Search Results (1,295)

Poor aqueous solubility and consequently low bioavailability of various NSAIDs (non-steroidal anti-inflammatory drugs) usually result in high and multiple dosing with potentially serious side effects. Therefore, systems for the effective transport of NSAIDs through the GIT (gastrointestinal tract), ensuring enhanced bioavailability, remain in high demand. In the present work, we studied chitosan (CS) hydrogel lyophilizates as carrier systems for a model NSAID, namely ibuprofen (IBU). The CS-IBU lyophilizates were prepared from homogeneous or heterogeneous CS-IBU hydrogels to assess their influence on the resulting lyophilizate microstructure and IBU dissolution profiles. To gain a complex view of the CS-IBU behavior and its practical consequences, dissolution profiles of free IBU (reference) and CS-associated IBU (CS-IBU) were examined and compared to each other at variable pH (1.2 and 6.5) in two separate dissolution systems and in one discontinuous dissolution system mimicking GIT conditions. The results of dissolution experiments were supported by kinetic model data. This study demonstrated that the dissolution of IBU from the CS-IBU lyophilizates is affected by two main pH-dependent competitive effects; i.e., dissolved CS acts as an IBU solubilizer and the undissolved CS matrix serves as an IBU trap, which could be used in the rational design of innovative stimuli (pH)-responsive oral dosage forms of IBU. Full article

In spite of plausible biology, the majority of oncology trials involving drug repurposing have failed to demonstrate any efficacy. Numerous factors can potentially cause failure, including issues with dosing, drug strength, the trial design itself, and patient diversity. A major, potentially correctable contributor is the absence of pharmacogenomic eligibility criteria. Here, we propose the Pharmacogenomic Stratification Framework for Drug Repurposing (PSDR), a novel framework for drug response that encompasses the triad of Exposure (E, pharmacokinetic adequacy), Target engagement (T, somatic tumor genomics), and Context competence (C, tumor microenvironment). These domains are represented as R = E × T × C, an eligibility model capturing the necessary, though not sufficient, conditions for anticancer drug activity. The model is not presented as an empirically validated quantitative law but as a conceptual framework to guide biomarker-stratified trial design. We derive five testable pharmacogenomic hypotheses for metformin, statins, beta-blockers, NSAIDs, and SSRIs, and propose a three-point PSDR eligibility scoring system. Prospective validation of each hypothesis in appropriately stratified cohorts is required before clinical implementation. The PSDR framework complements rather than replaces existing precision oncology resources (OncoKB, CIViC, PharmGKB, CPIC, DepMap, GDSC) by integrating germline pharmacokinetics, somatic genomics, and microenvironmental profiling for repurposed agents. If validated, PSDR-guided enrichment designs could substantially improve the efficiency and interpretability of repurposing trials. The PSDR framework should be considered a conceptual and hypothesis-generating model that requires prospective validation before clinical implementation. Full article

Spondyloarthritis associated with inflammatory bowel diseases (IBD-SpA), also known as enteropathic arthritis, is an independent entity belonging to the spondyloarthritis (SpA) group. In recent years, a great amount of new data has been published regarding the pathogenesis and treatment of the disease. In this narrative review we present the main pathogenetic pathways along the gut–joint axis, the genetics of IBD and SpA, the role of environmental factors and that of the microbiome, as well as the main immunopathological processes including immune cells and inflammatory mediators. We cover the clinical picture, the specifics of axial and peripheral SpA-IBD, and briefly discuss the diagnostics. There are common options in the pharmacotherapy of SpA and IBD; however, some drugs that control arthritis (e.g., NSAIDs, IL-17 inhibitors) might not be suitable for the treatment of IBD. Based on the pathogenetic role of the microbiome, it is suggested that pharmacotherapy can be supplemented with non-pharmacological remedies, such as diet including the administration of short-chain fatty acids (SCFAs). Finally, we briefly look at the future that might include rational, even personalized treatment. Full article

Background/Objectives: Diuretic resistance is a recognized complication in patients with heart failure (HF) and is associated with worse clinical outcomes; however, information regarding its frequency and associated factors in hospitalized patients in Mexico is limited. This study aimed to describe the frequency of diuretic resistance in patients hospitalized with HF in a hospital unit in western Mexico and to identify factors associated with diuretic resistance. Methods: This retrospective study used data obtained from clinical records. Patients older than 18 years with decompensated HF whose complete clinical records included the variables of interest were included. Patients were classified according to the presence or absence of diuretic resistance. Bivariate and multivariate analyses were performed to evaluate factors associated with diuretic resistance. Results: A total of 76 patients were analyzed, and the frequency of diuretic resistance was 35.5% (n = 27). In bivariate analysis, type 2 diabetes mellitus, chronic kidney disease, elevated creatinine, urea, blood urea nitrogen (BUN), and urine protein levels, decreased glomerular filtration rate (GFR) and serum albumin, and prior treatment with nonsteroidal anti-inflammatory drugs (NSAIDs) and angiotensin-converting enzyme inhibitors/angiotensin II receptor antagonists (ACEI/AARII) were significantly associated with diuretic resistance. In the multivariate logistic regression model, prior ACEI/AARII treatment, history of type 2 diabetes mellitus, BUN levels, and serum albumin levels remained independently associated with diuretic resistance classification. Conclusions: Diuretic resistance was frequent in this cohort of patients hospitalized with decompensated heart failure, and several clinical and biochemical factors were independently associated with its occurrence. These findings may help identify patients at higher risk of diuretic resistance, although they should be confirmed in future prospective studies. Full article

Non-steroidal anti-inflammatory drugs (NSAIDs) are used globally for their pain-relieving and fever-reducing properties. However, excessive intake of NSAIDs can have harmful effects on multiple body systems, including the cardiovascular, gastrointestinal, hepatic, renal, and nervous systems. The anti-inflammatory activity of 34 derivatives of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline was investigated in vivo. A relationship between the activity of the compounds and the nature of their substituents, as well as their positional and mutual arrangement in the C ring (1-Ar-), was established. In silico modeling of these 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline derivatives’ interaction with the COX-2 (PDB ID: 1PXX) active site revealed that the nitro-derivatives exhibited the highest stability owing to their superior capacity for electrostatic and hydrogen bond formation compared to brominated compounds. These data on the effects of the substituents –NH₂, –OH, and –OCH₃ in ring C (1-Ar-) of 1-aryl-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinolines on anti-inflammatory activity promote the search for new, highly effective derivatives within this series. Full article

Pharmaceutical and microbial pollution in urban rivers is an emerging concern, particularly in developing regions with limited wastewater treatment capacity, posing risks to human health and ecosystems. This study evaluated the risk profiles of selected pharmaceutical compounds and bacterial indicators in the Sand River, South Africa, and computed their ecological risks, antimicrobial resistance (AMR), and human health risk assessment. Surface water samples were collected from three sites during the wet season and analyzed for target antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) using High-Performance Liquid Chromatography (HPLC) with a photodiode array (PDA) detector, while total coliforms (TCs) and Escherichia coli (E. coli) were enumerated using the Colilert system. Ciprofloxacin, sulfamethoxazole, and erythromycin were the most abundant pharmaceuticals, with maximum concentrations of 2.50 µg/L, 2.76 µg/L, and 2.53 µg/L, respectively. TC and E. coli levels exceeded regulatory thresholds, indicating severe microbial contamination. Risk quotient analysis identified ciprofloxacin, erythromycin, and trimethoprim as high-risk compounds for potential resistance selection (RQ ≥ 1), while ciprofloxacin and erythromycin posed significant ecological risks to fish. Although non-carcinogenic health risk assessment remained below concern (HI < 1), children showed higher exposure levels. These findings underscore the urgent need for improved pharmaceutical waste management and wastewater treatment infrastructure. Full article

Background/Objectives: Reducing antibiotic use in the dairy sector is a critical objective. This study aimed to assess whether Danish farmers were able to achieve this objective appropriately without affecting animal health. Methods: Participants chose from three options—antibiotics (ABs), no treatment (NO), and non-steroidal anti-inflammatory drugs (NSAIDs)—and their decisions were compared against a laboratory-defined ‘gold standard’. Results: The results indicated that farmers’ professional judgment was unreliable; they frequently misallocated antibiotic treatments, often failing to treat cows that needed them while treating those that did not. Overall, producers administered significantly fewer antibiotics than laboratory results suggested were necessary. Although veterinarians achieved better results via in-clinic bacteriological examinations, their ability to identify specific bacterial species was insufficient. Consequently, cows remain at a significant risk of persistent infection following a clinical episode, regardless of the farmer’s chosen treatment. Conclusions: The study concludes that significant progress needs to be made both on farms and in veterinary clinics to ensure that the use of antibiotics is as little as possible, but as much as necessary. Until such reliability improves, unsuitable treatment will continue to compromise animal health. Full article

Background/Objectives: Chronic low back pain (CLBP) affects approximately 20% of the global population and is a leading cause of years lived with disability. Long-term, real-world evidence for inhaled cannabis in patients refractory to conventional multimodal therapy remains scarce. We assessed the five-year efficacy and safety of inhaled cannabis in CLBP patients who had documented failure of ≥1 year of opioid analgesics, anticonvulsants, antidepressants, NSAIDs, and physiotherapy, with each patient serving as their own historical control. Methods: We analyzed prospectively collected clinical data from 241 consecutive adults with treatment-refractory CLBP (mean age 49.3 ± 14.9 years; 37.8% female; mean pain duration 15.1 years) initiated on inhaled medical cannabis (predominantly smoking, THC 4–22%, CBD 2–22%) in a single-center tertiary orthopedic clinic between 2020 and 2025 (Hasharon Hospital, Rabin Medical Center, Israel; IRB protocols 0807-21-RMC and 0634-25-RMC). Year-0 outcomes during conventional therapy were compared with outcomes at Years 1–5 on cannabis. Primary outcomes were the Numeric Rating Scale (NRS), Oswestry Disability Index (ODI), and Brief Pain Inventory severity/interference (BPI-S/BPI-I). Concomitant-medication trajectories were a secondary outcome. The primary analysis was a mixed model for repeated measures (MMRM) with random intercept and slope, REML estimation, and time as a categorical fixed effect. Multiple imputation (MAR, m = 20, Rubin’s rules) was the primary missing-data approach; complete-case and tipping-point pattern-mixture sensitivity analyses were used. A multivariate Hotelling T² provided a joint test across the four correlated PROMs. Concomitant-medication discontinuation was modeled with GEE logistic regression and exact McNemar tests. Time to discontinuation was estimated by Kaplan–Meier and Cox regression. The Bonferroni-adjusted significance threshold for the four primary outcomes was α = 0.0125. BioWell gas-discharge-visualization (GDV) parameters were exploratory only. Results: Of 241 patients, 238 (98.8%) provided Year-5 data and 224 (92.9%) remained on cannabis at Year 5; only five patients (2.1%) discontinued for adverse events or inefficacy. All four primary PROMs improved markedly and durably. MMRM-estimated Year-5 minus Year-0 changes were: NRS −5.36 (95% CI −5.65, −5.07), ODI −17.68 (95% CI −19.73, −15.63), BPI-S −6.73 (95% CI −6.99, −6.47), and BPI-I −3.41 (95% CI −3.65, −3.16); all four contrasts had |z| ≥ 16.9 and p < 10⁻²⁰. MI-pooled estimates were within 0.05 of MMRM (FMI < 0.03 for all outcomes). Hotelling T² was F(4, 232) = 872.8, p < 10⁻²⁰. At Year 5, 89.2% achieved ≥30% NRS reduction, 77.2% ≥ 50%, and 93.4% met the NRS minimum clinically important difference (MCID); ODI MCID 65.6%, BPI-S MCID (≥1 pt) 98.3%, BPI-I MCID (≥1 pt) 91.3%. Concomitant opioid use fell from 100% at baseline to 4.6% at Year 5 (within-patient absolute risk reduction 95.4%, McNemar exact p = 1.16 × 10⁻⁶⁹), NSAID from 100% to 7.1%, SSRI/SNRI from 80.5% to 5.4%, and gabapentinoid from 38.6% to 2.5%. The ARR-derived NNT for opioid discontinuation was 1.05; this NNT is referenced to each patient’s own documented maximal-conventional-therapy state and is not equivalent to a between-arm randomized-trial NNT. Cannabis dose × time interaction was consistent with no pharmacological tolerance (β = −0.0044 per gram-month per year, p = 0.074). Across 1205 patient-years of cannabis exposure (calculated as 241 patients × 5 follow-up years from Year 1 through Year 5; baseline Year 0 represents pre-cannabis state and is not included in person-time on cannabis), 1338 organ-system AE events were recorded at 1.110/patient-year (Poisson 95% CI 1.05–1.17); 99.8% of graded events were mild (grade 1), with ocular (476 events, 0.40/PY), cognitive (460, 0.38/PY), and gastrointestinal (368, 0.31/PY) reactions predominating. The Year-3 retention dip reflected a documented telemedicine-clinic phenomenon during 2022–2024, with patients returning to in-person follow-up by Year 4–5. BioWell GDV discriminated NRS ≥ 4 only at chance level (BWS AUC 0.574, 95% CI 0.54–0.60; BWV AUC 0.51). Conclusions: In a treatment-refractory CLBP cohort with five-year longitudinal follow-up, inhaled cannabis was associated with large, sustained, and statistically robust improvements in pain, disability, and pain interference, accompanied by near-total displacement of opioids, NSAIDs, antidepressants, and gabapentinoids. These observational associations, although mechanically less susceptible to bias for the binary medication-discontinuation outcomes than for self-reported PROMs, cannot be interpreted causally in the absence of a concurrent randomized control arm and may reflect a combination of pharmacological effect, regression to the mean from a high pre-treatment baseline, expectancy and self-selection effects intrinsic to an actively chosen open-label therapy, and secular trends in pain reporting. The within-patient benefit-risk profile—ARR-derived NNT ≈ 1 for opioid sparing against a predominantly mild adverse-event burden—supports consideration of cannabis as a potentially clinically meaningful, opioid-sparing option in patients who have failed multimodal conventional therapy, pending confirmation in randomized comparative trials. Full article

Background/Objectives: The dual inhibition of the COX-2 and 5-LOX pathways, in addition to sEH inhibition, presents a superior approach to managing inflammation while mitigating the cardiovascular adverse effects typically associated with conventional NSAIDs. These multi-target agents are safer and more efficient as they inhibit the synthesis of pro-inflammatory leukotrienes while preserving cardioprotective epoxyeicosatrienoic acids. Methods: This study reports the development of multi-target inhibitors to mitigate inflammatory and cardiovascular conditions. We examined a series of tetrahydroindazole-sulfonamide hybrids (3a–g and 4a–e) against the enzymes COX-1/2, 5-LOX, and sEH. Results: Compound 3b outperformed celecoxib as a multi-target agent, inhibiting COX-2 (IC₅₀ = 0.08 µM, SI = 82), 5-LOX (IC₅₀ = 0.46 µM), and sEH (IC₅₀ = 21.95 nM) in many metrics. In cellular experiments, 3b showed strong cardioprotective and anti-inflammatory effects, significantly reducing TNF-α (65.58%), LDH (76.26%), and CK-MB (76.76%) levels compared to LPS-treated controls. Molecular docking validated these findings, indicating that 3b was comparable to celecoxib at the COX-2 site via a thorough six hydrogen-bond network and achieves considerable sEH affinity through specialized halogen bonding and aromatic stacking. These results indicate that 3b effectively provides dual anti-inflammatory and cardioprotective effects. Conclusions: Our findings suggest that targeting the COX/5-LOX/sEH pathways simultaneously offers a balanced multi-target profile for treating complex inflammatory diseases while minimizing cardiovascular risks. Full article

Background/Objectives: Nonsteroidal anti-inflammatory drug (NSAID) hypersensitivity comprises clinically distinct phenotypes, with different implications for diagnosis and future drug use. However, the biomarker literature in this field remains heterogeneous and difficult to interpret as a whole. We aimed to map how NSAID hypersensitivity biomarker studies are distributed across harmonized phenotype categories, biomarker classes, intended uses, and translational validation stages. Methods: We conducted a scoping review with systematic literature searching and descriptive evidence mapping. English-language records published between 1 January 2005 and 31 March 2026 were identified through PubMed and Embase. After staged screening and cross-database deduplication, eligible records were classified according to prespecified phenotype, biomarker, intended use, reference-standard, and validation-stage frameworks. Results: A total of 218 deduplicated records were retained in the master dataset. The mapped literature was heavily concentrated in NSAID-exacerbated respiratory disease/aspirin-exacerbated respiratory disease (NERD/AERD) (189/218, 86.7%). Genetic biomarkers were the most frequent class (118/218, 54.1%). The most frequent phenotype–biomarker class connection was between NERD/AERD and genetic biomarkers (n = 100). Most records were mapped to phenotype/endotype stratification (152/218, 69.7%), and most remained at Stage 0 exploratory discovery (197/218, 90.4%). Conclusions: The NSAID hypersensitivity biomarker literature is concentrated in a narrow phenotype space and remains dominated by exploratory research with limited later-stage validation. Future studies should prioritize clearer phenotype harmonization, stronger diagnostic anchoring, standardized biospecimen strategies, and independent validation to improve clinical translation. Full article

Background: The gut microbiota constitutes a metabolically active “second genome” that profoundly modulates drug pharmacokinetics, pharmacodynamics, and adverse reaction profiles. Beyond antibiotics, widely prescribed non-antibiotic pharmacotherapies exert clinically relevant pharmacomicrobiomic effects with implications for therapeutic optimisation and pharmacovigilance. Methods: This narrative review, conducted following PRISMA 2020 reporting principles (without PROSPERO pre-registration), searched PubMed/MEDLINE, Scopus, Web of Science, and Cochrane Library (January 2015–December 2024) for evidence on proton pump inhibitors (PPIs), metformin, NSAIDs, statins, SGLT2 inhibitors, and oral iron. Evidence tables included clinical human studies with molecular microbiota characterisation (16S rRNA or shotgun metagenomics), ≥20 participants, and a control arm; preclinical data informed mechanistic synthesis. Results: Of 68 eligible studies, 20 met criteria for the evidence tables. PPIs significantly remodelled gut microbiota composition with enrichment of oral-origin taxa (“oralisation of the gut”), associating with Clostridioides difficile infection and SIBO. Metformin enriched Akkermansia muciniphila and butyrate producers, contributing causally to glycaemic efficacy. NSAIDs compromised barrier integrity, with synergistic dysbiosis under PPI co-prescription. Statins correlated with reduced prevalence of the dysbiotic Bact2 enterotype. SGLT2 inhibitor data remained discordant. Oral iron consistently enriched Enterobacteriaceae at the expense of beneficial commensals. Full article

The increasing presence of pharmaceutical compounds in aquatic environments poses a significant challenge for wastewater treatment systems worldwide. Among these emerging contaminants, bicyclic non-steroidal anti-inflammatory drugs (NSAIDs) are particularly concerning due to their high consumption, partial metabolism, and long-lasting persistence in wastewater. This review was prepared critically based on popular databases such as PubMed and the Google Scholar website, and using the modern Nested Knowledge platform. The bibliometric analysis was performed using the VosViewer program with the keywords co-occurrence method. The review aims to systematically compile and synthesize current knowledge on the impact of bicyclic non-steroidal anti-inflammatory drugs (NSAIDs) on biological wastewater treatment systems, with particular emphasis on activated sludge. It discusses how these compounds influence microbial community composition, metabolic activity, sludge structure, and overall treatment performance. Furthermore, the distribution of these contaminants in the environment and their degradation efficiency were analyzed. By integrating evidence from both laboratory and industrial studies, this article provides a comprehensive perspective on the environmental risks posed by bicyclic NSAIDs. Our findings also underscore the urgent need for systematic monitoring and adaptive management to mitigate the ecological impact of these widely used pharmaceuticals in the future. Full article

Background/objectives: severe mastitis is one of the leading causes of mortality in dairy cows. Its primary complication is shock, predominantly associated with systemic inflammatory response syndrome, which remains extremely challenging for practitioners to manage. The average mortality rate is estimated at approximately 25%. Many authors recommend the use of fluoroquinolones for this indication. However, these antibiotics are classified as critically important for human health, and their use requires strict compliance with specific guidelines (bacteriological analysis and antimicrobial susceptibility testing). In addition, some practitioners remain reluctant to use this class of antibiotics in field conditions. Therefore, the present study aimed to evaluate the outcomes of systematic antibiotic therapy using fluoroquinolones in cases of severe mastitis and to identify factors that may influence treatment success. Methods: a total of 323 cows with severe mastitis were enrolled by eight participating veterinary clinics located across different regions of France. The study design included: (i) clinical scoring based on a standardized grid developed by practitioners routinely managing this condition, (ii) bacteriological analysis of milk samples (with antimicrobial susceptibility testing performed when Gram-negative bacteria were isolated), and (iii) post-treatment follow-up consisting of telephone interviews conducted at 5 and 15 days after inclusion. Cows presenting with a clinical score ≥3 (scale 0–36) in association with local signs of mastitis were classified as having severe mastitis and received an injection of 10 mg/kg marbofloxacin along with 2.2 mg/kg flunixin (unless another NSAID had been administered within the previous 24 h). When the clinical score was ≥6, cows additionally received intravenous fluid therapy consisting of 3 L of 7.2% NaCl, supplemented by oral drenching if spontaneous water intake was insufficient. Results: a total of 43 cows died or were euthanized during the study period, corresponding to a mortality rate of 13.3%. The mean clinical score at inclusion was 12.6. The clinical signs most strongly associated with mortality were decubitus and hypothermia at admission. Escherichia coli was isolated in 67.0% of severe mastitis cases, either as a single pathogen (82.9%) or in mixed infections (17.1%). Overall, Gram-negative bacteria (Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, other Gram-negative organisms) were identified in 79.0% of cases. A total of 188 coliform isolates were tested for antimicrobial susceptibility. All isolates (100%) were susceptible to marbofloxacin, as were all tested Gram-negative strains, whereas only 79.9% of E. coli isolates were susceptible to sulfonamide/trimethoprim. Compared with previously published data, the observed mortality rate was lower despite the poor clinical condition of cows at admission. Conclusion: the timeliness of initiating effective antimicrobial therapy appears to be a critical determinant of survival in cows with severe mastitis. Full article

Background/Objectives: Chronic inflammation is a key factor in the development and progression of colorectal cancer (CRC). When COX-2 levels and PGE₂ production increase, nonsteroidal anti-inflammatory drugs (NSAIDs), including aspirin (ASA) and selective COX-2 inhibitors, such as celecoxib and rofecoxib, are commonly employed. This paper presents the effect of anti-inflammatory drugs, primarilyNSAIDs, on the incidence of CRC. Methods: A comprehensive literature search (119 articles) was conducted with databases such as PubMed. During our research, we used keywords such as colorectal cancer (CRC), nonsteroidal anti-inflammatory drugs (NSAIDs), ASA, COX, precision oncology, and personalized medicine. Results: The development of CRC is primarily associated with chronic inflammation and the actions of COX-2 and prostaglandin E2 (PGE₂), which promote cancer cell proliferation and angiogenesis. Anti-inflammatory drugs act by inhibiting the secretion of COX-1 and COX-2 enzymes, which leads to reduced PGE₂ production and may limit tumor growth. Aspirin has the best-documented and studied anti-cancer effect; long-term use is associated with a reduced risk of CRC development and mortality through its anti-inflammatory and antiplatelet effects, thereby limiting metastasis. Particularly beneficial effects are observed in patients with mutations in the PIK3CA gene. Factors influencing the effectiveness of CRC treatment include molecular differences and tumor location. Conclusions: The future of CRC treatment and prevention lies in personalized medicine, which accounts for each patient’s genetic profile. Decisions regarding NSAIDs use and CRC prevention should consider the potential benefits and risks of side effects. Full article

Background/Objectives: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used for postpartum pain management. However, previous studies have indicated that NSAIDs may increase systolic blood pressure, particularly in patients receiving antihypertensive therapy. The aim of the present study was to assess whether postpartum ibuprofen administration is associated with a higher risk of severe postpartum hypertension and increased mean arterial pressure (MAP) compared with acetaminophen. Methods: A systematic literature search was conducted in PubMed, Scopus, and Web of Science to identify relevant studies. Only randomized controlled trials were considered eligible for inclusion. For dichotomous outcomes, effect sizes were expressed as risk ratios (RRs) with corresponding 95% confidence intervals (CIs). For continuous outcomes, mean differences (MDs) with 95% CIs were calculated. Statistical heterogeneity among studies was assessed using the I² statistic. A fixed-effects model was applied in cases of low heterogeneity (I² < 20%). Results: No significant difference was observed in the prevalence of severe postpartum hypertension between the ibuprofen and acetaminophen groups (RR 1.07, 95% CI 0.84 to 1.35; p = 0.59; I² = 0%). Similarly, MAP did not differ significantly between groups (MD −0.05 mmHg, 95% CI −1.53 to 1.42; p = 0.94; I² = 0%). Conclusions: No increased risk of postpartum hypertension or difference in mean arterial pressure was observed between the ibuprofen and acetaminophen groups, supporting the safety of ibuprofen for postpartum analgesia in women with hypertensive disorders of pregnancy. Full article