Aim. The β-lactam penicillin is often used in the treatment of soft tissue infections and osteomyelitis caused by penicillin susceptible Staphylococcus aureus. Oral antibiotic treatment has been shown to be non-inferior to intravenous (IV) therapy when used during the first 6 weeks in complex orthopedic infections (OVIVA trial). However, the use of oral β-lactams in osteomyelitis treatment remains a topic of debate due to low and variable bioavailability. The aim was to assess the time for which the unbound penicillin concentration exceeded targeted minimum inhibitory concentrations (fT>MIC) in cancellous bone and subcutaneous tissue after IV (penicillin G) and oral (penicillin V) treatment in a porcine microdialysis model. Method. 12 female pigs (75kg) were assigned to standard clinical regimens of either three doses of IV penicillin G (1.2g) or oral penicillin V (0.8g) every 6h over 18h. Microdialysis catheters were placed for sampling in tibial cancellous bone and adjacent subcutaneous tissue. Data was collected in the first dosing interval (0–6h; prophylactic situation) and the third dosing interval (12–18h; assumed steady state). Plasma samples were collected for reference. MIC targets of 0.125μg/mL (Staph. aureus breakpoint), 0.25μg/mL (Strep. Group A, B, C and G breakpoint) and 0.5μg/mL (4xMIC) were applied. Results. For all investigated MIC targets, IV penicillin G resulted in a longer mean fT>MIC in cancellous bone during the first dosing interval, and in both cancellous bone and subcutaneous tissue during the third dosing interval compared to oral penicillin V. Across compartments, mean fT>MIC for IV penicillin G (MIC: 0.125, 0.25 and 0.5μg/mL) were ≥97%, ≥84% and ≥75% during the first dosing interval, and 100%, ≥95% and ≥88%, during the third dosing interval. The mean fT>MIC for oral penicillin V were ≥40%, ≥24% and ≥7% during the first dosing interval, and ≥42%, ≥36% and ≥18% during the third dosing interval. Conclusions. The findings suggest that standard clinical dosing of IV penicillin G provides superior fT>MIC in cancellous bone and subcutaneous tissue compared to oral penicillin V, particularly in the third dosing interval. This emphasizes the importance of appropriate route of administration when applying penicillin treatment. Acknowledgements. Funding was received from The Kirsten and Freddy Johansen Foundation, The Novo Nordisk Foundation, The Beckett Foundation, The Hede Nielsen Family Foundation, King Christian the 10. th. Foundation, The A.P. Møller Foundation, The Dagmar Marshalls Foundation, and The Carl and Ellen Hertz Foundation

Aim. There is a lack of data supporting the use of doxycycline as a single agent after removing infected orthopaedic metalwork. We evaluated the efficacy and safety of doxycycline compared with other single antibiotic regimens used at our specialist orthopaedic hospital. Methods. A retrospective observational study including all adult patients diagnosed with an orthopaedic metalwork infection due to staphylococci. All patients were managed with the removal of metalwork, and multiple intraoperative samples were sent for culture, followed by the administration of at least four weeks of oral antibiotics. Antibiotic selection was on the recommendation of an infection consultant. Infection outcome was assessed as the proportion of patients meeting the OVIVA Trial definition of definite failure at follow-up. The probability of definite failure for doxycycline and the alternatives group was estimated using the Kaplan-Meier survival method. All adverse drug reactions (ADR) during treatment were analysed. Results. Seventy-nine orthopaedic metalwork infections were identified between July 2017 and July 2021. Forty-four were prosthetic joints, and 35 were fracture-related metalwork. In 54 cases, the infecting organism was Staphylococcus aureus, and 25 were due to coagulase-negative staphylococci. Forty-four were treated with doxycycline 100mg 12 hourly, and 35 were treated with alternatives (flucloxacillin 1g 6-hourly n=21 and clindamycin 450mg 6-hourly n=14). Overall, 70 patients (88.6%) were infection-free after a median follow-up of 23 months (IQR, 19 – 44). 38 (82.3%) were infection-free in the doxycycline group compared with 32 (91.4%) patients treated with alternatives. Of the failures in the alternatives group, all 3 received flucloxacillin. Survival analysis showed no significant difference in time to treatment failure between doxycycline and alternative antibiotics. Eighteen patients experienced an ADR: 2 nausea, one rash and one vaginal candidiasis due to doxycycline. Four diarrhoea, one reflux, two rashes and one headache due to clindamycin; 1 nausea and five diarrhoea due to flucloxacillin. Four patients required discontinuation therapy, two due to clindamycin and two due to flucloxacillin. Conclusions. In our cohort of patients, doxycycline monotherapy was an effective and well-tolerated oral option for treating staphylococcal infection following debridement and removal of orthopaedic metalwork

Direct oral anticoagulant (DOAC) use is becoming more widespread in the geriatric population. Depending on the type of DOAC, several days are required for its anticoagulant effects to resorb, which may lead to surgical delays. This can have an important impact on hip fracture patients who require surgery. The goal of the current study is to compare surgical delays, mortality and complications for hip fracture patients who were on a DOAC to those who were not. A retrospective cohort study was conducted at a university hospital in Sherbrooke. All hip fracture patients between 2012 and 2018 who were on a DOAC prior to their surgery were included. These patients were matched with similar patients who were not on an anticoagulant (non-DOAC) for age, sex, type of fracture and date of operation. Demographic and clinical data were collected for all patients. Surgical delay was defined as time of admission to time of surgery. Mortality and complications up to one year postoperative were also noted. Each cohort comprised of 74 patients. There were no statistically signification differences in Charleson Comorbidty Index and American Society of Anesthesiologists scores between cohorts. Surgical delay was significantly longer for DOAC patients (36.3±22.2 hours vs. 18.6±18.9 hours, p < 0 .001). Mortality (6.1%) and overall complication (33.8%) rates were similar between the two cohorts. However, there were more surgical reinterventions in DOAC patients than non-DOAC ones (16.2% vs. 0.0%, p < 0 .001). Among DOAC patients, mortality was greater for those operated after 48 hours (23.1% vs. 3.3%, p < 0 .05) and complications were more frequent for those operated after 24 hours (52.0% vs. 37.5%, p < 0 .05). Direct oral anticoagulant (DOAC) use in hip fracture patients is associated with longer surgical delays. Longer delays to surgery are associated with higher mortality and complication rates in hip fracture patients taking a DOAC. Hip fracture patients should have their surgery performed as soon as medically possible, regardless of anticoagulant use

Direct oral anticoagulant (DOAC) use is becoming more widespread in the geriatric population. Depending on the type of DOAC, several days are required for its anticoagulant effects to resorb, which may lead to surgical delays. This can have an important impact on hip fracture patients who require surgery. The goal of the current study is to compare surgical delays, mortality and complications for hip fracture patients who were on a DOAC to those who were not. A retrospective cohort study was conducted at a university hospital in Sherbrooke. All hip fracture patients between 2012 and 2018 who were on a DOAC prior to their surgery were included. These patients were matched with similar patients who were not on an anticoagulant (non-DOAC) for age, sex, type of fracture and date of operation. Demographic and clinical data were collected for all patients. Surgical delay was defined as time of admission to time of surgery. Mortality and complications up to one year postoperative were also noted. Each cohort comprised of 74 patients. There were no statistically signification differences in Charleson Comorbidty Index and American Society of Anesthesiologists scores between cohorts. Surgical delay was significantly longer for DOAC patients (36.3±22.2 hours vs. 18.6±18.9 hours, p < 0 .001). Mortality (6.1%) and overall complication (33.8%) rates were similar between the two cohorts. However, there were more surgical reinterventions in DOAC patients than non-DOAC ones (16.2% vs. 0.0%, p < 0 .001). Among DOAC patients, mortality was greater for those operated after 48 hours (23.1% vs. 3.3%, p < 0 .05) and complications were more frequent for those operated after 24 hours (52.0% vs. 37.5%, p < 0 .05). Direct oral anticoagulant (DOAC) use in hip fracture patients is associated with longer surgical delays. Longer delays to surgery are associated with higher mortality and complication rates in hip fracture patients taking a DOAC. Hip fracture patients should have their surgery performed as soon as medically possible, regardless of anticoagulant use

Aim. Flucloxacillin is conventionally administered intravenously for perioperative prophylaxis, while oral administration is typical for bacterial inoculation prophylaxis following smaller traumatic wounds. We aimed to assess the time, for which the free flucloxacillin concentration was maintained above the minimum inhibitory concentration (fT>MIC) for meticillin-susceptible Staphylococcus aureus in soft and bone tissue, after intravenous and oral administration, using microdialysis in a porcine model. Method. 16 pigs were randomly allocated to either intravenous (Group IV) or oral (Group PO) flucloxacillin 1 g every 6 h during 24 h. Microdialysis was used for sampling in cancellous and cortical bone, subcutaneous tissue, and the knee joint. In addition, plasma was sampled. The flucloxacillin fT>MIC was evaluated using a low MIC target (0.5 μg/mL) and a high MIC target (2.0 μg/mL). Results. Intravenous administration resulted in longer fT>MIC (0.5 μg/mL) compared to oral administration, except for cortical bone. In Group IV all pigs reached a concentration of 0.5 μg/mL in all compartments. The mean fT>MIC (0.5 μg/mL) was 149 min in subcutaneous tissue and 61–106 min in bone tissue. In Group PO 0/8 pigs reached a concentration of 0.5 μg/mL in all compartments. For the high MIC target (2.0 μg/mL), fT>MIC was close to 0 min in both groups across compartments. Conclusions. Although intravenous administration of flucloxacillin 1g provided higher fT>MIC for the low MIC target compared to oral administration, concentrations were surprisingly low, particularly for bone tissue. Achievement of sufficient bone and soft tissue flucloxacillin concentrations may require a dose increase or continuous administration. Acknowledgement. The study was supported by the following grants: Sofus Carl Emil Friis Foundation, Aase & Ejnar Danielsens Foundation, the Augustinus Foundation, Direkt⊘r Emil Hertz og hustru Inger Hertz Foundation, and the Novo Nordisk Foundation

Aim. The risk of haematogenic periprosthetic joint infection (PJI) after dental procedures is discussed controversially. To our knowledge, no study has evaluated infections according to the origin of infection based on the natural habitat of the bacteria. We investigated the frequency of positive monomicrobial cultures involving bacteria from oral cavity in patients with suspected PJI compared to bone and joint infections without joint prosthesis. Method. In this retrospective study we included all patients with suspected PJI or bone and joint infection without endoprosthesis, hospitalized at our orthopaedic clinic from January 2009 through March 2014. Excluded were patients with superficial surgical site infections or missing data. Demographic, clinical and microbiological data were collected using a standardized case report form. Groups were compared regarding infections caused by oral bacteria. χ2 test or Fisher's exact test was employed for categorical variables and t-test for continuous variables. Results. A total of 1673 patients were included, of whom 996 (60%) had a suspected PJI and 677 (40%) an osteoarticular infection without joint endoprosthesis (control group). In patients with suspected PJI the median age (standard deviation) was 67 (14) years; 407 (41%) were males. The anatomic location of the prosthesis was hip in 522 (52%) patients, knee in 437 (44%), megaprostheses in 14 (1%), shoulder in 8 (1%) and other endoprosthesis in 15 (2%) patients. In 437 (44%) of PJI cases pathogen(s) were detected, 271 (62%) were monomicrobial and 166 (38%) polymicrobial. Of 996 patients with suspected PJI, 2.4% (n = 24) had monomicrobial infections caused by bacteria belonging to the normal oral flora, predominantly oral streptococci (n = 21). In contrast, only 0.4% (n =3) of the control group without joint prosthesis had monomicrobial infections caused by oral bacteria. This difference was statistically significant (p = 0.002), whereas the patient age (p = 0.058) and the anatomic location of the joint prosthesis (p = 0.622) did not have any effect on the infections due to oral bacteria. Conclusions. The incidence of infections caused by oral bacteria was significantly higher in patients with endoprosthesis than in other osteoarticular infections (2.4% versus 0.4%). This finding indicates that joint prostheses are at risk of haematogenous PJI originating from oral cavity. Future prospective studies need to determine the exact risk of haematogenic PJI caused by oral bacteria, as well as the potential of preventing these infections by antibiotic prophylaxis

Aim. Prosthetic joint infection (PJI) is a devastating and costly complication of total joint arthroplasty (TJA). Use of extended oral antibiotic prophylaxis (EOAP) has become increasingly popular in the United States following a highly publicized study (Inabathula et al) from a single center demonstrating a significant protective effect (81% reduction) against PJI in ‘high-risk’ patients. However, these results have not been reproduced elsewhere and EOAP use directly conflicts with current antibiotic stewardship efforts. In order to study the role of EOAP in PJI prevention, consensus is needed for what defines ‘high-risk’ patients. The revision TJA (rTJA) population is an appropriate group to study due to having a higher incidence of PJI. The purpose of the current study was to rigorously determine which preoperative conditions described by Inabathula et al. (referred to as Inabathula criteria (IBC)) confer a higher rate of PJI in patients undergoing aseptic rTJA. Method. 2,256 patients that underwent aseptic rTJA at a single high-volume institution between 2016–2022 were retrospectively reviewed. Patient demographics and comorbidities were recorded to determine if they had 1 or more ‘IBC’, a long list of preoperative conditions including autoimmune diseases, active smoking, body mass index (BMI)>35, diabetes mellitus, and chronic kidney disease (CKD). Reoperation for PJI at 90-days and 1-year was recorded. Chi-squared or Fischer's exact tests were calculated to determine the association between preoperative presence/absence of IBC and PJI. Multivariable logistic regressions were conducted to determine if specific comorbidities within the IBC individually conferred an increased PJI risk. Results. 1223 patients (54.2%) had at least one IBC condition. IBC-positive patients were more likely to be female, have an increased ASA score, and higher BMI. IBC-positive patients had a significant increase in PJI risk at both 90-days (relative risk (RR)=2.32, p<0.0001) and 1-year (RR=2.14, p=0.002) versus IBC-negative patients. Within IBC-positive patients, every additional IBC condition conferred a 1.8× odds increase for 90-day PJI (p<0.0001), and 1.76× odds increase in 1-year PJI (p<0.0001). Multivariable logistic regression identified active smoking, BMI>35, CKD, and diabetes mellitus as being independently associated with PJI development (p<0.05). Conclusions. Over half of rTJA patients meet IBC and could be eligible to receive EOAP in the United States. However, the specific presence of active smoking, BMI>35, CKD, and diabetes mellitus appear to be responsible for the increased risk of PJI. Prospective studies investigating EOAP use for patients with these specific conditions are urgently needed to prevent unnecessary antibiotic use

Aim. Patients use antibiotics for various reasons before elective joint replacement surgery, but it is not known how common this is. The aim of this study was to investigate patients' use of oral antibiotics before elective joint replacement surgery and how this affects the risk for periprosthetic joint infection (PJI) in a one-year follow-up. Method. Patients with a primary hip or knee replacement performed in a tertiary care hospital between September 2002 and December 2013 were identified (23 171 joint replacements, 10 200 hips and 12 971 knees). Information on oral antibiotics purchased within 90 days before the operation was gathered from a national database. The occurrence of a PJI, identified by prospective infection surveillance, in a one-year follow-up was the primary outcome. The occurrence of any surgical site infection was analyzed as a secondary outcome. The association between antibiotic use and subsequent infection was examined using a multivariable logistic regression model that included information on the operated joint, age, gender, body mass index and patients' chronic diseases (according to medication data). Results. During the one-year follow-up, 158 (0.68%) PJIs were identified. 4 106 (18%) of the joint replacement operations were preceded by one or more courses of oral antibiotics. The most commonly prescribed group of antibiotics was 1st generation cephalosporins. The incidence of PJI for patients with preoperative oral antibiotic use was 0.29% (12/4 106), compared to 0.77% (146/19 065) in patients without preoperative antibiotics. A preoperative oral antibiotic course decreased the risk for subsequent PJI both in the univariate (OR 0.38, 95% CI 0.21 – 0.69) and multivariable model (OR 0.40, 95% CI 0.22–0.73). When superficial infection cases were included in the analysis, preoperative antibiotic use did not affect the overall risk for surgical site infection. Conclusions. The use of oral antibiotics before elective joint replacement surgery is common and is associated with a lower risk for subsequent PJI. Further studies are needed in order to confirm this finding and to evaluate factors affecting this result. Meanwhile, the indiscriminate use of antibiotics before elective joint replacement surgery cannot be recommended, even though the treatment of active infections remains important in the prevention of surgical site infections

BACKGROUND. Optimal perioperative fluid management has not been established in patients undergoing orthopaedic surgical procedures. Our purpose was to investigate the effects of perioperative fluid management on patients experiencing TKA. METHODS. One hundred thirty patients who met inclusion criteria undergoing primary unilateral TKA were prospectively randomized into traditional (TFG) vs. oral (OFG) perioperative fluid management groups. The TFG had a predetermined amount of intravenous fluids (IVF) administered in the perioperative period. The OFG began drinking a minimum of three, 20-ounces servings of clear fluids daily for three days prior to surgery. This cohort also drank 10-ounces of clear fluids 4 hours prior to surgery. Perioperative IVF were discontinued when the patient began oral intake or when the total amount of IVF reached 500mL. Outcome measures included: body-weight (BW) fluctuations, knee motion, leg girth, bioelectrical impendence, quadriceps activation, functional outcomes testing, KOOS JR, VR-12, laboratory values, vital signs, patient satisfaction, pain scores, and adverse events. RESULTS. The TFG had increased BW the evening of surgery (7.0±4.3 vs. 3.0±3.9, p=0.000), post-operative day (POD) #1 (9.1±4.3 vs. 4.7±3.9, p=0.000), and POD #2 (6.2±5.0 vs. 4.4±4.0, p=0.032). Bioelectrical impedance showed less limb edema in the OFG (4.2±29.7 vs. 17.8±30.3, p=0.000) on POD#1. Urine specific gravity differences were seen preoperatively between groups (OFG, more hydrated, p=0.002). Systolic blood pressure change from baseline was greater in the OFG upon arrival to the floor (19.4±13.5 vs. 10.6±12.8, p=0.000) and 8 (23.4±13.3 vs. 17.0±12.9, p=0.006) and 16 (25.8±13.8 vs. 25.8±13.8, p=0.046) hours after floor arrival. The TFG had more UOP on POD#1 (3369mL±1343mL vs. 2435mL±1151mL). CONCLUSIONS. Oral fluid intake with IVF restriction in the perioperative period after TKA may offer short-term benefits with swelling and BW fluctuations. The authors continue to limit perioperative IVFs and encourage patient initiated fluid intake

Aim. Prosthetic joint infection (PJI) concerns up to 20% of all prosthesis revision procedures. The IDSA recommends at least 2 weeks of intravenous antimicrobial therapy while most of the appropriate antibiotics in these settings have very high oral bioavailability (e.g., rifampicin, cotrimoxazole, fluoroquinolone, clindamycin, fusidic acid, linezolid and doxycycline). Method. AVAPOM is a monocentric retrospective non-inferiority study which included patients who received at least one of the highly bioavailable antibiotics listed above as a documented treatment (i.e., following the intravenous empirical post-operative antibiotic treatment) for PJIs in order to compare the remission rate of infection and the length of hospital stay (LOS). Patients were split between intravenous group (IV, from 1st January 2013 to 31st December 2014) and complete oral group (PO; since 1st January 2015) and were compared on both the PJI outcome regarding the last news available and the length of stay (LOS). Results. Out of a total of 216 patients, our intermediary analysis included 141 patients, with 73 receiving IV treatment (IV) and 68 oral treatment (PO). Remission was recorded in 21.9% IV patients and in 25.0% PO patients after a mean follow-up of 410.4 days ± 36.3 days (p=0.26). The global mortality reached 6.41% in IV group versus 1.25% in PO group (p=0.15). The medium LOS was 16.9 and 12.5 days for respectively IV and PO groups (p=0.0001). Conclusions. Our preliminary results suggest that complete oral and intravenous documented antibiotic treatment for patients with PJIs are comparable with regards to the patients' outcome but oral treatment is associated with a significant reduction of LOS

Background. The clinical benefit of chronic suppression with oral antibiotics as a salvage treatment for periprosthetic joint infection is unclear. The purpose of this study was to compare infection-free prosthetic survival rates between patients who received chronic oral antibiotics and those who did not following irrigation and debridement with polyethylene exchange or two-stage revision for periprosthetic joint infection. Methods. We reviewed the records on all irrigation and debridement procedures with polyethylene exchange and two-stage revisions performed at our institution from 1996 to 2010 for hip or knee periprosthetic joint infection. Of 625 patients treated with a total of 655 eligible revisions, ninety-two received chronic oral antibiotics for a minimum of six months and were eligible for inclusion in our study. These patients were compared with a matched cohort (ratio of 1:3) who did not receive chronic oral antibiotics. Results. The five-year infection-free prosthetic survival rate was 68.5% (95% confidence interval = 59.2% to 79.3%) for the antibiotic-suppression group and 41.1% (95% CI = 34.9% to 48.5%) for the non-suppression group (hazard ratio = 0.63, p = 0.008). Stratification by the type of surgery and the infecting organism showed a higher five-year survival rate for the patients in the suppression group who underwent irrigation and debridement with polyethylene exchange (64.7%) compared with those in the non-suppression group who underwent irrigation and debridement with polyethylene exchange (30.4%, p < 0.0001) and a higher five-year survival rate for the patients in the suppression group who had a Staphylococcus aureus infection (57.4%) compared with those in the non-suppression group who had a Staphylococcus aureus infection (40.1%, p = 0.047). Conclusions. Chronic suppression with oral antibiotics increased the infection-free prosthetic survival rate following surgical treatment for periprosthetic joint infection. Patients who underwent irrigation and debridement with polyethylene exchange and those who had a Staphylococcus aureus infection had the greatest benefit

Aim. Current standard of care in the management of bone and joint infection commonly includes a 4–6 week course of intravenous (IV) antibiotics but there is little evidence to suggest that oral antibiotic therapy results in worse outcomes. The primary objective was to determine whether oral antibiotics are non-inferior to IV antibiotics in this setting. Method. This was a parallel group, randomised (1:1), open label, non-inferiority trial across twenty-six NHS hospitals in the United Kingdom. Eligible patients were adults with a clinical diagnosis of bone, joint or orthopaedic metalware-associated infection who would ordinarily receive at least six weeks of antibiotics and who had received ≤7 days of IV therapy from the date of definitive surgery (or the start of planned curative treatment in patients managed non-operatively). Participants were randomised to receive either oral or IV antibiotics for the first 6 weeks of therapy. Follow-on oral therapy was permitted in either arm. The primary outcome was the proportion of participants experiencing definitive treatment failure within one year of randomisation. The non-inferiority margin was set at 7.5%. Results. Of 1054 participants randomised (527 to each arm) endpoint data were available for 1015 (96.30%). Definitive treatment failure was identified in 141/1015 (13.89%) participants, 74/506 (14.62%) of those randomised to IV therapy and 67/509 (13.16%) of those randomised to oral therapy. In the intention to treat analysis, the imputed risk difference (PO-IV) for definitive treatment failure was −1.38% (90% CI: −4.94, 2.19), thus meeting the non-inferiority criterion (i.e. the upper limit of 95%CI being <7.5%). A complete cases analysis, a per-protocol analysis and sensitivity analyses for missing data confirmed this result. With the exception of intravenous catheter complications, there was no significant difference between the two arms in the incidence of serious adverse events (SAEs). Health economic analysis suggests that the non-surgical treatment costs over one year for patients randomised to oral therapy were approximately £2,700 less than those of IV therapy. Conclusions. Oral antibiotic therapy is non-inferior to IV therapy when used during the first six weeks in the treatment for bone and joint infection, as assessed by definitive treatment failure within one year of randomisation. These findings challenge the current standard of care and provide an opportunity to realise significant benefits for patients, antimicrobial stewardship and the health economy. Funding. The OVIVA study was funded by the National Institute for Health Research Health Technology Assessment programme (Project number 11/36/29)

Background. Intraoperative blood loss is a known potential complication of total knee arthroplasty (TKA). Tranexamic acid (TXA) has been shown to reduce intraoperative blood loss and postoperative transfusion in patients undergoing TKA. While there are numerous studies demonstrating the efficacy of intravenous and topical TXA in patients undergoing TKA, there are comparatively few demonstrating the effectiveness and appropriate dosing recommendations of oral formulations. Methods. A retrospective cohort study of 2230 TKA procedures at a single institution identified 3 treatment cohorts: patients undergoing TKA without the use of TXA (no-OTA, n=968), patients undergoing TKA with administration of a single-dose of oral TXA (single-dose OTA, n=164), and patients undergoing TKR with administration of preoperative and postoperative oral TXA (two-dose OTA, n=1098). The primary outcome was transfusion rate. Secondary outcomes included maximum postoperative decline in hemoglobin, number of blood units transfused, length of hospital stay, total drain output, cell salvage volume, and operating room time. Results. Transfusion rates decreased from 24.1% in the no-OTA group to 13.6% in the single-dose OTA group (p<0.001) and 11.1% in the two-dose OTA group (p<0.001), with no significant difference in transfusion rates between single- and two-dose OTA groups (p=0.357). Operating room time was reduced from 154 minutes in the no-OTA group to 144 minutes in the one-dose OTA group and 144 minutes in the two-dose OTA group (p<0.01). Additionally, maximum postoperative decline in hemoglobin was reduced from 4.3 g/dL in the no-OTA group to 3.5 g/dL in the single-dose OTA group (p<0.01) and 3.4 g/dL in the two-dose OTA group (p<0.01), without a significant difference between the single- and two-dose regimens (p=0.233). Conclusions. OTA reduces transfusions and operating room time, with the potential advantages of greater ease of administration and improved cost effectiveness relative to other routes of administration. Further study such as a randomized clinical trial is needed to verify the effectiveness of OTA and further optimize dosing regimens in the TKA setting. Level of Evidence. Therapeutic Level III

Study Aim. To assess the impact of two oral thromboprophylaxis agents against Clexane with regard to range of movement (ROM) following TKR with or without haemostasis following tourniquet release. Methods & Results. Thromboprophylaxis choice following total knee replacement (TKR) has become of interest with the introduction of oral anticoagulants and support for these by NICE. Specific concerns with oral agents include a perceived elevated level of anti-coagulation and soft tissue complications. The population (n=264) was subclassified into cohorts regarding thromboprophylaxis cover: Clexane, Rivaroxaban and Dabigatran. Each subgroup was subdivided into whether surgery was performed with or without haemostasis following tourniquet release. This study demonstrates Clexane is associated with a better and earlier return of ROM post-operatively as compared to oral the thromboprophylaxis agents. This effect was more obvious when combined with haemostasis following early tourniquet release (p< 0.05). The oral thromboprophylaxis agents Rivaroxaban and Dabigatran had a relative negative effect on ROM as compared against Clexane. This was independent of whether the surgery was performed with or without haemostasis following tourniquet release. There was no different between the subgroups with repect to change of serum haemoglobin, symptomatic venous thromboembolism or rate of return to theatre. Conclusions. This study demonstrates Clexane to have a beneficial effect over the oral anticoagulants, Rivaroxaban and Dabigatran, on ROM and speed of recovery post TKR. This effect was significant (p< 0.05) when combined with genicular vessel haemostasis following early tourniquet release. We hypothesise independent of intra-operative haemostasis of genicular vessels after torniquet release, elevated small vessel ooze secondary to the oral thromboprophylaxis has a detrimental impact on ROM post TKR

There is currently no consensus on the use of suppressive antibiotic therapy (SAT) in prosthetic joint infections (PJI) (1). We describe herein the experience of a French Reference Centre for Complex Osteo-Articular Infections on use of oral cyclines (doxycline and minocycline) for SAT. A retrospective analysis was performed on consecutive patients with PJI who received oral cyclines (doxycycline or minocycline) for SAT between January 2006 and June 2014. All patients had surgical management, followed by systemic antibiotic treatment and SAT instauration thereafter. Remission was defined as an asymptomatic patient with a functioning prosthesis. Seventy-nine patients with a mean age of 63.8 ± 16.8 years were included. Sixteen patients (20%) had neoplasia, 9 (11%) diabetes mellitus, 10 (13%) rheumatoid arthritis, and 6 patients (8%) were receiving corticosteroids or chemotherapy. There were 37 knee (47%), 36 hip (46%), 4 elbow (5%), and 2 shoulder (3%) infections, with a mean delay from implantation of 7.37 ± 6.94 months (range 1–27). Surgical management consisted in debridement and implant retention for 60 patients (76%), or in implant exchange for 19 patients (24%). Main pathogens were coagulase-negative staphylococci (37%) and Staphylococcus aureus (41%); 23 patients had polymicrobial infection (29%). The most frequent initial antibiotic regimens debuted before SAT were rifampicin combinations (70%). Mean duration of curative antibiotic therapy was 103 ± 75 days. Indications of SAT were (i) patients unsuitable for or refusing further surgery (n=23), suboptimal (ii) surgery (n=26) or (iii) curative antibiotic therapy (n=11), (iv) complex orthopaedic surgery (n=11), and (v) immunosuppressive status (n=8). Seventy-three patients received doxycycline and 6 patients received minocycline as SAT (n=48). Mean SAT duration was 625± 536 days (range 30–2900), with a mean follow-up of 765 ± 572 days. Adverse events were reported in 13 patients (16%), leading to SAT discontinuation in 5 (6%). During follow-up, 59 patients were considered in remission (75%), and 20 failed including 13 relapses (16%) and 7 reinfections (9%). Among failure patients, 10 pathogens resistant to doxy/minocycline were identified, including 5 with acquisition of cycline resistance. In our study, SAT with cyclines is associated to a 75% remission rate, with an acceptable tolerability. Further studies are warranted to determine ideal regimens and optimal duration of SAT. We would like to thank Dron Hospital and Lille University Hospital medical teams. The authors declare that there are no conflicts of interest

Tranexamic acid is a potent antifibrinolytic which has shown efficacy in reducing blood loss in total knee arthroplasty when administered intravenously. We performed a randomised controlled trial of oral tranexamic acid in total knee arthroplasty in order to assess the blood sparing effect of this preparation. We investigated the effects of oral tranexamic acid on blood loss in 50 patients (25 treatment arm and 25 placebo) undergoing unilateral total knee replacement in a two year period starting January 2007. The treatment arm received 1500 mg of encapsulated oral tranexamic acid TDS pre-operatively, with the third dose occurring within two hours of surgery, and a fourth dose six hours post surgery. The control arm received an identically encapsulated non-active formulation at the same dosing intervals. Baseline pre-operative haemoglobin and heamatocrit measures were collected. Outcome measures were post-operative haemoglobin and haematocrit taken 12 to 24 hours post operatively and total blood loss in wound drains at 24 hours. Results showed a non-clinically significant trend towards decreased blood loss and transfusion rates in the treatment arm when compared to placebo. No significant adverse events occurred in relation to the use of oral Tranexamic acid in this study. The perioperative use of oral tranexamic acid in conjuntion with elective total knee arthroplasty appears safe; however, its efficacy as a blood sparing medication is less than that which has been recorded with intravenous dosing. The study supports further consideration of the availability of intravenous tranexamic acid for decreasing blood loss in orthopaedic arthroplasty

Introduction. Oral factor Xa inhibitors have recently been licensed for use as thromboprophylaxis in arthroplasty surgery. Phase IV trials have proven there efficacy in DVT/PE prevention with comparable rates in major adverse events, including major bleeding. We examined whether the introduction of rivaroxoban, an oral factor Xa inhibitor, increased total blood loss in patients undergoing primary arthroplasty surgery. Methods. Two groups were studied. The intervention group were prescribed rivaroxoban thrombophrophylaxis 6–10 hours post-surgery, and the control group were prescribed low molecular weight heparin (daltaparin 5,000u) 6–10 hours post-surgery. All other factors were kept constant. Pre- and post-operative haemoglobin levels (post-operative day 2) were recorded. Any requirement for transfusion was also documented. Actual drop in haemoglobin levels was compared between the two groups. Results. 91 patients were prescribed rivaroxoban (48 THR and 43 TKR), and 71 were included in the control group (34 THR and 37 TKR). Baseline pre-operative haemoglobin were comparable (p=0.43; 13.0 vs 13.2g/dL), however, post-operative blood loss was significantly increased in the rivaroxoban group (p=< 0.0001; 3.6 vs 2.8g/dL). Total knee replacements had a significant increase in post-operative blood loss in the rivaroxoban group (p=< 0.0001; 3.4 vs 2.6g/dL). Total hip replacement surgery had an increase in total blood loss in the rivaroxoban group, but this did not reach statistical significance (p=0.33; 3.8 vs 3.3g/dL). More patients undergoing TKR required transfusion in the rivaroxoban group (0.07% vs 0.03%). Conclusions. Oral factor Xa inhibitors significantly increase post-operative blood loss in total knee arthroplasty surgery when compared with LMWH. There is a subsequent increased requirement for blood transfusion and the potential complications related to bleeding and transfusion. These factors must be considered and balanced with the ease of oral anticoagulation when introducing these newer agents in arthroplasty patients

Most of current literatures advise on thromboprophylaxis with injectable LMWH for trauma patients. Injectable anticoagulants have got inherent problems of pain, bruising and difficulty in administering the drug, which leads to low compliance. Clexane is derived from a pig's intestinal mucosa, hence could be objectionable to certain proportion of patients because of their religious beliefs. Oral anticoagulants have been used as thromboprophylactic agents in hip and knee arthroplasty. However there is not enough literature supporting their use as thromboprophylactic agent in ambulatory trauma patients with ankle fracture being managed non-operatively as out-patient. This study looks into the efficacy of oral anticoagulant in preventing VTE in ambulatory trauma patients requiring temporary lower limb immobilisation for management of ankle fracture. The end point of this study was symptomatic deep vein thrombosis (either proximal or distal) and pulmonary embolism. Routine assessment with a VTE assessment risk proforma for all patients with temporary lower limb immobilisation following lower limb injury requiring plaster cast is done in the fracture clinic at this university hospital. These patients are categorised as low or high risk for a venous thromboembolic event depending on their risk factor and accordingly started on prophylactic dose of oral anticoagulant (Rivaroxaban - Factor Xa inhibitor). Before the therapy is started these patients have a routing blood check, which includes a full blood count and urea and electrolyte. Therapy is continued for the duration of immobilisation. Bleeding risk assessment is done using a proforma based on NICE guideline CG92. If there is any concern specialist haematologist advice is sought. A total of 200 consecutive patients who presented to the fracture clinic with ankle fracture, which was managed in plaster cast non-operatively, were included in this study. They were followed up for three months following injury. This was done by checking these patients’ radiology report including ultrasound and CT pulmonary scan (CTPA) test on hospital's electronic system. Fracture of the lateral malleolus which include Weber-A, Weber-B and Weber-C fractures were included in the study. Also included were bimalleolar fractures and isolated medial malleolus fractures. Complex pilon fractures, polytrauma and paediatric patients were excluded from the study. Only one case of plaster associated isolated distal deep vein (soleal vein) thrombosis was reported in this patient subgroup. There was no incidence of proximal deep vein thrombosis or pulmonary embolism. No significant bleeding event was reported. Injectable low molecular weight heparin (LMWH) rather than oral anticoagulant has been recommended by most of the studies and guidelines as main thromboprophylactic agent for lower limb trauma patients

Aims. NICE recommends oral anticoagulants after lower limb arthroplasty, as they are thought to lead to better outpatient compliance than injected anticoagulants. Having prescribed self-administered Dalteparin for many years, we began using oral Dabigatran in December 2010. The change afforded an opportunity to compare compliance and acceptability of the two treatments. Methods. Patients were recruited at discharge and telephoned at 28 days. Left over doses were counted to assess compliance. Side-effects, complications and patient views were also recorded. Results. 47 patients were discharged on dalteparin, 59 on dabigatran. Total compliance rates were 81% and 56% respectively (p<0.001). However, the mean pain score associated with dalteparin was 2.4 out of 10, and 31% of patients experienced significant bruising. No patient suffered pain or bruising with dabigatran (p<0.001), but two experienced dyspepsia and four suffered wound problems. Two thromboembolic events and one gastrointestinal bleed occurred in the dalteparin group. Conclusions. Our outpatient compliance is higher for injected anticoagulants than for oral anticoagulants. This runs contrary to some of the marketing for oral agents. However, Dabigatran offers better patient acceptability than Dalteparin. While not designed or powered to show statistically significant differences in complication rates, our study has prompted closer investigation of wound problems with both treatments

Introduction. The emergence of a new variant of subtrochanteric stress fractures of the femur affecting patients on oral bisphosphonate therapy has only recently been described. This fracture is often preceded by pain and distinctive radiographic changes, and associated with a characteristic fracture pattern. We undertook a review of this cohort of patients in our service. Method. A retrospective review was carried out looking for patients with subtrochanteric fractures who were taking oral bisphosphonates presenting with a low velocity injury over a two year period. Clinical data and radiographs were assessed. Results. 11 fractures were found in 10 patients matching the inclusion criteria outlined. All were female, and taking bisphosphonates for a mean of 4.3 years. 5 of the 10 patients described prodromal symptoms, for an average of 7.8 months before fracture. Although all fractures were deemed low velocity, 5 of 11 were atraumatic. 3 patients have had bilateral subtrochanteric fractures. Presence of the distinctive radiological ‘bleb’ was common. Surveillance on 2 patients shows lateral cortical blebs on the contralateral femur which merit close follow up. Conclusion. Patients taking oral bisphosphonate therapy may be at risk of a new variant of stress fracture of the proximal femur. Awareness of the symptoms is key to ensure appropriate investigations are undertaken. Following such a fracture surveillance of the contralateral femur is recommended, and the option of discontinuing bisphosphonates should be discussed