The current investigation was a prospective, observational, nonrandomized case-series of patients with bony infections (registered in ClinicalTrials.gov: NCT01677000). Study conduct, data management, patient consent (including the use of collected biomaterials for future studies), and ethics approval were as described previously (8). Baseline assessments were done at the time the patients consented to participate in the study. The follow-up (FU) period was 12 months with planned visits at 1, 6, and 12 months.
Inclusion and exclusion criteria
Adult patients (aged 18 years or older) with confirmed S. aureus (either methicillin resistant or sensitive) infection involving a long bone (femur, tibia, fibula, humerus, radius, ulna, and clavicle) due to fracture fixation, osteomyelitis or arthroplasty were eligible (8), disregarding the stage of disease progression and treatment history. S. aureus infections were confirmed by positive deep wound cultures from baseline examinations or by a prior definitive diagnosis of ongoing S. aureus infection (deep wound culture) from the surgical site by the treating surgeon. Prisoners, patients unable to give consent or could not attend the FU visits were excluded. Patients with history of substance abuse that would preclude reliable assessments were also excluded.
The aim of this article is to describe the results of the AO Trauma CPP Bone Infection Registry: its patient population, baseline characteristics, infection details, cryopreserved biomaterials, treatment details, complications, functional outcomes, and quality of life after treatment.
Patient attributes, medical history, comorbidities (Charlson comorbidity index) (9), medications, treatment approaches, and hospital course were recorded at baseline. Nasal swabs, deep wound swabs, serum, and whole blood samples were taken only at baseline; laboratory blood tests performed through the study sites and serum samples collected for later testing in central laboratories were taken at baseline, 6, and 12 months. Short Form-36 version 2 (SF-36 v2) (10, 11), Parker Mobility Score (PMS) (12), and Katz Index of Independence in Activities of Daily Living (Katz ADL) questionnaires (13, 14) were used to assess patients' physical and mental health, their mobility, and their degree of independence at baseline and at all FU visits.
As this registry did not interfere with standard of care, adverse events (AEs) as defined by ISO 14155 were not recorded. Procedure-related AEs (e.g. complications caused by collection of blood, nasal, and aerobic bacterial samples) were documented. In-hospital complications that led to prolonged hospitalization or re-admission were documented in the complication form; predefined events of medical relevance that required hospital admission or prolongation of existing hospitalization were also recorded.
SF-36 questionnaire consists of 36 questions in eight different scales assessing both physical and mental health status (10, 11). The scores range from 0 to 100 with higher scores representing better health status.
Parker Mobility Score
The PMS assesses patient mobility. The final score ranges from 0 to 9 points, with higher scores indicating higher function (12). If any of the three questions were missing, the total score was also set to missing.
Katz Index of Independence in Activities of Daily Living
Katz ADL is a 6-item questionnaire that assesses the independence in activities of daily living (bathing, dressing, toileting, transferring, continence, and feeding) (13, 14). If any of the six items was missing, the total grade was also marked as missing.
Healing status was assessed at each FU as cured, healing, or other by the individual investigational sites according to their standard of care.
Establishment of the annotated biorepository and clinical laboratory tests
S. aureus strains were identified from the wound samples taken at baseline, and characterized as MRSA, and/or methicillin sensitive S. aureus (OSSA/MSSA) by local laboratories. The individual strains were cultured, cryopreserved, and labeled with the patient’s deidentified registry number for subsequent analyses. Serum samples (~ 10 ml per patient) collected at baseline and the FU visits were cryopreserved and labeled with the patient’s deidentified registry number for subsequent analyses.
Descriptive analyses of the level of glycated hemoglobin, C-reactive protein, white blood cell count, and erythrocyte sedimentation rate were performed by the local laboratories. Since these values were not particularly informative, they are not presented in this manuscript.
The current study aimed to characterize the patient demographics, disease and treatment characteristics, and outcomes, therefore no sample size calculation was required. The target sample size of 300 was calculated to allow the possibility of building a prognostic model with nine variables of interest assuming a binary outcome with an incidence of 30 events per 100 patients.
The “full analysis population” was defined as all eligible patients who gave written consent and commenced treatment within the study. The “per protocol population” was defined as patients who completed all FU visits.
Patient baseline characteristics, type of infection, hospitalization, and treatment details were analyzed using descriptive analyses. Continuous variables were summarized using mean and standard deviation (SD) for normally distributed data, whereas median and interquartile range (IQR) as well as minimum and maximum, were used for non-normally distributed data. Number and percentages were used for categorical variables.
SF-36 and PMS scores were analyzed using both descriptive statistics and mixed-effects models for repeated measures with an unstructured covariance. Katz ADL scores were analyzed by descriptive statistics and the changes from baseline were analyzed using Wilcoxon sign rank test. Outcome scores were analyzed first using data from the full analysis population and then repeated for the per protocol population.
The aggregated SF-36 physical and mental component summary scores (PCS and MCS, respectively) were transformed using the norm-based scoring with mean = 50 and standard deviation = 10 using the US population norm because its documentation of the algorithm is the best. In short, all scores above 50 can be interpreted as being above the US population average and all scores below 50 can be interpreted as being below the US population average. Although our study population was global, using this norm-based scoring helped ease the interpretation of the scores. The questionnaire used for this study was the standard (4-week recall) form.
The healing status was analyzed for both full analysis population and complete cases, i.e., patients whose assessment was available at all FU visits. SAS software (V9.4 Analytics Software & Solutions, Cary, North Carolina 27513, USA) was used to perform all statistical analyses.