Aims

Machine-learning (ML) prediction models in orthopaedic trauma hold great promise in assisting clinicians in various tasks, such as personalized risk stratification. However, an overview of current applications and critical appraisal to peer-reviewed guidelines is lacking. The objectives of this study are to 1) provide an overview of current ML prediction models in orthopaedic trauma; 2) evaluate the completeness of reporting following the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) statement; and 3) assess the risk of bias following the Prediction model Risk Of Bias Assessment Tool (PROBAST) tool.

Aims

Lower limb reconstruction (LLR) has a profound impact on patients, affecting multiple areas of their lives. Many patient-reported outcome measures (PROMs) are employed to assess these impacts; however, there are concerns that they do not adequately capture all outcomes important to patients, and may lack content validity in this context. This review explored whether PROMs used with adults requiring, undergoing, or after undergoing LLR exhibited content validity and adequately captured outcomes considered relevant and important to patients.

Aims. The aim of this study was to perform a systematic review and bias evaluation of the current literature to create an overview of risk factors for re-revision following revision total knee arthroplasty (rTKA). Methods. A systematic search of MEDLINE and Embase was completed in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. The studies were required to include a population of index rTKAs. Primary or secondary outcomes had to be re-revision. The association between preoperative factors and the effect on the risk for re-revision was also required to be reported by the studies. Results. The search yielded 4,847 studies, of which 15 were included. A majority of the studies were retrospective cohorts or registry studies. In total, 26 significant risk factors for re-revision were identified. Of these, the following risk factors were consistent across multiple studies: age at the time of index revision, male sex, index revision being partial revision, and index revision due to infection. Modifiable risk factors were opioid use, BMI > 40 kg/m. 2. , and anaemia. History of one-stage revision due to infection was associated with the highest risk of re-revision. Conclusion. Overall, 26 risk factors have been associated with an increased risk of re-revision following rTKA. However, various levels of methodological bias were found in the studies. Future studies should ensure valid comparisons by including patients with identical indications and using clear definitions for accurate assessments. Cite this article: Bone Jt Open 2024;5(8):644–651

Aims. Spinopelvic characteristics influence the hip’s biomechanical behaviour. However, to date there is little knowledge defining what ‘normal’ spinopelvic characteristics are. This study aims to determine how static spinopelvic characteristics change with age and ethnicity among asymptomatic, healthy individuals. Methods. This systematic review followed the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to identify English studies, including ≥ 18-year-old participants, without evidence of hip or spine pathology or a history of previous surgery or interventional treatment, documenting lumbar lordosis (LL), sacral slope (SS), pelvic tilt (PT), and pelvic incidence (PI). From a total of 2,543 articles retrieved after the initial database search, 61 articles were eventually selected for data extraction. Results. When all ethnicities were combined the mean values for LL, SS, PT, and PI were: 47.4° (SD 11.0°), 35.8° (SD 7.8°), 14.0° (SD 7.2°), and 48.8° (SD 10°), respectively. LL, SS, and PT had statistically significant (p < 0.001) changes per decade at: −1.5° (SD 0.3°), −1.3° (SD 0.3°), and 1.4° (SD 0.1°). Asian populations had the largest age-dependent change in LL, SS, and PT compared to any other ethnicity per decade at: −1.3° (SD 0.3°) to −0.5° (SD 1.3°), –1.2° (SD 0.2°) to −0.3° (SD 0.3°), and 1.7° (SD 0.2°) versus 1.1° (SD 0.1°), respectively. Conclusion. Ageing alters the orientation between the spine and pelvis, causing LL, SS, and PT to modify their orientations in a compensatory mechanism to maintain sagittal alignment for balance when standing. Asian populations have the largest degree of age-dependent change to their spinopelvic parameters compared to any other ethnicity, likely due to their lower PI. Cite this article: Bone Joint Res 2023;12(4):231–244

Aims. The aim of this systematic review and meta-analysis was to gather epidemiological information on selected musculoskeletal injuries and to provide pooled injury-specific incidence rates. Methods. PubMed (National Library of Medicine) and Scopus (Elsevier) databases were searched. Articles were eligible for inclusion if they reported incidence rate (or count with population at risk), contained data on adult population, and were written in English language. The number of cases and population at risk were collected, and the pooled incidence rates (per 100,000 person-years) with 95% confidence intervals (CIs) were calculated by using either a fixed or random effects model. Results. The screening of titles yielded 206 articles eligible for inclusion in the study. Of these, 173 (84%) articles provided sufficient information to be included in the pooled incidence rates. Incidences of fractures were investigated in 154 studies, and the most common fractures in the whole adult population based on the pooled incidence rates were distal radius fractures (212.0, 95% CI 178.1 to 252.4 per 100,000 person-years), finger fractures (117.1, 95% CI 105.3 to 130.2 per 100,000 person-years), and hip fractures (112.9, 95% CI 82.2 to 154.9 per 100,000 person-years). The most common sprains and dislocations were ankle sprains (429.4, 95% CI 243.0 to 759.0 per 100,000 person-years) and first-time patellar dislocations (32.8, 95% CI 21.6 to 49.7 per 100,000 person-years). The most common injuries were anterior cruciate ligament (17.5, 95% CI 6.0 to 50.2 per 100,000 person-years) and Achilles (13.7, 95% CI 9.6 to 19.5 per 100,000 person-years) ruptures. Conclusion. The presented pooled incidence estimates serve as important references in assessing the global economic and social burden of musculoskeletal injuries. Cite this article: Bone Joint Res 2022;11(11):814–825

This systematic review examines the current literature regarding surgical techniques for restoring articular cartilage in the hip, from the older microfracture techniques involving perforation to the subchondral bone, to adaptations of this technique using nanofractures and scaffolds. This review discusses the autologous and allograft transfer systems and the autologous matrix-induced chondrogenesis (AMIC) technique, as well as a summary of the previously discussed techniques, which could become common practice for restoring articular cartilage, thus reducing the need for total hip arthroplasty. Using the British Medical Journal Grading of Recommendations, Assessment, Development and Evaluation (BMJ GRADE) system and Grade system. Comparison of the studies discussed shows that microfracture has the greatest quantity and quality of research, whereas the newer AMIC technique requires more research, but shows promise. Cite this article: W. E. Hotham, A. Malviya. A systematic review of surgical methods to restore articular cartilage in the hip. Bone Joint Res 2018;7:336–342. DOI: 10.1302/2046-3758.75.BJR-2017-0331

Aims. To analyze outcomes reported in studies of Ponseti correction of idiopathic clubfoot. Methods. A systematic review of the literature was performed to identify a list of outcomes and outcome tools reported in the literature. A total of 865 studies were screened following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and 124 trials were included in the analysis. Data extraction was completed by two researchers for each trial. Each outcome tool was assigned to one of the five core areas defined by the Outcome Measures Recommended for use in Randomized Clinical Trials (OMERACT). Bias assessment was not deemed necessary for the purpose of this paper. Results. In total, 20 isolated outcomes and 16 outcome tools were identified representing five OMERACT domains. Most outcome tools were appropriately designed for children of walking age but have not been embraced in the literature. The most commonly reported isolated outcomes are subjective and qualitative. The quantitative outcomes most commonly used are ankle range of motion (ROM), foot position in standing, and muscle function. Conclusions. There is a diverse range of outcomes reported in studies of Ponseti correction of clubfoot. Until outcomes can be reported unequivocally and consistently, research in this area will be limited. Completing the process of establishing and validating COS is the much-needed next step. Cite this article: Bone Joint Open 2020;1-8:457–464

Objectives

This review aims to summarize the outcomes used to describe effectiveness of treatments for paediatric wrist fractures within existing literature.

Aims. To systematically review the predominant complication rates and changes to patient-reported outcome measures (PROMs) following osteochondral allograft (OCA) transplantation for shoulder instability. Methods. This systematic review, following PRISMA guidelines and registered in PROSPERO, involved a comprehensive literature search using PubMed, Embase, Web of Science, and Scopus. Key search terms included “allograft”, “shoulder”, “humerus”, and “glenoid”. The review encompassed 37 studies with 456 patients, focusing on primary outcomes like failure rates and secondary outcomes such as PROMs and functional test results. Results. A meta-analysis of primary outcomes across 17 studies revealed a dislocation rate of 5.1% and an increase in reoperation rates from 9.3% to 13.7% post-publication bias adjustment. There was also a noted rise in conversion to total shoulder arthroplasty and incidence of osteoarthritis/osteonecrosis over longer follow-up periods. Patient-reported outcomes and functional tests generally showed improvement, albeit with notable variability across studies. A concerning observation was the consistent presence of allograft resorption, with rates ranging from 33% to 80%. Comparative studies highlighted similar efficacy between distal tibial allografts and Latarjet procedures in most respects, with some differences in specific tests. Conclusion. OCA transplantation presents a promising treatment option for shoulder instability, effectively addressing both glenoid and humeral head defects with favourable patient-reported outcomes. These findings advocate for the inclusion of OCA transplantation in treatment protocols for shoulder instability, while also emphasizing the need for further high-quality, long-term research to better understand the procedure’s efficacy profile. Cite this article: Bone Jt Open 2024;5(7):570–580

Aims. Machine learning (ML), a branch of artificial intelligence that uses algorithms to learn from data and make predictions, offers a pathway towards more personalized and tailored surgical treatments. This approach is particularly relevant to prevalent joint diseases such as osteoarthritis (OA). In contrast to end-stage disease, where joint arthroplasty provides excellent results, early stages of OA currently lack effective therapies to halt or reverse progression. Accurate prediction of OA progression is crucial if timely interventions are to be developed, to enhance patient care and optimize the design of clinical trials. Methods. A systematic review was conducted in accordance with PRISMA guidelines. We searched MEDLINE and Embase on 5 May 2024 for studies utilizing ML to predict OA progression. Titles and abstracts were independently screened, followed by full-text reviews for studies that met the eligibility criteria. Key information was extracted and synthesized for analysis, including types of data (such as clinical, radiological, or biochemical), definitions of OA progression, ML algorithms, validation methods, and outcome measures. Results. Out of 1,160 studies initially identified, 39 were included. Most studies (85%) were published between 2020 and 2024, with 82% using publicly available datasets, primarily the Osteoarthritis Initiative. ML methods were predominantly supervised, with significant variability in the definitions of OA progression: most studies focused on structural changes (59%), while fewer addressed pain progression or both. Deep learning was used in 44% of studies, while automated ML was used in 5%. There was a lack of standardization in evaluation metrics and limited external validation. Interpretability was explored in 54% of studies, primarily using SHapley Additive exPlanations. Conclusion. Our systematic review demonstrates the feasibility of ML models in predicting OA progression, but also uncovers critical limitations that currently restrict their clinical applicability. Future priorities should include diversifying data sources, standardizing outcome measures, enforcing rigorous validation, and integrating more sophisticated algorithms. This paradigm shift from predictive modelling to actionable clinical tools has the potential to transform patient care and disease management in orthopaedic practice. Cite this article: Bone Joint J 2024;106-B(11):1216–1222

Aims. Machine learning (ML) holds significant promise in optimizing various aspects of total shoulder arthroplasty (TSA), potentially improving patient outcomes and enhancing surgical decision-making. The aim of this systematic review was to identify ML algorithms and evaluate their effectiveness, including those for predicting clinical outcomes and those used in image analysis. Methods. We searched the PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases for studies applying ML algorithms in TSA. The analysis focused on dataset characteristics, relevant subspecialties, specific ML algorithms used, and their performance outcomes. Results. Following the final screening process, 25 articles satisfied the eligibility criteria for our review. Of these, 60% focused on tabular data while the remaining 40% analyzed image data. Among them, 16 studies were dedicated to developing new models and nine used transfer learning to leverage existing pretrained models. Additionally, three of these models underwent external validation to confirm their reliability and effectiveness. Conclusion. ML algorithms used in TSA demonstrated fair to good performance, as evidenced by the reported metrics. Integrating these models into daily clinical practice could revolutionize TSA, enhancing both surgical precision and patient outcome predictions. Despite their potential, the lack of transparency and generalizability in many current models poses a significant challenge, limiting their clinical utility. Future research should prioritize addressing these limitations to truly propel the field forward and maximize the benefits of ML in enhancing patient care. Cite this article: Bone Jt Open 2025;6(2):126–134

Aims. Older adults with hip fractures are at high risk of experiencing complications after surgery, but estimates of the rate of specific complications vary by study design and follow-up period. The aim of this systematic review was to determine the prevalence of complications in older adults after hip fracture surgery. Methods. MEDLINE, Embase, CINAHL, and CENTRAL databases were searched from inception until 30 June 2023. Studies were included if they reported prevalence data of complications in an unselected, consecutive population of older adults (aged ≥ 60 years) undergoing hip fracture surgery. Results. A total of 95 studies representing 2,521,300 patients were included. For surgery-specific complications, the 30-day prevalence of reoperation was 2.31%, surgical site infection 1.69%, and deep surgical site infection 0.98%; the 365-day prevalence of prosthesis dislocation was 1.11%, fixation failure 1.77%, and periprosthetic or peri-implant fracture 2.23%. For general complications, the 30-day prevalence of acute kidney injury was 1.21%, blood transfusion 25.55%, cerebrovascular accident 0.79%, lower respiratory tract infection 4.08%, myocardial infarction 1.98%, urinary tract infection 7.01%, and venous thromboembolism 2.15%. Conclusion. Complications are prevalent in older adults who have had surgery for a hip fracture. Studies reporting complications after hip fracture surgery varied widely in terms of quality, and we advocate for the routine monitoring of complications in registries and clinical trials to improve the quality of evidence. Cite this article: Bone Joint J 2025;107-B(2):139–148

Aims

The aim of this study was to review the current evidence surrounding curve type and morphology on curve progression risk in adolescent idiopathic scoliosis (AIS).

Aims. Autologous bone graft (ABG) is considered the ‘gold standard’ among graft materials for bone regeneration. However, complications including limited availability, donor site morbidity, and deterioration of regenerative capacity over time have been reported. P-15 is a synthetic peptide that mimics the cell binding domain of Type-I collagen. This peptide stimulates new bone formation by enhancing osteogenic cell attachment, proliferation, and differentiation. The objective of this study was to conduct a systematic literature review to determine the clinical efficacy and safety of P-15 peptide in bone regeneration throughout the skeletal system. Methods. PubMed, Embase, Web of Science, and Cochrane Library were searched for relevant articles on 13 May 2023. The systematic review was reported according to the PRISMA guidelines. Two reviewers independently screened and assessed the identified articles. Quality assessment was conducted using the methodological index for non-randomized studies and the risk of bias assessment tool for randomized controlled trials. Results. After screening, 28 articles were included and grouped by surgical indication, e.g. maxillofacial procedures (n = 18), spine (n = 9), and trauma (n = 1). Published results showed that P-15 peptide was effective in spinal fusion (n = 7) and maxillofacial (n = 11), with very few clinically relevant adverse events related to P-15 peptide. Conclusion. This systematic literature review concluded that moderate- (risk of bias, some concern: 50%) to high-quality (risk of bias, low: 46%) clinical evidence exists showing equivalent safety and efficacy in bone regeneration using a P-15 peptide enhanced bone graft substitute compared to ABG. P-15 peptide is safe and effective, resulting in rapid bone formation with a low probability of minor complications. Cite this article: Bone Joint Res 2025;14(2):77–92

Aims. Recurrent dislocation is both a cause and consequence of glenoid bone loss, and the extent of the bony defect is an indicator guiding operative intervention. Literature suggests that loss greater than 25% requires glenoid reconstruction. Measuring bone loss is controversial; studies use different methods to determine this, with no clear evidence of reproducibility. A systematic review was performed to identify existing CT-based methods of quantifying glenoid bone loss and establish their reliability and reproducibility. Methods. A Preferred Reporting Items for Systematic reviews and Meta-Analyses-compliant systematic review of conventional and grey literature was performed. Results. A total of 25 studies were initially eligible. Following screening, nine papers were included for review. Main themes identified compared 2D and 3D imaging, as well as linear- compared with area-based techniques. Heterogenous data were acquired, and therefore no meta-analysis was performed. Conclusion. No ideal CT-based method is demonstrated in the current literature, however evidence suggests that surface area methods are more reproducible and lead to fewer over-estimations of bone loss, provided the views used are standardized. A prospective imaging trial is required to provide a more definitive answer to this research question. Cite this article: Bone Jt Open 2022;3(2):114–122

Aims. This systematic review aims to compare the precision of component positioning, patient-reported outcome measures (PROMs), complications, survivorship, cost-effectiveness, and learning curves of MAKO robotic arm-assisted unicompartmental knee arthroplasty (RAUKA) with manual medial unicompartmental knee arthroplasty (mUKA). Methods. Searches of PubMed, MEDLINE, and Google Scholar were performed in November 2021 according to the Preferred Reporting Items for Systematic Review and Meta-­Analysis statement. Search terms included “robotic”, “unicompartmental”, “knee”, and “arthroplasty”. Published clinical research articles reporting the learning curves and cost-effectiveness of MAKO RAUKA, and those comparing the component precision, functional outcomes, survivorship, or complications with mUKA, were included for analysis. Results. A total of 179 articles were identified from initial screening, of which 14 articles satisfied the inclusion criteria and were included for analysis. The papers analyzed include one on learning curve, five on implant positioning, six on functional outcomes, five on complications, six on survivorship, and three on cost. The learning curve was six cases for operating time and zero for precision. There was consistent evidence of more precise implant positioning with MAKO RAUKA. Meta-analysis demonstrated lower overall complication rates associated with MAKO RAUKA (OR 2.18 (95% confidence interval (CI) 1.06 to 4.49); p = 0.040) but no difference in re-intervention, infection, Knee Society Score (KSS; mean difference 1.64 (95% CI -3.00 to 6.27); p = 0.490), or Western Ontario and McMaster Universities Arthritis Index (WOMAC) score (mean difference -0.58 (95% CI -3.55 to 2.38); p = 0.700). MAKO RAUKA was shown to be a cost-effective procedure, but this was directly related to volume. Conclusion. MAKO RAUKA was associated with improved precision of component positioning but was not associated with improved PROMs using the KSS and WOMAC scores. Future longer-term studies should report functional outcomes, potentially using scores with minimal ceiling effects and survival to assess whether the improved precision of MAKO RAUKA results in better outcomes. Cite this article: Bone Joint J 2022;104-B(5):541–548

Aims. Return to sport following undergoing total (TKA) and unicompartmental knee arthroplasty (UKA) has been researched with meta-analyses and systematic reviews of varying quality. The aim of this study is to create an umbrella review to consolidate the data into consensus guidelines for returning to sports following TKA and UKA. Methods. Systematic reviews and meta-analyses written between 2010 and 2020 were systematically searched. Studies were independently screened by two reviewers and methodology quality was assessed. Variables for analysis included objective classification of which sports are safe to participate in postoperatively, time to return to sport, prognostic indicators of returning, and reasons patients do not. Results. A total of 410 articles were found, including 58 duplicates. Seven articles meeting inclusion criteria reported that 34% to 100% of patients who underwent TKA or UKA were able to return to sports at 13 weeks and 12 weeks respectively, with UKA patients more likely to do so. Prior experience with the sport was the most significant prognostic indicator for return. These patients were likely to participate in low-impact sports, particularly walking, cycling, golf, and swimming. Moderate-impact sport participation, such as doubles tennis and skiing, may be considered on a case-by-case basis considering the patient’s prior experience. There is insufficient long-term data on the risks to return to high-impact sport, such as decreased implant survivorship. Conclusion. There is a consensus that patients can return to low-impact sports following TKA or UKA. Return to moderate-impact sport was dependent on a case-by-case basis, with emphasis on the patient’s prior experience in the sport. Return to high-impact sports was not supported. Patients undergoing UKA return to sport one week sooner and with more success than TKA. Future studies are needed to assess long-term outcomes following return to high-impact sports to establish evidence-based recommendations. This review summarizes all available data for the most up-to-date and evidence-based guidelines for returning to sport following TKA and UKA to replace guidelines based on subjective physician survey data. Cite this article: Bone Jt Open 2022;3(3):245–251

Background. Due to the overwhelming demand for trauma services, resulting from increasing emergency department attendances over the past decade, virtual fracture clinics (VFCs) have become the fashion to keep up with the demand and help comply with the BOA Standards for Trauma and Orthopaedics (BOAST) guidelines. In this article, we perform a systematic review asking, “How useful are VFCs?”, and what injuries and conditions can be treated safely and effectively, to help decrease patient face to face consultations. Our primary outcomes were patient satisfaction, clinical efficiency and cost analysis, and clinical outcomes. Methods. We performed a systematic literature search of all papers pertaining to VFCs, using the search engines PubMed, MEDLINE, and the Cochrane Database, according to the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA) checklist. Searches were carried out and screened by two authors, with final study eligibility confirmed by the senior author. Results. In total, 21 records were relevant to our research question. Six orthopaedic injuries were identified as suitable for VFC review, with a further four discussed in detail. A reduction of face to face appointments of up to 50% was reported with greater compliance to BOAST guidelines (46.4%) and cost saving (up to £212,000). Conclusions. This systematic review demonstrates that the VFC model can help deliver a safe, more cost-effective, and more efficient arm of the trauma service to patients. Cite this article: Bone Joint Open 2020;1-11:683–690

Aims. Open lower limb fracture is a life-changing injury affecting 11.5 per 100,000 adults each year, and causes significant morbidity and resource demand on trauma infrastructures. This study aims to identify what, and how, outcomes have been reported for people following open lower limb fracture over ten years. Methods. Systematic literature searches identified all clinical studies reporting outcomes for adults following open lower limb fracture between January 2009 and July 2019. All outcomes and outcome measurement instruments were extracted verbatim. An iterative process was used to group outcome terms under standardized outcome headings categorized using an outcome taxonomy. Results. A total of 532 eligible studies were identified, reporting 1,803 outcomes with 786 unique outcome terms, which collapsed to 82 standardized outcome headings. Overall 479 individual outcome measurement instruments were identified, including 298 outcome definitions, 27 patient- and 18 clinician-reported outcome measures, and six physical performance measures. The most-reported outcome was ‘bone union/healing’ reported in over 50% of included studies, while health-related quality of life was only measured in 6% of included studies. Conclusion. Outcomes reported for people recovering from open lower limb fracture are heterogeneous, liable to outcome reporting bias, and vary widely in the definitions and the measurement tools used to collect them. Outcomes likely to be important to patients, such as quality of life and measures of physical functioning, have been neglected. This systematic review identifies the need to unify outcome measures reported on patients recovering from open lower limb fracture; this may be addressed by creating a core outcome set. Cite this article: Bone Joint Res 2023;12(2):138–146

Aims. Giant cell tumour of bone (GCTB) treatment changed since the introduction of denosumab from purely surgical towards a multidisciplinary approach, with recent concerns of higher recurrence rates after denosumab. We evaluated oncological, surgical, and functional outcomes for distal radius GCTB, with a critically appraised systematic literature review. Methods. We included 76 patients with distal radius GCTB in three sarcoma centres (1990 to 2019). Median follow-up was 8.8 years (2 to 23). Seven patients underwent curettage, 38 curettage with adjuvants, and 31 resection; 20 had denosumab. Results. Recurrence rate was 71% (5/7) after curettage, 32% (12/38) after curettage with adjuvants, and 6% (2/31) after resection. Median time to recurrence was 17 months (4 to 77). Recurrences were treated with curettage with adjuvants (11), resection (six), or curettage (two). Overall, 84% (38/45) was cured after one to thee intralesional procedures. Seven patients had 12 months neoadjuvant denosumab (5 to 15) and sixmonths adjuvant denosumab; two recurred (29%). Twelve patients had six months neoadjuvant denosumab (4 to 10); five recurred (42%). Two had pulmonary metastases (2.6%), both stable after denosumab. Complication rate was 18% (14/76, with 11 requiring surgery). At follow-up, median MusculoSkeletal Tumour Society score was 28 (18 to 30), median Short Form-36 Health Survey was 86 (41 to 95), and median Disability of Arm, Shoulder, and Hand was 7.8 (0 to 58). Conclusion. Distal radius GCTB treatment might deviate from general GCTB treatment because of complexity of wrist anatomy and function. Novel insights on surgical treatment are presented in this multicentre study and systematic review. Intralesional surgery resulted in high recurrence-rate for distal radius GCTB, also with additional denosumab. The large majority of patients however, were cured after repeated curettage. Cite this article: Bone Jt Open 2022;3(7):515–528