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Nursing- and healthcare-associated pneumonia (NHCAP) constitutes most of the pneumonia in elderly patients including aspiration pneumonia in Japan. Lascufloxacin (LSFX) possesses broad antibacterial activity against respiratory pathogens, such as Streptococcus spp. And anaerobes inside the oral cavity. However, the efficacy and safety of LSFX in NHCAP treatment remains unknown. We aimed to evaluate the efficacy and safety of LSFX tablets in the treatment of patients with NHCAP. In this single-arm, open-label, uncontrolled study, LSFX was administered to patients with NHCAP at 24 facilities. The study participants were orally administered 75 mg LSFX once daily for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC). The secondary endpoints included clinical efficacy at the time of end of treatment (EOT), early clinical efficacy, microbiological efficacy, and safety analysis. During the study period, 75 patients provided written informed consent to participate and were included. Finally, 56 and 71 patients were eligible for clinical efficacy and safety analyses, respectively. The median age of the patients was significantly high at 86 years. All patients were classified as having moderate disease severity using the A-DROP scoring system. LSFX tablets demonstrated high efficacy rates of 78.6 % at TOC and 89.3 % at EOT. The risk factors for resistant bacteria or aspiration pneumonia did not affect clinical efficacy. No severe adverse events associated with the study drugs were observed. Oral LSFX is an acceptable treatment option for moderate NHCAP in elderly patients who can take oral medications. [ABSTRACT FROM AUTHOR]

Aim Methods Results Conclusions To compare the efficacy and safety of a fixed‐ratio combination of insulin glargine 100 U/mL plus lixisenatide (iGlarLixi) with premixed insulin, insulin degludec plus insulin aspart (IDegAsp), in Chinese people with type 2 diabetes (T2D) suboptimally controlled with oral antidiabetic drug(s) (OADs).In Soli‐D, a 24‐week, multicentre, open‐label, study, insulin‐naïve adults were randomized 1:1 to once‐daily injections of iGlarLixi (n = 291) or IDegAsp (n = 291), with continued metformin ± sodium‐glucose co‐transporter‐2 inhibitors. The primary endpoint was non‐inferiority in HbA1c change from baseline to week 24. Key secondary endpoints included superiority in HbA1c change and body weight (BW) change at week 24. Hypoglycaemia rates were also assessed.At week 24, iGlarLixi showed non‐inferiority and superiority over IDegAsp in HbA1c reduction (least squares [LS] mean difference: −0.20 [95% confidence interval {CI}: –0.33, −0.07]; P < .001 for non‐inferiority; [97.5% CI: –0.35, −0.05]; P = .003 for superiority). iGlarLixi decreased BW and IDegAsp increased BW from baseline to week 24, with a statistically significant LS mean difference of −1.49 kg in favour of iGlarLixi (97.5% CI: –2.32, −0.66; P < .001). Event rates (per person‐year) for American Diabetes Association (ADA) Level 1, 2 or 3 hypoglycaemia were lower for iGlarLixi (1.90) versus IDegAsp (2.72) (relative risk: 0.71; 95% CI: 0.52, 0.98). No ADA Level 3 hypoglycaemia or unexpected safety findings were reported.In Chinese people with T2D suboptimally controlled with OADs, once‐daily iGlarLixi provided better glycaemic control with BW benefit and lower hypoglycaemia event rates versus IDegAsp. [ABSTRACT FROM AUTHOR]

Accessible Summary What is known on the subject What the paper adds to existing knowledge What are the implications for practice Introduction Aim Method Results Discussion Implications for Practice People living with schizophrenia spectrum disorder (SSD) have a higher death rate which is caused, in part, by poorer adherence to treatment as compared to those with other mental illnesses. Using long‐acting injectable antipsychotic (LAI) medications can improve medication adherence and reduce hospitalizations for people living with SSD but are often underutilized. As compared to oral antipsychotic medications provided to patients with SSD at discharge from a psychiatric hospitalization, being provided with an LAI antipsychotic medication may reduce subsequent rehospitalization. Specifically, patients discharged on an atypical or second‐generation LAI medication are less likely to be readmitted to the hospital when compared to those discharged on a typical first‐generation oral medication. Because LAI antipsychotic medications are often underutilized as treatment options, the study findings suggest that this modality may be considered for patients with SSD when being discharged from a psychiatric hospitalization. Ideally, psychiatric‐mental health nurses can educate patients about indications, benefits, and risks of using atypical or second‐generation LAI antipsychotic medications during hospitalization and at discharge prevent the risk for future rehospitalizations. People living with schizophrenia spectrum disorder (SSD) have poorer medication adherence compared to those with other mental illnesses. Long‐acting injectable antipsychotic (LAI) medication use is associated with greater adherence, reduced re‐hospitalizations, and improved recovery outcomes when compared to oral formulations.To compare LAI antipsychotic medication use versus oral formulations on readmission to an inpatient hospital.Medical records (N = 707) from a state psychiatric hospital in the southern region of the United States were reviewed. Controlling for demographic variables, logistic regression analyses were used to examine LAI compared to oral formulations on readmission.Compared to patients discharged with oral antipsychotic medications, those with LAIs had a lower proportion of readmission rates in 6‐month and 1‐year periods, but not 30‐day or 2‐year periods. When controlling for demographic variables, those discharged with an atypical LAI had significantly lower odds of being readmitted within the 24‐year period compared to those discharged on a typical oral antipsychotic.Compared to orals, LAIs do not increase and may mitigate readmissions to psychiatric hospitalization.Psychiatric‐mental health nurses and other professionals may recommend LAIs when indicated for those with SSD. [ABSTRACT FROM AUTHOR]

Background: Functional drug testing (FDT) with patient-derived tumor cells in microfluidic devices is gaining popularity. However, the majority of previously reported microfluidic devices for FDT were limited by at least one of these factors: lengthy fabrication procedures, absence of tumor progenitor cells, lack of clinical correlation, and mono-drug therapy testing. Furthermore, personalized microfluidic models based on spheroids derived from oral cancer patients remain to be thoroughly validated. Overcoming the limitations, we develop 3D printed mold-based, dynamic, and personalized oral stem-like spheroids-on-a-chip, featuring unique serpentine loops and flat-bottom microwells arrangement. Results: This unique arrangement enables the screening of seven combinations of three drugs on chemoresistive cancer stem-like cells. Oral cancer patients-derived stem-like spheroids (CD 44+) remains highly viable (> 90%) for 5 days. Treatment with a well-known oral cancer chemotherapy regimen (paclitaxel, 5 fluorouracil, and cisplatin) at clinically relevant dosages results in heterogeneous drug responses in spheroids. These spheroids are derived from three oral cancer patients, each diagnosed with either well-differentiated or moderately-differentiated squamous cell carcinoma. Oral spheroids exhibit dissimilar morphology, size, and oral tumor-relevant oxygen levels (< 5% O2). These features correlate with the drug responses and clinical diagnosis from each patient's histopathological report. Conclusions: Overall, we demonstrate the influence of tumor differentiation status on treatment responses, which has been rarely carried out in the previous reports. To the best of our knowledge, this is the first report demonstrating extensive work on development of microfluidic based oral cancer spheroid model for personalized combinatorial drug screening. Furthermore, the obtained clinical correlation of drug screening data represents a significant advancement over previously reported personalized spheroid-based microfluidic devices. Finally, the maintenance of patient-derived spheroids with high viability under oral cancer relevant oxygen levels of less than 5% O2 is a more realistic representation of solid tumor microenvironment in our developed device. [ABSTRACT FROM AUTHOR]

Aim: Atezolizumab and bevacizumab (Atezo/Bev) combination immunotherapy regimens and direct oral anticoagulants (DOACs) are both associated with bleeding. Therefore, combining Atezo/Bev regimens with DOACs may exacerbate the bleeding risk. This study investigated the feasibility of the Atezo/Bev regimen in patients taking DOACs. Methods: This retrospective study included 141 patients with unresectable hepatocellular carcinoma (HCC) or advanced lung cancer (LC) treated with Atezo/Bev regimens. Patients who used antithrombotic agents other than DOACs were excluded. Bleeding events during the Atezo/Bev regimen were analyzed. Results: The incidence rates of bleeding of any grade in the DOAC (n = 11) and no antithrombotic agent (NAA) (n = 130) groups were 9.1% and 10.8%, respectively, with no significant differences. Moreover, no significant difference was found in the frequency of bleeding of grade ≥3 between the DOAC and NAA groups. No patients in the DOAC group discontinued the Atezo/Bev regimen because of severe bleeding. Although serum albumin levels, with a hazard ratio (HR) of 0.298 (95% confidence interval [CI]: 0.105–0.847), independently contributed to bleeding events (p = 0.023), DOAC administration did not (HR: 1.357; 95% CI: 0.157–10.54; p = 0.770). Among only patients with HCC (n = 59), none of the five patients taking DOACs experienced bleeding events. A high albumin–bilirubin score (HR: 9.083, 95% CI: 1.118–73.76) was associated with bleeding events (p = 0.039). Conclusions: DOACs did not have a considerable effect on bleeding events in the Atezo/Bev regimens for HCC or LC. Under careful surveillance for bleeding, Atezo/Bev regimens may be feasible in patients receiving DOACs. [ABSTRACT FROM AUTHOR]

Introduction: Expensive oral specialty drugs for advanced prostate cancer can be associated with treatment disparities. The 340B program allows hospitals to purchase medications at discounts, generating savings that can improve care of the socioeconomically disadvantaged. This study assessed the effect of hospital 340B participation on advanced prostate cancer. Methods: The authors performed a retrospective cohort study of Medicare beneficiaries with advanced prostate cancer from 2012 to 2019. The primary outcome was use of an oral specialty drug. Secondary outcomes included monthly out‐of‐pocket costs and treatment adherence. We evaluated the effects of 1) hospital 340B participation, 2) a regional measure vulnerability, the social vulnerability index (SVI), and 3) the interaction between hospital 340B participation and SVI on outcomes. Results: There were 2237 and 1100 men who received care at 340B and non‐340B hospitals. There was no difference in specialty drug use between 340B and non‐340B hospitals, whereas specialty drug use decreased with increased SVI (odds ratio, 0.95, p =.038). However, the interaction between hospital 340B participation and SVI on specialty drug use was not significant. Neither 340B participation, SVI, or their interaction were associated with out‐of‐pocket costs. Although hospital 340B participation and SVI were not associated with treatment adherence, their interaction was significant (p =.020). This demonstrated that 340B was associated with better adherence among socially vulnerable men. Conclusions: The 340B program was not associated with specialty drug use in men with advanced prostate cancer. However, among those who were started on therapy, 340B was associated with increased treatment adherence in more socially vulnerable men. Men with advanced prostate cancer who received care at a hospital participating in the 340B program had similar utilization of oral specialty drugs as those cared for at nonparticipating hospitals, regardless of social vulnerability. However, care at a 340B hospital was associated with better treatment adherence among those who started on therapy. Further refinement of the program could focus on providing hospitals specific guidance on using savings to benefit the most vulnerable patients. [ABSTRACT FROM AUTHOR]

This review used traditional and network meta-analyses (NMA) to conduct a comprehensive study of antithrombotic therapies in children with thromboembolic disease. We searched the PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov databases from their inception to 26 February, 2023. And we finally included 16 randomized controlled trials. In the prevention of thromboembolic events (TEs), the use of anticoagulants had a low risk of TEs (relative risk (RR) 0.73, 95% CI 0.56 to 0.94) and a high risk of minor bleeding (RR 1.43, 95% CI 1.09 to 1.86) compared with no anticoagulants. In the treatment of TEs, direct oral anticoagulants (DOACs) were not inferior to standard anticoagulation in terms of efficacy and safety outcomes. In NMA, rivaroxaban and apixaban showed the lowest risk for TEs and major or clinically relevant nonmajor bleeding. According to the overall assessment of efficacy and safety, dabigatran may be the best choice for children with thromboembolic disease. The results of our study will provide references and suggestions for clinical drug selection. [ABSTRACT FROM AUTHOR]

A notable increase in direct oral anticoagulant (DOAC) use has been observed in the last decade. This trend has surpassed the prescription of vitamin K antagonists (VKAs) due to the absence of the need for regular laboratory monitoring and the more favorable characteristics in terms of efficacy and safety. However, it is very common that patients on DOACs need an interventional or surgical procedure, requiring a careful evaluation and a challenging approach. Therefore, perioperative anticoagulation management of patients on DOACs represents a growing concern for clinicians. Indeed, while several surgical interventions require temporary discontinuation of DOACs, other procedures that involve a lower risk of bleeding can be conducted, maintaining a minimal or uninterrupted DOAC strategy. Therefore, a comprehensive evaluation of patient characteristics, including age, susceptibility to stroke, previous bleeding complications, concurrent medications, renal and hepatic function, and other factors, in addition to surgical considerations, is mandatory to establish the optimal discontinuation and resumption timing of DOACs. A multidisciplinary approach is required for managing perioperative anticoagulation in order to establish how to face these circumstances. This narrative review aims to provide physicians with a practical guide for DOAC perioperative management, addressing the most controversial issues. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS), also known as Hughes syndrome, is an acquired autoimmune and procoagulant condition that predisposes individuals to recurrent thrombotic events and obstetric complications. Central is the role of three types of antiphospholipid antibodies that target phospholipid-binding proteins: lupus anticoagulant (LAC), anti-β2-glycoprotein I (β2-GPI-Ab), and anti-cardiolipin (aCL). Together with clinical data, these antibodies are the diagnostic standard. However, the diagnosis of APS in older adults may be challenging and, in the diagnostic workup of thromboembolic complications, it is an underestimated etiology. The therapeutic management of APS requires distinguishing two groups with differential risks of thromboembolic complications. The standard therapy is based on low-dose aspirin in the low-risk group and vitamin K antagonists in the high-risk group. The value of direct oral anticoagulants is currently controversial. The potential role of monoclonal antibodies is investigated. For example, rituximab is currently recommended in catastrophic antiphospholipid antibody syndrome. Research is ongoing on other monoclonal antibodies, such as daratumumab and obinutuzumab. This narrative review illustrates the pathophysiological mechanisms of APS, with a particular emphasis on cardiovascular complications and their impact in older adults. This article also highlights advancements in the diagnosis, risk stratification, and management of APS. [ABSTRACT FROM AUTHOR]

Background: Plasma exchange (PLEX) therapy is indicated for several disorders. The 5% albumin is often used as a sole replacement fluid during most PLEX. However, each 1.0 plasma volume exchange depletes coagulation factors by ~65%. Although most coagulation factors recover to hemostatic levels within 24 h post‐PLEX, fibrinogen requires 48–72 h to recover. Fibrinogen is the key coagulation protein for hemostasis. Therefore, fibrinogen is often monitored during the acute course of PLEX, and plasma is supplemented to prevent bleeding if fibrinogen is <100 mg/dL. Study Design and Methods: We conducted a prospective, single‐center, observational study to evaluate bleeding risk in adults who received an acute course of PLEX with a fibrinogen level of 80–100 mg/dL without plasma supplementation during the procedure or before central venous catheter removal. The study group was compared to patients with plasma fibrinogen >100 mg/dL. Results: Among the 275 patients who received 1406 PLEXes, 62 patients (23%) who underwent 323 PLEXes met the inclusion criteria, and only 2 (3%) patients had bleeding while on oral anticoagulants. In contrast, out of 275 patients, 143 (52%) with fibrinogen levels >100 mg/dL received 751 PLEX treatments, and bleeding occurred in 2 (1%) while on low‐molecular‐weight heparin. Conclusions: Our findings suggest that a pre‐procedure fibrinogen threshold of 80–100 mg/dL without plasma supplementation does not increase bleeding risk unless patients were on anticoagulation. See editorial on page 959–962, in this issue [ABSTRACT FROM AUTHOR]

Oral anticoagulant therapy (OAT) for managing atrial fibrillation (AF) encompasses vitamin K antagonists (VKAs, such as warfarin), which was the mainstay of anticoagulation therapy before 2010, and direct-acting oral anticoagulants (DOACs, namely dabigatran etexilate, rivaroxaban, apixaban, edoxaban), approved for the prevention of AF stroke over the last thirteen years. Due to the lower risk of major bleeding associated with DOACs, anticoagulant switching is a common practice in AF patients. Nevertheless, there are issues related to OAT switching that still need to be fully understood, especially for patients in whom AF and heart failure (HF) coexist. Herein, the effective impact of the therapeutic switching from warfarin to DOACs in HF patients with AF, in terms of cardiac remodeling, clinical status, endothelial function and inflammatory biomarkers, was assessed by a machine learning (ML) analysis of a clinical database, which ultimately shed light on the real positive and pleiotropic effects mediated by DOACs in addition to their anticoagulant activity. [ABSTRACT FROM AUTHOR]

Cardioembolic stroke accounts for over 20% of ischemic strokes and is associated with worse outcomes than other types of strokes. Atrial fibrillation (AF) is the most common risk factor for cardioembolic stroke. In this narrative review, we present an update about cardioembolic stroke mainly related to AF and atrial cardiopathy. Direct oral anticoagulants (DOACs) have revolutionized stroke prevention in patients with AF; however, their efficacy in preventing recurrent embolic stroke of unknown source remains uncertain. Various cardiac monitoring methods are used to detect AF, which is crucial for preventing stroke recurrence. DOACs are preferred over warfarin for AF-related stroke prevention; however, the timing of initiation after acute ischemic stroke is debated. Resuming anticoagulation after intracerebral hemorrhage in AF patients requires careful assessment of the risks. While catheter ablation may reduce the incidence of cardiovascular events, its effect on stroke prevention is unclear, especially in heart failure patients. Atrial cardiopathy is the emerging cause of embolic stroke of unknown source, which indicates atrial structural and functional disorders that can precede AF. Future research should focus on refining stroke risk prediction models, optimizing AF detection, understanding the roles of ablation and anticoagulation in stroke prevention, and establishing atrial cardiopathy as a therapeutic target, which could significantly reduce the burden of stroke. [ABSTRACT FROM AUTHOR]

Pancreatic ductal adenocarcinoma (PDAC) accounts for more than 90% of all pancreatic cancers and is the most fatal of all cancers. The treatment response from combination chemotherapies is far from satisfactory and surgery remains the mainstay of curative strategies. These challenges warrant identifying effective treatments for combating this deadly cancer. PDAC tumor progression is associated with the robust activation of the coagulation system. Notably, cancer-associated thrombosis (CAT) is a significant risk factor in PDAC. CAT is a concept whereby cancer cells promote thromboembolism, primarily venous thromboembolism (VTE). Of all cancer types, PDAC is associated with the highest risk of developing VTE. Hypoxia in a PDAC tumor microenvironment also elevates thrombotic risk. Direct oral anticoagulants (DOACs) or low-molecular-weight heparin (LMWH) are used only as thromboprophylaxis in PDAC. However, a precision medicine approach is recommended to determine the precise dose and duration of thromboprophylaxis in clinical setting. [ABSTRACT FROM AUTHOR]

Summary: Hip fracture is a common serious injury among older adults, yet the management of hip fractures for patients taking direct oral anticoagulants remains inconsistent worldwide. Drawing from a synthesis of available evidence and expert opinion, best practice approaches for managing patients with a hip fracture and who are taking direct oral anticoagulants pre‐operatively were considered by a working group of the Fragility Fracture Network Hip Fracture Audit Special Interest Group. The literature and related clinical guidelines were reviewed and a two‐round modified Delphi study was conducted with a panel of experts from 16 countries and involved seven clinical specialities. Four consensus statements were achieved: peripheral nerve blocks can reasonably be performed on presentation for patients with hip fracture who are receiving direct oral anticoagulants; hip fracture surgery can reasonably be performed for patients taking direct oral anticoagulants < 36 h from last dose; general anaesthesia could reasonably be administered for patients with hip fracture and who are taking direct oral anticoagulants < 36 h from last dose (assuming eGFR > 60 ml.min‐1.1.73 m‐2); and it is generally reasonable to consider recommencing direct oral anticoagulants (considering blood loss and haemoglobin) < 48 h after hip fracture surgery. No consensus was achieved regarding timing of spinal anaesthesia. The consensus statements were developed to aid clinicians in their decision‐making and to reduce practice variations in the management of patients with hip fracture and who are taking direct oral anticoagulants. Each statement will need to be considered specific to each individual patient's treatment. [ABSTRACT FROM AUTHOR]

Safety and efficacy are the most critical factors for the development of modern medications. For oral drugs, evaluating drug exposure under various conditions is one of the most important outcomes for clinical trials. These data will help to better understand the safety and efficacy of new drugs. Studies involving potential drug-drug interactions, proton pump inhibitors, and intake of food are often conducted to assess the above. Among the above, the influence of food on exposure to the drug is one of the key data sets for regulatory submission. Since food may have either a positive or negative effect on drug exposure, it is important to obtain an early assessment of the food effect. To better forecast and plan for clinical studies, substantial efforts have been made in the industry to develop modeling and in-vitro and in–vivo assays. Despite the efforts, predicting the effect of food on exposure without integrating the dynamic of the gastrointestinal tract in the assessment remains challenging. In this study, we evaluated the utilization of the dynamic Gastro-Intestinal Model (Tiny-TIM) for the food effect of over 20 drugs/formulations in development or on the market that covers all BCS classes. In general, the Tiny-TIM predicted food effects were in good agreement with the reported data in humans. This suggests that Tiny-TIM can successfully capture the impact of physicochemical properties on absorption under the influence of food. [ABSTRACT FROM AUTHOR]

Aims: To investigate the negative attitudes of Japanese psychiatrists toward atypical long‐acting injectable (LAI) antipsychotics, which are the current mainstream LAIs in Japan. Methods: We surveyed 69 Japanese psychiatrists using a 5‐point Likert scale to assess their attitudes toward atypical LAI antipsychotics. Our assessment referenced concerns identified in a study conducted in Japan a decade ago, which found significant differences when compared with a survey of German psychiatrists. We also identified the factors influencing these negative attitudes. Additionally, the results were compared with those of previous Japanese and German studies. Results: More than 50% of Japanese psychiatrists expressed negative attitudes toward atypical LAI antipsychotics in various areas. These concerns included apprehensions about cost, reluctance to recommend them initially, pain from injections, complexity of switching to LAI, usage in first‐episode cases, and sufficient medication adherence with oral drugs. In all three studies, cost and adequate adherence to oral medication were concerns that exceeded the average of the three negative comments. Age and experience in psychiatry influenced the psychiatrists' attitudes toward using these drugs in first‐episode cases. Conclusions: These findings shed light on the reasons for the underutilization of atypical LAI antipsychotics and suggest opportunities to enhance their appropriate use in clinical settings. [ABSTRACT FROM AUTHOR]

Direct oral anticoagulants (DOACs) are increasingly used and can be involved in clinically relevant drug-drug interactions (DDIs) that increase the risk of major bleeding or thromboembolism. Skilled drug interaction management is essential to ensure safe and effective use of DOACs. In this study, we aimed to investigate the impact of the detection and management of DDIs with DOACs in a real-life community pharmacy setting on the pharmacotherapy of DOAC users. We conducted an intervention study in 201 community pharmacies in Belgium. On random days, patients purchasing DOACs or drugs known to interact with them were screened. When a DDI with the DOAC was detected, the pharmacist contacted the prescribing physician to discuss the management of the interaction. A previously developed practice-oriented DDI list accompanied by management plans for ambulatory care was used for both screening and management of the DDIs. In total, 751 patients were included, among whom 875 DDIs were identified, primarily pharmacodynamic DDIs (95.7 %). Predominant interacting drug classes included selective serotonin or serotonin and norepinephrine reuptake inhibitors (32.9 %), antiplatelets (30.9 %), and non-steroidal anti-inflammatory drugs (28.9 %). In 43.0 % of DDIs, an intervention was decided upon. At three-month follow-up, proposed pharmacotherapy changes had been implemented in 79.1 % of these DDIs. This study demonstrates that active screening and management of DDIs with DOACs in community pharmacies, in close collaboration with prescribing physicians, resulted in changes in pharmacotherapy in a substantial number of patients. This may contribute significantly to the safer utilisation of DOACs in high-risk populations. • DOACs may be implicated in DDIs with significant clinical relevance. • Skilled drug interaction management is thus essential to ensure safe use of DOACs. • Studies on DDI management with DOACs in real-life ambulatory care are lacking. • We conducted an intervention study in over 200 community pharmacies in Belgium. • Active DDI management significantly impacted DOAC pharmacotherapy. [ABSTRACT FROM AUTHOR]

This systematic review assesses the likelihood of developing dementia and cognitive impairment in patients with atrial fibrillation (AF) receiving non-vitamin K antagonist oral anticoagulants (NOACs) as opposed to vitamin K antagonists (VKAs). We performed a systematic review with meta-analysis and trial sequential analysis (TSA), which encompassed both randomized controlled trials (RCTs) and observational studies. The objective was to assess the impact of NOACs and VKAs on the incidence of dementia in individuals diagnosed with AF. Out of 1914 studies that were screened, 31 studies were included in the final analysis, which consisted of nine RCTs or their subsequent post-hoc analyses, in addition to 22 observational studies. The meta-analysis shows that NOACs were associated with a decreased probability of developing dementia of any cause [Rate Ratio (RR): 0.88; 95 % confidence interval (95 % CI): 0.82–0.94], especially in patients below the age of 75 (RR: 0.78; 95 % CI: 0.73–0.84). Consistent patterns were observed across all forms of dementia and cognitive function decline. The overall evidence indicates notable variability in the outcome with a moderate-to-low degree of certainty. The TSA suggests that the total sample size of the included trials (155,647 patients) was significantly smaller than the required information size of 784,692 patients to discern the true effect of NOAC versus VKA in terms of reducing dementia risk. NOACs may reduce the likelihood of developing dementia in patients with AF, particularly in those under the age of 75. This review highlights the urgent necessity for thorough research to determine the efficacy of NOACs in safeguarding cognitive health. • The optimal treatment to lower incidence of dementia for AF patients remained elusive. • NOACs were associated with a decreased probability of developing all-cause dementia. • The negative association between NOACs and risk of dementia is more prominent in patients <75 years old. • Insufficient required information size was noted to determine the true effect of NOACs. [ABSTRACT FROM AUTHOR]

Falls are one of the most fearsome events in anticoagulated older adults. The evidence concerning safety of direct oral anticoagulants (DOACs) in falling elderly patients with atrial fibrillation (AF) is still limited. We prospectively enrolled consecutive anticoagulant-naïve patients aged 65 years and older, starting anticoagulation with DOACs for AF. The study cohort was stratified in fallers vs. non-fallers, according to the occurrence of at least one fall during the 2-year follow-up and bleeding outcomes were evaluated. We enrolled 524 consecutive patients. Mean age was 80.8 years and they were mostly women (54.0%). Among the study cohort, 148 patients (28.2%) presented at least one fall episode during the study period. After the adjustment for potential confounders, no difference was found between fallers and non-fallers for all the study outcomes: major bleeding [HR: 1.04 (95%CI: 0.58–1.85)], intracranial haemorrhage [HR: 1.63 (95%CI: 0.69–3.80)], clinically relevant non-major bleeding [HR: 1.21 (95%CI: 0.83–1.76)], and all-cause death [HR: 1.51 (95%CI: 0.85–2.69)]. The presence of a prior cerebrovascular event [HR: 2.27 (95%CI: 1.12–4.62); p-value: 0.02] and polypharmacy [HR: 1.60 (95%CI: 1.08–2.39); p-value: 0.02] were the main drivers for major and clinically relevant non-major bleedings, respectively. Falls in an anticoagulant-naïve population aged 65 years and over starting a DOAC for AF do not increase the bleeding risk. Thus, the presence of falls should not discourage clinicians from prescribing DOACs also in this subset of patients. • Safety of DOACs in older adults with AF and falls was evaluated. • Falls did not increase the bleeding risk in older adults with AF on DOACs. • The presence of falls should not dissuade from prescribing DOACs in this population. • DOACs dose reduction should be adopted only when the appropriate criteria are met. • Cerebrovascular events and polypharmacy showed to be key predictors of bleeding. [ABSTRACT FROM AUTHOR]

Patients aged ≥65 years not only account for the majority of patients with atrial fibrillation (AF) and venous thromboembolism (VTE), they are also at a higher risk of morbidity, mortality, and undertreatment than younger patients. Several age-related physiological changes with effects on drug pharmacokinetics/−dynamics and blood vessel fragility as well as the higher prevalence of geriatric conditions such as frailty, multimorbidity, polypharmacy, fall risk, dementia, and malnutrition make older persons more vulnerable to disease- and anticoagulation-related complications. Moreover, because older patients with AF/VTE are underrepresented in oral anticoagulation (OAC) trials, evidence on OAC in older adults with AF/VTE is mainly based on subgroup analyses from clinical trials and observational studies. A growing body of such limited evidence suggests that direct oral anticoagulants (DOACs) may be superior in terms of efficacy and safety compared to vitamin K antagonists in older persons with AF/VTE and that specific DOACs may have a differing risk-benefit profile. In this narrative review, we summarize the evidence on epidemiology of AF/VTE, impact of age-related physiological changes, efficacy/safety of OAC, specifically considering individuals with common geriatric conditions, and review OAC guideline recommendations for older adults with AF/VTE. We also propose a research agenda to improve the evidence basis on OAC older individuals with AF/VTE, including the conduct of advanced age-specific and pragmatic studies using less restrictive eligibility criteria and patient-reported health outcomes, in order to compare the effectiveness and safety of different DOACs, and investigate lower-dose regimens and optimal OAC durations in older patients. • Older adults are underrepresented in anticoagulation trials and guidelines for AF and VTE • Advanced age and several geriatric conditions increase the risk of thromboembolic events and bleeding • Limited evidence suggests that DOACs may be more effective and safer than vitamin K antagonists in older adults • Apixaban and edoxaban might have the most favorable risk-benefit profile in older individuals [ABSTRACT FROM AUTHOR]

Background: Utilization of oral anticoagulants for acute ischemic stroke (AIS) prevention in patients with atrial fibrillation (AF) increased in the United States over the last decade. Whether this increase has been accompanied by any change in AF prevalence in AIS at the population level remains unknown. The aim of this study is to evaluate trends in AF prevalence in AIS hospitalizations in various age, sex, and racial subgroups over the last decade. Methods: We used data contained in the 2010–2020 National Inpatient Sample to conduct a serial cross-sectional study. Primary AIS hospitalizations with and without comorbid AF were identified using International Classification of Diseases Codes. Joinpoint regression was used to compute annualized percentage change (APC) in prevalence and to identify points of change in prevalence over time. Results: Of 5,190,148 weighted primary AIS hospitalizations over the study period, 25.1% had comorbid AF. The age- and sex-standardized prevalence of AF in AIS hospitalizations increased across the entire study period 2010–2020 (average APC: 1.3%, 95% confidence interval (CI): 0.8–1.7%). Joinpoint regression showed that prevalence increased in the period 2010–2015 (APC: 2.8%, 95% CI: 1.9–3.9%) but remained stable in the period 2015–2020 (APC: –0.3%, 95% CI: –1.0 to 1.9%). Upon stratification by age and sex, prevalence increased in all age/sex groups from 2010 to 2015 and continued to increase throughout the entire study period in hospitalizations in men 18–39 years (APC: 4.0%, 95% CI: 0.2–7.9%), men 40–59 years (APC: 3.4%, 95% CI: 1.9–4.9%) and women 40–59 years (APC: 4.4%, 95% CI: 2.0–6.8%). In contrast, prevalence declined in hospitalizations in women 60–79 (APC: –1.0%, 95% CI: –0.5 to –1.5%) and women ⩾ 80 years over the period 2015–2020 but plateaued in hospitalizations in similar-aged men over the same period. Conclusion: AF prevalence in AIS hospitalizations in the United States increased over the period 2010–2015, then plateaued over the period 2015–2020 due to declining prevalence in hospitalizations in women ⩾ 60 years and plateauing prevalence in hospitalizations in men ⩾ 60 years. [ABSTRACT FROM AUTHOR]

Background: Recent years have seen a change in the use of anticoagulants in the general population due to the availability of direct oral anticoagulants (DOACs) as an alternative to vitamin K antagonists (VKAs) and increased detection of atrial fibrillation. It is important to have updated epidemiological data to understand how this change is impacting on the occurrence and outcome of intracerebral hemorrhage (ICH). Patients and methods: Our prospective population-based registry included patients with first-ever ICH occurring from January 2011 to December 2020. Oral anticoagulants (OAC)-related ICH was defined as an ICH occurring within 48 h from the intake of DOAC or VKAs, regardless of the measured international normalized ratio on hospital admission. Results: We included 748 first-ever ICH, of whom 108 (14.4%) were OAC-related. Specifically, 75 (69.4%) ICHs occurred on VKA and 33 (30.6%) on DOAC. The incidence of oral anticoagulation-associated intracerebral hemorrhage (OAC-ICH) was stable over time (p = 0.226). Among OAC-ICHs, we observed an increase in the overall incidence of DOAC-ICH (p for trend < 0.001) which overcome that of VKA-ICH in 2020 (incidence rate ratio (IRR) 4.71, 95% confidence interval (CI): 1.22–33.54; p = 0.022). Patients with OAC-ICH showed higher 30-day case fatality rates than those with non-OAC-ICH (48.1% vs 34.1%; p = 0.007). Conclusion: No changes over time were detected in the incidence of OAC-ICH, but throughout the study period, there was a change in OAC-ICH from mostly VKA-related to mostly DOAC-related. Mortality in patients with OAC-ICH was higher than in patients with non-OAC-ICH. [ABSTRACT FROM AUTHOR]

patients with atrial fibrillation (AF) under treatment with chronic oral anticoagulation (OAC) often require coronary angiography with or without percutaneous coronary intervention (PCI). Deciding the management of OAC during this periprocedural period requires balancing the risks of hemorrhage and thrombotic complications. Guidelines recommend an uninterrupted strategy in patients receiving Vitamin-K Antagonists (VKA). However, for patients undergoing coronary angiography or PCI while on direct oral anticoagulants (DOACs), withdrawal 12–24 h prior to the procedure is still recommended. This is based on expert opinions given the lack of evidence. Therefore, whether DOAC discontinuation prior to trans-radial coronary procedures should be the strategy of choice is a matter of debate and solid evidence is needed to guide clinical decision making. The DOAC-NOSTOP study is a prospective, single-arm, open-label study evaluating the safety of DOACs continuation in 200 patients undergoing transradial percutaneous coronary procedures. DOAC treatment will not be interrupted throughout the periprocedural period. Primary outcome will be Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 events, assessed at a 30-day follow-up. The DOAC-NOSTOP is the first study prospectively assessing the risk of bleeding with uninterrupted DOAC in patients undergoing trans-radial percutaneous coronary procedures. Timeline of the DOAC-NOSTOP study. DOAC: Direct-acting oral anticoagulation; BARC: Bleeding Academic Research Consortium. [Display omitted] • Current guidelines suggest DOAC withdrawal pre-procedure based on expert consensus due to limited trial data. • The DOAC-NOSTOP aims to evaluate the safety of uninterrupted DOAC use in these procedures. • The results could impact clinical practice refining recommendations for DOAC management in this context. [ABSTRACT FROM AUTHOR]

As an essential branch of targeted drug delivery, oral targeted delivery is attracting growing attention in recent years. In addition to site-specific delivery for the treatment of locoregional diseases in the gastrointestinal tract (GIT), oral targeted delivery to remote sites beyond the GIT emerges as a cutting-edge research topic. This review aims to provide an overview of the fundamental concepts and most recent advances in this field. Owing to the physiological barriers existing in the GIT, carrier systems should be transported across the enteric epithelia to target remote sites. Recently, pioneer investigations have validated the transport of intact micro- or nanocarriers across gastrointestinal barriers and subsequently to various distal organs and tissues. The microfold (M) cell pathway is the leading mechanism underlying the oral absorption of particulates, but the contribution of the transcellular and paracellular pathways should not be neglected either. In addition to well-acknowledged physicochemical and biological factors, the formation of a protein corona may also influence the biological fate of carrier systems. Although in an early stage of conceptualization, oral targeted delivery to remote diseases has demonstrated promising potential for the treatment of inflammation, tumors, and diseases inflicting the lymphatic and mononuclear phagocytosis systems. [Display omitted] • Peroral targeting of CDDSs to sites beyond the GIT has emerged as an intriguing research topic. • Transepithelial absorption of micro/nanocarriers is a prerequisite for oral targeted delivery. • Pioneering studies have revealed the oral absorption and subsequent distribution of nanocarriers to different post-GIT tissues and organs. • M cell-to-lymphatic transport is the leading mechanism underlying the oral absorption of nanocarriers. • Targeting to lymph, MPS, tumor, and inflammatory sites represents the major application of peroral targeting. [ABSTRACT FROM AUTHOR]

Pulmonary embolus (PE) carries a significant impending morbidity and mortality, especially in intermediate and high-risk patients, and the choice of initial anticoagulation that allows for therapeutic adjustment or manipulation is important. The preferred choice of anticoagulation management includes direct oral anticoagulants. Vitamin K antagonists and low-molecular-weight heparin are preferred in special populations or selected patients such as breastfeeding mothers, those with end-stage renal disease, or obese patients, among others. This article reviews the primary and longer-term considerations for anticoagulation management in patients with PE and highlights special patient populations and risk factor considerations. [ABSTRACT FROM AUTHOR]

Spontaneous intracerebral hemorrhage (SICH) remains a devastating form of stroke. Prior use of antiplatelets or warfarin before SICH is associated with poor outcomes, but the effects of direct oral anticoagulants (DOACs) remain unclear. This study aimed to clarify trends in prior antithrombotic use and to assess the associations between prior use of antithrombotics and in-hospital mortality using a multicenter prospective registry in Japan. In total, 1085 patients were analyzed. Prior antithrombotic medication included antiplatelets in 14.2%, oral anticoagulants in 8.1%, and both in 1.8%. Prior warfarin use was significantly associated with in-hospital mortality (odds ratio [OR] 5.50, 95% confidence interval [CI] 1.30–23.26, P < 0.05) compared to no prior antithrombotic use. No such association was evident between prior DOAC use and no prior antithrombotic use (OR 1.34, 95% CI 0.44–4.05, P = 0.606). Concomitant use of antiplatelets and warfarin further increased the in-hospital mortality rate (37.5%) compared to warfarin alone (17.2%), but no such association was found for antiplatelets plus DOACs (8.3%) compared to DOACs alone (11.9%). Prior use of warfarin remains an independent risk factor for in-hospital mortality after SICH in the era of DOACs. Further strategies are warranted to reduce SICH among patients receiving oral anticoagulants and to prevent serious outcomes. [ABSTRACT FROM AUTHOR]

Warfarin remains the most prescribed oral anticoagulant of choice in atrial fibrillation (AF) patient in resource-limited settings. Despite evidence linking Time in Therapeutic Range (TTR) to patient outcomes, its use in clinical practice is not widespread. This prospective study explores the impact of a TTR-INR guided Warfarin adjustment protocol on TTR in AF patients. Conducted at the Warfarin clinic of King Chulalongkorn Memorial Hospital. TTR was calculated using the Rosendaal linear interpolation method at baseline, and then at 6 and 12 months post-protocol implementation. The primary outcome was the improvement in TTR following the protocol's implementation. The study analyzed 57 patients, with a mean age of 72 years and an even gender distribution. At baseline, 53% of patients had a TTR of less than 65%. However, TTR significantly improved from 65% at baseline to 80% after 12 months of protocol implementation (p < 0.001). Furthermore, there was a significant increase in the proportion of patients with a TTR of 65% or more, from 47 to 88% (p < 0.001). During the follow-up period in the first 12 months, three patients died, but no ischemic or major bleeding events occurred. The significant improvement in TTR after 12 months of protocol implementation suggests that this strategy could provide additional value in improving TTR and outcomes in AF patients receiving Warfarin. [ABSTRACT FROM AUTHOR]

Ursodeoxycholic acid (UDCA) is a tertiary bile acid synthesized by the liver and has various functions such as promoting bile secretion, antibacterial effect, inflammatory treatment, cholesterol reduction, and degradation. UDCA seems to be a material that can be applied in many aspects, such as adding it to implant coating materials or wound coatings. However, until now, only experiments and studies have been conducted to administer UDCA orally as a drug. In this paper, research was conducted to serve as a foothold for the application of UDCA to in vitro research. In this study, polymer fibers were prepared using electrospinning technology by mixing UDCA with Polycaprolactone(PCL), a biocompatible polymer. Through various analyses, it was confirmed that UDCA was contained in the electrospun membrane. In addition, it was confirmed that UDCA functions properly through the appearance of antimicrobial properties in antimicrobial experiments. The PCL/UDCA electrospun fiber prepared in this study and the analysis results using it show that UDCA can be applied not only to oral drugs but also to various fields such as wound coverings and stent coating membranes. [ABSTRACT FROM AUTHOR]

Background/Objective: No guidelines indicate surgical risk factors for the elderly because of the lack of data from general neurosurgeons. To better understand the management of surgical risk in elderly patients with meningiomas based on a national database in Japan. Methods: Results of surgically treated meningiomas were explored in 8138 patients registered in the Diagnosis Procedure Combination database in Japan during 2010–2015. Age (<65, 65–74, and ≥75 years), sex, Barthel index (BI), medical history, tumor location, oral medication prescriptions on admission, and stroke complications were evaluated. Multivariate logistic regression analysis identified risk factors for stroke complications, BI deterioration between admission and discharge, and in-hospital mortality. Results: Advanced age was the prominent risk factor for BI deterioration (odds ratio: 3.26; 95% confidence interval: 2.69–3.95) but not for in-hospital mortality. Lower BI (60–80) on admission increased the risk of BI deterioration in all age groups; however, BI < 60 demonstrated a significant inverse risk (0.47; 0.32–0.69) in the elderly (≥75 years). Location (falx, parasagittal, and deep) and anticoagulants were not significant risk factors for BI deterioration in patients aged ≥ 75 years, despite being significant risk factors in patients aged <65 and/or 65–74 years. Conclusions: Although advanced age could lead to postoperative functional decline at discharge, it was not sufficiently significant enough to be associated with in-hospital mortality. Because of the possibility of recovery even in elderly patients with severe disabilities, appropriate surgical selection and optimal management may lead to favorable functional outcomes in elderly patients with meningiomas. [ABSTRACT FROM AUTHOR]

Background: Oral anticoagulation reduces stroke risk for patients with atrial fibrillation (AF). Prior research demonstrates lower anticoagulant prescribing in Black than in White individuals but few studies have examined racial differences in facility-level anticoagulant prescribing for AF. Objective: To assess variation in anticoagulant initiation by race within Veterans Health Administration (VA) facilities. Design: Retrospective cohort study. Participants: Black and White patients enrolled in the VA with incident AF from 2020 through 2021. Main Measures: The primary outcome was rate of any anticoagulant initiation (i.e., warfarin or direct oral anticoagulant [DOAC]) or any DOAC therapy within 90 days of an AF diagnosis, overall and for Black and White patients at each facility. We also estimated the adjusted Black-White risk difference. Key Results: In 82 VA facilities serving 26,832 Black and White patients, overall unadjusted rates of any anticoagulant therapy ranged from 56.8 to 87.1% across facilities; the corresponding ranges for Black and White patients were 47.6 to 91.3% and 58.2 to 87.1%, respectively. Overall unadjusted rates of DOAC therapy ranged from 55.1 to 85.5% by facility; ranges for Black and White patients were 42.8 to 86.9% and 56.4 to 85.5%, respectively. The adjusted risk difference between Black and White patients ranged from − 29.9 (95% CI, − 54.9 to − 4.8) to 14.2 (95% CI, − 9.1 to 25.0) across facilities for any anticoagulant therapy and from − 28.8 (95% CI, − 58.3 to 0.8) to 15.0 (95% CI, − 8.0 to 38.1) for DOAC therapy. For any anticoagulant therapy there were 3 facilities where prescribing was statistically higher in White than Black patients; for DOAC therapy there were 5 such facilities. Conclusions: In a national cohort of patients with AF, we observed large facility-level variation and adjusted risk differences in any anticoagulant and DOAC initiation, overall and by race. These findings represent a target for local quality improvement in AF care. [ABSTRACT FROM AUTHOR]

Portal vein thrombosis (PVT) worsens the long-term prognosis of patients with cirrhosis; however, the optimal treatment remains to be determined. Reports on the efficacy of direct oral anticoagulants are increasing, and further evidence is needed. Therefore, we investigated the effectiveness of treatment with edoxaban in patients with PVT. We retrospectively reviewed the outcomes of edoxaban and warfarin as antithrombotic therapies for PVT. The median overall survival time was 4.2 years in patients with PVT, with a 1-year survival rate of 70.7% and a 5-year survival rate of 47.9%. The leading cause of death was hepatocellular carcinoma. The overall response rate for thrombolysis in the edoxaban group was 76.7% compared to 29.4% in the warfarin group, and edoxaban significantly improved PVT compared to warfarin. In addition, edoxaban provided long-term improvement of PVT. Warfarin, on the other hand, was temporarily effective but did not provide long-term benefits. The Child–Pugh and albumin-bilirubin scores did not change after edoxaban or warfarin use. No deaths occurred due to adverse events associated with edoxaban or warfarin. Edoxaban as a single agent can achieve long-term recanalization without compromising the hepatic reserves. Edoxaban is easy to initiate, even in an outpatient setting, and could become a major therapeutic agent for the treatment of PVT. [ABSTRACT FROM AUTHOR]

Purpose: Midostaurin, approved for treating FLT-3-mutated acute myeloid leukemia and advanced systemic mastocytosis, is metabolized by cytochrome P450 (CYP) 3A4 to two major metabolites, and may inhibit and/or induce CYP3A, CYP2B6, and CYP2C8. Two studies investigated the impact of midostaurin on CYP substrate drugs and oral contraceptives in healthy participants. Methods: Using sentinel dosing for participants' safety, the effects of midostaurin at steady state following 25-day (Study 1) or 24-day (Study 2) dosing with 50 mg twice daily were evaluated on CYP substrates, midazolam (CYP3A4), bupropion (CYP2B6), and pioglitazone (CYP2C8) in Study 1; and monophasic oral contraceptives (containing ethinylestradiol [EES] and levonorgestrel [LVG]) in Study 2. Results: In Study 1, midostaurin resulted in a 10% increase in midazolam peak plasma concentrations (Cmax), and 3–4% decrease in total exposures (AUC). Bupropion showed a 55% decrease in Cmax and 48–49% decrease in AUCs. Pioglitazone showed a 10% decrease in Cmax and 6% decrease in AUC. In Study 2, midostaurin resulted in a 26% increase in Cmax and 7–10% increase in AUC of EES; and a 19% increase in Cmax and 29–42% increase in AUC of LVG. Midostaurin 50 mg twice daily for 28 days ensured that steady-state concentrations of midostaurin and the active metabolites were achieved by the time of CYP substrate drugs or oral contraceptive dosing. No safety concerns were reported. Conclusion: Midostaurin neither inhibits nor induces CYP3A4 and CYP2C8, and weakly induces CYP2B6. Midostaurin at steady state has no clinically relevant PK interaction on hormonal contraceptives. All treatments were well tolerated. [ABSTRACT FROM AUTHOR]

In clinical practice, the number of patients treated with direct oral anticoagulants (DOACs) has consistently increased over the years. Since anticoagulant therapy has been associated with an annual incidence of major bleeding (MB) events of approximately 2% to 3.5%, it is of paramount importance to understand how to manage anticoagulated patients with major or life-threatening bleeding. A considerable number of these patients' conditions necessitate hospitalization, and the administration of reversal agents may be imperative to manage and control bleeding episodes effectively. Importantly, effective strategies for reversing the anticoagulant effects of DOACs have been well recognized. Specifically, idarucizumab has obtained regulatory approval for the reversal of dabigatran, and andexanet alfa has recently been approved for reversing the effects of apixaban or rivaroxaban in patients experiencing life-threatening or uncontrolled bleeding events. Moreover, continuous endeavors are being made to develop supplementary reversal agents. In emergency scenarios where specific reversal agents might not be accessible, non-specific hemostatic agents such as prothrombin complex concentrate can be utilized to neutralize the anticoagulant effects of DOACs. However, it is paramount to emphasize that specific reversal agents, characterized by their efficacy and safety, should be the preferred choice when suitable. Moreover, it is worth noting that adherence to the guidelines for the reversal agents is poor, and there is a notable gap between international recommendations and actual clinical practices in this regard. This narrative review aims to provide physicians with a practical approach to managing specific reversal agents. [ABSTRACT FROM AUTHOR]

Long‐acting technologies (LATs) for hepatitis C virus (HCV) are under development as a strategy to improve linkage to care, treatment adherence and outcomes. We conducted a survey of HCV treatment prescribers and HCV policymakers in low‐ and middle‐income countries (LMICs) regarding acceptability and feasibility of HCV LATs. We included one‐time intramuscular injection, subdermal implant and transdermal patch as potential LAT options. We surveyed participants regarding optimal health system and patient characteristics, concerns, potential barriers, overall feasibility and preferences for HCV LAT as compared to daily oral medication. Overall, 122 providers and 50 policymakers from 42 LMICs completed the survey. Among providers, 93% (113/122) expressed willingness to prescribe LAT and 72% (88/120) of providers preferred LAT if provided at comparable efficacy, safety and cost as current oral treatments. Of providers preferring HCV LAT to daily oral medication, 67% (59/88) preferred injection, 24% (21/88) preferred patch and 9% (8/88) preferred implant. Only 20% (24/122) would prescribe LAT if it were more costly than oral treatment. In regression analysis, no provider characteristics were associated with preference for LAT over oral treatment. Policymakers reported high likelihood that LAT would be included in treatment guidelines (42/50; 84%) and national drug formularies (39/50; 78%) if efficacy, safety and cost were similar to oral treatment. HCV LATs could advance progress to HCV elimination in LMICs by diversifying treatment options to improve treatment coverage and outcomes. Provider preferences from LMICs are a critical consideration in the development of HCV LATs to ensure its early and equitable availability in LMICs. [ABSTRACT FROM AUTHOR]

While there are some recommendations about early insulin therapy in newly diagnosed Type 2 Diabetes Mellitus (T2DM) patients, there is not sufficient evidence on this strategy's cost-effectiveness. This study compared early insulin therapy versus oral anti-diabetic drugs (OADs) for managing T2DMusing a cost-effectiveness analysis approach in Iran. In this economic evaluation, a decision analytic model was designed. The target population was newly diagnosed type 2 diabetic patients, and the study was carried out from the perspective of Iran's healthcare system with a one-year time horizon. Basal insulin, Dipeptidyl peptidase-4 (DPP-4) inhibitors, and Thiazolidinediones (TZDs) were compared in this evaluation. The main outcome for assessing the effectiveness of each intervention was the reduction in the occurrence of diabetes complications. Strategies were compared using the incremental cost-effectiveness ratio (ICER), and deterministic and probabilistic sensitivity analyses were carried out. The DPP-4 inhibitors strategy was the dominant strategy with the highest effectiveness and the lowest cost. Early insulin therapy was dominated (ICER: $-53,703.18), meaning that it was not cost-effective. The sensitivity analyses consistently affirmed the robustness of the base case findings. The probabilistic sensitivity analysis indicated probabilities of 77%, 22%, and 1% for DPP-4 inhibitors, TZDs strategies, and early insulin therapy, respectively, in terms of being cost-effective. In terms of cost-effectiveness, early insulin therapy was not cost-effective compared to OADs for managing newly diagnosed T2DM patients. Future studies in this regard, utilizing more comprehensive evidence, can yield more accurate results. [ABSTRACT FROM AUTHOR]

Studies have revealed that sex can predict differences in multiple aspects of atrial fibrillation (AF). These differences are underreported in the Middle East. This study aims to describe sex-specific differences in risk factors, symptomatology, management, and outcomes in Middle Eastern patients with AF. The JoFib (Jordan-Atrial-Fibrillation) study is an observational, prospective, multicenter, nationwide registry in AF. Comparisons were made between female and male patients using Pearson chi-square and Mann-Whitney U tests. Multivariable regression models were constructed to investigate whether the female sex was predictive of any AF-related outcomes (all-cause death, cardiovascular death, ischemic stroke or systemic embolism [IS/SE], major bleeding, and clinically relevant non-major bleeding). Of 2,020 patients with AF, 54% (n = 1091) were females. Females with AF were older (median age 71 vs. 69, p <.001), but had less heart failure (20.9% vs. 27.2%, p =.001) and coronary artery disease (7.5% vs. 14.7%, p <.001). Females with AF were more symptomatic (74.7% vs. 66.5%, p <.001) and frequently received anticoagulant therapy (84.4% vs. 78.9%, p =.001). Rhythm control was pursued less frequently in females (23.4% vs. 27.3%, p =.04). All studied outcomes occurred with similar frequencies in females and males, and sex was not significantly predictive of any outcome. Females with AF are more symptomatic, yet they are treated less with rhythm control. Despite higher risk, females have similar risk-adjusted all-cause cardiovascular death and stroke rates compared to males. Future studies should explore how treatments and interventions can influence quality-of-life and cardiovascular outcomes in females with AF. [ABSTRACT FROM AUTHOR]

Background and Objective: Post-stroke epilepsy represents an important clinical challenge as it often requires both treatment with direct oral anticoagulants (DOACs) and antiseizure medications (ASMs). Levetiracetam (LEV), an ASM not known to induce metabolizing enzymes, has been suggested as a safer alternative to enzyme-inducing (EI)-ASMs in patients treated with DOACs; however, current clinical guidelines suggest caution when LEV is used with DOACs because of possible P-glycoprotein induction and competition (based on preclinical studies). We investigated whether LEV affects apixaban and rivaroxaban concentrations compared with two control groups: (a) patients treated with EI-ASMs and (b) patients not treated with any ASM. Methods: In this retrospective observational study, we monitored apixaban and rivaroxaban peak plasma concentrations (Cmax) in 203 patients treated with LEV (n = 28) and with EI-ASM (n = 33), and in patients not treated with any ASM (n = 142). Enzyme-inducing ASMs included carbamazepine, phenytoin, phenobarbital, primidone, and oxcarbazepine. We collected clinical and laboratory data for analysis, and DOAC Cmax of patients taking LEV were compared with the other two groups. Results: In 203 patients, 55% were female and the mean age was 78 ± 0.8 years. One hundred and eighty-six patients received apixaban and 17 patients received rivaroxaban. The proportion of patients with DOAC Cmax below their therapeutic range was 7.1% in the LEV group, 10.6% in the non-ASM group, and 36.4% in the EI-ASM group (p < 0.001). The odds of having DOAC Cmax below the therapeutic range (compared with control groups) was not significantly different in patients taking LEV (adjusted odds ratio 0.70, 95% confidence interval 0.19–2.67, p = 0.61), but it was 12.7-fold higher in patients taking EI-ASM (p < 0.001). In an analysis in patients treated with apixaban, there was no difference in apixaban Cmax between patients treated with LEV and non-ASM controls, and LEV clinical use was not associated with variability in apixaban Cmax in a multivariate linear regression. Conclusions: In this study, we show that unlike EI-ASMs, LEV clinical use was not significantly associated with lower apixaban Cmax and was similar to that in patients not treated with any ASM. Our findings suggest that the combination of LEV with apixaban and rivaroxaban may not be associated with decreased apixaban and rivaroxaban Cmax. Therefore, prospective controlled studies are required to examine the possible non-pharmacokinetic mechanism of the effect of the LEV-apixaban or LEV-rivaroxaban combination on patients' outcomes. [ABSTRACT FROM AUTHOR]

• There have been still limited data on the transition of management strategies and clinical outcomes after introduction of direct oral anticoagulant (DOAC) for cancer-associated venous thromboembolism (VTE) in the real-world clinical practice. • In the current historical comparison of cancer-associated VTE between the 2 large real-world registries, there was a striking change in the treatment strategies with decreased risks of recurrent VTE and major bleeding in the DOAC era (COMAAND VTE Registry-2) compared with those in the warfarin era (COMAAND VTE Registry-1). • The risks of recurrent VTE has decreased significantly with the transition to the DOAC era, while there seemed to be unmet needs of clinically relevant nonmajor bleeding, DOAC-related gastrointestinal bleeding, and home treatment for pulmonary embolism patients with cancer. There have been still limited data on the transition of management strategies and clinical outcomes after introduction of direct oral anticoagulant (DOAC) for cancer-associated venous thromboembolism (VTE) in the real-world clinical practice. Using the 2 series of multicenter COMMAND VTE registries in Japan enrolling consecutive patients with acute symptomatic VTE, we compared 695 patients with cancer-associated VTE in the Registry-1 of the warfarin era and 1507 patients in the Registry-2 of the DOAC era. Regarding oral anticoagulation therapy, 576 patients (82.9 %) in the Registry-1 received warfarin, whereas 1119 patients (79.6 %) in the Registry-2 received DOACs. The cumulative 3-year incidence of discontinuation of anticoagulation was not significantly different between the 2 registries (56.7 % vs. 62.7 %, P = 0.11). The cumulative 5-year incidence of recurrent VTE was significantly lower in the Registry-2 than in the Registry-1 (17.7 % vs. 10.1 %, P < 0.001). The cumulative 5-year incidence of major bleeding was significantly lower in the Registry-2 than in the Registry-1 (26.6 % vs. 20.4 %, P = 0.045). The proportion of gastrointestinal bleeding numerically increased from the Registry-1 to the Registry-2 (46.7 % and 49.5 %), whereas that of intracranial bleeding numerically decreased from the Registry-1 to the Registry-2 (17.1 % and 14.1 %). In the current historical comparison of cancer-associated VTE between the 2 large real-world registries, there was a striking change in the treatment strategies with decreased risks of recurrent VTE and major bleeding in the DOAC era compared with those in the warfarin era, while there seemed to be unmet needs of DOAC-related gastrointestinal bleeding. URL: http://www.umin.ac.jp/ctr/index.htm UMIN000044816. We compared the management strategies and clinical outcomes of patients with cancer-associated VTE between the COMMAND VTE Registry-1 (Warfarin era) and Registry-2 (DOAC era). The lower adjusted risk of the Registry-2 relative to the Registry-1 was significant for recurrent VTE, but not for major bleeding. CRNMB, clinically relevant nonmajor bleeding; DOAC, direct oral anticoagulant; VTE, venous thromboembolism; CI, confidence interval; HR, hazard ratio [Display omitted] [ABSTRACT FROM AUTHOR]

Aims: Knowledge on the prescriptive practice of direct oral anticoagulants (DOACs) in older subjects with atrial fibrillation (AF) hospitalized in acute medical wards is limited. This study aimed to evaluate the prevalence and appropriateness of DOAC prescriptions in hospitalized older subjects with AF, discharged from acute medical wards. Methods: We analysed a cohort of 609 subjects with AF, aged ≥65 years (mean age 85 years) enrolled from 39 geriatric and nephrology wards in Italy. DOAC prescriptive appropriateness was evaluated according to the summary of product characteristics (smPC), 2019 Beers and STOPP criteria, and drug–drug interactions (DDIs). Results: At hospital discharge, 33% of patients with AF were prescribed with DOAC, 26% with vitamin‐K antagonist, while 41% did not receive any anticoagulant. Among subjects on DOAC therapy, 31% presented a violation of the smPC criteria (mainly underdosage—17%), while 48% and 18% presented a Beers/STOPP inappropriate prescription, or a DDI, respectively. Older age, lower body mass index (BMI), cancer and higher estimated glomerular filtration rate (eGFR) were independently associated with DOAC underdosage or missed prescription (age: adjusted odds ratio [aOR] 1.06, 95% confidence interval [95% CI] 1.00–1.12 for underdosage; eGFR: aOR 1.04, 95% CI 1.02–1.07 for underdosage; BMI: aOR 0.95, 95% CI 0.91–0.99 for missed prescription; cancer: aOR 1.93, 95% CI 1.19–3.13 for missed prescription). Conclusions: This study showed a suboptimal DOAC prescriptive practice in older in‐patients, with frequent missed prescription and DOAC underdosage. Contrary to current recommendations, physicians appear overly concerned by bleeding risk in real‐life older and frailer subjects. Strategies should be developed to promote appropriate DOAC prescription in the hospital setting. [ABSTRACT FROM AUTHOR]

Background: Patients with cirrhosis have a 30-day readmission rate of over 30%. Novel care delivery models are needed to reduce healthcare costs and utilization associated with cirrhosis care. One such model is Home Hospital (HH), which provides inpatient-level care at home. Limited evidence currently exists supporting HH for cirrhosis patients. Aims: The aims of this study were to characterize patients with cirrhosis who received hospital-level care at home in a two-site clinical trial and to describe the care they received. Secondary aims included describing their outcomes, including adverse events, readmissions and mortality. Methods: We identified all patients with cirrhosis who enrolled in HH as part of a two-site clinical trial between 2017 and 2022. HH services include daily clinician visits, intravenous and oral medications, continuous vital sign monitoring, and telehealth specialist consultation. We collected sociodemographic data and analyzed HH stays, including interventions, outcomes, adverse events, and follow-up. Results: 22 patients with cirrhosis (45% Hispanic; 50% limited English proficiency, median MELD-Na 12) enrolled in HH during the study period. Interventions included lab chemistries (82%), intravenous medications (77%), specialist consultation (23%), and advanced diagnostics/procedures (23%). The median length of stay was 7 days (IQR 4–12); 186 bed-days were saved. Two patients (9%) experienced adverse events (AKI). No patients required escalation of care; 9% were readmitted within 30 days. Conclusions: In this two-site study, HH was feasible for patients with cirrhosis, holding promise as a hepatology delivery model. Future randomized trials are needed to further evaluate the efficacy of HH for patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Management of venous thromboembolism (VTE) in patients with primary and metastatic brain tumors (BT) is challenging because of the risk of intracranial hemorrhage (ICH). There are no prospective clinical trials evaluating safety and efficacy of direct oral anticoagulants (DOACs), specifically in patients with BT, but they are widely used for VTE in this population. A group of neuro‐oncology experts convened to provide practical clinical guidance for the off‐label use of DOACs in treating VTE in patients with BT. We searched PubMed for the following terms: BTs, glioma, glioblastoma (GBM), brain metastasis, VTE, heparin, low‐molecular‐weight heparin (LWMH), DOACs, and ICH. Although prospective clinical trials are needed, the recommendations presented aim to assist clinicians in making informed decisions regarding DOACs for VTE in patients with BT. There are no prospective clinical trials evaluating safety and efficacy of direct oral anticoagulants, specifically in brain tumor patients, but they are widely used for venous thromboembolism in this population. A group of neuro‐oncology experts convened to provide practical clinical guidance for the off‐label use of direct oral anticoagulants in treating venous thromboembolism in patients with brain tumors. [ABSTRACT FROM AUTHOR]

Background: Glucagon-like peptide 1 receptor agonists (GLP1RAs) are used in the treatment of diabetes and obesity. Their slowing effect of gastric emptying might change oral drug absorption, potentially affecting pharmacokinetics, particularly in the case of medications with a narrow therapeutic index. Purpose: The purpose of this systematic review is to summarize data on drug-drug interactions between GLP1RAs and oral drugs. Data Sources: The PubMed and EMBASE databases were searched up to November, 1st 2023. Study Selection: We selected pharmacokinetic studies of any injectable GLP1RA given with an oral medication, and product prescribing sheets reporting data without access to the original study. Data Extraction: Two authors independently extracted the data. Data Synthesis: Twenty-two reports and six prescribing sheets were included. Treatment with GLP1RAs resulted in unaffected or reduced Cmax and delayed tmax of drugs with high solubility and permeability (warfarin, contraceptive pills, acetaminophen), drugs with high solubility and low permeability (angiotensin converting enzyme inhibitors), drugs with low solubility and high permeability (statins) and drugs with low solubility and permeability (digoxin). However, the use of GLP1RAs did not exert clinically significant changes in the AUC or differences in clinically relevant endpoints. Limitations: The major limitations of the studies that are included in this systematic review are the enrollment of healthy subjects and insufficient data in conditions that might affect pharmacokinetics (e.g., kidney dysfunction). Conclusions: To conclude, reduced Cmax and delayed tmax of drugs co-administered with GLP1RAs are consistent with the known delayed gastric output by the latter. Nevertheless, the overall drug exposure was not considered clinically significant. Dose adjustments are probably not required for simultaneous use of GLP1RAs with oral medications. Still, results should be carefully generalized to cases of background kidney dysfunction or when using drugs with narrow therapeutic index. The study is registered in PROSPERO: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022332339. [ABSTRACT FROM AUTHOR]

Summary: Immune thrombocytopenia (ITP) is characterized by low platelet counts (PLTs) and an increased risk of bleeding. Fostamatinib, a spleen tyrosine kinase inhibitor, has been approved as a second‐line treatment for ITP. Real‐world data on fostamatinib are lacking. This observational, retrospective, multicentre study, conducted in the Andalusia region of Spain, evaluated 44 adult primary ITP patients (47.7% female; median age 58 years; newly diagnosed ITP 6.8%; persistent 13.6%; chronic 79.5%; median four prior treatments) after ≥ 4 weeks of fostamatinib therapy. The median PLT at the initiation of fostamatinib was 15 × 109/L. Common reasons for starting fostamatinib were refractoriness or intolerance to prior therapy, oral medication preference, history of thrombosis and cardiovascular risk. Dosing was individualized based on efficacy and tolerance. After 2 weeks, global response rate was 56.8% (response and complete response). Response rates were 70.5%, 62.5% and 64% at 4 weeks, 12 weeks and at the end of the study respectively. Adverse events were mild, and no patients discontinued as a result. This real‐world study demonstrated a response rate similar to fostamatinib as seen in the pivotal clinical trials while including newly diagnosed patients and allowing for individualized dosing. [ABSTRACT FROM AUTHOR]

The use of direct oral anticoagulants (DOACs) in breastfeeding women is currently challenging due to limited safety data for breastfeeding infants, and there have been no previous studies on the drug concentration in breastfeeding infants. We treated 2 patients (one case was twin pregnancy) with venous thromboembolisms in breastfeeding women administered rivaroxaban at our institution. Blood samples from the mothers and breastmilk samples were collected at time 0 and 2 h after the rivaroxaban administration, breastfeeding was conducted 2 h after the rivaroxaban administration, and blood samples from the infants were collected 2 h after breastfeeding (4 h after maternal rivaroxaban administration). The milk-to-plasma (M:P) ratios were 0.27 in Case 1 and 0.32 in Case 2. The estimated relative infant dose (RID) was 0.82 % in Case 1 Children 1 and 2, and 1.27 % in Case 2. The rivaroxaban concentration in the infant plasma was below the lower limit of quantification in all infants. In addition, even in the high-exposure case simulation based on 5 days of breastfeeding in Case 2, the infant plasma concentration level was below the lower limit of quantification. At 3 months of follow-up, breastfeeding was continued, and all infants grew and developed without any health problems including bleeding events. The current case series showed that there were no pharmacokinetic or clinical concerns for breastfeeding women or breastfed infants, and provides support for rivaroxaban as a safe treatment option for these patients. • Direct oral anticoagulants (DOACs) are challenging in breastfeeding women. • We administered rivaroxaban in 2 breastfeeding women with venous thromboembolism. • There were no pharmacokinetic concerns on rivaroxaban for breastfeeding women. • Rivaroxaban might be a potential option for breastfeeding women with infants. [ABSTRACT FROM AUTHOR]

Given the growing number of patients receiving direct oral anticoagulant (DOAC), patients requiring rapid neutralization is also increasing in case of major bleedings or urgent surgery/procedures. Idarucizumab is commercialized as a specific antidote to dabigatran while andexanet alfa has gained the Food and Drug Administration and the European Medicines Agency approval as an oral anti-factor Xa inhibitors antidote. Other antidotes or hemostatic agents are still under preclinical or clinical development, the most advanced being ciraparantag. DOAC plasma levels measurement allows to appropriately select patient for antidote administration and may prevent unnecessary prescription of expensive molecules in some acute clinical settings. However, these tests might be inconclusive after some antidote administration, namely andexanet alfa and ciraparantag. The benefit of laboratory monitoring following DOAC reversal remains unclear. Here, we sought to provide an overview of the key studies evaluating the safety and efficacy of DOAC reversal using the most developed/commercialized specific antidotes, to discuss the potential role of the laboratory monitoring in the management of patients receiving DOAC specific antidotes and to highlight the areas that deserve further investigations in order to establish the exact role of laboratory monitoring in the appropriate management of DOAC specific antidotes. Anticoagulation monitoring and specific reversal agent targets DOAC: direct oral anticoagulant; dTT: diluted thrombin time; ECA: ecarin chromogenic assay; ECT: ecarin cloting time. [Display omitted] • Antidotes for direct oral anticoagulant (DOAC) reversal have been developed. • The role of laboratory monitoring in DOAC reversal using antidotes is unclear. • Dabigatran level prior to idarucizumab could predict reversal outcome. • Oral FXa inhibitor levels cannot be easily measured following andexanet alfa. • DOAC measurement using commercialized assays is not possible after ciraparantag. [ABSTRACT FROM AUTHOR]

The effects of direct oral anticoagulants (DOACs) in patients with non-valvular atrial fibrillation (NVAF) and liver disease remain poorly understood. Our multinational cohort study assessed the effectiveness and safety of DOACs in this high-risk population. We assembled two population-based cohorts in United Kingdom and in Québec of NVAF patients with liver disease initiating DOACs or vitamin K antagonists (VKAs) between 2011 and 2020. Using an as-treated exposure definition, we compared DOACs to VKAs and apixaban to rivaroxaban. After inverse probability of treatment weighting, Cox proportional hazards models estimated site-specific hazard ratios (HRs) and 95 % confidence intervals (CIs) of ischemic stroke and major bleeding. Site-specific estimates were pooled using random-effects models. Analyses were repeated among NVAF patients with cirrhosis. There were 11,881 NVAF patients with liver disease (2683 with cirrhosis). Among those, 8815 initiated DOACs (4414 apixaban, 2497 rivaroxaban) and 3696 VKAs. The HRs (95 % CIs) for DOACs compared to VKAs were 1.01 (0.76–1.34) for ischemic stroke and 0.87 (0.77–0.99) for major bleeding. Results were consistent among patients with cirrhosis. The HRs (95 % CIs) for apixaban compared to rivaroxaban were 0.85 (0.60–1.20) for ischemic stroke and 0.80 (0.68–0.95) for major bleeding. This decreased bleeding risk was not observed among patients with cirrhosis (HR, 1.01; 95 % CI 0.72–1.43). Among NVAF patients with liver disease, DOACs were as effective and slightly safer than VKAs, and apixaban was as effective but safer than rivaroxaban. The safety benefit with apixaban was not present among patients with cirrhosis. • Our multinational cohort study compared DOACs vs VKAs in AF patients with liver disease. • We also compared apixaban vs rivaroxaban in the same population. • DOACs were as effective but slightly safer compared to VKAs. • Apixaban was as effective but safer compared to rivaroxaban. • The safety benefit with apixaban was not present in AF patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Spinal subdural hematoma is uncommon but may become more prevalent with increasing anticoagulant use. Early diagnosis from symptoms like lower back pain and leg paralysis is crucial for timely intervention. [ABSTRACT FROM AUTHOR]

Aim: PIONEER REAL Canada examined real‐world clinical outcomes associated with the use of once‐daily oral semaglutide in adults with type 2 diabetes. Materials and Methods: This was a 34‐ to 44‐week, multicentre, prospective, open‐label, non‐interventional study in adults who were treatment‐naive to injectable glucose‐lowering medication and initiated oral semaglutide in routine clinical practice. The primary endpoint was the change in glycated haemoglobin (HbA1c) from baseline to the end of the study (EoS). Secondary endpoints assessed at EoS were change from baseline in body weight (BW); the proportion of participants reaching HbA1c levels <7% and the composite endpoints, HbA1c reduction ≥1% point with BW reduction ≥3% and ≥5%; and treatment satisfaction measured using Diabetes Treatment Satisfaction Questionnaires (DTSQ) status and change. Primary analyses were based on the in‐study observation period. Results: In total, 182 participants initiated oral semaglutide (mean age, 58.6 years; HbA1c, 8.0%; BW, 93.7 kg). The estimated changes (95% confidence interval) from baseline to EoS in HbA1c and BW were −1.09% points (−1.24, −0.94; p <.0001) and −7.17% (−8.24, −6.11; p <.0001), respectively. At EoS, 53.7% of participants had HbA1c levels <7%; 39.3% and 31.6% reached HbA1c reduction ≥1% point plus BW reduction ≥3% and ≥5%, respectively. Treatment satisfaction significantly increased (DTSQ status, +4.47 points; DTSQ change, 11.83 points; both p <.0001). At EoS, 75.3% of participants remained on oral semaglutide (55.5% received oral semaglutide 14 mg). No new safety signals were identified for oral semaglutide. Conclusions: In PIONEER REAL Canada, participants treated with oral semaglutide in routine clinical practice experienced clinically relevant reductions in HbA1c and BW and increased treatment satisfaction. [ABSTRACT FROM AUTHOR]

This literature review from the journal Neuro-Ophthalmology provides summaries of various studies on topics related to neuro-ophthalmology. The studies cover a range of subjects, including the risk of optic neuritis following COVID-19 vaccination, prognostic factors for optic neuritis, outcomes of cerebrospinal fluid diversion surgery, diagnosing myasthenia gravis, ocular neuromyotonia, and the use of peribulbar corticosteroids for ocular myasthenia gravis. The summaries highlight key findings from each study, such as the effectiveness of peribulbar corticosteroids, facilitators and barriers to weight loss, manifestations of giant-cell arteritis, characteristics of functional visual loss, and the potential use of automated pupillometry as a prognostic marker for acute brain injury. These summaries provide valuable insights for researchers and individuals interested in neuro-ophthalmology. [Extracted from the article]

Previous studies have rarely investigated the role of non-vitamin K oral anticoagulants (NOAC) and warfarin in the secondary prevention of ischemic stroke patients with nonvalvular atrial fibrillation (NVAF). In this study, we compared the effectiveness and safety of NOAC and warfarin for secondary prevention in Korean ischemic stroke patients with NVAF. Based on the Korean National Health Insurance Service Database, this study included 21,064 oral anticoagulants-naïve acute ischemic stroke patients with NVAF between July 2015 and June 2019. The main study outcomes included ischemic stroke, systemic embolism, major bleeding, and death. During the observational periods, NOAC users had a significantly decreased risk of ischemic stroke + systemic embolism (adjusted hazard ratio [aHR] 0.86; 95% confidence interval [CI] 0.78–0.95), ischemic stroke (aHR 0.89; 95% CI 0.81–0.99), major bleeding (aHR 0.78; 95% CI 0.68–0.89), and all-cause death (aHR 0.87; 95% CI 0.81–0.93). Standard-dose NOAC users had a lower risk of ischemic stroke, systemic embolism, and major bleeding events than warfarin users. In contrast, low-dose NOAC users did not differ in risk from warfarin users for all outcomes. In conclusion, NOACs were associated with a lower risk of secondary thromboembolic events and bleeding complications in Korean ischemic stroke patients with NVAF than warfarin. [ABSTRACT FROM AUTHOR]