Gastrointestinal Effects Research Articles

Prevalence and Predictors of Adverse Events Associated With Dipeptidyl Peptidase-4 (DPP-4) Inhibitors in Type 2 Diabetic Patients: A Cross-sectional Study.

Dipeptidyl peptidase-4 (DPP-4) inhibitors are oral hypoglycemic agents widely prescribed in India despite safety concerns. However, studies focused on their safety profile are scarce, especially in South India. To evaluate the prevalence and predictors of adverse events (AEs) with DPP-4 inhibitors in patients with type 2 diabetes mellitus (T2DM). This retrospective cross-sectional study analyzed data from medical records of T2DM patients prescribed DPP-4 inhibitors admitted to the medicine department from 2019 to 2021 at a South Indian tertiary care hospital. The causality of AEs was assessed using the WHO-Uppsala Monitoring Centre (WHO-UMC) criteria and the Naranjo scale, and severity using the Modified Hartwig and Seigel scale. We applied a Generalized model with a binary response and logit-link function to understand the factors that best explain the AE. The best-fit models were chosen based on least Akaike's information criterion and highest PseudoR 2 and presented the odds ratio (OR) with a 95% confidence interval. The analyses were performed in R software version 4.2.1. Among the 796 patients included in the study, 26% experienced AEs. A total of 212 AEs were observed, and Saxagliptin-associated AEs were the most prevalent (66.6%). Hepatic AEs were predominant (37.7%), followed by gastrointestinal events (16.5%) and electrolyte imbalances (12.3%). Most AEs were possible based on WHO-UMC criteria (78.7%) and the Naranjo scale (86.7%), with 58% being of moderate severity and 42% mild. In the multivariate analysis, aspartate transaminase [OR: 1.013 (0.006-1.020)], alkaline phosphatase [OR: 1.004 (1.001-1.007)] and patients already on DPP-4 inhibitors [OR 1.191(1.012-1.366)] were significant predictors for AEs with DPP-4 inhibitors. The study highlighted a high prevalence of AEs with DPP-4 inhibitors and identified significant predictors of these AEs. These findings underscore the necessity of vigilant monitoring and risk assessment while prescribing DPP-4 inhibitors to the Indian population.

Nose to brain delivery of flurbiprofen from a solid lipid nanoparticles-based thermosensitive in-situ gel.

Flurbiprofen, a non-steroidal anti-inflammatory drug (NSAID), has selective amyloid-lowering characteristics and can be utilized for Alzheimer's disease treatment. Oral flurbiprofen has poor brain bioavailability and high dose-related gastrointestinal adverse effects. To overcome these issues, the study aimed to formulate intranasal flurbiprofen solid lipid nanoparticles (SLN) based thermosensitive in-situ gel. SLN were formulated by the High-speed homogenization method. A 23 factorial design technique was utilized for optimization, wherein the influence of two independent variables, critical process parameters (X1 = surfactant concentration, X2 = D:L ratio) on critical quality attributes (Y1 = particle size, Y2=Percent Drug Loading, Y3=Percent Entrapment Efficiency) was ascertained at three distinct levels. The optimized SLN were then prepared into an SLN-based intranasal thermosensitive in-situ gel with Poloxamer 188 P (1.2% w/v) and Poloxamer 407 P (18% w/v). The in-vitro flurbiprofen release study demonstrated a 100% release of flurbiprofen from the SLN-based thermosensitive in-situ gel at 6 h. The ex-vivo flurbiprofen release study revealed a complete release of flurbiprofen from the SLN-based thermosensitive in-situ gel at 8 h. In the in-vivo tests, the in-situ gel (2 mg/kg) administered intranasally in rats demonstrated nearly three times greater brain bioavailability (Cmax = 490.3 ng/ml) than the oral marketed formulation of flurbiprofen, Ansaid® (10 mg/kg) (Cmax = 145.1 ng/ml). The plasma concentration obtained with intranasal in-situ gel (Cmax = 2.5 μg/ml) was lower than the oral marketed formulation (Cmax = 3.4 μg/ml). The time necessary to establish the maximal flurbiprofen concentration (Tmax) in the brain was 2 and 0.5 h for oral and intranasal formulations, respectively. Hence, the intranasal formulation could achieve maximal drug concentration in the brain in less time. Thus, flurbiprofen SLN-based thermosensitive in-situ gel can be a potential encouraging safe, non-invasive, and efficacious replacement to oral formulations for achieving direct brain targeting through nose-to-brain drug delivery, thereby treating neuroinflammatory conditions like Alzheimer's disease.

Comprehensive analysis of nationwide anticancer drug-related complications in Korea: incidence, types, and cancer-specific considerations in contemporary oncology.

The rising global incidence of cancer has increased the demand for chemotherapy, which is a crucial treatment modality. Recent advancements in cancer treatment, including targeted agents and immunotherapy, have introduced complications owing to their specific mechanisms. However, comprehensive studies of the combined complications of these approaches are lacking. This study aimed to comprehensively assess and analyze the overall incidence of anticancer drug-related complications in a nationwide patient cohort, utilizing a customized National Health Insurance Sharing Service database in Korea. Retrospective cohort study. We included patients who were prescribed anticancer drugs (excluding endocrine agents) and diagnosed with cancer. For the type of cancer classification, the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) was used and anticancer drugs were classified based on the Anatomical Therapeutic Chemical code. We classified cancer into 18 types based on the ICD-10 code and delineated cancer-related complications into 12 categories. Complications included hematological, gastrointestinal, infectious, cardiovascular, major bleeding, endocrine, neurotoxic, nephrotoxic, dermatological, pulmonary, musculoskeletal, and hepatotoxic effects. We included 294,544 patients diagnosed with cancer and administered anticancer drugs between 2016 and 2018, with follow-up continuing until 2021. We identified 486,929 anticancer drug-related complications, with an incidence of 1843.6 per 1000 person-years (PY). Anemia was the most common complication, with a rate of 763.7 per 1000 PY, followed by febrile neutropenia (295.7) and nausea/vomiting (246.9). Several complications peaked during the first months following the initiation of anticancer drug therapy; however, herpes, skin infection, heart failure, and peripheral neuropathy peaked at 6-12 months. Among major cancers, breast cancer had the lowest overall incidence of complications. Targeted therapies revealed lower complication rates than cytotoxic chemotherapy; however, they also required careful monitoring of rash. This study highlights the importance of the proactive management of anticancer drug-related complications for patient care improvement.

Treatment of mammary gland tumors in bitches: effects of sodium dichloroacetate as neoadjuvant therapy.

Mastectomy is the standard treatment for mammary gland tumors in dogs. In addition to traditional therapy, sodium dichloroacetate (DCA) can act as target therapy, as it may promote autophagy, reduce metastatic potential, and tumor proliferation in mammary tumor cell lines. This study aimed to analyze the effects of DCA as preoperative therapy for mammary tumors in bitches. Nineteen animals were selected, and they received DCA at a dose of 10 mg/kg orally every 12 hr, for 15 days. The periodic evaluation included hematological analysis (complete blood count and biochemical markers), evaluation of gastrointestinal adverse effects, evaluation of tumor volume, histopathological analysis, and immunohistochemical evaluation (Ki67 and cyclooxygenase-2/COX-2 markers). After treatment, there was a significant reduction in hematocrit (P=0.02) and leukocyte (P=0.04) means. Despite the variations for these two hematological parameters, the means remained within the reference range for the species. There were two cases of vomiting and one case of diarrhea. Most cases were classified as carcinoma in mixed tumor (n=7, 36.8%), followed by solid carcinoma (n=6, 31.6%). Nine cases (47.4%) showed reduced tumor volume, nine (47.4%) had stable disease, and one showed progressive disease. While there was no sample with a COX-2 score higher than 6, tumor samples with COX-2 scores 3 and 4 were significantly associated with stable disease or progression. DCA preoperative treatment for bitches with mammary gland tumors showed safety and potential cytoreduction in some cases.

Advances in the study of metal-organic frameworks and their biomolecule composites for osteoporosis therapeutic applications.

With the population aging, osteoporosis (OP) is becoming more and more common, seriously affecting patients' quality of life and their families, and how to prevent and treat osteoporosis has become a hot topic. However, the current conventional method of treating OP is oral anti-osteoporosis medication, which has drawbacks such as first-pass elimination and gastrointestinal adverse effects. At the same time, osteoporosis can lead to microbial infections and the need to promote angiogenesis for bone healing, among other needs that often cannot be met with conventional treatments, and there is a risk of resistance to oral antibiotics for microbial infections. Metal-organic frameworks (MOFs) having a high specific surface area, high porosity, controlled degradation, and variable composition; they can not only be used as a carrier to control drug release, but can also play multiple roles in the treatment of OP and microbial infections by releasing metal ions, etc., so they have inherent advantages for OP, which is a disease that requires long-term treatment. Therefore, this paper reviews the research progress of MOFs and their biomacromolecular composites in therapeutic applications for osteoporosis, categorized by MOF type, and briefly describes the mechanism of osteoporosis, and different synthesis methods of MOFs and MOF-based composites, and finally presents the main existing problems and future perspectives, aiming to make MOFs more helpful for OP treatment.

Synthesis and elucidation of strained galactopyronose esters as selective cyclooxygenase-2 inhibitor: a comprehensive computational approach.

Cyclooxygenase-2 (COX-2) is critically implicated in various pathologies, including inflammation, cancer, disorders involving the nervous system, and multidrug resistance. In both academic and pharmaceutical research, the development of COX-2 selective drugs as anti-inflammatory and anti-tumor therapeutics is a key focus. Traditional nonsteroidal anti-inflammatory drugs (NSAIDs) have ulcerogenic, gastrointestinal adverse effects, and myocardial infarction risk, which resulted in their limited applications. In response to this challenge, we synthesized a series of glycoconjugates featuring six-membered sugar rings and acyl chains of varying lengths attached at the C-6 position. Using molecular docking techniques, we identified galactose esters with optimal acyl chain lengths that selectively and effectively bind to the active site of COX-2 over COX-1. These compounds exhibited enhanced binding affinity and superior inhibition constants (pK i) for COX-2, thereby offering selective inhibition with potentially reduced ulcerogenic risks, as COX-1 inhibition is thought to contribute to these side effects. The molecular docking study identified two potential compounds, G6 and G8, which were validated via MD simulation for the assessment of their stability and were compared to the complex of the standard drugs, aspirin and rofecoxib. In addition, compound structures were optimized using the DFT method under the B3LYP/6-31+g(d,p) basis set to study their physio-spectral properties, frontier molecular orbitals (HOMO-LUMO), and their energy gap that correlates to their reactivity and stability. ADMET, drug-likeness, and PASS analyses were also carried out to assess their drug-ability and toxicity profiling.

Exploring the Potential of Ribes nigrum L., Aronia melanocarpa (Michx.) Elliott, and Sambucus nigra L. Fruit Polyphenol-Rich Composition and Metformin Synergy in Type 2 Diabetes Management.

Type 2 diabetes, characterized by insulin resistance and impaired glucose homeostasis, is commonly managed through lifestyle interventions and medications such as metformin. Although metformin is generally well-tolerated, it may cause gastrointestinal adverse effects and, in rare cases, precipitate lactic acidosis, necessitating cautious use in individuals with renal dysfunction. Additionally, concerns regarding its impact on hepatic function have led to its discontinuation in cirrhotic patients. This study explores the potential synergistic benefits of a polyphenol-rich blend containing black currant, chokeberry, and black elderberry extracts alongside metformin in managing type 2 diabetes. In vitro results highlighted distinct effects of AMPK pathway modulation, showcasing reductions in cholesterol and triglyceride levels alongside a notable enhancement in glucose uptake. The blend, when combined with metformin, significantly reduced insulin levels and fasting glucose concentrations in an in vivo model. Furthermore, hepatic analyses unveiled a modulation in cellular pathways, suggesting a potential influence on lipid metabolism, attenuation of inflammatory pathways, a decrease in cellular stress response, and antioxidant defense mechanisms, collectively implying a potential reduction in liver fat accumulation. The findings suggest a potential complementary role of polyphenols in enhancing the efficacy of metformin, possibly allowing for reduced metformin dosage and mitigating its side effects. Further clinical studies are warranted to validate these findings and establish the safety and efficacy of this nutraceutical approach in managing type 2 diabetes.

Paranoid psychosis after a single parenteral dose of indomethacin administered for headache diagnosis: A case and review of the literature

Background: Indomethacin is a non-steroidal anti-inflammatory used to diagnose and treat hemicrania continua and paroxysmal hemicrania. Treatment can be complicated by gastrointestinal adverse effects; less commonly reported are idiosyncratic neuropsychiatric adverse effects with indomethacin. Methods: A 50-year-old male with lateralized brief attacks of headache associated with cranial autonomic symptoms was administered a single 200 mg dose of intramuscular indomethacin. Within an hour, he developed acute psychosis, with paranoid delusions and verbal and physical aggression lasting 5 h, followed by recovery to baseline. We used search terms “indomethacin psychosis,” “indomethacin psychiatric,” “indomethacin side effects,” “non-steroidal anti-inflammatory psychosis,” and “non-steroidal anti-inflammatory psychiatric” within PubMed to identify previous reports and literature in this area. Results: Neuropsychiatric adverse effects of indomethacin have been reported since 1965 in a dose-dependent manner, usually with oral courses. They may be more common in the elderly, postpartum women and postoperative patients. Conclusion: Neuropsychiatric adverse effects should be considered in headache medicine, particularly in at-risk groups when indomethacin is administered. Patients, particularly those at highest risk, should be counseled about the risk of neuropsychiatric side effects on indomethacin which may be dose-dependent and are generally reversible on stopping the drug.

Efficacy and safety of enteral nutrition in prone position among critically ill ventilated patients: a meta-analysis.

Prone positioning in critical care units may reduce mortality in specific patients who have been admitted with severe conditions. The current meta-analysis aims to assess the impact of prone compared to supine position besides the safety and tolerability of different enteral feeding techniques in critically ill patients regarding mortality, pneumonia, aspiration, and vomiting. A systematic literature search found 25 relevant trials involving 1984 participants at the start of the study. Statistical analysis using the dichotomous analysis methods was used within the fixed model to calculate the odds ratio (OR) with 95% confidence intervals (CIs). In comparison with the post-pyloric nutrition group, gastric feeding had no significant impact on the mortality rate (OR = 1; 95% CI: 0.76-1.32). While the findings showed a significantly higher incidence of pneumonia with gastric feeding compared with post-pyloric nutrition (OR = 1.92; 95% CI: 1.43--2.57), there was no significant difference regarding pulmonary aspiration and vomiting (OR = 1.41; 95% CI: 0.75-2.65 and OR = 0.92; 95% CI:, 0.66-1.27, respectively). Reflux gastric content was significantly higher with gastric nutrition (OR = 8.23; 95% CI: 2.43-27.89). From reduced gastrointestinal events to significantly higher vomiting rates, prone position during enteral feeding showed mixed effects. Post-pyloric feeding is more tolerated and safer compared with gastric feeding. The mortality rate is not significantly different between techniques.

Analgesic Efficacy of Selective COX -2 Inhibitors in Post Endodontic Pain: A Systematic Review

Background: Endodontic treatment is considered a harrowing experience for patients in dental practice. COX-2 is a prime agent in inflammation and cell growth due to its relation with pro- inflammatory cytokines. Non -steroidal anti-inflammatory drugs are the most suited for treatment of post endodontic pain owing to their anti-inflammatory properties with the avoidance of cumbersome side effects such as nausea, vomiting, and respiratory problems associated with opioids. Aim: To assess the clinical efficacy of selective COX -2 inhibitors in comparison with other analgesics for managing postendodontic pain. Methods: This is an updated systematic review of studies between 2000 and 2023. Google Scholar, Web of science, Cochrane and PubMed databases were used to explore studies regarding our subject. The keywords included “selective COX-2 inhibitors; selective non- steroidal anti-inflammatory drug; endodontic pain; meloxicam; etoricoxib; metabolic complications” and were used in various combinations. In addition, original research reporting the clinical efficacy of selective COX -2 inhibitors in managing endodontic pain was evaluated. Full-text publications served as the inclusion criterion. Results: Among 100 articles were obtained, only nine met the inclusion criteria. All the studies were double-blinded randomized clinical trials. The study population was comprised of 1645 patients with endodontic pain. Conclusion: Selective COX -2 Inhibitors was an effective choice in managing endodontic pain. Celebrex was more effective than Celecoxib in relieving post-endodontic pain. When comparing Ibuprofen and Celecoxib, both were equally effective in relieving post-endodontic pain. Celecoxib was more effective than Naproxen in treating post-endodontic pain with minor gastrointestinal effects. Furthermore, etoricoxib considerably reduces post-endodontic pain with a single dosage.

Эффективность и безопасность использования метформина у больных с сахарным диабетом, развившимся на фоне панкреатита

Pancreatogenic diabetes mellitus (DM-P) is a topical multidisciplinary problem, many aspects of which need further research. The purpose is to study the efficacy and safety of metformin as a component of hypoglycemic therapy in patients with DM–P in prospective follow-up. Material and methods. The study included 81 patients with DM-P aged 54.7 (9.3) years, with a history of pancreatic lesions from 5 months to 4.5 years. In group A (n = 37), insulin preparations were used as hypoglycemic agents, in group B (n = 44) metformin (at HbA1c levels > 8% and fasting glycemia > 10 mmol/l insulin preparations were added to it). The follow-up was 10.6 (2.7) months. Results. Initially, hypoglycemic treatment as metformin monotherapy was prescribed to 43.1% patients of group B, that insured adequate glycemic control in 27.3% of cases. During treatment, the average HbA1c levels decreased in group A from 9.8 (1.9) % to 8.6 (1.6) %, in group B — from 9.4 (1.8) % to 8.1 (1.4) %, respectively, p < 0.05. In group B, the proportion of people who achieved the target levels of HbA1c was significantly higher (61.3%) than in group A (35.1%), p < 0.05. The addition of metformin to insulin preparations in group B allowed reducing the insulin dose by ≥ 20% in 36% of patients. The treatment tolerability in both groups was satisfactory. The development of episodes of grade 1–2 hypoglycemia was noted in 20 (54.0%) and 18 (40.9%) patients in groups A and B; grade 3 — in 6 (16.2%) and 6 (13.6%), respectively, p > 0.05. The development of gastrointestinal effects of metformin was noted in 29.5% of patients and was transient. Conclusions. The use of metformin in DM-P as monotherapy or in combination with insulin preparations was satisfactorily tolerated, contributed to improved glycemic control, allowed reducing insulin doses, and was associated with a decrease of pancreatitis recurrence.

Moderate physical exercise and ATP modulate the P2X7 receptor and improve cisplatin-induced gastric emptying delay in rats.

Patients undergoing chemotherapy with cisplatin commonly present gastrointestinal effects such as constipation and gastric emptying (GE) delay. Both the purinergic system and physical exercise modulate the gastrointestinal (GI) tract. In the current study, we investigated the role of ATP, physical exercise, and P2X7 receptor blocking on GE delay induced by cisplatin in rats. Male rats were divided into the following groups: control (C), cisplatin (Cis), exercise (Ex), Brilliant Blue G (BBG), ATP, Cis+Ex, Cis+ATP, Cis+BBG, Cis+Ex+BBG, Cis+Ex+BBG+ATP, and Cis+ATP+BBG. GE delay was induced by treatment with 1 mg/kg cisplatin (1 time/week for 5 weeks, ip). The moderate physical exercise was swimming (1 h/day, 5 days/week for 5 weeks). At the end of the treatment or exercise and 30 min before the GE assessment, some groups received BBG (50 mg/kg, sc) or ATP (2 mg/kg, sc). Then, GE was assessed after a 10-min postprandial period. Chronic use of Cis decreased GE delay (P<0.05) compared to the control group. Both exercise and ATP prevented (P<0.05) GE delay compared to Cis. The pretreatment with BBG significantly inhibited (P<0.05) the effect of exercise and ATP. On the other hand, the association between exercise and ATP reversed (P<0.05) the effect of the BBG and prevented GE delay. Therefore, we suggest that both exercise and treatment with ATP activate P2X7 receptors and prevent GE delay induced by cisplatin in rats.

Efficacy and Safety of Colchicine for the Prevention of Postoperative Atrial Fibrillation Among Patients Undergoing Major Cardiothoracic Surgery: A Meta-analysis and Meta-regression of Randomized Controlled Trials.

The role of colchicine for the prevention of postoperative atrial fibrillation (POAF) after cardiothoracic surgery is not well-established. We aimed to evaluate its potential in preventing POAF using data from randomized controlled trials (RCTs). A literature search was performed to identify studies reporting POAF as an outcome after cardiac or thoracic surgery in adult patients randomized to either colchicine or placebo. Primary outcome measured was incidence of POAF. Secondary outcomes included gastrointestinal (GI) adverse effects, sepsis, and length of stay. Subgroup analyses based on treatment durations and type of surgery were also performed, as well as regression analyses to control for covariates. We identified a total of 5377 patients (colchicine = 2,689, placebo = 2688). Although colchicine use was associated with a significantly reduced risk of POAF, risk of GI adverse effects were significantly higher. The rates of infection and length of stay were similar across the groups. Subgroup analyses showed that colchicine was effective for POAF prevention in cardiac surgery, but not in thoracic surgery. Prevention of POAF and incidence of GI adverse effects were similar in short-term and long-term colchicine treatment. Colchicine significantly reduces the incidence of POAF in patients undergoing cardiac surgery, but not in thoracic surgery.

Enhancing Awareness of Diclofenac as an Over-the-Counter Analgesic in the Northern Border Region of Saudi Arabia

Introduction: Diclofenac was identified by the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency as a high-risk NSAID in terms of its effects on the heart and circulation when administered systemically, i.e. capsules, tablets or injections.&#x0D; Objective: To evaluate the knowledge and awareness about over the counter analgesic medication (Diclofenac) among people living in northern border region – Saudi Arabia.&#x0D; Methodology: Self-administered cross-sectional study conducted during a period of two months (October and November 2023) on random sample of 430 Saudi people living in the Northern Border Region. The data was analyzed by Microsoft excel program by means of Descriptive statistics.&#x0D; Results: Toothache and headache were the most worried pain among participants (32%) and (31%) respectively, majority (72%) of participants buy OTC medication for pain from community pharmacy on the advice of pharmacist. Small percentage (20%) thought that medications containing diclofenac have very few side effects, 76% didn’t know any side effect of diclofenac, 47% didn’t know that diclofenac in high dose has adverse effects on kidney, 71% didn’t know that diclofenac cause gastrointestinal adverse effects. About one fifth of participants (21%) didn’t know the maximum dose of diclofenac when they use it, tablet is the preferred dosage form of diclofenac (27%) followed by granules (16%), dosage of 100 mg is the most frequently used (36%) followed by 50 mg (16%). &#x0D; Conclusion: Saudi people’s knowledge about diclofenac as one member of non-steroidal anti-inflammatory drugs was insufficient. Knowledge about related adverse effects of diclofenac was lacked which exposes to misusage that may carry accidents and severe side effects especially among high-risk population.

Cannabis use in the United States and its impact on gastrointestinal health.

In recent years, the legalization and social acceptability of cannabis use have increased in the United States. Concurrently, the prevalence of cannabis use has continued to rise, and cannabis products have diversified. There are growing concerns regarding the health effects of regular and high-potency cannabis use, and new research has shed light on its potentially negative effects. Here, we review evidence of the gastrointestinal (GI) effects of cannabis and cannabinoids. Dysregulation of the endocannabinoid system might contribute to various GI disorders, including irritable bowel syndrome and cyclic vomiting syndrome, and endocannabinoids have been found to regulate visceral sensation, nausea, vomiting, and the gut microbiome. Cannabis has been shown to have antiemetic properties, and the US Food and Drug Administration has approved cannabis-based medications for treating chemotherapy-induced nausea and vomiting. Yet, chronic heavy cannabis use has been linked to recurrent episodes of severe nausea and intractable vomiting (cannabinoid hyperemesis syndrome). Given the considerable heterogeneity in the scientific literature, it is unclear if cannabinoid hyperemesis syndrome is truly a distinct entity or a subtype of cyclic vomiting that is unmasked by heavy cannabis use and the associated dysregulation of the endocannabinoid system. The changes in cannabis legalization, availability, and public risk perceptions have outpaced research in this area and there is a need for robust, prospective, large-scale studies to understand the effects of cannabis use on GI health.

Assessment of Gastrointestinal Adverse Effects during the First Six Months of "Biktarvy" Antiretroviral Therapy: Age-Related Patterns and Their Relation with Changes of 5 kg Weight Loss/Gain in the Initial Treatment Period.

The battle against HIV has led to the development of antiretroviral therapy (ART), including BIKTARVY®, which combines three potent agents. However, concerns about gastrointestinal side effects during the early phases of treatment have emerged, potentially impacting patient adherence and outcomes. This retrospective cohort study, conducted over four years in Romania, examined 222 patients initiated on BIKTARVY® therapy. Data were collected from electronic medical records, and stringent inclusion and exclusion criteria were applied to ensure data accuracy and relevance. Statistical analysis was performed to assess age-related patterns in gastrointestinal symptoms and their relation with significant weight loss. This study revealed significant differences in the prevalence of gastrointestinal symptoms between age groups, with older patients experiencing more symptoms. Notably, diarrhea did not exhibit a statistically significant age-related difference. Furthermore, weight loss exceeding 5 kg was more common in older patients. Of the patients who continued BIKTARVY® therapy, 84.9% showed an increase in CD4 cell counts, and most expressed satisfaction with treatment. Understanding age-related patterns and gastrointestinal side effects of BIKTARVY® is crucial for optimizing HIV patient care. Future research should aim to corroborate and expand upon these findings, potentially leading to improved therapeutic approaches in the ongoing fight against HIV.

Nutritional Strategies to Mitigate Post-Weaning Challenges in Pigs: A Focus on Glucans, Vitamin D, and Selenium.

This review examines the challenges faced by the pig industry, with a specific focus on improving the health and growth of weaned pigs. It emphasizes the immediate necessity of investigating alternative approaches to managing pig nutrition and health due to restrictions on the use of antibiotics and the prohibition of zinc oxide in weaned pig diets. The weaning phase is identified as a critical stage in piglet development, characterized by stressors that affect their gastrointestinal health, immune responses, and overall physiology. The primary challenge during weaning arises from transitioning piglets from a digestible milk-based diet to a less digestible cereal-based feed, causing nutritional stress. This manifests as reduced feed intake, leading to gastrointestinal disturbances, intestinal inflammation, and adverse effects on intestinal structure and microbiota. To address these challenges and optimize piglet development, various nutritional strategies have been explored. Notably, glucans, particularly β-glucans from fungi, cereals, algae, and yeast, show promise in alleviating weaning-related issues. Furthermore, it is important to highlight the critical roles played by Vitamin D and selenium in piglet nutrition. These essential nutrients can be sourced naturally from enriched mushrooms that are specifically enriched with Vitamin D and selenium, providing a sustainable dietary option. In conclusion, effective nutritional strategies, including glucans, Vitamin D, selenium, and enriched mushrooms, are beneficial for addressing weaning-related challenges.

Continued Treatment With Tirzepatide for Maintenance of Weight Reduction in Adults With Obesity

The effect of continued treatment with tirzepatide on maintaining initial weight reduction is unknown. To assess the effect of tirzepatide, with diet and physical activity, on the maintenance of weight reduction. This phase 3, randomized withdrawal clinical trial conducted at 70 sites in 4 countries with a 36-week, open-label tirzepatide lead-in period followed by a 52-week, double-blind, placebo-controlled period included adults with a body mass index greater than or equal to 30 or greater than or equal to 27 and a weight-related complication, excluding diabetes. Participants (n = 783) enrolled in an open-label lead-in period received once-weekly subcutaneous maximum tolerated dose (10 or 15 mg) of tirzepatide for 36 weeks. At week 36, a total of 670 participants were randomized (1:1) to continue receiving tirzepatide (n = 335) or switch to placebo (n = 335) for 52 weeks. The primary end point was the mean percent change in weight from week 36 (randomization) to week 88. Key secondary end points included the proportion of participants at week 88 who maintained at least 80% of the weight loss during the lead-in period. Participants (n = 670; mean age, 48 years; 473 [71%] women; mean weight, 107.3 kg) who completed the 36-week lead-in period experienced a mean weight reduction of 20.9%. The mean percent weight change from week 36 to week 88 was -5.5% with tirzepatide vs 14.0% with placebo (difference, -19.4% [95% CI, -21.2% to -17.7%]; P < .001). Overall, 300 participants (89.5%) receiving tirzepatide at 88 weeks maintained at least 80% of the weight loss during the lead-in period compared with 16.6% receiving placebo (P < .001). The overall mean weight reduction from week 0 to 88 was 25.3% for tirzepatide and 9.9% for placebo. The most common adverse events were mostly mild to moderate gastrointestinal events, which occurred more commonly with tirzepatide vs placebo. In participants with obesity or overweight, withdrawing tirzepatide led to substantial regain of lost weight, whereas continued treatment maintained and augmented initial weight reduction. ClinicalTrials.gov Identifier: NCT04660643.

Safety outcomes of antipsychotics classes in drug-naïve patients with first-episode schizophrenia: A nationwide cohort study in South Korea

IntroductionGiven the similar efficacies across antipsychotic medications for schizophrenia, understanding their safety profiles, particularly concerning receptor-binding differences, is crucial for optimal drug selection, especially for patients with first episode schizophrenia. We aimed to compare the safety outcomes of second-generation antipsychotics. MethodsWe conducted a retrospective cohort study with new user active comparator design using a nationwide claims database in South Korea. Participants were drug-naïve adult patients with first-episode schizophrenia. Three representative drugs with different pharmacologic profiles were compared: risperidone, olanzapine, and aripiprazole. Propensity scores were used to match the study groups, and the Cox proportional hazard model was used to calculate hazard ratios. Sensitivity analyses were performed in various epidemiological settings. Seventeen safety outcomes, including neuropsychiatric, cardiometabolic and gastrointestinal events, were assessed, with upper-respiratory-tract infection as a negative control outcome. ResultsA total of 1044, 2078, and 3634 participants were matched for olanzapine vs. risperidone, olanzapine vs. aripiprazole, and risperidone vs. aripiprazole comparisons, respectively. For parkinsonism, there was a significant difference in outcomes between the risperidone and aripiprazole groups (HR 1.80 [95% CI 1.13–2.91]), with consistent sensitivity analysis results. There were no significant differences in other neuropsychiatry outcomes or in the risk of cardiometabolic and gastrointestinal outcomes between any of the comparative group pairs. ConclusionsThe risk of drug-induced parkinsonism was significantly higher with risperidone than with aripiprazole. Although olanzapine is known for its metabolic risk, there were no significant differences in risk between the other pairs.

Two Novel Metformin Carboxylate Salts and the Accidental Discovery of Two 1,3,5-Triazine Antihyperglycemic Agent.

Metformin (MET), commonly marketed as a hydrochloride salt (MET-HCl) for better pharmacokinetic profile over the free base, would release a high concentration of chloride ions and cause adverse gastrointestinal effects. The preparation of chloride-free MET salts could potentially circumvent this issue. In this study, seven carboxylic acids (formic acid, acetic acid, malonic acid, succinic acid, fumaric acid, cinnamic acid, and acetylsalicylic acid) were used for preparing MET carboxylate salts. When compared with MET-HCl, all MET salts/salt hydrates show lower dissolution rates in pH 6.8 phosphate buffer. However, the cinnamic acid and acetylsalicylic acid show significantly higher dissolution rates in the forms of MET salt/salt hydrate. In the permeability test, the permeability of the MET in all of the salts was not improved. However, the permeability of cinnamic acid in the MET cinnamate is reduced, and the permeability of acetylsalicylic acid in the MET acetylsalicylate is increased. Meanwhile, at a higher crystallization temperature, the acetone solvent and a hydrolyzed product of acetylsalicylic acid react with MET respectively, leading to two unexpected 1,3,5-triazine derivatives. The results of in vitro bioactivity assays indicate that one of the triazine molecules promote glucose consumption more effectively than MET-HCl, and had relatively weak lactate production ability at low concentration. This glucose metabolism regulating compound may serve as a novel lead antihyperglycemic agent for further optimization.