Reduction Criteria Research Articles

Analyzing the economic ramifications of the broad implementation of generic prasugrel

Abstract Introduction The 2023 European Acute Coronary Syndrome (ACS) guidelines state that prasugrel (PRG) should be considered in preference to ticagrelor (TCG) in patients (pts) who proceed to percutaneous coronary angioplasty (PCI). In Portugal, PRG is less available due to earlier evidence considering pretreatment and contraindications for each drug. PRG (10mg) is currently a generic drug, while TCG is not. We aimed to evaluate the proportion of pts that could be switched from TCG to PRG, and the economic impact of a widespread national adoption. Methods To determine eligibility for generic PRG 10mg, we examined a single center prospective database of consecutive ACS pts undergoing PCI in a full year. Eligibility for TCG and PRG was based on drug specific contraindications, previous stroke for PRG and chronic liver disease (CLD) for TCG, and indication for PRG dose reduction (≤60 kg and ≥75 years). To estimate hospital costs we used the price per pill indicated by the pharmacy (0.98€ TCG, 0.67€ PRG). To obtain post-discharge and NHS savings we used the INFARMED public information. We estimated 3500 PCIs per year on a national level, based on published data. Results A total of 780 pts were included, median age 68±10.4years, 523 (67.1%) were male, 51.9% (n=406) had non-ST elevation ACS. Mean admission time was 8.36 days. Considering PRG and TCG contraindications, 157 pts (20.3%) had a previous history of stroke and 20pts (2.6%) had CLD. 150 pts (19.2%) had PRG dose reduction criteria. Eligible for PRG 10mg and TCG 90mg were 434 pts (57.8% of total PCI pts). Cost per admission would be 33 697.35€ for TCG and 17 617.28€ for PRG. At a national level, hospital costs can be reduced by 16080.07€. Considering the 1-year outpatient setting and a widespread generic PRG 10mg adoption, NHS savings are estimated in 898 323.59€, and patient savings in 401248.25€ (198.38€ per patient). Conclusions ACS pts in real-world scenarios exhibit both eligibility for PRG and TCG. Considering the lower cost, the NHS can potentially save 914 403,66€ (figure 1) annually through the widespread adoption of generic PRG 10mg.

Plasma apixaban levels and thrombin generation assay in patients with atrial fibrillation with dose reduction criteria of apixaban

Abstract Background Off-label reduced-dose apixaban is commonly prescribed in patients with atrial fibrillation (AF). However, the pharmacokinetic data of apixaban according to the dosage and label is limited especially in those with dose reduction criteria of apixaban. Purpose We investigated the apixaban plasma concentration (PC) and thrombin generation assay (TGA) parameters across different apixaban dose settings. Methods We enrolled 398 non-valvular AF patients with more than single-dose reduction criteria of apixaban and divided them into three groups: (1) on-label standard dose (single dose-reduction criterion with standard-dose of apixaban 5mg twice daily, n=173); (2) off-label reduced-dose (single dose-reduction criterion with apixaban 2.5mg twice daily, n=61); and (3) on-label reduced-dose (two or more dose-reduction criteria with apixaban 2.5mg twice daily, n=164). Apixaban PC by anti-Xa assay and TGA parameters of these three groups were compared at the trough level. Results The on-label standard dose group showed a higher PC than the on-label reduced dose (124.7 vs. 80.3 ng/mL, p<0.001), and the on-label reduced dose exhibited a higher PC than the off-label reduced dose (80.3 vs. 53.2 ng/mL, p=0.031) (Figure). The TGA parameters displayed a similar pattern of differences, with the on-label standard dose group tends to show the least thrombogenic profiles (Figure). Lower creatinine clearance (CrCl), older age, and female sex were statistically significant predictors for a higher apixaban PC by multivariable regression model (p<0.001, p=0.043, and 0.023, respectively), and CrCl was the most influential variable to dichotomize apixaban PC in all three groups (Figure). Conclusions Off-label reduced-dose apixaban group exhibited significantly lower apixaban level than both on-label standard dose and on-label reduced-dose apixaban groups, suggesting the importance of adhering to current dose-reduction criteria for maintaining appropriate apixaban levels. Caution is particularly advised in off-label under-dosing for patients with high creatinine clearance. Further investigation into the impact of off-label under-dosing on clinical outcomes is essential to guide optimal therapeutic strategies.

Efficacy and safety of long-term edoxaban treatment for low body weight cancer patients with isolated distal deep vein thrombosis: a post-hoc subgroup analysis of the ONCO DVT study

Abstract Background Low body weight is known to be a bleeding risk in the anticoagulation treatment. ONCO DVT study revealed that 12-month edoxaban treatment for cancer patients with isolated distal deep vein thrombosis (DVT) reduced a composite outcome of a symptomatic recurrent venous thromboembolism (VTE) or VTE-related death compared with 3-month edoxaban treatment. However, the efficacy and safety of long-term edoxaban treatment for cancer patients with low body weight is unclear. Purpose In this subgroup analysis, we assessed the efficacy and safety of 12-month edoxaban treatment for low body weight cancer patients with isolated distal DVT. Methods We conducted a post-hoc subgroup analysis of the ONCO DVT study in the low body weight patients. ONCO DVT study was a multicenter, open-label, adjudicator-blinded, randomized clinical trial. Cancer patients with isolated distal DVT were assigned to 12-month or 3-month edoxaban treatment. The primary endpoint was a composite outcome of a symptomatic recurrent VTE or VTE-related death at 12 months. The major secondary endpoint was major bleeding at 12 months. We enrolled patients who met low body weight defined in Japanese Version of High Bleeding Risk criteria (<55 kg for men, <50 kg for women) and evaluated the efficacy and safety of 12-month edoxaban treatment using logistic regression models and log-rank test. Results Among 601 patients in the intention-to-treat population of ONCO DVT study, 322 patients (53.6%) met low body weight: 151 patients were in 12-month edoxaban group and 171 patients were in 3-month edoxaban group. The body weight was similar between two group (47.1±5.2 kg in 12-month edoxaban group vs. 46.9±5.4 kg in 3-month edoxaban group; P=0.77). All of them used a lower dose edoxaban (30 mg once daily) following the dose reduction criteria. 12-month edoxaban group had lower rates of the primary endpoint compared with 3-month edoxaban group (2 patients (1.3%) vs. 10 patients (5.8%); Odds ratio 0.22 [95% CI, 0.05–1.00]; Log-rank P=0.036). There was no significant difference in the major secondary endpoint of major bleeding (12 patients (7.9%) in 12-month edoxaban group vs. 16 patients (9.4%) in 3-month edoxaban group; Odds ratio 0.83 [95% CI, 0.38–1.83]; Log-rank P=0.65). All clinically relevant bleeding events occurred in 22 patients (14.6%) in 12-month edoxaban group and in 27 patients (15.8%) in 3-month edoxaban group (Odds ratio 1.40 [0.90–2.19]; Log rank P=0.13), resulting in the comparable risk of bleeding in the 12-month edoxaban group. Conclusions Our study suggests that 12-month edoxaban treatment for low body weight cancer patients with isolated distal DVT prevents recurrent VTE or VTE-related death without increasing the risk of bleeding compared to 3-month edoxaban treatment.primary endpointsecondary endpoint

Is It Time to Expand the Criteria for Bronchoscopic Lung Volume Reduction in Very Low FEV1 and DLCO Emphysema.

Is It Time to Expand the Criteria for Bronchoscopic Lung Volume Reduction in Very Low FEV1 and DLCO Emphysema.

The countdown to carbon neutrality: Implications for passive investors

In 2019 the European Union (EU) Climate Benchmarks Regulation established a set of standardized emission reduction criteria for financial benchmarks. This study examines the risk-adjusted performance of equity exchange-traded funds (ETFs) tracking EU Climate Transition Benchmarks (CTBs) and EU Paris-Aligned Benchmarks (PABs). Our findings reveal that, after the implementation of the regulation, equity CTB ETFs have exhibited no significant risk-adjusted performance difference compared to their non-sustainable twin ETFs. Conversely, equity PAB ETFs, which adhere to more stringent environmental standards, have underperformed their non-sustainable counterparts. Our results suggest that stringent emission reduction objectives have a negative effect on investors’ returns.

P032 THE IMPACT OF NATURE IMMERSION THERAPY ON BLOOD PRESSURE IN HYPERTENSIVE SUBJECTS: A PILOT STUDY

Background and Objective: Conscious nature immersion therapy, termed “Vitamin N”, has shown promise in reducing blood pressure levels in individuals with or without hypertension. This pilot study aims to assess the effect of nature immersion on blood pressure specifically in hypertensive subjects. Methods: A convenience sample of stable hypertensive individuals participated in a standardized 3-hour nature immersion session. Systolic and diastolic blood pressure levels were recorded before the intervention (Phase I), after 30 minutes of the intervention (Phase II), and 48 hours post-intervention (Phase III). Statistical analysis employed a one-way non-parametric ANOVA, Kruskal-Wallis test, and Dunn's post hoc test, with a bilateral significance level of 95%. A criterion of at least 3 mmHg reduction in blood pressure was set for clinical significance. Results Eighteen participants, comprising 12 women (64.67%) and 6 men (33.33%), with a mean age of 60±9.04 years and 61±6.88 years, respectively, were included. Six individuals had a medical history of Diabetes Mellitus Type 2, and one had a history of coronary heart disease. Significant differences in median systolic (MSP) and diastolic pressures (MDP) were observed across the three phases (p<0.05). Notably, Phase II and Phase III showed consistent reductions in blood pressure compared to Phase I, exceeding the established 3 mmHg reduction criterion. Conclusions: Conscious nature immersion therapy (“Vitamin N”) exhibited a significant effect in lowering both systolic and diastolic blood pressure levels among hypertensive individuals. These findings suggest the potential of nature immersion as a non-pharmacological intervention for managing hypertension.

Random forests regression for soft interval data

Analyzing soft interval data for uncertainty quantification has attracted much attention recently. Within this context, regression methods for interval data have been extensively studied. As most existing works focus on linear models, it is important to note that many problems in practice are nonlinear in nature and the development of nonlinear regression tools for interval data is crucial. This paper proposes an interval-valued random forests model that defines the splitting criterion of variance reduction based on an L 2 type metric in the space of compact intervals. The model simultaneously considers the centers and ranges of the interval data as well as their possible interactions. Unlike most linear models that require additional constraints to ensure mathematical coherences, the proposed random forests model estimates the regression function in a nonparametric way, and so the predicted interval length is naturally nonnegative without any constraints. Simulation studies show that the new method outperforms typical existing regression methods for various linear, semi-linear, and nonlinear data archetypes and under different error measures. To demonstrate the applicability, a real data example is presented where the price range data of the Dow Jones Industrial Average index and its component stocks are analyzed.

Failed Ahmed glaucoma valves: trabeculectomy versus repeat shunt surgery

IntroductionTo investigate the outcomes of trabeculectomy (TRAB) versus repeat Ahmed glaucoma valve (re-AGV) implantation in eyes with Ahmed glaucoma valve (AGV) failure.MethodsThis quasi-experimental study includes patients with failed AGV implants requiring additional surgical intervention between 2018 and 2022. Patients in the TRAB group underwent a fornix-based procedure with mitomycin C 0.01% injection (0.1 mL). Eyes in the re-AGV group underwent repeat shunt surgery. The choice of the procedure was based on conjunctival condition. The primary outcome measure was surgical success rate based on various intraocular pressure (IOP) targets and percentages of IOP reduction from baseline: IOP ≤ 21 mmHg and 20% reduction (conventional criteria), IOP ≤ 18 and > 20% reduction (criterion A), IOP ≤ 15 and > 25% reduction (criterion B), and IOP ≤ 12 and > 30% reduction (criterion C).ResultsForty-eight eyes of 48 patients were operated and reported herein, consisting of 22 eyes of 22 patients undergoing TRAB and 26 eyes of 26 subjects undergoing re-AGV. No significant difference was observed between the study groups in terms of initial diagnoses, baseline IOP or the number of prior surgeries. The cumulative probability of survival at one year was significantly higher in the trabeculectomy group using the three stricter success definitions. In both study groups, IOP was significantly reduced from baseline at all postoperative visits, and was significantly lower in the TRAB group at all time points beyond one month. At 12 months, 5% of TRAB versus 48% of re-AGV eyes required glaucoma medications (P < 0.001). The rate of complications was comparable between the study groups (P = 0.76) but there was a trend toward a greater need for repeat surgery in the re-AGV group (4 eyes versus nil, P = 0.07).ConclusionsTrabeculectomy can be considered a safe and effective surgical option in eyes with failed AGV leading to significantly lower IOP levels and more favorable success rates than re-AGV in selected patients.

Hepatitis C Elimination in Egypt: Story of Success.

Egypt has long been overwhelmed by the hepatitis C virus (HCV) infection, and it used to be the country with the world's highest prevalence rates. The disease had been a significant public health problem, affecting millions of Egyptians and posing severe economic and social challenges. By the early 2000s, it was estimated that around 10% of the Egyptian population was infected with HCV. However, in recent years, with the availability of direct-acting antiviral therapies, the country has made enormous steps in combating this public health threat. The combination of innovative health strategies and political will enabled Egypt to establish a successful model of care for HCV management and to be the first country to eliminate hepatitis C, setting a model for the rest of the world. In 2023, Egypt became the first country to fulfill the World Health Organization's set programmatic criteria of reduction of hepatitis C incidence and mortalities to levels close to elimination of disease or achieve the "gold tier" status on the path to disease elimination.

Augmentation-Free Graph Contrastive Learning of Invariant-Discriminative Representations.

Graph contrastive learning (GCL) is a promising direction toward alleviating the label dependence, poor generalization and weak robustness of graph neural networks, learning representations with invariance, and discriminability by solving pretasks. The pretasks are mainly built on mutual information estimation, which requires data augmentation to construct positive samples with similar semantics to learn invariant signals and negative samples with dissimilar semantics to empower representation discriminability. However, an appropriate data augmentation configuration depends heavily on lots of empirical trials such as choosing the compositions of data augmentation techniques and the corresponding hyperparameter settings. We propose an augmentation-free GCL method, invariant-discriminative GCL (iGCL), that does not intrinsically require negative samples. iGCL designs the invariant-discriminative loss (ID loss) to learn invariant and discriminative representations. On the one hand, ID loss learns invariant signals by directly minimizing the mean square error (MSE) between the target samples and positive samples in the representation space. On the other hand, ID loss ensures that the representations are discriminative by an orthonormal constraint forcing the different dimensions of representations to be independent of each other. This prevents representations from collapsing to a point or subspace. Our theoretical analysis explains the effectiveness of ID loss from the perspectives of the redundancy reduction criterion, canonical correlation analysis (CCA), and information bottleneck (IB) principle. The experimental results demonstrate that iGCL outperforms all baselines on five node classification benchmark datasets. iGCL also shows superior performance for different label ratios and is capable of resisting graph attacks, which indicates that iGCL has excellent generalization and robustness. The source code is available at https://github.com/lehaifeng/ T-GCN/tree/master/iGCL.

Which type of supra-syndesmal fractures Weber C or Equivalent Weber C have the best reduction of the distal tibio-fibular syndesmosis? A prospective CT-scan investigation on 60 ankles

IntroductionThe reduction of the distal tibiofibular syndesmosis (SyTFd) is a crucial factor in the functional prognosis following a suprasyndesmotic ankle fracture. Few studies have compared, using computed tomography (CT), the quality of SyTFd reduction in Weber C ankle fractures (WebC) and Equivalent Weber C (EqWebC) fractures, where there is a medial ligament injury instead of a bony malleolar lesion. This CT-based study aimed to answer the following questions: (1) Do Weber C fractures allow for better reduction of the distal tibiofibular syndesmosis compared to Equivalent Weber C fractures? (2) Are the functional outcomes one year postoperatively better for Weber C fractures compared to Equivalent Weber C fractures? HypothesisThe hypothesis was that WebC fractures would present better reduction of the SyTFd than EqWebC fractures due to the restoration of bone anatomy, considering the bony nature of the medial ligament involvement. Materials and methodsSince December 2021, all patients presenting with an ankle fracture were included in a database. Suprasyndesmotic fractures were extracted, and between December 2021 and February 2022, 60 patients underwent surgery for a suprasyndesmotic fracture (28 WebC – 32 EqWebC). All patients were operated on using the same technique and underwent a postoperative bilateral CT scan in axial slices with both ankles in a neutral position (foot at 90 ° to the leg). An analysis of 8 measurements was performed under the same conditions. Each fractured ankle was compared to the healthy contralateral ankle, and a delta was obtained for each measurement. The follow-up was standardized. At one year, an AOFAS Score and a Maryland Foot Score (MFS) were recorded. Statistical differences between the two groups were measured using the Student's t-test and Chi-square test. ResultsThere was a significant difference between the WebC and EqWebC groups for clinical scores at one year postoperatively: AOFAS: 92.0 ± 6.3 [78–100] vs. 80.1 ± 5.4 [62–100], p < 0.05; MFS: 90.9 ± 6.4 [78–100] vs. 81.6 ± 5.2 [64–100], p < 0.05. CT scan analysis of the SyTFd reduction found significantly better reduction in the WebC group. DiscussionWebC fractures showed better clinical scores associated with better SyTFd reduction on postoperative CT scans. The anatomical reduction related to the bone reduction criteria during surgery could explain our findings. Level of evidenceIII; Case-Control Comparative Study.

Analysis of the therapeutic effect of trochanteric flip osteotomy combined with Kocher-Langenbeck approach for high acetabular posterior wall fracture

Evaluation of the clinical efficacy of f trochanteric flip osteotomy combined with Kocher-Langenbeck approach for high acetabular posterior wall fracture. Between January 2020 and December 2022, 20 patients with high acetabular posterior wall fractures were retrospectively analyzed, including 12 males and 8 females, aged 18 to 75 years old. They were divided into two groups according to the different surgical methods. Ten patients were treated with greater trochanteric osteotomy combined with Kocher-Langenbeck approach as the observation group, including 5 males and 5 females, aged from 18 to 75 years old. Ten patients were treated with Kocher-Langenbeck approach alone as the control group, including 7 males and 3 females, aged from 18 to 71 years old. Matta reduction criteria were used to evaluate the reduction quality of the two groups, and Harris score was used to compare the hip function of the two groups at the latest follow-up. The operation time, blood loss and postoperative complications of the two groups were analyzed. All patients were followed up for 10 to 24 months. According to the Matta fracture reduction quality evaluation criteria, the observation group achieved anatomical reduction in 6 cases, satisfactory reduction in 3 cases, and unsatisfactory reduction in 1 case, while the control group only achieved anatomical reduction in 3 cases, satisfactory reduction in 3 cases, and unsatisfactory reduction in 4 cases. At the final follow-up, the Harris hip score ranged from 71.4 to 96.6 in the observation group and 65.3 to 94.5 in the control group. According to the results of Harris score. The hip joint function of the observation group was excellent in 6 cases, good in 3 cases, and fair in 1 case. The hip joint function of the control group was excellent in 2 cases, good in 3 cases, fair in 3 cases, and poor in 2 cases. In the observation group, the intraoperative blood loss ranged from 300 to 700 ml, and the operation duration ranged from 120 to 180 min;in the control group, the intraoperative blood loss ranged from 300 to 650 ml, and the operation duration ranged from 100 to 180 min. Complications in the observation group included 1 case of traumatic arthritis and 1 case of heterotopic ossification, while complications in the control group included 3 cases of traumatic arthritis, 3 cases of heterotopic ossification and 1 case of hip abduction weakness. Trochanteric flip osteotomy combined with the Kocher-Langenbeck approach significantly improved anatomical fracture reduction rates, enhanced excellent and good hip joint function outcomes, and reduced surgical complication incidence compared to the Kocher-Langenbeck approach alone. Clinical application of this combined approach is promising, although larger studies are needed for further validation.

Combining robotics and 3D printing facilitates closed reduction of humeral shaft fractures using a minimally invasive plate as a reduction template: A proof-of-concept study.

Minimally invasive percutaneous plate osteosynthesis for humeral shaft fractures (HSFs) has limitations due to malreduction and radiation exposure. To address these limitations, we integrated robotics and 3D printing by incorporating plates as reduction templates. The innovative technology facilitated closed reduction of HSFs in the operating theatre using 18 models with cortical marking holes. The dataset of the precontoured plate was imported into 3D planning software for virtual fixation and screw path planning. The models were divided into half to simulate transverse fractures. During the operation, the software generated drilling trajectories for robot navigation, and precise plate installation achieved automatic fracture reduction. The evaluation results of reduction accuracy revealed variations in length, apposition, alignment, and rotation that meet the criteria for anatomic reduction. High interoperator reliabilities were observed for all parameters. The proposed technology achieved anatomic reduction in simulated bones.

Catalysed Aryl Amine Syntheses via Azides: From Azidation of Aryl Halides to Azide Reduction and Direct Amination

AbstractThis review summarises and discusses aryl amine and azide syntheses from aryl halides employing azides. The majority of the reported reactions proceed with copper catalysis or mediation. Often, an aryl azide is formed in the first step, which is then reduced in situ to an aryl amine in a second step. The occurrence of the second step, the reduction, depends on the chosen reaction conditions and the substrates. The formation of only aryl azides through Cu‐mediated C−N bond formations is discussed, followed by mediated and catalytic aryl azide reduction employing different catalytic systems, and azidation with in situ azide reduction to amines, viz. azidation‐amination strategies. The azidation‐amination allows for the synthesis of complex heterocycles in multi‐step one‐pot procedures, of which several are summarised here. Examples of the application of azidation‐amination for synthesising important aryl amines employed in or as biologically active compounds, catalysis and materials science are also summarised. Finally, conducted control reactions have been collected and discussed in combination with mechanistic proposals. This literature survey allows us to pinpoint design criteria for the azide reduction to valuable amines, which includes the choice of reaction conditions such as solvent system and additives, involved metal and promising substrates.

Key strategies for achieving net-zero carbon buildings and promoting carbon credits in construction markets: A case of an emerging economy

While achieving net-zero carbon buildings (NZCBs) offers significant environmental and economic benefits, particularly in developing economies, research on effective strategies and their interplay with carbon credit systems remains limited. This knowledge gap hinders the widespread adoption of sustainable construction practices and the full potential of carbon markets for incentivizing change. This study aims to bridge this gap by investigating and assessing 15 key strategies for achieving NZCBs and promoting carbon credit implementation. Data from 109 construction professionals in Vietnam was analyzed using several statistical techniques. The results of one-way analysis of variance (ANOVA) and Tukey's post-hoc analysis showed no significant differences in the key strategies for promoting carbon credits among key stakeholders (policymakers, contractors, suppliers, and architects/designers). However, distinct variations were identified in the strategies for achieving NZCBs. Furthermore, the findings revealed that the top-priority strategies for NZCBs included: (1) raising awareness, (2) developing project-specific emission reduction roadmaps, and (3) increasing renewable energy utilization. For promoting carbon credits, the prioritized strategies involved: (1) tax reduction, (2) integrating emission reduction criteria into tender documents, and (3) awarding technical points to contractors with emission reduction solutions. Theoretically, this study breaks new ground by simultaneously examining key strategies for achieving NZCBs and carbon credits implementation within the specific context of an emerging economy. Practically, this paper offers valuable recommendations for Vietnamese policymakers and industry leaders, enabling them to navigate a roadmap for a greener and more sustainable built environment, not just in Vietnam but also in other emerging economies facing similar challenges.

Clinical characteristics of apixaban prescription in AF patients with single dose-reduction criterion: the ASPIRE (efficAcy and safety of aPixaban in rEal-world practice in Korean frail patients with atrial fibrillation) study.

Data on off-label reduced dose risk among patients with atrial fibrillation (AF) who qualify for a single-dose reduction of apixaban is scarce. We prospectively assessed apixaban dosing and clinical characteristics in AF patients meeting a dose reduction criterion. The multicentre, prospective cohort study, the efficAcy and Safety of aPixaban In REal-world practice in Korean frail patients with AF (ASPIRE), encompasses patients with AF who met the criteria for a single-dose reduction of apixaban and were given varying doses of apixaban, either the on-label standard dose or the off-label reduced dose. Of 2,000 patients (mean age 74.3 ± 7.9 years, 55.8% women), 29.7% were ≥80 years, 62.6% weighed ≤60 kg, and 7.8% had serum creatinine ≥1.5 mg/dL. Of these, 51.3% were prescribed an off-label reduced dose of apixaban. The off-label group was characterized with older age, more comorbidities, and antiplatelet agents, while the on-label group had more prior strokes. Physicians preferred off-label reduced dose in the "marginal zone," defined as age 75-80 years, weight 60-65 kg, and creatinine levels 1.2-1.5 mg/dL. In real-world clinical setting of the Korean population, off-label reduced dose apixaban was administered to nearly half of the patients who qualified for a single dose reduction. This reduced dosage was more commonly prescribed to patients with frail characteristics, while patients with a history of stroke were more often given the standard dose as per the label. A future study is planned to contrast the safety and effectiveness of the standard dose against the reduced dose of apixaban in this population.

Off-Label Reduced Dose Apixaban in Older Adults With Atrial Fibrillation and Associated Outcomes.

Apixaban is commonly used to prevent stroke in older adults with nonvalvular atrial fibrillation (AF). Although its package insert has specific dose reduction criteria, providers may dose reduce outside of these parameters based on clinical scenarios. The primary objective was to determine the incidence of apixaban off-label reduced dosing, while secondarily determining the safety and efficacy outcomes associated with such dosing. A retrospective analysis of patients aged 65 and older with orders for apixaban for AF was institutional review board (IRB)-approved and conducted across 3 academic medical centers. Patients receiving off-label reduced-dose apixaban (ie, "underdosed") were matched to a cohort of patients dosed according to the package insert at the standard dosing (5 mg twice daily) using stratified random sampling. Secondary outcomes included 1-year incidence of major bleeding, clinically relevant non-major bleeding (CRNMB), stroke or transient ischemic attack (TIA), and mortality. The Fisher exact tests were used to compare between-group differences. Of the 1172 patients meeting initial inclusion criteria, 201 (17%) were dosed off-label, with 175 (15%) "underdosed." The 147 "underdosed" patients with documented follow-up were matched with 139 patients receiving standard Food and Drug Administration (FDA)-labeled dosing. There were no significant differences in incidence of stroke (2.7% vs 2.2%), major bleeding (0% vs 0.7%), and CRNMB (2.7% vs 1.4%) in the off-label reduced dosing versus standard dosing groups. All-cause mortality was higher in the off-label reduced-dose group (16 [10.9%] vs 2 [1.4%], P < 0.05). Older adults with nonvalvular AF are commonly prescribed lower-than-recommended doses of apixaban. However, no significant association was found between empiric off-label reduced dosing and stroke or bleeding outcomes.

A Stable Fixed-Dose Combination of Benzalkonium chloride-free Latanoprost and Once-a-day Timolol

Abstract Objective This study outlines the development of a stable fixed dose combination solution formulation of Benzalkonium chloride (BKC)-free latanoprost with once-a-day timolol in a gel-free reservoir (GFR) vehicle. Methods A fixed-dose combination (FDC) formulation of latanoprost and timolol maleate was prepared by mixing polymers, buffers, and ionic preservatives followed by parylene coating of plastic bottles that were used for stability studies. Key findings The FDC formulation was a clear, colorless, slightly viscous solution. The adsorption of latanoprost on the parylene coated plastic bottle surface was reduced. Promoting stability for 36 months. The assay and impurities and other physicochemical quality attributes, such as color, clarity, osmolality, and pH met the required standards of both latanoprost and timolol. The sterility and antimicrobial effectiveness testing (AET) also complied with the United States Pharmacopeia (USP) requirements. Stability was proven for 30 days in simulated in-use conditions. It showed clinically relevant (&amp;gt;2 mm Hg) intraocular pressure (IOP) reduction in a normotensive dog model. It also showed an higher IOP reduction (efficacy) over individual or concomitantly administered drug components and numerically better IOP reduction than the marketed FDC formulation in a conventional vehicle. Faster action was seen within 2-h on first day and recovery took 5 days post treatment cessation. Conclusion A stable FDC formulation in parylene-coated plastic bottles was successfully developed meeting the clinically relevant IOP reduction criteria. Comparable efficacy insptto existing treatment, this FDC is preferable option for patients with conditions such as dry eye and ocular surface disease.

Treatment of Tile type C pelvic ring fracture using orthopedic robot combined with Starr pelvis reduction frame

To investigate the clinical effect of orthopedic robot combined with Starr pelvic reduction frame in the treatment of Tile type C pelvic ring fracture. From October 2019 to May 2021, 14 patients with type C pelvic ring fracture were treated with robotic combined with Starr pelvic reduction frame, including 9 males and 5 females. The age ranged from 33 to 69 years. All the 14 patients had fresh closed fractures without femur, tibia and fibula fracture. Surgery was completed from 4 to 7 d after hospital admission. During the operation, the X-ray carbon bed was used, the pelvic ring was reduced by Starr pelvis reduction frame, and pelvic ring fracture was treated by orthopedic robot. Operation time, bleeding volume, fluoroscopy times of single screw placement, fracture reduction quality, affected limb function and complications were observed. Radiological reduction was evaluated using Matta scoring standard, and clinical efficacy was evaluated by Majeed pelvic function scoring system at the final follow-up. All of 14 patients successfully completed the operation, the operation time was 84 to 141 min, the bleeding volume was 20 to 50 ml, and the fluoroscopy times of single screw insertion was 4 to 9 times. All of 14 patients were followed up for 12 to 24 months. The healing time was 3 to 7 months. No complications such as fracture of internal fixation, screw loosening, infection and nerve injury were found. According to the evaluation criteria of Matta imaging reduction, 9 cases were excellent, 4 cases were good, and 1 case was fair. At the final follow-up, Majeed pelvic function scoring system was used:10 cases were excellent, 4 cases were good. The treatment of type C pelvic ring fracture with robotic combined Starr pelvis reduction frame is simple, time-saving, less trauma, less complications and effective.

Intraoperative slide rail CT assistance in percutaneous sacroiliac joint screws for the treatment of pelvic posterior ring injury

To compare the clinical efficacy of intraoperative slide rail CT combined with C-arm X-ray assistance and just C-arm for percutaneous screw in the treatment of pelvic posterior ring injury. A retrospective analysis was performed on the patient data of 76 patients with posterior pelvic ring injury admitted to the Department of Orthopedic Trauma from December 2018 to February 2022. Among them, 39 patients in the CT group were treated with C-arm combined with slide rail CT-assisted inline fixation including 23 males and 16 females with an average age of (44.98±7.33) years old;and the other 37 patients in the C-arm group were treated with intraline fixation treatment under only C-arm fluoroscopy including 24 males and 13 females with an average age of (44.37±10.82) years old. Among them, 42 patients with anterior ring fractures were treated with percutaneous inferior iliac spines with internal fixation (INFIX) or suprapubic support screws to fix the anterior pelvic ring. Postoperative follow-up time, operation time, complications of the two groups were compared. Results of Matta reduction criteria, Majed efficacy evaluation, the CT grading and the rate of secondary surgical revision were compared. The nailing time of (32.63±7.33) min in CT group was shorter than that of (52.95±10.64) min in C-arm group (t=-9.739, P<0.05). The follow-up time between CT group (11.97±1.86) months and C-arm group (12.03±1.71) months were not statistically significant(P>0.05). The postoperative complication rates between two groups were not statistically significant (χ2=0.159, P>0.05). Results of Matta reduction criteria (Z=2.79, P<0.05), Majeed efficacy evaluation(Z=2.79, P<0.05), CT grading (Z=2.83, P<0.05) in CT group were better than those in C-arm group(P<0.05); the secondary surgical revision rate in the CT group was significantly lower than that in the C-arm group (χ2=5.641, P<0.05). Compared with traditional C-arm fluoroscopy, intraoperative slide rail CT combined with C-arm assisted percutaneous sacroiliac joint screw placement surgery has the characteristics of short operation time, high accuracy and safety, and significant decrease in postoperative secondary revision rate, and is one of the effective methods for re-establishing the stability of the posterior ring of pelvic fracture.