International Lower Limb Collaborative (INTELLECT) study: a multicentre, international retrospective audit of lower extremity open fractures

Sixty-two centres in 16 countries contributed with 2,694 open fractures cases to an international, multi-centric, retrospective cohort study involving different healthcare settings. The INTELLECT study results show that there are significant disparities on the management of open lower limb fractures internationally. A timely, multidisciplinary, guideline-directed care is a protective factor for developing infective complications, non-union and requiring an amputation.


Introduction
Trauma remains a major cause of mortality and disability across the world 1 , with a higher burden in developing nations 2 . Open lower extremity injuries are devastating events from a physical 3 , mental health 4 , and socioeconomic 5 standpoint. The potential sequelae, including risk of chronic infection and amputation, can lead to delayed recovery and major disability 6 . This international study aimed to describe global disparities, timely intervention, guideline-directed care, and economic aspects of open lower limb injuries.

Methods
The INTELLECT (International Lower Limb Collaborative) study was an international, multicentre, retrospective audit supported by the Reconstructive Surgery Trials Network. Investigators in participating centres were tasked to retrieve demographic and clinical data for patients who had an open lower extremity fracture treated between 1 January 2017 and 31 December 2018. Primary outcomes were soft tissue infection, deep infection, non-union, and amputation. Secondary outcomes were median time to discharge and instances of deep venous thrombosis. Details of the study protocol and inclusion criteria can be found in Appendix S1 and Table S1 respectively. According to National Health Service Health Research Authority guidance, this study was not considered to be research, but an audit. Therefore, no formal ethics approval was required for centres in the UK. For other countries, local policies regarding information governance were adhered to.

Results
Sixty-two centres in 16 countries contributed with 2694 patients, a median of 17 per unit each year. Mean age at presentation was 44.5 (range 2-100) years, and 104 patients (3.9 per cent) were aged less than 16 years. Some 71 per cent of the affected individuals identified as male, and median follow-up was 11 (range 0-47) months (Fig. S1). The most common mechanism of injury was road traffic accidents (52.6 per cent), followed by low-energy (18.7 per cent) and high-energy (11 per cent) falls (Table S2). A descriptive summary, including demographic information, treatment provided and outcomes, can be found in Tables 1 and 2.
A multivariate logistic regression analysis adjusting for age, mechanism of injury, and country income group showed that patients with Gustilo IIIB and IIIC fractures had a higher  (Table S3). Joint treatment by orthopaedic or trauma surgeons working with plastic surgeons from the time of the debridement onwards was identified as protective factor for secondary amputation (OR 0.41; P = 0.008).
Two-thirds of injuries that required soft tissue reconstruction were previously classified as Gustilo IIIB and IIIC, 76 per cent in high-income countries with guidelines, 58 per cent in high-income countries with no guidelines, and 63 per cent in low-and middle-income countries. There were differences in surgical-site infections and duration of follow-up ( Table 3). Multivariable analysis showed that being treated in a setting with national guidelines [7][8][9] was protective with respect to developing a deep tissue infection (OR 0.66; P = 0.040) or non-union (OR 0.66; P = 0.043), with a 34 per cent lower likelihood of developing either of these.

Discussion
Moderate interobserver reliability has been reported for the Gustilo classification 10 , but it was unexpected to find that one-third of open tibial fractures requiring soft tissue reconstruction were classified as Gustilo I, II, and IIIA fractures initially. This proportion was higher in countries with no guidelines. Patients treated in high-income countries with established clinical guidelines had better access to healthcare and outcomes. Under-representation of studies conducted in less economically developed settings poses the risk of skewing data towards practices in higher-income nations. Guidelines for the management of open lower limb fractures advocate a multidisciplinary approach and global partnerships may offer quality improvement initiatives [11][12][13] . Patients treated in middle-and low-income settings experienced delays in accessing treatment, which was rarely delivered by multidisciplinary teams. Considering that lifelong limb prosthesis is costly, a tendency towards limb preservation in resource-constrained settings is expected 14 . There are inherent challenges associated with a methodology that relies on patient records in some institutions, including selection, information, detection, and collection   biases. A prospective study would provide more reliable data that could include mental health and quality-of-life measures to refine global cooperative plans.