the stomach. The study aimed to assess the prevalence of upper gastrointestinal complications in patients taking chronic medications, the severity of these symptoms, and whether they take any gastro-protective drugs or not. METHODOLOGY: This was a cross-sectional study through face-to-face questionnaires from internal outpatient clinics at a specialized hospital. Patients with chronic diseases who were taking at least one chronic medication were included in the study. Data Collection Form was used to gather information. The Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ) was used to evaluate the severity of the upper gastrointestinal symptoms. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS) version 21. RESULTS: A total of 400 patients with chronic diseases and using multiple medications were included. Among them, 53.8% were females and 56% were married, 58.5% were unemployed, 70% were not smokers, the mean age was 54.7 ± 17.5 years. The most common comorbid diseases among the patients were diabetes, hypertension, and arthritis, with percentages of 44.3%, 38%, and 27.3%, respectively. The mean number of chronic medications used was 3.36 ± 1.6 with a range of 1 to 9. The most commonly used was aspirin with a percentage of 50%, followed by atorvastatin, bisoprolol, and insulin with percentages of 29.5%, 25%, and 20.3%, respectively. Among the 400 participants, 362 (90.5%) suffered from upper gastrointestinal side effects like indigestion (65.8%), heartburn (78.3%), nausea (48.8%), and regurgitation (52.0%). Based on SF-LDQ scoring, of the 400 respondents, 235(58.8%), 109(27.3%) and 18(4.5%) suffered from mild, moderate and severe dyspepsia, respectively. A high percentage 325 (81.3%) of participants were prescribed gastro-protective medications. Proton pump inhibitors were the most prescribed group in 209 (52.3%) patients. Dyspepsia was significantly associated with older age (p-value = 0.001), being educated (p-value = 0.031), not being single (p-value < 0.001), having health insurance (p-value = 0.021), being a smoker (p-value = 0.003), and using ≥ 5 medications (p-value < 0.001). CONCLUSION: Upper gastrointestinal complications among patients with chronic diseases were very common. Fortunately, the symptoms were mild in most cases. The risk increased with age and using a higher number of medications. It is important to review patients' medications and avoid overuse of them, in addition to use gastro-protective agents when needed.

Gastrointestinal challenges in nephropathic cystinosis: clinical perspectives.

Gastrointestinal (GI) sequelae, such as vomiting, hyperacidity, dysphagia, dysmotility, and diarrhea, are nearly universal among patients with nephropathic cystinosis. These complications result from disease processes (e.g., kidney disease, cystine crystal accumulation in the GI tract) and side effects of treatments (e.g., cysteamine, immunosuppressive therapy). GI involvement can negatively impact patient well-being and jeopardize disease outcomes by compromising drug absorption and patient adherence to the strict treatment regimen required to manage cystinosis. Given improved life expectancy due to advances in kidney transplantation and the transformative impact of cystine-depleting therapy, nephrologists are increasingly focused on addressing extra-renal complications and quality of life in patients with cystinosis. However, there is a lack of clinical data and guidance to inform GI-related monitoring, interventions, and referrals by nephrologists. Various publications have examined the prevalence and pathophysiology of selected GI complications in cystinosis, but none have summarized the full picture or provided guidance based on the literature and expert experience. We aim to comprehensively review GI sequelae associated with cystinosis and its treatments and to discuss approaches for monitoring and managing these complications, including the involvement of gastroenterology and other disciplines.

A comprehensive review on potential drug-drug interactions of proton pump inhibitors with antidiabetic drugs metformin and DPP-4 inhibitors.

A drug interaction is a condition in which two or more drugs are taken at the same time. Type 2 diabetes mellitus is a significant contributor to polypharmacy. Proton pump inhibitors (PPIs) are often prescribed in combination with metformin or DPP-4 inhibitors (sitagliptin, saxagliptin, linagliptin, and alogliptin) or a combined dose of metformin and DPP-4 inhibitor to treat gastritis in diabetic patients. This review article mainly focused on evaluating the potential drug-drug interactions (DDIs) between PPIs (i.e. esomeprazole, lansoprazole, omeprazole, pantoprazole, and rabeprazole) with metformin and PPIs with DPP-4 inhibitors. The findings demonstrated the existence of pharmacokinetic and pharmacodynamic DDIs between the aforementioned PPIs with metformin and DPP-4 inhibitors, which could impact the biological activities (i.e., hypoglycemia) of these drugs. Moreover, this review suggested that esomeprazole could be the best drug in the PPI group to be prescribed simultaneously with metformin and DPP-4 inhibitors, as most of the antidiabetic drugs of this study did not show any interaction with esomeprazole. The findings of this study also revealed that both antidiabetic drugs and PPIs could have positive interactions as PPIs have the potential to lessen the gastrointestinal side effects of metformin and DPP-4 inhibitors. To achieve the greatest therapeutic impact with the fewest side effects, careful dose control of these drugs is required. So, more extensive research on both human and animal subjects are needed to ascertain the veracity of this hypothesis.

Gut Microbiota Changes during Dimethyl Fumarate Treatment in Patients with Multiple Sclerosis.

The gut microbiota is involved in the development of the immune system and can modulate the risk for immune-mediated disorders such as multiple sclerosis (MS). Dysbiosis has been demonstrated in MS patients and its restoration by disease-modifying treatments (DMTs) is hypothesized. We aimed to study the changes in gut microbiota composition during the first 6 months of treatment with dimethyl fumarate (DMF), an oral DMT, and to identify the microorganisms associated with DMF side effects. We collected and analyzed the gut microbiota of 19 MS patients at baseline and after 1, 3, and 6 months of DMF treatment. We then cross-sectionally compared gut microbiota composition according to the presence of gastrointestinal (GI) symptoms and flushing. Overall, the gut microbiota biodiversity showed no changes over the 6-month follow-up. At the genus level, DMF was associated with decreased Clostridium abundance after 6 months. In subjects reporting side effects, a higher abundance of Streptococcus, Haemophilus, Clostridium, Lachnospira, Blautia, Subdoligranulum, and Tenericutes and lower of Bacteroidetes, Barnesiella, Odoribacter, Akkermansia, and some Proteobacteria families were detected. Our results suggest that gut microbiota may be involved in therapeutic action and side effects of DMF, representing a potential target for improving disease course and DMT tolerability.

Preparation and evaluation of sublingual film of ketorolac tromethamine.

OBJECTIVE: This research aimed to formulate fast-dissolving sublingual films of Ketorolac tromethamine to improve therapeutic efficacy, patient compliance and overcome the drug's gastrointestinal side effects by avoiding direct contact with the gastric mucosa. METHODS: This research produced Ketorolac tromethamine sublingual film by solvent casting method using a variable ratio of polymer and plasticizer but a fixed quantity of other excipients and solvent ratio to evaluate the effect of these components on the overall formulation. Total 9 (F1 to F9) formulations were prepared where the ratio of Kollicoat®IR as polymer and Polyethylene glycol 400 as plasticizer were 2.0:1, 3.0:1, 4.0:1, 4.0:1, 4.8:1, 5.6:1, 5.33:1, 6.0:1, 6.66:1 respectively. The prepared films were evaluated through morphological and organoleptic properties, weight uniformity, folding endurance, surface pH, thickness, percentage of moisture loss, dispersion, dissolution, and drug content uniformity. Also, API-excipients compatibility was evaluated by FTIR spectroscopy. RESULTS: Formulation-2 (F2) demonstrated better film with optimum folding endurance where the ratio of Kollicoat®IR and Polyethylene glycol 400 was 3.0:1. The film's surface and distribution of polymers and drugs were examined by trinocular microscopic imaging where drug molecule showed uniform distribution which was supported by the assay (100.1%) and content uniformity (100.1 ± 1.97%). Performed dissolution studies showed 99.3% of drug dissolution occurred in just 3 min at pH 6.8. CONCLUSION: Prepared films were found to have thin, fast dispersion and dissolution properties. Therefore, the patients can use the sublingual film to get rapid relief of pain with minimal side effects in the gastrointestinal tract.

Tolerability of Oral Supplementation with Microencapsulated Ferric Saccharate Compared to Ferrous Sulphate in Healthy Premenopausal Woman: A Crossover, Randomized, Double-Blind Clinical Trial.

A single-center, crossover, randomized, double-blind, and controlled clinical study was conducted to assess the tolerability profile, especially with regard to gastrointestinal complaints, of oral supplementation with AB-Fortis®, a microencapsulated ferric saccharate (MFS), as compared with conventional ferrous sulphate (FS) in healthy premenopausal women. A dose of 60 mg/day of elemental iron was used. The test products were administered for 14 consecutive days with a washout period of two menstrual episodes and a minimum of one month between the two intervention periods. The subjects completed simple-to-answer questionnaires daily for 14 days during both the intervention and the washout periods, capturing the symptoms associated with oral iron supplementation and overall health aspects. Following product consumption, the incidences of symptoms, numbers of complaints/symptoms, overall intensity, and total days with symptoms were found to be significantly higher for FS consumption as compared to MFS. The better tolerability profile of MFS over FS was further substantiated when both products were compared to a real-life setting (i.e., the washout period). Overall, the administration of both study products was safe with no serious or significant adverse events reported. In summary, the current study shows the better tolerability of the MFS preparation when compared to that of the FS, presenting MFS as a well-tolerated and safe option for improving iron nutrition.

USE OF NON-STEROIDAL ANTI-INFLAMMATORY DRUGS IN PATIENTS WITH ADVANCED ACTIVE RHEUMATOID ARTHRITIS.

This study aimed to determine whether patients with active rheumatoid arthritis (RA) regularly take non-steroidal anti-inflammatory drugs (NSAIDs) and to clarify whether their decision to take NSAIDs depends on disease activity, intensity of pain, or functional status. The study also aimed to identify the risk factors for gastrointestinal side effects. Over 6 months, we conducted a cross-sectional single-center study of consecutively hospitalized patients with confirmed RA. Activities of daily living, pain intensity, and disease activity were evaluated by the Health Assessment Questionnaire, visual analog scale, and disease activity score, respectively, in 28 joints. Of 73 patients diagnosed with RA, 48 (66%) regularly took NSAIDs. Compared to non-users, NSAID users used glucocorticoids less frequently. The decision to use NSAIDs was independent of disease activity, pain intensity, degree of functional impairment, or presence of gastrointestinal risk factors. However, a higher degree of functional impairment was associated with a longer duration of continuous NSAID and glucocorticoid use. NSAIDs are still relevant for RA treatment. The decision to use them is not necessarily affected by disease activity or pain intensity, but their prolonged use is required in patients with a higher degree of functional disability. NSAIDs enable exclusion of glucocorticoid use, sparing patients of glucocorticoid-related side effects.

Secukinumab as a potential trigger of inflammatory bowel disease in ankylosing spondylitis or psoriatic arthritis patients.

OBJECTIVE: Real-world secukinumab gastrointestinal-related adverse events (GIRAE) data during treatment for AS and PsA are lacking. We aimed to obtain this through baseline evaluation of pre-existing IBD rates and predictors of GIRAE. METHODS: Patient electronic and paper records commencing secukinumab from 10 UK hospitals between 2016 and 2019 were reviewed. GIRAE after initiation were defined as: definite [objective evidence of IBD (biopsy proven), clear temporal association, resolution of symptoms on drug withdrawal, no alternative explanation felt more likely], probable (as per definite, but without biopsy confirmation) or possible (gastrointestinal symptoms not fulfilling definite or probable criteria). RESULTS: Data for all 306 patients started on secukinumab were analysed: 124 (40.5%) AS and 182 (59.5%) PsA. Twenty-four of 306 (7.8%) experienced GIRAE after starting secukinumab. Amongst patients who developed GIRAE, four (1.3%) had definite, seven (2.3%) probable and 13 (4.2%) possible IBD. All definite cases were patients with AS and stopped secukinumab; two had pre-existing IBD and two (0.7%) were de novo cases of which one required surgical intervention. Seven patients (2.3%) had pre-existing diagnoses of IBD prior to initiation, of which five patients experienced GIRAE. CONCLUSION: Absolute rates of new IBD in patients starting secukinumab are low. The majority of patients developing new GIRAE did not develop objective evidence of IBD or stop therapy. For patients with pre-existing IBD and AS the risk of GIRAE is much higher, and prescribing alternatives should be considered.

Comparative Effectiveness of Calcimimetic Agents for Secondary Hyperparathyroidism in Adults: A Systematic Review and Network Meta-analysis.

RATIONALE & OBJECTIVE: Comparative benefits and harms of calcimimetic agents used for the treatment of secondary hyperparathyroidism have not been well characterized. We sought to compare the effectiveness of 3 calcimimetic agents using published data. STUDY DESIGN: Systematic review of randomized controlled trials and network meta-analysis. SETTING & STUDY POPULATION: Adults with chronic kidney disease enrolled in a clinical trial of a calcimetic agent. SEARCH STRATEGY & SOURCES: MEDLINE, EMBASE, CENTRAL (from February 7, 2013, to November 21, 2019), and a published meta-analysis. DATA EXTRACTION: Two reviewers independently extracted the study data, assessed risk of bias, and rated evidence certainty using Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. ANALYTICAL APPROACH: Frequentist network meta-analysis was conducted. The primary review outcomes were achievement of a target reduction in serum parathyroid hormone (PTH) levels and hypocalcemia. Additional outcomes were nausea, vomiting, serious adverse events, all-cause mortality, cardiovascular mortality, heart failure, and fracture. RESULTS: 36 trials (11,247 participants) were included. All except 4 trials involved dialysis patients. Median follow-up was 26 weeks (range, 1 week to 21.2 months). Compared with placebo, calcimimetic agents had higher odds of achieving target PTH levels with high or moderate certainty. Etelcalcetide had the highest odds of achieving a PTH target compared with evocalcet (OR, 4.93; 95% CI, 1.33-18.2) and cinacalcet (OR, 2.78; 95% CI, 1.19-6.67). Etelcalcetide appeared to cause more hypocalcemia than cinacalcet and evocalcet. Cinacalcet and to a lesser extent etelcalcetide appeared to cause more nausea than placebo. Differences in risk for mortality, cardiovascular end points, or fractures across calcimimetic agents could not be discerned with sufficient certainty. LIMITATIONS: Lack of longer-term data; heterogeneous end point definitions. CONCLUSIONS: Evidence of the benefits of calcimimetic therapy is limited to short-term assessment of a putative surrogate outcome (serum PTH). Although etelcalcetide was associated with the largest reduction in PTH levels, side-effect profiles differed across the 3 calcimimetic agents, making it not possible to identify 1 preferred agent.

Ranking Self-reported Gastrointestinal Side Effects of Pharmacotherapy in Sarcoidosis.

BACKGROUND: Clinical manifestations of sarcoidosis vary widely, depending on the intensity of the inflammation and the organ systems affected. So far, no curative treatment exists; the disease can only be suppressed. All treatment options cause side effects affecting quality of life. The aim of this study was to establish and rank the prevalence of self-reported gastrointestinal side effects of drugs used in the treatment of sarcoidosis. METHODS: A cross-sectional web-based anonymous survey about complaints and side effects was conducted among sarcoidosis patients in the Netherlands, United Kingdom, and United States of America. RESULTS: Of the participants, 70% were being treated with one or more drugs. The most important reported side effect was weight gain, associated with increased appetite among prednisone users (as monotherapy as well as in combination with other drugs). Methotrexate (MTX) users especially experienced nausea, with monotherapy as well as combination therapy. Vomiting and weight loss were most prominent among azathioprine and mycophenolate mofetil (MMF) users, whereas diarrhoea was frequently mentioned by MMF and MTX users. The reported side effects of hydroxychloroquine were generally rather mild. CONCLUSION: The current study ranked the gastrointestinal side effects associated with pharmacotherapy in sarcoidosis patients. Pharmacotherapy does have multiple gastrointestinal side effects. The strongest association between a reported side effect and drug use was that of weight gain associated with increased appetite among prednisone users. It would therefore be useful for future research to look further into dietary interventions to counter these side effects and reduce their burden.

The Effectiveness of Daily and Alternate Day Oral Iron Supplementation in Athletes With Suboptimal Iron Status (Part 2).

The authors compared the effectiveness of daily (DAY) versus alternate day (ALT) oral iron supplementation in athletes with suboptimal iron. Endurance-trained runners (nine males and 22 females), with serum ferritin (sFer) concentrations <50 µg/L, supplemented with oral iron either DAY or ALT for 8 weeks. Serum ferritin was measured at baseline and at fortnightly intervals. Hemoglobin mass (Hbmass) was measured pre- and postintervention in a participant subset (n = 10). Linear mixed-effects models were used to assess the effectiveness of the two strategies on sFer and Hbmass. There were no sFer treatment (p = .928) or interaction (p = .877) effects; however, sFer did increase (19.7 µg/L; p < .001) over the 8-week intervention in both groups. In addition, sFer was 21.2 µg/L higher (p < .001) in males than females. No Hbmass treatment (p = .146) or interaction (p = .249) effects existed; however, a significant effect for sex indicated that Hbmass was 140.85 g higher (p = .004) in males compared with females. Training load (p = .001) and dietary iron intake (p = .015) also affected Hbmass. Finally, there were six complaints of severe gastrointestinal side effects in DAY, but only one in ALT. In summary, both supplement strategies increased sFer in athletes with suboptimal iron status; however, the ALT approach was associated with lower incidence of gastrointestinal upset.

The Effectiveness of Transdermal Iron Patches in Athletes With Suboptimal Iron Status (Part 1).

The authors compared the effectiveness of two modes of daily iron supplementation in athletes with suboptimal iron stores: oral iron (PILL) versus transdermal iron (PATCH). Endurance-trained runners (nine males and 20 females), with serum ferritin concentrations <50 µg/L, supplemented with oral iron or iron patches for 8 weeks, in a parallel group study design. Serum ferritin was measured at baseline and fortnightly intervals. Hemoglobin mass and maximal oxygen consumption (V˙O2max) were measured preintervention and postintervention in PATCH. A linear mixed effects model was used to assess the effectiveness of each mode of supplementation on sFer. A repeated-measures analysis of variance was used to assess hemoglobin mass and V˙O2max outcomes in PATCH. There was a significant time effect (p < .001), sex effect (p = .013), and Time × Group interaction (p = .009) for sFer. At Week 6, PILL had significantly greater sFer compared with PATCH (15.27 µg/L greater in PILL; p = .019). Serum ferritin was 15.53 µg/L greater overall in males compared with females (p = .013). There were no significant differences in hemoglobin mass (p = .727) or V˙O2max (p = .929) preintervention to postintervention in PATCH. Finally, there were six complaints of severe gastrointestinal side effects in PILL and none in PATCH. Therefore, this study concluded that PILL effectively increased sFer in athletes with suboptimal iron stores, whereas PATCH showed no beneficial effects.

Platinum-based chemotherapy: gastrointestinal immunomodulation and enteric nervous system toxicity.

The efficacy of chemotherapeutic treatment of colorectal cancer is challenged by severe gastrointestinal side effects, which include nausea, vomiting, constipation, and diarrhea. These symptoms can persist long after the treatment has been ceased. An emerging concept is the ability of platinum-based drugs to stimulate immunity, which is in contrast to conventional chemotherapeutic agents that are immunosuppressive. Here, we review the immunomodulatory aspects of platinum-based anticancer chemotherapeutics and their impact on gastrointestinal innervation. Given the bidirectional communication between the enteric nervous system and gastrointestinal immune system; exploring the consequences of platinum-induced immunogenicity will facilitate better understanding of gut dysfunction caused by chemotherapeutic agents. We propose that the development of future successful chemotherapeutics should rely on targeting the mechanisms underlying long-term gastrointestinal side effects.

Effectiveness of interventions by community pharmacists to reduce risk of gastrointestinal side effects in nonselective nonsteroidal anti-inflammatory drug users.

PURPOSE: Upper gastrointestinal (UGI) complications in elderly users of nonselective nonsteroidal anti-inflammatory drugs (ns-NSAIDs) without concomitant use of gastroprotective agents (GPAs) were a leading cause of potentially avoidable drug-related hospital admissions in the Netherlands. We aimed to determine the effectiveness of community pharmacists' interventions to improve safety in ns-NSAID use in patients at UGI risk. METHODS: In this prospective cohort study, pharmacists in participating pharmacies (intervention group, IG) received feedback on drug dispensing in ns-NSAID users of ≥60 years of age at risk for UGI damage and were instructed to select patients to improve ns-NSAID prescribing, in collaboration with primary care physicians. Ns-NSAID users from other pharmacies without concomitant GPA use were followed in parallel as a control group (CG). Changes in the UGI risk of ns-NSAID users between baseline and follow-up measurement, assessed either by the addition of GPAs or the cessation of ns-NSAIDs, were compared between the two study arms. RESULTS: At baseline, 14% of ns-NSAID users at UGI risk did not receive GPAs. Persistent ns-NSAID users from the selected IG patients had an additional 7% likelihood of reduced UGI risk at follow-up (odds ratio 0.93, 95% confidence interval 0.89-0.97) compared with CG patients. In the IG, 91% of selected IG patients at UGI risk from ns-NSAIDs at baseline were no longer at increased risk at follow-up because of cessation of ns-NSAIDS or to concomitant GPA use. CONCLUSION: Although concomitant gastroprotection use in susceptible ns-NSAID users in the Netherlands is high, pharmacist-led interventions could further improve prescribing of ns-NSAIDs.

Effectiveness of indomethacin in preventing Heterotopic Ossification: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Heterotopic ossification (HO) is a frequent complication of joint trauma or surgery, commonly occurring after hip replacements, acetabular or other joint injuries, or surgeries. Indomethacin has long been used to prevent HO and is considered the first-line therapy. However, its effectiveness and necessity for HO prevention are still debated due to mixed evidence about its efficacy and potential side effects. METHODS: Following PRISMA guidelines, this systematic review and meta-analysis evaluated randomized controlled trials using the PICO framework. Searches were conducted across PubMed, Embase, Cochrane Library, and Web of Science. Data were extracted and assessed based on the evidence levels of the selected articles. This study was registered with the International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY). RESULTS: This analysis included 665 patients, with 347 in the Indomethacin group and 318 in the No Indomethacin group. The outcomes analyzed-HO, Gastrointestinal Side Effects, and Bone Ununion-indicated that indomethacin effectively prevents HO. The meta-analysis revealed that the Indomethacin group experienced a significant reduction in the occurrence of grade I-II HO compared to the No Indomethacin group, but not for grade III-IV HO. Gastrointestinal side effects were notably higher in the Indomethacin group. The incidence of bone nonunion was higher in the Indomethacin group, although not statistically significant. CONCLUSIONS: The meta-analysis suggests that indomethacin is effective in preventing HO, particularly for Brooker grade I-II, rather than Brooker grade III-IV. Special attention should be given to gastrointestinal complications when using indomethacin. Further prospective randomized controlled studies are required to confirm these findings.

Alternate day versus consecutive day oral iron supplementation in iron-depleted women: a randomized double-blind placebo-controlled study.

Background: Guidelines to treat iron deficiency recommend daily provision of oral iron, but this may decrease fractional iron absorption and increase side effects. Our objective was to compare consecutive-day versus alternate-day iron supplementation. Methods: In a double-masked, randomized, placebo-controlled trial, young Swiss women (n = 150; serum ferritin ≤30 µg/L) were assigned to: daily 100 mg iron for 90 d, followed by daily placebo for another 90 d (consecutive-day group) or the same daily dose of iron and placebo on alternate days for 180 d (alternate-day group). The study period was 24/11/2021-10/8/2022. Co-primary outcomes, at equal total iron doses, were serum ferritin and gastrointestinal side effects; secondary outcomes were iron deficiency and serum hepcidin. Compliance and side effects were recorded daily using a mobile application. Data were analysed using mixed models and longitudinal prevalence ratios (LPR). The trial was registered at ClinicalTrials.gov (NCT05105438). Findings: 75 women were assigned to each group and included in the intention-to-treat analysis. Capsule adherence and side effect reporting was >97% in both groups. At equal total iron doses, comparing consecutive-day and alternate-day groups, median serum ferritin was 43.8 µg/L (31.7-58.2) versus 44.8 µg/L (33.8-53.6) (P = 0.98), the LPR for gastrointestinal side effects on days of iron intake was 1.56 (95% CI: 1.38, 1.77; P < 0.0001), and median serum hepcidin was 3.0 nM (IQR 2.0-5.0) versus 1.9 nM (1.4-2.9) (P < 0.0001). Iron deficiency prevalence after 3 months was 5.5% versus 4.3% (P = 0.74) and after 6 months was 11.4% and 3.0% (P = 0.049). Interpretation: At equal total iron doses, compared to consecutive day dosing of iron, alternate day dosing did not result in higher serum ferritin but reduced iron deficiency at 6 months and triggered fewer gastrointestinal side effects. Funding: Swiss National Science Foundation, Bern, Switzerland.

Factors associated with gastrointestinal side effects after liraglutide treatment for type 2 diabetes.

Aim: To identify risk factors predictive of or associated with gastrointestinal side effects (GISE) of liraglutide in patients with type 2 diabetes (T2DM). Methods: T2DM patients treated with liraglutide for the first time were obtained and grouped into patients without GSEA and patients with GSEA. Baseline variables, including age, sex, body mass index (BMI), glycemia profiles, alanine aminotransferase, serum creatinine, thyroid hormones, oral hypoglycemic drugs and history of gastrointestinal diseases, were tested for possible associations with GSEA outcome. Significant variables were entered into univariate and multivariate logistic regression (forward LR) analyses. Receiver operating characteristic (ROC) curves to determine clinically useful cutoff values. Results: A total of 254 patients (95 female) were included in this study. 74 cases (29.13%) reported GSEA and 11 cases (4.33%) discontinued treatment. The results of univariate analyses showed that sex, age, thyroid stimulating hormone (TSH), free triiodothyronine, α-glucosidase inhibitor (AGI), and concomitant gastrointestinal diseases were associated with GSEA occurrence (all p <0.05). In the final regression model, AGI use (adjusted OR=4.01, 95%CI: 1.90-8.45, p<0.001), gastrointestinal diseases (adjusted OR=3.29, 95%CI: 1.51-7.18, p=0.003), TSH (adjusted OR=1.79, 95%CI: 1.28-2.50, p=0.001) and male sex (adjusted OR=0.19, 95%CI: 0.10-0.37, p<0.001) were independently associated with GSEA. Furthermore, ROC curve analysis confirmed that TSH values of 1.33 and 2.30 in females and males, respectively, were useful thresholds for predicting GSEA. Conclusion: This study suggests that the combination of AGI, concomitant gastrointestinal diseases, female sex and higher TSH levels are independent risk factors of GSEA of liraglutide treatment in patients with T2DM. Further research is warranted to elucidate these interactions.

Real-World Analysis Affirms the High Persistence and Adherence Observed with Diroximel Fumarate in Patients with Multiple Sclerosis.

INTRODUCTION: Adherence to disease-modifying therapies is key for achieving optimal outcomes in multiple sclerosis (MS). Diroximel fumarate (DRF) is an oral fumarate approved for treatment of relapsing forms of MS. It has the same pharmacologically active metabolite as dimethyl fumarate (DMF) and similar efficacy and safety profiles, but with demonstrated fewer gastrointestinal (GI) related adverse events (AEs). There are limited data characterizing persistence and adherence to DRF in the real world. METHODS: This retrospective analysis of the AcariaHealth Specialty Pharmacy Program included patients with MS initiating DRF from 1 December 2019 to 30 January 2021. This analysis evaluated persistence, measured as proportion of patients remaining on therapy; discontinuation rate due to GI AEs; and adherence measured by proportion of days covered (PDC). RESULTS: Overall, 1143 patients were included; 433 (37.9%) patients had been treated with prior DMF and switched to DRF. Persistence was high in both groups: the estimated proportion of patients remaining on DRF at 16 months was 82.3% [95% confidence internal (CI) 77.2-86.3%], and 90.1% (95% CI 82.2-94.6%) in the DMF to DRF group. Fifty-two (4.5%) patients overall and 15 (3.5%) in the DMF switch subgroup discontinued DRF due to GI AEs. Mean PDC was 90.8% (95% CI 89.2-92.5%), and 85.4% (95% CI 83.3-87.4%) of patients achieved PDC ≥ 80% in the overall population. In the DMF to DRF group, mean PDC was 90.7% (95% CI 88.0-93.5%), and 84.8% (95% CI 81.4-88.1%) of patients achieved PDC ≥ 80%. CONCLUSION: In this analysis of  > 1000 patients treated with DRF in real-world clinical practice, overall persistence at 16 months was high, treatment discontinuation due to GI AEs was low, and patients were highly adherent to therapy. Of 433 patients who switched from DMF to DRF, most (> 90%) were able to tolerate and persist on DRF after switching. Graphical abstract available for this article.

Simotang Alleviates the Gastrointestinal Side Effects of Chemotherapy by Altering Gut Microbiota.

Simotang oral liquid (SMT) is a traditional Chinese medicine (TCM) consisting of four natural plants and is used to alleviate gastrointestinal side effects after chemotherapy and functional dyspepsia (FD). However, the mechanism by which SMT helps cure these gastrointestinal diseases is still unknown. Here, we discovered that SMT could alleviate gastrointestinal side effects after chemotherapy by altering gut microbiota. C57BL/6J mice were treated with cisplatin (DDP) and SMT, and biological samples were collected. Pathological changes in the small intestine were observed, and the intestinal injury score was assessed. The expression levels of the inflammatory factors IL-1ß and IL-6 and the adhesive factors Occludin and ZO-1 in mouse blood or small intestine tissue were also detected. Moreover, the gut microbiota was analyzed by high-throughput sequencing of 16S rRNA amplicons. SMT was found to effectively reduce gastrointestinal mucositis after DDP injection, which lowered inflammation and tightened the intestinal epithelial cells. Gut microbiota analysis showed that the abundance of the anti-inflammatory microbiota was downregulated and that the inflammatory microbiota was upregulated in DDP-treated mice. SMT upregulated anti-inflammatory and anticancer microbiota abundance, while the inflammatory microbiota was downregulated. An antibiotic cocktail (ABX) was also used to delete mice gut microbiota to test the importance of gut microbiota, and we found that SMT could not alleviate gastrointestinal mucositis after DDP injection, showing that gut microbiota might be an important mediator of SMT treatment. Our study provides evidence that SMT might moderate gastrointestinal mucositis after chemotherapy by altering gut microbiota.

Comparing the effect of acupressure and ginger on chemotherapy gastrointestinal side-effects in children with leukemia.

The biosocial data of 90 children with acute lymphoblastic leukemia, were collected along with assessment of gastrointestinal side-effects of chemotherapy using visual analogue scale. Ginger lozenges has more effect than acupressure in alleviating nausea and vomiting. Acupressure alleviate the nausea best in the group aged 13-15 years. Ginger helped more the other two groups (7-12 years, 69 % of the group didn't suffer from nausea), versus 50 % aged 13-15). Both acupressure and ginger affected girls more than boys in alleviating nausea. The acupressure effect on vomiting incidence didn't differ in both males and males, whilst ginger helped the males more.