Uncovering the Role of Direct Oral Anticoagulants in Stroke Prevention for Atrial Fibrillation: A Review of the Literature.

Atrial fibrillation (AF) is a predominant contributor to morbidity and mortality, and stroke prevention remains the mainstay for the management of AF. The precise mechanism involved in thrombus formation remains unknown. However, factors such as stretch-induced fibrosis, endothelial dysfunction, disordered atrial contractions, and pro-thrombotic states have been postulated for the development of AF. Various risk assessment strategies have been acknowledged for determining the risk of stroke in AF, of which the congestive heart failure, hypertension, age ≥75, diabetes, stroke, vascular disease, age between 65-74, and female sex (CHA2DS2-VASc) score remains the ultimate risk stratification tool. For the longest time, vitamin K antagonists (VKA) were the only oral anticoagulants available but were associated with an increased risk of bleeding. Recently, direct oral anticoagulants (DOACs) were approved and considered more efficient and safer than or as secure as warfarin in stroke prevention and lowering intra-cranial bleeding events. The pharmacodynamics and pharmacokinetics of DOACs were also clarified in this article. This review article compiles current evidence-based data on the role of DOACs, uncovering their underlying mechanisms, and comparing their efficacy with warfarin in stroke prevention in AF.

Reduction of Overactive Bladder Medications in Spinal Cord Injury With Self-Administered Neuromodulation; a Randomized Trial.

PURPOSE: To evaluate if self-administered bladder neuromodulation with transcutaneous tibial nerve stimulation can safely replace overactive bladder medications in people with spinal cord injury. MATERIALS AND METHODS: We performed a 3-month, randomized, investigator-blinded, tibial nerve stimulation vs sham-control trial in adults with spinal cord injury and neurogenic bladder performing intermittent catheterization and taking overactive bladder medications. The primary outcome was a reduction in bladder medications while maintaining stable bladder symptoms and quality of life based on pre-post Neurogenic Bladder Symptom Score and the Incontinence-QOL questionnaire, respectively. Secondary outcomes included changes in pre-post cystometrogram, 2-day voiding diaries, and an anticholinergic medication side effect survey. RESULTS: Fifty people consented to the study, with 42 completing the trial. No dropouts were due to stimulation issues. All baseline demographics and surveys were comparable at baseline. Cystometrogram parameters were also comparable at baseline, except the stimulation group had a higher proportion of loss of bladder compliance compared to the control group. At the end of the trial, a significantly greater percentage of the tibial nerve stimulation group were able to reduce medications (95% v 68%), by a 26.2% difference in medication reduction (95% confidence interval 1.17%-51.2%). Function and quality of life surveys and cystometrograms at the end of the trial were alike between groups. Transcutaneous tibial nerve stimulation satisfaction surveys and adherence to protocol were high. CONCLUSIONS: In people with chronic spinal cord injury performing intermittent catheterization, transcutaneous tibial nerve stimulation can be an option to reduce or replace overactive bladder medications.

Why do oestrogens matter: systematic review and meta-analysis assessing GnRH antagonists, considering add-back therapy, for endometriosis-associated pain.

Gonadotrophin-releasing hormone (GnRH) antagonists have been demonstrated to reduce endometriosis-associated pain. Because of the hypo-oestrogenic state they induce, however, higher dosages of GnRH antagonists are not recommended for used long term. This unwanted effect may be eliminated by so-called add-back therapy (ABT). This review was conducted to assess the safety and efficacy of GnRH antagonists, with or without add-back hormonal replacement therapy. Out of the 345 studies selected through the initial search, seven randomized controlled trials were included, comparing different oral GnRH antagonists at varying dosages, from a minimum of 50 mg to a maximum of 200 mg once or twice daily. Women treated with the lowest dose of GnRH antagonists had significantly greater mean pain score reductions from baseline throughout treatment compared with those treated with placebo (odds ratio [OR] -13.12, 95% CI -17.35 to -8.89 and OR -3.08, 95% CI -4.39 to -1.76 for dysmenorrhoea and non-menstrual pelvic pain, respectively). Compatible with the dose-response effect, a positive correlation was found between response rates and adverse event rates. While GnRH antagonists offer an advantage in terms of pain reduction for endometriosis, the more recent literature suggests using GnRH antagonists with ABT, which, while mitigating the hypo-oestrogenic effects of GnRH antagonists, maintain their efficacy, while allowing their long-term use.

Rare Case Report of Primary Active Pulmonary Tuberculosis During Ixekizumab Treatment for Plaque Psoriasis.

Biologic agents have become a mainstay in the treatment of psoriasis, particularly in moderate to severe, refractory, and special types of the disease. Among these, ixekizumab is a humanized IgG4 monoclonal antibody targeting interleukin-17A, approved for the treatment of moderate to severe plaque psoriasis. Its adverse effects include infections such as nasopharyngitis, upper respiratory tract infections, and injection site reactions. While the incidence of tuberculosis (TB) associated with IL-17A antagonists is extremely low, this paper reports a case of active pulmonary tuberculosis occurring after ten doses of ixekizumab treatment for chronic plaque psoriasis. This highlights the importance for clinicians to remain vigilant regarding tuberculosis infection in patients undergoing therapy with this class of medications, emphasizing the need for enhanced screening and monitoring for tuberculosis during treatment.

Management of Patients Receiving Anticoagulation Therapy in Dental Practice: A Systematic Review.

BACKGROUND: Anticoagulant drugs are a valuable tool for minimizing thrombotic risks in at-risk patients. The purpose of this study is to conduct a literature review highlighting the management of these drugs during daily clinical dental practice. MATERIALS AND METHODS: We limited our search to English-language papers published between 1 January 1989, and 7 March 2024, in PubMed, Scopus and Web of Science that were relevant to our topic. In the search approach, the Boolean keywords "anticoagulant AND dentistry" were used. RESULTS: Twenty-five clinical trials were included for final review from 623 articles obtained from the databases Web of Science (83), PubMed (382), and Scopus (158), eliminating duplicates and 79 off-topic items, resulting in 419 articles after removing 315 entries and confirming eligibility. Overall, these studies support the use of local hemostatic measures to manage the risk of bleeding in patients on anticoagulant therapy undergoing dental procedures and highlight the importance of greater education and collaboration among healthcare professionals. CONCLUSIONS: Research and clinical investigation have improved understanding and management of dental procedures in patients undergoing anticoagulant or antiplatelet therapy. Hemostatic agents, clinical protocols, risk factors, and continuous education are essential for navigating the complexities of anticoagulant therapy, ensuring optimal outcomes and enhancing patient well-being.

Improving oxygenation in severe ARDS treated with VV-ECMO: comparative efficacy of moderate hypothermia and landiolol in a swine ARDS model.

BACKGROUND: Acute respiratory distress syndrome (ARDS) remains a significant challenge in critical care, with high mortality rates despite advancements in treatment. Venovenous extracorporeal membrane oxygenation (VV-ECMO) is employed as salvage therapy for refractory cases. However, some patients may continue to experience persistent severe hypoxemia despite being treated with VV-ECMO. To achieve this, moderate hypothermia and short-acting selective ß1-blockers have been proposed. METHODS: Using a swine model of severe ARDS treated with VV-ECMO, this study investigated the efficacy of moderate hypothermia or ß-blockade in improving arterial oxygen saturation (SaO2) three hours after VV-ECMO initiation. Primary endpoints included the ratio of VV-ECMO flow to cardiac output and arterial oxygen saturation before VV-ECMO start (H0) and three hours after ECMO start (H3). Secondary safety criteria encompassed hemodynamics and oxygenation parameters. RESULTS: Twenty-two male pigs were randomized into three groups: control (n = 6), hypothermia (n = 9) and ß-blockade (n = 7). At H0, all groups demonstrated similar hemodynamic and respiratory parameters. Both moderate hypothermia and ß-blockade groups exhibited a significant increase in the ratio of VV-ECMO flow to cardiac output at H3, resulting in improved SaO2. At H3, despite a decrease in oxygen delivery and consumption in the intervention groups compared to the control group, oxygen extraction ratios across groups remained unchanged and lactate levels were normal. CONCLUSIONS: In a swine model of severe ARDS treated with VV-ECMO, both moderate hypothermia and ß-blockade led to an increase in the ratio of VV-ECMO flow to cardiac output resulting in improved arterial oxygen saturation without any impact on tissue perfusion.

Dexamethasone-sparing strategies in anthracycline and cyclophosphamide-based chemotherapy with a focus on 5-HT3 receptor antagonists: a network meta-analysis.

Background: The effectiveness of a dexamethasone-sparing strategy in the treatment of breast cancer with anthracycline-cyclophosphamide therapy when combined with first-generation 5-HT3 receptor antagonists (RAs) and neurokinin-1 RAs is unclear. This is attributable to a lack of evidence from direct comparison of multiple doses of DEX to a single dose of DEX in combination with first-generation 5-HT3 RAs in anthracycline-cyclophosphamide therapy. Our goal was to clarify the impact of dexamethasone-sparing strategies that involve both first-generation 5-HT3 RAs and palonosetron when combined with neurokinin-1 RAs, using a network meta-analysis. Materials and methods: A literature search was conducted on PubMed/Medline for articles published up to July 4, 2023. We included randomized controlled trials which assessed the efficacy of antiemetic regimens which combined 5-HT3 RAs and dexamethasone, with or without neurokinin-1 RAs, for the initial dose in anthracycline-cyclophosphamide therapy for patients with breast cancer. The primary outcome was the proportion of patients achieving a complete response during the delayed phase (CR-DP). Results: The difference in the proportion of patients achieving CR-DP between multiple and single doses of dexamethasone was 0.1% (95%CI: -12.4 to 12.5) with palonosetron and neurokinin-1 RAs, compared to 5.3% (95%CI: -13.4 to 23.0) with a single dose of a first-generation 5-HT3 receptor antagonist. Additionally, the difference was 12.7% (95% CI: -2.8 to 28.2) when comparing palonosetron against first-generation 5-HT3 RAs in combination with a single dose of dexamethasone and neurokinin-1 RAs. Conclusion: Palonosetron is recommended rather than a single dose of first-generation 5-HT3 RAs in dexamethasone-sparing strategies for anthracycline-cyclophosphamide therapy.

Identification of sanguinarine as a novel antagonist for perfluorooctanoate/perfluorooctane sulfonate-induced senescence of hepatocytes: An integrated computational and experimental analysis.

Perfluorooctanoate (PFOA) and perfluorooctane sulfonate (PFOS), two prominent per- and polyfluoroalkyl substances (PFASs), are potentially harmful to many human organs. However, there only exist limited methods to mitigate their health hazards. The aim of this study is to combine a bioinformatics analysis with in vitro experiments to discover small molecules that can alleviate liver damage caused by PFOA/PFOS. We identified 192 and 82 key genes related to hepatocytes exposed to PFOA and PFOS, respectively. The functional enrichment analysis of key genes suggested cellular senescence may be important in PFOA/PFOS-induced hepatotoxicity. The in vitro models revealed that PFOA/PFOS led to hepatocyte senescence by increasing the activity of SA-ß-gal, inducing mitochondrial dysfunction, impacting cell cycle arrest, and elevating the expressions of p21, p53, IL-1ß, and SASP-related cytokines. The drug-target gene set enrichment analysis method was employed to compare the transcriptome data from the Gene Expression Omnibus database (GEO), Comparative Toxicogenomics Database (CTD), and the high-throughput experiment- and reference-guided database (HERB), and 21 traditional Chinese medicines (TCMs) were identified that may alleviate PFOA/PFOS-induced liver aging. The experimental results of co-exposure to PFOA/PFOS and TCMs showed that sanguinarine has particular promise in alleviating cellular senescence caused by PFOA/PFOS. Further investigations revealed that the mTOR-p53 signaling pathway was involved in PFOA/PFOS-mediated hepatic senescence and can be blocked using sanguinarine.

AM/PM dosing of LAMA for COPD: a randomized controlled trial protocol using digital recruitment and registries.

Rationale: Long-acting muscarinic antagonists (LAMAs) reduce the risk of acute exacerbations of chronic obstructive pulmonary disease (AECOPD), usually taken once daily in the morning. However, the circadian activity of autonomic regulation suggests that the highest need for anticholinergic therapy may be in the late night/early morning. This is supported by evidence that AECOPD most often begins in the morning. Furthermore, the trough spirometry effect of LAMA is lower than the peak effect, which further argues that evening dosing may be more optimal than morning dosing. This trial aims to determine whether evening administration of LAMA reduces hospitalization-requiring AECOPD or death from all causes within 1 year as compared to morning administration of the same LAMA. Methods: Randomized controlled open-label trial. Persons aged 30 years or older with a once-daily LAMA prescription and a confirmed COPD diagnosis were recruited. Participants were randomized in a 1:1 ratio to either morning or evening LAMA administration. Complete follow-up for the primary outcome, hospitalization-requiring AECOPD, or death from all causes within 1 year was captured from the Danish National Health Register, as were patient-reported outcome assessments at 6 and 12 months. Results: A total of 10,013 participants were randomized, and the recruitment process started on 9 March 2023. Secondary outcomes include (i) moderate COPD exacerbations; (ii) all-cause hospitalization; (iii) ICU admission; (iv) need for non-invasive ventilation; and (v) all-cause mortality, among others. All outcomes will be evaluated 12 months after recruitment.Clinical trial registration:ClinicalTrials.gov, NCT05563675.

Data mining and safety analysis of dual orexin receptor antagonists (DORAs): a real-world pharmacovigilance study based on the FAERS database.

Objective: Using the Food and Drug Administration Adverse Event Reporting System (FAERS) database, four signal detection methods were applied to mine adverse drug events (ADEs) related to use of dual orexin receptor antagonists (DORAs) to provide reference for safe clinical use. Research design and Methods: Data collected from Q3rd 2014 to Q4th 2023 were obtained from the FAERS database. According to the preferred terminology (PT) and systematic organ classification (SOC) of MedDRA v.26.0, the reporting odds ratio (ROR), proportional reporting ratio (PRR), multi-item gamma Poisson shrinker (MGPS), and Bayesian confidence propagation neural network (BCPNN) were used to detect ADE signals. Results: A total of 11,857 DORAs-related adverse reactions were detected, reported with suvorexant, lemborexant, and daridorexant as the main suspected drugs was 8717584, and 2556, respectively. A higher proportion of females than males were reported (57.27% vs. 33.04%). The top 20 positive PT signals from three DORAs showed that "sleep paralysis" ranked first. "Brain fog" was stronger following daridorexant but was not detected for the other two drugs, and "sleep sex" and "dyssomnia" were stronger in suvorexant but not in the other two drugs. Additionally, some PTs occurred that were not included in drug instructions, such as "hangover" and "hypnagogic hallucination." Conclusion: In this study, four algorithms (ROR, PRR, BCPNN, and MGPS) were used to mine the safety signals of DORAs. We identified some potential ADE signals that can promote the rational use of DORAs and improve their safety.

Certolizumab-induced sarcoidosis in a patient with psoriatic arthritis - a case report and review of literature.

Tumour necrosis factor-α (TNF- α) antagonists are considered a significant therapeutic option in the treatment of sarcoidosis. Nevertheless, their use can also paradoxically result in sarcoidosis-like reactions. Here, we present a case of a 56-year-old patient with psoriatic arthritis who after 3 months of certolizumab therapy developed pulmonary sarcoidosis. Therefore, certolizumab was discontinued and prednisone initiated. Subsequently, 4 months later a complete remission of interstitial lesions was observed. Due to insufficient control of psoriatic arthritis, upadacitinib and methotrexate were prescribed and despite initial improvement, a couple of months later a massive exacerbation of skin psoriasis occurred and the treatment was switched to secukinumab. As of today, no evidence of sarcoidosis recurrence has been noted. Drug-induced sarcoidosis-like reactions (DISR) appear to be less frequently associated with certolizumab rather than with other anti-TNF-α agents. However, specific mechanisms of this phenomenon remain unclear and require future investigation.

Safety assessment of neurokinin-1 receptor antagonist: real-world adverse event analysis from the FAERS database.

Background: Aprepitant, fosaprepitant, and netupitant are three common neurokinin-1 receptor antagonists (NK-1RAs) used to prevent chemotherapy-induced nausea and vomiting, following highly or moderately emetogenic chemotherapy. Understanding their different adverse event (AE) profiles may help clinicians make appropriate treatment decisions. Methods: All data collected from the FDA Adverse Event Reporting System (FAERS) database from the first quarter of 2004 to the fourth quarter of 2023 underwent disproportionality analysis to detect, evaluate, and compare AE signals of the three NK-1RAs. Results: A total of 3,904, 1,123, and 243 AE reports related to aprepitant, fosaprepitant, and netupitant, respectively, were extracted from the FAERS database. Of these, more than 50% of respondents were female, and most of them were aged 45-65 years. General disorders and administration-site conditions, and gastrointestinal disorders were the most frequent signals in the system organ class of the three NK-1RA drugs. In addition, aprepitant was strongly associated with joint deposit (ROR = 26.27) and fosaprepitant was closely related to seizure-like phenomena (ROR = 26.90); two preferred terms (PTs) were not mentioned in the manual. Statistically, netupitant was likely to induce death (N = 63, ROR = 8.78, 95% CI: 6.75-11.42). Additionally, neutropenic colitis, colitis, and stomatitis were unique to netupitant. Furthermore, the AE profiles of the three NK-1RA drugs were different by gender. Conclusion: The AE profiles for aprepitant, fosaprepitant, and netupitant were different. In addition to paying attention to common AEs, clinicians need to pay attention to new emerging AEs, such as joint deposit, seizure-like phenomena, neutropenic colitis, colitis, and stomatitis, regarding the three NK-1RA drugs. Furthermore, the AE compositions of the three NK-1RA drugs were different in different genders, and clinicians should take these factors into account when selecting NK-1RAs for CINV treatment.

The discovery and development of gefapixant as a novel antitussive therapy.

INTRODUCTION: Gefapixant, a P2X 3 receptor antagonist, shows considerable potential in managing refractory or unexplained chronic cough. Clinical trials have consistently demonstrated its efficacy in significantly reducing cough frequency and alleviating associated symptoms. However, its adverse effect profile, particularly taste disturbances such as dysgeusia and hypogeusia, the incidence of which is dose-dependent, poses a significant challenge to patient compliance and overall treatment satisfaction. AREAS COVERED: The authors review the mechanism of action of gefapixant, the dose-dependent nature of its adverse effects and the findings from various clinical trials, including Phase 1, Phase 2, and Phase 3 studies. The authors also cover its regulatory status, post-marketing data, and its main competitors. EXPERT OPINION: Gefapixant represents a significant advancement in treating chronic cough. However, balancing efficacy and tolerability is crucial. Lower effective doses and potential combination therapies may mitigate taste disturbances. Patient education and close monitoring during treatment are also important for optimal outcomes. Further research is needed to refine dosing strategies to minimize side effects while maintaining therapeutic efficacy. This research and personalized treatment approaches are key to optimizing gefapixant therapy, ensuring improved management of chronic cough while reducing adverse effects. However, pharmaceutical trials and proposals must be adapted to align with each regulatory body's specific requirements and concerns.

A new mode of inhibition.

Complementary structural biology approaches reveal how an agonist and a covalent inhibitor simultaneously bind to a nuclear receptor.

Efficacy and Safety of Non-Vitamin K Antagonist Oral Anticoagulants Compared with Vitamin K Antagonists in Patients with Atrial Fibrillation and Type 2 Valvular Heart Disease: A Systematic Review and Meta-Analysis.

PURPOSE: This meta-analysis aimed to evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) compared with vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) and type 2 valvular heart disease (VHD). METHODS: We searched the PubMed, LILACS, and MEDLINE databases to retrieve, randomized controlled trials (RCTs) comparing NOACs and VKAs in patients with AF and type 2 VHD, excluding mitral stenosis (moderate to severe, of rheumatic origin) or mechanical heart valves. The efficacy outcomes assessed were stroke and systemic embolism (SE), while safety outcomes included major bleeding and intracranial hemorrhage (ICH). RESULTS: Seven RCTs, including 16,070 patients with AF and type 2 VHD, were included. NOACs reduced the risk of stroke/SE (relative risk [RR], 0.75; 95% confidence interval [CI], 0.64-0.89; P = 0.0005), with no significant difference in major bleeding (RR, 0.88; 95% CI, 0.64-1.21; P = 0.43). The risk of ICH was reduced with NOACs (RR, 0.46; 95% CI, 0.27-0.77; P = 0.003). For patients with AF and bioprosthetic heart valve (five trials, 2805 patients), stroke/SE risks (RR, 0.65, 95% CI, 0.44-0.96) with NOACs were superior to VKAs. Major bleeding risks without ENVISAGE TAVI AF trial (RR, 0.53; 95% CI, 0.30-0.94; P = 0.03) with NOACs were superior to VKAs. The risks of ICH (RR, 0.61; 95% CI 0.34-1.09; P = 0.09) with NOACs were comparable to VKAs. CONCLUSIONS: NOACs demonstrate efficacy and safety in patients with AF and type 2 VHD and reduce the risk of stroke/SE and ICH when compared with those with VKAs.

Epidemiology of headache presentations to United States emergency departments from 2016 to 2023.

INTRODUCTION: Headaches are a common condition seen in the Emergency Department (ED), with numerous trials focused on improving care for these patients. However, there is limited recent large-scale, robust data available on the incidence, admission rates, evaluation, and treatment in the ED setting. METHODS: This was a cross-sectional study of ED presentations for headache from 1/1/2016 to 12/31/2023 using the Epic Cosmos national database. All ED visits with headache-relevant ICD-10 coding were included. Outcomes included percentage of total ED visits, admission rates, computed tomography (CT) brain imaging, lumbar puncture (LP) performance, and medication administration. Medications were analyzed by class (NSAIDs, acetaminophen, dopamine antagonists, diphenhydramine, opioids, intravenous fluids, caffeine, and magnesium sulfate). Subgroup analyses were performed by specific types of dopamine antagonists. RESULTS: Of 188,482,644 ED encounters, 6,007,090 (3.2%) were due to headache. Of these, 246,082 (4.1%) were admitted. Nearly half (46.6%) of patients received at least one CT. Rates of CT head without contrast increased from 38.2% to 47.9% over time, while rates of CT angiography rose from 2.8% to 10.2%. 1.4% of all patients received an LP, with rates decreasing from 1.8% to 1.1% over time. The most common medication was NSAIDs (45.3%), followed by dopamine antagonists (44.8%), diphenhydramine (38.1%), acetaminophen (24.8%), opioids (16.3%), magnesium sulfate (0.2%), and caffeine (0.1%). 50.8% of patients received intravenous fluids. Rates of opioids declined over time, while dopamine antagonists, acetaminophen, and intravenous fluid administration increased. CONCLUSION: Headaches represent a common reason for ED presentation, with approximately 4% of patients being admitted. Imaging is frequently performed, with rises in CT without contrast and CT angiography rates over time, while LP rates have been declining. NSAIDs remain the most common medication given, with opioids declining over time while non-opioid agents such as dopamine antagonists have increased. These findings can help inform health policy initiatives, such as those focused on radiologic imaging and evidence-based medication administration.

Factor Xa Inhibitors Versus Vitamin K Antagonists in Atrial Fibrillation Patients with End-Stage Kidney Disease on Dialysis: A Meta-Analysis.

BACKGROUND: Atrial fibrillation (AF) is prevalent among patients with end-stage kidney disease (ESKD) undergoing dialysis, and both conditions are associated with a heightened risk of cardiovascular diseases. Anticoagulation is essential for preventing thromboembolic complications in these patients. This study aimed to evaluate the effects of factor Xa inhibitors compared to vitamin K antagonists (VKAs) for AF patients on dialysis. METHODS: A comprehensive search of PubMed and Embase databases was conducted to identify relevant studies published up to June 2024. Eligible studies compared factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) with VKAs in AF patients on dialysis, with primary outcomes of stroke or systemic embolism(SSE) and major bleeding. RESULTS: A total of 7 studies (3 randomized controlled trials and 4 observational cohorts) were included. For the RCTs, the use of factor Xa inhibitors was associated with a reduced risk of SSE compared to VKAs (odds ratio [OR] = 0.37, 95% confidence interval [CI]:0.15-0.93). There was no significant difference in the risk of major bleeding events between the two groups (OR = 0.65, 95%CI:0.32-1.33). Observational cohort studies yielded similar results with a decreased risk of SSE (hazard ratio [HR] = 0.74, 95%CI:0.57-0.96) and no significant difference in major bleeding (HR = 0.87, 95%CI:0.62-1.22). No differences in treatment effect between apixaban and rivaroxaban were observed for efficacy (p-interaction = 0.44) and safety (p-interaction = 0.21) outcomes. CONCLUSION: Factor Xa inhibitors, particularly apixaban and rivaroxaban, were associated with a lower risk of SEE without an increase in major bleeding, which might be convenient alternatives to VKAs in managing AF in patients with ESKD on dialysis.

Naldemedine-induced perforation of a diverticulum in the sigmoid colon of a patient with opioid-related constipation: a case report.

BACKGROUND: Naldemedine is an orally available peripherally acting µ-opioid receptor antagonist approved to treat opioid-induced constipation (OIC). It is contraindicated for patients with known or suspected gastrointestinal obstruction to protect against naldemedine-induced perforation. Here, we report a clinical case of suspected perforation of a diverticulum in the sigmoid colon associated with naldemedine. CASE PRESENTATION: The patient was a 65-year-old man with a history of oral cancer who had been prescribed oxycodone (20 mg/day) for cancer pain. On day 0, the patient started naldemedine 0.2 mg once daily before bedtime for OIC. The dose of oxycodone was increased for pain control up to 60 mg/day. On day 35 of naldemedine treatment, the patient developed fever and abdominal pain, and his frequency of defecation had decreased. Initial laboratory results showed a C-reactive protein (CRP) level of 28.5 mg/dL and white blood cell (WBC) count of 13,500/µL. On day 37, the patient still had tenderness in his lower abdomen. Abdominal computed tomography revealed free air in the abdominal cavity suggesting an intestinal perforation. A Hartmann procedure was performed. Histopathological findings showed numerous diverticula in the sigmoid colon, some of which were perforated. CONCLUSIONS: These results suggest that the effects of OIC may have compressed the intestinal tract, which was followed by naldemedine-activation of peristalsis, which led to the onset of intestinal perforation. In patients with pre-existing diverticular disease, we should monitor for increased WBC counts and CRP levels after the initiation of treatment with naldemedine, and consider performing appropriate tests early in the event of abdominal complaints.

Effect of Direct Oral Anticoagulants in Patients with Splanchnic Vein Thrombosis: A Systematic Reviews and Meta-Analysis.

BACKGROUND: Since several studies have examined the use of direct oral anticoagulants (DOACs) in treating patients with splanchnic vein thrombosis (SVT), we conducted a meta-analyses to assess the safety and efficacy of DOACs compared to vitamin K antagonists (VKAs) in this population. METHODS: We conducted a comprehensive search using the PubMed, Embase, and Cochrane Library databases until June 2024. We used odds ratios (ORs) and 95% confidence intervals (CIs) as the effect measures to compare DOACs with VKAs. RESULTS: A total of 9 observational studies were included. The pooled analysis revealed that a trend towards higher complete recanalization rates with DOACs (71.4%) compared to VKAs (55.3%), though not statistically significant (OR 1.95; 95%CI 0.70 to 5.44). For SVT extension, a significant effect was observed favoring DOACs (OR 0.12; 95%CI 0.03 to 0.54). No significant differences were found in other efficacy outcomes or safety outcomes, except for major bleeding, which was significantly lower with DOACs (OR 0.27; 95%CI 0.13 to 0.56). CONCLUSION: DOACs are superior to VKAs in SVT extension and major bleeding, suggesting that DOACs may be a favorable treatment option in the treatment of SVT.

Antihistamine and COVID-19 outcomes in outpatients.

The World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic on March 11, 2020. Since then, researchers have been investigating the efficacy and side effects of its medication, up until now. From the viewpoint of Persian medicine, some medications such as antihistamines may cause retention of secretions and lead to exacerbation and spread of the disease in the body. There are studies with conflicting results regarding the effectiveness of antihistamines in COVID-19. Systematic reviews found a lack of data on beneficial effect of antihistamine-decongestant-analgesic combinations for the common cold and a limited short-term effect of antihistamines on severity of overall symptoms. This prospective cohort study was designed to investigate the relationship between the use of antihistamines and the severity of COVID-19 symptoms. Three hundred patients with a diagnosis of COVID-19 participated in the study in Shiraz, Iran from December 4, 2021 until January 24, 2022. The interviews were conducted via phone call by a single interviewer. Patients were followed weekly for 4 weeks. We collected information by using a data collection form, containing demographic information, underlying disease, COVID-19 symptoms, treatment methods, medications, and a list of antihistamines and herbs that might have been used. Generalized estimating equations were applied to assess the relationship between the severity of COVID-19 and the use of antihistamines, taking into account potential confounding factors such as time and herbal consumption. The difference in the severity of COVID-19 disease in antihistamine users compared to nonusers was not significant in 4 weeks despite the higher baseline severity in nonusers. The comparison of two groups of antihistamine users and nonusers showed that there was a significant difference (p = 0.001) regarding the use of herbal medicines.