Early venous thromboembolism chemoprophylaxis in traumatic brain injury requiring neurosurgical intervention: Safe and effective.

BACKGROUND: Traumatic brain injury patients who require neurosurgical intervention are at the highest risk of worsening intracranial hemorrhage. This subgroup of patients has frequently been excluded from prior research regarding the timing of venous thromboembolism chemoprophylaxis. This study aims to assess the efficacy and safety of early venous thromboembolism chemoprophylaxis in patients with traumatic brain injuries requiring neurosurgical interventions. METHODS: This is a single-center retrospective review (2016-2020) of traumatic brain injury patients requiring neurosurgical intervention admitted to a level I trauma center. Interventions included intracranial pressure monitoring, subdural drain, external ventricular drain, craniotomy, and craniectomy. Exclusion criteria included neurosurgical intervention after chemoprophylaxis initiation, death within 5 days of admission, and absence of chemoprophylaxis. The total population was stratified into Early (≤72 hours of intervention) versus Late (>72 hours after intervention) chemoprophylaxis initiation. RESULTS: A total of 351 patients met the inclusion criteria, of whom 204 (58%) had early chemoprophylaxis initiation. Overall, there were no significant differences in baseline and admission characteristics between cohorts. The Early chemoprophylaxis cohort had a statistically significant lower venous thromboembolism rate (5% vs 13%, P < .001) with no increased risk of worsening intracranial hemorrhage (10% vs 13%, P = .44) or neurosurgical reintervention (8% vs 10%, P = .7). On subgroup analysis, a total of 169 patients required either a craniotomy or a craniectomy before chemoprophylaxis. The Early chemoprophylaxis cohort had statistically significant lower venous thromboembolism rates (2% vs 11%, P < .001) with no increase in intracranial hemorrhage (8% vs 11%, P = .6) or repeat neurosurgical intervention (8% vs 10%, P = .77). CONCLUSION: Venous thromboembolism prophylaxis initiation within 72 hours of neurosurgical intervention is safe and effective. Further prospective research is warranted to validate the results of this study.

Randomized Field Trial to Assess the Safety and Efficacy of Dihydroartemisinin-Piperaquine for Seasonal Malaria Chemoprevention in School-Aged Children in Bandiagara, Mali.

BACKGROUND: Owing to the increased cases of malaria in older children, the World Health Organization has recently recommended extending seasonal malaria chemoprevention (SMC) to children >5 years of age and using other effective drugs for malaria. In this study, we report the safety and efficacy of dihydroartemisinin-piperaquine (DHA-PQ) for SMC in school-aged children in Mali. METHOD: This randomized, controlled trial included 345 participants aged 6-15 years randomized to receive DHA-PQ, sulfadoxine-pyrimethamine plus amodiaquine (SP-AQ), or no chemoprevention (albendazole) at a 1:1:1 ratio. Four rounds of SMC were conducted from September to December 2021. The participants were assessed 7 days after each round for safety and efficacy of the interventions. RESULTS: Abdominal pain (11.8% vs 29.2%), headache (11.2% vs 19.2%), and vomiting (5.7% vs 15.2%) were frequently reported in the DHA-PQ and SP-AQ arms. On Day 120 of follow up, the incidence of clinical malaria was 0.01 episodes/person-month in the DHA-PQ and SP-AQ arms and 0.17 episodes/person-month in the control arm (P < .0001). Gametocytes were detected in 37 participants in all arms. CONCLUSIONS: Children in DHA-PQ arm reported less adverse events compared to the SP-AQ arm. Both drugs were effective against clinical malaria and infection.

Feasibility and safety of integrating mass drug administration for helminth control with seasonal malaria chemoprevention among Senegalese children: a randomized controlled, observer-blind trial.

BACKGROUND: The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal. METHODS: Female and male children aged 1-14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1-3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1-3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1-3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed. RESULTS: From 9 to 22 June 2022, 627 children aged 1-14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13-5.00, p = 0.63). CONCLUSIONS: Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model. TRIAL REGISTRATION: The study is registered at Clinical Trial.gov NCT05354258.

Chemoprophylaxis for heterotopic ossification following hip arthroscopy: A systematic review.

INTRODUCTION: Heterotopic ossification (HO) is a known complication diagnosed following hip arthroscopy. PURPOSE/HYPOTHESIS: This study sought to review the current literature on chemoprophylaxis for HO following hip arthroscopy and to describe what agents and doses are being utilized. STUDY DESIGN: Systematic Review. METHODS: A systematic review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines on the use of chemoprophylactic medications for HO prevention following hip arthroscopy. Mechanical and radiation prophylaxis were not included in the current analysis. RESULTS: A total of 203 studies were identified, of which 15 were included with 6463 patients. There was one randomized control trial (RCT) and 4 additional comparative studies. The most commonly utilized chemoprophylactic agents were the following: naproxen (n â€‹= â€‹8), celecoxib (n â€‹= â€‹3), indomethacin (n â€‹= â€‹3), aspirin (n â€‹= â€‹1), etoricoxib (n â€‹= â€‹1), and etodolac (n â€‹= â€‹1), and non-specific non-steroidal anti-inflammatory drugs (NSAIDs) (n â€‹= â€‹1). Naproxen was either given at a dose of 500 â€‹mg once or twice daily for 2-4 weeks. RCTs and additional comparative studies showed significant HO prevention using chemoprophylactic agents following hip arthroscopy. CONCLUSIONS: HO is a known and common complication following hip arthroscopy. The current systematic review found significant heterogeneity across the literature with respect to specific chemoprophylactic agents and their dosing regimens aimed to reduce the incidence and severity of HO following hip arthroscopy. Additionally, this review demonstrates that most studies that utilize chemoprophylaxis use NSAIDs with successful reduction in the incidence of HO. LEVEL OF EVIDENCE: Level IV Evidence.

Venous thromboembolism in aneurysmal subarachnoid hemorrhage: Risk factors and timing of chemoprophylaxis.

INTRODUCTION: Venous thromboembolism (VTE) is a significant contributor to morbidity and mortality among patients recovering from aneurysmal subarachnoid hemorrhage (aSAH). Prophylactic heparin reduces the risk of VTE, but the optimal timing for its initiation among aSAH patients remains unclear. OBJECTIVE: To conduct a retrospective study assessing risk factors for VTE and optimal timing of chemoprophylaxis in patients treated for aSAH. METHODS: From 2016-2020, 194 adult patients were treated for aSAH at our institution. Patient demographics, clinical diagnoses, complications, pharmacologic interventions, and outcomes were recorded. Risk factors for symptomatic VTE (sVTE) were analyzed via Chi-squared, univariate, and multivariate regression. RESULTS: In total 33 patients presented with sVTE (25 DVT, 14 PE). Patients with sVTE had longer hospital stays (p < 0.01) and worse outcomes at one-month (p < 0.01) and three-month follow-up (p = 0.02). Univariate predictors of sVTE included male sex (p = 0.03), Hunt Hess score (p = 0.01), Glasgow Coma scale (p = 0.02), intracranial hemorrhage (p = 0.03), hydrocephalus requiring external ventricular drain (EVD) placement (p < 0.01), and mechanical ventilation (p < 0.01). Only hydrocephalus requiring EVD (p = 0.01) and ventilator use (p = 0.02) remained significant upon multivariate analysis. Patients with delayed heparin introduction were significantly more likely to sustain sVTE on univariate analysis (p = 0.02) with a trend-level significance on multivariate analysis (p = 0.07). CONCLUSIONS: Patients with aSAH are more likely to develop sVTE following use of perioperative EVD or mechanical ventilation. sVTE leads to longer hospital stays and worse outcomes among patients treated for aSAH. Delayed heparin initiation increases the risk of sVTE. Our results may help guide surgical decision-making during recovery from aSAH and improve VTE-related postoperative outcomes.

Inadequate Venous Thromboembolism Chemoprophylaxis Is Associated With Higher Venous Thromboembolism Rates Among Trauma Patients With Epidurals.

INTRODUCTION: Guidelines encourage higher doses of low molecular weight heparin (LMWH) for prophylaxis in trauma patients. The risks of LMWH must be considered for patients who require an epidural catheter. We compared adequate and inadequate prophylaxis to determine if venous thromboembolism (VTE) and complication rates differed among patients with epidural catheters. METHODS: Trauma patients who required an epidural catheter between 2012 and 2019 were reviewed for VTE and epidural-related complications. Adequate dosing was defined as enoxaparin 30 mg or 40 mg twice daily. Inadequate dosing was defined as unfractionated heparin subcutaneously or enoxaparin once daily. RESULTS: Over the 8-y study period, 113 trauma patients required an epidural catheter of which 64.6% were males with a mean age of 55.8 y and injury severity score of 14. Epidural catheters were associated with 11 (9.7%) patients developing an acute deep vein thrombosis (DVT) and 2 (1.8%) patients with an acute pulmonary embolism. Those patients who received adequate doses of enoxaparin were less likely to have any VTE or DVT. Complications associated with epidural catheters were not dependent on the type of pharmacological prophylaxis. CONCLUSIONS: Given the high VTE rate observed in trauma patients who required an epidural catheter, along with the low complication rate that was observed independent of the type of pharmacological prophylaxis given, the data indicate that current efforts for higher doses of LMWH appear to be safe and associated with a lower VTE rate.

Chemoprophylaxis Timing Is Not Associated With Postoperative Bleeding After Spinal Trauma Surgery.

BACKGROUND: Little is known regarding appropriate timing for chemical venous thromboembolism (VTE) prophylaxis initiation in operative traumatic spinal injuries. We hypothesized that the incidence of post-operative bleeding leading to neurological decline or re-operation would not increase in patients who received early VTE prophylaxis (≤2 days post-surgery) as compared to those who received late VTE prophylaxis (≥ 3 days post-surgery). METHODS: This is a retrospective cohort study. Spine trauma patients who underwent spinal surgery, defined as anterior cervical discectomy and fusion, posterior cervical spinal fusion, anterior or posterior thoracic/lumbar spinal fusion, or vertebral percutaneous fixation from July 2015 to July 2020 were included. Demographics, pre-injury anti-thrombotics, operative characteristics, pre- and post-operative VTE prophylaxis, and post-operative complications, including spinal bleeding, and VTE were collected. Univariate analysis was performed, comparing baseline characteristics, VTE prophylaxis timing, and complications between the early and late groups. RESULTS: Two-hundred-eighty-two patients were included; 189 were in the early group (1.7 ± 0.5 days), and 93 were in the late (4.4 ± 2.1 days) group. The late group received enoxaparin more often than patients in the early group (41.9 % vs. 19 %, p < 0.001). Baseline characteristics, hospital course, and surgical management were similar between the groups. The rate of post-operative complications, including hematoma and VTE was similar between the groups. None of the patients in the early group had post-operative bleeding. CONCLUSION: In this retrospective cohort study, VTE prophylaxis timing was not associated with clinically significant post-operative spinal bleeding and VTE in trauma patients.

Low-Dose Heparin Infusion as Venous Thromboembolism Chemoprophylaxis in Patients With Blunt Cerebrovascular Injury.

INTRODUCTION: Blunt cerebrovascular injury (BCVI) can result in devastating stroke. Because of operative inaccessibility, the most common treatment for BCVI is aspirin or a low-dose systemic heparin infusion. While it is assumed that low dose heparin infusion imparts venous thromboembolism (VTE) prophylaxis, this has not been evaluated in the BCVI population. The purpose of this study was to evaluate VTE rates in patients receiving low-dose heparin infusion as treatment for BCVI. METHODS: Patients diagnosed with BCVI between 2014 and 2018 were reviewed for initiation of low-dose systemic heparin treatment. VTE was defined as a deep vein thrombosis or pulmonary embolism. BCVI patients without systemic heparin treatment were compared to BCVI patients with heparin treatment for overall VTE rates. Comparisons were also made to injured patients without a BCVI in our Trauma Activation Protocol (TAP) database. RESULTS: During the 5-year study period, 265 patients were identified with a BCVI. The majority (61%) were men with a median injury severity score (ISS) 22 (interquartile range [IQR]:14-33). Of these patients, 146 (55.1%) received a heparin infusion to treat BCVI. VTE was identified in eight of these patients (5.5%). Compared to TAP patients (n = 1020) who received standard dosing of VTE chemoprophylaxis, there was no difference in VTE rates compared to BCVI patients who were started on a low dose heparin infusion (3% versus 5.5%, P = 0.16). Area under the receiver operating characteristics (AUROC) was used to evaluate the predictive power of time to initiation of heparin infusion (AUC = 0.64 95% CI 0.42-0.85, P = 0.2) and time to reaching PTT goal (AUC = 0.52 95% CI 0.27-0.77, P = 0.83) as a predictor VTE events. CONCLUSIONS: Low dose heparin infusion is frequently used as an initial treatment of BCVI. In injured patients with BCVI, a low dose heparin infusion is associated with a low rate of VTE, comparable to injured patients without BCVI that received standard VTE chemoprophylaxis.

Timing of venous thromboembolism chemoprophylaxis with major surgery of lower-extremity long bone fractures.

BACKGROUND: There is debate on the need to withhold chemical venous thromboembolism (VTE) prophylaxis in patients requiring major orthopedic surgery. We hypothesized that the incidence of clinically significant hemorrhage (CSH) does not differ by the timing of prophylaxis in such patients. METHODS: This was a multicenter, retrospective cohort study conducted at five US trauma centers that included trauma patients admitted between January 1, 2018, to March 1, 2020, requiring surgical fixation of the femoral shaft, hip, or tibia and received VTE chemoprophylaxis during the hospitalization. Exclusions were major and moderate head or spinal injuries, chronic anticoagulant use, or multiple long bone surgeries. Timing of VTE chemoprophylaxis was examined as four groups: (1) initiated preoperatively without interruption for surgery; (2) initiated preoperatively but held perioperatively; (3) initiated within 12 hours postoperatively; and (4) initiated >12 hours postoperatively. The primary outcome was incidence of CSH (%), defined as overt hemorrhage within 24 hours postoperative that was actionable. Multivariate logistic regression evaluated differences in CSH based on timing of VTE chemoprophylaxis. RESULTS: There were 786 patients, and 65 (8.3%) developed a CSH within 24 hours postoperatively. Nineteen percent of patients received chemoprophylaxis preoperatively without interruption for surgery, 13% had preoperative initiation but dose(s) were held for surgery, 21% initiated within 12 hours postoperatively, and 47% initiated more than 12 hours postoperatively. The incidence and adjusted odds of CSH were similar across groups (11.3%, 9.1%, 7.1%, and 7.3% respectively; overall p = 0.60). The incidence of VTE was 0.9% and similar across groups ( p = 0.47); however, six of seven VTEs occurred when chemoprophylaxis was delayed or interrupted. CONCLUSION: This study suggests that early and uninterrupted VTE chemoprophylaxis is safe and effective in patients undergoing major orthopedic surgery for long bone fractures. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level IV.

Chemoprophylaxis against Pneumocystis jirovecii pneumonia in Japanese patients with ANCA-associated vasculitis: An observational study.

OBJECTIVES: This study investigated the current practice of prophylactic treatment against Pneumocystis jirovecii pneumonia (PCP) and its effectiveness in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV). METHODS: This study included 319 patients registered from 53 institutions in Japan and newly diagnosed with AAV. During the 2-year observation period, we examined the frequency of usage, effectiveness and safety of prophylactic drugs against PCP. RESULTS: Most patients received prophylactic drugs against PCP with the initiation of immunosuppressive agents, and >50% of them remained on chemoprophylaxis against PCP at 2 years after. The initial daily dose of oral prednisolone and the proportion of cyclophosphamide administration were higher in patients who received chemoprophylaxis against PCP than in those who did not. PCP occurred in nine patients (3%) and resulted in the death of four. The incidence rate of PCP in patients who received chemoprophylaxis was 1.13/100 patient-years (95% confidence interval, 0.38-2.68) and that in those who did not was 2.74 (1.04-6.02). The incidence rate ratio was 0.41 (0.11-1.53). CONCLUSIONS: The markedly low incidence of PCP may be attributed to the continuous chemoprophylaxis against PCP received by >50% of Japanese patients with AAV, although the effectiveness of chemoprophylaxis against PCP was not statistically confirmed.

[Risk factors and chemoprophylaxis of ulcerative colitis-colorectal cancer].

Ulcerative colitis-colorectal cancer (UC-CRC) is one of the most serious complications in patients with ulcerative colitis (UC), with worse prognosis and higher mortality than sporadic colorectal cancer (CRC). Since most UC-CRC developed through the "inflammation-dysplasia-carcinoma" approach, early detection of dysplasia through identification of high-risk groups reasonable monitoring and active prevention are extremely important. However, there is no consensus on the risk factors of UC carcinogenesis and the drugs that can be used for chemoprevention currently. This article combined with relevant literature at home and abroad, reviewed the current risk factors and chemopreventive drugs for UC carcinogenesis, in order to provide reference for early prevention, early detection and early diagnosis of UC-CRC.

Assessment of BMI and Venous Thromboembolism Rates in Patients on Standard Chemoprophylaxis Regimens After Undergoing Free Tissue Transfer to the Head and Neck.

Importance: Venous thromboembolism (VTE) is a severe complication after free tissue transfer to the head and neck (H&N). Enoxaparin 30 mg twice daily (BID) is a common regimen for chemoprophylaxis. However, differences in enoxaparin metabolism based on body weight may influence its efficacy and safety profile. Objective: To assess the association between BMI and postoperative VTE and hematoma rates in patients treated with prophylactic enoxaparin 30 mg BID. Design, Setting, and Participants: This was a retrospective review of a prospectively collected cohort from 2012 to 2022. Postoperative VTE, hematoma, and free flap pedicle thrombosis were recorded within 30 days of index surgery. The setting was a tertiary academic referral center. Participants included patients undergoing H&N reconstruction with free flaps that received fixed-dose subcutaneous enoxaparin 30 mg BID postoperatively. Statistical analysis was conducted from April to May 2022. Main Outcomes and Measures: Outcomes include incidence of VTE, hematoma, and flap pedicle thrombosis events within 30 days of the surgery. Univariate and multivariable regression models were used to evaluate associations between BMI and other patient factors with these outcomes. Results: Among the 765 patients included, 262 (34.24%) were female; mean (SD) age was 60.85 (12.64) years; and mean (SD) BMI was 26.36 (6.29). The rates of VTE and hematoma in the cohort were 3.92% (30 patients) and 5.09% (39 patients), respectively. After adjusting for patient factors, BMI was the only factor associated with VTE (OR, 1.07; 95% CI, 1.015-1.129). Obesity (BMI >30) was associated with increased odds of VTE (OR, 2.782; 95% CI, 1.197-6.564). Hematoma was not associated with BMI (OR, 0.988; 95% CI, 0.937-1.041). Caprini score of at least 9 was not associated with VTE (OR, 1.259; 95% CI, 0.428-3.701). Conclusions and Relevance: This cohort study found that obesity was associated with an increased risk of VTE in patients after microvascular H&N reconstruction and while on standard postoperative chemoprophylaxis regimens. This association may suggest insufficient VTE prophylaxis in this group and a potential indication for weight-based dosing.

Hepatocellular Carcinoma Chemoprevention with Generic Agents.

Liver cancer, mainly hepatocellular carcinoma (HCC), remains a major cause of cancer-related death worldwide. With the global epidemic of obesity, the major HCC etiologies have been dynamically shifting from viral to metabolic liver diseases. This change has made HCC prevention difficult with increasingly elusive at-risk populations as rational target for preventive interventions. Besides ongoing efforts to reduce obesity and metabolic disorders, chemoprevention in patients who already have metabolic liver diseases may have a significant impact on the poor HCC prognosis. Hepatitis B- and hepatitis C-related HCC incidences have been substantially reduced by the new antivirals, but HCC risk can persist over a decade even after successful viral treatment, highlighting the need for HCC-preventive measures also in these patients. Experimental and retrospective studies have suggested potential utility of generic agents such as lipophilic statins and aspirin for HCC chemoprevention given their well-characterized safety profile, although anticipated efficacy may be modest. In this review, we overview recent clinical and translational studies of generic agents in the context of HCC chemoprevention under the contemporary HCC etiologies. We also discuss newly emerging approaches to overcome the challenges in clinical testing of the agents to facilitate their clinical translation.

Cost-Effective Modeling of Thromboembolic Chemoprophylaxis for Total Ankle Arthroplasty.

BACKGROUND: Symptomatic venous thromboembolism (VTE) following total ankle arthroplasty (TAA) can cause substantial morbidity and mortality. To prevent this complication, surgeons often prescribe postoperative chemoprophylaxis. However, much controversy exists regarding the efficacy of chemoprophylaxis because of the limited studies exploring its use. Furthermore, even less is known about its cost-effectiveness. Therefore, this study sought to determine the cost-effectiveness of commonly prescribed chemoprophylactic agents using a break-even analysis economic model. METHODS: The literature was searched, and an online database was used to identify patients who developed a symptomatic VTE after undergoing TAA. Our institutional records were used to estimate the cost of treating a symptomatic VTE, and an online drug database was used to obtain the cost of commonly prescribed chemoprophylactic agents. A break-even analysis was then performed to determine the final break-even rate necessary to make a drug cost-effective. RESULTS: The low and high rates of symptomatic VTE were determined to be 0.46% and 9.8%. From 2011 to 2021, a total of 3455 patients underwent total ankle arthroplasty. Of these patients, 16 developed a postoperative symptomatic VTE (1.01%). Aspirin 81 mg was cost-effective if the initial symptomatic VTE rates decreased by an absolute risk reduction (ARR) of 0.0003% (NNT = 31 357). Aspirin 325 mg was also cost-effective if the initial rates decreased by an ARR 0.02% (NNT = 5807). Likewise, warfarin (5 mg) was cost-effective at all initial rates with an ARR of 0.02% (NNT = 4480). In contrast, enoxaparin (40 mg) and rivaroxaban (20 mg) were only cost-effective at higher initial symptomatic VTE rates with ARRs of 1.48% (NNT = 68) and 5.36% (NNT = 19). Additional analyses demonstrated that enoxaparin (40 mg) and rivaroxaban (20 mg) become cost-effective when costs of treating a symptomatic VTE are higher than our estimates. CONCLUSION: Chemoprophylaxis following TAA can be cost-effective. A tailored approach to VTE prophylaxis with cost-effectiveness in mind may be beneficial to the patient and health system.

Does Aspirin Provide Adequate Chemoprophylaxis for Venous Thromboembolic Events in Operative Pelvic and Acetabular Fractures?

Background: Several strategies exist to prevent venous thromboembolism (VTE) in operative pelvic and acetabular fractures, however literature lacks consensus on the optimal thromboprophylaxis. Even more debated, and perhaps controversial, is whether aspirin provides adequate thromboprophylaxis in the setting of these injuries. The primary objective was to evaluate the efficacy of aspirin in the prevention of venous thromboembolism (VTE) events, including deep vein thrombosis (DVT) and pulmonary embolism (PE) in operative pelvic and acetabular fractures compared to other anticoagulants. Methods: A retrospective chart review of pelvic and acetabular fractures that underwent operative fixation was completed. The incidence of VTE and hematoma formation was evaluated and compared between patients who received aspirin versus enoxaparin or heparin. Multivariate analysis was performed to control for confounding demographic, comorbidity, and injury-related variables. The outcome measurements included development of DVT and/or PE and hematoma formation. Results: Of patients with operative pelvic and acetabular fractures, 4.2% developed a DVT and 3.5% developed a PE, with 1.4% developing both. Of these patients 37.5% were treated with aspirin versus the 62.5% treated with heparin or enoxaparin. There was no significant difference in the incidence of DVT or PE between cohorts (p=0.498 and p=0.262). Aspirin trended toward significance as protective against post-operative hematoma (p=0.085). Conclusion: This study suggests that aspirin is an acceptable method of VTE thromboprophylaxis with no inferior results to other common anticoagulants used in operative pelvis and acetabular fractures. As a chemoprophylactic agent, aspirin is an efficacious option in these complex injuries that shows no increase in the incidence in symptomatic VTE events. Level of Evidence: III.

Optimizing Perioperative Venous Thromboembolism Chemoprophylaxis on a Gynecologic Oncology Service.

BACKGROUND: Perioperative venous thromboembolism (VTE) is a significant cause of morbidity and mortality after gynecologic cancer surgery. Here we report a quality improvement intervention to increase perioperative VTE chemoprophylaxis compliance. STUDY DESIGN: All operations performed by a gynecologic oncologist at a tertiary urban university medical center admitted to the hospital for at least one midnight were included. Using a pre/post design with a washout period, we sought to increase perioperative VTE chemoprophylaxis compliance from 22% in the historical control (HC) cohort to 90% in the quality improvement (QI) cohort. The perioperative VTE chemoprophylaxis process was standardized by addressing four domains: preoperative VTE chemoprophylaxis, surgical time-out, postoperative VTE chemoprophylaxis, and intervention education and compliance tracking. Pearson's chi-square test was used to compare HC vs QI cohort compliance. RESULTS: There were 130 surgical cases in the HC cohort and 131 in the QI cohort. Forty-two percent underwent laparotomy, and 57% had cancer at the time of operation. VTE chemoprophylaxis compliance improved from 22% in the HC cohort to 82% in the QI cohort (p < 0.001). Preoperative VTE chemoprophylaxis compliance improved from 76% in the HC cohort to 94% in the QI cohort (p < 0.001), and postoperative VTE chemoprophylaxis compliance improved from 27% to 87% (p < 0.001). Thirty-day postoperative VTE occurred in three patients (2%) in the HC cohort and none in the QI cohort (p = 0.08). CONCLUSIONS: A low-cost and low-technology QI initiative intervention improved perioperative compliance with VTE chemoprophylaxis.

Provider education program on the Khorana score to promote venous thromboembolism chemoprophylaxis in patients with gynecologic cancer.

OBJECTIVE: To evaluate the efficacy of a healthcare improvement initiative to improve provider compliance with the American Society of Clinical Oncology (ASCO) guidelines for venous thromboembolism chemoprophylaxis in patients with gynecologic cancer receiving chemotherapy. METHODS: A healthcare improvement initiative was implemented at our institution to improve compliance with American Society of Clinical Oncology venous thromboembolism chemoprophylaxis guidelines in patients receiving chemotherapy with a Khorana score ≥2. Baseline Khorana score and venous thromboembolism data were retrospectively collected for chemotherapy-naïve patients with gynecologic cancer initiating chemotherapy between December 2018 and November 2019. Data for the post-intervention period from December 2019 to December 2020 were captured prospectively. Primary outcome was compliance with American Society of Clinical Oncology guidelines. Secondary outcomes were incidence of venous thromboembolism and complications surrounding venous thromboembolism chemoprophylaxis. RESULTS: We identified 62 patients in the pre-implementation cohort. Approximately half had a Khorana score of ≥2 (52%). Median Khorana score was 2 (range 1-4). None of these patients received prophylactic chemoprophylaxis. Seven (11%) of these patients were diagnosed with venous thromboembolism. Multivariate logistic regression showed increasing Khorana score was associated with increased venous thromboembolism risk (OR 4.9, p=0.01). With cut-off Khorana score of 2, there was no significant increase in venous thromboembolism. However, with a cut-off Khorana score of 3, patients were 15 times more likely to have venous thromboembolism (OR 15.2, p=0.04). In the post-intervention cohort, 22 patients were eligible for chemoprophylaxis and 11 patients were given anticoagulation (50% compliance with guidelines), with no incidence of venous thromboembolism or adverse effects of therapy noted among those receiving chemoprophylaxis. CONCLUSION: Notifying providers of a patient's Khorana score improves compliance with American Society of Clinical Oncology guidelines for venous thromboembolism chemoprophylaxis among chemotherapy patients.

Effect of Nicotinamide in Skin Cancer and Actinic Keratoses Chemoprophylaxis, and Adverse Effects Related to Nicotinamide: A Systematic Review and Meta-Analysis.

BACKGROUND: Oral nicotinamide is recommended in individuals with a field of cancerization or with ≥1 previous cutaneous squamous cell carcinoma (cSCC). OBJECTIVE: To evaluate the effect of nicotinamide in prevention of skin cancers. METHODS: We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the effect of nicotinamide. We used Medline, EMBASE, CENTRAL, and Web of Science databases from their inception to October 2020 to search the following concepts: "nicotinamide"; "randomized controlled trial" (validated filters). Two independent reviewers screened titles and abstracts for intervention and study design before searching full texts for eligibility criteria. To be eligible, ≥1 outcome had to be covered. We used a standardized collection grid to complete data extraction in duplicate. The primary outcome was skin cancers (all types). Secondary outcomes were basal cell carcinomas (BCCs); cSCCs; actinic keratoses; melanomas; digestive, cutaneous, and biochemical adverse effects (AEs). Subgroup analyses were planned a priori. RESULTS: We screened 4730 citations and found 29 trials (3039 patients) meeting inclusion criteria. Nicotinamide was associated with a significant reduction in skin cancers compared to control (rate ratio 0.50 (95% CI, 0.29-0.85; I 2 = 64%; 552 patients; 5 trials); moderate strength of the evidence). Heterogeneity was explained by risk of bias. Nicotinamide was associated with a significant reduction in BCCs and cSCCs, and increased risk of digestive AEs. CONCLUSION: Oral nicotinamide should be considered in healthy patients or organ transplant recipients with history of skin cancer (GRADE: weak recommendation; moderate-quality evidence), in particular of BCC and cSCC.

Incidence of Venous Thromboembolism following Knee Arthroscopy: Effectiveness of a Risk-Based Stratified Chemoprophylaxis Protocol.

The incidence of symptomatic venous thromboembolism (VTE) has been reported in up to 10.9% of patients undergoing knee arthroscopy without chemoprohylaxis. The purpose of this study was to evaluate the effectiveness of a chemoprophylaxis protocol in patients undergoing knee arthroscopy. A retrospective review of prospectively enrolled patients in a new institutional VTE prophylaxis protocol identified all patients undergoing knee arthroscopy during a 5-year period. This risk-based chemoprophylaxis protocol was instituted based on the Caprini model: patients at more than minimal risk were prescribed enoxaparin 40 mg daily for 3 weeks, while all others were instructed to take aspirin 325 mg twice daily. The primary outcome measure was incidence of VTE within 60 days postoperatively. Demographic characteristics and other risk factors for VTE were also recorded, as well as any postoperative complications. Among the 1,276 knee arthroscopies, there were 26 VTE events (2.0%), including 23 with deep vein thrombosis (DVT), two pulmonary emboli (PE), and one patient with both DVT and PE. There were no deaths or complications requiring hospitalization or reoperation. The VTE diagnosis occurred at, on average, 9 days postoperatively. Patients in the high-risk group treated with enoxaparin had a lower VTE incidence (1.49%) than those instructed to take aspirin (2.0%); p = 0.75. Those undergoing an anterior cruciate ligament (ACL) reconstruction had the highest VTE incidence (2.87%). This study found that a chemoprophylaxis protocol with preferential use of aspirin or low-molecular weight heparin based on risk factors reduced the VTE incidence below to 2.0%, which is lower than most historical controls.

Enoxaparin titrated by anti-Xa levels reduces venous thromboembolism in trauma patients.

BACKGROUND: Trauma is a major risk factor for the development of a venous thromboembolism (VTE). After observing higher than expected VTE rates within our center's Trauma Quality Improvement Program data, we instituted a change in our VTE prophylaxis protocol, moving to enoxaparin dosing titrated by anti-Xa levels. We hypothesized that this intervention would lower our symptomatic VTE rates. METHODS: Adult trauma patients at a single institution meeting National Trauma Data Standard criteria from April 2015 to September 2019 were examined with regards to VTE chemoprophylaxis regimen and VTE incidence. Two groups of patients were identified based on VTE protocol-those who received enoxaparin 30 mg twice daily without routine anti-Xa levels ("pre") versus those who received enoxaparin 40 mg twice daily with dose titrated by serial anti-Xa levels ("post"). Univariate and multivariate analyses were performed to define statistically significant differences in VTE incidence between the two cohorts. RESULTS: There were 1698 patients within the "pre" group and 1406 patients within the "post" group. The two groups were essentially the same in terms of demographics and risk factors for bleeding or thrombosis. There was a statistically significant reduction in VTE rate (p = 0.01) and deep vein thrombosis rate (p = 0.01) but no significant reduction in pulmonary embolism rate (p = 0.21) after implementation of the anti-Xa titration protocol. Risk-adjusted Trauma Quality Improvement Program data showed an improvement in rate of symptomatic pulmonary embolism from fifth decile to first decile. CONCLUSION: A protocol titrating prophylactic enoxaparin dose based on anti-Xa levels reduced VTE rates. Implementation of this type of protocol requires diligence from the physician and pharmacist team. Further research will investigate the impact of protocol compliance and time to appropriate anti-Xa level on incidence of VTE. LEVEL OF EVIDENCE: Therapeutic/care management, Level IV.