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Background and objective Osteoarthritis (OA) is the most common arthritis in the world. Despite the high disease burden, there is no therapy to prevent, halt, or reverse OA, and many clinical trials relied on radiographic biomarkers for therapy response. It is important to identify patients with early OA who will eventually need arthroplasty, the end-stage treatment for osteoarthritis. This pilot study evaluates a novel MRI biomarker, cartilage loss fraction, for association with future arthroplasty and evaluates its feasibility of use and effect size estimates. Materials and methods Publicly available knee MRIs from the Osteoarthritis Initiative were used. A total of 38 participants with Kellgren-Lawrence (K-L) grade >1 and 38 participants with K-L grade ≤ 1 at enrollment were matched in age, sex, race, and BMI, and assessed for the degree of full-thickness cartilage loss, or cartilage loss fraction. Univariate conditional logistic regression analysis was performed for differences in cartilage loss fractions between groups. Receiver operating characteristic (ROC) curve analysis was performed to assess the association of MRI biomarkers and knee arthroplasty during the eight-year follow-up. Results The medial femoral condyle, medial tibial plateau, total, and two-year progression cartilage loss fractions were significantly higher in participants with K-L grade >1 (p < 0.01 for all) and showed high area under the curve (AUC) values on ROC analysis (812, 0.827, 0.917, and 0.933, respectively). These results were comparable or more strongly associated with other OA grading schemes. Conclusion MRI biomarker cartilage loss fractions are significantly higher in subjects with K-L grade >1 and show a strong association with arthroplasty. After further validation, cartilage loss fracture may be used to predict future arthroplasty.
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PURPOSE: This study evaluates sex differences and predictors of anti-osteoporosis medication (AOM) use following a hip fracture, with a focus on older men who exhibit higher mortality rates post-fracture compared to women over the age of 65. METHODS: Participants included 151 men and 161 women aged 65 and older with hip fractures. The outcome, AOM use, was assessed at baseline (≤ 22 days of hospitalization) and at 2, 6, and 12 months post-hip fracture. Generalized estimating equations (GEE) modeled sex differences and predictors of AOM use during the year post-fracture in 255 participants with complete baseline data and ≥ 1 follow-up observation. RESULTS: Of the 312 participants, only 53 used AOM at baseline, and 35 initiated use during follow-up. In the unadjusted GEE model, AOM use was significantly less likely in men (OR = 0.42; 95% CI, 0.22-0.78) compared to women. For both men and women, baseline use of AOM was a significant predictor (OR = 28.3; 95% CI, 5.4-148.0 vs. 41.6; 95% CI, 14.0-123.0). The other significant predictors by sex were osteoporosis diagnosis (OR = 3.19; 95% CI, 1.16-8.77) and minimal alcohol use (OR = 3.26; 95% CI, 1.34-7.94) for women versus age (OR = 1.09; 95% CI, 1.01-1.18) for men. CONCLUSION: In older adults with hip fractures, AOM use is low over the year post-fracture and men are less likely to report AOM use compared to women which has implications for important sex differences in predictors of use. Further research is needed to address overall disparities and sex differences in AOM use.
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IgG4-related disease (IgG4-RD) is a fibro-inflammatory condition that can affect various organs. Localized sinonasal IgG4-RD is a rare condition characterized by bone and soft-tissue invasion. In this report, we present a case of a patient initially diagnosed with chronic rhinosinusitis, who underwent endoscopic sinus surgery and was later found to have biopsy proven IgG4-related sinonasal disease despite having normal serum levels of IgG4, resulting in erosion of the right lamina papyracea.
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BACKGROUND: Persistent inflammation is associated with adverse health outcomes, but its impact on mortality has not been investigated previously among hip fracture patients. This article aims to investigate the influence of changes in levels of cytokines in the 2 months after a hip fracture repair on 5-year mortality. METHODS: This is a prospective cohort study from the Baltimore Hip Studies (BHS) with 191 community-dwelling older men and women (≥65 years) who had recently undergone surgical repair of an acute hip fracture, with recruitment from May 2006 to June 2011. Plasma interleukin-6 (IL-6), soluble tumor necrosis factor alpha receptor1 (sTNFα-R1), and interleukin-1 receptor agonist (IL-1RA) were obtained within 22 days of admission and at 2 months. All-cause mortality over 5 years was determined. Logistic regression analysis tested the associations between the cytokines' trajectories and mortality over 5 years, adjusted for covariates (age, sex, education, body mass index, lower extremity physical activities of daily living, and Charlson comorbidity index). RESULTS: High levels of IL-6 and sTNFα-R1 at baseline with small or no decline at 2 months were associated with higher odds of 5-year mortality compared with those with lower levels at baseline and greater decline at 2 months after adjustment for age, and other potential confounders (OR = 4.71, p = 0.01 for IL-6; OR = 15.03, p = 0.002 for sTNFα-R1). Similar results that failed to reach significance were found for IL-1RA (OR = 2.40, p = 0.18). Those with higher levels of cytokines at baseline with greater decline did not have significantly greater mortality than the reference group, those with lower levels at baseline and greater decline. CONCLUSION: Persistent elevation of plasma IL-6 and sTNFα-R1 levels within the first 2 months after hospital admission in patients with hip fracture is associated with higher 5-year mortality. These patients may benefit from enhanced care and earlier intensive interventions to reduce the risk of death.
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OBJECTIVE: To evaluate the relationship of gardening/yardwork with symptomatic and structural progression in those with pre-existing radiographic knee osteoarthritis (OA) in the Osteoarthritis Initiative (OAI), an observational study designed to evaluate potential and known biomarkers and risk factors of knee OA. METHODS: We conducted a cohort study nested within the OAI, including participants ≥ 50 years old with radiographic OA in at least one knee at the time of OAI enrollment. A participant reported the level of gardening/yardwork activity in a self-administered survey. Logistic regression analyses were used to evaluate the association of gardening/yardwork on new frequent knee pain, Kellgren-Lawrence (KL) worsening, medial joint space narrowing (JSN) worsening, and improved frequent knee pain. RESULTS: Of 1808 knees (1203 participants), over 60% of knees had KL grade = 2, 65% had medial JSN, and slightly more than a third had frequent knee symptoms. Gardeners/yardworkers and non-gardners/yardworkers had similar "worsening" outcomes for new knee pain (29% vs. 29%), KL worsening (19% vs. 18%), and medial JSN (23% vs. 24%). The adjusted odds ratio (OR) for the "worsening" outcomes of new knee pain, KL worsening, and medial JSN worsening were 1.0 (0.7-1.3), 1.0 (0.8-1.3), and 1.1 (0.9-1.4), respectively. The gardeners/yardworkers had an adjusted OR of 1.2 (0.9-1.7) for improved knee pain compared with non-gardners/yardworkers. CONCLUSION: Gardening/yardwork is not associated with knee OA progression and should not be discouraged in those with knee OA. Key Points ⢠Gardening/yardwork is not associated with knee OA symptomatic or structural progression. ⢠Gardening/yardwork should not be discouraged in people with knee OA.
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Osteoartritis de la Rodilla , Humanos , Persona de Mediana Edad , Osteoartritis de la Rodilla/complicaciones , Osteoartritis de la Rodilla/diagnóstico por imagen , Estudios de Cohortes , Jardinería , Progresión de la Enfermedad , Articulación de la Rodilla/diagnóstico por imagen , Dolor/complicacionesRESUMEN
INTRODUCTION: This study aimed to evaluate the relationship between a history of bicycling and symptomatic and structural outcomes of knee osteoarthritis (OA), the most common form of arthritis. METHODS: This was a retrospective, cross-sectional study within the Osteoarthritis Initiative (OAI), where we investigated OAI participants with complete data on bicycling, knee pain, and radiographic evidence of knee OA. We used a self-administered questionnaire at the 96-month OAI visit to identify participation in bicycling during four time periods throughout a participant's lifetime (ages 12-18, 19-34, 35-49, and >50 yr). Using logistic regression, we evaluated the influence of prior bicycling status (any history, history for each time period, number of periods cycling) on three outcomes at the 48-month OAI visit: frequent knee pain, radiographic OA (ROA), and symptomatic radiographic OA (SOA), adjusting for age and gender. RESULTS: A total of 2607 participants were included: 44.2% were male, mean age was 64.3 (SD, 9.0) yr, and body mass index was 28.5 (SD, 4.9) kg·m -2 . The adjusted risk ratios for the outcome of frequent knee pain, ROA, and SOA among those who reported any history of bicycling compared with non-bicyclers were 0.83 (0.73-0.92), 0.91 (0.85-0.98), and 0.79 (0.68-0.90), respectively. We observed a dose-response among those who participated in bicycling during more time periods. CONCLUSIONS: People who participated in bicycling had a lower prevalence of frequent knee pain, ROA, and SOA. The benefit appeared cumulative. This study indicates that bicycling may be favorable to knee health and should be encouraged.
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Ciclismo , Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/epidemiología , Masculino , Femenino , Ciclismo/fisiología , Estudios Transversales , Estudios Retrospectivos , Persona de Mediana Edad , Anciano , Radiografía , Adulto , Encuestas y Cuestionarios , ArtralgiaRESUMEN
BACKGROUND: Mechanistic factors on the pathway to improving independent ambulatory ability among hip fracture patients by a multicomponent home-based physical therapy intervention that emphasized aerobic, strength, balance, and functional training are unknown. The aim of this study was to determine the effects of 2 different home-based physical therapy programs on muscle area and attenuation (reflects muscle density) of the lower extremities, bone mineral density (BMD), and aerobic capacity. METHODS: Randomized controlled trial of home-based 16 weeks of strength, endurance, balance, and function exercises (PUSH, nâ =â 19) compared to seated active range-of-motion exercises and transcutaneous electrical neurostimulation (PULSE, nâ =â 18) in community-dwelling adults >60 years of age within 26 weeks of hip fracture. RESULTS: In PUSH and PULSE groups combined, the fractured leg had lower muscle area and muscle attenuation and higher subcutaneous fat than the nonfractured leg (pâ <â .001) at baseline. At 16 weeks, mean muscle area of the fractured leg was higher in the PUSH than PULSE group (pâ =â .04). Changes in muscle area were not significantly different when compared to the comparative PULSE group. There was a clinically relevant difference in change in femoral neck BMD between groups (pâ =â .05) that showed an increase after PULSE and decrease after PUSH. There were generally no between-group differences in mean VO2peak tests at 16-week follow-up, except the PUSH group reached a higher max incline (pâ =â .04). CONCLUSIONS: The treatment effects of a multicomponent home-based physical therapy intervention on muscle composition, BMD, and aerobic capacity were not significantly different than an active control intervention in older adults recovering from hip fracture. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01783704.
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Densidad Ósea , Fracturas de Cadera , Anciano , Humanos , Ejercicio Físico , Terapia por Ejercicio , Fracturas de Cadera/rehabilitación , MúsculosRESUMEN
OBJECTIVE: To assess how changes in depressive symptoms influence physical function over time among those with radiographic knee osteoarthritis (OA). METHODS: Participants from the Osteoarthritis Initiative with radiographic knee OA (n = 2,212) and complete data were identified at baseline. Depressive symptoms were assessed as a time-varying score at baseline and the first three annual follow-up visits using the Center for Epidemiological Studies Depression Scale (CES-D) Scale. Physical function was measured at the first four follow-up visits using 20-meter gait speed meters per second. The following two marginal structural models were fit: one assessing the main effect of depressive symptoms on gait speed and another assessing time-specific associations. RESULTS: Time-adjusted results indicated that higher CES-D scores were significantly associated with slower gait speed (-0.0048; 95% confidence interval -0.0082 to -0.0014), and time-specific associations of CES-D were largest during the first follow-up interval (-0.0082; 95% confidence interval -0.0128 to -0.0035). During subsequent follow-up time points, the influence of depressive symptoms on gait speed diminished. CONCLUSION: The negative effect of depressive symptoms on physical function may decrease over time as knee OA progresses.
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Depresión , Osteoartritis de la Rodilla , Velocidad al Caminar , Humanos , Osteoartritis de la Rodilla/psicología , Osteoartritis de la Rodilla/fisiopatología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Depresión/psicología , Factores de Tiempo , Estado Funcional , Articulación de la Rodilla/fisiopatología , Articulación de la Rodilla/diagnóstico por imagen , Progresión de la EnfermedadRESUMEN
BACKGROUND: Depressive symptoms are common in knee osteoarthritis (OA), exacerbate knee pain severity and may influence outcomes of oral analgesic treatments. The aim was to assess whether oral analgesic effectiveness in knee OA varies by fluctuations in depressive symptoms. METHODS: The sample included Osteoarthritis Initiative (OAI) participants not treated with oral analgesics at enrolment (n = 1477), with radiographic disease at the first follow-up visit (defined as the index date). Oral analgesic treatment and depressive symptoms, assessed with the Center for Epidemiological Studies Depression [(CES-D) score ≥16] Scale, were measured over three annual visits. Knee pain severity was measured at visits adjacent to treatment and modifier using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale (rescaled range = 0-100). Structural nested mean models (SNMMs) estimated causal mean differences in knee pain severity comparing treatment versus no treatment. RESULTS: The average causal effects of treated versus not treated for observations without depressive symptoms showed negligible differences in knee pain severity. However, causal mean differences in knee pain severity comparing treatment versus no treatment among observations with depressive symptoms increased over time from -0.10 [95% confidence interval (CI): -9.94, 9.74] to -16.67 (95% CI: -26.33, -7.01). Accordingly, the difference in average causal effects regarding oral analgesic treatment for knee pain severity between person-time with and without depressive symptoms was largest (-16.53; 95% CI: -26.75, -6.31) at the last time point. Cumulative treatment for 2 or 3 years did not yield larger causal mean differences. CONCLUSIONS: Knee OA patients with persistent depressive symptoms and chronic pain may derive more analgesic treatment benefit than those without depressive symptoms and less pain.
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Osteoartritis de la Rodilla , Humanos , Osteoartritis de la Rodilla/complicaciones , Osteoartritis de la Rodilla/tratamiento farmacológico , Depresión/tratamiento farmacológico , Estudios Prospectivos , Progresión de la Enfermedad , Dolor/tratamiento farmacológico , Dolor/etiología , Analgésicos/uso terapéuticoRESUMEN
OBJECTIVES: This study aims to evaluate non-melanoma skin cancer (NMSC) risk associated with abatacept treatment for rheumatoid arthritis (RA). METHODS: This evaluation included 16 abatacept RA clinical trials and 6 observational studies. NMSC incidence rates (IRs)/1000 patient-years (p-y) of exposure were compared between patients treated with abatacept versus placebo, conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and other biological/targeted synthetic (b/ts)DMARDs. For observational studies, a random-effects model was used to pool rate ratios (RRs). RESULTS: ~49 000 patients receiving abatacept were analysed from clinical trials (~7000) and observational studies (~42 000). In randomised trials (n=4138; median abatacept exposure, 12 (range 2-30) months), NMSC IRs (95% CIs) were not significantly different for abatacept (6.0 (3.3 to 10.0)) and placebo (4.0 (1.3 to 9.3)) and remained stable throughout the long-term, open-label period (median cumulative exposure, 28 (range 2-130 months); 21 335 p-y of exposure (7044 patients over 3 years)). For registry databases, NMSC IRs/1000 p-y were 5-12 (abatacept), 1.6-10 (csDMARDs) and 3-8 (other b/tsDMARDs). Claims database IRs were 19-22 (abatacept), 15-18 (csDMARDs) and 14-17 (other b/tsDMARDs). Pooled RRs (95% CIs) from observational studies for NMSC in patients receiving abatacept were 1.84 (1.00 to 3.37) vs csDMARDs and 1.11 (0.98 to 1.26) vs other b/tsDMARDs. CONCLUSIONS: Consistent with the warnings and precautions of the abatacept label, this analysis suggests a potential increase in NMSC risk with abatacept use compared with csDMARDs. No significant increase was observed compared with b/tsDMARDs, but the lower limit of the 95% CI was close to unity.
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Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Neoplasias Cutáneas , Humanos , Abatacept/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Artritis Reumatoide/complicaciones , Productos Biológicos/uso terapéutico , Incidencia , Ensayos Clínicos Controlados Aleatorios como Asunto , Neoplasias Cutáneas/inducido químicamente , Neoplasias Cutáneas/epidemiologíaRESUMEN
OBJECTIVE: Mendelian randomization (MR) has increasingly been utilized as a tool for establishing causal relations between modifiable exposures and osteoarthritis (OA). The goal of this review was to summarize available MR studies of OA that evaluate the causal role of modifiable risk factors on OA. METHODS: This review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Extension for Scoping Reviews model. We performed a literature search for relevant studies published before December 2021 across multiple databases using the search terms "osteoarthritis" and ("Mendelian randomization" or "polygenic risk score"). We reported the MR estimates of causal associations between exposures and OA and then assessed methodologic quality of abstracted studies according to their efforts to validate the three key MR assumptions. RESULTS: Our search identified 45 studies reporting on 141 exposure-association analyses. All studies performed a formal instrumental variable analysis to estimate the causal effect of exposure on OA. Causal associations (P < 0.05) were reported in 60 of these analyses representing 36 unique publications, and MR-Egger sensitivity analyses were performed in 45 of these analyses. MR studies provided support for causal associations of OA with increased levels of adiposity, coffee consumption, bone mineral density, and sleep disturbance, and decreased levels of serum calcium and low-density lipoprotein cholesterol. CONCLUSION: These results highlight the potential benefits of weight reduction and improvement of sleep quality to reduce the risk of OA and call for a better understanding of the relations of coffee consumption and serum calcium to OA risk.
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Análisis de la Aleatorización Mendeliana , Osteoartritis , Humanos , Análisis de la Aleatorización Mendeliana/métodos , Café , Calcio , Causalidad , Osteoartritis/etiología , Osteoartritis/genética , Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVE: We aimed to evaluate the relationship of a history of strength training with symptomatic and structural outcomes of knee osteoarthritis (OA). METHODS: This study was a retrospective, cross-sectional study within the Osteoarthritis Initiative (OAI), a multicenter prospective longitudinal observational study. Data were collected at four OAI clinical sites: Memorial Hospital of Rhode Island, the Ohio State University, the University of Pittsburgh, and the University of Maryland/Johns Hopkins. The study included 2,607 participants with complete data on strength training, knee pain, and radiographic evidence of knee OA (male, 44.2%; mean ± SD age 64.3 ± 9.0 years; mean ± SD body mass index 28.5 ± 4.9 kg/m2 ). We used a self-administered questionnaire at the 96-month OAI visit to evaluate the exposure of strength training participation during four time periods throughout a participant's lifetime (ages 12-18, 19-34, 35-49, and ≥50 years old). The outcomes (dependent variables) were radiographic OA (ROA), symptomatic radiographic OA (SOA), and frequent knee pain. RESULTS: The fully adjusted odds ratios (95% confidence interval) for frequent knee pain, ROA, and SOA among those who participated in strength training any time in their lives were 0.82 (0.68-0.97), 0.83 (0.70-0.99), and 0.77 (0.63-0.94), respectively. Findings were similar when looking at the specific age ranges. CONCLUSION: Strength training is beneficial for future knee health, counteracting long-held assumptions that strength training has adverse effects.
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Osteoartritis de la Rodilla , Entrenamiento de Fuerza , Humanos , Masculino , Persona de Mediana Edad , Anciano , Osteoartritis de la Rodilla/diagnóstico por imagen , Estudios Longitudinales , Estudios Prospectivos , Estudios Retrospectivos , Estudios Transversales , Articulación de la Rodilla/diagnóstico por imagen , Dolor/etiologíaRESUMEN
OBJECTIVE: To evaluate risk of infections requiring hospitalization and opportunistic infections, including tuberculosis, in patients with rheumatoid arthritis (RA) treated with abatacept versus conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs) and other biologic/targeted synthetic (b/ts) DMARDs. METHODS: Five international observational data sources were used: two biologic registries (Sweden, Germany), a disease registry (USA) and two healthcare claims databases (Canada, USA). Crude incidence rates (IRs) per 1000 patient-years, with 95 % CIs, were used to estimate rate ratios (RRs) comparing abatacept versus csDMARDs or other b/tsDMARDs. RRs were adjusted for demographic factors, comorbidities, and other potential confounders and then pooled across data sources using a random effects model (REM). RESULTS: The data sources included 6450 abatacept users, 136,636 csDMARD users and 54,378 other b/tsDMARD users, with a mean follow-up range of 2.2-6.2 years. Across data sources, the IRs for infections requiring hospitalization ranged from 16 to 56 for abatacept, 19-46 for csDMARDs, and 18-40 for other b/tsDMARDs. IRs for opportunistic infections were 0.4-7.8, 0.3-4.3, and 0.5-3.8; IRs for tuberculosis were 0.0-8.4, 0.0-6.0, and 0.0-6.3, respectively. The pooled adjusted RR (95 % CI), only reported for infections requiring hospitalization, was 1.2 (0.6-2.2) for abatacept versus csDMARDs and 0.9 (0.6-1.3) versus other b/tsDMARDs. CONCLUSIONS: Data from this international, observational study showed similar hospitalized infection risk for abatacept versus csDMARDs or other b/tsDMARDs. IRs for opportunistic infections, including tuberculosis, were low. These data are consistent with the known safety profile of abatacept.
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Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Infecciones Oportunistas , Tuberculosis , Humanos , Abatacept/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/epidemiología , Infecciones Oportunistas/inducido químicamente , Infecciones Oportunistas/epidemiología , Productos Biológicos/efectos adversos , Tuberculosis/inducido químicamente , Tuberculosis/epidemiología , MercadotecníaRESUMEN
OBJECTIVE: To evaluate the risk of malignancy (overall, breast, lung, and lymphoma) in patients with rheumatoid arthritis treated with abatacept, conventional synthetic (cs) disease-modifying antirheumatic drugs (DMARDs), and other biologic/targeted synthetic (b/ts)DMARDs in clinical practice. METHODS: Four international observational data sources were included: ARTIS (Sweden), RABBIT (Germany), FORWARD (USA), and BC (Canada). Crude incidence rates (IRs) per 1000 patient-years of exposure with 95% confidence intervals (CIs) for a malignancy event were calculated; rate ratios (RRs) were estimated and adjusted for demographics, comorbidities, and other potential confounders. RRs were then pooled in a random-effects model. RESULTS: Across data sources, mean follow-up for patients treated with abatacept (n = 5182), csDMARDs (n = 73,755), and other b/tsDMARDs (n = 37,195) was 3.0-3.7, 2.9-6.2, and 3.1-4.7 years, respectively. IRs per 1000 patient-years for overall malignancy ranged from 7.6-11.4 (abatacept), 8.6-13.2 (csDMARDs), and 5.0-11.8 (other b/tsDMARDs). IRs ranged from: 0-4.4, 0-3.3, and 0-2.5 (breast cancer); 0.1-2.8, 0-3.7, and 0.2-2.9 (lung cancer); and 0-1.1, 0-0.9, and 0-0.6 (lymphoma), respectively, for the three treatment groups. The numbers of individual cancers (breast, lung, and lymphoma) in some registries were low; RRs were not available. There were a few cases of lymphoma in some of the registries; ARTIS observed an RR of 2.8 (95% CI 1.1-6.8) with abatacept versus csDMARDs. The pooled RRs (95% CIs) for overall malignancy with abatacept were 1.1 (0.8-1.5) versus csDMARDs and 1.0 (0.8-1.3) versus b/tsDMARDs. CONCLUSIONS: This international, post-marketing observational safety study did not find any statistically significant increase in the risk of overall malignancies in pooled data in patients treated with abatacept compared with csDMARDs or with other b/tsDMARDs. Assessment of larger populations is needed to further evaluate the risks for individual cancers, especially lymphoma.
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Antirreumáticos , Artritis Reumatoide , Productos Biológicos , Neoplasias Pulmonares , Linfoma , Humanos , Abatacept/efectos adversos , Antirreumáticos/efectos adversos , Artritis Reumatoide/tratamiento farmacológico , Artritis Reumatoide/epidemiología , Artritis Reumatoide/inducido químicamente , Neoplasias Pulmonares/tratamiento farmacológico , Linfoma/inducido químicamente , Linfoma/tratamiento farmacológico , Mercadotecnía , Productos Biológicos/uso terapéuticoRESUMEN
Objective: To assess the feasibility of a 24-week, center-based, aerobic exercise program plus duloxetine to treat symptomatic knee osteoarthritis (OA) and major depression. Design: Patients with symptomatic knee OA and major depression were recruited between August 2021 and November 2022 from the University of Maryland and VA Maryland Health Care Systems and Baltimore metropolitan area using medical records and advertisements. The intervention included 1) supervised treadmill walking 3 times weekly and 2) duloxetine starting at 30 âmg each day and titrating up to the optimal dosage of 60 âmg daily. Data collection occurred at baseline and 12- and 24-weeks follow-up. Feasibility was evaluated from recruitment rates, reasons for drop out, and treatment adherence. Clinical measures included the Knee Injury and Osteoarthritis Outcome Score (KOOS) and the Hamilton Depression Rating Scale (HAM-D). Results: Among 377 interested participants, 9 patients were enrolled, and 1 completed treatment. The most common reason reported for not prescreening was time commitment (n â= â39), many patients did not satisfy depression screening criteria (n â= â45), and most enrolled participants were not experiencing a major depressive episode (n â= â6). The single treated participant was 100 â% adherent to duloxetine and depression severity decreased (HAM-D â= â25 to 1), but compliance to supervised exercise was only 26 â%, and knee pain severity changed little (KOOS â= â41.7 to 44.4). Conclusions: This intervention had low feasibility. Time commitment to supervised exercise sessions reduced accessibility, and depression defined by diagnostic criteria precluded knee OA patients with depressive symptoms not a meeting case-level diagnosis from receiving treatment. Clinical trial registration number: NCT04111627.
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Drs Lawrence E. Shulman and Mary Betty Stevens were the giants of rheumatology at Johns Hopkins during the latter half of the twentieth century. Together, they made immense contributions to our knowledge of systemic lupus erythematosus as well as other systemic autoimmune rheumatic diseases, provided excellent clinical care to thousands of patients with rheumatoid arthritis, systemic lupus erythematosus, and other systemic autoimmune rheumatic diseases, and trained almost 100 postdoctoral fellows, many of whom went on to highly successful careers in academic medicine, including the Directors of Divisions of Rheumatology and the Chairs of Departments of Medicine.
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Artritis Reumatoide , Lupus Eritematoso Sistémico , Enfermedades Reumáticas , Reumatología , HumanosRESUMEN
OBJECTIVE: Due to the risk of rapidly progressive osteoarthritis (RPOA), the phase III studies of subcutaneous (SC) tanezumab in patients with moderate to severe hip or knee osteoarthritis (OA) included comprehensive joint safety surveillance. This pooled analysis summarizes these findings. METHOD: Joint safety events in the phase III studies of SC tanezumab (2 placebo- and 1- nonsteroidal anti-inflammatory drug [NSAID]-controlled) were adjudicated by a blinded external committee. Outcomes of RPOA1 and RPOA2, primary osteonecrosis, subchondral insufficiency fracture, and pathological fracture comprised the composite joint safety endpoint (CJSE). Potential patient- and joint-level risk factors for CJSE, RPOA, and total joint replacement (TJR) were explored. RESULTS: Overall, 145/4541 patients (3.2%) had an adjudicated CJSE (0% placebo; 3.2% tanezumab 2.5â¯mg; 6.2% tanezumab 5â¯mg; 1.5% NSAID). There was a dose-dependent risk of adjudicated CJSE, RPOA1, and TJR with tanezumab vs NSAID. Patient-level cross-tabulation found associations between adjudicated RPOA with more severe radiographic/symptomatic (joint pain, swelling, and physical limitation) OA. Risk of adjudicated RPOA1 was highest in patients with Kellgren-Lawrence (KL) grade 2 or 3 OA at baseline. Risk of adjudicated RPOA2 or TJR was highest in patients with KL grade 4 joints at baseline. A higher proportion of joints with adjudicated RPOA2 had a TJR (14/26) than those with adjudicated RPOA1 (16/106). CONCLUSION: In placebo- and NSAID controlled studies of SC tanezumab for OA, adjudicated CJSE, RPOA, and TJR most commonly occurred in patients treated with tanezumab and with more severe radiographic or symptomatic OA. NCT02697773; NCT02709486; NCT02528188.
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Anticuerpos Monoclonales Humanizados , Osteoartritis de la Cadera , Osteoartritis de la Rodilla , Humanos , Antiinflamatorios no Esteroideos/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Osteoartritis de la Cadera/tratamiento farmacológico , Osteoartritis de la Rodilla/tratamiento farmacológico , Resultado del Tratamiento , Ensayos Clínicos Fase III como AsuntoRESUMEN
Nerve growth factor (a-NGF) inhibitors have been developed for pain treatment including symptomatic osteoarthritis (OA) and have proven analgesic efficacy and improvement in functional outcomes in patients with OA. However, despite initial promising data, a-NGF clinical trials focusing on OA treatment had been suspended in 2010. Reasons were based on concerns regarding accelerated OA progression but were resumed in 2015 including detailed safety mitigation based on imaging. In 2021, an FDA advisory committee voted against approving tanezumab (one of the a-NGF compounds being evaluated) and declared that the risk evaluation and mitigation strategy was not sufficient to mitigate potential safety risks. Future clinical trials evaluating the efficacy of a-NGF or comparable molecules will need to define strict eligibility criteria and will have to include strategies to monitor safety closely. While disease-modifying effects are not the focus of a-NGF treatments, imaging plays an important role to evaluate eligibility of potential participants and to monitor safety during the course of these studies. Aim is to identify subjects with on-going safety findings at the time of inclusion, define those potential participants that are at increased risk for accelerated OA progression and to withdraw subjects from on-going studies in a timely fashion that exhibit imaging-confirmed structural safety events such as rapid progressive OA. OA efficacy- and a-NGF studies apply imaging for different purposes. In OA efficacy trials image acquisition and evaluation aims at maximizing sensitivity in order to capture structural effects between treated and non-treated participants in longitudinal fashion. In contrast, the aim of imaging in a-NGF trials is to enable detection of structural tissue alterations that either increase the risk of a negative outcome (eligibility) or may result in termination of treatment (safety).
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PURPOSE: To compare the evaluation metrics for deep learning methods that were developed using imbalanced imaging data in osteoarthritis studies. MATERIALS AND METHODS: This retrospective study utilized 2996 sagittal intermediate-weighted fat-suppressed knee MRIs with MRI Osteoarthritis Knee Score readings from 2467 participants in the Osteoarthritis Initiative study. We obtained probabilities of the presence of bone marrow lesions (BMLs) from MRIs in the testing dataset at the sub-region (15 sub-regions), compartment, and whole-knee levels based on the trained deep learning models. We compared different evaluation metrics (e.g., receiver operating characteristic (ROC) and precision-recall (PR) curves) in the testing dataset with various class ratios (presence of BMLs vs. absence of BMLs) at these three data levels to assess the model's performance. RESULTS: In a subregion with an extremely high imbalance ratio, the model achieved a ROC-AUC of 0.84, a PR-AUC of 0.10, a sensitivity of 0, and a specificity of 1. CONCLUSION: The commonly used ROC curve is not sufficiently informative, especially in the case of imbalanced data. We provide the following practical suggestions based on our data analysis: 1) ROC-AUC is recommended for balanced data, 2) PR-AUC should be used for moderately imbalanced data (i.e., when the proportion of the minor class is above 5% and less than 50%), and 3) for severely imbalanced data (i.e., when the proportion of the minor class is below 5%), it is not practical to apply a deep learning model, even with the application of techniques addressing imbalanced data issues.
Asunto(s)
Enfermedades de los Cartílagos , Aprendizaje Profundo , Osteoartritis de la Rodilla , Humanos , Estudios Retrospectivos , Benchmarking , Articulación de la Rodilla/patología , Imagen por Resonancia Magnética/métodos , Osteoartritis de la Rodilla/diagnóstico por imagen , Osteoartritis de la Rodilla/patología , Enfermedades de los Cartílagos/patologíaRESUMEN
BACKGROUND: Orthopedists and other clinicians assess recovery potential of hip fracture patients at 2 months post-fracture for care planning. It is unclear if examining physical performance (e.g., balance, gait speed, chair stand) during this follow-up visit can identify individuals at a risk of poor functional recovery, especially mobility, beyond available information from medical records and self-report. METHODS: Data came from 162 patients with hip fracture enrolled in the Baltimore Hip Studies-7th cohort. Predictors of mobility status (ability to walk 1 block at 12 months post-fracture) were the Short Physical Performance Battery (SPPB) comprising balance, walking and chair rise tasks at 2 months; baseline medical chart information (sex, age, American Society of Anesthesiologist physical status rating, type of fracture and surgery, and comorbidities); and self-reported information about the physical function (ability to walk 10 feet and 1 block at pre-fracture and at 2 months post-fracture). Prediction models of 12-month mobility status were built using two methods: (1) logistic regression with least absolute shrinkage and selection operator (LASSO) regularization, and (2) classification and regression trees (CART). Area under ROC curves (AUROC) assessed discrimination. RESULTS: The participants had a median age of 82 years, and 49.3% (n = 80) were men. Two-month SPPB and gait speed were selected as predictors of 12-month mobility by both methods. Compared with an analytic model with medical chart and self-reported information, the model that additionally included physical performance measures had significantly better discrimination for 12-month mobility (AUROC 0.82 vs. 0.88, p = 0.004). CONCLUSION: Assessing SPPB and gait speed at 2 months after a hip fracture in addition to information from medical records and self-report significantly improves prediction of 12-month mobility. This finding has important implications in providing tailored clinical care to patients at a greater risk of being functionally dependent who would not otherwise be identified using regularly measured clinical markers.