Prophylactic Dose Research Articles

Effect of dexamethasone administration for postoperative nausea and vomiting prophylaxis on glucose levels in adults with diabetes undergoing elective surgery: a systematic review with meta-analysis.

The objective of this review was to evaluate the effect of intravenous dexamethasone given intraoperatively for postoperative nausea and vomiting prophylaxis on maximal blood glucose level within the initial 24 hours following elective surgery for patients with diabetes. Postoperative nausea and vomiting is a prevalent adverse effect of anesthesia that leads to morbidity, increased health care costs, and unanticipated hospital admissions. Dexamethasone is an effective prophylactic agent that confers secondary analgesic and anti-inflammatory benefits. However, its use in patients with diabetes remains controversial due to the potential for increased postoperative blood glucose levels. This review considered studies with participants 18 years of age or older with type 1 or 2 diabetes undergoing an elective surgical procedure. Eligible studies reported postoperative blood glucose levels in adults with diabetes after receiving a single 4-10 mg prophylactic dose of intravenous dexamethasone intraoperatively for postoperative nausea and vomiting. The primary outcome was maximum blood glucose level in the first 24 hours after surgery. All study designs were eligible for inclusion. Studies were excluded if they lacked a control group with diabetes or if they did not report maximum blood glucose values in both groups. A search of MEDLINE, CINAHL Complete, Embase, Web of Science, TRIP database, and the Cochrane Database of Systematic Reviews was completed in October 2021. Gray literature resources were also searched. No date or language restrictions were applied. Methodological quality was assessed using JBI appraisal tools for randomized controlled trials, cohort studies, and case-control studies. A meta-analysis of maximal postoperative blood glucose level within 24 hours of surgery was performed, as well as subgroup analyses by dexamethasone dose, insulin treatment, and study design type. Eleven studies (4 randomized controlled trials, 6 cohort studies, and 1 case-control study) were included in this review, with 1 study excluded from meta-analysis and results reported narratively. The total sample size of studies included in meta-analysis was 2567. The administration of dexamethasone significantly increased maximal blood glucose levels in the 24 hours immediately following surgery compared with control groups with diabetes, as demonstrated by randomized controlled trials (mean difference [MD] 39.56 mg/dL; 95% CI 16.18 to 62.94; P < 0.001; I2 = 87%) and observational studies (MD 26.31 mg/dL; 95% CI 7.10 to 45.52; P = 0.007; I2 = 92%). This increase in blood glucose was significant for all doses of dexamethasone: 4 mg (MD 40.81 mg/dL; 95% CI 2.42 to 79.19; P = 0.001; I2 = 91%), 8 mg (randomized controlled trials only; MD 39.45 mg/dL; 95% CI 15.32 to 63.58; P = 0.001; I2 = 86%), and mixed 4-10 mg dose (MD 30.82 mg/dL; 95% CI 6.75 to 54.88; P < 0.012; I2 = 93%). Postoperative hyperglycemia persisted in studies using insulin treatment as well as those not using insulin protocols. The overall certainty of the findings ranged from very low for outcomes that included cohort studies to moderate when outcomes from randomized controlled trials were analyzed separately. However, the quantitative findings of the experimental and observational studies were clinically similar. Risk of bias presented minimal concerns in all included studies. Dexamethasone leads to transient postoperative hyperglycemia in patients with diabetes undergoing elective surgery when given as a single 4-10 mg intravenous dose for postoperative nausea and vomiting prophylaxis. The clinical relevance of hyperglycemia is debatable given its small magnitude and transient nature. Without more tightly controlled data, methodological consistency, and baseline blood glucose values, it is impossible to test causal links between hyperglycemia and pre-existing patient factors (eg, hemoglobin A1C levels) or postoperative complications. PROSPERO CRD42020185607.

The Prophylactic Effect of Eucheuma spinosum on Total Blood Cholesterol Levels in Rattus norvegicus Dexamethasone-Induced

Hyperlipidemia is one of the main risk factors for heart disease caused by the formation of atherosclerosis. Eucheuma spinosum contains a natural antioxidant flavonoid, which has an antiatherogenic effect that can inhibit the formation of cholesterol in the liver so that it can prevent the development of atherosclerosis. This study aims to determine the effect of prophylactic administration of Eucheuma spinosum on the total cholesterol levels of Rattus novergicus induced by dexamethasone. This study was an experimental design with a post-test-only control group design. This study would use 24 white male Rattus norvegicus divided into three groups; a negative control group (K-) without treatment, a positive control group (K+) induced dexamethasone 8 mg/Kg BW on day 14 until day 20, treatment group (KP) given Eucheuma spinosum extract 200 mg/Kg BW on day 8 until day 20 as Prophylactic and on day 14 until day 20 induced dexamethasone 8 mg/Kg BW. After completing the treatment period, all groups were terminated and taken total calculation of cholesterol levels through the aorta of rats. Data was analyzed statistically computerized. The results of the study of total cholesterol levels that used Kruskal-Wallis test showed differences between groups (p&lt;0.001). There was a decrease in total cholesterol levels in the treatment group (p&lt;0.024) compared with the positive control group. The administration of Eucheuma spinosum extract as a prophylactic dose of 200 mg/Kg BW for 14 days could reduce the total cholesterol level of Rattus norvegicus induced by dexamethasone compared to those not given Eucheuma spinosum extract.

Prognostic value of D-dimers in patients with COVID-19: narrative synthesis

Introduction. Contemporary researchers have suggested and demonstrated the hypothesis that the elevated level of D-dimers, which is a valuable marker of coagulation and fibrinolysis activation, can predict the severity of COVID-19, pulmonary complications, and thromboembolic events before they occur. Material and methods. The bibliographic resources were analyzed and selected from databases such as PubMed, Hinari, SpringerLink, and Google Search using keywords such as “COVID-19,” “SARS-CoV-2,” “coronavirus,” “D-dimers,” “biomarkers,” and “severity prediction,” which were used in various combinations to maximize search efficiency. Therefore, the manuscript contains 51 representative articles for the purpose of this synthesis article. Results. The D-dimer levels are significantly higher in patients with severe forms of COVID-19 compared to those with non-severe forms, in patients with acute respiratory distress syndrome compared to those without acute respiratory distress syndrome, and in deceased patients compared to those who have survived. D-dimers positively correlate with the degree of severity and the increased risk of progression to severe disease, inversely proportional to the survival rate. They can predict prognosis, determine therapeutic strategies, prevent complications, positively influence the disease’s course, and monitor the prognosis. Conclusions. D-dimers should be used as a pre-radiographic screening tool as early as possible after admission and as an indicator for risk stratification of venous thromboembolism in hospitalized patients with COVID-19. Based on the increase in D-dimer levels, adjusting therapeutic doses of anticoagulants is more beneficial for patients compared to administering prophylactic doses.

Potential of anticoagulant therapy in cardiology practice for thrombocytopenia. Literature review

The review article discusses the issues of anticoagulant therapy in cardiovascular patients with thrombocytopenia (TP), gives the concept of ethylenediaminetetraacetic acidand heparin-induced TP. The management of patients with heparin-induced TP is analyzed in detail, which consists in the discontinuation of unfractionated and low molecular weight heparin administration with replacement to direct thrombin inhibitors (lepirudin or argatroban), fondaparinux or direct oral anticoagulants.The authors emphasize that the anticoagulant administration to most patients with platelet count &gt;50×109/l is possible in full prophylactic and therapeutic doses. Reducing the level of platelets to 25-50×109/l in most cases requires a reduction in the anticoagulant dose by 50%. At a platelet level of 20-25×109/l or less, anticoagulant therapy should be avoided in most patients.In addition to the scope of anticoagulant therapy, TP also determines the choice of anticoagulant as follows: in patients with acute coronary syndrome, bivalirudin or fondaparinux are recommended, while in patients with cancer and stable TP, warfarin or direct oral anticoagulants can be prescribed. In progressive TP (if heparin-induced TP is ruled out), low molecular weight heparins should be used.

The Role of Anticoagulants and Antiplatelets in Reducing Mortality in COVID-19 Patients: A Systematic Review and Meta-Analysis of Studies Reporting Adjusted Data.

The coronavirus disease 2019 (COVID-19) is associated with prolonged prothrombin time (PT), active partial thromboplastin time (aPTT), and increased D-dimer levels. Therefore, we aim to investigate if anticoagulants (AC) and antiplatelet (AP) therapy playa role in mitigating COVID-19 and its associated thrombosis along with its effect on the mortality rate, the need for mechanical ventilation, and the risk of hospital admission. Electronic databases were searched from their inception to July 19, 2022. The studies were divided into two groups: Group A (any dose of AC/AP versus no AC/AP) and Group B (therapeutic dose of AC (tAC)/AP versus prophylactic dose of AC (pAC)/AP). Review Manager (RevMan) version 5.4.1 (The Nordic Cochrane Centre, The Cochrane Collaboration, Copenhagen, Denmark) was used for all statistical analyses. Adjusted data ratios were extracted from all included studies and pooled using the random effects model. A total of 33 studies were taken for the analysis of two groups (Group A: 285,065COVID-19-positive patients, Group B: 2,421 COVID-19-positive patients). Overall analysis in Group A showed that the AC/AP group had a low risk of mortality in COVID-19 patients compared to the control group (risk ratio (RR): 0.77, 95% confidence interval (CI): 0.69-0.86). There was no significant difference in the need for mechanical ventilation (RR: 0.80, 95% CI: 0.60-1.08) and hospital admission (RR: 1.12, 95% CI: 0.78-1.59) between the AC/AP and no AC/AP group. Alongside, in Group B, tAC/AP did not demonstrate a significant decrease in mortality as compared to pAC/AP (RR: 0.62, 95% CI: 0.37-1.06). Treatment with AC and AP drugs can significantly decrease the mortality rate in COVID-19-infected patients, while AC also significantly reduces the need for mechanical ventilation.

Effects of inflammation on thrombosis and outcomes in COVID-19: secondary analysis of the ATTACC/ACTIV-4a trial

BackgroundPatients hospitalized for COVID-19 are at high risk of thrombotic complications and organ failure, and often exhibit severe inflammation, which may contribute to hypercoagulability. ObjectivesTo determine whether patients hospitalized for COVID-19 experience differing frequencies of thrombotic and organ failure complications and derive variable benefits from therapeutic-dose heparin dependent on the extent of systemic inflammation and whether observed benefit from therapeutic-dose anticoagulation varies depending on the degree of systemic inflammation. MethodsWe analyzed data from 1346 patients hospitalized for COVID-19 enrolled in the ATTACC and ACTIV-4a platforms who were randomized to therapeutic-dose heparin or usual care for whom levels of C-reactive protein (CRP) were reported at baseline. ResultsIncreased CRP was associated with worse patient outcomes, including a >98% posterior probability of increased organ support requirement, hospital length of stay, risk of 28-day mortality, and incidence of major thrombotic events or death (patients with CRP 40-100 mg/L or ≥100 mg/L compared to patients with CRP <40 mg/L). Patients with CRP 40 to 100 mg/L experienced the greatest degree of benefit from treatment with therapeutic doses of unfractionated or low molecular weight heparin compared with usual-care prophylactic doses. This was most significant for an increase in organ support-free days (odds ratio: 1.63; 95% confidence interval, 1.09-2.40; 97.9% posterior probability of beneficial effect), with trends toward benefit for other evaluated outcomes. ConclusionModerately ill patients hospitalized for COVID-19 with CRP between 40 mg/L and 100 mg/L derived the greatest benefit from treatment with therapeutic-dose heparin.

The Impact of Continuous Veno-Venous Hemodiafiltration on the Efficacy of Administration of Prophylactic Doses of Enoxaparin: A Prospective Observational Study.

Critically ill patients frequently require continuous renal replacement therapy (CRRT). During CRRT, particles up to 10 kDa in size, such as enoxaparin, may be removed. The aim of this study was to determine if patients receiving prophylactic doses of enoxaparin and treated with continuous veno-venous hemodiafiltration (CVVHDF) reach prophylactic values of anti-Xa factor activity. In this observational trial, we compared two groups: 20 patients treated with CVVHDF and 20 patients not treated with CVVHDF. All of them received prophylactic doses of 40 mg of enoxaparin subcutaneously. Anti-Xa factor activity was determined on the third day of receiving a prophylactic dose of enoxaparin. The first blood sample was taken just before the administration of enoxaparin, and other samples were taken 3 h, 6 h, and 9 h after the administration of a prophylactic dose of enoxaparin. At 3 and 6 h after administration of enoxaparin in both groups, we observed a significant increase in anti-Xa factor activity from baseline, with the peak after 3 h of administration. There were no significant differences in the numbers of patients who had anti-Xa factor activity within the prophylactic range between CVVHDF and control groups. CVVHDF has only a mild effect on the enoxaparin prophylactic effect measured by anti-Xa factor activity. Thus, it seems there is no need to increase the dose of enoxaparin for patients requiring CVVHDF.

A microCT-based platform to quantify drug targeting

BackgroundHeterotopic ossification (HO) is a frequent and debilitating complication of traumatic musculoskeletal injuries and orthopedic procedures. Prophylactic dosing of botulinum toxin type A (BTxA) holds potential as a novel treatment option if accurately distributed throughout soft-tissue volumes where protection is clinically desired. We developed a high-resolution, microcomputed tomography (microCT)-based imaging strategy to assess drug distribution and validated this platform by quantifying distribution achieved via a prototype delivery system versus a single-bolus injection.MethodsWe injected an iodine-containing contrast agent (iodixanol 320 mg I/mL) into dissected rabbit musculature followed by microCT imaging and analysis. To contrast the performance of distributed versus bolus injections, a three-dimensional (3D) 64-cm3-printed soft-tissue holder was developed. A centered 2-cm3 volume of interest (VOI) was targeted with a single-bolus injection or an equal volume distributed injection delivered via a 3D-printed prototype. VOI drug coverage was quantified as a percentage of the VOI volume that was < 1.0 mm from the injected fluid.ResultsThe microCT-based approach enabled high-resolution quantification of injection distribution within soft tissue. The distributed dosing prototype provided significantly greater tissue coverage of the targeted VOI (72 ± 3%, mean ± standard deviation) when compared to an equal volume bolus dose (43 ± 5%, p = 0.031) while also enhancing the precision of injection targeting.ConclusionsA microCT-based imaging technique precisely quantifies drug distribution within a soft-tissue VOI, providing a path to overcome a barrier for clinical translation of prophylactic inhibition of HO by BTxA.Relevance statementThis platform will facilitate rapid optimization of injection parameters for clinical devices used to effectively and safely inhibit the formation of heterotopic ossification.Key points• MicroCT provides high-resolution quantification of soft-tissue drug distribution.• Distributed dosing is required to maximize soft-tissue drug coverage.• Imaging platform will enable rapid screening of 3D-printed drug distribution prototypes.Graphical

Effects of anti-Xa activity monitoring on the outcome of high-risk pregnancies treated with a prophylactic dose of low-molecular-weight heparin.

To evaluate if anti-Xa level monitoring and dose adjustment in women using a prophylactic dose of enoxaparin can decrease placenta-mediated pregnancy complications. This retrospective observational cohort study included pregnant women receiving enoxaparin prophylaxis, who were followed at the Thrombosis and Hemostasis Outpatient clinic between 2010 and 2017. The dose was adjusted according to enoxaparin anti-Xa levels in the study group or the weight of individuals in the control group. Of 585 women surveyed, 110 met the inclusion criteria; 63 of them were included in the study group and 47 in the control group. Mean starting dose was 46 versus 43 mg (p = .25), mean final dose was 52 mg versus 45 mg (p = .03) and dose adjustment was required in 37% versus 11% (p = .002) in the study and control groups, respectively. Twenty-eight percent of anti-Xa measurements in the second trimester were beneath the prophylactic threshold, compared to 11% and 16% in the first and third trimesters, respectively (p = .02). Labors ended with live birth in 91% versus 94% of cases (p = .5), 85% versus 68% of pregnancies were term (p = .05), 11% versus 23% of newborns were low birth weight (p = .1) and placenta-mediated pregnancy complications were documented in 9% versus 19%, (p = .17) in the study group relative to controls, respectively. The most prominent decrease in anti-Xa levels was observed in the second trimester. Monitored women had significantly more term deliveries and demonstrated a trend toward higher birth weight and fewer placenta-mediated pregnancy complications. Larger studies are needed to confirm improved pregnancy outcome in monitored women.

Prevention of maternal and neonatal death/infections with a single oral dose of azithromycin in women in labour in low-income and middle-income countries (A-PLUS): a study protocol for a multinational, randomised placebo-controlled clinical trial

IntroductionMaternal and neonatal infections are among the most frequent causes of maternal and neonatal mortality, and current antibiotic strategies have been ineffective in preventing many of these deaths. A randomised...

Effect of single versus multiple prophylactic antibiotic doses on prosthetic joint infections following primary total hip arthroplasty in patients with osteoarthritis at public and private hospitals in Denmark: protocol for a nationwide cross-over, cluster randomised, non-inferiority trial [The Pro-Hip-Quality Trial]

IntroductionA feared complication after total hip arthroplasty (THA) is prosthetic joint infection (PJI), associated with high morbidity and mortality. Prophylactic antibiotics can reduce the risk of PJI. However, there is...

Adoption of a National Prophylactic Anticoagulation Guideline for Hospitalized Pregnant Women With COVID-19: Retrospective Cohort Study.

Both COVID-19 and pregnancy are associated with hypercoagulability. Due to the increased risk for thrombosis, the United States National Institute of Health's recommendation for prophylactic anticoagulant use for pregnant patients has expanded from patients hospitalized for severe COVID-19 manifestation to all patients hospitalized for the manifestation of COVID-19 (no guideline: before December 26, 2020; first update: December 27, 2022; second update: February 24, 2022-present). However, no study has evaluated this recommendation. The objective of this study was to characterize prophylactic anticoagulant use among hospitalized pregnant people with COVID-19 from March 20, 2020, to October 19, 2022. This was a retrospective cohort study in large US health care systems across 7 states. The cohort of interest was pregnant patients who were hospitalized with COVID-19, without previous coagulopathy or contraindication to anticoagulants (n=2767). The treatment group consisted of patients prescribed prophylactic dose anticoagulation between 2 days before and 14 days after COVID-19 treatment onset (n=191). The control group was patients with no anticoagulant exposure between 14 days before and 60 days after COVID-19 treatment onset (n=2534). We ascertained the use of prophylactic anticoagulants with attention to the updates in guidelines and emerging SARS-CoV-2 variants. We propensity score matched the treatment and control group 1:1 on the most important features contributing to the prophylactic anticoagulant administration status classification. Outcome measures included coagulopathy, bleeding, COVID-19-related complications, and maternal-fetal health outcomes. Additionally, the inpatient anticoagulant administration rate was validated in a nationwide population from Truveta, a collective of 700 hospitals across the United States. The overall administration rate of prophylactic anticoagulants was 7% (191/2725). It was lowest after the second guideline update (no guideline: 27/262, 10%; first update: 145/1663, 8.72%; second update: 19/811, 2.3%; P<.001) and during the omicron-dominant period (Wild type: 45/549, 8.2%; Alpha: 18/129, 14%; Delta: 81/507, 16%; and Omicron: 47/1551, 3%; P<.001). Models developed on retrospective data showed that the variable most associated with the administration of inpatient prophylactic anticoagulant was comorbidities prior to SARS-CoV-2 infection. The patients who were administered prophylactic anticoagulant were also more likely to receive supplementary oxygen (57/191, 30% vs 9/188, 5%; P<.001). There was no statistical difference in a new diagnosis of coagulopathy, bleeding, or maternal-fetal health outcomes between those who received treatment and the matched control group. Most hospitalized pregnant patients with COVID-19 did not receive prophylactic anticoagulants across health care systems as recommended by guidelines. Guideline-recommended treatment was administered more frequently to patients with greater COVID-19 illness severity. Given the low rate of administration and differences between treated and untreated cohorts, efficacy could not be assessed.

The effect of intravenous granisetron on prophylactic ephedrine for preventing hypotension after general anaesthesia induction in elderly patients: a randomized controlled trial

Serotonin 3 receptor antagonists, a commonly used drug for preventing postoperative nausea and vomiting, have recently been reported to decrease the incidence of hypotension and the need for vasoactive drugs after spinal anaesthesia in obstetric surgery. However, it remains unknown whether they could also prevent hypotension after induction of general anaesthesia. In the current study, we aimed to investigate the effect of intravenous granisetron on prophylactic ephedrine for preventing hypotension after general anaesthesia induction in elderly patients. Sixty elderly patients were randomly assigned to receive granisetron or saline control 30 min before induction of general anaesthesia. The first patient in each group received a prophylactic dose of ephedrine (0.15 mg kg−1) to prevent hypotension. The prophylactic dose for each patient was increased or decreased by 0.05 mg/kg based on the efficacy results of the previous patient. The up-down sequential allocation analysis and probit regression was used to calculate the effective dose for 50% of patients (ED50) with prophylactic ephedrine. In the up-down sequential allocation analysis, the ED50 of ephedrine was significantly lower in group granisetron (0.08 mg kg−1 [95% CI, 0.06–0.11 mg kg−1]) when compared with group control (0.14 mg kg−1 [95% CI, 0.13–0.16 mg kg−1]) (P < 0.001). The conclusion was further supported by probit regression analysis (0.09 mg kg−1 [95% CI, 0.05–0.12 mg kg−1] in group granisetron and 0.14 mg kg−1 [95% CI, 0.12–0.16 mg kg−1] in group control). Intravenous granisetron reduced the requirement of prophylactic ephedrine in preventing hypotension after general anaesthesia induction in elderly patients.

Clinical Impact of a Standardized Risk-Stratified Thromboprophylaxis Protocol for Multisystem Inflammatory Syndrome in Children

To evaluate the clinical impact of an institutional thromboprophylaxis protocol in patients with multisystem inflammatory syndrome in children (MIS-C), who are at increased risk for thromboembolism (TE). We conducted a single-center retrospective cohort study of children less than 18years between March 2020 and December 2021. Eligible patients were confirmed with MIS-C and were managed with a standardized multidisciplinary treatment approach that included a thromboprophylaxis protocol to guide and unify clinical practice. For high-risk patients, prophylactic dose enoxaparin (target anti-Factor Xa 0.1-0.3 U/mL) was added. In high-risk patients with TE risk factors persistent at hospital discharge, thromboprophylaxis was prescribed for an additional 30days. Of 135 patients with MIS-C, 124 (92%) required intensive care unit stay and 64 (47%) required a central venous catheter for a median duration of 5days (IQR, 4-7). Prophylactic dose enoxaparin was initiated in 116 out of 121 patients (96%) deemed high-risk per our protocol at a median of 1day after admission [IQR, 0-3] achieving target levels at a median of 1day [IQR, 1-2]. The median initial anti-Factor Xa level was 0.13 u/mL [IQR, 0.05-0.19]. One patient (0.7%) developed symptomatic noncatheter related superficial vein thrombosis requiring therapeutic anticoagulation. Thromboprophylaxis was extended for 30days after discharge in 108 out of 135 patients (80%). Bleeding events occurred in 5 patients during hospitalization (4.2%). All bleeding events were clinically relevant nonmajor bleeding. There were no deaths. Implementation of an institutional standardized thromboprophylaxis protocol in MIS-C was feasible and led to timely initiation of prophylactic anticoagulation and low rates of TEs and bleeding complications.

Diagnosis, prevention and treatment of vitamin D deficiency in adults: Ukrainian experts consensus statement

Background. Vitamin D deficiency (VDD) is widespread in the world; its proportion varies considerably in different populations and depends on many causes. Up to now, there were no National recommendations for the diagnosis, prevention, and treatment of VDD in adults in Ukraine. Their creation became the purpose of this work. Methodology. Consensus was created using the Delphi method, voting was conducted using the SurveyMonkey® platform. After approval of the composition of the Consensus Group, agreement on the order of formation and structure of the Consensus, creation and correction of the main statements, and two voting rounds, the main Consensus statements were formed and were successfully voted on. The 15 authors of the article are 15 experts who participated in the voting. The final 14 Consensus statements are presented in this article. Each statement is preceded by a justification based on high-quality evidence available in the current literature. Results. Despite the reduction of VDD in the Ukrainian population in recent years, experts have recommen­ded increasing the awareness of the medical community and the Ukrainian population about the problem and ways to overcome it, with a screening of the total serum level of 25-hydroxyvitamin D (25(OH)D) in subjects from the groups of risk to achieve the target concentration of 30–50 ng/ml (75–125 nmol/l). To ensure it, we recommend the individual selection of a prophylactic dose of vitamin D (800–2000 IU/d for young healthy persons and 3000–5000 IU/d for patients with diseases and conditions that affect the metabolism of vitamin D). For the treatment of VDD, we recommend short-term intake of higher doses (4000–10,000 IU/d) of vitamin D with control of the 25(OH)D level after 4–12 weeks of treatment and subsequent use of maintenance doses. Also, we re­commend the determination of serum 25(OH)D level before the initiation of antiosteoporotic therapy in patients with osteoporosis and its complications to prevent its ineffectiveness and increase the safety profile.

Acute thrombosis of the lower limb arteries on the background of the XBB.1.5 ("Kraken") subvariant of omicron SARS-COV-2 - medical or surgical treatment?

Comparative analysis of the results of open thrombectomy and conservative therapy in patients with acute thrombosis of the lower limb arteries against the background of the XBB.1.5 ("Kraken") subvariant of Omicron Severe acute respiratory syndrome-related coronavirus-2 (Sars-cov-2). The present prospective, open, multicenter comparative study for the period 04/01/2022 to 12/01/2023 included 167 patients with acute thrombosis of the lower limb arteries against the background of the XBB.1.5 ("Kraken") subvariant of the XBB.1.5 ("Kraken") subvariant of Omicron Sars-cov-2.Depending on the treatment strategy, two groups were formed: group 1 - open thrombectomy (n = 136) and drug treatment with an anticoagulant (unfractionated heparin in a therapeutic dosage) and an antiplatelet (acetylsalicylic acid 125mg once a day); group 2 - only drug therapy (n = 31). This group consisted of patients who refused surgical revascularization and were on a prophylactic dose of unfractionated heparin (5000 U 3 times a day subcutaneously). On the development of acute arterial thrombosis, 80 U/kg (maximum 5000 U) of unfractionated heparin was injected intravenously in a bolus, followed by transfer to intravenous infusion using an infusion pump with an initial rate of 18 U/kg per hour under control of activated partial thromboplastin time. Analgesic and antiplatelet therapy was also prescribed (acetylsalicylic acid 125mg once a day). No significant intergroup differences either in mortality rates (group 1: n = 58, 38.2%; group 2: n = 7, 22.6%; p = 0.09) or limb amputation (group 1: n = 63, 46.3%; group 2: n = 9, 29.0%; p = 0.07) were found. However, there was a trend towards a decrease in the incidence of these events in the drug treatment group. After open thrombectomy, rethrombosis developed in 50.7% (n = 69) cases; and thrombosis after rethrombectomy followed by amputation in 46.3% (n = 63). There were no hemorrhagic complications in both groups. Myocardial infarction and ischemic strokes were not recorded. Anticoagulant therapy demonstrates several advantages over aggressive surgical management. However, probably due to the small size of the studied sample, significant differences were not obtained. Further study of this issue is required with the identification of the optimal reperfusion method in this complex cohort of patients.

Simoctocog alfa (Nuwiq®) in previously untreated patients with severe haemophilia A-Final efficacy and safety results from the NuProtect study.

Simoctocog alfa (Nuwiq®) is a 4th generation recombinant FVIII with proven efficacy for the prevention and treatment of bleeding episodes (BEs) in previously treated patients with severe haemophilia A. The NuProtect study assessed the immunogenicity, efficacy and safety of simoctocog alfa in 108 previously untreated patients (PUPs). The incidence of high-titre inhibitors was 16.2% and no patients with non-null F8 mutations developed inhibitors. To report the efficacy and safety results from the NuProtect study. PUPs received simoctocog alfa for prophylaxis, treatment of BEs, or as surgical prophylaxis. The efficacy of prophylaxis (during inhibitor-free periods) was assessed using annualised bleeding rates (ABRs). The efficacy in treating BEs and in surgical prophylaxis was assessed using a 4-point scale. Adverse events were recorded throughout the study. Of 108 PUPs treated with simoctocog alfa, 103 received at least one prophylactic dose and 50 received continuous prophylaxis for at least 24 weeks. In patients on continuous prophylaxis, the median ABR was 0 (mean 0.5) for spontaneous BEs and 2.5 (mean 3.6) for all BEs. In 85 patients who had BEs, efficacy of BE treatment was excellent or good for 92.9% (747/804) of rated BEs; 92.3% of BEs were treated with 1 or 2 infusions. The efficacy of surgical prophylaxis was excellent or good for 94.7% (18/19) of rated procedures. There were no safety concerns and no thromboembolic events. Simoctocog alfa was efficacious and well tolerated as prophylaxis, surgical prophylaxis and for the treatment of BEs in PUPs with severe haemophilia A.

Impact of Reduced Enoxaparin Prophylactic Dosing on Bleeding and Thrombotic Risk for Low Body Weight Post-Operative Colorectal Surgery Patients.

Introduction: Colorectal surgery (CORS) patients are at the highest risk of any general surgery population for the development of post-operative venous thromboembolism (VTE) and are also at an increased risk for post-operative bleeding, especially with procedures related to early cancer stages. Low molecular weight heparin (LMWH) is recommended for VTE prophylaxis in this surgical population. Current guidelines and primary literature along with institutional protocols support dosage adjustments for obesity and impaired renal function, but literature providing optimal VTE prophylactic LMWH dosing is extremely limited for underweight, surgical patients. Objectives: The aim of this study was to evaluate both bleeding and VTE rates for hospitalized underweight colorectal surgery patients receiving post-operative VTE prophylaxis with standard enoxaparin 40 mg subcutaneously (SQ) every 24 hours versus reduced dose enoxaparin 30 mg SQ every 24 hours. Methods: This trial was a multicenter, retrospective chart review with data collected on post-operative CORS patients over a 10-year period. Patients were included if aged 18 years and older, weighed less than 50 kg, and received at least 1 dose of enoxaparin 40 mg or 30 mg post-operatively. The primary endpoint was a descriptive comparison of post-operative bleeding with use of standard enoxaparin 40 mg SQ every 24 hours compared to reduced dose enoxaparin 30 mg SQ every 24 hours for post-operative VTE prophylaxis. The secondary endpoint was the descriptive comparison of post-operative thrombotic event rates in the same population. Results: The total population investigated included 146 patients. One hundred twenty-nine (88.4%) received standard enoxaparin and 17 (11.6%) received reduced enoxaparin. Overall, 9 bleeding events (7.0%) and 2 major VTE events (1.6%) occurred, all within the standard enoxaparin group. Conclusion: Standard dose enoxaparin for post-operative VTE prophylaxis demonstrated increased bleeding and thrombotic events requiring medical and surgical intervention in comparison to reduced dose enoxaparin for low body weight CORS patients. The results of this study are hypothesis generating and continued research involving more robust systematic reviews are needed to evaluate both safety and efficacy of reduced VTE prophylaxis with LMWH in the underweight, surgical patient population.

Periinterventional Management of Edoxaban in Major Procedures: Results from the DRESDEN NOAC REGISTRY.

Background Edoxaban is a non-vitamin K dependent oral anticoagulant (NOAC) licensed for venous thromboembolism (VTE) treatment or stroke prevention in atrial fibrillation. Major surgical procedures are not uncommon in anticoagulated patients but data on perioperative edoxaban management are scarce. Patients and Methods Using data from the prospective DRESDEN NOAC REGISTRY, we extracted data on major surgical procedures in edoxaban patients. Periinterventional edoxaban management patterns and rates of outcome events were evaluated until day 30 after procedure. Results Between 2011 and 2021, 3,448 procedures were identified in edoxaban patients, including 287 (8.3%) major procedures. A scheduled interruption of edoxaban was observed in 284/287 major procedures (99%) with a total median edoxaban interruption time of 11.0 days (25-75th percentile: 5.0-18.0 days). Heparin bridging was documented in 183 procedures (46 prophylactic dosages, 111 intermediate and 26 therapeutic dosages). Overall, 7 (2.4%; 95% CI: 1.2-4.9%) major cardiovascular events (5 VTE, 2 arterial thromboembolic events) and 38 major bleedings (13.2%; 95% CI: 9.8-17.7%) were observed and 6 patients died (2.1%; 95% CI: 1.0-4.5%). Rates of major cardiovascular events with or without heparin bridging were comparable (4/137; 2.9%; 95% CI: 1.1-7.3% vs. 3/82; 3.7%; 95% CI: 1.3-10.2%). Major bleedings occurred numerically more frequent in patients receiving heparin bridging (23/137; 16.8%; 95% CI: 11.5-23.9%) versus procedures without heparin bridging (9/82; 11.0%; 95% CI: 5.9-19.6%). Conclusion Within the limitations of our study design, real-world periprocedural edoxaban management seems effective and safe. Use of heparin bridging seems to have limited effects on reducing vascular events but may increase bleeding risk.

Review of the national usage of antibiotics in arthroplasty surgery: a need for evidence-based prescribing.

Surgical site infections (SSI) remain one of the most serious complications of arthroplasty surgery. The role of antibiotic prophylaxis in preventing SSI post-arthroplasty is well established. However, there is considerable heterogeneity in prophylactic prescribing across the United Kingdom (UK), which is contradicted by the contemporaneous evidence. This descriptive study aimed to compare the current first-line antibiotic recommendations across hospitals in the UK and The Republic of Ireland for elective arthroplasty procedures. The MicroGuide mobile phone application was used to access hospital antibiotic guidelines. First-line antibiotic recommendation and dosing regimen for primary elective arthroplasties were recorded. A total of nine distinct antibiotic regimens were identified through our search. The most frequently used first-line antibiotic was cefuroxime. This was recommended by 30 of the 83 (36.1%) hospitals in the study. This was followed by a combination of flucloxacillin and gentamicin, which was used by 38 of 124 (31%) hospitals. There was also significant heterogeneity in dosing regimens. A single prophylactic dose was most commonly recommended (52%); 4% of hospitals recommended two prophylactic doses, 19% three doses and 23% four doses. Single-dose prophylaxis is recognised as at least noninferior to multiple-dose prophylaxis in primary arthroplasty. There is considerable variation in the local antibiotic recommendations for surgical site prophylaxis post-primary arthroplasty surgery, with respect to both recommended first-line antibiotic and dosing regimens. With increasing emphasis on the importance of antibiotic stewardship and the emergence of antibiotic resistance, this study highlights the need for an evidence-based approach to prophylactic dosing across the UK.