Background Magnetic Resonance Imaging (MRI) is considered the imaging modality of choice for identifying meniscal pathology. However, it can be challenging to differentiate intrameniscal signal changes from tears. Given that meniscal tears may be more conspicuous when loaded, weight-bearing imaging may better visualize tears. We hypothesized that weight-bearing CT arthrography (WBCTa) would demonstrate meniscal pathology not visualized on MRI. Methods This cross-sectional, observational study compared WBCTa with MRI to evaluate rates of detection of meniscal pathology. Sixty-five subjects (age >18) who underwent clinical MRI to evaluate suspected meniscal pathology received WBCTa of the knee an average of 6 days later. Meniscal tears, extrusion, and cysts were semi-quantitatively scored using the MOAKS scoring system. Results 65 participants (mean age, 48.4 ± 13.9 years, 45 women) were evaluated. Medial meniscal body tears were detected by WBCTa for 45% of the 40 knees that were visually normal or demonstrated only non-specific signal abnormality on MRI. WBCTa identified medial extrusion of the medial meniscus in 53.3% of 30 knees that did not have this finding on MRI. Scoring of lateral meniscal tears and extrusion as well as meniscal root tears, and cysts generally agreed between WBCTa and MRI. Conclusion WBCTa detected a higher rate of medial meniscal tears (complete/partial maceration; complex, partial, and horizontal tears) and a higher rate of medial meniscal extrusions than were visualized on MRI in this study. Visualization of lateral meniscal tears, meniscal root tears, and cysts did not differ between WBCTa and MRI.

PURPOSE:The purpose of this study was to evaluate the relationship between subchondral insufficiency fracture (SIF) of the knee and radial meniscal tears on magnetic resonance imaging (MRI) and to examine within the medial compartment the potential mediating role of meniscal extrusion in this relationship. MATERIALS AND METHODS:A retrospective matched case-control study of knee MRI examinations obtained from November 2021 to November 2024 was performed. MRIs were reviewed for SIF, meniscal tear morphology, and meniscal extrusion grade. Associations between radial tears and SIF (overall and medial compartment) were evaluated using conditional logistic regression adjusted for age, sex, and body mass index. Medial-compartment mediation was examined using a natural effects model with medial meniscal extrusion as the mediator. RESULTS:The cohort included 343 patients with SIF (65.4 ± 10.1 [standard deviation] years; 226 women) and 343 patients without SIF (66.4 ± 10.0 [standard deviation] years; 224 women). Compared with knees without radial tears, odds of SIF were higher in the presence of radial root tears (odds ratio [OR], 7.62; 95% confidence interval [CI]: 4.40-13.21) and radial non-root tears (OR, 5.26; 95% CI: 2.48-11.15), with similar findings in the medial compartment. In mediation analysis, medial radial root tears showed an indirect association with medial SIF through medial meniscal extrusion (OR, 1.46; 95% CI: 1.16-1.84), accounting for 16.6% of the total effect. CONCLUSION:Radial root and non-root tears are strongly associated with SIF on MRI, particularly in the medial compartment. Meniscal extrusion explained a small proportion of this association, suggesting that additional biomechanical pathways are likely in play.

OBJECTIVE:Gait affects knee loading. Modifying gait could reduce load and protect against cartilage loss. Our objective is to look for modifiable gait parameters and determine their relation to worsening cartilage damage. METHODS:We studied participants from the Multicenter Osteoarthritis Study (MOST) ages 45 to 90 years with, or at risk for, knee osteoarthritis (OA). Gait assessment used inertial measurement units (APDM, Inc) on the pelvis and ankles during a 20-m walk. Knee magnetic resonance imaging (MRI) was acquired at baseline and two years later. Cartilage damage worsening was assessed using MRI Osteoarthritis Knee Scores in 14 knee subregions. We examined change (yes/no) in each subregion. We used ensemble machine learning to discriminate subregions with and without cartilage damage. Predictors tested included gait variables, radiographic OA, baseline cartilage damage, age, sex, height, weight, depressive symptoms, and race/clinic site. Data were split 70% training and 30% test sets. We identified the 10 variables that, across 100 repetitions, most frequently contributed to risk of damage. We used G-computation to evaluate causal risk differences of worsening cartilage damage for each variable. RESULTS:We studied 1,703 participants (mean [±SD] age 61.4 [±9.4] years, 56% female). At two years, 46% had worse cartilage damage in at least one knee subregion. Of gait variables, longer step length was associated with increased risk of damage, especially in knees with more baseline damage. CONCLUSION:Longer step length was associated with worse cartilage damage over two years. Interventions to shorten step length might reduce risk of worsening cartilage damage.

PURPOSE:The purpose of this study was to evaluate the association between systemic low bone mineral density (BMD) and subchondral insufficiency fracture (SIF) of the knee in women, and to explore whether this association is modified by radial meniscal tears. MATERIALS AND METHODS:In this case-control study, women with and without MRI-confirmed SIF who had available dual-energy X-ray absorptiometry T-score measurements were included. Systemic BMD was categorized using T-scores. Multivariable logistic regression models with BMD as the exposure and SIF as the outcome, adjusting for age and body mass index were fitted. An exploratory stratified analysis to assess potential effect modification by meniscal radial tear status was also conducted. RESULTS:A total of 121 women with SIF (mean age, 69.1 ± 7.5 [standard deviation] years) and 124 controls (70.4 ± 8.3 [standard deviation] years) were analyzed. After adjustment, osteoporosis was associated with higher odds of SIF (odds ratio [OR], 2.29; 95% confidence interval [CI]: 1.03-5.09), whereas osteopenia (OR, 1.33; 95% CI: 0.69-2.55) showed no significant association. In exploratory stratified analysis to test for effect modification, there were no significant interactions between low BMD and radial root tears (P-interaction = 0.178). However, small strata likely limited the power to detect a significant effect modification, as evidenced by overlapping wide 95% CIs. CONCLUSION:Osteoporosis is associated with higher odds of SIF of the knee in women, while osteopenia is not.

BACKGROUND:Transfusion of packed red blood cells (pRBCs) below a hemoglobin concentration of 7.0 g/dL is common, but it is unclear if the timing of transfusion during hospitalization modifies transfusion effectiveness. We sought to determine if effects of pRBC transfusion are heterogenous based on time from hospital admission. METHODS:Multicenter retrospective cohort study including hospitals in the Premier Inc. AI Healthcare Database between 2016 and 2022. Hospital encounters for adults with at least one hemoglobin concentration measured between hospital Days 1-7 were included. For each day, the lowest hemoglobin concentration was identified; patient-days were then separated into seven analytic cohorts based on the day in which a hemoglobin concentration was recorded (index day). We used regression discontinuity to quantify the effect of index day pRBC transfusion versus no transfusion on an outcome of hospital mortality or discharge to hospice (risk difference [RD]) at a hemoglobin concentration threshold of 7.0 g/dL in each cohort. RESULTS:A total of 2,293,021 index days across 997,277 inpatient encounters were included. The association between pRBC transfusion and hospital mortality or discharge to hospice differed based on days from admission, shifting from benefit on Day 1 (RD: -2.9 [95% CI: -5.9, -0.04] %) to harm on index Days 6 and 7 (Day 6, RD: 3.3 [95% CI: 0.4, 6.1] %; Day 7, RD: 4.1 [95% CI: 0.8, 7.3] %, p-interaction < .0001). CONCLUSIONS:Transfusion during hospitalization was associated with benefit early in hospitalization and harm at later time points.

OBJECTIVE:Opioid use remains common despite effective therapies for axial spondyloarthritis (axSpA). We assessed whether early tumor necrosis factor inhibitor (TNFi) use is associated with reduced risk of chronic opioid use. METHODS:Using the Merative MarketScan Commercial Database containing health insurance billing claims data, we conducted a time-stratified, propensity score (PS)-matched cohort study of adults aged 18 to 65 years with axSpA. Early TNFi exposure was defined using pharmacy and medical claims as any incident TNFi use within 6 months of axSpA diagnosis. We used PSs to match early TNFi users 1:1 to those not starting a TNFi within 6 months in 1-year cohort accrual blocks. We compared the risk of chronic opioid use (≥90 days' prescription) among early TNFi users versus comparators using Cox proportional hazard models, overall and stratified by prior opioid use (within 12 months). RESULTS:We included 8,508 individuals with axSpA after PS matching (4,254 early TNFi initiators and 4,254 comparators) with a mean age of 42 years; 50% were female. Chronic opioid use occurred in 20.9% (22.3% early TNFi initiators and 19.6% comparators). Early TNFi initiators had 17% higher risk of chronic opioid use versus matched comparators (95% confidence interval [CI] 1.06-1.28), with higher risk of chronic opioid use for early TNFi initiators in the opioid-naive but not in the opioid-experienced stratum (hazard ratio [HR] 1.96; 95% CI 1.41-2.74 vs HR 1.06; 95% CI 0.96-1.17). CONCLUSION:Early TNFi initiation was not associated with reduced risk of chronic opioid use versus later or no TNFi initiation. Confounding by indication in administrative claims data limit result interpretation.

The effects of sodium-glucose cotransporter-2 (SGLT2) inhibitors on reducing cardiovascular events in different subgroups of diabetic patients are under investigation. The current systematic review and meta-analysis investigated the effects of SGLT2 inhibitors on preventing cardiovascular events and mortality and their adverse events in patients with active cancer and diabetes undergoing cardiotoxic cancer treatment. We searched PubMed, Embase, Web of Science, and Scopus to find studies investigating the effects of SGLT2 inhibitors on patients with diabetes and confirmed cancer until 19 August 2024. Meta-analyses were conducted using the random-effects model to compare all-cause mortality, cancer-associated mortality, heart failure (HF) hospitalization, arrhythmia, and adverse event rates such as ketoacidosis, hypoglycemia, urinary tract infection, and sepsis between patients with or without SGLT2 inhibitors use. Risk ratios (RRs) with 95

BACKGROUND:Corticosteroids are a mainstay of treatment for acute exacerbations of idiopathic pulmonary fibrosis (AE-IPF), but dosing practices vary. We leveraged between-hospital variation in propensity to administer pulse dose corticosteroids to determine the association between pulse dose corticosteroids and patient outcomes in AE-IPF. RESEARCH QUESTION:Do outcomes differ for hospitalized patients who recieve pulse dose corticosteroids vs low dose corticosteroids for AE-IPF? STUDY DESIGN AND METHODS:We designed an instrumental variable study informed by a target trial framework using the Premier Healthcare Database (2016-2022). We identified adults ≥ 50 years of age with AE-IPF who received a dose of IV methylprednisolone within 2 days of admission. Our exposure of interest was receipt of pulse dose methylprednisolone (≥ 250 mg); our instrument was admission to a hospital with high use of pulse dosing. We assessed association with in-hospital death/discharge to hospice and discharge home without invasive mechanical ventilation. In subgroup analyses, we tested for interaction with unit of admission (admission to ICU/intermediate care units vs ward units). RESULTS:We identified 3,049 patients with AE-IPF at 177 US hospitals (pulse dose: n = 1,094; low dose: n = 1,955). Patients who received a pulse dose vs low dose had a risk difference for death/hospice of 1.2% (95% CI, -6.0% to 8.5%); for discharge home without invasive mechanical ventilation, this was 5.3% (95% CI, -2.6% to 13.1%). In subgroup analysis, receipt of pulse dosing was associated with differential risk of death/hospice by admission unit (risk difference: ICU/intermediate care: 26.3%; 95% CI, 10.1%-42.6% vs ward units: 0.1%; 95% CI, -11.1% to 11.3%; P interaction = .009), but not with differential risk of discharge home without invasive mechanical ventilation (P interaction = .18). INTERPRETATION:We observed no significant benefit or harm associated with the receipt of pulse dose corticosteroids for patients with AE-IPF. However, in the subgroup of patients admitted to ICU/intermediate care, there was an increased risk of in-hospital death/discharge to hospice. Future studies should explore the use of pulse vs low-dose corticosteroids in critically ill populations with AE-IPF.

Objective. Radiographic axial spondyloarthritis (r-axSpA) has a 7-year average diagnostic delay. Although the effects of sex or gender on time to diagnosis have been evaluated, the role of social determinants of health remains understudied. We assessed whether time from initial clinical documentation of r-axSpA symptoms to r-axSpA diagnosis (diagnostic delay) varies based on sex, race, ethnicity, and/or the presence of social needs. Methods. We studied patients with r-axSpA from a tertiary center from 2000 to 2022. The cohort was built with the Observational Health Data Sciences and Informatics (OHDSI) network. For the primary analysis, we assessed the time from back pain and/or spinal pain to r-axSpA diagnosis and, secondarily, the time to r-axSpA from any other r-axSpA-related condition. To estimate differences in diagnostic delay, we employed an accelerated failure time parametric survival model. Results. We included 404 patients (mean age 49 years; 38.6% female), with 25.5% identifying as Black, 31.1% as other or unknown race, and 14.1% as Hispanic. Patients with a documented social need had a 21% increase in time from back pain to r-axSpA diagnosis (95% CI 0.93-1.56). In patients with any r-axSpA-related condition, time to diagnosis similarly increased by 21% (95% CI 0.92-1.57). Considering that there is an average time to diagnosis of 34 months, a social need increased time to diagnosis by 7 months. Conclusion. This study reveals a trend toward diagnostic delay in r-axSpA related to social need, sex, race, and ethnicity. Future studies should focus on referral strategies to enable prompt diagnosis and optimize care.

OBJECTIVE:A paradoxical relationship between pain during exercise and the hypoalgesic effect of exercise has not been studied well in the knee osteoarthritis (OA) population. We sought to investigate the relation of pain evoked during exercise to exercise-induced hypoalgesia (EIH) and to determine if the efficiency of conditioned pain modulation (CPM), a proxy of the descending pain inhibitory system, mediates this relationship in people with knee OA. METHODS:We used baseline data from two clinical trials for people with symptomatic knee OA (n = 68). The maximum pain rating (0-10) during a series of knee exercises was defined as the outcome. EIH was assessed as an increase (ie, improvement) in the pressure pain threshold (PPT) after a bout of exercises. Efficient CPM was defined as an increase (ie, improvement) in PPT after a painful conditioning stimulus (forearm ischemia). We performed a causal mediation analysis to examine the association between pain during exercise and EIH as well as the mediating role of CPM efficiency on the relation of pain during exercise with EIH. RESULTS:People with knee OA who had at least a one-unit increase in pain with exercise were 43% more likely (odds ratio [OR] 1.43, 95% confidence interval [CI] 1.05-1.94) to experience subsequent EIH than those without pain increase. The efficiency of CPM did not mediate the relationship between pain during exercise and EIH (OR 1.00, 95% CI 0.96-1.04). CONCLUSION:Our finding suggests that some amount of discomfort or pain during exercise may have beneficial analgesic effects; however, this is not likely via activation of the descending pain inhibitory system.

OBJECTIVE:People with axial spondyloarthritis (axSpA) have increased fracture risk relative to the general population, possibly related to chronic inflammation. We assessed the impact of treatment with receiving tumor necrosis factor inhibitors (TNFis) and nonbiologic conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) on hip and spine fractures in patients with axSpA, relative to receiving nonsteroidal anti-inflammatory drugs (NSAIDs). METHODS:We conducted a nested case-control study using 2006 to 2021 data from the Merative MarketScan Database. We included adults 18 to 65 years old with at least one inpatient or at least two outpatient axSpA International Classification of Diseases, Ninth Revision (ICD-9), or International Classification of Diseases, Tenth Revision (ICD-10), diagnosis codes separated by at least seven days. The primary outcome was hip and/or spine fracture, defined by ICD-9 or ICD-10 diagnosis or procedure codes. For each patient with fracture (cases), we selected up to 10 controls without fracture. We evaluated medication exposure (TNFis, csDMARDs, NSAIDs [referent], or none) hierarchically using pharmacy claims and procedure codes. We assessed the relation of medication exposure with hip and spine fracture risk using unconditional logistic regression with confounder adjustment. RESULTS:Our main analysis included 13,519 individuals with axSpA, comprising 1,229 patients with fracture and 12,290 controls. Individuals receiving TNFis had 29% lower odds of fracture compared to those receiving NSAIDs (odds ratio [OR] 0.71, 95% confidence interval [CI] 0.59-0.85), accounting for age, sex, and diagnosis year. Results were similar in the fully adjusted model (OR 0.75, 95% CI 0.62-0.91) and when stratified by sex. CONCLUSION:Using a large US insurance claims database, we found evidence for a protective effect of receiving TNFis on fracture risk in patients with axSpA underscoring a potential impact of TNFis in diminishing comorbidities linked with axSpA.

OBJECTIVE:Prolonged opioid use occurs in 25% of individuals with axial spondyloarthritis (axSpA). Whether introduction of tumor necrosis factor inhibitors (TNFi) influenced secular trends in opioid prescription in axSpA is unknown. We examined opioid prescription trends in axSpA, relative to nonsteroidal anti-inflammatory drugs (NSAIDs) and TNFi, using two observational databases. METHODS:We used data from IQVIA Medical Research Database (IMRD), a UK electronic health records-based database from 2000 to 2020, and Merative MarketScan (MarketScan), a US administrative claims-based database from 2006 to 2021. We included adults (18-89 years, IMRD; 18-65 years, MarketScan) with axSpA. We calculated annual prescription rates for opioids, NSAIDs, and TNFi (only in MarketScan) and estimated percentage changes in annual prescription rates by medication class using joinpoint regression. RESULTS:We included 1,689 individuals from IMRD (mean age 47 years; 74% male) and 18,858 individuals from MarketScan (mean age 45 years; 51% male). In IMRD, annual opioid prescription rates decreased by 2.5% (95% confidence interval [CI] -9.1 to 1.9) between 2001 and 2007, increased by 3.9% (95% CI -3.0 to 14.2) between 2007 and 2016, and decreased by 0.4% (95% CI -11.2 to 2.9) between 2016 and 2020. In MarketScan, annual opioid prescription rates decreased by 1.5% (95% CI -3.0 to 2.0) in 2008 to 2016 and decreased by 8.6% (95% CI -15.2 to -5.7) in 2016 to 2021. TNFi prescriptions increased by 1.8% (95% CI 1.1 to 2.5) in 2008 to 2021. CONCLUSION:Opioid prescription rates remained stable over time in the United Kingdom, whereas they slightly decreased in the United States as TNFi uptake increased. These trends may reflect a US nationwide change in guidance for opioid prescriptions issued in 2016.

OBJECTIVE:The objective of this study was to identify gait alterations related to worsening knee pain and worsening physical function, using machine learning approaches applied to wearable sensor-derived data from a large observational cohort. METHODS:Participants in the Multicenter Osteoarthritis Study (MOST) completed a 20-m walk test wearing inertial sensors on their lower back and ankles. Parameters describing spatiotemporal features of gait were extracted from these data. We used an ensemble machine learning technique ("super learning") to optimally discriminate between those with and without worsening physical function and, separately, those with and without worsening pain over two years. We then used log-binomial regression to evaluate associations of the top 10 influential variables selected with super learning with each outcome. We also assessed whether the relation of altered gait with worsening function was mediated by changes in pain. RESULTS:Of 2,324 participants, 29% and 24% had worsening knee pain and function over two years, respectively. From the super learner, several gait parameters were found to be influential for worsening pain and for worsening function. After adjusting for confounders, greater gait asymmetry, longer average step length, and lower dominant frequency were associated with worsening pain, and lower cadence was associated with worsening function. Worsening pain partially mediated the association of cadence with function. CONCLUSION:We identified gait alterations associated with worsening knee pain and those associated with worsening physical function. These alterations could be assessed with wearable sensors in clinical settings. Further research should determine whether they might be therapeutic targets to prevent worsening pain and worsening function.

Purpose (the aim of the study): There is a paucity of effective drug treatments for osteoarthritis (OA) despite expensive efforts at drug development. Repurposing drugs used to treat other diseases has often been successful in identifying new treatments for a disease. Drugs used to treat diabetes, all with anti-inflammatory effects, have special promise as drugs that could be repurposed for OA. Since substantial weight loss reduces OA incidence and OA outcomes, GLP1 agonists (GLP1a) which induce 15-20% weight loss are very promising as treatments and have been shown in a cohort study to improve OA outcomes.

Purpose (the aim of the study): Gait affects loading of the knee. Thus, modifying gait could reduce some aspects of load so as to protect against cartilage loss in persons with knee OA. There have been no large-scale, prospective studies examining wearable-sensor derived gait measures and their relation to later cartilage worsening. Our objective was to determine the relation of wearable-sensor derived gait measures with cartilage worsening over 2 years using machine learning and causal inference approaches in the Multicenter Osteoarthritis Study (MOST).

IMPORTANCE:. The opioid crisis is impacting people across the country and deserves attention to be able to curb the rise in opioid-related deaths. OBJECTIVES:. To evaluate practice patterns in opioid infusion administration and dosing for patients with acute respiratory failure receiving invasive mechanical ventilation. DESIGN:. Retrospective cohort study. SETTING AND PARTICIPANTS:. Patients from 21 hospitals in Kaiser Permanente Northern California and 96 hospitals in Philips electronic ICU Research Institute. MAIN OUTCOMES AND MEASURES:. We assessed whether patients received opioid infusion and the dose of said opioid infusion. RESULTS:. We identified patients with a diagnosis of acute respiratory failure who were initiated on invasive mechanical ventilation. From each patient, we determined if opioid infusions were administered and, among those who received an opioid infusion, the median daily dose of fentanyl infusion. We used hierarchical regression models to quantify variation in opioid infusion use and the median daily dose of fentanyl equivalents across hospitals. We included 13,140 patients in the KPNC cohort and 52,033 patients in the eRI cohort. A total of 7,023 (53.4%) and 16,311 (31.1%) patients received an opioid infusion in the first 21 days of mechanical ventilation in the KPNC and eRI cohorts, respectively. After accounting for patient- and hospital-level fixed effects, the hospital that a patient was admitted to explained 7% (95% CI, 3–11%) and 39% (95% CI, 28–49%) of the variation in opioid infusion use in the KPNC and eRI cohorts, respectively. Among patients who received an opioid infusion, the median daily fentanyl equivalent dose was 692 µg (interquartile range [IQR], 129–1341 µg) in the KPNC cohort and 200 µg (IQR, 0–1050 µg) in the eRI cohort. Hospital explained 4% (95% CI, 1–7%) and 20% (95% CI, 15–26%) of the variation in median daily fentanyl equivalent dose in the KPNC and eRI cohorts, respectively. CONCLUSIONS AND RELEVANCE:. In the context of efforts to limit healthcare-associated opioid exposure, our findings highlight the considerable opioid exposure that accompanies mechanical ventilation and suggest potential under and over-treatment with analgesia. Our results facilitate benchmarking of hospitals’ analgesia practices against risk-adjusted averages and can be used to inform usual care control arms of analgesia and sedation clinical trials.