Machine Learning Can Improve Clinical Detection of Low BMD: The DXA-HIP Study.

BACKGROUND: Identification of those at high risk before a fracture occurs is an essential part of osteoporosis management. This topic remains a significant challenge for researchers in the field, and clinicians worldwide. Although many algorithms have been developed to either identify those with a diagnosis of osteoporosis or predict their risk of fracture, concern remains regarding their accuracy and application. Scientific advances including machine learning methods are rapidly gaining appreciation as alternative techniques to develop or enhance risk assessment and current practice. Recent evidence suggests that these methods could play an important role in the assessment of osteoporosis and fracture risk. METHODS: Data used for this study included Dual-energy X-ray Absorptiometry (DXA) bone mineral density and T-scores, and multiple clinical variables drawn from a convenience cohort of adult patients scanned on one of 4 DXA machines across three hospitals in the West of Ireland between January 2000 and November 2018 (the DXA-Heath Informatics Prediction Cohort). The dataset was cleaned, validated and anonymized, and then split into an exploratory group (80%) and a development group (20%) using the stratified sampling method. We first established the validity of a simple tool, the Osteoporosis Self-assessment Tool Index (OSTi) to identify those classified as osteoporotic by the modified International Society for Clinical Densitometry DXA criteria. We then compared these results to seven machine learning techniques (MLTs): CatBoost, eXtreme Gradient Boosting, Neural network, Bagged flexible discriminant analysis, Random forest, Logistic regression and Support vector machine to enhance the discrimination of those classified as osteoporotic or not. The performance of each prediction model was measured by calculating the area under the curve (AUC) with 95% confidence interval (CI), and was compared against the OSTi. RESULTS: A cohort of 13,577 adults aged ≥40 yr at the age of their first scan was identified including 11,594 women and 1983 men. 2102 (18.13%) females and 356 (17.95%) males were identified with osteoporosis based on their lowest T-score. The OSTi performed well in our cohort in both men (AUC 0.723, 95% CI 0.659-0.788) and women (AUC 0.810, 95% CI 0.787-0.833). Four MLTs improved discrimination in both men and women, though the incremental benefit was small. eXtreme Gradient Boosting showed the most promising results: +4.5% (AUC 0.768, 95% CI 0.706-0.829) for men and +2.3% (AUC 0.833, 95% CI 0.812-0.853) for women. Similarly MLTs outperformed OSTi in sensitivity analyses-which excluded those subjects taking osteoporosis medications-though the absolute improvements differed. CONCLUSION: The OSTi retains an important role in identifying older men and women most likely to have osteoporosis by bone mineral density classification. MLTs could improve DXA detection of osteoporosis classification in older men and women. Further exploration of MLTs is warranted in other populations, and with additional data.

Utility of Osteoporosis Self-Assessment Tool as a Screening Tool for Osteoporosis in Irish Men and Women: Results of the DXA-HIP Project.

Many algorithms have been developed and publicised over the past 2 decades for identifying those most likely to have osteoporosis or low BMD, or at increased risk of fragility fracture. The Osteoporosis Self-assessment Tool index (OSTi) is one of the oldest, simplest, and widely used for identifying men and women with low BMD or osteoporosis. OSTi has been validated in many cohorts worldwide but large studies with robust analyses evaluating this or other algorithms in adult populations residing in the Republic of Ireland are lacking, where waiting times for public DXA facilities are long. In this study we evaluated the validity of OSTi in men and women drawn from a sampling frame of more than 36,000 patients scanned at one of 3 centres in the West of Ireland. 18,670 men and women aged 40 years and older had a baseline scan of the lumbar spine femoral neck and total hip available for analysis. 15,964 (86%) were female, 5,343 (29%) had no major clinical risk factors other than age, while 5,093 (27%) had a prior fracture. Approximately 2/3 had a T-score ≤-1.0 at one or more skeletal sites and 1/3 had a T-score ≤-1.0 at all 3 skeletal sites, while 1 in 5 had a DXA T-score ≤-2.5 at one or more skeletal sites and 5% had a T-score ≤-2.5 at all 3 sites. OSTi generally performed well in our population with area under the curve (AUC) values ranging from 0.581 to 0.881 in men and 0.701 to 0.911 in women. The performance of OSTi appeared robust across multiple sub-group analyses. AUC values were greater for women, proximal femur sites, those without prior fractures and those not taking osteoporosis medication. Optimal OSTi cut-points were '2' for men and '0' for women in our study population. OSTi is a simple and effective tool to aid identification of Irish men and women with low BMD or osteoporosis. Use of OSTi could improve the effectiveness of DXA screening programmes for older adults in Ireland.

Significance of Distal Runoff Score as a Key Influencer on Clinical Outcomes after Endovascular Interventions for Superficial Femoral Artery Disease.

BACKGROUND: Endovascular therapy (EVT) is being adopted by many surgeons as a suitable first choice in the treatment of most femoropopliteal disease when clinically indicated. However, there are multiple factors affecting the outcome of EVT including the anatomy of lesions and distal runoff status. The evidence of runoff effect on the outcome of superficial femoral artery (SFA) interventions is still scarce and not well studied in the current literature. The aim of this study was to investigate the effect of runoff score on the outcomes of SFA endovascular interventions. METHODS: Retrospective analysis was carried out on prospectively collected data on patients who underwent SFA endovascular intervention for critical limb ischemia (CLI) in a single tertiary center. Patients with Rutherford categories 4, 5, and 6 who did not have any previous vascular interventions were included in the study. The modified SVS runoff score was used after calculating scores from popliteal and all tibial vessels. Runoff was stratified into good (score <5), compromised (score 5-10), and poor (score >10). Amputation-free survival, patency rates, and overall survival were compared between all groups at 5 years. RESULTS: Between 2011 and 2018, 254 procedures were performed in 220 patients. Technical success was >92%; 66 patients required SFA stents, and 55 had concomitant tibial angioplasty. There was no significant difference between good, compromised, or poor runoff groups regarding complication rates, with 3.5% overall perioperative mortality (5 cases in the compromised group and 4 in the poor runoff group). A runoff score of <5 was associated with significantly marked clinical improvement (P < 0.001). Patency rates were significantly worse in the compromised and poor runoff groups, with 5-year cumulative primary patency rates of 80%, 50%, and 22% in the good, compromised, and poor runoff groups, respectively (P < 0.001). Amputation-free survival worsened as the runoff got poorer with 98%, 91%, and 78% in the good, compromised, and poor runoff groups, respectively, at 5 years (P < 0.001). SFA stenting and concomitant tibial angioplasty led to slight improvement in patency rates in the poor runoff group. CONCLUSIONS: Poor runoff with a score of >10 was associated with significantly reduced amputation-free survival and patency rates at 5 years in patients undergoing SFA endovascular intervention for CLI. Patients with a runoff score of <5 showed marked clinical improvement postoperatively when compared with patients with a runoff score of ≥5.

Modelling future bone mineral density: Simplicity or complexity?

BACKGROUND: Osteoporotic fractures are a major global public health issue, leading to patient suffering and death, and considerable healthcare costs. Bone mineral density (BMD) measurement is important to identify those with osteoporosis and assess their risk of fracture. Both the absolute BMD and the change in BMD over time contribute to fracture risk. Predicting future fracture in individual patients is challenging and impacts clinical decisions such as when to intervene or repeat BMD measurement. Although the importance of BMD change is recognised, an effective way to incorporate this marginal effect into clinical algorithms is lacking. METHODS: We compared two methods using longitudinal DXA data generated from subjects with two or more hip DXA scans on the same machine between 2000 and 2018. A simpler statistical method (ZBM) was used to predict an individual's future BMD based on the mean BMD and the standard deviation of the reference group and their BMD measured in the latest scan. A more complex deep learning (DL)-based method was developed to cope with multidimensional longitudinal data, variables extracted from patients' historical DXA scan(s), as well as features drawn from the ZBM method. Sensitivity analyses of several subgroups was conducted to evaluate the performance of the derived models. RESULTS: 2948 white adults aged 40-90 years met our study inclusion: 2652 (90 %) females and 296 (10 %) males. Our DL-based models performed significantly better than the ZBM models in women, particularly our Hybrid-DL model. In contrast, the ZBM-based models performed as well or better than DL-based models in men. CONCLUSIONS: Deep learning-based and statistical models have potential to forecast future BMD using longitudinal clinical data. These methods have the potential to augment clinical decisions regarding when to repeat BMD testing in the assessment of osteoporosis.

An overview of the management of osteoporosis in the aging female population.

Osteoporosis is a systemic skeletal disease that is a cause of morbidity and mortality. It can affect all ages but most frequently postmenopausal women. It is a silent condition, however, osteoporotic fractures can lead to significant pain and disability. In this review article, we aim to review the clinical approach to the management of postmenopausal osteoporosis. We include risk assessment, investigations, and the various pharmacological and non-pharmacological options used in the treatment of osteoporosis. We have discussed the pharmacological options individually including their mechanism of action, safety profile, effects on bone mineral density and fracture risks, and duration of use. Potential new treatments are also discussed. The importance of sequence in the use of osteoporotic medicine is also highlighted in the article. An understanding of the different treatment options will hopefully help in the management of this very common and debilitating condition.

Role of Adipose Derived Stem Cells in Patients with Diabetic Foot Ulcers: Systematic Review and Meta-Analysis of Randomised Controlled Trials.

Few studies to date have investigated the role of adipose derived stem cells (ADSCs) in patients with diabetic foot ulcers (DFU). We aimed to conduct a systematic search of the literature to explore the available evidence behind ADSCs application in patients with DFU to establish if it has any added benefit regarding healing rate and healing time in this cohort of patients. The PubMed and Embase databases were searched for eligible studies. Only randomised controlled trials which investigated the impact of ADSCs alone on the healing of DFU were considered eligible and were included for the review. Reported healing rates, time to healing and procedure related complications were collected and analysed. The initial search resulted in 160 papers. Following duplicate removal, 131 papers were screened for eligibility. Only four trials met the study criteria and were included for the final review and analysis. 97 out of 189 patients who were included in the four studies received ADSCs for treatment of DFU whereas the remaining 92 patients received standard measures (control). The median participant age was 62, predominantly male (72.5%). Complete healing was achieved in 83.5% (n = 81) of patients in the ADSC group compared to 52% (n = 48) for patients in the control group at 12 months (OR = 4.8, 95%CI = 2.25 to 10.24, P < 0.0001). Mean healing time in the ADSC group ranged from 31 to 85 days whereas mean healing time in the control group ranged from 42 to 85 days (Pooled weighted mean difference = -10.832856, 95%CI = -22.44 to 0.77, P = 0.0673). No significant procedure related complications were reported in either group. The use of ADSCs in patients with DFU appears to demonstrate improved healing rates. The procedure of ADSC harvest and administration appears to be safe based on the initial reports. Large, randomised trials are needed to establish its role in patients with diabetic foot wounds.

Prevalence of Low Bone Mass and Osteoporosis in Ireland: the Dual-Energy X-Ray Absorptiometry (DXA) Health Informatics Prediction (HIP) Project.

Osteoporosis is a common disease that has a significant impact on patients, healthcare systems, and society. World Health Organization (WHO) diagnostic criteria for postmenopausal women were established in 1994 to diagnose low bone mass (osteopenia) and osteoporosis using dual-energy X-ray absorptiometry (DXA)-measured bone mineral density (BMD) to help understand the epidemiology of osteoporosis, and identify those at risk for fracture. These criteria may also apply to men ≥50 years, perimenopausal women, and people of different ethnicity. The DXA Health Informatics Prediction (HIP) project is an established convenience cohort of more than 36,000 patients who had a DXA scan to explore the epidemiology of osteoporosis and its management in the Republic of Ireland where the prevalence of osteoporosis remains unknown. In this article we compare the prevalence of a DXA classification low bone mass (T-score < -1.0) and of osteoporosis (T-score ≤ -2.5) among adults aged ≥40 years without major risk factors or fractures, with one or more major risk factors, and with one or more major osteoporotic fractures. A total of 33,344 subjects met our study inclusion criteria, including 28,933 (86.8%) women; 9362 had no fractures or major risk factors, 14,932 had one or more major clinical risk factors, and 9050 had one or more major osteoporotic fractures. The prevalence of low bone mass and osteoporosis increased significantly with age overall. The prevalence of low bone mass and osteoporosis was significantly greater among men and women with major osteoporotic fractures than healthy controls or those with clinical risk factors. Applying our results to the national population census figure of 5,123,536 in 2022 we estimate between 1,039,348 and 1,240,807 men and women aged ≥50 years have low bone mass, whereas between 308,474 and 498,104 have osteoporosis. These data are important for the diagnosis of osteoporosis in clinical practice, and national policy to reduce the illness burden of osteoporosis. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Bone mineral density and fractures in patients with rheumatoid arthritis: the DXA-HIP project.

Objectives: RA is a chronic disabling disease affecting 0.5-1% of adults worldwide. People with RA have a greater prevalence of multimorbidity, particularly osteoporosis and associated fractures. Recent studies suggest that fracture risk is related to both non-RA and RA factors, whose importance is heterogeneous across studies. This study seeks to compare baseline demographic and DXA data across three cohorts: healthy controls, RA patients and a non-RA cohort with major risk factors and/or prior major osteoporotic fracture (MOF). Methods: This is a cross-sectional study using data collected from three DXA centres in the west of Ireland from January 2000 to November 2018. Results: Data were available for 30 503 subjects who met our inclusion criteria: 9539 (31.3%) healthy controls, 1797 (5.9%) with RA and 19 167 (62.8%) others. Although age, BMI and BMD were similar between healthy controls, the RA cohort and the other cohort, 289 (16.1%) RA patients and 5419 (28.3%) of the non-RA cohort had prior MOF. In the RA and non-RA cohorts, patients with previous MOF were significantly older and had significantly lower BMD at the femoral neck, total hip and spine. Conclusion: Although age, BMI and BMD were similar between a healthy control cohort and RA patients and others with major fracture risk factors, those with a previous MOF were older and had significantly lower BMD at all three measured skeletal sites. Further studies are needed to address the importance of these and other factors for identifying those RA patients most likely to experience fractures.

Conceptual design of the dual X-ray absorptiometry health informatics prediction system for osteoporosis care.

Osteoporotic fractures are a major and growing public health problem, which is strongly associated with other illnesses and multi-morbidity. Big data analytics has the potential to improve care for osteoporotic fractures and other non-communicable diseases (NCDs), reduces healthcare costs and improves healthcare decision-making for patients with multi-disorders. However, robust and comprehensive utilization of healthcare big data in osteoporosis care practice remains unsatisfactory. In this paper, we present a conceptual design of an intelligent analytics system, namely, the dual X-ray absorptiometry (DXA) health informatics prediction (HIP) system, for healthcare big data research and development. Comprising data source, extraction, transformation, loading, modelling and application, the DXA HIP system was applied in an osteoporosis healthcare context for fracture risk prediction and the investigation of multi-morbidity risk. Data was sourced from four DXA machines located in three healthcare centres in Ireland. The DXA HIP system is novel within the Irish context as it enables the study of fracture-related issues in a larger and more representative Irish population than previous studies. We propose this system is applicable to investigate other NCDs which have the potential to improve the overall quality of patient care and substantially reduce the burden and cost of all NCDs.

How does proximal femur BMD of healthy Irish adults compare to NHANES III? Results of the DXA-HIP Project.

This study examines the distribution of proximal femur bone mineral density in a cohort of healthy Irish adults. These values are similar to those of the NHANES III Caucasian cohorts, supporting international recommendations to use this reference group for calculating DXA T-scores and Z-scores in Irish adults. INTRODUCTION: Bone mineral density (BMD) is widely used in the assessment and monitoring of osteoporosis. International guidelines recommend referencing proximal femur BMD measurements to NHANES III values to calculate T-scores and Z-scores, but their validity for the Irish population has not been established. In this study, we compare BMD values of healthy Irish Caucasian adults to those of Caucasian men and women in the NHANES III cohort study. METHODS: Men and women without bone disease and/or major risk factors for fracture, and/or not taking osteoporosis medication who had a screening DXA scan (GE Lunar, Madison, USA) at one of 3 centres in the West of Ireland were selected for this study. We calculated the mean and standard deviation (SD) used by GE for calculating white female NHANES III T-scores at the femoral neck and total hip sites, and used these values to calculate white female T-scores for men and women across each decade in our study sample. We calculated mean white female T-scores for each decade for both Caucasian men and women in the NHANES III cohort using the published data. Finally, we plotted these results against those of our study population. RESULTS: In total, 6729 (18.5%) of 36,321 adults were included in our analyses, including 5923 (88%) women. The majority of the study population were aged between 40 and 89 years. Our results show that the proximal femur BMD of healthy Irish men and women is broadly similar to that of the NHANES III reference population, especially middle-aged adults. Results differ for very young and very old adults, likely reflecting the small sample size and a referral bias. Further studies of these populations and other manufacturers could help clarify these uncertainties. CONCLUSIONS: Our results support using the NHANES III reference population to calculate proximal femur adult T-scores and Z-scores to establish the presence or prevalence of osteoporosis in Ireland.

The Irish dual-energy X-ray absorptiometry (DXA) Health Informatics Prediction (HIP) for Osteoporosis Project.

PURPOSE: The purpose of the Irish dual-energy X-ray absorptiometry (DXA) Health Informatics Prediction (HIP) for Osteoporosis Project is to create a large retrospective cohort of adults in Ireland to examine the validity of DXA diagnostic classification, risk assessment tools and management strategies for osteoporosis and osteoporotic fractures for our population. PARTICIPANTS: The cohort includes 36 590 men and women aged 4-104 years who had a DXA scan between January 2000 and November 2018 at one of 3 centres in the West of Ireland. FINDINGS TO DATE: 36 590 patients had at least 1 DXA scan, 6868 (18.77%) had 2 scans and 3823 (10.45%) had 3 or more scans. There are 364 unique medical disorders, 186 unique medications and 46 DXA variables identified and available for analysis. The cohort includes 10 349 (28.3%) individuals who underwent a screening DXA scan without a clear fracture risk factor (other than age), and 9947 (27.2%) with prevalent fractures at 1 of 44 skeletal sites. FUTURE PLANS: The Irish DXA HIP Project plans to assess current diagnostic classification and risk prediction algorithms for osteoporosis and fractures, identify the risk predictors for osteoporosis and develop novel, accurate and personalised risk prediction tools, by using the large multicentre longitudinal follow-up cohort. Furthermore, the dataset may be used to assess, and possibly support, multimorbidity management due to the large number of variables collected in this project.

Virtual Reality (VR) Technology: Empowering Managers to Reduce and Eliminate Accessibility Barriers for People with Autism Spectrum Disorders.

Barriers to accessibility are defined as 'factors in a person's environment that, through their absence or presence, limit functioning and create disability' [1]. There are four elements that are incorporated into this term which includes: physical environment, lack of assistive technology, attitudes of others and the lack of or restrictive services, systems and policies [1]. These barriers to accessibility are present for 13% of the Irish population. Many initiatives have been developed and implemented for people with physical disabilities; however, people with intellectual disabilities (ID) remain invisible. This invisible population accounts for 9.7% of our population or 75% of the population of people with disabilities [2]. Thus, it is imperative that we commence to implement Universal Design (UD) approaches that increase accessibility and empower the invisible to become visible. One such invisible group that holds substantial potential to bring immense value to companies is that of people with Autism Spectrum Disorders (ASD) [3]. ASD currently impacts 1 in 68 people worldwide with this figure growing annually at a rate of 10-17% [4]. 80% of people with ASD are either unemployed or underemployed; this can be attributed to barriers to accessibility [5]. Two of the most common barriers to accessibility experienced by those with ASD are environmental and attitudes of others [6,7]. These barriers have the potential to be overcome through the use of Virtual Reality (VR) technology to provide training and education to managers. VR technology is being used to empower managers to reduce these barriers, increase accessibility and develop inclusive environments and cultures. VR technology can be used to empower managers to recognise and reduce the barriers facing those with ASD. VR is a catalyst for managers to be able to identify the environmental barriers facing people with ASD within a work environment. This solution also provides them with the skills necessary to commence making adaptations to the environment to reduce or eliminate these barriers. The use of this technology and paradigm shift brings many benefits for the individual and the company. A mixed method approach has been used for the purposes of data collection. The tools that were utilised were interviews with HR managers and people with ASD; and surveys were circulated to HR managers, senior managers, Chief Executive Officers and people with ASD. The results of these were positive and clearly verified that there is a need to empower managers to increase accessibility within their organisations.

Long-term safety and efficacy of biosimilar infliximab among patients with inflammatory arthritis switched from reference product.

PURPOSE: To evaluate the efficacy and safety of the biosimilar infliximab in adult patients with inflammatory arthritis switched from reference product in our center. PATIENTS AND METHODS: In April 2014, patients attending our rheumatology service for infliximab infusions were switched from reference product to the biosimilar infliximab following consent and hospital approval. RESULTS: Around 34 patients with inflammatory arthritis were switched from reference product to biosimilar infliximab in 2014: 50% female, mean age 55 years (standard deviation=12.9), mean disease duration 14.79 years (9.7), median duration on infliximab 57 months, and two-thirds on oral disease-modifying antirheumatic drugs. There was no difference in efficacy or safety in the first 6 months of therapy. By the end of 2015, the mean follow-up on biosimilar infliximab was 15.8 (standard deviation=6.3) months. Our results showed no significant difference in Health Assessment Questionnaire score, patient global assessment of disease activity, number of disease flares, or the medication dose between the originator and the biosimilar infliximab. However, reported pain and C-reactive protein values were significantly higher during the longer follow-up period (p=0.043, 0.001 respectively). There was no significant difference in the number of adverse events or infusion reactions during follow-up periods. Only five (14.7%) patients discontinued the biosimilar infliximab. CONCLUSION: Our patients experienced similar efficacy and safety for managing their arthritis with the biosimilar infliximab as the reference product infliximab, but at a much lower cost.

Predictive and prognostic factors influencing outcomes of rituximab therapy in systemic lupus erythematosus (SLE): A systematic review.

BACKGROUND: The clinical outcomes following rituximab (RTX) treatment in patients with systemic lupus erythematosus (SLE) is highly variable. We aimed to identify predictive and prognostic factors associated with RTX therapy outcomes in patients with SLE. METHODS: Studies in adults and paediatric patients with SLE were included. We included randomized clinical trials (RCTs) for predictors of differential treatment effect and cohort studies for potential prognostic factors in patients treated with RTX (global clinical, cutaneous and renal either response or relapse, and side effects). Methodological quality was assessed using Cochrane Collaboration Risk of Bias tool and the Quality In Prognosis Studies Tool (QUIPS) for RCTs and cohort studies, respectively. The quality of subgroup analyses testing predictors of differential treatment response was also evaluated. A best evidence synthesis was performed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS: Sixteen articles were included (3 from 2 RCTs and 13 from 6 cohort studies). The overall quality of evidence (QoE) was low to very low (GRADE framework). QoE for predictive factors based on RCTs analysing sociodemographic variables, was rated very low due to the lack of interaction tests, limited power of subgroup analyses, study limitations, and imprecisions. Disease-related factors including clinical phenotype and severity, baseline anti-ENA antibodies and anti-Ro antibodies, interleukin (IL) 2/21 single nucleotide polymorphism (SNP), as well as post-RTX complete B-cell depletion and earlier B-cell repopulation showed some evidence for prognostic value, but were rated low to very low QoE because of early phase of investigation (exploratory analysis), insufficient adjustment for confounding in most studies, high risk of bias, inconsistency, and imprecisions. CONCLUSIONS: To date, studies addressing prognostic factors are hypothesis generating and cannot be used to make any specific recommendations for routine clinical practice. A number of potential predictors/prognostic factors were identified, which require to be validated as being specific for response to RTX therapy and to enable more personalised use of this agent.

Cardiovascular risk and its modification in patients with connective tissue diseases.

It is well documented that patients with systemic lupus erythematosus (SLE) are at an increased risk of atherosclerotic cardiovascular (CV) disease. There is evidence that traditional risk factors and disease-related factors are involved in this increased risk. Less is known about CV risk and outcomes in other connective tissue diseases (CTDs). Future longitudinal observational studies may help to answer these important questions; however, because CTDs are rare, collaboration between clinicians with similar research interests is needed to ensure sufficiently large cohorts are available to address these issues. Here, we review the evidence available for CV risk in CTDs and discuss the benefits of longitudinal observational studies in identifying CV outcomes. Structured care protocols for the management of CV risk in CTDs are lacking. We propose a target-based approach to assessing and managing CV risk in CTDs.