Jinhui Ma

Fragility fracture is a major cause of chronic disease morbidity leading to reduced life quality and quantity in middle-aged and older women. Many risk factors have been identified but the relative contribution of each of them when being considered simultaneously remains unclear. We conducted a secondary analysis using data from a large Canadian prospective cohort study to investigate, among all the known risk factors, which are statistically independently associated with a first incident fragility fracture in middle-aged and older women after mutual adjustment. A total of 10,930 female participants with a mean age of 61.70 ± SD 10.00 years old were included in the analytical sample. 1048 fracture events were self reported during the six-year follow-up. Multivariate logistic regression considering only variables feasible to obtain during a single primary care visit revealed that eight factors were associated with increased fracture risk and were robust across all analyses including adjustment for bone mineral density T-score total hip and after multiple imputation for missing data. These factors are currently taking antidepressants [OR 1.29 (1.18, 1.42), p=.0060], impaired balance [OR 1.34 (1.21, 1.49), p=.0041], epilepsy [OR 2.18 (1.66, 2.87), p=.0043], lower hand grip strength [OR 0.97 (0.96, 0.98) per kg, p<.0001], greater height [OR 1.03 (1.02, 1.03) per cm, p<.0001], osteoarthritis [OR 1.19 (1.10, 1.29), p=.0234], parental hip fracture after age 50 [OR 1.30 (1.18, 1.43), p=.0068] and a personal history of fall in the past 12 months [OR 1.78 (1.61, 1.96), p<.0001]. These findings suggest that middle-aged and older women with such factors may be at higher risk of sustaining fracture in near future and could benefit from clinical attention and targeted preventive strategies.

Background: Geographic atrophy (GA), an advanced form of age-related macular degeneration (AMD), leads to legal blindness in approximately 16% of affected individuals within 6 years. Numerous trials have evaluated interventions to slow GA progression, and many studies are ongoing. However, the comparative benefits and harms of treatments within this rapidly evolving therapeutic landscape have not yet been systematically synthesized. Objectives: To present a protocol for a living systematic review and network meta-analysis (NMA) addressing the effects of available interventions for the management of GA. Methods: We systematically searched Medline, EMBASE, Cochrane CENTRAL, Web of Science, and ClinicalTrials.gov from inception for randomized controlled trials comparing any pharmacologic or non-pharmacologic treatment versus another, placebo, sham, or standard care in adults with unilateral or bilateral GA secondary to AMD. Paired reviewers will independently screen studies, extract data, and assess risk of bias. Outcomes of interest include best-corrected visual acuity (BCVA), untransformed and square root-transformed total GA lesion area, vision-related quality of life, low luminance BCVA, reading speed, mean macular sensitivity, adverse events leading to discontinuation, macular neovascularization, need for rescue treatment, ischemic optic neuropathy, serious ocular adverse events, and serious non-ocular adverse events. For each outcome, if feasible, we will conduct frequentist random-effects NMAs. We will assess the certainty of evidence and interpret findings using the GRADE approach. To maintain this review as a living systematic review, we will conduct updates every six months. Discussion: This review will provide a comprehensive, trustworthy, and up-to-date summary of evidence on treatments for GA secondary to AMD. Registration: Open Science Framework ( https://doi.org/10.17605/OSF.IO/W4JHR ).

Introduction: Anterior cruciate ligament reconstruction (ACLR) is complicated by high failure rates in young, active individuals, which is associated with worse outcomes and higher rates of osteoarthritis (OA). Failure of ACLR limits activity, reduces quality of life and substantially increases socio-economic costs. Thus, strategies to reduce ACLR failure are imperative. In the STABILITY 1 trial, we showed that adding a lateral extra-articular tenodesis (LET) to ACLR with a hamstring tendon (HT) graft provided greater stability than HT alone (Relative Risk Reduction (RRR)=0.38; 95% CI 0.21 to 0.52; p<0001). Recent meta-analyses suggest patellar tendon (bone patellar tendon bone (BPTB)) grafts provide better stability than HT although with greater donor site morbidity. Recently, the quadriceps tendon (QT) graft has become popular, claiming similar stability to BPTB without donor site morbidity. However, no high-quality studies have shown it to be better and no study has determined if the reduced rate of ACLR failure seen with the addition of a LET to a HT graft is still present when using stronger, stiffer BPTB or QT grafts. Therefore, this study will evaluate whether in patients at high risk of rerupture, graft type (QT, BPTB, HT) with or without a LET offers a greater reduction in rate of clinical failure, better performance-based function and patient-reported symptoms, function and quality of life or higher rates of return to sport 2 years after ACLR. And does graft type±LET affect muscle strength recovery or increase the risk of donor site morbidity or lateral compartment articular cartilage degeneration? Do females, who are more often quadriceps dominant in their landing biomechanics, experience better outcomes if their ACLR uses a BPTB and/or QT autograft compared with a HT+LET autograft? Finally, is a particular graft type±LET a more cost-effective approach to ACLR? Methods and analysis: Across 31 centres (9 Canadian, 8 European, 14 USA), we will randomly assign 1292 patients with an ACL rupture who are at high risk of failure to either QT (±LET) or BPTB (±LET). Eligible participants will be 14–25 years of age, with at least two of the following: (1) Grade 2 pivot shift or greater; (2) returning to high-risk pivoting sport; (3) generalised ligamentous laxity; or (4) knee recurvatum of 10 degrees or more. Surgeons with similar expertise and no preference for either graft type will use traditional randomisation; two centres will use an expertise-based approach. Outcomes include ACLR clinical failure, patient-reported outcomes that assess symptoms, activity, participation and quality of life, measures of impaired range of motion and muscle function (quadriceps and hamstring strength), performance-based measures of physical function (hop tests, drop vertical jump), return to preinjury sports, adverse outcomes, intervention-related donor site morbidity and complications. Clinical failure and performance-based outcomes will be assessed by blinded evaluators over 2 years following ACLR. Analyses will combine STABILITY 2 and STABILITY 1 data in a mixed effects model where fixed effects include study, graft type, meniscal repair status and sex, while time, patient and surgeon are random effects variables. Ethics and dissemination: Ethics approval was granted for each centre prior to beginning recruitment. If successful, the results of this study will inform the optimal treatment of ACL rupture in young athletes, and women specifically, who are at risk for persistent rotational laxity/instability and graft rerupture. Reducing the risk of ACLR clinical failure will reduce the need for revision ACLR and the associated decreased quality of life and socio-economic burden that occurs because of ongoing knee instability and the increased risk for OA. Trial registration number: https://clinicaltrials.gov/study/NCT03935750 .

Background: Artificial intelligence (AI) and automation offer opportunities to enhance the efficiency, timeliness, and sustainability of living guidelines (LGs). However, how AI and automation have been integrated into existing LG development frameworks remains unclear. This scoping review represents the first step in a broader programme of work aimed at developing a framework which aims to guide responsible and coordinated AI adoption across all phases of LG development. Objective: To identify existing frameworks, methods, and approaches that integrate AI or automation into any stage of LG development. Methods: We conducted a structured search of PubMed, Embase, Web of Science, Scopus, Cochrane Database for Systematic Review and Cochrane Central Register of Controlled Trials from inception to March 12, 2026. We included peer‐reviewed articles describing frameworks, models, or methods that applied AI or automation in the development of LGs. We extracted data into a standardised form, capturing study characteristics, AI methods, targeted guideline processes, and key findings and synthesised findings using a thematic narrative approach. Results: Of 1090 records identified, three studies met the inclusion criteria. The included studies described AI or automation applied to select components of the LG process, to support continuous evidence surveillance, to semi‐automate study screening, and incremental updating of living systematic reviews. None addressed multiple stages of LG development in an integrated manner. Conclusions: Current evidence demonstrates fragmented and narrowly focused AI or automation applications within LG development processes. Our findings highlight opportunities for future work to develop and evaluate more comprehensive frameworks that span multiple stages of the LG lifecycle.

Introduction: Exercise therapy is the most recommended treatment for chronic low back pain (LBP), with evidence supporting modest effects, likely due to the heterogeneity of patient presentations. Evidence suggests that matching individuals to the most appropriate exercise type could improve outcomes. Systematic reviews also emphasise that effective exercise interventions should be patient centred, target paraspinal muscle health and be of sufficient duration. This study addresses these gaps using a targeted care approach to identify a homogenous sample that is more likely to respond to our interventions. The inclusion of a sample with predominant nociceptive pain profile will be performed with the integration of the Pain and Disability Drivers Management Model (PDDM) and the Lumbar Spine Instability Questionnaire (LSIQ). The primary aim of this two-arm randomised controlled trial is to compare the effectiveness of motor control plus isolated lumbar extension exercises (MC+ILEX, arm 1) to free-weight resistance training (arm 2) in reducing LBP-related disability. Secondary aims include examining whether changes in multifidus composition mediate disability improvements comparing intervention effects on muscle size and quality, strength, mobility, pain, quality of life, sleep, physical activity and satisfaction; exploring baseline LSIQ scores and sex/gender as moderators of treatment response; and investigating participants’ perceptions and experiences of exercise therapy. Methods and analysis: A total of 106 participants will be recruited through primary and secondary care and randomised (1:1) to receive either MC+ILEX or free-weight resistance training. Both groups will complete 48 exercise sessions over 16 weeks. The primary outcome will be disability at 16 weeks, measured by the Oswestry Disability Index. Secondary outcomes include multifidus muscle composition and size, lumbar and gluteal muscle strength, hip range of motion, pain, physical and mental function, satisfaction and recovery, health-related quality of life, sleep quality and physical activity levels. Linear mixed-effects models will be used to assess primary and secondary outcomes. Regression analyses will explore whether baseline LSIQ scores moderate treatment effects on multifidus composition and other outcomes. A subsample of participants will undergo semistructured interviews before and after the intervention to explore their illness perceptions, illness mindsets, perceptions of exercise therapy, as well as their experiences and satisfaction with the two exercise interventions. Reflexive thematic analysis will be used to analyse qualitative data. Ethics and dissemination: This study received ethics approval from the Central Ethics Research Committee of the Quebec Minister of Health and Social Services (CCER-25-26-14). Results will be submitted to peer-reviewed journals and scientific meetings. Trial registration number: ISRCTN14864451 .

Chronic illnesses and their treatments in childhood pose significant risks of bone fragility due to osteoporosis. Bisphosphonates (BP) are commonly used for treatment, yet evidence remains limited and heterogeneous. This systematic review aims to consolidate current empirical evidence on BP efficacy and safety in children, youth and young adults aged ≤ 21 years with secondary osteoporosis. Ovid MEDLINE and EMBASE, PubMed, Web of Science, Cumulative Index to Nursing and Allied Health, and Cochrane Central Register of Controlled Trials were searched by May 29th, 2025. This review followed the PRISMA guidelines the GRADE approach. This review was registered at PROSPERO (CRD42021242156). Seventeen studies were included (fifteen randomized controlled trials (RCTs), two quasi-RCTs) evaluating BP. Meta-analysis indicated that BP improved lumbar spine bone mineral density (BMD) z-score (mean difference (MD): 0.67; 95% confidence interval (CI): 0.37, 0.97) and lumbar spine bone mineral content (BMC) (MD: 2.90 g; 95% CI: 0.91, 4.90). There were no studies adequately powered to assess vertebral and non-vertebral fractures. Patient-reported outcomes showed no consistent results. Adverse events (AEs) were comparable between treatment and control groups (relative risk (RR): 1.08; 95% CI: 0.94, 1.23). When limited to short-term periods after the first infusion, AEs were more likely in the treatment group (RR: 2.24; 95% CI: 1.22, 4.11). BP treatment benefits pediatric secondary osteoporosis by improving lumbar spine BMD and BMC. However, small sample sizes and heterogeneity among the study methods continue to challenge the reliability of results, and larger RCTs are needed to assess fracture rates.