Periprocedural Edoxaban Management and Clinical Outcomes in Patients Undergoing Transcatheter Cardiovascular Procedures in the EMIT-AF/VTE Program.

Clinical trial registration number: NCT02950168, NCT02951039.

A Randomized Controlled Trial of Topical Analgesia Post-Hemorrhoidectomy (TAPH Trial).

BACKGROUND: Postoperative pain remains the greatest problem after hemorrhoidectomy. Pain is hypothesized to arise from bacterial infection, sphincter spasm, and local inflammation. OBJECTIVE: A randomized controlled factorial trial was conducted to assess the effects of metronidazole, diltiazem, and lidocaine on post-hemorrhoidectomy pain. DESIGN: A double blinded randomized controlled factorial trial. SETTINGS: A multicenter trial was conducted in Auckland, New Zealand. PATIENTS: 192 Participants were randomized (1:1:1:1) into four parallel arms. INTERVENTIONS: Participants were randomized into one of four groups receiving topical treatment with 10% metronidazole (M), 10% metronidazole + 2% diltiazem (MD), 10% metronidazole + 4% lidocaine (ML), or 10% metronidazole + 2% diltiazem + 4% lidocaine (MDL). Participants were instructed to apply to the anal verge 3 times daily for 7 days. MAIN OUTCOME MEASURES: The primary outcome was pain on the visual analogue scale on day 4. The secondary outcomes included analgesia usage, pain on bowel motion, and functional recovery index. RESULTS: There was no significant difference in the pain and recovery scores when diltiazem or lidocaine was added to metronidazole (score difference between presence and absence of D in the formulation: -3.69, 95% CI: -13.3, 5.94, p = 0.46; between presence and absence of L: -5.67, 95% CI: -15.5, 3.80, p = 0.24). The combination of MDL did not further reduce pain. Secondary analysis revealed a significant difference between the best (ML) and worst (MDL) groups in both pain and functional recovery scores. There were no significant differences in analgesic usage, complications, or return to work between the groups. No clinically important adverse events were reported. The adverse event rate did not change in the intervention groups. LIMITATIONS: Topical metronidazole was utilized in the control group, rather than a pure placebo. CONCLUSION: There was no significant difference in pain when topical diltiazem or lidocaine, or both, was added to topical metronidazole. CLINICAL TRIAL REGISTRATION IDENTIFIER: NCT04276298.

Is routine histopathological analysis of hemorrhoidectomy specimens necessary? A systematic review and meta-analysis.

BACKGROUND: Hemorrhoidectomy is a common procedure used to treat symptomatic hemorrhoids. However, the necessity and cost-effectiveness of routinely conducting histopathological analysis on excised tissue samples are uncertain. METHODS: A systematic review was conducted using MEDLINE and EMBASE up to December 2023 for studies assessing the histopathological outcomes of hemorrhoidectomy specimens. Meta-analysis was performed on articles with combinable results to determine the pooled proportions of cancer and anal intraepithelial neoplasia (AIN) using the random effects model. RESULTS: From 2974 initial search results, 12 studies were included in the review, with 48,365 resected specimens from hemorrhoidectomy. Among these, there were 11 retrospective studies and one prospective study. A meta-analysis of 11 studies revealed that the prevalence of anal cancer was low, at 0.13% (95% CI: 0.05%-0.31%). The prevalence of anal cancer and AIN combined was 1.16% (95% CI: 0.53%-2.52%). CONCLUSION: This literature review estimated the probability of malignancy detection in hemorrhoid specimens sent for histopathological evaluation. The low incidence of malignant findings implies that routine analysis of hemorrhoidectomy samples may not be cost-effective. However, existing studies have yet to establish definitive risk factors for abnormal histological diagnoses to aid in the selection of specimens for selective histopathology.

Assessment of bovine cortical bone fracture behavior using impact microindentation as a surrogate of fracture toughness.

The fracture behavior of bone is critically important for evaluating its mechanical competence and ability to resist fractures. Fracture toughness is an intrinsic material property that quantifies a material's ability to withstand crack propagation under controlled conditions. However, properly conducting fracture toughness testing requires the access to calibrated mechanical load frames and the destructive testing of bone samples, and therefore fracture toughness tests are clinically impractical. Impact microindentation mimicks certain aspects of fracture toughness measurements, but its relationship with fracture toughness remains unknown. In this study, we aimed to compare measurements of notched fracture toughness and impact microindentation in fresh and boiled bovine bone. Skeletally mature bovine bone specimens (n = 48) were prepared, and half of them were boiled to denature the organic matrix, while the other half remained preserved in frozen conditions. All samples underwent a notched fracture toughness test to determine their resistance to crack initiation (KIC) and an impact microindentation test using the OsteoProbe to obtain the Bone Material Strength index (BMSi). Boiling the bone samples increased the denatured collagen content, while mineral density and porosity remained unaffected. The boiled bones also showed significant reduction in both KIC (P < .0001) and the average BMSi (P < .0001), leading to impaired resistance of bone to crack propagation. Remarkably, the average BMSi exhibited a high correlation with KIC (r = 0.86; P < .001). A ranked order difference analysis confirmed the excellent agreement between the 2 measures. This study provides the first evidence that impact microindentation could serve as a surrogate measure for bone fracture behavior. The potential of impact microindentation to assess bone fracture resistance with minimal sample disruption could offer valuable insights into bone health without the need for cumbersome testing equipment and sample destruction.

Pharmacokinetics, Pharmacodynamics, and Safety of Edoxaban in Pediatric Subjects: A Phase I Single-Dose Study.

This was an open-label, single-dose, phase I study to characterize the pharmacokinetics (PKs), pharmacodynamics (PDs), and safety of edoxaban in pediatric subjects from birth to 18 years at risk for venous thromboembolism (VTE). Children requiring anticoagulant therapy were enrolled into 5 age cohorts (0 to < 6 months (N = 12), 0.5 to < 2 years (N = 13), 2 to < 6 years (N = 13), 6 to < 12 years (N = 13), and 12 to < 18 years (N = 15)) receiving tablet or oral suspension of edoxaban at doses expected to be equivalent to 30 or 60 mg once daily (q.d.) in adult subjects with VTE. Sixty-six pediatric subjects were enrolled and completed the study. Edoxaban plasma concentration peaked between 1 and 3 hours and declined rapidly until 4-8 hours. The range of mean total apparent clearance across 5 age cohorts at low and high doses was 0.47 to 1.11 L/h/kg. The ranges of mean volume of central compartment and apparent peripheral volume were 2.31 to 3.59 L/kg and 1.92 to 4.14 L/kg, respectively. Across all age groups, the estimated median exposures were within the 0.5- to 1.5-fold of the median area under the plasma drug concentration-time curve (AUC) in adult subjects receiving corresponding doses (30 mg q.d. for low dose and 60 mg q.d. for high dose). In all age groups, PD parameters (prothrombin time, activated partial thromboplastin time, and anti-Factor Xa activity) showed a linear PK-PD relationship and were in line with previous adult data. The results support further evaluation of the pediatric doses in larger pivotal trials.

Outcomes after TAVI in patients with atrial fibrillation and a history of recent PCI: Results from the ENVISAGE-TAVI AF trial.

BACKGROUND: Patients with atrial fibrillation (AF) and a recent (≤ 90 days) percutaneous coronary intervention (PCI) undergoing transcatheter aortic valve implantation (TAVI) are at high bleeding risk due to the addition of oral antiplatelet (OAP) agents on top of oral anticoagulants. Data on outcomes of these patients are needed to optimize antithrombotic treatment. METHODS: This analysis compared annualized clinical event rates in patients with and without a recent PCI enrolled in ENVISAGE-TAVI AF, a prospective, randomized, open-label, adjudicator-masked trial comparing edoxaban and vitamin K antagonists in AF patients after TAVI. The primary efficacy and safety outcomes were net adverse clinical events (NACE) and major bleeding. RESULTS: Overall, 132 (94.3%) patients with a recent PCI (n = 140) received OAP after TAVI, compared with 692 (55.9%) patients without a recent PCI (n = 1237). Among patients with a recent PCI on OAP agents, use of dual antiplatelet therapy decreased to 5.5%, and use of single antiplatelet therapy (SAPT) increased to 78.0% over 3 months post-randomization. Conversely, use of SAPT predominated at all time points in patients without a recent PCI history. There were no significant differences in the incidence of NACE or other outcomes assessed, except for major bleeding events, which were more frequent in patients with vs without a recent PCI history (hazard ratio [95% confidence interval]: 2.17 [1.27, 3.73]; P = 0.005). CONCLUSIONS: Patients with AF undergoing TAVI with a recent PCI have a similar risk of ischemic events and mortality, but an increased risk of major bleeding compared with patients without a recent PCI.

Management of edoxaban therapy and clinical outcomes in patients undergoing major or nonmajor surgery: a subanalysis of the EMIT-AF/VTE study.

BACKGROUND: Optimising periprocedural management of direct oral anticoagulation in patients with atrial fibrillation on chronic treatment undergoing major surgeries is an important aspect of balancing the risk of surgery-related bleeding with the risk of thromboembolic events, which may vary by surgery type. METHODS: This subanalysis of the prospective EMIT-AF/VTE programme assessed periprocedural-edoxaban management, according to physicians' decisions, and bleeding and thromboembolic event rates in patients who underwent major vs. nonmajor surgeries. Edoxaban interruption and clinical outcomes were compared between major vs. nonmajor surgeries and between renal function subgroups (creatinine clearance [CrCL] ≤ 50 mL/min vs. > 50 mL/min). RESULTS: We included 276 major and 512 nonmajor surgeries. The median pre- and postprocedural duration of edoxaban interruption in major vs. nonmajor surgeries was 4 vs. 1 days, whereas median duration of interruption for those with preprocedural-only and postprocedural-only interruption was 2 vs. 1 days and 2 vs. 0 days, respectively (P < 0.0001). Rates of all bleeding and clinically relevant nonmajor bleeding were numerically higher in major vs. nonmajor surgeries. Event rates (number of events per 100 surgeries) were low overall (< 6 events per 100 surgeries), independent of renal function subgroups. CONCLUSION: In this subanalysis of the EMIT-AF/VTE programme, periprocedural-edoxaban interruption was significantly longer in patients undergoing major vs. nonmajor surgery. This clinician-driven approach was associated with low rates of bleeding and thromboembolic events following both major and nonmajor surgeries. TRIAL REGISTRATION: NCT02950168, registered October 31, 2016; NCT02951039, registered November 1, 2016.

The effectiveness of venous thromboembolism prophylaxis interventions in trauma patients: A systematic review and network meta-analysis.

BACKGROUND: Venous thromboembolism (VTE) is a major complication of trauma. Currently, there are few studies summarising the evidence for prophylaxis in trauma settings. This review provides evidence for the use of VTE prophylactic interventions in trauma patients to produce evidence-based guidelines. METHODS: A PRISMA-compliant review was conducted from Sep 2021 to June 2023, using Embase, Medline and Google Scholar. The inclusion criteria were: randomized-controlled trials (RCTs) in English published after 2000 of adult trauma patients comparing VTE prophylaxis interventions, with a sample size higher than 20. The network analysis was conducted using RStudio. The results of the pairwise comparisons were presented in the form of a league table. The quality of evidence and heterogeneity sensitivity were assessed. The primary outcome focused on venous thromboembolism (VTE), and examined deep vein thrombosis (DVT) and pulmonary embolism (PE) as separate entities. The secondary outcomes included assessments of bleeding and mortality. PROSPERO registration: CRD42021266393. RESULTS: Of the 7,948 search results, 23 studies with a total of 21,312 participants fulfilled screening criteria, which included orthopaedic, spine, solid organ, brain, spinal cord, and multi-region trauma. Of the eight papers comparing chemical prophylaxis medications in patients with hip or lower limb injuries, fondaparinux and enoxaparin were found to be significantly superior to placebo in respect of prevention of DVT, with no increased risk of bleeding. Regarding mechanical prophylaxis, meta-analysis of two studies of inferior vena cava filters failed to provide significant benefits to major trauma patients. CONCLUSION: Enoxaparin and fondaparinux are safe and effective options for VTE prevention in trauma patients, with fondaparinux being a cheaper and easier administration option between the two. Inconclusive results were found in mechanical prophylaxis, requiring more larger-scale RCTs.

Treatment Satisfaction and Convenience for Patients With Atrial Fibrillation on Edoxaban or Vitamin K Antagonists After Transcatheter Aortic Valve Replacement: A Post Hoc Analysis from the ENVISAGE-TAVI AF Trial.

ENVISAGE-TAVI AF (Edoxaban versus Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation-Atrial Fibrillation; NCT02943785) was a prospective, randomized, open-label trial comparing non-vitamin K oral anticoagulant (NOAC) edoxaban with vitamin K antagonists (VKAs) in patients with atrial fibrillation after successful transcatheter aortic valve replacement (TAVR). The effect of edoxaban- or VKA-based therapy on patient-reported outcomes remains unknown, as most studies focus on efficacy and safety. Pre-TAVR patient-reported expectations and post-TAVR Treatment Satisfaction and Convenience with edoxaban or VKA treatment (at months 3 and 12) were analyzed using the Perception of Anticoagulation Treatment Questionnaire (PACT-Q). This analysis included randomized and dosed patients with an evaluable PACT-Q1 assessment at baseline and ≥1 postbaseline assessment (PACT-Q2). Subanalyses included patients stratified by pre-TAVR anticoagulant (NOAC, VKA, no NOAC/VKA). Edoxaban- (n = 585) and VKA-treated (n = 522) patients had similar baseline characteristics and treatment expectations. Pre-TAVR anticoagulant use did not affect treatment expectations. After TAVR, edoxaban-treated patients had significantly higher Treatment Satisfaction and Convenience scores compared with VKA-treated patients at all time points (p <0.001 for all). Among edoxaban-treated patients, those who received VKAs pre-TAVR were significantly more satisfied with treatment than those who received NOACs (p <0.001) or no NOACs/VKAs (p = 0.003); however, there was no significant difference in the perception of convenience (p = 0.927 and p = 0.092, respectively). Conversely, among VKA-treated patients, the type of anticoagulant used pre-TAVR did not affect Treatment Satisfaction or Convenience scores post-TAVR. In conclusion, patients with atrial fibrillation who received edoxaban post-TAVR reported significantly higher Treatment Satisfaction and Convenience scores compared with those who received VKAs, resulting in a clinically meaningful difference between treatment groups.

Predictors of All-Cause Mortality After Successful Transcatheter Aortic Valve Implantation in Patients With Atrial Fibrillation.

Prevalent and incident atrial fibrillation are common in patients who undergo transcatheter aortic valve implantation and are associated with impaired postprocedural outcomes, including mortality. We determined predictors of long-term mortality in patients with atrial fibrillation after successful transcatheter aortic valve implantation. The EdoxabaN Versus standard of care and theIr effectS on clinical outcomes in pAtients havinG undergonE Transcatheter Aortic Valve Implantation-Atrial Fibrillation (ENVISAGE-TAVI AF) trial (NCT02943785) was a multicenter, prospective, randomized controlled trial in patients with prevalent or incident atrial fibrillation after successful transcatheter aortic valve implantation who received edoxaban or vitamin K antagonists. A Cox proportional hazard model was performed to identify predictors of all-cause mortality using a stepwise approach for multiple regression analysis. In addition, we assessed the performance of different risk scores and prediction models using ENVISAGE-TAVI AF data. Of 1,426 patients in ENVISAGE-TAVI AF, 178 (12.5%) died during the follow-up period (median 548 days). Our stepwise approach identified greater risk of mortality with older age, impaired renal function, nonparoxysmal atrial fibrillation, excessive alcohol use, New York Heart Association heart failure class III/IV, peripheral artery disease, and history of major bleeding or predisposition to bleeding. The present model (concordance statistic [c-statistic] 0.67) was a better discriminator than were other frequently used risk scores, such as the Society of Thoracic Surgeons score (c-statistic 0.56); Congestive heart failure, Hypertension, Age ≥75, Diabetes, Stroke, Vascular disease, Age 65 to 74 years, and Sex category (CHA2DS2-VASc) score (c-statistic 0.54); or Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly, and Drugs/alcohol concomitantly (HAS-BLED) score (c-statistic 0.58). In ENVISAGE-TAVI AF, several modifiable and nonmodifiable clinical characteristics were significantly associated with greater long-term all-cause mortality. Improved risk stratification to estimate the probability of mortality after successful transcatheter aortic valve implantation in patients with atrial fibrillation may improve long-term patient prognosis.

Predictive Factors and Clinical Events Associated with Edoxaban Interruption and Heparin Bridging Strategy: EMIT-AF/VTE.

Patients treated with edoxaban may require diagnostic and therapeutic procedures that involve edoxaban interruption. Although heparin bridging strategies are not recommended, heparin is frequently used in clinical practice. However, whether heparin use decreases thromboembolic risk remains unclear, and the potential for increased periprocedural bleeding remains a concern. Here, we report factors predicting edoxaban interruption and the use of heparin bridging strategies and associated clinical events from Global EMIT-AF/VTE, a multicenter, prospective, noninterventional study (Clinicaltrials.gov NCT02950168). Eligible patients are adults with atrial fibrillation or venous thromboembolism treated with edoxaban who underwent a diagnostic or therapeutic procedure. Edoxaban interruption, heparin bridging strategies, and clinical event data were collected from 5 days before procedure through 29 days afterwards. Edoxaban was interrupted in 1222/2089 procedures (58.5%); a heparin bridging strategy was used during 178 (14.6%) of these interruptions. Patients who received periprocedural heparin had higher baseline HAS-BLED (2.4±1.0 vs 1.9±1.1, P <0.0001) scores and similar CHA2DS2-VASc (3.6±1.6 vs 3.4±1.6, P = 0.09) scores versus patients who did not. HAS-BLED score >3 and high EHRA procedural risk predicted both edoxaban interruption and the use of a heparin bridging strategy, whereas CHA2DS2-VASc scores did not predict either. Bleeding and ischemic event rates were low; the all-bleeding rate was higher with the use of a heparin bridging strategy versus without (6.2% vs 3.1%, P = 0.04). Periprocedural heparin use was associated with higher bleeding rates, but not with lower thromboembolic risk. Individual patient and procedural bleeding risks appear to contribute more than stroke risk to clinicians' consideration of a heparin bridging strategy.

Assessment of bovine cortical bone fracture behavior using impact microindentation as a surrogate of fracture toughness.

The fracture behavior of bone is critically important for assessing its mechanical competence and ability to resist fractures. Fracture toughness, which quantifies a material's resistance to crack propagation under controlled geometry, is regarded as the gold standard for evaluating a material's resistance to fracture. However properly conducting this test requires access to calibrated mechanical load frames the destruction of the bone samples, making it impractical for obtaining clinical measurement of bone fracture. Impact microindentation offers a potential alternative by mimicking certain aspects of fracture toughness measurements, but its relationship with mechanistic fracture toughness remains unknown. In this study, we aimed to compare measurements of notched fracture toughness and impact microindentation in fresh and boiled bovine bone. Skeletally mature bovine bone specimens (n=48) were prepared, and half of them were boiled to denature the organic matrix, while the other half remained preserved in frozen conditions. Notched fracture toughness tests were conducted on all samples to determine Initiation toughness (KIC), and an impact microindentation test using the OsteoProbe was performed to obtain the Bone Material Strength index. Boiling the bone samples resulted increased the denatured collagen without affecting mineral density or porosity. The boiled bones also showed significant reduction in both KIC (p < 0.0001) and the average Bone Material Strength index (p < 0.0001), leading to impaired resistance of bone to crack propagation. Remarkably, the average Bone Material Strength index exhibited a high correlation with KIC (r = 0.86; p < 0.001). The ranked order difference analysis confirmed excellent agreement between the two measures. This study provides the first evidence that impact microindentation could serve as a surrogate measure for bone fracture behavior. The potential of impact microindentation to non-destructively assess bone fracture resistance could offer valuable insights into bone health without the need for elaborate testing equipment and sample destruction.

Achieving global surgical excellence: an evidence-based framework to guide surgical quality improvement programs in low and middle income countries.

Objectives: There is a lack of evidence-based guidelines for enhancing global surgical care delivery. We propose a set of recommendations to serve as a framework to guide surgical quality improvement and scale-up initiatives in low and middle income countries (LMICs). Methods: From January-December 2019, we reviewed the available literature and their application toward LMIC settings. The first initiative was the establishment of Best Practices Recommendations intended to summarize best-level evidence around quality improvement processes that have shown to decrease morbidity and mortality in LMICs. The GRADE level of evidence and strength of the recommendation were assigned in accordance with the WHO handbook for guidelines development. The second initiative was the scale-up of principles and practices by establishing international expert consensus on the optimal organization of surgical services in LMICs using a modified Delphi methodology. Results: Recommendations for three topic areas were established: reducing surgical site infections, improving quality of trauma systems, and interventions to reduce maternal and perinatal mortality. 27 studies were included in a quantitative synthesis and meta-analysis for interventions reducing surgical site infections, 27 studies for interventions improving the quality of trauma systems, and 14 studies for interventions reducing maternal and perinatal mortality. Using Delphi methodology, an international expert panel established consensus that district hospitals should place the highest priority on developing surgical services for low complexity, high volume conditions. At the national level, emergency and essential surgical care should be integrated within national Universal Health Coverage frameworks. Conclusions: This project fills a critical cap in the rapidly developing field of global surgery: gathering evidence-based, practical, and cost-effective solutions that will serve as a guide for the efficient planning and allocation of resources necessary to promote quality and safe essential surgical services in LMICs.

Edoxaban use in the context of dental procedures: analysis from the EMIT-AF/VTE database.

INTRODUCTION: Literature reviews support continuing anticoagulation during dental procedures. However, studies often present grouped anticoagulation data, and information on individual anticoagulant management would be helpful to dentists. The Edoxaban Management in Diagnostic and Therapeutic Procedures (EMIT-AF/VTE) programme (NCT02950168; NCT02951039) demonstrated low periprocedural bleeding and thrombotic event rates in patients with atrial fibrillation receiving edoxaban. AIMS: To report periprocedural edoxaban interruption and clinical events in patients from EMIT-AF/VTE who underwent dental procedures. METHODS: Dental procedures were categorised by type (cleaning/noncleaning). Edoxaban interruption, bleeding events, and thrombotic events were observed 5 days preprocedure through 29 days postprocedure. RESULTS: Overall, 196 patients underwent 350 cleaning and/or noncleaning procedures; most patients (171/196 [87.2%]) underwent noncleaning procedures (282/350 [80.6%]), whereas 48/196 (24.5%) underwent 68/350 (19.4%) cleaning procedures. Edoxaban was uninterrupted for most cleanings (53/68 [77.9%]). Preprocedural interruption was common for single and multiple tooth extractions (single, 67/100 [67.0%]; multiple, 16/30 [53.3%]). The only major bleeding occurred after an unrelated cleaning. Minor bleeding occurred in 1/68 (1.5%) cleaning and 4/282 (1.4%) noncleaning procedures. There were no thrombotic events. CONCLUSIONS: For most cleanings, edoxaban was not interrupted, whereas preprocedural interruption was more common for tooth extractions. Overall, bleeding rates were low, and no thrombotic events occurred.

Can Targeting Sphincter Spasm Reduce Post-Haemorrhoidectomy Pain? A Systematic Review and Meta-Analysis.

BACKGROUND: Haemorrhoidectomy is often complicated by significant post-operative pain, to which spasm of the internal anal sphincter is thought to be a contributing factor. This study appraises the evidence behind interventions aimed at lowering sphincter spasm to relieve post-haemorrhoidectomy pain. METHODS: A Preferred Reporting Items for Systematic Reviews and Meta-analyses compliant systematic review was conducted. Medline, EMBASE, and CENTRAL databases were systematically searched. All RCTs which compared interventions targeting the internal anal sphincter to relieve pain post excisional haemorrhoidectomy were included. The primary outcome measure was pain on the visual analogue scale. RESULTS: Of the initial 10,221 search results, 39 articles were included in a qualitative synthesis, and 33 studies were included in a meta-analysis. Topical glyceryl trinitrate (GTN) reduced pain on day 7 (7 studies, 485 participants), with a mean difference and 95% confidence interval (MD, 95% CI) of -1.34 (-2.31; -0.37), I2 = 91%. Diltiazem reduced pain on day 3 on the VAS, and the MD was -2.75 (-398; -1.51) shown in five studies (n = 227). Botulinum toxin reduced pain on day 7, in four studies with 178 participants, MD -1.43 (-2.50; -0.35) I2 = 62%. The addition of Lateral Internal Sphincterotomy to haemorrhoidectomy reduced pain on day 2 in three studies with 275 participants, MD of -2.13 (-3.49; -0.77) I2 = 92%. The results were limited by high heterogeneity and risk of bias. CONCLUSION: Evidence suggests that lateral sphincterotomy, administration of botulinum toxin and the application of topical diltiazem or GTN can reduce post-operative pain after haemorrhoidectomy. Lateral sphincterotomy should not be routinely used due to the risk of incontinence.

Sex Differences Among Patients Receiving Edoxaban vs Vitamin K Antagonist for Atrial Fibrillation After TAVR.

Background: In the ENVISAGE-TAVI AF (Edoxaban vs Standard of Care and Their Effects on Clinical Outcomes in Patients Having Undergone Transcatheter Aortic Valve Implantation-Atrial Fibrillation) trial, edoxaban was noninferior to vitamin K antagonists (VKA) for a composite outcome of ischemic and bleeding complications but increased major bleeding in patients with atrial fibrillation after successful transcatheter aortic valve replacement. Women are at higher risk of bleeding and stroke than men after transcatheter aortic valve replacement. It is unclear whether the effect of edoxaban on these complications varies in relation to sex. Objectives: This study was to assess the effect of edoxaban vs VKA according to sex in the ENVISAGE-TAVI AF trial. Methods: The primary outcomes were net adverse cardiovascular events (NACE) and major bleeding, assessed considering the effective time on study medication (safety analysis). Results: Out of 1,377 patients, 658 (47.8%) were women. Risks for ischemic and major bleeding outcomes were similar between women and men. Edoxaban compared to VKA was associated with a similar risk of NACE in women (HR: 1.16; 95% CI: 0.81-1.65) and men (HR: 1.08; 95% CI: 0.76-1.53; P for interaction = 0.820) and a higher risk of major bleeding in both sexes (P for interaction = 0.170). The risk increase of major bleeding was attenuated in women (HR: 1.11; 95% CI: 0.69-1.79) as compared to men (HR: 1.75; 95% CI: 1.07-2.85). There were no treatment-related differences for ischemic complications in both sexes. Conclusions: Edoxaban compared to VKA was associated with a similar risk of NACE and higher risk of major bleeding in both sexes. The increase in bleeding complications with edoxaban was attenuated in women.

Edoxaban vs. Vitamin K Antagonist for Atrial Fibrillation After Transcatheter Aortic Valve Replacement in Japanese Patients　- A Subanalysis of the ENVISAGE-TAVI AF Trial.

BACKGROUND: Japanese patients undergoing transcatheter aortic valve replacement (TAVR) are often female and have a small body size, potentially impacting bleeding risk with antithrombotic therapy. Outcomes of direct oral anticoagulant use in these patients with atrial fibrillation (AF) need to be clarified.Methods and Results: This prespecified analysis included Japanese patients from ENVISAGE-TAVI AF, a prospective, randomized, open-label, adjudicator-masked trial that compared treatment with edoxaban and vitamin K antagonists (VKAs) in patients with AF after TAVR. The primary efficacy and safety outcomes were net adverse clinical events (NACE; composite of all-cause death, myocardial infarction, ischemic stroke, systemic embolic event, valve thrombosis, and International Society on Thrombosis and Haemostasis [ISTH]-defined major bleeding) and ISTH-defined major bleeding, respectively. Intention-to-treat (ITT) and on-treatment analyses were performed. Overall, 159 Japanese patients were enrolled (edoxaban group: 82, VKA group: 77) and followed for on average 483 days. Mean patient age was 83.8 years; 52.2% were female. In the ITT analysis, NACE rates were 10.9%/year with edoxaban and 12.5%/year with VKA (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.38-1.90); major bleeding occurred in 8.9%/year and 7.3%/year, respectively (HR, 1.17; 95% CI, 0.45-3.05). In edoxaban- and VKA-treated patients, rates of ischemic stroke were 1.8%/year and 1.0%/year, respectively; fatal bleeding rates were 0.9%/year and 2.0 %/year. On-treatment results were similar to ITT. CONCLUSIONS: In Japanese patients with AF after successful TAVR, edoxaban and VKA treatment have similar safety and efficacy profiles.

Have Factors Influencing Female Medical Students' Intention to Pursue a Career in Surgery Changed over the Last 10 Years? A Systematic Review.

In 2012, a systematic review reported on factors influencing female medical students, career intentions for surgery. This current review is a direct follow-up of that article with the aim of assessing whether factors affecting female medical student career choices have changed over the last decade. This review has identified access to research opportunities as a new factor that can be used to promote female medical student and trainee interest in surgery. Other factors have largely remained unchanged over the last 10 years, such as lack of access to leave, part-time work, and same-gender role models.

Evaluation of the inflammatory profile following uncomplicated elective colectomy.

BACKGROUND: Attenuation of the inflammatory response in patients undergoing colectomy with modern perioperative care and laparoscopic surgery has been a focus of research in recent years. Despite reported benefits, significant heterogeneity remains with studies including patients undergoing both rectal and colon surgery and including surgery with postoperative complications. Therefore, the aim of the study was to evaluate the inflammatory response in patients undergoing elective colectomy without complications, specifically comparing open and laparoscopic approaches. METHODS: A multicenter prospective study was conducted across four public hospitals in Auckland and Christchurch, New Zealand. Consecutive adults undergoing elective colectomy were included over a 3-year period. Perioperative blood samples were collected and analysed for the following inflammatory markers: IL-6, IL-1ß, TNFα, IL-10, CRP, leucocyte and neutrophil count. Statistical analysis was performed using SPSS statistical software. RESULTS: A total of 168 colectomy patients without complications were included in the analysis. Patients that underwent laparoscopy had significantly reduced IL-6, neutrophils and CRP on postoperative day (POD) 1 (p < 0.05) compared to an open approach. IL-10 and TNFα were significantly reduced on POD 2 (p < 0.05) in laparoscopic patients. Patients with a Body Mass Index (BMI) greater than 30 kg/m2 had significantly higher levels of CRP regardless of operative approach. Statins altered both preoperative and postoperative inflammatory markers. CONCLUSION: The postoperative inflammatory response is influenced by surgical approach, perioperative medications, and patient factors. These findings have important implications in the utility of biomarkers in the diagnosis of postoperative surgical complications, in particular in the early diagnosis of anastomotic leak.