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Bone & Joint Open
Vol. 5, Issue 6 | Pages 524 - 531
24 Jun 2024
Woldeyesus TA Gjertsen J Dalen I Meling T Behzadi M Harboe K Djuv A

Aims. To investigate if preoperative CT improves detection of unstable trochanteric hip fractures. Methods. A single-centre prospective study was conducted. Patients aged 65 years or older with trochanteric hip fractures admitted to Stavanger University Hospital (Stavanger, Norway) were consecutively included from September 2020 to January 2022. Radiographs and CT images of the fractures were obtained, and surgeons made individual assessments of the fractures based on these. The assessment was conducted according to a systematic protocol including three classification systems (AO/Orthopaedic Trauma Association (OTA), Evans Jensen (EVJ), and Nakano) and questions addressing specific fracture patterns. An expert group provided a gold-standard assessment based on the CT images. Sensitivities and specificities of surgeons’ assessments were estimated and compared in regression models with correlations for the same patients. Intra- and inter-rater reliability were presented as Cohen’s kappa and Gwet’s agreement coefficient (AC1). Results. We included 120 fractures in 119 patients. Compared to radiographs, CT increased the sensitivity of detecting unstable trochanteric fractures from 63% to 70% (p = 0.028) and from 70% to 76% (p = 0.004) using AO/OTA and EVJ, respectively. Compared to radiographs alone, CT increased the sensitivity of detecting a large posterolateral trochanter major fragment or a comminuted trochanter major fragment from 63% to 76% (p = 0.002) and from 38% to 55% (p < 0.001), respectively. CT improved intra-rater reliability for stability assessment using EVJ (AC1 0.68 to 0.78; p = 0.049) and for detecting a large posterolateral trochanter major fragment (AC1 0.42 to 0.57; p = 0.031). Conclusion. A preoperative CT of trochanteric fractures increased detection of unstable fractures using the AO/OTA and EVJ classification systems. Compared to radiographs, CT improved intra-rater reliability when assessing fracture stability and detecting large posterolateral trochanter major fragments. Cite this article: Bone Jt Open 2024;5(6):524–531


Bone & Joint Open
Vol. 4, Issue 9 | Pages 659 - 667
1 Sep 2023
Nasser AAHH Osman K Chauhan GS Prakash R Handford C Nandra RS Mahmood A

Aims. Periprosthetic fractures (PPFs) following hip arthroplasty are complex injuries. This study evaluates patient demographic characteristics, management, outcomes, and risk factors associated with PPF subtypes over a decade. Methods. Using a multicentre collaborative study design, independent of registry data, we identified adults from 29 centres with PPFs around the hip between January 2010 and December 2019. Radiographs were assessed for the Unified Classification System (UCS) grade. Patient and injury characteristics, management, and outcomes were compared between UCS grades. A multinomial logistic regression was performed to estimate relative risk ratios (RRR) of variables on UCS grade


Bone & Joint Open
Vol. 3, Issue 12 | Pages 953 - 959
23 Dec 2022
Raval P See A Singh HP

Aims. Distal third clavicle (DTC) fractures are increasing in incidence. Due to their instability and nonunion risk, they prove difficult to treat. Several different operative options for DTC fixation are reported but current evidence suggests variability in operative fixation. Given the lack of consensus, our objective was to determine the current epidemiological trends in DTC as well as their management within the UK. Methods. A multicentre retrospective cohort collaborative study was conducted. All patients over the age of 18 with an isolated DTC fracture in 2019 were included. Demographic variables were recorded: age; sex; side of injury; mechanism of injury; modified Neer classification grading; operative technique; fracture union; complications; and subsequent procedures. Baseline characteristics were described for demographic variables. Categorical variables were expressed as frequencies and percentages. Results. A total of 859 patients from 18 different NHS trusts (15 trauma units and three major trauma centres) were included. The mean age was 57 years (18 to 99). Overall, 56% of patients (n = 481) were male. The most common mechanisms of injury were simple fall (57%; n = 487) and high-energy fall (29%; n = 248); 87% (n = 748) were treated conservatively and 54% (n = 463) were Neer type I fractures. Overall, 32% of fractures (n = 275) were type II (22% type IIa (n = 192); 10% type IIb (n = 83)). With regards to operative management, 89% of patients (n = 748) who underwent an operation were under the age of 60. The main fixation methods were: hook plate (n = 47); locking plate (n = 34); tightrope (n = 5); and locking plate and tight rope (n = 7). Conclusion. Our study is the largest epidemiological review of DTC fractures in the UK. It is also the first to review the practice of DTC fixation. Most fractures are being treated nonoperatively. However, younger patients, suffering a higher-energy mechanism of injury, are more likely to undergo surgery. Hook plates are the predominantly used fixation method followed by locking plate. The literature is sparse on the best method of fixation for optimal outcomes for these patients. To answer this, a pragmatic RCT to determine optimal fixation method is required. Cite this article: Bone Jt Open 2022;3(12):953–959


Bone & Joint Open
Vol. 3, Issue 10 | Pages 746 - 752
1 Oct 2022
Hadfield JN Omogbehin TS Brookes C Walker R Trompeter A Bretherton CP Gray A Eardley WGP

Aims. Understanding of open fracture management is skewed due to reliance on small-number lower limb, specialist unit reports and large, unfocused registry data collections. To address this, we carried out the Open Fracture Patient Evaluation Nationwide (OPEN) study, and report the demographic details and the initial steps of care for patients admitted with open fractures in the UK. Methods. Any patient admitted to hospital with an open fracture between 1 June 2021 and 30 September 2021 was included, excluding phalanges and isolated hand injuries. Institutional information governance approval was obtained at the lead site and all data entered using Research Electronic Data Capture. Demographic details, injury, fracture classification, and patient dispersal were detailed. Results. In total, 1,175 patients (median age 47 years (interquartile range (IQR) 29 to 65), 61.0% male (n = 717)) were admitted across 51 sites. A total of 546 patients (47.1%) were employed, 5.4% (n = 63) were diabetic, and 28.8% (n = 335) were smokers. In total, 29.0% of patients (n = 341) had more than one injury and 4.8% (n = 56) had two or more open fractures, while 51.3% of fractures (n = 637) occurred in the lower leg. Fractures sustained in vehicle incidents and collisions are common (38.8%; n = 455) and typically seen in younger patients. A simple fall (35.0%; n = 410) is common in older people. Overall, 69.8% (n = 786) of patients were admitted directly to an orthoplastic centre, 23.0% (n = 259) were transferred to an orthoplastic centre after initial management elsewhere, and 7.2% were managed outwith specialist units (n = 81). Conclusion. This study describes the epidemiology of open fractures in the UK. For a decade, orthopaedic surgeons have been practicing in a guideline-driven, network system without understanding the patient features, injury characteristics, or dispersal processes of the wider population. This work will inform care pathways as the UK looks to the future of trauma networks and guidelines, and how to optimize care for patients with open fractures. Cite this article: Bone Jt Open 2022;3(10):746–752


Bone & Joint Open
Vol. 5, Issue 6 | Pages 452 - 456
1 Jun 2024
Kennedy JW Rooney EJ Ryan PJ Siva S Kennedy MJ Wheelwright B Young D Meek RMD

Aims. Femoral periprosthetic fractures are rising in incidence. Their management is complex and carries a high associated mortality. Unlike native hip fractures, there are no guidelines advising on time to theatre in this group. We aim to determine whether delaying surgical intervention influences morbidity or mortality in femoral periprosthetic fractures. Methods. We identified all periprosthetic fractures around a hip or knee arthroplasty from our prospectively collated database between 2012 and 2021. Patients were categorized into early or delayed intervention based on time from admission to surgery (early = ≤ 36 hours, delayed > 36 hours). Patient demographics, existing implants, Unified Classification System fracture subtype, acute medical issues on admission, preoperative haemoglobin, blood transfusion requirement, and length of hospital stay were identified for all patients. Complication and mortality rates were compared between groups. Results. A total of 365 patients were identified: 140 in the early and 225 in the delayed intervention group. Mortality rate was 4.1% at 30 days and 19.2% at one year. There was some indication that those who had surgery within 36 hours had a higher mortality rate, but this did not reach statistical significance at 30 days (p = 0.078) or one year (p = 0.051). Univariate analysis demonstrated that age, preoperative haemoglobin, acute medical issue on admission, and the presence of postoperative complications influenced 30-day and one-year mortality. Using a multivariate model, age and preoperative haemoglobin were independently predictive factors for one-year mortality (odds ratio (OR) 1.071; p < 0.001 and OR 0.980; p = 0.020). There was no association between timing of surgery and postoperative complications. Postoperative complications were more likely with increasing age (OR 1.032; p = 0.001) and revision arthroplasty compared to internal fixation (OR 0.481; p = 0.001). Conclusion. While early intervention may be preferable to reduce prolonged immobilization, there is no evidence that delaying surgery beyond 36 hours increases mortality or complications in patients with a femoral periprosthetic fracture. Cite this article: Bone Jt Open 2024;5(6):452–456


Bone & Joint Open
Vol. 3, Issue 8 | Pages 623 - 627
8 Aug 2022
Francis JL Battle JM Hardman J Anakwe RE

Aims. Fractures of the distal radius are common, and form a considerable proportion of the trauma workload. We conducted a study to examine the patterns of injury and treatment for adult patients presenting with distal radius fractures to a major trauma centre serving an urban population. Methods. We undertook a retrospective cohort study to identify all patients treated at our major trauma centre for a distal radius fracture between 1 June 2018 and 1 May 2021. We reviewed the medical records and imaging for each patient to examine patterns of injury and treatment. We undertook a binomial logistic regression to produce a predictive model for operative fixation or inpatient admission. Results. Overall, 571 fractures of the distal radius were treated at our centre during the study period. A total of 146 (26%) patients required an inpatient admission, and 385 surgical procedures for fractures of the distal radius were recorded between June 2018 and May 2021. The most common mechanism of injury was a fall from a height of one metre or less. Of the total fractures, 59% (n = 337) were treated nonoperatively, and of those patients treated with surgery, locked anterior-plate fixation was the preferred technique (79%; n = 180). Conclusion. The epidemiology of distal radius fractures treated at our major trauma centre replicated the classical bimodal distribution described in the literature. Patient age, open fractures, and fracture classification were factors correlated with the decision to treat the fracture operatively. While most fractures were treated nonoperatively, locked anterior-plate fixation remains the predominant method of fixation for fractures of the distal radius; this is despite questions and continued debate about the best method of surgical fixation for these injuries. Cite this article: Bone Jt Open 2022;3(8):623–627


Bone & Joint Open
Vol. 2, Issue 4 | Pages 227 - 235
1 Apr 2021
Makaram NS Leow JM Clement ND Oliver WM Ng ZH Simpson C Keating JF

Aims. The primary aim of this study was to identify independent predictors associated with nonunion and delayed union of tibial diaphyseal fractures treated with intramedullary nailing. The secondary aim was to assess the Radiological Union Scale for Tibial fractures (RUST) score as an early predictor of tibial fracture nonunion. Methods. A consecutive series of 647 patients who underwent intramedullary nailing for tibial diaphyseal fractures were identified from a trauma database. Demographic data, comorbidities, smoking status, alcohol consumption, use of non-steroidal anti-inflammatory drugs (NSAIDs), and steroid use were documented. Details regarding mechanism of injury, fracture classification, complications, and further surgery were recorded. Nonunion was defined as the requirement for revision surgery to achieve union. Delayed union was defined as a RUST score < 10 at six months postoperatively. Results. There were 41 nonunions (6.3%), of which 13 were infected (31.7%), and 77 delayed unions (11.9%). There were 127 open fractures (19.6%). Adjusting for confounding variables, NSAID use (odds ratio (OR) 3.50; p = 0.042), superficial infection (OR 3.00; p = 0.026), open fractures (OR 5.44; p < 0.001), and high-energy mechanism (OR 2.51; p = 0.040) were independently associated with nonunion. Smoking (OR 1.76; p = 0.034), open fracture (OR 2.82; p = 0.001), and high-energy mechanism (OR 1.81; p = 0.030) were independent predictors associated with delayed union. The RUST score at six-week follow-up was highly predictive of nonunion (sensitivity and specificity of 75%). Conclusion. NSAID use, high-energy mechanisms, open fractures, and superficial infection were independently associated with nonunion in patients with tibial diaphyseal fractures treated with intramedullary nailing. The six-week RUST score may be useful in identifying patients at risk of nonunion. Cite this article: Bone Jt Open 2021;2(4):227–235


Bone & Joint Open
Vol. 4, Issue 8 | Pages 584 - 593
15 Aug 2023
Sainio H Rämö L Reito A Silvasti-Lundell M Lindahl J

Aims

Several previously identified patient-, injury-, and treatment-related factors are associated with the development of nonunion in distal femur fractures. However, the predictive value of these factors is not well defined. We aimed to assess the predictive ability of previously identified risk factors in the development of nonunion leading to secondary surgery in distal femur fractures.

Methods

We conducted a retrospective cohort study of adult patients with traumatic distal femur fracture treated with lateral locking plate between 2009 and 2018. The patients who underwent secondary surgery due to fracture healing problem or plate failure were considered having nonunion. Background knowledge of risk factors of distal femur fracture nonunion based on previous literature was used to form an initial set of variables. A logistic regression model was used with previously identified patient- and injury-related variables (age, sex, BMI, diabetes, smoking, periprosthetic fracture, open fracture, trauma energy, fracture zone length, fracture comminution, medial side comminution) in the first analysis and with treatment-related variables (different surgeon-controlled factors, e.g. plate length, screw placement, and proximal fixation) in the second analysis to predict the nonunion leading to secondary surgery in distal femur fractures.


Bone & Joint Open
Vol. 4, Issue 7 | Pages 516 - 522
10 Jul 2023
Mereddy P Nallamilli SR Gowda VP Kasha S Godey SK Nallamilli RR GPRK R Meda VGR

Aims

Musculoskeletal infection is a devastating complication in both trauma and elective orthopaedic surgeries that can result in significant morbidity. Aim of this study was to assess the effectiveness and complications of local antibiotic impregnated dissolvable synthetic calcium sulphate beads (Stimulan Rapid Cure) in the hands of different surgeons from multiple centres in surgically managed bone and joint infections.

Methods

Between January 2019 and December 2022, 106 patients with bone and joint infections were treated by five surgeons in five hospitals. Surgical debridement and calcium sulphate bead insertion was performed for local elution of antibiotics in high concentration. In all, 100 patients were available for follow-up at regular intervals. Choice of antibiotic was tailor made for each patient in consultation with microbiologist based on the organism grown on culture and the sensitivity. In majority of our cases, we used a combination of vancomycin and culture sensitive heat stable antibiotic after a thorough debridement of the site. Primary wound closure was achieved in 99 patients and a split skin graft closure was done in one patient. Mean follow-up was 20 months (12 to 30).


Bone & Joint Open
Vol. 5, Issue 1 | Pages 46 - 52
19 Jan 2024
Assink N ten Duis K de Vries JPM Witjes MJH Kraeima J Doornberg JN IJpma FFA

Aims

Proper preoperative planning benefits fracture reduction, fixation, and stability in tibial plateau fracture surgery. We developed and clinically implemented a novel workflow for 3D surgical planning including patient-specific drilling guides in tibial plateau fracture surgery.

Methods

A prospective feasibility study was performed in which consecutive tibial plateau fracture patients were treated with 3D surgical planning, including patient-specific drilling guides applied to standard off-the-shelf plates. A postoperative CT scan was obtained to assess whether the screw directions, screw lengths, and plate position were performed according the preoperative planning. Quality of the fracture reduction was assessed by measuring residual intra-articular incongruence (maximum gap and step-off) and compared to a historical matched control group.


Bone & Joint Open
Vol. 5, Issue 8 | Pages 621 - 627
1 Aug 2024
Walter N Loew T Hinterberger T Alt V Rupp M

Aims

Fracture-related infections (FRIs) are a devastating complication of fracture management. However, the impact of FRIs on mental health remains understudied. The aim of this study was a longitudinal evaluation of patients’ psychological state, and expectations for recovery comparing patients with recurrent FRI to those with primary FRI.

Methods

A prospective longitudinal study was conducted at a level 1 trauma centre from January 2020 to December 2022. In total, 56 patients treated for FRI were enrolled. The ICD-10 symptom rating (ISR) and an expectation questionnaire were assessed at five timepoints: preoperatively, one month postoperatively, and at three, six, and 12 months.


Bone & Joint Open
Vol. 4, Issue 5 | Pages 378 - 384
23 May 2023
Jones CS Eardley WGP Johansen A Inman DS Evans JT

Aims

The aim of this study was to describe services available to patients with periprosthetic femoral fracture (PPFF) in England and Wales, with focus on variation between centres and areas for care improvement.

Methods

This work used data freely available from the National Hip Fracture Database (NHFD) facilities survey in 2021, which asked 21 questions about the care of patients with PPFFs, and nine relating to clinical decision-making around a hypothetical case.


Bone & Joint Open
Vol. 5, Issue 6 | Pages 457 - 463
2 Jun 2024
Coviello M Abate A Maccagnano G Ippolito F Nappi V Abbaticchio AM Caiaffa E Caiaffa V

Aims

Proximal femur fractures treatment can involve anterograde nailing with a single or double cephalic screw. An undesirable failure for this fixation is screw cut-out. In a single-screw nail, a tip-apex distance (TAD) greater than 25 mm has been associated with an increased risk of cut-out. The aim of the study was to examine the role of TAD as a risk factor in a cephalic double-screw nail.

Methods

A retrospective study was conducted on 112 patients treated for intertrochanteric femur fracture with a double proximal screw nail (Endovis BA2; EBA2) from January to September 2021. The analyzed variables were age, sex, BMI, comorbidities, fracture type, side, time of surgery, quality of reduction, pre-existing therapy with bisphosphonate for osteoporosis, screw placement in two different views, and TAD. The last follow-up was at 12 months. Logistic regression was used to study the potential factors of screw cut-out, and receiver operating characteristic curve to identify the threshold value.


Bone & Joint Open
Vol. 5, Issue 2 | Pages 147 - 153
19 Feb 2024
Hazra S Saha N Mallick SK Saraf A Kumar S Ghosh S Chandra M

Aims

Posterior column plating through the single anterior approach reduces the morbidity in acetabular fractures that require stabilization of both the columns. The aim of this study is to assess the effectiveness of posterior column plating through the anterior intrapelvic approach (AIP) in the management of acetabular fractures.

Methods

We retrospectively reviewed the data from R G Kar Medical College, Kolkata, India, from June 2018 to April 2023. Overall, there were 34 acetabulum fractures involving both columns managed by medial buttress plating of posterior column. The posterior column of the acetabular fracture was fixed through the AIP approach with buttress plate on medial surface of posterior column. Mean follow-up was 25 months (13 to 58). Accuracy of reduction and effectiveness of this technique were measured by assessing the Merle d’Aubigné score and Matta’s radiological grading at one year and at latest follow-up.


Bone & Joint Open
Vol. 5, Issue 11 | Pages 962 - 970
4 Nov 2024
Suter C Mattila H Ibounig T Sumrein BO Launonen A Järvinen TLN Lähdeoja T Rämö L

Aims

Though most humeral shaft fractures heal nonoperatively, up to one-third may lead to nonunion with inferior outcomes. The Radiographic Union Score for HUmeral Fractures (RUSHU) was created to identify high-risk patients for nonunion. Our study evaluated the RUSHU’s prognostic performance at six and 12 weeks in discriminating nonunion within a significantly larger cohort than before.

Methods

Our study included 226 nonoperatively treated humeral shaft fractures. We evaluated the interobserver reliability and intraobserver reproducibility of RUSHU scoring using intraclass correlation coefficients (ICCs). Additionally, we determined the optimal cut-off thresholds for predicting nonunion using the receiver operating characteristic (ROC) method.


Bone & Joint Open
Vol. 4, Issue 4 | Pages 273 - 282
20 Apr 2023
Gupta S Yapp LZ Sadczuk D MacDonald DJ Clement ND White TO Keating JF Scott CEH

Aims

To investigate health-related quality of life (HRQoL) of older adults (aged ≥ 60 years) after tibial plateau fracture (TPF) compared to preinjury and population matched values, and what aspects of treatment were most important to patients.

Methods

We undertook a retrospective, case-control study of 67 patients at mean 3.5 years (SD 1.3; 1.3 to 6.1) after TPF (47 patients underwent fixation, and 20 nonoperative management). Patients completed EuroQol five-dimension three-level (EQ-5D-3L) questionnaire, Lower Limb Function Scale (LEFS), and Oxford Knee Scores (OKS) for current and recalled prefracture status. Propensity score matching for age, sex, and deprivation in a 1:5 ratio was performed using patient level data from the Health Survey for England to obtain a control group for HRQoL comparison. The primary outcome was the difference in actual (TPF cohort) and expected (matched control) EQ-5D-3L score after TPF.


Bone & Joint Open
Vol. 5, Issue 4 | Pages 294 - 303
11 Apr 2024
Smolle MA Fischerauer SF Vukic I Leitner L Puchwein P Widhalm H Leithner A Sadoghi P

Aims

Patients with proximal femoral fractures (PFFs) are often multimorbid, thus unplanned readmissions following surgery are common. We therefore aimed to analyze 30-day and one-year readmission rates, reasons for, and factors associated with, readmission risk in a cohort of patients with surgically treated PFFs across Austria.

Methods

Data from 11,270 patients with PFFs, treated surgically (osteosyntheses, n = 6,435; endoprostheses, n = 4,835) at Austrian hospitals within a one-year period (January to December 2021) was retrieved from the Leistungsorientierte Krankenanstaltenfinanzierung (Achievement-Oriented Hospital Financing). The 30-day and one-year readmission rates were reported. Readmission risk for any complication, as well as general medicine-, internal medicine-, and surgery/injury-associated complications, and factors associated with readmissions, were investigated.


Bone & Joint Open
Vol. 3, Issue 10 | Pages 741 - 745
1 Oct 2022
Baldock TE Dixon JR Koubaesh C Johansen A Eardley WGP

Aims

Patients with A1 and A2 trochanteric hip fractures represent a substantial proportion of trauma caseload, and national guidelines recommend that sliding hip screws (SHS) should be used for these injuries. Despite this, intramedullary nails (IMNs) are routinely implanted in many hospitals, at extra cost and with unproven patient outcome benefit. We have used data from the National Hip Fracture Database (NHFD) to examine the use of SHS and IMN for A1 and A2 hip fractures at a national level, and to define the cost implications of management decisions that run counter to national guidelines.

Methods

We used the NHFD to identify all operations for fixation of trochanteric fractures in England and Wales between 1 January 2021 and 31 December 2021. A uniform price band from each of three hip fracture implant manufacturers was used to set cost implications alongside variation in implant use.


Bone & Joint Open
Vol. 3, Issue 7 | Pages 566 - 572
18 Jul 2022
Oliver WM Molyneux SG White TO Clement ND Duckworth AD

Aims

The primary aim was to estimate the cost-effectiveness of routine operative fixation for all patients with humeral shaft fractures. The secondary aim was to estimate the health economic implications of using a Radiographic Union Score for HUmeral fractures (RUSHU) of < 8 to facilitate selective fixation for patients at risk of nonunion.

Methods

From 2008 to 2017, 215 patients (mean age 57 yrs (17 to 18), 61% female (n = 130/215)) with a nonoperatively managed humeral diaphyseal fracture were retrospectively identified. Union was achieved in 77% (n = 165/215) after initial nonoperative management, with 23% (n = 50/215) uniting after surgery for nonunion. The EuroQol five-dimension three-level health index (EQ-5D-3L) was obtained via postal survey. Multiple regression was used to determine the independent influence of patient, injury, and management factors upon the EQ-5D-3L. An incremental cost-effectiveness ratio (ICER) of < £20,000 per quality-adjusted life-year (QALY) gained was considered cost-effective.


Bone & Joint Open
Vol. 3, Issue 4 | Pages 284 - 290
1 Apr 2022
O'Hara NN Carullo J Joshi M Banoub M Claeys KC Sprague S Slobogean GP O'Toole RV

Aims

There is increasing evidence to support the use of topical antibiotics to prevent surgical site infections. Although previous research suggests a minimal nephrotoxic risk with a single dose of vancomycin powder, fracture patients often require multiple procedures and receive additional doses of topical antibiotics. We aimed to determine if cumulative doses of intrawound vancomycin or tobramycin powder for infection prophylaxis increased the risk of drug-induced acute kidney injury (AKI) among fracture patients.

Methods

This cohort study was a secondary analysis of single-centre Program of Randomized Trials to Evaluate Pre-operative Antiseptic Skin Solutions in Orthopaedic Trauma (PREP-IT) trial data. We included patients with a surgically treated appendicular fracture. The primary outcome was drug-induced AKI. The odds of AKI per gram of vancomycin or tobramycin powder were calculated using Bayesian regression models, which adjusted for measured confounders and accounted for the interactive effects of vancomycin and tobramycin.